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Title of Information Collection can u buy ventolin over the counter. Evaluation of Risk Adjustment Data Validation (RADV) Appeals and Health Insurance Exchange Outreach Training Sessions. Use. CMS recognizes that the success of accurately identifying risk-adjustment payments and payment errors is dependent upon the data submitted by Medicare Advantage Organizations (MAOs), and is strongly committed to providing appropriate education and technical outreach to MAOs and third-party administrators can u buy ventolin over the counter (TPAs).

In addition, CMS is strongly committed to providing appropriate education and technical outreach to States, issuers, self-insured group health plans and TPAs participating in the Marketplace and/or market stabilization programs mandated by the Affordable Care Act (ACA). CMS will strengthen outreach and engagement with MAOs and stakeholders in the Marketplace through satisfaction surveys following contract-level (CON) RADV audit and Health Insurance Exchange training events. The survey results will help to determine stakeholders' level of satisfaction with trainings, identify any issues with training and technical assistance delivery, clarify stakeholders' needs and preferences, and define best practices for can u buy ventolin over the counter training and technical assistance. Form Number.

CMS-10764 (OMB control number. 0938-NEW). Frequency. Occasionally.

Affected Public. Private Sector. Number of Respondents. 4,270.

Total Annual Responses. 4,270. Total Annual Hours. 1,068.

(For questions regarding this collection contact Melissa Barkai at 410-786-4305.) 2. Type of Information Collection Request. Extension of a currently approved collection. Title of information Collection.

Disclosure of State Rating Requirements. Use. The final rule “Patient Protection and Affordable Care Act. Health Insurance Market Rules.

Rate Review” implements sections 2701, 2702, and 2703 of the Public Health Service Act (PHS Act), as added and amended by the Affordable Care Act, and sections 1302(e) and 1312(c) of the Affordable Care Act. The rule directs that states submit to CMS certain information about state rating and risk pooling requirements for their individual, small group, and large group markets, as applicable. Specifically, states will inform CMS of age rating ratios that are narrower than 3:1 for adults. Tobacco use rating ratios that are narrower than 1.5:1.

A state-established uniform age curve. Geographic rating areas. Whether premiums in the small and large group market are required to be based on average enrollee amounts (also known as composite premiums). And, in states that do not permit any rating variation based on age or tobacco use, uniform family tier structures and corresponding multipliers.

In addition, states that elect to merge their individual and small group market risk pools into a combined pool will notify CMS of such election. This information will allow CMS to determine whether state-specific rules apply or Federal default rules apply. It will also support the accuracy of the federal risk adjustment methodology. Form Number.

CMS-10454 (OMB control number 0938-1258). Frequency. Occasionally. Affected Public.

State, Local, or Tribal Governments. Number of Respondents. 3. Total Annual Responses.

3. Total Annual Hours. 17. (For policy questions regarding this collection contact Russell Tipps at 301-869-3502.) 3.

Type of Information Collection Request. Extension of a currently approved collection. Title of Information Collection. Quality Improvement Organization (QIO) Assumption of Responsibilities and Supporting Regulations.

Use. The Peer Review Improvement Act of 1982 amended Title XI of the Social Security Act to create the Utilization and Quality Control Peer Review Organization (PRO) program which replaces the Professional Standards Review Organization (PSRO) program and streamlines peer review activities. The term PRO has been renamed Quality Improvement Organization (QIO). This information collection describes the review functions to be performed by the QIO.

It outlines relationships among QIOs, providers, practitioners, beneficiaries, intermediaries, and carriers. Form Number. CMS-R-71 (OMB control number. 0938-0445).

Frequency. Yearly. Affected Public. Business or other for-profit and Not-for-profit institutions.

Number of Respondents. 6,939. Total Annual Responses. 972,478.

Total Annual Hours. 1,034,655. (For policy questions regarding this collection contact Kimberly Harris at 401-837-1118.) 4. Type of Information Collection Request.

Extension of a currently approved collection. Titles of Information Collection. ASC Forms for Medicare Program Certification. Use.

The form CMS-370 titled “Health Insurance Benefits Agreement” is used for the purpose of establishing an ASC's eligibility for payment under Title XVIII of the Social Security Act (the “Act”). This agreement, upon acceptance by the Secretary of Health &. Human Services, shall be binding on the ASC and the Secretary. The agreement may be Start Printed Page 73722terminated by either party in accordance with regulations.

In the event of termination of this agreement, payment will not be available for the ASC's services furnished to Medicare beneficiaries on or after the effective date of termination. The CMS-377 form is used by ASCs to initiate both the initial and renewal survey by the State Survey Agency, which provides the certification required for an ASC to participate in the Medicare program. An ASC must complete the CMS-377 form and send it to the appropriate State Survey Agency prior to their scheduled accreditation renewal date. The CMS-377 form provides the State Survey Agency with information about the ASC facility's characteristics, such as, determining the size and the composition of the survey team on the basis of the number of ORs/procedure rooms and the types of surgical procedures performed in the ASC.

Form Numbers. CMS-370 and CMS-377 (OMB control number. 0938-0266). Frequency.

Occasionally. Affected Public. Private Sector—Business or other for-profit and Not-for-profit institutions. Number of Respondents.

1,567. Total Annual Responses. 1,567. Total Annual Hours.

1,012. (For policy questions regarding this collection contact Caroline Gallaher at 410-786-8705.) 5. Type of Information Collection Request. Revision of a currently approved collection.

Title of Information Collection. Home Health Agency Survey and Deficiencies Report. Use. In order to participate in the Medicare Program as a Home Health Agency (HHA) provider, the HHA must meet federal standards.

This form is used to record information and patients' health and provider compliance with requirements and to report the information to the federal government. Form Number. CMS-1572 (OMB control number. 0938-0355).

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Participants Figure How much does levitra cost per pill 1 ventolin action. Figure 1. Enrollment and ventolin action Randomization.

The diagram represents all enrolled participants through November 14, 2020. The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements ventolin action for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1.

Table 1. Demographic Characteristics ventolin action of the Participants in the Main Safety Population. Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 sites worldwide (United States, 130 sites.

Argentina, 1 ventolin action. Brazil, 2. South Africa, 4.

Germany, 6 ventolin action. And Turkey, 9) in the phase 2/3 portion of the trial. A total ventolin action of 43,448 participants received injections.

21,720 received BNT162b2 and 21,728 received placebo (Figure 1). At the data cut-off date of October 9, a total ventolin action of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height in meters] of at least 30.0), and 21% had at least one coexisting condition.

The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local Reactogenicity Figure 2 ventolin action. Figure 2.

Local and Systemic Reactions Reported within 7 Days after Injection of BNT162b2 ventolin action or Placebo, According to Age Group. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown in Panel A.

Pain at the injection site was assessed according to the following ventolin action scale. Mild, does not interfere with activity. Moderate, interferes with ventolin action activity.

Severe, prevents daily activity. And grade ventolin action 4, emergency department visit or hospitalization. Redness and swelling were measured according to the following scale.

Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 ventolin action to 10.0 cm in diameter. Severe, >10.0 cm in diameter.

And grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis ventolin action (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated in the key.

Medication use ventolin action was not graded. Additional scales were as follows. Fatigue, headache, chills, new or worsened muscle pain, new or worsened ventolin action joint pain (mild.

Does not interfere with activity. Moderate. Some interference with activity.

Or severe. Prevents daily activity), vomiting (mild. 1 to 2 times in 24 hours.

Moderate. >2 times in 24 hours. Or severe.

Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate.

4 to 5 loose stools in 24 hours. Or severe. 6 or more loose stools in 24 hours).

Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants. Overall, BNT162b2 recipients reported more local reactions than placebo recipients.

Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose.

78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction.

In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days. Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients.

51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients). The frequency of any severe systemic event after the first dose was 0.9% or less.

Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1.

38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose. Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter. Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose.

No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3). More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%).

This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial.

Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo.

No asthma treatment–associated deaths were observed. No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment.

Efficacy Table 2. Table 2. treatment Efficacy against asthma treatment at Least 7 days after the Second Dose.

Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2.

Figure 3. Figure 3. Efficacy of BNT162b2 against asthma treatment after the First Dose.

Shown is the cumulative incidence of asthma treatment after the first dose (modified intention-to-treat population). Each symbol represents asthma treatment cases starting on a given day. Filled symbols represent severe asthma treatment cases.

Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point.

The time period for asthma treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior asthma , 8 cases of asthma treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6.

Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of asthma treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4).

treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%. 95% CI, 68.7 to 99.9. Case split.

BNT162b2, 2 cases. Placebo, 44 cases). Figure 3 shows cases of asthma treatment or severe asthma treatment with onset at any time after the first dose (mITT population) (additional data on severe asthma treatment are available in Table S5).

Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.Participants From July 22 to August 7, 2020, a total of 593 persons underwent screening for enrollment in cohort 1 (including 1a and 1b combined) (Fig. S1). Of these persons, 405 were enrolled and 402 received the first dose of Ad26.COV2.S.

These participants had received the second dose by November 7, 2020. From August 3 to August 24, 2020, a total of 660 persons underwent screening for cohort 3. Of these participants, 405 were enrolled and 403 received the first dose of Ad26.COV2.S.

(Details regarding age distribution are provided in Table S2.) Analyses of data obtained from participants in cohort 3 after the administration of the second dose, as well as durability and longer-term safety data, are ongoing. Table 1. Table 1.

Characteristics of the Participants at Baseline. At baseline, the percentage of participants who were seropositive for asthma S-specific antibodies was 2% in cohort 1a and 1% in cohort 3. The baseline characteristics of the participants were broadly similar across the groups (Table 1).

treatment Safety and Reactogenicity Figure 1. Figure 1. Solicited Adverse Events in Cohorts 1 and 3 after the First treatment Dose.

Shown are solicited adverse events in participants who received the Ad26.COV2.S treatment at a dose of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) per milliliter or placebo. Healthy adults between the ages of 18 and 55 years were included in cohort 1 (Panel A), and those 65 years of age or older were included in cohort 3 (Panel B). The younger group was divided into cohorts 1a and 1b, with the latter designated as an exploratory cohort for in-depth analysis of immunogenicity.

As shown here, data for cohorts 1a and 1b have been pooled. Data for patients in cohort 1a who received a second dose of treatment are provided in Figure S2 in the Supplementary Appendix.Data regarding both solicited and unsolicited adverse events and serious adverse events were available for more than 99% of the participants who returned diary cards. The investigator’s assessment of reactogenicity after the administration of the first dose of treatment was available for 402 participants in cohort 1 and for 403 participants in cohort 3.

In the two cohorts, solicited local adverse events were mostly of grade 1 or 2. The most frequent event was injection-site pain. In cohort 1, solicited local adverse events were reported in 103 of 162 low-dose recipients (64%), in 123 of 158 high-dose recipients (78%), and in 7 of 82 placebo recipients (9%) (Figure 1A and Table S3).

In cohort 3, solicited local adverse events were reported in 66 of 161 low-dose recipients (41%), in 68 of 161 high-dose recipients (42%), and in 11 of 81 placebo recipients (14%) (Figure 1B). In the two cohorts, most solicited systemic adverse events were of grade 1 or 2. The most frequent events were fatigue, headache, and myalgia.

In cohort 1, solicited systemic adverse events were reported in 105 low-dose recipients (65%), in 133 high-dose recipients (84%), and in 21 placebo recipients (26%). In cohort 3, solicited systemic adverse events were reported in 74 low-dose recipients (46%), in 88 high-dose recipients (55%), and in 19 placebo recipients (23%). In cohort 1, solicited grade 3 systemic adverse events were reported in 15 low-dose recipients (9%) and in 32 high-dose recipients (20%).

No placebo recipients reported such events. In cohort 1a, among the participants between the ages of 18 and 30 years who had one or more solicited grade 3 adverse events, 24% had received the low dose and 26% had received the high dose. In those between the ages of 31 and 45 years, the corresponding percentages were 43% and 14%.

And in those between the ages of 46 and 55 years, the corresponding percentages were 3% and 11%. In cohort 3, grade 3 solicited systemic adverse events were reported in 1 low-dose recipient (1%) and in 4 high-dose recipients (2%). No placebo recipients reported having such events.

In cohort 1, fever was reported in 25 low-dose recipients (15%) and in 62 high-dose recipients (39%). Grade 3 fever (temperature range, 39.0 to 40.0°C) was reported in 8 low-dose recipients (5%) and in 15 high-dose recipients (9%). In cohort 3, fever was reported in 7 low-dose recipients (4%) and in 14 high-dose recipients (9%).

Grade 3 fever was reported in no low-dose recipients and in 2 high-dose recipients (1%). No participants in the placebo group in either cohort reported having fever. All cases of fever occurred within 2 days after immunization and resolved within 1 or 2 days.

More than 80% of the participants with fever received an antipyretic drug at the onset of symptoms. In cohort 1, unsolicited adverse events were reported in 34 low-dose recipients (21%), in 56 high-dose recipients (35%), and in 14 placebo recipients (17%). In cohort 3, unsolicited adverse events were reported in 27 low-dose recipients (17%), in 38 high-dose recipients (24%), and in 13 placebo recipients (16%) (Table S4).

No grade 4 adverse events (solicited or unsolicited) were reported in any cohort. In cohort 1a, safety data after the administration of the second dose of treatment were available for 363 participants (Fig. S2).

One or more solicited adverse events were noted in 77% and 80% of the participants in the low-dose and high-dose groups, respectively, as compared with 34% and 31% of those who received placebo as a second dose after a first dose of treatment and in 22% of those who received placebo for both doses. Solicited adverse events of grade 3 or higher were noted in 1% of low-dose recipients and in 7% of high-dose recipients. The corresponding percentages were 1% and 2% among participants in the placebo group who received a first dose of treatment and in no participants who received placebo for both doses.

No grade 3 fevers were reported in any group after a second dose of treatment. No participant discontinued the trial because of an adverse event. Five serious adverse events occurred.

One case of hypotension that was deemed by the investigator to be unrelated to the treatment because of a history of recurrent hypotension. One case of bilateral nephrolithiasis in a participant with a history of kidney stones (not related). One case of legionella pneumonia (not related).

One worsening of multiple sclerosis, which had remained undiagnosed for approximately 8 to 10 years on the basis of findings on magnetic resonance imaging (not related). And one case of fever that resulted in hospitalization because of suspicion of asthma treatment. In the last case, the participant recovered within 12 hours, and the fever was subsequently deemed by the investigator to be related to the treatment.

Details regarding all safety data are provided in the Supplementary Appendix. Immunogenicity and Seroconversion Figure 2. Figure 2.

Humoral Immunogenicity. Shown are measures of humoral immunogenicity in serum samples obtained from the participants in cohort 1a (left side) and cohort 3 (right side), according to the receipt of the low or high dose of Ad26.COV2.S or placebo. In cohort 1a, the participants received two injections of high-dose or low-dose treatment or placebo, as indicated with slashes (e.g., placebo/placebo if they received two injections of placebo).

The samples were measured on enzyme-linked immunosorbent assay (ELISA) in ELISA units (EU) per milliliter (Panel A) and on wild-type ventolin neutralization assay, with seropositivity defined as a half maximal inhibitory concentration (IC50) titer of more than 58 at the lower limit of quantitation (Panel B). Logarithmic values are reported as the geometric mean concentration (GMC) in the ELISA analyses and as the geometric mean titer (GMT) in the neutralizing-antibody analyses. The values were measured at baseline and at day 29 after vaccination in all the participants and on days 57 and 71 in those in cohort 1a.

The two horizontal dotted lines in each panel indicate the lower and upper limits of quantitation of the respective assay. Values below the lower line have been imputed to half the lower limit of quantitation. Н™¸ bars indicate 95% confidence intervals.

HCS denotes human convalescent serum.Immunogenicity data for this interim analysis were unblinded according to dose level. In all five groups in cohort 1a, the binding-antibody geometric mean concentration (GMC), as reported in ELISA units per milliliter, was measured against a stabilized asthma full-length spike protein. At baseline, the GMC values in all the participants were lower than the lower limit of quantitation.

By day 29 after vaccination, the values had increased to 478 (95% confidence interval [CI], 379 to 603) in the low-dose/placebo group, 586 (95% CI, 445 to 771) in the low-dose/low-dose group, 625 (95% CI, 505 to 773) in the high-dose/placebo group, and 788 (95% CI, 628 to 988) in the high-dose/high-dose group, with an incidence of seroconversion of 99% or more in all the groups (Figure 2A and Fig. S3A). By day 57, the corresponding GMC values had further increased to 660 (95% CI, 513 to 849), 754 (95% CI, 592 to 961), 873 (95% CI, 701 to 1087), and 1100 (95% CI, 908 to 1332).

After the first dose, the incidence of seroconversion was 100% in all but the high-dose/placebo group (97%). Fourteen days after the second dose, the GMC was 1677 (95% CI, 1334 to 2109) in the low-dose/low-dose group and 2292 (95% CI, 1846 to 2845) in the high-dose/high-dose group, with 100% seroconversion in each group. On day 71, in the low-dose/placebo and high-dose/placebo groups, the GMC was 600 (95% CI, 443 to 814) and 951 (95% CI, 696 to 1,300), respectively, values that were similar to those on day 57.

In cohort 3, the GMCs in all the participants were also below the lower limit of quantitation at baseline. By day 15 after vaccination, the GMC had increased to 122 (95% CI, 97 to 152) in the low-dose group and to 141 (95% CI, 114 to 175) in the high-dose group, with a seroconversion incidence of 75% and 77%, respectively. By day 29, the GMC was 312 (95% CI, 246 to 396) in the low-dose group and 350 (95% CI, 281 to 429) in the high-dose group, with 96% seroconversion.

The asthma neutralizing-antibody titer (IC50) was measured in a random subgroup of participants in cohorts 1a and 3. In cohort 1a, the geometric mean titer (GMT) was below the lower limit of quantitation at baseline and by day 29 after vaccination had increased to 224 (95% CI, 158 to 318) in the low-dose/placebo group, 224 (95% CI, 168 to 298) in the low-dose/low-dose group, 215 (95% CI, 169 to 273) in the high-dose/placebo group, and 354 (95% CI, 220 to 571) in the high-dose/high-dose group, with an incidence of seroconversion of 96%, 88%, 96%, and 92%, respectively (Figure 2B and Fig. S3B).

By day 57, the GMT had further increased to 310 (95% CI, 228 to 422), 288 (95% CI, 221 to 376), 370 (95% CI, 268 to 511), and 488 (95% CI, 334 to 714), respectively, with a 100% incidence of seroconversion in the low-dose/placebo group and 96% seroconversion in the other groups. In cohort 1a, 14 days after the second dose, the GMT was 827 (95% CI, 508 to 1183) in the low-dose/low-dose group and 1266 (95% CI, 746 to 2169) in the high-dose/high-dose group, with 100% seroconversion in the two dose groups. On day 71, the GMT was 321 (95% CI, 227 to 438) in the low-dose/placebo group and 388 (95% CI, 290 to 509) in the high-dose/placebo group, values that were similar to those on day 57.

The incidence of seroconversion was 100% in both groups. In cohort 3, the GMTs in all the participants were below the lower limit of quantitation at baseline and had increased to 212 (95% CI, 137 to 284) in the low-dose group and 172 (95% CI, 119 to 269) in the high-dose group on day 15 and to 277 (95% CI, 193 to 307) and 212 (95% CI, 163 to 266), respectively, on day 29. The incidence of seroconversion was 91% and 84%, respectively, on day 15 and 96% and 88%, respectively, on day 29.

These data were confirmed on IC80 analysis (Fig. S4). Antibody levels as measured on wild-type ventolin neutralization assay and ELISA were strongly correlated in the two cohorts (Fig.

S5). However, the correlation had a wider elliptical shape in cohort 3, which suggested more variability in the relationship between the neutralizing-antibody titer and the binding-antibody titer in the older adults. Antibody levels in the different human convalescent serum panels that were included in assays for humoral-immunity assessment that were performed in different laboratories and in serum samples that were obtained from treatment recipients were in the same range.

Details regarding differences in values according to demographic characteristics are provided in Tables S5 and S6 in the Supplementary Appendix. Levels of Ad26 neutralizing antibodies at baseline or after the first dose of treatment did not correlate with the levels of asthma neutralizing antibodies on either day 29 or day 71 (Fig. S6).

S-Specific T-Cell Responses Figure 3. Figure 3. Cellular Immunogenicity of Ad26.COV2.S.

In CD4+ T cells, the response to low-dose or high-dose treatment or placebo in type 1 helper T (Th1) cells was characterized by the expression of interferon-γ, interleukin-2, or both, without cytokines expressed by type 2 helper T (Th2) cells (Panel A). The response in CD4+ Th2 cells was characterized by the expression of interleukin-4, interleukin-5, or interleukin-13 (or all three cytokines) plus CD40L (Panel B). In CD8+ T cells, the response was measured by the expression of interferon-γ, interleukin-2, or both (Panel C).

In all three panels, the horizontal bars indicate median values on intracellular cytokine staining for individual responses to a asthma S protein peptide pool in peripheral-blood mononuclear cells at baseline and 15 days after vaccination in a subgroup of participants in cohort 1a (left side) and cohort 3 (right side), according to the receipt of the low or high dose of Ad26.COV2.S or placebo. The horizontal dotted line in each panel indicates the lower limit of quantitation (LLOQ). Values below the line have been imputed to half the LLOQ.The treatment-elicited responses in S-specific CD4+ Th1 and Th2 cells and in CD8+ T cells were assessed in a subgroup of participants at baseline and 15 days after the first dose.

In cohort 1a, a Th1 response to S peptides was detected in 76% (95% CI, 65 to 86) of low-dose recipients and in 83% (95% CI, 73 to 91) of high-dose recipients. The corresponding values in cohort 3 were 60% (95% CI, 46 to 74) and 67% (95% CI, 53 to 79), respectively (Figure 3A). In cohort 1a, the median CD4+ Th1 response to S peptides increased from an undetectable level at baseline to a median of 0.08% (interquartile range [IQR], 0.05 to 0.16) in low-dose recipients and 0.11% (IQR, 0.07 to 0.16) in high-dose recipients on day 15.

In cohort 3, the corresponding values were 0.09% (IQR, 0.04 to 0.17) and 0.11% (IQR, 0.04 to 0.15), respectively. A low-dose recipient in cohort 1a and a high-dose recipient in cohort 3 had a measurable Th2 response (Figure 3B). However, all the participants who had a measurable Th1 or Th2 response had a Th1:Th2 ratio that was well above 1, which indicated a treatment-induced Th1-skewed response.

S-specific CD8+ T-cell responses, as identified by the expression of interferon-γ or interleukin-2 cytokines on S-peptide stimulation, were absent at baseline in the two cohorts (Figure 3C). On day 15 in cohort 1a, a CD8+ T-cell response was detected in 51% of participants (95% CI, 39 to 63) in the low-dose group and in 64% (95% CI, 52 to 75) in the high-dose group, with a median S-specific CD8+ T-cell response of 0.07% (IQR, 0.03 to 0.19) and 0.09% (IQR, 0.05 to 0.19), respectively. In cohort 3, CD8+ T-cell responses were lower, with an incidence of 36% (95% CI, 23 to 51) in the low-dose group and 24% (95% CI, 13 to 37) in the high-dose group, with a median response of 0.06% (IQR, 0.02 to 0.12) and 0.02% (IQR, 0.01 to 0.08), respectively.

The correlation between CD4+ Th1 and CD8+ T-cell response was poor in the two cohorts (Fig. S7).Trial Oversight This phase 3 randomized, stratified, observer-blinded, placebo-controlled trial enrolled adults in medically stable condition at 99 U.S. Sites.

Participants received the first trial injection between July 27 and October 23, 2020. The trial is being conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Good Clinical Practice guidelines, and applicable government regulations. The central institutional review board approved the protocol and the consent forms.

All participants provided written informed consent before enrollment. Safety is reviewed by a protocol safety review team weekly and by an independent data and safety monitoring board on a continual basis. The trial Investigational New Drug sponsor, Moderna, was responsible for the overall trial design (with input from the Biomedical Advanced Research and Development Authority, the NIAID, the asthma treatment Prevention Network, and the trial cochairs), site selection and monitoring, and data analysis.

Investigators are responsible for data collection. A medical writer funded by Moderna assisted in drafting the manuscript for submission. The authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol.

The trial is ongoing, and the investigators remain unaware of participant-level data. Designated team members within Moderna have unblinded access to the data, to facilitate interface with the regulatory agencies and the data and safety monitoring board. All other trial staff and participants remain unaware of the treatment assignments.

Participants, Randomization, and Data Blinding Eligible participants were persons 18 years of age or older with no known history of asthma and with locations or circumstances that put them at an appreciable risk of asthma , a high risk of severe asthma treatment, or both. Inclusion and exclusion criteria are provided in the protocol (available with the full text of this article at NEJM.org). To enhance the diversity of the trial population in accordance with Food and Drug Administration Draft Guidance, site-selection and enrollment processes were adjusted to increase the number of persons from racial and ethnic minorities in the trial, in addition to the persons at risk for asthma in the local population.

The upper limit for stratification of enrolled participants considered to be “at risk for severe illness” at screening was increased from 40% to 50%.17 Participants were randomly assigned in a 1:1 ratio, through the use of a centralized interactive response technology system, to receive treatment or placebo. Assignment was stratified, on the basis of age and asthma treatment complications risk criteria, into the following risk groups. Persons 65 years of age or older, persons younger than 65 years of age who were at heightened risk (at risk) for severe asthma treatment, and persons younger than 65 years of age without heightened risk (not at risk).

Participants younger than 65 years of age were categorized as having risk for severe asthma treatment if they had at least one of the following risk factors, based on the Centers for Disease Control and Prevention (CDC) criteria available at the time of trial design. Chronic lung disease (e.g., emphysema, chronic bronchitis, idiopathic pulmonary fibrosis, cystic fibrosis, or moderate-to-severe asthma). Cardiac disease (e.g., heart failure, congenital coronary artery disease, cardiomyopathies, or pulmonary hypertension).

Severe obesity (body mass index [the weight in kilograms divided by the square of the height in meters] ≥40). Diabetes (type 1, type 2, or gestational). Liver disease.

Or with the human immunodeficiency ventolin.18 treatment dose preparation and administration were performed by pharmacists and treatment administrators who were aware of treatment assignments but had no other role in the conduct of the trial. Once the injection was completed, only trial staff who were unaware of treatment assignments performed assessments and interacted with the participants. Access to the randomization code was strictly controlled at the pharmacy.

The data and safety monitoring board reviewed efficacy data at the group level and unblinded safety data at the participant level. Trial treatment The mRNA-1273 treatment, provided as a sterile liquid at a concentration of 0.2 mg per milliliter, was administered by injection into the deltoid muscle according to a two-dose regimen. Injections were given 28 days apart, in the same arm, in a volume of 0.5 ml containing 100 μg of mRNA-1273 or saline placebo.1 treatment mRNA-1273 was stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and vaccination.

No dilution was required. Doses could be held in syringes for up to 8 hours at room temperature before administration. Safety Assessments Safety assessments included monitoring of solicited local and systemic adverse events for 7 days after each injection.

Unsolicited adverse reactions for 28 days after each injection. Adverse events leading to discontinuation from a dose, from participation in the trial, or both. And medically attended adverse events and serious adverse events from day 1 through day 759.

Adverse event grading criteria and toxicity tables are described in the protocol. Cases of asthma treatment and severe asthma treatment were continuously monitored by the data and safety monitoring board from randomization onward. Efficacy Assessments The primary end point was the efficacy of the mRNA-1273 treatment in preventing a first occurrence of symptomatic asthma treatment with onset at least 14 days after the second injection in the per-protocol population, among participants who were seronegative at baseline.

End points were judged by an independent adjudication committee that was unaware of group assignment. asthma treatment cases were defined as occurring in participants who had at least two of the following symptoms. Fever (temperature ≥38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder, or as occurring in those who had at least one respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia) and at least one nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if the participant was hospitalized) that was positive for asthma by reverse-transcriptase–polymerase-chain-reaction (RT-PCR) test.

Participants were assessed for the presence of asthma–binding antibodies specific to the asthma nucleocapsid protein (Roche Elecsys, Roche Diagnostics International) and had a nasopharyngeal swab for asthma RT-PCR testing (Viracor, Eurofins Clinical Diagnostics) before each injection. asthma–infected volunteers were followed daily, to assess symptom severity, for 14 days or until symptoms resolved, whichever was longer. A nasopharyngeal swab for RT-PCR testing and a blood sample for identifying serologic evidence of asthma were collected from participants with symptoms of asthma treatment.

The consistency of treatment efficacy at the primary end point was evaluated across various subgroups, including age groups (18 to <65 years of age and ≥65 years), age and health risk for severe disease (18 to <65 years and not at risk. 18 to <65 years and at risk. And ≥65 years), sex (female or male), race and ethnic group, and risk for severe asthma treatment illness.

If the number of participants in a subgroup was too small, it was combined with other subgroups for the subgroup analyses. A secondary end point was the efficacy of mRNA-1273 in the prevention of severe asthma treatment as defined by one of the following criteria. Respiratory rate of 30 or more breaths per minute.

Heart rate at or exceeding 125 beats per minute. Oxygen saturation at 93% or less while the participant was breathing ambient air at sea level or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen below 300 mm Hg. Respiratory failure.

Acute respiratory distress syndrome. Evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or a need for vasopressors). Clinically significant acute renal, hepatic, or neurologic dysfunction.

Admission to an intensive care unit. Or death. Additional secondary end points included the efficacy of the treatment at preventing asthma treatment after a single dose or at preventing asthma treatment according to a secondary (CDC), less restrictive case definition.

Having any symptom of asthma treatment and a positive asthma test by RT-PCR (see Table S1 in the Supplementary Appendix, available at NEJM.org). Statistical Analysis For analysis of the primary end point, the trial was designed for the null hypothesis that the efficacy of the mRNA-1273 treatment is 30% or less. A total of 151 cases of asthma treatment would provide 90% power to detect a 60% reduction in the hazard rate (i.e., 60% treatment efficacy), with two planned interim analyses at approximately 35% and 70% of the target total number of cases (151) and with a one-sided O’Brien–Fleming boundary for efficacy and an overall one-sided error rate of 0.025.

The efficacy of the mRNA-1273 treatment could be demonstrated at either the interim or the primary analysis, performed when the target total number of cases had been observed. The Lan–DeMets alpha-spending function was used for calculating efficacy boundaries at each analysis. At the first interim analysis on November 15, 2020, treatment efficacy had been demonstrated in accordance with the prespecified statistical criteria.

The treatment efficacy estimate, based on a total of 95 adjudicated cases (63% of the target total), was 94.5%, with a one-sided P value of less than 0.001 to reject the null hypothesis that treatment efficacy would be 30% or less. The data and safety monitoring board recommendation to the oversight group and the trial sponsor was that the efficacy findings should be shared with the participants and the community (full details are available in the protocol and statistical analysis plan). treatment efficacy was assessed in the full analysis population (randomized participants who received at least one dose of mRNA-1273 or placebo), the modified intention-to-treat population (participants in the full analysis population who had no immunologic or virologic evidence of asthma treatment on day 1, before the first dose), and the per-protocol population (participants in the modified intention-to-treat population who received two doses, with no major protocol deviations).

The primary efficacy end point in the interim and primary analyses was assessed in the per-protocol population. Participants were evaluated in the treatment groups to which they were assigned. treatment efficacy was defined as the percentage reduction in the hazard ratio for the primary end point (mRNA-1273 vs.

Placebo). A stratified Cox proportional hazards model was used to assess the treatment efficacy of mRNA-1273 as compared with placebo in terms of the percentage hazard reduction. (Details regarding the analysis of treatment efficacy are provided in the Methods section of the Supplementary Appendix.) Safety was assessed in all participants in the solicited safety population (i.e., those who received at least one injection and reported a solicited adverse event).

Descriptive summary data (numbers and percentages) for participants with any solicited adverse events, unsolicited adverse events, unsolicited severe adverse events, serious adverse events, medically attended adverse events, and adverse events leading to discontinuation of the injections or withdrawal from the trial are provided by group. Two-sided 95% exact confidence intervals (Clopper–Pearson method) are provided for the percentages of participants with solicited adverse events. Unsolicited adverse events are presented according to the Medical Dictionary for Regulatory Activities (MedDRA), version 23.0, preferred terms and system organ class categories.

To meet the regulatory agencies’ requirement of a median follow-up duration of at least 2 months after completion of the two-dose regimen, a second analysis was performed, with an efficacy data cutoff date of November 21, 2020. This second analysis is considered the primary analysis of efficacy, with a total of 196 adjudicated asthma treatment cases in the per-protocol population, which exceeds the target total number of cases (151) specified in the protocol. This was an increase from the 95 cases observed at the first interim analysis data cutoff on November 11, 2020.

Results from the primary analysis are presented in this report. Subsequent analyses are considered supplementary.Patients The cohort consisted of 3082 patients from 680 acute care facilities across the United States (Figure 1). Table 1 shows key characteristics of the patients, stratified into three groups according to anti–asthma IgG antibody levels (based on signal-to-cutoff ratios).

Overall, 61% of the patients were men, 23% were Black, 37% were Hispanic, 69% were younger than 70 years of age, and two thirds had received transfusions before invasive mechanical ventilation. The median number of patients per site was 2 (interquartile range, 1 to 6). The maximum number of patients from any single site was 59.

As shown in Table 1, the three groups (patients who received plasma transfusions with high, medium, and low IgG antibody levels) were generally similar in terms of demographic characteristics, risk factors associated with severe asthma treatment, and concomitant use of therapeutic agents for asthma treatment. The percentages of patients with hypoxemia and concomitant use of hydroxychloroquine (both of which were variables that were included in adjustment models) were lower in the high-titer group than in the other two groups. Primary Outcome Table 2.

Table 2. Models of the Association between Anti–asthma Antibody Levels in Transfused Plasma and the Risk of Death. Death within 30 days after plasma transfusion occurred in 26.9% of all the patients (830 of 3082 patients.

95% confidence interval [CI], 25.4 to 28.5). This primary-outcome event occurred in 29.6% (166 of 561 patients) in the low-titer group, 27.4% (549 of 2006 patients) in the medium-titer group, and 22.3% (115 of 515 patients) in the high-titer group. Patients in the high-titer group had a lower relative risk of death within 30 days after transfusion than patients in the low-titer group (relative risk, 0.75.

95% CI, 0.61 to 0.93) (Table 2). Additional analyses with adjustment for patient demographic characteristics (age, weight status, and race) and clinical characteristics (receipt of invasive mechanical ventilation, use of concomitant therapeutics, and hypoxemia) were conducted to evaluate the overall effect of the anti–asthma IgG antibody level on the risk of death within 30 days after transfusion (Table S1 in the Supplementary Appendix). The adjusted models (as defined in Table 2) generally showed a similar association — a lower relative risk of death among patients who received plasma transfusions with high anti–asthma IgG antibody levels (model 2, relative risk, 0.79 [95% CI, 0.65 to 0.96], and model 3 [with additional adjustment], relative risk, 0.82 [95% CI, 0.67 to 1.00]) (Table 2).

The findings of the sensitivity analysis in which patients were excluded at discharge were qualitatively similar to each of these findings. Subgroup Analysis Table 3. Table 3.

Characteristics of Patients with asthma treatment Who Were Not Receiving Mechanical Ventilation and Who Received Convalescent Plasma, According to Anti–asthma IgG Level. In the cohort of 3082 patients, 2014 patients did not receive mechanical ventilation before transfusion. Table 3 shows key patient characteristics of the subgroup of patients who were not receiving mechanical ventilation, stratified according to anti–asthma IgG antibody levels.

In the subgroup of patients who were not receiving mechanical ventilation, death within 30 days after plasma transfusion occurred in 81 of 365 patients (22.2%. 95% CI, 18.2 to 26.7) in the low-titer group, 251 of 1297 patients (19.4%. 95% CI, 17.3 to 21.6) in the medium-titer group, and 50 of 352 patients (14.2%.

95% CI, 10.9 to 18.2) in the high-titer group. Table S4 shows these results in the subgroup of patients who were receiving mechanical ventilation. In the subgroup of patients who were receiving mechanical ventilation, death within 30 days after plasma transfusion occurred in 80 of 183 patients (43.7%.

95% CI, 36.7 to 51.0) in the low-titer group, 277 of 666 patients (41.6%. 95% CI, 37.9 to 45.4) in the medium-titer group, and 64 of 158 patients (40.5. 95% CI, 33.2 to 48.3) in the high-titer group.

In both subgroups, the characteristics of the patients were well balanced across the three antibody-titer groups. In the fully adjusted relative risk regression model, the lower risk of death within 30 days after plasma transfusion in the high-titer group than in the low-titer group was observed among patients who were not receiving mechanical ventilation before transfusion (relative risk, 0.66. 95% CI, 0.48 to 0.91).

No effect on mortality was observed among patients who received mechanical ventilation before transfusion (relative risk, 1.02. 95% CI, 0.78 to 1.32). Table S2 shows relative-risk regression with or without full adjustment for patient demographic characteristics, anti–asthma IgG antibody levels, clinical characteristics, and study time period, including all three models (the base model, model 2, and model 3), for the subgroup of patients who were not receiving mechanical ventilation.

Table S3 shows relative-risk regression for the subgroup of patients who were receiving mechanical ventilation. Figure 2. Figure 2.

Relative Risk of Death within 30 Days after Convalescent Plasma Transfusion. Forest plots of the relative risks of death associated with medium versus low antibody levels (Panel A) and high versus low antibody levels (Panel B) are shown. The subgroups are 12 mutually exclusive categories of the time period of the study in 2020, patient age, and ventilator support in patients who received transfusions of convalescent plasma.

Shown are the estimated relative risks of death among patients who received convalescent plasma with IgG signal-to-cutoff ratios in the range of 4.62 to 18.45 (medium titer) or more than 18.45 (high titer), as compared with the relative risks among those who received plasma with IgG signal-to-cutoff ratios below 4.62 (low titer). The pooled estimates from all the subgroups are based on the Mantel–Haenszel estimator. Table S5 provides the sample sizes and number of deaths in each subgroup.

Н™¸ bars indicate 95% confidence intervals.These findings were further supported by a stratified-data analytic approach that provided direct analytic control for the key variables associated with the risk of death (age, receipt of invasive mechanical ventilation, and study time period) (Figure 2). The pooled (or common) relative risk of death among all the patients within 30 days after plasma transfusion in the high-titer group, as compared with the low-titer group, was 0.80 (95% CI, 0.65 to 0.97) (Figure 2). Figure S1 shows the risk of death within 7 days after transfusion of convalescent plasma, as determined with this stratified data analytic approach.

Exploratory Analyses Among patients who received mechanical ventilation before transfusion, the mean (±SD) number of days between the diagnosis of asthma treatment and the transfusion of convalescent plasma was 10.0±7.7. This was nearly double the mean number of days among patients who were not receiving mechanical ventilation (5.4±4.8). The unadjusted mortality within 30 days after transfusion was lower among patients who received a transfusion within 3 days after receiving a diagnosis of asthma treatment (point estimate, 22.2%.

95% CI, 19.9 to 24.8) than among those who received a transfusion 4 or more days after receiving a diagnosis of asthma treatment (point estimate, 29.5%. 95% CI, 27.6 to 31.6). In model 3, the replacement of ventilation status with a binary classification of days to transfusion resulted in a relative risk of death of 1.18 (95% CI, 1.04 to 1.35) among patients who received a transfusion 4 or more days after receiving the diagnosis.

This effect size was lower than that observed in patients who had previously received mechanical ventilation in model 3 (relative risk, 2.16. 95% CI, 1.90 to 2.46). The trained gradient-boosting machine was used to estimate the relationship between key variables associated with risk of death within 30 days after plasma transfusion and mortality at 30 days.

Two methods were used to explore how this machine-learning technique linked the key variables with the mortality predictions. In the first method, a variable importance plot was generated for each variable included in the model (Fig. S2).

The “importance” of the variable is the relative amount by which it improves the prediction, both in terms of location in the decision trees (where more observations are classified higher up in the decision tree) and in the number of times it is used in the collection of trees. The primary variables associated with a risk of death at 30 days were age. Evidence of an advanced clinical course of asthma treatment, such as the receipt of invasive mechanical ventilation and admission to an intensive care unit (ICU).

And the anti–asthma antibody level, in order of variable importance. The second method used to explore the association between a given variable and prediction of mortality was by means of a partial dependence plot. The partial dependence plot shows that after adjustment for all other variables included in the model, anti–asthma IgG antibody levels maintained an inverse relationship with the risk of death.

Figure S3 shows similar partial dependence plots for the primary analysis model in which the antibody levels were treated as a continuous variable with the use of a natural spline with four evenly spaced knots. In this model, the partial dependence plot for the overall sample aligned closely with the pattern observed in the gradient-boosting machine model. The inverse relationship with antibody levels was again observed in the patients who were not receiving mechanical ventilation, and there was a general lack of a clear association in these patients.Patients Figure 1.

Figure 1. Enrollment and Randomization. Of the 1114 patients who were assessed for eligibility, 1062 underwent randomization.

541 were assigned to the remdesivir group and 521 to the placebo group (intention-to-treat population) (Figure 1). 159 (15.0%) were categorized as having mild-to-moderate disease, and 903 (85.0%) were in the severe disease stratum. Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned.

Fifty-two patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death and 10 withdrew consent. Of those assigned to receive placebo, 517 patients (99.2%) received placebo as assigned. Seventy patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death and 14 withdrew consent.

A total of 517 patients in the remdesivir group and 508 in the placebo group completed the trial through day 29, recovered, or died. Fourteen patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. A total of 54 of the patients who were in the mild-to-moderate stratum at randomization were subsequently determined to meet the criteria for severe disease, resulting in 105 patients in the mild-to-moderate disease stratum and 957 in the severe stratum.

The as-treated population included 1048 patients who received the assigned treatment (532 in the remdesivir group, including one patient who had been randomly assigned to placebo and received remdesivir, and 516 in the placebo group). Table 1. Table 1.

Demographic and Clinical Characteristics of the Patients at Baseline. The mean age of the patients was 58.9 years, and 64.4% were male (Table 1). On the basis of the evolving epidemiology of asthma treatment during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1 in the Supplementary Appendix).

Overall, 53.3% of the patients were White, 21.3% were Black, 12.7% were Asian, and 12.7% were designated as other or not reported. 250 (23.5%) were Hispanic or Latino. Most patients had either one (25.9%) or two or more (54.5%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (50.2%), obesity (44.8%), and type 2 diabetes mellitus (30.3%).

The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12) (Table S2). A total of 957 patients (90.1%) had severe disease at enrollment. 285 patients (26.8%) met category 7 criteria on the ordinal scale, 193 (18.2%) category 6, 435 (41.0%) category 5, and 138 (13.0%) category 4.

Eleven patients (1.0%) had missing ordinal scale data at enrollment. All these patients discontinued the study before treatment. During the study, 373 patients (35.6% of the 1048 patients in the as-treated population) received hydroxychloroquine and 241 (23.0%) received a glucocorticoid (Table S3).

Primary Outcome Figure 2. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries.

Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen. Panel B), in those with a baseline score of 5 (receiving oxygen. Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation.

Panel D), and in those with a baseline score of 7 (receiving mechanical ventilation or extracorporeal membrane oxygenation [ECMO]. Panel E).Table 2. Table 2.

Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3. Figure 3.

Time to Recovery According to Subgroup. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients.Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 10 days, as compared with 15 days.

Rate ratio for recovery, 1.29. 95% confidence interval [CI], 1.12 to 1.49. P<0.001) (Figure 2 and Table 2).

In the severe disease stratum (957 patients) the median time to recovery was 11 days, as compared with 18 days (rate ratio for recovery, 1.31. 95% CI, 1.12 to 1.52) (Table S4). The rate ratio for recovery was largest among patients with a baseline ordinal score of 5 (rate ratio for recovery, 1.45.

95% CI, 1.18 to 1.79). Among patients with a baseline score of 4 and those with a baseline score of 6, the rate ratio estimates for recovery were 1.29 (95% CI, 0.91 to 1.83) and 1.09 (95% CI, 0.76 to 1.57), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal score of 7), the rate ratio for recovery was 0.98 (95% CI, 0.70 to 1.36).

Information on interactions of treatment with baseline ordinal score as a continuous variable is provided in Table S11. An analysis adjusting for baseline ordinal score as a covariate was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a similar treatment-effect estimate (rate ratio for recovery, 1.26.

95% CI, 1.09 to 1.46). Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.37 (95% CI, 1.14 to 1.64), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.20 (95% CI, 0.94 to 1.52) (Figure 3). The benefit of remdesivir was larger when given earlier in the illness, though the benefit persisted in most analyses of duration of symptoms (Table S6).

Sensitivity analyses in which data were censored at earliest reported use of glucocorticoids or hydroxychloroquine still showed efficacy of remdesivir (9.0 days to recovery with remdesivir vs. 14.0 days to recovery with placebo. Rate ratio, 1.28.

95% CI, 1.09 to 1.50, and 10.0 vs. 16.0 days to recovery. Rate ratio, 1.32.

95% CI, 1.11 to 1.58, respectively) (Table S8). Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.5. 95% CI, 1.2 to 1.9, adjusted for disease severity) (Table 2 and Fig.

S7). Mortality Kaplan–Meier estimates of mortality by day 15 were 6.7% in the remdesivir group and 11.9% in the placebo group (hazard ratio, 0.55. 95% CI, 0.36 to 0.83).

The estimates by day 29 were 11.4% and 15.2% in two groups, respectively (hazard ratio, 0.73. 95% CI, 0.52 to 1.03). The between-group differences in mortality varied considerably according to baseline severity (Table 2), with the largest difference seen among patients with a baseline ordinal score of 5 (hazard ratio, 0.30.

95% CI, 0.14 to 0.64). Information on interactions of treatment with baseline ordinal score with respect to mortality is provided in Table S11. Additional Secondary Outcomes Table 3.

Table 3. Additional Secondary Outcomes. Patients in the remdesivir group had a shorter time to improvement of one or of two categories on the ordinal scale from baseline than patients in the placebo group (one-category improvement.

Median, 7 vs. 9 days. Rate ratio for recovery, 1.23.

95% CI, 1.08 to 1.41. Two-category improvement. Median, 11 vs.

14 days. Rate ratio, 1.29. 95% CI, 1.12 to 1.48) (Table 3).

Patients in the remdesivir group had a shorter time to discharge or to a National Early Warning Score of 2 or lower than those in the placebo group (median, 8 days vs. 12 days. Hazard ratio, 1.27.

95% CI, 1.10 to 1.46). The initial length of hospital stay was shorter in the remdesivir group than in the placebo group (median, 12 days vs. 17 days).

5% of patients in the remdesivir group were readmitted to the hospital, as compared with 3% in the placebo group. Among the 913 patients receiving oxygen at enrollment, those in the remdesivir group continued to receive oxygen for fewer days than patients in the placebo group (median, 13 days vs. 21 days), and the incidence of new oxygen use among patients who were not receiving oxygen at enrollment was lower in the remdesivir group than in the placebo group (incidence, 36% [95% CI, 26 to 47] vs.

44% [95% CI, 33 to 57]). For the 193 patients receiving noninvasive ventilation or high-flow oxygen at enrollment, the median duration of use of these interventions was 6 days in both the remdesivir and placebo groups. Among the 573 patients who were not receiving noninvasive ventilation, high-flow oxygen, invasive ventilation, or ECMO at baseline, the incidence of new noninvasive ventilation or high-flow oxygen use was lower in the remdesivir group than in the placebo group (17% [95% CI, 13 to 22] vs.

24% [95% CI, 19 to 30]). Among the 285 patients who were receiving mechanical ventilation or ECMO at enrollment, patients in the remdesivir group received these interventions for fewer subsequent days than those in the placebo group (median, 17 days vs. 20 days), and the incidence of new mechanical ventilation or ECMO use among the 766 patients who were not receiving these interventions at enrollment was lower in the remdesivir group than in the placebo group (13% [95% CI, 10 to 17] vs.

23% [95% CI, 19 to 27]) (Table 3). Safety Outcomes In the as-treated population, serious adverse events occurred in 131 of 532 patients (24.6%) in the remdesivir group and in 163 of 516 patients (31.6%) in the placebo group (Table S17). There were 47 serious respiratory failure adverse events in the remdesivir group (8.8% of patients), including acute respiratory failure and the need for endotracheal intubation, and 80 in the placebo group (15.5% of patients) (Table S19).

No deaths were considered by the investigators to be related to treatment assignment. Grade 3 or 4 adverse events occurred on or before day 29 in 273 patients (51.3%) in the remdesivir group and in 295 (57.2%) in the placebo group (Table S18). 41 events were judged by the investigators to be related to remdesivir and 47 events to placebo (Table S17).

The most common nonserious adverse events occurring in at least 5% of all patients included decreased glomerular filtration rate, decreased hemoglobin level, decreased lymphocyte count, respiratory failure, anemia, pyrexia, hyperglycemia, increased blood creatinine level, and increased blood glucose level (Table S20). The incidence of these adverse events was generally similar in the remdesivir and placebo groups. Crossover After the data and safety monitoring board recommended that the preliminary primary analysis report be provided to the sponsor, data on a total of 51 patients (4.8% of the total study enrollment) — 16 (3.0%) in the remdesivir group and 35 (6.7%) in the placebo group — were unblinded.

26 (74.3%) of those in the placebo group whose data were unblinded were given remdesivir. Sensitivity analyses evaluating the unblinding (patients whose treatment assignments were unblinded had their data censored at the time of unblinding) and crossover (patients in the placebo group treated with remdesivir had their data censored at the initiation of remdesivir treatment) produced results similar to those of the primary analysis (Table S9)..

Participants Figure How much does levitra cost per pill 1 can u buy ventolin over the counter. Figure 1. Enrollment and Randomization can u buy ventolin over the counter. The diagram represents all enrolled participants through November 14, 2020.

The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an can u buy ventolin over the counter October 9, 2020, data cut-off date. The further procedures that one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1. Table 1. Demographic Characteristics of the can u buy ventolin over the counter Participants in the Main Safety Population.

Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 sites worldwide (United States, 130 sites. Argentina, 1 can u buy ventolin over the counter. Brazil, 2. South Africa, 4.

Germany, 6 can u buy ventolin over the counter. And Turkey, 9) in the phase 2/3 portion of the trial. A total of can u buy ventolin over the counter 43,448 participants received injections. 21,720 received BNT162b2 and 21,728 received placebo (Figure 1).

At the data cut-off date of October 9, a total of 37,706 can u buy ventolin over the counter participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height in meters] of at least 30.0), and 21% had at least one coexisting condition. The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local Reactogenicity Figure can u buy ventolin over the counter 2.

Figure 2. Local and Systemic Reactions Reported can u buy ventolin over the counter within 7 Days after Injection of BNT162b2 or Placebo, According to Age Group. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown in Panel A.

Pain at the injection site can u buy ventolin over the counter was assessed according to the following scale. Mild, does not interfere with activity. Moderate, interferes can u buy ventolin over the counter with activity. Severe, prevents daily activity.

And grade 4, emergency department visit can u buy ventolin over the counter or hospitalization. Redness and swelling were measured according to the following scale. Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to can u buy ventolin over the counter 10.0 cm in diameter.

Severe, >10.0 cm in diameter. And grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis can u buy ventolin over the counter (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated in the key.

Medication use was can u buy ventolin over the counter not graded. Additional scales were as follows. Fatigue, headache, can u buy ventolin over the counter chills, new or worsened muscle pain, new or worsened joint pain (mild. Does not interfere with activity.

Moderate. Some interference with activity. Or severe. Prevents daily activity), vomiting (mild.

1 to 2 times in 24 hours. Moderate. >2 times in 24 hours. Or severe.

Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate. 4 to 5 loose stools in 24 hours.

Or severe. 6 or more loose stools in 24 hours). Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants.

Overall, BNT162b2 recipients reported more local reactions than placebo recipients. Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose.

78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction. In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days.

Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients. 51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients).

The frequency of any severe systemic event after the first dose was 0.9% or less. Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1. 38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose.

Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter. Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose. No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3).

More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%). This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial.

Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo. No asthma treatment–associated deaths were observed.

No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment. Efficacy Table 2. Table 2.

treatment Efficacy against asthma treatment at Least 7 days after the Second Dose. Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2.

Figure 3. Figure 3. Efficacy of BNT162b2 against asthma treatment after the First Dose. Shown is the cumulative incidence of asthma treatment after the first dose (modified intention-to-treat population).

Each symbol represents asthma treatment cases starting on a given day. Filled symbols represent severe asthma treatment cases. Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days.

Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for asthma treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior asthma , 8 cases of asthma treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6.

Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of asthma treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4). treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%.

95% CI, 68.7 to 99.9. Case split. BNT162b2, 2 cases. Placebo, 44 cases).

Figure 3 shows cases of asthma treatment or severe asthma treatment with onset at any time after the first dose (mITT population) (additional data on severe asthma treatment are available in Table S5). Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.Participants From July 22 to August 7, 2020, a total of 593 persons underwent screening for enrollment in cohort 1 (including 1a and 1b combined) (Fig. S1). Of these persons, 405 were enrolled and 402 received the first dose of Ad26.COV2.S.

These participants had received the second dose by November 7, 2020. From August 3 to August 24, 2020, a total of 660 persons underwent screening for cohort 3. Of these participants, 405 were enrolled and 403 received the first dose of Ad26.COV2.S. (Details regarding age distribution are provided in Table S2.) Analyses of data obtained from participants in cohort 3 after the administration of the second dose, as well as durability and longer-term safety data, are ongoing.

Table 1. Table 1. Characteristics of the Participants at Baseline. At baseline, the percentage of participants who were seropositive for asthma S-specific antibodies was 2% in cohort 1a and 1% in cohort 3.

The baseline characteristics of the participants were broadly similar across the groups (Table 1). treatment Safety and Reactogenicity Figure 1. Figure 1. Solicited Adverse Events in Cohorts 1 and 3 after the First treatment Dose.

Shown are solicited adverse events in participants who received the Ad26.COV2.S treatment at a dose of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) per milliliter or placebo. Healthy adults between the ages of 18 and 55 years were included in cohort 1 (Panel A), and those 65 years of age or older were included in cohort 3 (Panel B). The younger group was divided into cohorts 1a and 1b, with the latter designated as an exploratory cohort for in-depth analysis of immunogenicity. As shown here, data for cohorts 1a and 1b have been pooled.

Data for patients in cohort 1a who received a second dose of treatment are provided in Figure S2 in the Supplementary Appendix.Data regarding both solicited and unsolicited adverse events and serious adverse events were available for more than 99% of the participants who returned diary cards. The investigator’s assessment of reactogenicity after the administration of the first dose of treatment was available for 402 participants in cohort 1 and for 403 participants in cohort 3. In the two cohorts, solicited local adverse events were mostly of grade 1 or 2. The most frequent event was injection-site pain.

In cohort 1, solicited local adverse events were reported in 103 of 162 low-dose recipients (64%), in 123 of 158 high-dose recipients (78%), and in 7 of 82 placebo recipients (9%) (Figure 1A and Table S3). In cohort 3, solicited local adverse events were reported in 66 of 161 low-dose recipients (41%), in 68 of 161 high-dose recipients (42%), and in 11 of 81 placebo recipients (14%) (Figure 1B). In the two cohorts, most solicited systemic adverse events were of grade 1 or 2. The most frequent events were fatigue, headache, and myalgia.

In cohort 1, solicited systemic adverse events were reported in 105 low-dose recipients (65%), in 133 high-dose recipients (84%), and in 21 placebo recipients (26%). In cohort 3, solicited systemic adverse events were reported in 74 low-dose recipients (46%), in 88 high-dose recipients (55%), and in 19 placebo recipients (23%). In cohort 1, solicited grade 3 systemic adverse events were reported in 15 low-dose recipients (9%) and in 32 high-dose recipients (20%). No placebo recipients reported such events.

In cohort 1a, among the participants between the ages of 18 and 30 years who had one or more solicited grade 3 adverse events, 24% had received the low dose and 26% had received the high dose. In those between the ages of 31 and 45 years, the corresponding percentages were 43% and 14%. And in those between the ages of 46 and 55 years, the corresponding percentages were 3% and 11%. In cohort 3, grade 3 solicited systemic adverse events were reported in 1 low-dose recipient (1%) and in 4 high-dose recipients (2%).

No placebo recipients reported having such events. In cohort 1, fever was reported in 25 low-dose recipients (15%) and in 62 high-dose recipients (39%). Grade 3 fever (temperature range, 39.0 to 40.0°C) was reported in 8 low-dose recipients (5%) and in 15 high-dose recipients (9%). In cohort 3, fever was reported in 7 low-dose recipients (4%) and in 14 high-dose recipients (9%).

Grade 3 fever was reported in no low-dose recipients and in 2 high-dose recipients (1%). No participants in the placebo group in either cohort reported having fever. All cases of fever occurred within 2 days after immunization and resolved within 1 or 2 days. More than 80% of the participants with fever received an antipyretic drug at the onset of symptoms.

In cohort 1, unsolicited adverse events were reported in 34 low-dose recipients (21%), in 56 high-dose recipients (35%), and in 14 placebo recipients (17%). In cohort 3, unsolicited adverse events were reported in 27 low-dose recipients (17%), in 38 high-dose recipients (24%), and in 13 placebo recipients (16%) (Table S4). No grade 4 adverse events (solicited or unsolicited) were reported in any cohort. In cohort 1a, safety data after the administration of the second dose of treatment were available for 363 participants (Fig.

S2). One or more solicited adverse events were noted in 77% and 80% of the participants in the low-dose and high-dose groups, respectively, as compared with 34% and 31% of those who received placebo as a second dose after a first dose of treatment and in 22% of those who received placebo for both doses. Solicited adverse events of grade 3 or higher were noted in 1% of low-dose recipients and in 7% of high-dose recipients. The corresponding percentages were 1% and 2% among participants in the placebo group who received a first dose of treatment and in no participants who received placebo for both doses.

No grade 3 fevers were reported in any group after a second dose of treatment. No participant discontinued the trial because of an adverse event. Five serious adverse events occurred. One case of hypotension that was deemed by the investigator to be unrelated to the treatment because of a history of recurrent hypotension.

One case of bilateral nephrolithiasis in a participant with a history of kidney stones (not related). One case of legionella pneumonia (not related). One worsening of multiple sclerosis, which had remained undiagnosed for approximately 8 to 10 years on the basis of findings on magnetic resonance imaging (not related). And one case of fever that resulted in hospitalization because of suspicion of asthma treatment.

In the last case, the participant recovered within 12 hours, and the fever was subsequently deemed by the investigator to be related to the treatment. Details regarding all safety data are provided in the Supplementary Appendix. Immunogenicity and Seroconversion Figure 2. Figure 2.

Humoral Immunogenicity. Shown are measures of humoral immunogenicity in serum samples obtained from the participants in cohort 1a (left side) and cohort 3 (right side), according to the receipt of the low or high dose of Ad26.COV2.S or placebo. In cohort 1a, the participants received two injections of high-dose or low-dose treatment or placebo, as indicated with slashes (e.g., placebo/placebo if they received two injections of placebo). The samples were measured on enzyme-linked immunosorbent assay (ELISA) in ELISA units (EU) per milliliter (Panel A) and on wild-type ventolin neutralization assay, with seropositivity defined as a half maximal inhibitory concentration (IC50) titer of more than 58 at the lower limit of quantitation (Panel B).

Logarithmic values are reported as the geometric mean concentration (GMC) in the ELISA analyses and as the geometric mean titer (GMT) in the neutralizing-antibody analyses. The values were measured at baseline and at day 29 after vaccination in all the participants and on days 57 and 71 in those in cohort 1a. The two horizontal dotted lines in each panel indicate the lower and upper limits of quantitation of the respective assay. Values below the lower line have been imputed to half the lower limit of quantitation.

Н™¸ bars indicate 95% confidence intervals. HCS denotes human convalescent serum.Immunogenicity data for this interim analysis were unblinded according to dose level. In all five groups in cohort 1a, the binding-antibody geometric mean concentration (GMC), as reported in ELISA units per milliliter, was measured against a stabilized asthma full-length spike protein. At baseline, the GMC values in all the participants were lower than the lower limit of quantitation.

By day 29 after vaccination, the values had increased to 478 (95% confidence interval [CI], 379 to 603) in the low-dose/placebo group, 586 (95% CI, 445 to 771) in the low-dose/low-dose group, 625 (95% CI, 505 to 773) in the high-dose/placebo group, and 788 (95% CI, 628 to 988) in the high-dose/high-dose group, with an incidence of seroconversion of 99% or more in all the groups (Figure 2A and Fig. S3A). By day 57, the corresponding GMC values had further increased to 660 (95% CI, 513 to 849), 754 (95% CI, 592 to 961), 873 (95% CI, 701 to 1087), and 1100 (95% CI, 908 to 1332). After the first dose, the incidence of seroconversion was 100% in all but the high-dose/placebo group (97%).

Fourteen days after the second dose, the GMC was 1677 (95% CI, 1334 to 2109) in the low-dose/low-dose group and 2292 (95% CI, 1846 to 2845) in the high-dose/high-dose group, with 100% seroconversion in each group. On day 71, in the low-dose/placebo and high-dose/placebo groups, the GMC was 600 (95% CI, 443 to 814) and 951 (95% CI, 696 to 1,300), respectively, values that were similar to those on day 57. In cohort 3, the GMCs in all the participants were also below the lower limit of quantitation at baseline. By day 15 after vaccination, the GMC had increased to 122 (95% CI, 97 to 152) in the low-dose group and to 141 (95% CI, 114 to 175) in the high-dose group, with a seroconversion incidence of 75% and 77%, respectively.

By day 29, the GMC was 312 (95% CI, 246 to 396) in the low-dose group and 350 (95% CI, 281 to 429) in the high-dose group, with 96% seroconversion. The asthma neutralizing-antibody titer (IC50) was measured in a random subgroup of participants in cohorts 1a and 3. In cohort 1a, the geometric mean titer (GMT) was below the lower limit of quantitation at baseline and by day 29 after vaccination had increased to 224 (95% CI, 158 to 318) in the low-dose/placebo group, 224 (95% CI, 168 to 298) in the low-dose/low-dose group, 215 (95% CI, 169 to 273) in the high-dose/placebo group, and 354 (95% CI, 220 to 571) in the high-dose/high-dose group, with an incidence of seroconversion of 96%, 88%, 96%, and 92%, respectively (Figure 2B and Fig. S3B).

By day 57, the GMT had further increased to 310 (95% CI, 228 to 422), 288 (95% CI, 221 to 376), 370 (95% CI, 268 to 511), and 488 (95% CI, 334 to 714), respectively, with a 100% incidence of seroconversion in the low-dose/placebo group and 96% seroconversion in the other groups. In cohort 1a, 14 days after the second dose, the GMT was 827 (95% CI, 508 to 1183) in the low-dose/low-dose group and 1266 (95% CI, 746 to 2169) in the high-dose/high-dose group, with 100% seroconversion in the two dose groups. On day 71, the GMT was 321 (95% CI, 227 to 438) in the low-dose/placebo group and 388 (95% CI, 290 to 509) in the high-dose/placebo group, values that were similar to those on day 57. The incidence of seroconversion was 100% in both groups.

In cohort 3, the GMTs in all the participants were below the lower limit of quantitation at baseline and had increased to 212 (95% CI, 137 to 284) in the low-dose group and 172 (95% CI, 119 to 269) in the high-dose group on day 15 and to 277 (95% CI, 193 to 307) and 212 (95% CI, 163 to 266), respectively, on day 29. The incidence of seroconversion was 91% and 84%, respectively, on day 15 and 96% and 88%, respectively, on day 29. These data were confirmed on IC80 analysis (Fig. S4).

Antibody levels as measured on wild-type ventolin neutralization assay and ELISA were strongly correlated in the two cohorts (Fig. S5). However, the correlation had a wider elliptical shape in cohort 3, which suggested more variability in the relationship between the neutralizing-antibody titer and the binding-antibody titer in the older adults. Antibody levels in the different human convalescent serum panels that were included in assays for humoral-immunity assessment that were performed in different laboratories and in serum samples that were obtained from treatment recipients were in the same range.

Details regarding differences in values according to demographic characteristics are provided in Tables S5 and S6 in the Supplementary Appendix. Levels of Ad26 neutralizing antibodies at baseline or after the first dose of treatment did not correlate with the levels of asthma neutralizing antibodies on either day 29 or day 71 (Fig. S6). S-Specific T-Cell Responses Figure 3.

Figure 3. Cellular Immunogenicity of Ad26.COV2.S. In CD4+ T cells, the response to low-dose or high-dose treatment or placebo in type 1 helper T (Th1) cells was characterized by the expression of interferon-γ, interleukin-2, or both, without cytokines expressed by type 2 helper T (Th2) cells (Panel A). The response in CD4+ Th2 cells was characterized by the expression of interleukin-4, interleukin-5, or interleukin-13 (or all three cytokines) plus CD40L (Panel B).

In CD8+ T cells, the response was measured by the expression of interferon-γ, interleukin-2, or both (Panel C). In all three panels, the horizontal bars indicate median values on intracellular cytokine staining for individual responses to a asthma S protein peptide pool in peripheral-blood mononuclear cells at baseline and 15 days after vaccination in a subgroup of participants in cohort 1a (left side) and cohort 3 (right side), according to the receipt of the low or high dose of Ad26.COV2.S or placebo. The horizontal dotted line in each panel indicates the lower limit of quantitation (LLOQ). Values below the line have been imputed to half the LLOQ.The treatment-elicited responses in S-specific CD4+ Th1 and Th2 cells and in CD8+ T cells were assessed in a subgroup of participants at baseline and 15 days after the first dose.

In cohort 1a, a Th1 response to S peptides was detected in 76% (95% CI, 65 to 86) of low-dose recipients and in 83% (95% CI, 73 to 91) of high-dose recipients. The corresponding values in cohort 3 were 60% (95% CI, 46 to 74) and 67% (95% CI, 53 to 79), respectively (Figure 3A). In cohort 1a, the median CD4+ Th1 response to S peptides increased from an undetectable level at baseline to a median of 0.08% (interquartile range [IQR], 0.05 to 0.16) in low-dose recipients and 0.11% (IQR, 0.07 to 0.16) in high-dose recipients on day 15. In cohort 3, the corresponding values were 0.09% (IQR, 0.04 to 0.17) and 0.11% (IQR, 0.04 to 0.15), respectively.

A low-dose recipient in cohort 1a and a high-dose recipient in cohort 3 had a measurable Th2 response (Figure 3B). However, all the participants who had a measurable Th1 or Th2 response had a Th1:Th2 ratio that was well above 1, which indicated a treatment-induced Th1-skewed response. S-specific CD8+ T-cell responses, as identified by the expression of interferon-γ or interleukin-2 cytokines on S-peptide stimulation, were absent at baseline in the two cohorts (Figure 3C). On day 15 in cohort 1a, a CD8+ T-cell response was detected in 51% of participants (95% CI, 39 to 63) in the low-dose group and in 64% (95% CI, 52 to 75) in the high-dose group, with a median S-specific CD8+ T-cell response of 0.07% (IQR, 0.03 to 0.19) and 0.09% (IQR, 0.05 to 0.19), respectively.

In cohort 3, CD8+ T-cell responses were lower, with an incidence of 36% (95% CI, 23 to 51) in the low-dose group and 24% (95% CI, 13 to 37) in the high-dose group, with a median response of 0.06% (IQR, 0.02 to 0.12) and 0.02% (IQR, 0.01 to 0.08), respectively. The correlation between CD4+ Th1 and CD8+ T-cell response was poor in the two cohorts (Fig. S7).Trial Oversight This phase 3 randomized, stratified, observer-blinded, placebo-controlled trial enrolled adults in medically stable condition at 99 U.S. Sites.

Participants received the first trial injection between July 27 and October 23, 2020. The trial is being conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Good Clinical Practice guidelines, and applicable government regulations. The central institutional review board approved the protocol and the consent forms. All participants provided written informed consent before enrollment.

Safety is reviewed by a protocol safety review team weekly and by an independent data and safety monitoring board on a continual basis. The trial Investigational New Drug sponsor, Moderna, was responsible for the overall trial design (with input from the Biomedical Advanced Research and Development Authority, the NIAID, the asthma treatment Prevention Network, and the trial cochairs), site selection and monitoring, and data analysis. Investigators are responsible for data collection. A medical writer funded by Moderna assisted in drafting the manuscript for submission.

The authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. The trial is ongoing, and the investigators remain unaware of participant-level data. Designated team members within Moderna have unblinded access to the data, to facilitate interface with the regulatory agencies and the data and safety monitoring board. All other trial staff and participants remain unaware of the treatment assignments.

Participants, Randomization, and Data Blinding Eligible participants were persons 18 years of age or older with no known history of asthma and with locations or circumstances that put them at an appreciable risk of asthma , a high risk of severe asthma treatment, or both. Inclusion and exclusion criteria are provided in the protocol (available with the full text of this article at NEJM.org). To enhance the diversity of the trial population in accordance with Food and Drug Administration Draft Guidance, site-selection and enrollment processes were adjusted to increase the number of persons from racial and ethnic minorities in the trial, in addition to the persons at risk for asthma in the local population. The upper limit for stratification of enrolled participants considered to be “at risk for severe illness” at screening was increased from 40% to 50%.17 Participants were randomly assigned in a 1:1 ratio, through the use of a centralized interactive response technology system, to receive treatment or placebo.

Assignment was stratified, on the basis of age and asthma treatment complications risk criteria, into the following risk groups. Persons 65 years of age or older, persons younger than 65 years of age who were at heightened risk (at risk) for severe asthma treatment, and persons younger than 65 years of age without heightened risk (not at risk). Participants younger than 65 years of age were categorized as having risk for severe asthma treatment if they had at least one of the following risk factors, based on the Centers for Disease Control and Prevention (CDC) criteria available at the time of trial design. Chronic lung disease (e.g., emphysema, chronic bronchitis, idiopathic pulmonary fibrosis, cystic fibrosis, or moderate-to-severe asthma).

Cardiac disease (e.g., heart failure, congenital coronary artery disease, cardiomyopathies, or pulmonary hypertension). Severe obesity (body mass index [the weight in kilograms divided by the square of the height in meters] ≥40). Diabetes (type 1, type 2, or gestational). Liver disease.

Or with the human immunodeficiency ventolin.18 treatment dose preparation and administration were performed by pharmacists and treatment administrators who were aware of treatment assignments but had no other role in the conduct of the trial. Once the injection was completed, only trial staff who were unaware of treatment assignments performed assessments and interacted with the participants. Access to the randomization code was strictly controlled at the pharmacy. The data and safety monitoring board reviewed efficacy data at the group level and unblinded safety data at the participant level.

Trial treatment The mRNA-1273 treatment, provided as a sterile liquid at a concentration of 0.2 mg per milliliter, was administered by injection into the deltoid muscle according to a two-dose regimen. Injections were given 28 days apart, in the same arm, in a volume of 0.5 ml containing 100 μg of mRNA-1273 or saline placebo.1 treatment mRNA-1273 was stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and vaccination. No dilution was required. Doses could be held in syringes for up to 8 hours at room temperature before administration.

Safety Assessments Safety assessments included monitoring of solicited local and systemic adverse events for 7 days after each injection. Unsolicited adverse reactions for 28 days after each injection. Adverse events leading to discontinuation from a dose, from participation in the trial, or both. And medically attended adverse events and serious adverse events from day 1 through day 759.

Adverse event grading criteria and toxicity tables are described in the protocol. Cases of asthma treatment and severe asthma treatment were continuously monitored by the data and safety monitoring board from randomization onward. Efficacy Assessments The primary end point was the efficacy of the mRNA-1273 treatment in preventing a first occurrence of symptomatic asthma treatment with onset at least 14 days after the second injection in the per-protocol population, among participants who were seronegative at baseline. End points were judged by an independent adjudication committee that was unaware of group assignment.

asthma treatment cases were defined as occurring in participants who had at least two of the following symptoms. Fever (temperature ≥38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder, or as occurring in those who had at least one respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia) and at least one nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if the participant was hospitalized) that was positive for asthma by reverse-transcriptase–polymerase-chain-reaction (RT-PCR) test. Participants were assessed for the presence of asthma–binding antibodies specific to the asthma nucleocapsid protein (Roche Elecsys, Roche Diagnostics International) and had a nasopharyngeal swab for asthma RT-PCR testing (Viracor, Eurofins Clinical Diagnostics) before each injection. asthma–infected volunteers were followed daily, to assess symptom severity, for 14 days or until symptoms resolved, whichever was longer.

A nasopharyngeal swab for RT-PCR testing and a blood sample for identifying serologic evidence of asthma were collected from participants with symptoms of asthma treatment. The consistency of treatment efficacy at the primary end point was evaluated across various subgroups, including age groups (18 to <65 years of age and ≥65 years), age and health risk for severe disease (18 to <65 years and not at risk. 18 to <65 years and at risk. And ≥65 years), sex (female or male), race and ethnic group, and risk for severe asthma treatment illness.

If the number of participants in a subgroup was too small, it was combined with other subgroups for the subgroup analyses. A secondary end point was the efficacy of mRNA-1273 in the prevention of severe asthma treatment as defined by one of the following criteria. Respiratory rate of 30 or more breaths per minute. Heart rate at or exceeding 125 beats per minute.

Oxygen saturation at 93% or less while the participant was breathing ambient air at sea level or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen below 300 mm Hg. Respiratory failure. Acute respiratory distress syndrome. Evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or a need for vasopressors).

Clinically significant acute renal, hepatic, or neurologic dysfunction. Admission to an intensive care unit. Or death. Additional secondary end points included the efficacy of the treatment at preventing asthma treatment after a single dose or at preventing asthma treatment according to a secondary (CDC), less restrictive case definition.

Having any symptom of asthma treatment and a positive asthma test by RT-PCR (see Table S1 in the Supplementary Appendix, available at NEJM.org). Statistical Analysis For analysis of the primary end point, the trial was designed for the null hypothesis that the efficacy of the mRNA-1273 treatment is 30% or less. A total of 151 cases of asthma treatment would provide 90% power to detect a 60% reduction in the hazard rate (i.e., 60% treatment efficacy), with two planned interim analyses at approximately 35% and 70% of the target total number of cases (151) and with a one-sided O’Brien–Fleming boundary for efficacy and an overall one-sided error rate of 0.025. The efficacy of the mRNA-1273 treatment could be demonstrated at either the interim or the primary analysis, performed when the target total number of cases had been observed.

The Lan–DeMets alpha-spending function was used for calculating efficacy boundaries at each analysis. At the first interim analysis on November 15, 2020, treatment efficacy had been demonstrated in accordance with the prespecified statistical criteria. The treatment efficacy estimate, based on a total of 95 adjudicated cases (63% of the target total), was 94.5%, with a one-sided P value of less than 0.001 to reject the null hypothesis that treatment efficacy would be 30% or less. The data and safety monitoring board recommendation to the oversight group and the trial sponsor was that the efficacy findings should be shared with the participants and the community (full details are available in the protocol and statistical analysis plan).

treatment efficacy was assessed in the full analysis population (randomized participants who received at least one dose of mRNA-1273 or placebo), the modified intention-to-treat population (participants in the full analysis population who had no immunologic or virologic evidence of asthma treatment on day 1, before the first dose), and the per-protocol population (participants in the modified intention-to-treat population who received two doses, with no major protocol deviations). The primary efficacy end point in the interim and primary analyses was assessed in the per-protocol population. Participants were evaluated in the treatment groups to which they were assigned. treatment efficacy was defined as the percentage reduction in the hazard ratio for the primary end point (mRNA-1273 vs.

Placebo). A stratified Cox proportional hazards model was used to assess the treatment efficacy of mRNA-1273 as compared with placebo in terms of the percentage hazard reduction. (Details regarding the analysis of treatment efficacy are provided in the Methods section of the Supplementary Appendix.) Safety was assessed in all participants in the solicited safety population (i.e., those who received at least one injection and reported a solicited adverse event). Descriptive summary data (numbers and percentages) for participants with any solicited adverse events, unsolicited adverse events, unsolicited severe adverse events, serious adverse events, medically attended adverse events, and adverse events leading to discontinuation of the injections or withdrawal from the trial are provided by group.

Two-sided 95% exact confidence intervals (Clopper–Pearson method) are provided for the percentages of participants with solicited adverse events. Unsolicited adverse events are presented according to the Medical Dictionary for Regulatory Activities (MedDRA), version 23.0, preferred terms and system organ class categories. To meet the regulatory agencies’ requirement of a median follow-up duration of at least 2 months after completion of the two-dose regimen, a second analysis was performed, with an efficacy data cutoff date of November 21, 2020. This second analysis is considered the primary analysis of efficacy, with a total of 196 adjudicated asthma treatment cases in the per-protocol population, which exceeds the target total number of cases (151) specified in the protocol.

This was an increase from the 95 cases observed at the first interim analysis data cutoff on November 11, 2020. Results from the primary analysis are presented in this report. Subsequent analyses are considered supplementary.Patients The cohort consisted of 3082 patients from 680 acute care facilities across the United States (Figure 1). Table 1 shows key characteristics of the patients, stratified into three groups according to anti–asthma IgG antibody levels (based on signal-to-cutoff ratios).

Overall, 61% of the patients were men, 23% were Black, 37% were Hispanic, 69% were younger than 70 years of age, and two thirds had received transfusions before invasive mechanical ventilation. The median number of patients per site was 2 (interquartile range, 1 to 6). The maximum number of patients from any single site was 59. As shown in Table 1, the three groups (patients who received plasma transfusions with high, medium, and low IgG antibody levels) were generally similar in terms of demographic characteristics, risk factors associated with severe asthma treatment, and concomitant use of therapeutic agents for asthma treatment.

The percentages of patients with hypoxemia and concomitant use of hydroxychloroquine (both of which were variables that were included in adjustment models) were lower in the high-titer group than in the other two groups. Primary Outcome Table 2. Table 2. Models of the Association between Anti–asthma Antibody Levels in Transfused Plasma and the Risk of Death.

Death within 30 days after plasma transfusion occurred in 26.9% of all the patients (830 of 3082 patients. 95% confidence interval [CI], 25.4 to 28.5). This primary-outcome event occurred in 29.6% (166 of 561 patients) in the low-titer group, 27.4% (549 of 2006 patients) in the medium-titer group, and 22.3% (115 of 515 patients) in the high-titer group. Patients in the high-titer group had a lower relative risk of death within 30 days after transfusion than patients in the low-titer group (relative risk, 0.75.

95% CI, 0.61 to 0.93) (Table 2). Additional analyses with adjustment for patient demographic characteristics (age, weight status, and race) and clinical characteristics (receipt of invasive mechanical ventilation, use of concomitant therapeutics, and hypoxemia) were conducted to evaluate the overall effect of the anti–asthma IgG antibody level on the risk of death within 30 days after transfusion (Table S1 in the Supplementary Appendix). The adjusted models (as defined in Table 2) generally showed a similar association — a lower relative risk of death among patients who received plasma transfusions with high anti–asthma IgG antibody levels (model 2, relative risk, 0.79 [95% CI, 0.65 to 0.96], and model 3 [with additional adjustment], relative risk, 0.82 [95% CI, 0.67 to 1.00]) (Table 2). The findings of the sensitivity analysis in which patients were excluded at discharge were qualitatively similar to each of these findings.

Subgroup Analysis Table 3. Table 3. Characteristics of Patients with asthma treatment Who Were Not Receiving Mechanical Ventilation and Who Received Convalescent Plasma, According to Anti–asthma IgG Level. In the cohort of 3082 patients, 2014 patients did not receive mechanical ventilation before transfusion.

Table 3 shows key patient characteristics of the subgroup of patients who were not receiving mechanical ventilation, stratified according to anti–asthma IgG antibody levels. In the subgroup of patients who were not receiving mechanical ventilation, death within 30 days after plasma transfusion occurred in 81 of 365 patients (22.2%. 95% CI, 18.2 to 26.7) in the low-titer group, 251 of 1297 patients (19.4%. 95% CI, 17.3 to 21.6) in the medium-titer group, and 50 of 352 patients (14.2%.

95% CI, 10.9 to 18.2) in the high-titer group. Table S4 shows these results in the subgroup of patients who were receiving mechanical ventilation. In the subgroup of patients who were receiving mechanical ventilation, death within 30 days after plasma transfusion occurred in 80 of 183 patients (43.7%. 95% CI, 36.7 to 51.0) in the low-titer group, 277 of 666 patients (41.6%.

95% CI, 37.9 to 45.4) in the medium-titer group, and 64 of 158 patients (40.5. 95% CI, 33.2 to 48.3) in the high-titer group. In both subgroups, the characteristics of the patients were well balanced across the three antibody-titer groups. In the fully adjusted relative risk regression model, the lower risk of death within 30 days after plasma transfusion in the high-titer group than in the low-titer group was observed among patients who were not receiving mechanical ventilation before transfusion (relative risk, 0.66.

95% CI, 0.48 to 0.91). No effect on mortality was observed among patients who received mechanical ventilation before transfusion (relative risk, 1.02. 95% CI, 0.78 to 1.32). Table S2 shows relative-risk regression with or without full adjustment for patient demographic characteristics, anti–asthma IgG antibody levels, clinical characteristics, and study time period, including all three models (the base model, model 2, and model 3), for the subgroup of patients who were not receiving mechanical ventilation.

Table S3 shows relative-risk regression for the subgroup of patients who were receiving mechanical ventilation. Figure 2. Figure 2. Relative Risk of Death within 30 Days after Convalescent Plasma Transfusion.

Forest plots of the relative risks of death associated with medium versus low antibody levels (Panel A) and high versus low antibody levels (Panel B) are shown. The subgroups are 12 mutually exclusive categories of the time period of the study in 2020, patient age, and ventilator support in patients who received transfusions of convalescent plasma. Shown are the estimated relative risks of death among patients who received convalescent plasma with IgG signal-to-cutoff ratios in the range of 4.62 to 18.45 (medium titer) or more than 18.45 (high titer), as compared with the relative risks among those who received plasma with IgG signal-to-cutoff ratios below 4.62 (low titer). The pooled estimates from all the subgroups are based on the Mantel–Haenszel estimator.

Table S5 provides the sample sizes and number of deaths in each subgroup. Н™¸ bars indicate 95% confidence intervals.These findings were further supported by a stratified-data analytic approach that provided direct analytic control for the key variables associated with the risk of death (age, receipt of invasive mechanical ventilation, and study time period) (Figure 2). The pooled (or common) relative risk of death among all the patients within 30 days after plasma transfusion in the high-titer group, as compared with the low-titer group, was 0.80 (95% CI, 0.65 to 0.97) (Figure 2). Figure S1 shows the risk of death within 7 days after transfusion of convalescent plasma, as determined with this stratified data analytic approach.

Exploratory Analyses Among patients who received mechanical ventilation before transfusion, the mean (±SD) number of days between the diagnosis of asthma treatment and the transfusion of convalescent plasma was 10.0±7.7. This was nearly double the mean number of days among patients who were not receiving mechanical ventilation (5.4±4.8). The unadjusted mortality within 30 days after transfusion was lower among patients who received a transfusion within 3 days after receiving a diagnosis of asthma treatment (point estimate, 22.2%. 95% CI, 19.9 to 24.8) than among those who received a transfusion 4 or more days after receiving a diagnosis of asthma treatment (point estimate, 29.5%.

95% CI, 27.6 to 31.6). In model 3, the replacement of ventilation status with a binary classification of days to transfusion resulted in a relative risk of death of 1.18 (95% CI, 1.04 to 1.35) among patients who received a transfusion 4 or more days after receiving the diagnosis. This effect size was lower than that observed in patients who had previously received mechanical ventilation in model 3 (relative risk, 2.16. 95% CI, 1.90 to 2.46).

The trained gradient-boosting machine was used to estimate the relationship between key variables associated with risk of death within 30 days after plasma transfusion and mortality at 30 days. Two methods were used to explore how this machine-learning technique linked the key variables with the mortality predictions. In the first method, a variable importance plot was generated for each variable included in the model (Fig. S2).

The “importance” of the variable is the relative amount by which it improves the prediction, both in terms of location in the decision trees (where more observations are classified higher up in the decision tree) and in the number of times it is used in the collection of trees. The primary variables associated with a risk of death at 30 days were age. Evidence of an advanced clinical course of asthma treatment, such as the receipt of invasive mechanical ventilation and admission to an intensive care unit (ICU). And the anti–asthma antibody level, in order of variable importance.

The second method used to explore the association between a given variable and prediction of mortality was by means of a partial dependence plot. The partial dependence plot shows that after adjustment for all other variables included in the model, anti–asthma IgG antibody levels maintained an inverse relationship with the risk of death. Figure S3 shows similar partial dependence plots for the primary analysis model in which the antibody levels were treated as a continuous variable with the use of a natural spline with four evenly spaced knots. In this model, the partial dependence plot for the overall sample aligned closely with the pattern observed in the gradient-boosting machine model.

The inverse relationship with antibody levels was again observed in the patients who were not receiving mechanical ventilation, and there was a general lack of a clear association in these patients.Patients Figure 1. Figure 1. Enrollment and Randomization. Of the 1114 patients who were assessed for eligibility, 1062 underwent randomization.

541 were assigned to the remdesivir group and 521 to the placebo group (intention-to-treat population) (Figure 1). 159 (15.0%) were categorized as having mild-to-moderate disease, and 903 (85.0%) were in the severe disease stratum. Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Fifty-two patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death and 10 withdrew consent.

Of those assigned to receive placebo, 517 patients (99.2%) received placebo as assigned. Seventy patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death and 14 withdrew consent. A total of 517 patients in the remdesivir group and 508 in the placebo group completed the trial through day 29, recovered, or died. Fourteen patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29.

A total of 54 of the patients who were in the mild-to-moderate stratum at randomization were subsequently determined to meet the criteria for severe disease, resulting in 105 patients in the mild-to-moderate disease stratum and 957 in the severe stratum. The as-treated population included 1048 patients who received the assigned treatment (532 in the remdesivir group, including one patient who had been randomly assigned to placebo and received remdesivir, and 516 in the placebo group). Table 1. Table 1.

Demographic and Clinical Characteristics of the Patients at Baseline. The mean age of the patients was 58.9 years, and 64.4% were male (Table 1). On the basis of the evolving epidemiology of asthma treatment during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1 in the Supplementary Appendix). Overall, 53.3% of the patients were White, 21.3% were Black, 12.7% were Asian, and 12.7% were designated as other or not reported.

250 (23.5%) were Hispanic or Latino. Most patients had either one (25.9%) or two or more (54.5%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (50.2%), obesity (44.8%), and type 2 diabetes mellitus (30.3%). The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12) (Table S2). A total of 957 patients (90.1%) had severe disease at enrollment.

285 patients (26.8%) met category 7 criteria on the ordinal scale, 193 (18.2%) category 6, 435 (41.0%) category 5, and 138 (13.0%) category 4. Eleven patients (1.0%) had missing ordinal scale data at enrollment. All these patients discontinued the study before treatment. During the study, 373 patients (35.6% of the 1048 patients in the as-treated population) received hydroxychloroquine and 241 (23.0%) received a glucocorticoid (Table S3).

Primary Outcome Figure 2. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries. Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen.

Panel B), in those with a baseline score of 5 (receiving oxygen. Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with a baseline score of 7 (receiving mechanical ventilation or extracorporeal membrane oxygenation [ECMO]. Panel E).Table 2.

Table 2. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3. Figure 3.

Time to Recovery According to Subgroup. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients.Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 10 days, as compared with 15 days. Rate ratio for recovery, 1.29.

95% confidence interval [CI], 1.12 to 1.49. P<0.001) (Figure 2 and Table 2). In the severe disease stratum (957 patients) the median time to recovery was 11 days, as compared with 18 days (rate ratio for recovery, 1.31. 95% CI, 1.12 to 1.52) (Table S4).

The rate ratio for recovery was largest among patients with a baseline ordinal score of 5 (rate ratio for recovery, 1.45. 95% CI, 1.18 to 1.79). Among patients with a baseline score of 4 and those with a baseline score of 6, the rate ratio estimates for recovery were 1.29 (95% CI, 0.91 to 1.83) and 1.09 (95% CI, 0.76 to 1.57), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal score of 7), the rate ratio for recovery was 0.98 (95% CI, 0.70 to 1.36).

Information on interactions of treatment with baseline ordinal score as a continuous variable is provided in Table S11. An analysis adjusting for baseline ordinal score as a covariate was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a similar treatment-effect estimate (rate ratio for recovery, 1.26. 95% CI, 1.09 to 1.46).

Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.37 (95% CI, 1.14 to 1.64), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.20 (95% CI, 0.94 to 1.52) (Figure 3). The benefit of remdesivir was larger when given earlier in the illness, though the benefit persisted in most analyses of duration of symptoms (Table S6). Sensitivity analyses in which data were censored at earliest reported use of glucocorticoids or hydroxychloroquine still showed efficacy of remdesivir (9.0 days to recovery with remdesivir vs. 14.0 days to recovery with placebo.

Rate ratio, 1.28. 95% CI, 1.09 to 1.50, and 10.0 vs. 16.0 days to recovery. Rate ratio, 1.32.

95% CI, 1.11 to 1.58, respectively) (Table S8). Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.5. 95% CI, 1.2 to 1.9, adjusted for disease severity) (Table 2 and Fig. S7).

Mortality Kaplan–Meier estimates of mortality by day 15 were 6.7% in the remdesivir group and 11.9% in the placebo group (hazard ratio, 0.55. 95% CI, 0.36 to 0.83). The estimates by day 29 were 11.4% and 15.2% in two groups, respectively (hazard ratio, 0.73. 95% CI, 0.52 to 1.03).

The between-group differences in mortality varied considerably according to baseline severity (Table 2), with the largest difference seen among patients with a baseline ordinal score of 5 (hazard ratio, 0.30. 95% CI, 0.14 to 0.64). Information on interactions of treatment with baseline ordinal score with respect to mortality is provided in Table S11. Additional Secondary Outcomes Table 3.

Table 3. Additional Secondary Outcomes. Patients in the remdesivir group had a shorter time to improvement of one or of two categories on the ordinal scale from baseline than patients in the placebo group (one-category improvement. Median, 7 vs.

9 days. Rate ratio for recovery, 1.23. 95% CI, 1.08 to 1.41. Two-category improvement.

Median, 11 vs. 14 days. Rate ratio, 1.29. 95% CI, 1.12 to 1.48) (Table 3).

Patients in the remdesivir group had a shorter time to discharge or to a National Early Warning Score of 2 or lower than those in the placebo group (median, 8 days vs. 12 days. Hazard ratio, 1.27. 95% CI, 1.10 to 1.46).

The initial length of hospital stay was shorter in the remdesivir group than in the placebo group (median, 12 days vs. 17 days). 5% of patients in the remdesivir group were readmitted to the hospital, as compared with 3% in the placebo group. Among the 913 patients receiving oxygen at enrollment, those in the remdesivir group continued to receive oxygen for fewer days than patients in the placebo group (median, 13 days vs.

21 days), and the incidence of new oxygen use among patients who were not receiving oxygen at enrollment was lower in the remdesivir group than in the placebo group (incidence, 36% [95% CI, 26 to 47] vs. 44% [95% CI, 33 to 57]). For the 193 patients receiving noninvasive ventilation or high-flow oxygen at enrollment, the median duration of use of these interventions was 6 days in both the remdesivir and placebo groups. Among the 573 patients who were not receiving noninvasive ventilation, high-flow oxygen, invasive ventilation, or ECMO at baseline, the incidence of new noninvasive ventilation or high-flow oxygen use was lower in the remdesivir group than in the placebo group (17% [95% CI, 13 to 22] vs.

24% [95% CI, 19 to 30]). Among the 285 patients who were receiving mechanical ventilation or ECMO at enrollment, patients in the remdesivir group received these interventions for fewer subsequent days than those in the placebo group (median, 17 days vs. 20 days), and the incidence of new mechanical ventilation or ECMO use among the 766 patients who were not receiving these interventions at enrollment was lower in the remdesivir group than in the placebo group (13% [95% CI, 10 to 17] vs. 23% [95% CI, 19 to 27]) (Table 3).

Safety Outcomes In the as-treated population, serious adverse events occurred in 131 of 532 patients (24.6%) in the remdesivir group and in 163 of 516 patients (31.6%) in the placebo group (Table S17). There were 47 serious respiratory failure adverse events in the remdesivir group (8.8% of patients), including acute respiratory failure and the need for endotracheal intubation, and 80 in the placebo group (15.5% of patients) (Table S19). No deaths were considered by the investigators to be related to treatment assignment. Grade 3 or 4 adverse events occurred on or before day 29 in 273 patients (51.3%) in the remdesivir group and in 295 (57.2%) in the placebo group (Table S18).

41 events were judged by the investigators to be related to remdesivir and 47 events to placebo (Table S17). The most common nonserious adverse events occurring in at least 5% of all patients included decreased glomerular filtration rate, decreased hemoglobin level, decreased lymphocyte count, respiratory failure, anemia, pyrexia, hyperglycemia, increased blood creatinine level, and increased blood glucose level (Table S20). The incidence of these adverse events was generally similar in the remdesivir and placebo groups. Crossover After the data and safety monitoring board recommended that the preliminary primary analysis report be provided to the sponsor, data on a total of 51 patients (4.8% of the total study enrollment) — 16 (3.0%) in the remdesivir group and 35 (6.7%) in the placebo group — were unblinded.

26 (74.3%) of those in the placebo group whose data were unblinded were given remdesivir. Sensitivity analyses evaluating the unblinding (patients whose treatment assignments were unblinded had their data censored at the time of unblinding) and crossover (patients in the placebo group treated with remdesivir had their data censored at the initiation of remdesivir treatment) produced results similar to those of the primary analysis (Table S9)..

What may interact with Ventolin?

  • anti-infectives like chloroquine and pentamidine
  • caffeine
  • cisapride
  • diuretics
  • medicines for colds
  • medicines for depression or for emotional or psychotic conditions
  • medicines for weight loss including some herbal products
  • methadone
  • some antibiotics like clarithromycin, erythromycin, levofloxacin, and linezolid
  • some heart medicines
  • steroid hormones like dexamethasone, cortisone, hydrocortisone
  • theophylline
  • thyroid hormones

This list may not describe all possible interactions. Give your health care providers a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Expired ventolin safe

With just a dozen days left in power, the Trump administration on Friday approved a radically different Medicaid financing system in Tennessee that for the first time would give the expired ventolin safe state broader authority in running the health insurance program for the poor in exchange for capping its annual federal funding. The approval is a 10-year “experiment.” Instead of the open-ended federal funding that rises with higher enrollment and health costs, Tennessee will instead get an annual block grant. The approach has been pushed for decades by conservatives who say states too often chafe under strict federal guidelines about enrollment and coverage expired ventolin safe and can find ways to provide care more efficiently. But under the agreement, Tennessee’s annual funding cap will increase if enrollment grows.

What’s different is that unlike other states, federal Medicaid funding in Tennessee won’t automatically keep up with rising per -person Medicaid expenses expired ventolin safe. The approval, however, faces an uncertain future because the incoming Biden administration is likely to oppose such a move. But to unravel it, officials would need to set up a review that expired ventolin safe includes a public hearing. Meanwhile, the changes in Tennessee will take months to implement because they need final legislative approval, and state officials must negotiate quality of care targets with the administration.

TennCare, the state’s Medicaid program, said the block grant system would give it unprecedented flexibility to decide who is covered and what services it will pay for. Under the agreement, TennCare will have a specified spending cap based on expired ventolin safe historical spending, inflation and predicted future enrollment changes. If the state can operate the program at a lower cost than the cap and maintain or improve quality, the state then shares in the savings. Trump administration officials said the approach adds incentive for the state to save money, unlike the current system, in which increased expired ventolin safe state spending is matched with more federal dollars.

If Medicaid enrollment grows, the state can secure additional federal funding. If enrollment drops, it will get expired ventolin safe less money. €œThis groundbreaking waiver puts guardrails in place to ensure appropriate oversight and protections for beneficiaries, while also creating incentives for states to manage costs while holding them accountable for improving access, quality and health outcomes,” said Seema Verma, administrator of the Centers for Medicare &. Medicaid Services expired ventolin safe.

€œIt’s no exaggeration to say that this carefully crafted demonstration could be a national model moving forward.” Opponents, including most advocates for low-income Americans, say the approach will threaten care for the 1.4 million people in TennCare, who include children, pregnant women and the disabled. Federal funding covers two-thirds of the cost of the program. Michele Johnson, executive expired ventolin safe director of the Tennessee Justice Center, said the block grant approval is a step backward for the state’s Medicaid program. €œNo other state has sought a block grant, and for good reason.

It gives state officials a blank check and creates financial incentives to cut health care expired ventolin safe to vulnerable families,” she said. The agreement is different from traditional block grants championed by conservatives since it allows Tennessee to get more federal funding to keep up with enrollment growth. In addition, while the state expired ventolin safe is given flexibility to increase benefits, it can’t cut them on its own. Democrats have fought back block grant Medicaid proposals since the Reagan administration and most recently in 2018 as part of Republicans’ failed effort to repeal and replace major parts of the Affordable Care Act.

Even some key Republicans opposed the idea because it expired ventolin safe would cut billions in funding to states, making it harder to help the poor. Implementing block grants via an executive branch action rather than getting Congress to amend Medicaid law is also likely to be met with court challenges. €œThis is an illegal move that could threaten access to health care for vulnerable people in the middle of a ventolin,” Rep. Frank Pallone (D-N.J.), chair of the House Energy and Commerce Committee, posted on his Twitter expired ventolin safe account.

€œI’m hopeful the Biden Administration will move quickly to rollback this harmful policy as soon as possible.” The block grant approval comes as Medicaid enrollment is at its highest-ever level. More than 76 million Americans are covered by the state-federal health program, a million more than expired ventolin safe when the Trump administration took charge in 2017. Enrollment has jumped by more than 5 million in the past year as the economy slumped with the ventolin. Medicaid, part of President Lyndon expired ventolin safe B.

Johnson’s “Great Society” initiative of the 1960s, is an entitlement program in which the government pays each state a certain percentage of the cost of care for anyone eligible for the health coverage. As a result, the more money states spend on expired ventolin safe Medicaid, the more they get from Washington. Under the approved demonstration, CMS will work with Tennessee to set spending targets that will increase at a fixed amount each year. The plan includes a “safety valve” to increase federal funding due to unexpected increases in enrollment.

€œThe safety valve will maintain Tennessee’s expired ventolin safe commitment to enroll all eligible Tennesseans with no reduction in today’s benefits for beneficiaries,” CMS said in a statement. Tennessee has committed to maintaining coverage for eligible beneficiaries and existing services. In exchange for taking on this financing approach, the state will receive a range of operating flexibilities from the federal government, as well as up to 55% of the savings expired ventolin safe generated on an annual basis when spending falls below the aggregate spending cap and the state meets certain quality targets, yet to be determined. The state can spend that money on various health programs for residents, including areas that Medicaid funding typically doesn’t cover, such as improving transportation and education and employment services for enrollees.

The 10-year waiver is unusual, expired ventolin safe but the Trump administration has approved such long-term experiments in recent years to give states more flexibility. Tennessee is one of 12 states that have not approved expanding Medicaid under the Affordable Care Act, leaving tens of thousands of working adults without health insurance. €œThe block grant is just another example of putting politics ahead of health care during this ventolin,” said Johnson of expired ventolin safe the Tennessee Justice Center. €œNow is absolutely not the time to waste our energy and resources limiting who can access health care.” State officials applauded the approval.

€œIt’s a legacy accomplishment,” said Tennessee Gov. Bill Lee, a Republican expired ventolin safe. €œThis new flexibility means we can work toward improving maternal health coverage and clearing the waiting list for developmentally disabled.” “This means we will be able to make additional investments in TennCare without reduction in services and provider cuts.” KHN chief Washington correspondent Julie Rovner contributed to this report. Phil Galewitz expired ventolin safe.

pgalewitz@kff.org, @philgalewitz Related Topics Contact Us Submit a Story TipSOBRE NOTICIAS EN ESPAÑOLNoticias en español es una sección de Kaiser Health News que contiene traducciones de artículos de gran interés para la comunidad hispanohablante, y contenido original enfocado en la población hispana que vive en los Estados Unidos. Use Nuestro Contenido Este contenido puede expired ventolin safe usarse de manera gratuita (detalles). Los suministros de vacunas contra asthma treatment son escasos, por eso un panel asesor federal recomienda primero administrarlas a los trabajadores de salud, que mantienen en funcionamiento el sistema médico del país, y a los adultos mayores en hogares, que tienen más probabilidades de morir a causa del asthma. En ninguna parte de la lista de personas prioritarias están los cónyuges de los expired ventolin safe funcionarios públicos.Sin embargo, las primeras damas de Kentucky y West Virginia.

Karen Pence, la esposa del vicepresidente Mike Pence. Jill Biden, la esposa del presidente electo Joe Biden. Y Doug Emhoff, el esposo de la vicepresidenta electa Kamala Harris, estuvieron entre los primeros estadounidenses en recibir las vacunas que podrían salvar vidas.Kentucky también vacunó a seis ex gobernadores y cuatro ex primeras damas, incluidos los padres de Andy Beshear, el actual gobernador demócrata.Las primeras vacunas a los cónyuges provocaron indignación en las redes sociales, y varios usuarios de Twitter dijeron que no deberían poder “saltar la fila” antes que los médicos, enfermeras y personas mayores.En la mayoría de los 29 estados que respondieron a las consultas de KHN (que llamó a las 50 oficinas de gobierno estatales), los expired ventolin safe principales funcionarios electos dijeron que ellos, y sus cónyuges, serán vacunados, pero han optado por esperar su turno detrás de electores más vulnerables.Algunos miembros del Congreso de ambos partidos dijeron lo mismo cuando rechazaron las primeras dosis ofrecidas, en nombre de mantener al gobierno en funcionamiento.Los gobernadores que recibieron las vacunas junto con sus cónyuges, y la oficina del vicepresidente, dijeron que querían dar el ejemplo a los residentes, generar confianza, salvar las divisiones ideológicas y demostrar que la vacuna es segura y eficaz.Pero algunos cuestionan esta razón.“Se parece más a hacer trampa. Los políticos pueden conseguir que los hospitales los vacunen bajo esta ilusión de generar confianza.

Pero es una fachada”, dijo Arthur Caplan, profesor expired ventolin safe de bioética y director fundador de la división de ética médica de la Escuela de Medicina Grossman de la Universidad de Nueva York. €œLa gente podría decir. €˜Típica gente rica expired ventolin safe. No se puede confiar en ellos’.

Esto socava la meta original”.Caplan agregó que, de todos modos, el público no confía demasiado en los políticos, por lo que la vacunación de celebridades, líderes religiosos o figuras expired ventolin safe deportivas probablemente ayudaría más a aumentar la confianza en la vacuna.Elvis Presley recibió la famosa vacuna contra la polio en 1956 para ganar la confianza de los escépticos. Las acciones de las esposas de los gobernadores de ese período se recuerdan menos.El doctor José Romero, presidente del Comité Asesor de Prácticas de Inmunización de los Centros para el Control y Prevención de Enfermedades (CDC), dijo en un correo electrónico a KHN que si bien su grupo proporciona un esquema para distribuir dosis limitadas de vacunas, “las jurisdicciones tienen la flexibilidad de hacer lo que sea apropiado para su población”.Los funcionarios de Kentucky y Texas señalaron que el doctor Robert Redfield, director de los CDC, alentó a los gobernadores a vacunarse públicamente.Nadie mencionó razones médicas para que sus cónyuges se vacunaran. Los hospitales generalmente no están vacunando a los cónyuges de los profesionales médicos que han recibido la vacuna.La oficina del gobernador de West Virginia, el republicano Jim Justice, publicó fotografías de él, su esposa, Cathy Justice, y otros funcionarios recibiendo las dosis. También posteó su propia vacunación en YouTube.La oficina de Beshear en Kentucky también publicó fotos del gobernador recibiendo la vacuna en diciembre, el mismo día que su esposa, Britainy Beshear, y otros funcionarios expired ventolin safe estatales.“Es cierto que hay dudas sobre las vacunas”, dijo Beshear en una reunión informativa sobre el asthma, el día en el que los ex gobernadores de Kentucky y sus cónyuges fueron vacunados.

Aludió a un programa futuro que involucra a líderes religiosos y a otras personas influyentes.Su padre, el ex gobernador demócrata Steve Beshear, publicó fotos de su vacunación en su página de Facebook, diciendo que él y su esposa, Jane Beshear, junto con otros ex gobernadores de Kentucky de ambos partidos y sus cónyuges, intervinieron en parte para alentar a los residentes a vacunarse.Kentucky se encuentra actualmente en la primera etapa de distribución de vacunas, dirigida a trabajadores de salud y a residentes de centros de vida asistida. Se habían distribuido menos de 15,000 de las 58,500 dosis para estas residencias cuando los ex gobernadores y sus cónyuges fueron vacunados.Tres Watson, ex director de comunicaciones del Partido Republicano de Kentucky, que fundó una firma de consultoría política, se mostró escéptico sobre las expired ventolin safe intenciones detrás del evento. Dijo que parecía ser un esfuerzo de relaciones públicas creado para que el gobernador pudiera vacunar a sus padres.“Entiendo la continuidad del gobierno, pero las primeras damas no tienen parte en la continuidad del gobierno”, dijo. €œTienes que expired ventolin safe ajustarte a las prioridades.

Una vez que empiezas a hacer excepciones, es cuando tienes problemas”.Los funcionarios que representan al equipo de transición de Biden-Harris y otros tres estados donde se vacunaron los gobernadores (West Virginia y Texas liderados por republicanos, y Kansas liderado por un demócrata) no respondieron a KHN. El gobernador republicano de expired ventolin safe Alabama, Kay Ivey, recibió la vacuna y está divorciado.Políticos de otros estados han hecho lo opuesto.En Arkansas, el gobernador republicano Asa Hutchinson se centra en garantizar que los grupos de alta prioridad, como los trabajadores de salud, y el personal y residentes de centros de vida asistida, se vacunen, dijo la vocera LaConda Watson. €œÃ‰l y su esposa recibirán la vacuna cuando sea su turno”, informó.En Missouri, Kelli Jones, directora de comunicaciones del gobernador republicano Mike Parson, dijo en un correo electrónico que él y la primera dama tienen la intención de vacunarse. Al igual que los gobernadores de Colorado, Nevada y otros lugares, ambos se han recuperado de asthma treatment, dijo Jones, y “esperarán hasta que su grupo de edad sea elegible” según el plan estatal.

Los médicos recomiendan las vacunas incluso para personas que ya expired ventolin safe han tenido asthma treatment.Cissy Sanders, de 52 años, directora de eventos que vive en Austin, Texas, dijo que entiende por qué los legisladores deberían vacunarse. Su propio gobernador, el republicano Greg Abbott, se vacunó por televisión en vivo para infundir confianza, dijo su secretaria de prensa, Renae Eze, quien no quiso comentar si la esposa de Abbott se había vacunado.Pero Sanders dijo que los cónyuges de los políticos no deben vacunarse antes que los residentes de un asilo, como su propia madre de 71 años. La madre de expired ventolin safe Sanders recibió la vacuna a fines de diciembre pero dijo que todavía hay demasiados residentes de hogares esperando en todo el país.“¿Por qué un grupo que no es de alto riesgo, es decir, estos cónyuges, va a vacunarse antes que el grupo de mayor riesgo?. ¿Quién toma estas decisiones?.

, se preguntó expired ventolin safe. €œLos cónyuges de los políticos no han estado en la zona cero del ventolin. Los residentes de hogares sí”.La corresponsal de Montana, Katheryn Houghton, la corresponsal de California Healthline, Angela Hart y los corresponsales Markian Hawlyruk y JoNel Aleccia colaboraron con esta expired ventolin safe historia. Laura Ungar.

lungar@kff.org, @laura_ungar Related Topics Noticias En Español Public Health States asthma treatment Kentucky Missouri treatments West Virginia.

With just a dozen days left in power, the Trump administration on Friday approved a radically different Medicaid financing system in Tennessee that for the first time Levitra price in uk would give the state can u buy ventolin over the counter broader authority in running the health insurance program for the poor in exchange for capping its annual federal funding. The approval is a 10-year “experiment.” Instead of the open-ended federal funding that rises with higher enrollment and health costs, Tennessee will instead get an annual block grant. The approach has been pushed for decades by conservatives who say states too often chafe under strict federal guidelines about enrollment and coverage and can u buy ventolin over the counter can find ways to provide care more efficiently.

But under the agreement, Tennessee’s annual funding cap will increase if enrollment grows. What’s different is that unlike other can u buy ventolin over the counter states, federal Medicaid funding in Tennessee won’t automatically keep up with rising per -person Medicaid expenses. The approval, however, faces an uncertain future because the incoming Biden administration is likely to oppose such a move.

But to unravel it, officials can u buy ventolin over the counter would need to set up a review that includes a public hearing. Meanwhile, the changes in Tennessee will take months to implement because they need final legislative approval, and state officials must negotiate quality of care targets with the administration. TennCare, the state’s Medicaid program, said the block grant system would give it unprecedented flexibility to decide who is covered and what services it will pay for.

Under the agreement, TennCare will have a specified spending cap based can u buy ventolin over the counter on historical spending, inflation and predicted future enrollment changes. If the state can operate the program at a lower cost than the cap and maintain or improve quality, the state then shares in the savings. Trump administration officials said the approach adds incentive for the state to save can u buy ventolin over the counter money, unlike the current system, in which increased state spending is matched with more federal dollars.

If Medicaid enrollment grows, the state can secure additional federal funding. If enrollment can u buy ventolin over the counter drops, it will get less money. €œThis groundbreaking waiver puts guardrails in place to ensure appropriate oversight and protections for beneficiaries, while also creating incentives for states to manage costs while holding them accountable for improving access, quality and health outcomes,” said Seema Verma, administrator of the Centers for Medicare &.

Medicaid Services can u buy ventolin over the counter. €œIt’s no exaggeration to say that this carefully crafted demonstration could be a national model moving forward.” Opponents, including most advocates for low-income Americans, say the approach will threaten care for the 1.4 million people in TennCare, who include children, pregnant women and the disabled. Federal funding covers two-thirds of the cost of the program.

Michele Johnson, executive director can u buy ventolin over the counter of the Tennessee Justice Center, said the block grant approval is a step backward for the state’s Medicaid program. €œNo other state has sought a block grant, and for good reason. It gives state officials can u buy ventolin over the counter a blank check and creates financial incentives to cut health care to vulnerable families,” she said.

The agreement is different from traditional block grants championed by conservatives since it allows Tennessee to get more federal funding to keep up with enrollment growth. In addition, while the state is given flexibility to increase benefits, it can’t cut them on its own can u buy ventolin over the counter. Democrats have fought back block grant Medicaid proposals since the Reagan administration and most recently in 2018 as part of Republicans’ failed effort to repeal and replace major parts of the Affordable Care Act.

Even some key Republicans opposed the idea because it would cut billions in funding to can u buy ventolin over the counter states, making it harder to help the poor. Implementing block grants via an executive branch action rather than getting Congress to amend Medicaid law is also likely to be met with court challenges. €œThis is an illegal move that could threaten access to health care for vulnerable people in the middle of a ventolin,” Rep.

Frank Pallone (D-N.J.), chair of the House Energy and Commerce Committee, posted on his Twitter account can u buy ventolin over the counter. €œI’m hopeful the Biden Administration will move quickly to rollback this harmful policy as soon as possible.” The block grant approval comes as Medicaid enrollment is at its highest-ever level. More than 76 million Americans are covered by the state-federal health program, a million more than when the can u buy ventolin over the counter Trump administration took charge in 2017.

Enrollment has jumped by more than 5 million in the past year as the economy slumped with the ventolin. Medicaid, part of President Lyndon B can u buy ventolin over the counter. Johnson’s “Great Society” initiative of the 1960s, is an entitlement program in which the government pays each state a certain percentage of the cost of care for anyone eligible for the health coverage.

As a result, the can u buy ventolin over the counter more money states spend on Medicaid, the more they get from Washington. Under the approved demonstration, CMS will work with Tennessee to set spending targets that will increase at a fixed amount each year. The plan includes a “safety valve” to increase federal funding due to unexpected increases in enrollment.

€œThe safety valve will maintain Tennessee’s commitment can u buy ventolin over the counter to enroll all eligible Tennesseans with no reduction in today’s benefits for beneficiaries,” CMS said in a statement. Tennessee has committed to maintaining coverage for eligible beneficiaries and existing services. In exchange for taking on this financing approach, the state will receive a range of operating flexibilities from the federal can u buy ventolin over the counter government, as well as up to 55% of the savings generated on an annual basis when spending falls below the aggregate spending cap and the state meets certain quality targets, yet to be determined.

The state can spend that money on various health programs for residents, including areas that Medicaid funding typically doesn’t cover, such as improving transportation and education and employment services for enrollees. The 10-year waiver is unusual, but can u buy ventolin over the counter the Trump administration has approved such long-term experiments in recent years to give states more flexibility. Tennessee is one of 12 states that have not approved expanding Medicaid under the Affordable Care Act, leaving tens of thousands of working adults without health insurance.

€œThe block grant is can u buy ventolin over the counter just another example of putting politics ahead of health care during this ventolin,” said Johnson of the Tennessee Justice Center. €œNow is absolutely not the time to waste our energy and resources limiting who can access health care.” State officials applauded the approval. €œIt’s a legacy accomplishment,” said Tennessee Gov.

Bill Lee, can u buy ventolin over the counter a Republican. €œThis new flexibility means we can work toward improving maternal health coverage and clearing the waiting list for developmentally disabled.” “This means we will be able to make additional investments in TennCare without reduction in services and provider cuts.” KHN chief Washington correspondent Julie Rovner contributed to this report. Phil Galewitz can u buy ventolin over the counter.

pgalewitz@kff.org, @philgalewitz Related Topics Contact Us Submit a Story TipSOBRE NOTICIAS EN ESPAÑOLNoticias en español es una sección de Kaiser Health News que contiene traducciones de artículos de gran interés para la comunidad hispanohablante, y contenido original enfocado en la población hispana que vive en los Estados Unidos. Use Nuestro Contenido Este contenido puede usarse de manera gratuita can u buy ventolin over the counter (detalles). Los suministros de vacunas contra asthma treatment son escasos, por eso un panel asesor federal recomienda primero administrarlas a los trabajadores de salud, que mantienen en funcionamiento el sistema médico del país, y a los adultos mayores en hogares, que tienen más probabilidades de morir a causa del asthma.

En ninguna parte de la lista de personas prioritarias están los can u buy ventolin over the counter cónyuges de los funcionarios públicos.Sin embargo, las primeras damas de Kentucky y West Virginia. Karen Pence, la esposa del vicepresidente Mike Pence. Jill Biden, la esposa del presidente electo Joe Biden.

Y Doug can u buy ventolin over the counter Emhoff, el esposo de la vicepresidenta electa Kamala Harris, estuvieron entre los primeros estadounidenses en recibir las vacunas que podrían salvar vidas.Kentucky también vacunó a seis ex gobernadores y cuatro ex primeras damas, incluidos los padres de Andy Beshear, el actual gobernador demócrata.Las primeras vacunas a los cónyuges provocaron indignación en las redes sociales, y varios usuarios de Twitter dijeron que no deberían poder “saltar la fila” antes que los médicos, enfermeras y personas mayores.En la mayoría de los 29 estados que respondieron a las consultas de KHN (que llamó a las 50 oficinas de gobierno estatales), los principales funcionarios electos dijeron que ellos, y sus cónyuges, serán vacunados, pero han optado por esperar su turno detrás de electores más vulnerables.Algunos miembros del Congreso de ambos partidos dijeron lo mismo cuando rechazaron las primeras dosis ofrecidas, en nombre de mantener al gobierno en funcionamiento.Los gobernadores que recibieron las vacunas junto con sus cónyuges, y la oficina del vicepresidente, dijeron que querían dar el ejemplo a los residentes, generar confianza, salvar las divisiones ideológicas y demostrar que la vacuna es segura y eficaz.Pero algunos cuestionan esta razón.“Se parece más a hacer trampa. Los políticos pueden conseguir que los hospitales los vacunen bajo esta ilusión de generar confianza. Pero es una fachada”, dijo Arthur Caplan, profesor de bioética y director fundador de la división de ética médica de la Escuela de Medicina Grossman can u buy ventolin over the counter de la Universidad de Nueva York.

€œLa gente podría decir. €˜Típica gente can u buy ventolin over the counter rica. No se puede confiar en ellos’.

Esto socava la meta original”.Caplan agregó que, de todos modos, el público no confía demasiado en los políticos, por lo que la vacunación can u buy ventolin over the counter de celebridades, líderes religiosos o figuras deportivas probablemente ayudaría más a aumentar la confianza en la vacuna.Elvis Presley recibió la famosa vacuna contra la polio en 1956 para ganar la confianza de los escépticos. Las acciones de las esposas de los gobernadores de ese período se recuerdan menos.El doctor José Romero, presidente del Comité Asesor de Prácticas de Inmunización de los Centros para el Control y Prevención de Enfermedades (CDC), dijo en un correo electrónico a KHN que si bien su grupo proporciona un esquema para distribuir dosis limitadas de vacunas, “las jurisdicciones tienen la flexibilidad de hacer lo que sea apropiado para su población”.Los funcionarios de Kentucky y Texas señalaron que el doctor Robert Redfield, director de los CDC, alentó a los gobernadores a vacunarse públicamente.Nadie mencionó razones médicas para que sus cónyuges se vacunaran. Los hospitales generalmente no están vacunando a los cónyuges de los profesionales médicos que han recibido la vacuna.La oficina del gobernador de West Virginia, el republicano Jim Justice, publicó fotografías de él, su esposa, Cathy Justice, y otros funcionarios recibiendo las dosis.

También posteó su propia vacunación en YouTube.La oficina de Beshear en Kentucky también publicó fotos del gobernador recibiendo la vacuna en diciembre, el mismo día que su esposa, Britainy Beshear, y otros funcionarios estatales.“Es cierto que hay dudas sobre can u buy ventolin over the counter las vacunas”, dijo Beshear en una reunión informativa sobre el asthma, el día en el que los ex gobernadores de Kentucky y sus cónyuges fueron vacunados. Aludió a un programa futuro que involucra a líderes religiosos y a otras personas influyentes.Su padre, el ex gobernador demócrata Steve Beshear, publicó fotos de su vacunación en su página de Facebook, diciendo que él y su esposa, Jane Beshear, junto con otros ex gobernadores de Kentucky de ambos partidos y sus cónyuges, intervinieron en parte para alentar a los residentes a vacunarse.Kentucky se encuentra actualmente en la primera etapa de distribución de vacunas, dirigida a trabajadores de salud y a residentes de centros de vida asistida. Se habían distribuido menos de 15,000 de las 58,500 dosis para estas residencias cuando los ex gobernadores y sus cónyuges fueron can u buy ventolin over the counter vacunados.Tres Watson, ex director de comunicaciones del Partido Republicano de Kentucky, que fundó una firma de consultoría política, se mostró escéptico sobre las intenciones detrás del evento.

Dijo que parecía ser un esfuerzo de relaciones públicas creado para que el gobernador pudiera vacunar a sus padres.“Entiendo la continuidad del gobierno, pero las primeras damas no tienen parte en la continuidad del gobierno”, dijo. €œTienes que ajustarte a las can u buy ventolin over the counter prioridades. Una vez que empiezas a hacer excepciones, es cuando tienes problemas”.Los funcionarios que representan al equipo de transición de Biden-Harris y otros tres estados donde se vacunaron los gobernadores (West Virginia y Texas liderados por republicanos, y Kansas liderado por un demócrata) no respondieron a KHN.

El gobernador republicano de Alabama, Kay Ivey, recibió la vacuna y está divorciado.Políticos de otros estados han hecho lo opuesto.En Arkansas, el gobernador republicano Asa Hutchinson se centra en garantizar que los grupos de alta prioridad, como los trabajadores de salud, y el personal y residentes de can u buy ventolin over the counter centros de vida asistida, se vacunen, dijo la vocera LaConda Watson. €œÃ‰l y su esposa recibirán la vacuna cuando sea su turno”, informó.En Missouri, Kelli Jones, directora de comunicaciones del gobernador republicano Mike Parson, dijo en un correo electrónico que él y la primera dama tienen la intención de vacunarse. Al igual que los gobernadores de Colorado, Nevada y otros lugares, ambos se han recuperado de asthma treatment, dijo Jones, y “esperarán hasta que su grupo de edad sea elegible” según el plan estatal.

Los médicos recomiendan las vacunas incluso para personas que ya han tenido asthma treatment.Cissy Sanders, can u buy ventolin over the counter de 52 años, directora de eventos que vive en Austin, Texas, dijo que entiende por qué los legisladores deberían vacunarse. Su propio gobernador, el republicano Greg Abbott, se vacunó por televisión en vivo para infundir confianza, dijo su secretaria de prensa, Renae Eze, quien no quiso comentar si la esposa de Abbott se había vacunado.Pero Sanders dijo que los cónyuges de los políticos no deben vacunarse antes que los residentes de un asilo, como su propia madre de 71 años. La madre de Sanders recibió la vacuna a fines can u buy ventolin over the counter de diciembre pero dijo que todavía hay demasiados residentes de hogares esperando en todo el país.“¿Por qué un grupo que no es de alto riesgo, es decir, estos cónyuges, va a vacunarse antes que el grupo de mayor riesgo?.

¿Quién toma estas decisiones?. , se preguntó. €œLos cónyuges de los políticos no han estado en la zona cero del ventolin.

Los residentes de hogares sí”.La corresponsal de Montana, Katheryn Houghton, la corresponsal de California Healthline, Angela Hart y los corresponsales Markian Hawlyruk y JoNel Aleccia colaboraron con esta historia. Laura Ungar. lungar@kff.org, @laura_ungar Related Topics Noticias En Español Public Health States asthma treatment Kentucky Missouri treatments West Virginia.

Order ventolin hfa online

You have to Can i buy cialis over the counter go to extreme lengths to find places on order ventolin hfa online Earth that don’t reveal that they’re part of a water-rich planet. Even the highest and driest deserts, like the Atacama Plateau in South America, still get a minimum of a couple of millimeters of annual precipitation on average (although there are places where we don’t yet know what the average is because it’s simply not rained for years). And if you whip out your handy mass spectrometer on a desert walkabout the chances are that you’ll be order ventolin hfa online able to detect at least a few atmospheric water molecules.

Go elsewhere, and it’s hard to imagine anything but a water-logged world. More than 70 percent of Earth’s surface is covered in oceans and roughly 97 percent of the surface water is in those oceans, leaving a scant 1 percent as freshwater. Water is also seldom static, whether it’s flowing in ocean currents or order ventolin hfa online being evaporated and precipitated.

Averaged out over the planet there is about 100 centimeters of rainfall a year, but that’s across a total surface area of around 5.1x1018 square centimeters. In other words, doing the back-of-the-envelope calculation, some 510 trillion metric tons of water gets evaporated and then re-precipitated every year on Earth. But the catch is that we don’t really know where all of this water came from in the order ventolin hfa online first place.

For a long while our picture of the formation of a rocky planet like the Earth has involved a violent, hot assembly some 4.5 billion years ago out of comparatively dry material in the inner solar system. Water would have come along later, with proposals for possible delivery by comets from the chill, frozen outer solar system, or by rocky but still volatile-rich meteoritic infall. But these options have proven tricky to justify order ventolin hfa online completely for a variety of reasons.

Comets, for instance, often (but not always) have a deuterium concentration that doesn’t match what we see in Earth’s water—limiting their likely contribution. Similarly, water-rich rocky meteoritic material—so-called carbonaceous chondrites—have isotopic differences that could also limit how much they contributed order ventolin hfa online to a young planet. At the same time, the representative type of material for building the entirety of a rocky Earth (and matching the planet’s overall isotopic composition in elements like oxygen and calcium) seems to closely resemble what’s called enstatite chondrite.

Chunks of enstatite chondrite are still around in the solar system, and occasionally fall as meteorites. But they’ve been thought to be too dry to order ventolin hfa online be involved in Earth’s water supply. Now, in a work reported by Piani, et al.

In the journal Science, an analysis of the composition of 13 enstatite chondrite meteorite samples reveals a much higher than expected hydrogen content. Extrapolating from these numbers the researchers claim that if this is the type of protoplanetary material order ventolin hfa online that built Earth, it could have resulted in a total, initial water content of at least three times the present mass of water in our oceans. The same material could have also provided a starter mix of atmospheric nitrogen to the young planet.

This possibility is enormously appealing for its relative simplicity. Our wet world was simply made this way from the very beginning, with little order ventolin hfa online need to invoke any more complex evolution except for a small drizzling from comets and other outer solar system material. Whether or not this idea holds up to further scientific scrutiny, it’s a beautiful reminder that even the simplest things in our lives, like a glass of water or a shower in the morning, are actually windows into the deepest origins of everything we know.Scientists just completed one of the most comprehensive investigations of Earth’s climate history—and the findings aren’t favorable.

They found that the planet could eventually warm to levels it hasn’t reached in at least 34 million years. The researchers, led by Thomas Westerhold of the University of order ventolin hfa online Bremen in Germany, constructed datasets using chemical analyses of ancient sediments, drilled from the bottom of the ocean. These sediments, some of which are 66 million years old, are filled with the preserved shells of tiny organisms that can tell scientists about the temperature and chemical composition of the ocean when they were formed.

The sediments, collected from around the world over the course of many years, allowed the order ventolin hfa online researchers to reconstruct Earth’s climate history going back to the mass extinction that killed three-quarters of the planet’s species, including dinosaurs. They found that the planet has passed through four distinct climate phases. Warmhouse, hothouse, coolhouse and icehouse states.

Transitions from one state to another have generally order ventolin hfa online depended on changing greenhouse gas levels, often driven by volcanic eruptions and other natural processes, and shifts in the Earth’s orbit that affected the amount of solar energy reaching the planet. In the hottest phases, more than 50 million years ago, temperatures on Earth were more than 10 degrees Celsius hotter than they are today. But it’s important to note that it took the planet thousands or even millions of years to reach these levels—and that was long before humans ever walked the Earth.

That’s in stark contrast to the kind of climate order ventolin hfa online change that human activity is driving today. For several million years now, the world has been in an icehouse state. But that’s quickly changing.

If human societies do nothing to curb their greenhouse gas emissions, in just a few centuries the Earth could once again reach a temperature threshold not seen for at least 34 order ventolin hfa online million years. Before the industrial era, such a magnitude of warming would have taken thousands of years to occur, at least. €œIf you look at the worst-case scenario [by 2300], the change in mean global temperature is larger than most of the natural variability going back over the last 66 million years order ventolin hfa online related to changes in the Earth’s orbit,” said Jim Zachos, a paleoclimatologist at the University of California, Santa Cruz, and a co-author of the new study, which was published Thursday in the journal Science.

It’s not an inevitable future. With immediate and stringent action to reduce climate change, the world can keep global temperatures from rising more than a few degrees above their preindustrial levels. But the study does warn that without these efforts, Earth is on track for some of the strongest, fastest climate change order ventolin hfa online the planet has ever experienced.

The study may also provide some important insights into how climate change could unfold in the coming decades and centuries. Earth’s climate doesn’t always shift in linear, predictable ways. There are all kinds of order ventolin hfa online feedback processes that can speed things up or slow things down—such as the speed at which glaciers and sea ice melt or the way that clouds change in response to future warming.

In the ancient past, for instance, the study suggests that the world’s ice sheets played an important role in regulating the pace and predictability of the Earth’s climate response to natural changes in greenhouse gases or orbital shifts. Today, scientists believe that the world’s melting ice may also have a big impact on future climate change. These kinds of feedback processes can make it challenging to predict future change, especially over relatively short order ventolin hfa online periods of time.

Reconstructing the Earth’s long-term climate history can help scientists test the models they use to predict its future. If a model can accurately simulate the past, scientists may have more confidence in its ability to simulate present-day climate processes. €œThat’s the beauty of this record,” Zachos order ventolin hfa online said.

€œIt’s something we’ve always wanted to have because of the applicability to testing climate theory.” Reprinted from Climatewire with permission from E&E News. E&E provides daily coverage of essential energy and environmental news at order ventolin hfa online www.eenews.net.Woo-hoo, d’oh, or meh?. Which of these Simpsonian reactions is appropriate to the fact, revealed by a 2019 survey conducted by researchers at Penn State University and the National Center for Science Education (NCSE), that about two in three—67 percent—of public high school biology teachers are presenting evolution forthrightly, emphasizing the broad scientific consensus on evolution while not giving any credence to creationism?.

Only in the context of the long and contentious history of evolution education in the United States is it clear what the most plausible answer is. American teachers have not always been afforded the luxury of order ventolin hfa online teaching evolution forthrightly. John Thomas Scopes, for example, was famously prosecuted for violating Tennessee’s ban on teaching evolution in 1925.

Although his conviction was subsequently overturned, a national survey of high school biology teachers conducted in 1939–1940 revealed that only about half were teaching evolution as a central principle of biology. And bans on teaching evolution remained in place order ventolin hfa online in Arkansas, Mississippi and Tennessee until 1970. New obstacles then emerged, particularly requirements to teach various forms of creationism as alternatives to evolution.

As recently as 15 years ago, in Dover, Pennsylvania, the local school board attempted to require its high school biology teachers to read a statement to their ninth-grade students describing “Darwin’s theory of evolution” as “not a fact,” and commending “intelligent design”—then a trendy slogan for creationism—to their attention as a scientifically credible alternative. The teachers, to their order ventolin hfa online credit, unanimously refused to comply. But their refusal, together with the controversy surrounding the related trial over the constitutionality of the board’s actions, Kitzmiller v.

Dover, intrigued two parents a hundred miles to order ventolin hfa online the northwest, in State College, Pa. Michael Berkman and Eric Plutzer were not just any concerned parents, though. They were political scientists at Penn State with a particular interest in education policy.

What—they wondered—are high school biology teachers teaching about evolution, and what factors influence their teaching practices? order ventolin hfa online. To satisfy their curiosity, Berkman and Plutzer conducted the first modern national survey of high school biology teachers in 2007. The results were dire.

Only a slight majority, 51 percent, reported that they emphasized the broad scientific consensus on evolution while not giving any credence to creationism, as if to suggest no progress in the 67 years since the less rigorous survey of 1939–1940 order ventolin hfa online. That’s why the results of the 2019 survey—a collaboration between Plutzer and the NCSE—are so encouraging. Between 2007 and 2019, there definitely was progress.

From 51 percent of high school biology teachers reporting emphasizing evolution and not creationism in order ventolin hfa online 2007 to 67 percent in 2019. It was matched by a drop from 23 to 12 percent of teachers who offer mixed messages by endorsing both evolution and creationism as a valid scientific alternative to evolution, from 18 to 15 percent of teachers who endorse neither evolution nor creationism, and from 8.6 to 5.6 percent of teachers who endorse creationism while not endorsing evolution. Credit.

National Center for Science Education order ventolin hfa online What accounts for the improvement?. Did intelligent design’s crushing defeat in the Kitzmiller trial make the difference?. Probably order ventolin hfa online not.

Science teachers are guided not by case law but by state science standards, which specify what students in the state’s public schools are expected to learn. Standards thus influence the content of textbooks, statewide testing, and coursework for pre-service and in-service teachers. Importantly, they order ventolin hfa online also provide a shield for teachers facing misguided community pressure over socially contentious topics like evolution.

The results of the 2019 survey suggest that a concerted effort to improve state science standards helped to improve evolution education. The Next Generation Science Standards (NGSS), which debuted in 2013, include “Biological Evolution. Unity and Diversity” as a disciplinary core idea of the life sciences at order ventolin hfa online the middle and high school levels.

By now, 20 states (plus the District of Columbia) have adopted the NGSS, and a further 24 states have adopted standards based on the same evolution-friendly framework on which the NGSS are based. Were states that adopted the NGSS especially hospitable to the teaching of evolution?. Not order ventolin hfa online really.

In 2007, their teachers were less likely to endorse evolution and not creationism than the national average. By 2019, they were more likely. While a variety of explanations are possible, teachers in NGSS states reported having taken more pre-service and in-service order ventolin hfa online coursework in evolution than their colleagues elsewhere, suggesting that the increased expectations impelled both novice and veteran teachers to upgrade their content knowledge of evolution.

Despite the encouraging trend over a mere dozen years, there is still reason for concern. After all, order ventolin hfa online more than one in six high school biology teachers, 17.6 percent, are still presenting creationism as a scientifically credible alternative to evolution. And almost as many high school biology teachers, 15 percent, are still failing to emphasize the broad scientific consensus on evolution, despite its general prevalence in state science standards and despite encouragement from professional organizations.

D’oh!. With 13,500-odd local school districts having primary responsibility for curriculum and instruction, changes to science order ventolin hfa online education are inevitably going to be slow, scattered and incremental. Still, with the aid of uncounted scientists, educators, policymakers, administrators and concerned citizens in general (and perhaps even a certain episode of The Simpsons), clear and convincing improvements for evolution education were demonstrably attained in just a dozen years.

It is a victory worth not only celebrating—woo-hoo!. €”but also enlarging upon.ARGENTINA The earliest dinosaurs laid soft-shelled eggs, paleontologists order ventolin hfa online say. A new chemical analysis of a more than 200-million-year-old fossilized egg from Patagonia—and a clutch of more recent eggs from Mongolia, found in the Gobi Desert—revealed a thin film matching the characteristics of modern soft-shelled eggs.

ENGLAND Archaeologists found that 20 deep shafts, previously thought to be natural sinkholes and ponds, were dug by Neolithic humans. The shafts form a circle two order ventolin hfa online kilometers in diameter, with the Durrington Walls monument at its center, just three kilometers from Stonehenge. BRAZIL In a new paper, researchers documented the largest lightning bolt ever recorded.

The “mega-flash,” which extended order ventolin hfa online for more than 700 kilometers in southern Brazil in 2018, was detected by a new advanced weather satellite in geostationary orbit. ISRAEL Researchers sequenced DNA samples from the Dead Sea Scrolls, identifying fragments made from sheep skin and others made from cow hide. The technique could help match fragments together and unravel the artifacts' geographic origins.

INDONESIA Scientists identified order ventolin hfa online an elusive nose-horned dragon lizard in the forests of North Sumatra. Despite appearing in the mythology of the indigenous Bataks, the visually striking species had been spotted by scientists only once before—almost 130 years ago. AUSTRALIA Submarine drones uncovered an extensive system of underwater “rivers” of dense, salty water along Australia's continental shelf.

These flows carry organic matter from the coast into the deep ocean, and their volume varies seasonally, peaking order ventolin hfa online in winter.The items below are highlights from the free newsletter, “Smart, useful, science stuff about asthma treatment.” To receive newsletter issues daily in your inbox, sign-up here.. Please consider a monthly contribution to support this newsletter. At Nature, Nicky Phillips, David Cyranoski and Smriti Mallapaty covered the announcement that a collaboration between researchers at AstraZeneca and the University of Oxford is pausing Phase 3 treatment-candidate experiments due to a “suspected adverse event” in a study participant in the UK (9/9/20).

The collaboration’s order ventolin hfa online Phase 3 studies are being paused in the U.S., Brazil, South Africa and the UK, Nature reports. €œThe news highlights the importance of waiting for the results of large, properly designed trials [experiments] to assess safety before approving a treatment for widespread use,” the story states. Investigators will start by trying to find out if the participant received the treatment candidate or a placebo, the story states.

And then if it was the treatment, they will assess whether the participant’s reaction order ventolin hfa online is related or unrelated to receiving it. €œI have every confidence that this group [of investigators] will very quickly assess this adverse event and make the results of that investigation known,” said a McGill University bioethicist quoted in the story. Presumably in order ventolin hfa online response to reports of political pushing for approvals this fall, the chief executive officers (CEOs) of 9 pharmaceutical companies released a pledge (dated 9/8/20) to “uphold the integrity of the scientific process as they work towards potential global regulatory filings and approvals of the first asthma treatments.” The CEOs — including those for AstraZeneca, BioNTech, GlaxoSmithKline, Johnson &.

Johnson, Merck, Moderna, and Pfizer — assert they will “only submit for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as [the U.S. Food and Drug Administration].” In other words, they don’t plan to cut any corners in their research nor to yield to political pressure. For more contextualized commentary on what Ed order ventolin hfa online Silverman describes as a “highly unusual turn of events," see his column at STAT (9/7/20).

Meanwhile, the U.S. Food and Drug Administration (FDA) has quickly taken measures to block any political influence over ongoing research to develop treatments to protect us from asthma, report Anna Edney, Drew Armstrong, and Robert Langreth for Bloomberg (9/8/20). One measure reportedly includes the FDA “sticking by" June guidance that the order ventolin hfa online agency will only consider for approval treatment candidates that are at least 50% effective.

Lower down in the story, the reporters write, “There is no guarantee the treatments furthest along in development will be the most effective, or be safe.” And it could take “months more” for Phase 3 findings to be conclusive, the story suggests. Still, the story ends with estimates by drug makers for how soon they might complete their Phase 3 studies (efficacy and safety experiments in thousands of study subjects) of asthma treatment candidates. Moderna reportedly says as soon order ventolin hfa online as Thanksgiving, and Pfizer reportedly has been saying next month.

I remain reasonably skeptical. On Twitter, I came across a searchable web site called “Dear ventolin,” which order ventolin hfa online bills itself as an “interdisciplinary all-female team of researchers and clinicians with expertise including nursing, mental health, demography, health policy/economics, and epidemiology.” Posts date back to July but the site appears to have officially launched 9/10/20. Their mission is to “educate and empower individuals to successfully navigate the asthma treatment information overwhelm.” About two-thirds of the way down the home page, there’s a “submit a question” link.

And below that, previous posts are indexed by topic and dates. The risk of catching asthma on an airplane is “relatively low” if travelers are screened for sickness, wear order ventolin hfa online masks, and are spaced out among seats, according to experts interviewed by Noah Y. Kim for Kaiser Health News (9/10/20).

The air exchange rate and use of HEPA (high-efficiency particulate air) filters on planes also significantly reduce the risk of catching the ventolin from travelers who are several rows away, according to the story. There is order ventolin hfa online still a risk from an infected person seated nearby, the story states. And air filtration alone is insufficient to prevent transmission even when travelers are distanced in the plane, Kim writes.

Delta, Hawaiian, Southwest and JetBlue currently keep middle seats open, the story states. Security checks order ventolin hfa online and waiting at gates also pose some transmission risk. The U.S.

Centers for Disease Control has not confirmed any asthma transmission aboard a U.S. Flight, an airline industry source says order ventolin hfa online in the story, but that might reflect the difficulty of determining where people in the U.S. Contract the ventolin, Kim writes.

€œEven though flying is a relatively low-risk activity,” the story states, “traveling should still be avoided unless absolutely necessary.” An undated, recently published ESPN interactive, bylined by Kyle Bonagura, illustrates its analysis and mapping of anonymized order ventolin hfa online cellphone tracking data for three 2019 U.S. College football games. The maps provide a sense of where fans travel to and disperse to after games and thus the regional concentration of potential asthma (and other infectious disease) spread resulting from the mixing of people before, during and after big match-ups.

The piece includes updates on some of the football conferences’ order ventolin hfa online plans and protocols for the 2020 season. The Big Ten and Pac-12 have postponed their seasons, whereas the SEC (Southeastern Conference) seems to be allowing each school to set its own attendance guidelines. I can’t pretend to follow NCAA (National Collegiate Athletic Association) football designations but some or all of the NCAA teams drew “more than 47.5 million" attendees last season, the piece states.

€œEven with fewer teams in action and limited-capacity crowds, the prospect that college football could play a role in spreading the order ventolin hfa online asthma is too obvious to ignore,” the story states. Thanks to a reader for alerting me to this piece. Check out “To build emotional strength, expand your brain,” by Kerry Hannon at The New York Times (9/2/20).

It basically asserts that learning new material, such as a language order ventolin hfa online or craft, that expands your horizons helps you deal with change and crisis, such as the asthma ventolin. Near the end, the piece lists some free or low-cost online class sites and some programs that allow nontraditional students to audit classes or work on projects with enrolled graduate and undergraduate students. You might enjoy “Looks like I wasn’t muted during our Zoom meeting,” by Susie Aquilina, for McSweeney’s (9/10/20)..

You have can u buy ventolin over the counter to go to extreme lengths to find places on Earth that don’t reveal that they’re part of a water-rich planet. Even the highest and driest deserts, like the Atacama Plateau in South America, still get a minimum of a couple of millimeters of annual precipitation on average (although there are places where we don’t yet know what the average is because it’s simply not rained for years). And if you whip out your handy can u buy ventolin over the counter mass spectrometer on a desert walkabout the chances are that you’ll be able to detect at least a few atmospheric water molecules. Go elsewhere, and it’s hard to imagine anything but a water-logged world.

More than 70 percent of Earth’s surface is covered in oceans and roughly 97 percent of the surface water is in those oceans, leaving a scant 1 percent as freshwater. Water is also seldom static, can u buy ventolin over the counter whether it’s flowing in ocean currents or being evaporated and precipitated. Averaged out over the planet there is about 100 centimeters of rainfall a year, but that’s across a total surface area of around 5.1x1018 square centimeters. In other words, doing the back-of-the-envelope calculation, some 510 trillion metric tons of water gets evaporated and then re-precipitated every year on Earth.

But the catch is that we don’t really know where all of can u buy ventolin over the counter this water came from in the first place. For a long while our picture of the formation of a rocky planet like the Earth has involved a violent, hot assembly some 4.5 billion years ago out of comparatively dry material in the inner solar system. Water would have come along later, with proposals for possible delivery by comets from the chill, frozen outer solar system, or by rocky but still volatile-rich meteoritic infall. But these options have proven tricky to justify completely can u buy ventolin over the counter for a variety of reasons.

Comets, for instance, often (but not always) have a deuterium concentration that doesn’t match what we see in Earth’s water—limiting their likely contribution. Similarly, water-rich rocky meteoritic can u buy ventolin over the counter material—so-called carbonaceous chondrites—have isotopic differences that could also limit how much they contributed to a young planet. At the same time, the representative type of material for building the entirety of a rocky Earth (and matching the planet’s overall isotopic composition in elements like oxygen and calcium) seems to closely resemble what’s called enstatite chondrite. Chunks of enstatite chondrite are still around in the solar system, and occasionally fall as meteorites.

But they’ve been thought to be can u buy ventolin over the counter too dry to be involved in Earth’s water supply. Now, in a work reported by Piani, et al. In the journal Science, an analysis of the composition of 13 enstatite chondrite meteorite samples reveals a much higher than expected hydrogen content. Extrapolating from can u buy ventolin over the counter these numbers the researchers claim that if this is the type of protoplanetary material that built Earth, it could have resulted in a total, initial water content of at least three times the present mass of water in our oceans.

The same material could have also provided a starter mix of atmospheric nitrogen to the young planet. This possibility is enormously appealing for its relative simplicity. Our wet world was simply made this way from the very beginning, with little need to invoke any more complex evolution except for a small can u buy ventolin over the counter drizzling from comets and other outer solar system material. Whether or not this idea holds up to further scientific scrutiny, it’s a beautiful reminder that even the simplest things in our lives, like a glass of water or a shower in the morning, are actually windows into the deepest origins of everything we know.Scientists just completed one of the most comprehensive investigations of Earth’s climate history—and the findings aren’t favorable.

They found that the planet could eventually warm to levels it hasn’t reached in at least 34 million years. The researchers, led by Thomas Westerhold of the University of Bremen in Germany, constructed datasets using chemical analyses of ancient sediments, drilled from the bottom of the ocean can u buy ventolin over the counter. These sediments, some of which are 66 million years old, are filled with the preserved shells of tiny organisms that can tell scientists about the temperature and chemical composition of the ocean when they were formed. The sediments, can u buy ventolin over the counter collected from around the world over the course of many years, allowed the researchers to reconstruct Earth’s climate history going back to the mass extinction that killed three-quarters of the planet’s species, including dinosaurs.

They found that the planet has passed through four distinct climate phases. Warmhouse, hothouse, coolhouse and icehouse states. Transitions from one state to another have generally depended on changing greenhouse gas levels, often driven by volcanic eruptions and other natural processes, and shifts in the Earth’s orbit can u buy ventolin over the counter that affected the amount of solar energy reaching the planet. In the hottest phases, more than 50 million years ago, temperatures on Earth were more than 10 degrees Celsius hotter than they are today.

But it’s important to note that it took the planet thousands or even millions of years to reach these levels—and that was long before humans ever walked the Earth. That’s in can u buy ventolin over the counter stark contrast to the kind of climate change that human activity is driving today. For several million years now, the world has been in an icehouse state. But that’s quickly changing.

If human societies do nothing to curb their greenhouse gas emissions, in just a few centuries the Earth could once again reach a can u buy ventolin over the counter temperature threshold not seen for at least 34 million years. Before the industrial era, such a magnitude of warming would have taken thousands of years to occur, at least. €œIf you look at the worst-case scenario [by 2300], the change in mean can u buy ventolin over the counter global temperature is larger than most of the natural variability going back over the last 66 million years related to changes in the Earth’s orbit,” said Jim Zachos, a paleoclimatologist at the University of California, Santa Cruz, and a co-author of the new study, which was published Thursday in the journal Science. It’s not an inevitable future.

With immediate and stringent action to reduce climate change, the world can keep global temperatures from rising more than a few degrees above their preindustrial levels. But the study does warn that without these efforts, Earth is on track for some of the can u buy ventolin over the counter strongest, fastest climate change the planet has ever experienced. The study may also provide some important insights into how climate change could unfold in the coming decades and centuries. Earth’s climate doesn’t always shift in linear, predictable ways.

There are all kinds of feedback processes that can speed things up or slow things down—such can u buy ventolin over the counter as the speed at which glaciers and sea ice melt or the way that clouds change in response to future warming. In the ancient past, for instance, the study suggests that the world’s ice sheets played an important role in regulating the pace and predictability of the Earth’s climate response to natural changes in greenhouse gases or orbital shifts. Today, scientists believe that the world’s melting ice may also have a big impact on future climate change. These kinds of feedback processes can can u buy ventolin over the counter make it challenging to predict future change, especially over relatively short periods of time.

Reconstructing the Earth’s long-term climate history can help scientists test the models they use to predict its future. If a model can accurately simulate the past, scientists may have more confidence in its ability to simulate present-day climate processes. €œThat’s the can u buy ventolin over the counter beauty of this record,” Zachos said. €œIt’s something we’ve always wanted to have because of the applicability to testing climate theory.” Reprinted from Climatewire with permission from E&E News.

E&E provides daily coverage of essential energy can u buy ventolin over the counter and environmental news at www.eenews.net.Woo-hoo, d’oh, or meh?. Which of these Simpsonian reactions is appropriate to the fact, revealed by a 2019 survey conducted by researchers at Penn State University and the National Center for Science Education (NCSE), that about two in three—67 percent—of public high school biology teachers are presenting evolution forthrightly, emphasizing the broad scientific consensus on evolution while not giving any credence to creationism?. Only in the context of the long and contentious history of evolution education in the United States is it clear what the most plausible answer is. American teachers have not always been afforded can u buy ventolin over the counter the luxury of teaching evolution forthrightly.

John Thomas Scopes, for example, was famously prosecuted for violating Tennessee’s ban on teaching evolution in 1925. Although his conviction was subsequently overturned, a national survey of high school biology teachers conducted in 1939–1940 revealed that only about half were teaching evolution as a central principle of biology. And bans on teaching evolution remained in place in can u buy ventolin over the counter Arkansas, Mississippi and Tennessee until 1970. New obstacles then emerged, particularly requirements to teach various forms of creationism as alternatives to evolution.

As recently as 15 years ago, in Dover, Pennsylvania, the local school board attempted to require its high school biology teachers to read a statement to their ninth-grade students describing “Darwin’s theory of evolution” as “not a fact,” and commending “intelligent design”—then a trendy slogan for creationism—to their attention as a scientifically credible alternative. The teachers, to their credit, unanimously refused to can u buy ventolin over the counter comply. But their refusal, together with the controversy surrounding the related trial over the constitutionality of the board’s actions, Kitzmiller v. Dover, intrigued two parents a hundred miles to the northwest, in can u buy ventolin over the counter State College, Pa.

Michael Berkman and Eric Plutzer were not just any concerned parents, though. They were political scientists at Penn State with a particular interest in education policy. What—they wondered—are high school biology teachers teaching about evolution, and what factors can u buy ventolin over the counter influence their teaching practices?. To satisfy their curiosity, Berkman and Plutzer conducted the first modern national survey of high school biology teachers in 2007.

The results were dire. Only a slight majority, 51 percent, reported that they emphasized the can u buy ventolin over the counter broad scientific consensus on evolution while not giving any credence to creationism, as if to suggest no progress in the 67 years since the less rigorous survey of 1939–1940. That’s why the results of the 2019 survey—a collaboration between Plutzer and the NCSE—are so encouraging. Between 2007 and 2019, there definitely was progress.

From 51 percent of high school biology teachers can u buy ventolin over the counter reporting emphasizing evolution and not creationism in 2007 to 67 percent in 2019. It was matched by a drop from 23 to 12 percent of teachers who offer mixed messages by endorsing both evolution and creationism as a valid scientific alternative to evolution, from 18 to 15 percent of teachers who endorse neither evolution nor creationism, and from 8.6 to 5.6 percent of teachers who endorse creationism while not endorsing evolution. Credit. National Center for Science can u buy ventolin over the counter Education What accounts for the improvement?.

Did intelligent design’s crushing defeat in the Kitzmiller trial make the difference?. Probably not can u buy ventolin over the counter. Science teachers are guided not by case law but by state science standards, which specify what students in the state’s public schools are expected to learn. Standards thus influence the content of textbooks, statewide testing, and coursework for pre-service and in-service teachers.

Importantly, they also can u buy ventolin over the counter provide a shield for teachers facing misguided community pressure over socially contentious topics like evolution. The results of the 2019 survey suggest that a concerted effort to improve state science standards helped to improve evolution education. The Next Generation Science Standards (NGSS), which debuted in 2013, include “Biological Evolution. Unity and Diversity” as a disciplinary core idea of can u buy ventolin over the counter the life sciences at the middle and high school levels.

By now, 20 states (plus the District of Columbia) have adopted the NGSS, and a further 24 states have adopted standards based on the same evolution-friendly framework on which the NGSS are based. Were states that adopted the NGSS especially hospitable to the teaching of evolution?. Not really can u buy ventolin over the counter. In 2007, their teachers were less likely to endorse evolution and not creationism than the national average.

By 2019, they were more likely. While a variety can u buy ventolin over the counter of explanations are possible, teachers in NGSS states reported having taken more pre-service and in-service coursework in evolution than their colleagues elsewhere, suggesting that the increased expectations impelled both novice and veteran teachers to upgrade their content knowledge of evolution. Despite the encouraging trend over a mere dozen years, there is still reason for concern. After all, more than one in six high school biology teachers, 17.6 percent, are still presenting creationism as a scientifically can u buy ventolin over the counter credible alternative to evolution.

And almost as many high school biology teachers, 15 percent, are still failing to emphasize the broad scientific consensus on evolution, despite its general prevalence in state science standards and despite encouragement from professional organizations. D’oh!. With 13,500-odd local school districts having primary responsibility can u buy ventolin over the counter for curriculum and instruction, changes to science education are inevitably going to be slow, scattered and incremental. Still, with the aid of uncounted scientists, educators, policymakers, administrators and concerned citizens in general (and perhaps even a certain episode of The Simpsons), clear and convincing improvements for evolution education were demonstrably attained in just a dozen years.

It is a victory worth not only celebrating—woo-hoo!. €”but also enlarging upon.ARGENTINA The earliest dinosaurs can u buy ventolin over the counter laid soft-shelled eggs, paleontologists say. A new chemical analysis of a more than 200-million-year-old fossilized egg from Patagonia—and a clutch of more recent eggs from Mongolia, found in the Gobi Desert—revealed a thin film matching the characteristics of modern soft-shelled eggs. ENGLAND Archaeologists found that 20 deep shafts, previously thought to be natural sinkholes and ponds, were dug by Neolithic humans.

The shafts form a circle two kilometers in diameter, with the Durrington Walls monument at its center, just three kilometers can u buy ventolin over the counter from Stonehenge. BRAZIL In a new paper, researchers documented the largest lightning bolt ever recorded. The “mega-flash,” which extended for more than 700 can u buy ventolin over the counter kilometers in southern Brazil in 2018, was detected by a new advanced weather satellite in geostationary orbit. ISRAEL Researchers sequenced DNA samples from the Dead Sea Scrolls, identifying fragments made from sheep skin and others made from cow hide.

The technique could help match fragments together and unravel the artifacts' geographic origins. INDONESIA Scientists identified an elusive nose-horned dragon lizard can u buy ventolin over the counter in the forests of North Sumatra. Despite appearing in the mythology of the indigenous Bataks, the visually striking species had been spotted by scientists only once before—almost 130 years ago. AUSTRALIA Submarine drones uncovered an extensive system of underwater “rivers” of dense, salty water along Australia's continental shelf.

These flows carry organic matter from the coast into the deep ocean, and their volume varies seasonally, peaking in winter.The items below are highlights from the can u buy ventolin over the counter free newsletter, “Smart, useful, science stuff about asthma treatment.” To receive newsletter issues daily in your inbox, sign-up here.. Please consider a monthly contribution to support this newsletter. At Nature, Nicky Phillips, David Cyranoski and Smriti Mallapaty covered the announcement that a collaboration between researchers at AstraZeneca and the University of Oxford is pausing Phase 3 treatment-candidate experiments due to a “suspected adverse event” in a study participant in the UK (9/9/20). The collaboration’s Phase 3 studies are can u buy ventolin over the counter being paused in the U.S., Brazil, South Africa and the UK, Nature reports.

€œThe news highlights the importance of waiting for the results of large, properly designed trials [experiments] to assess safety before approving a treatment for widespread use,” the story states. Investigators will start by trying to find out if the participant received the treatment candidate or a placebo, the story states. And then if it was the treatment, they will assess whether the participant’s can u buy ventolin over the counter reaction is related or unrelated to receiving it. €œI have every confidence that this group [of investigators] will very quickly assess this adverse event and make the results of that investigation known,” said a McGill University bioethicist quoted in the story.

Presumably in response to reports of political pushing for approvals this fall, the chief executive officers (CEOs) of 9 can u buy ventolin over the counter pharmaceutical companies released a pledge (dated 9/8/20) to “uphold the integrity of the scientific process as they work towards potential global regulatory filings and approvals of the first asthma treatments.” The CEOs — including those for AstraZeneca, BioNTech, GlaxoSmithKline, Johnson &. Johnson, Merck, Moderna, and Pfizer — assert they will “only submit for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as [the U.S. Food and Drug Administration].” In other words, they don’t plan to cut any corners in their research nor to yield to political pressure. For more contextualized commentary on what Ed Silverman describes can u buy ventolin over the counter as a “highly unusual turn of events," see his column at STAT (9/7/20).

Meanwhile, the U.S. Food and Drug Administration (FDA) has quickly taken measures to block any political influence over ongoing research to develop treatments to protect us from asthma, report Anna Edney, Drew Armstrong, and Robert Langreth for Bloomberg (9/8/20). One measure reportedly includes the FDA “sticking can u buy ventolin over the counter by" June guidance that the agency will only consider for approval treatment candidates that are at least 50% effective. Lower down in the story, the reporters write, “There is no guarantee the treatments furthest along in development will be the most effective, or be safe.” And it could take “months more” for Phase 3 findings to be conclusive, the story suggests.

Still, the story ends with estimates by drug makers for how soon they might complete their Phase 3 studies (efficacy and safety experiments in thousands of study subjects) of asthma treatment candidates. Moderna reportedly says as soon as Thanksgiving, and can u buy ventolin over the counter Pfizer reportedly has been saying next month. I remain reasonably skeptical. On Twitter, can u buy ventolin over the counter I came across a searchable web site called “Dear ventolin,” which bills itself as an “interdisciplinary all-female team of researchers and clinicians with expertise including nursing, mental health, demography, health policy/economics, and epidemiology.” Posts date back to July but the site appears to have officially launched 9/10/20.

Their mission is to “educate and empower individuals to successfully navigate the asthma treatment information overwhelm.” About two-thirds of the way down the home page, there’s a “submit a question” link. And below that, previous posts are indexed by topic and dates. The risk of catching asthma on an airplane is “relatively low” if travelers are screened for sickness, wear masks, and are spaced out can u buy ventolin over the counter among seats, according to experts interviewed by Noah Y. Kim for Kaiser Health News (9/10/20).

The air exchange rate and use of HEPA (high-efficiency particulate air) filters on planes also significantly reduce the risk of catching the ventolin from travelers who are several rows away, according to the story. There is still a risk from an infected person seated nearby, can u buy ventolin over the counter the story states. And air filtration alone is insufficient to prevent transmission even when travelers are distanced in the plane, Kim writes. Delta, Hawaiian, Southwest and JetBlue currently keep middle seats open, the story states.

Security checks can u buy ventolin over the counter and waiting at gates also pose some transmission risk. The U.S. Centers for Disease Control has not confirmed any asthma transmission aboard a U.S. Flight, an airline can u buy ventolin over the counter industry source says in the story, but that might reflect the difficulty of determining where people in the U.S.

Contract the ventolin, Kim writes. €œEven though flying is a relatively low-risk activity,” the story states, can u buy ventolin over the counter “traveling should still be avoided unless absolutely necessary.” An undated, recently published ESPN interactive, bylined by Kyle Bonagura, illustrates its analysis and mapping of anonymized cellphone tracking data for three 2019 U.S. College football games. The maps provide a sense of where fans travel to and disperse to after games and thus the regional concentration of potential asthma (and other infectious disease) spread resulting from the mixing of people before, during and after big match-ups.

The piece includes updates on some of the football conferences’ can u buy ventolin over the counter plans and protocols for the 2020 season. The Big Ten and Pac-12 have postponed their seasons, whereas the SEC (Southeastern Conference) seems to be allowing each school to set its own attendance guidelines. I can’t pretend to follow NCAA (National Collegiate Athletic Association) football designations but some or all of the NCAA teams drew “more than 47.5 million" attendees last season, the piece states. €œEven with fewer teams in action and limited-capacity crowds, the prospect that college football could play a role in spreading the asthma is too obvious to ignore,” the story can u buy ventolin over the counter states.

Thanks to a reader for alerting me to this piece. Check out “To build emotional strength, expand your brain,” by Kerry Hannon at The New York Times (9/2/20). It basically can u buy ventolin over the counter asserts that learning new material, such as a language or craft, that expands your horizons helps you deal with change and crisis, such as the asthma ventolin. Near the end, the piece lists some free or low-cost online class sites and some programs that allow nontraditional students to audit classes or work on projects with enrolled graduate and undergraduate students.

You might enjoy “Looks like I wasn’t muted during our Zoom meeting,” by Susie Aquilina, for McSweeney’s (9/10/20)..

Ventolin hfa 8gm

The World Health Organization (WHO) try these out today listed the Comirnaty asthma treatment mRNA treatment for emergency use, making the Pfizer/BioNTech treatment the first to receive emergency validation from WHO since the outbreak began a ventolin hfa 8gm year ago.The WHO’s Emergency Use Listing (EUL) opens the door for countries to expedite their own regulatory approval processes to import and administer the treatment. It also enables UNICEF and the Pan-American Health Organization to procure the treatment for distribution to countries in need.“This is a very positive step towards ensuring global access to asthma treatments. But I want to emphasize the need for an even greater global effort to achieve enough treatment supply to meet the needs of priority populations everywhere,” said Dr ventolin hfa 8gm Mariângela Simão, WHO Assistant-Director General for Access to Medicines and Health Products. €œWHO and our partners are working night and day to evaluate other treatments that have reached safety and efficacy standards.

We encourage even more developers to come forward for review and assessment. It’s vitally important that we secure the critical supply ventolin hfa 8gm needed to serve all countries around the world and stem the ventolin.” Regulatory experts convened by WHO from around the world and WHO’s own teams reviewed the data on the Pfizer/BioNTech treatment’s safety, efficacy and quality as part of a risk-versus-benefit analysis. The review found that the treatment met the must-have criteria for safety and efficacy set out by WHO, and that the benefits of using the treatment to address asthma treatment offset potential risks.The treatment is also under policy review. WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) will convene on 5 January, 2021, to formulate treatment specific policies and recommendations for this product’s use ventolin hfa 8gm in populations, drawing from the SAGE population prioritization recommendations for asthma treatments in general, issued in September 2020.The Comirnaty treatment requires storage using an ultra-cold chain.

It needs to be stored at -60°C to -90°C degrees. This requirement makes the treatment more challenging to deploy in settings where ultra-cold chain equipment may not be available or reliably accessible. For that reason, WHO is working to support countries in assessing their delivery plans and preparing for use where possible.How the emergency use listing worksThe emergency use ventolin hfa 8gm listing (EUL) procedure assesses the suitability of novel health products during public health emergencies. The objective is to make medicines, treatments and diagnostics available as rapidly as possible to address the emergency while adhering to stringent criteria of safety, efficacy and quality.

The assessment weighs the threat posed by the emergency as well as the benefit that would accrue from the use of the product against any potential risks.The EUL pathway involves a rigorous assessment of late phase II and phase III clinical trial data as well as substantial additional data on safety, efficacy, quality and a risk management plan. These data are reviewed by independent experts and WHO teams who consider the current body of evidence on the treatment under consideration, the plans for monitoring its use, and plans for further ventolin hfa 8gm studies.Experts from individual national authorities are invited to participate in the EUL review. Once a treatment has been listed for WHO emergency use, WHO engages its regional regulatory networks and partners to inform national health authorities on the treatment and its anticipated benefits based on data from clinical studies to date.In addition to the global, regional, and country regulatory procedures for emergency use, each country undertakes a policy process to decide whether and in whom to use the treatment, with prioritization specified for the earliest use. Countries also undertake a treatment readiness assessment which informs the treatment deployment and introduction plan for the implementation of the treatment under the EUL.As part of the EUL process, the company producing the treatment must commit to continue to generate data to enable full licensure and WHO prequalification of the treatment ventolin hfa 8gm.

The WHO prequalification process will assess additional clinical data generated from treatment trials and deployment on a rolling basis to ensure the treatment meets the necessary standards of quality, safety and efficacy for broader availability.More information:[embedded content]Dr Tedros Adhanom Ghebreyesus, WHO Director-GeneralAs people around the world celebrated New Year's Eve 12 months ago, a new global threat emerged. Since that moment, the asthma treatment ventolin has taken so many lives and caused massive disruption to families, societies and economies all over the world. But it also triggered the fastest and most wide-reaching response to a global health ventolin hfa 8gm emergency in human history. The hallmarks of this response have been an unparalleled mobilization of science, a search for solutions and a commitment to global solidarity.

Acts of generosity, large and small, equipped hospitals with the tools that health workers needed to stay safe and care for their ventolin hfa 8gm patients. Outpourings of kindness have helped society’s most vulnerable through troubled times. treatments, therapeutics and diagnostics have been developed and rolled out, at record speed, thanks to collaborations including the Access to asthma treatment Tools Accelerator. Equity is the essence of the ventolin hfa 8gm ACT Accelerator, and its treatment arm, COVAX, which has secured access to 2 billion doses of promising treatment candidates.

treatments offer great hope to turn the tide of the ventolin. But to protect the world, we must ensure that all people at risk everywhere – not just in countries who can afford treatments – are immunized. To do this, COVAX needs just over 4 billion US dollars urgently to buy treatments for low- and lower-middle ventolin hfa 8gm income countries. This is the challenge we must rise to in the new year.

My brothers and sisters, the events of 2020 have provided telling lessons, and reminders, for ventolin hfa 8gm us all to take into 2021. First and foremost, 2020 has shown that governments must increase investment in public health, from funding access to asthma treatments for all people, to making our systems better prepared to prevent and respond to the next, inevitable, ventolin. At the heart of this is investing in universal health coverage to make health for all a reality. Second, as it will take time to vaccinate everyone against asthma treatment, we must keep adhering to ventolin hfa 8gm tried and tested measures that keep each and all of us safe.

This means maintaining physical distance, wearing face masks, practicing hand and respiratory hygiene, avoiding crowded indoor places and meeting people outside. These simple, yet effective measures will save lives and reduce the suffering that so many people encountered in ventolin hfa 8gm 2020. Third, and above all, we must commit to working together in solidarity, as a global community, to promote and protect health today, and in the future. We have seen how divisions in politics and communities feed the ventolin and foment the crisis.

But collaboration ventolin hfa 8gm and partnership save lives and safeguard societies. In 2020, a health crisis of historic proportions showed us just how closely connected we all are. We saw how acts of kindness and care helped neighbors through times of great struggle. But we also witnessed how ventolin hfa 8gm acts of malice, and misinformation, caused avoidable harm.

Going into 2021, we have a simple, yet profound, choice to make. Do we ignore the lessons of 2020 and allow insular, partisan approaches, conspiracy theories and attacks on science to prevail, resulting in unnecessary suffering to people’s health and society at large? ventolin hfa 8gm. Or do we walk the last miles of this crisis together, helping each other along the way, from sharing treatments fairly, to offering accurate advice, compassion and care to all who need, as one global family. The choice is easy.

There is light at the end of the tunnel, and we will ventolin hfa 8gm get there by taking the path together. WHO stands with you – We Are Family and we are In This Together. I wish you and your loved ones a peaceful, safe and healthy new year..

The World Health Organization (WHO) today listed the Comirnaty asthma treatment mRNA treatment for emergency use, making the can u buy ventolin over the counter Pfizer/BioNTech treatment the first to receive emergency validation from WHO since the outbreak began a year ago.The WHO’s Emergency Use Listing (EUL) opens the door for countries to expedite their own regulatory approval processes to import and administer the treatment read what he said. It also enables UNICEF and the Pan-American Health Organization to procure the treatment for distribution to countries in need.“This is a very positive step towards ensuring global access to asthma treatments. But I want to emphasize the need for an even greater global effort to achieve enough treatment supply to meet can u buy ventolin over the counter the needs of priority populations everywhere,” said Dr Mariângela Simão, WHO Assistant-Director General for Access to Medicines and Health Products. €œWHO and our partners are working night and day to evaluate other treatments that have reached safety and efficacy standards.

We encourage even more developers to come forward for review and assessment. It’s vitally important that we secure the critical supply needed to serve all countries around the world and stem the ventolin.” Regulatory experts convened by can u buy ventolin over the counter WHO from around the world and WHO’s own teams reviewed the data on the Pfizer/BioNTech treatment’s safety, efficacy and quality as part of a risk-versus-benefit analysis. The review found that the treatment met the must-have criteria for safety and efficacy set out by WHO, and that the benefits of using the treatment to address asthma treatment offset potential risks.The treatment is also under policy review. WHO’s Strategic Advisory can u buy ventolin over the counter Group of Experts on Immunization (SAGE) will convene on 5 January, 2021, to formulate treatment specific policies and recommendations for this product’s use in populations, drawing from the SAGE population prioritization recommendations for asthma treatments in general, issued in September 2020.The Comirnaty treatment requires storage using an ultra-cold chain.

It needs to be stored at -60°C to -90°C degrees. This requirement makes the treatment more challenging to deploy in settings where ultra-cold chain equipment may not be available or reliably accessible. For that reason, WHO is working to support countries in assessing their can u buy ventolin over the counter delivery plans and preparing for use where possible.How the emergency use listing worksThe emergency use listing (EUL) procedure assesses the suitability of novel health products during public health emergencies. The objective is to make medicines, treatments and diagnostics available as rapidly as possible to address the emergency while adhering to stringent criteria of safety, efficacy and quality.

The assessment weighs the threat posed by the emergency as well as the benefit that would accrue from the use of the product against any potential risks.The EUL pathway involves a rigorous assessment of late phase II and phase III clinical trial data as well as substantial additional data on safety, efficacy, quality and a risk management plan. These data are reviewed by independent experts and WHO teams who consider the current body of evidence on the can u buy ventolin over the counter treatment under consideration, the plans for monitoring its use, and plans for further studies.Experts from individual national authorities are invited to participate in the EUL review. Once a treatment has been listed for WHO emergency use, WHO engages its regional regulatory networks and partners to inform national health authorities on the treatment and its anticipated benefits based on data from clinical studies to date.In addition to the global, regional, and country regulatory procedures for emergency use, each country undertakes a policy process to decide whether and in whom to use the treatment, with prioritization specified for the earliest use. Countries also undertake a treatment readiness assessment which informs the treatment deployment and introduction plan for the implementation of the treatment under the EUL.As part of the EUL process, the company producing the treatment must commit to continue to generate data to enable can u buy ventolin over the counter full licensure and WHO prequalification of the treatment.

The WHO prequalification process will assess additional clinical data generated from treatment trials and deployment on a rolling basis to ensure the treatment meets the necessary standards of quality, safety and efficacy for broader availability.More information:[embedded content]Dr Tedros Adhanom Ghebreyesus, WHO Director-GeneralAs people around the world celebrated New Year's Eve 12 months ago, a new global threat emerged. Since that moment, the asthma treatment ventolin has taken so many lives and caused massive disruption to families, societies and economies all over the world. But it also triggered can u buy ventolin over the counter the fastest and most wide-reaching response to a global health emergency in human history. The hallmarks of this response have been an unparalleled mobilization of science, a search for solutions and a commitment to global solidarity.

Acts of generosity, large and small, equipped hospitals with the tools that health workers needed to stay safe can u buy ventolin over the counter and care for their patients. Outpourings of kindness have helped society’s most vulnerable through troubled times. treatments, therapeutics and diagnostics have been developed and rolled out, at record speed, thanks to collaborations including the Access to asthma treatment Tools Accelerator. Equity is the essence of the ACT Accelerator, and its treatment arm, COVAX, which has secured can u buy ventolin over the counter access to 2 billion doses of promising treatment candidates.

treatments offer great hope to turn the tide of the ventolin. But to protect the world, we must ensure that all people at risk everywhere – not just in countries who can afford treatments – are immunized. To do this, COVAX needs can u buy ventolin over the counter just over 4 billion US dollars urgently to buy treatments for low- and lower-middle income countries. This is the challenge we must rise to in the new year.

My brothers and sisters, the events of 2020 have provided telling lessons, and reminders, for us all to take into can u buy ventolin over the counter 2021. First and foremost, 2020 has shown that governments must increase investment in public health, from funding access to asthma treatments for all people, to making our systems better prepared to prevent and respond to the next, inevitable, ventolin. At the heart of this is investing in universal health coverage to make health for all a reality. Second, as it will take time to vaccinate everyone against asthma treatment, we must keep adhering to tried and tested measures that keep each and all can u buy ventolin over the counter of us safe.

This means maintaining physical distance, wearing face masks, practicing hand and respiratory hygiene, avoiding crowded indoor places and meeting people outside. These simple, yet effective measures will save lives and reduce the suffering that so many people encountered in can u buy ventolin over the counter 2020. Third, and above all, we must commit to working together in solidarity, as a global community, to promote and protect health today, and in the future. We have seen how divisions in politics and communities feed the ventolin and foment the crisis.

But collaboration and partnership save lives can u buy ventolin over the counter and safeguard societies. In 2020, a health crisis of historic proportions showed us just how closely connected we all are. We saw how acts of kindness and care helped neighbors through times of great struggle. But we also witnessed how acts of malice, and misinformation, caused can u buy ventolin over the counter avoidable harm.

Going into 2021, we have a simple, yet profound, choice to make. Do we ignore the lessons of 2020 can u buy ventolin over the counter and allow insular, partisan approaches, conspiracy theories and attacks on science to prevail, resulting in unnecessary suffering to people’s health and society at large?. Or do we walk the last miles of this crisis together, helping each other along the way, from sharing treatments fairly, to offering accurate advice, compassion and care to all who need, as one global family. The choice is easy.

There is light at the end of the tunnel, and we will get there by taking the path together. WHO stands with you – We Are Family and we are In This Together. I wish you and your loved ones a peaceful, safe and healthy new year..

Novo salbutamol vs ventolin

Start Preamble novo salbutamol vs ventolin Start Printed Page Ventolin online 40921 U.S. Small Business Administration. Interim final novo salbutamol vs ventolin rule.

This interim final rule implements changes related to the forgiveness of loans made under the Paycheck Protection Program (PPP), which was originally established under the asthma Aid, Relief, and Economic Security Act (CARES Act) to provide economic relief to small businesses nationwide adversely impacted by the asthma Disease 2019 (asthma treatment), as amended. SBA has issued a number of interim final rules implementing the PPP Program. This interim final rule further streamlines the forgiveness process for PPP loans novo salbutamol vs ventolin of $150,000 or less by allowing lenders to use a asthma treatment Revenue Reduction Score at the time of forgiveness to document the required revenue reduction for Second Draw PPP Loans, and establishing a direct borrower forgiveness process for lenders that choose to opt-in as an alternative method of processing loan forgiveness applications.

This interim final rule also extends the loan deferment period for those PPP loans where the borrower timely files an appeal of a final SBA loan review decision with the SBA Office of Hearings and Appeals. Effective date novo salbutamol vs ventolin. The provisions of this interim final rule are effective July 28, 2021.

Applicability date. The asthma treatment Revenue Reduction Score portion of this interim final novo salbutamol vs ventolin rule applies to all Second Draw PPP Loans for which the lender has not yet issued a loan forgiveness decision to SBA as of the effective date of this rule. The direct borrower forgiveness process portion of this rule applies to all PPP loans for which a loan forgiveness application has not been submitted by the borrower to the lender as of the effective date of this rule.

The deferment portion of the rule applies to PPP appeals filed after the effective date of this rule and to those PPP appeals filed before the effective date of this rule for which a Notice and Order has not been issued. Comment date novo salbutamol vs ventolin. Comments must be received on or before August 30, 2021.

You may submit comments, identified by docket number SBA-2021-0015 through novo salbutamol vs ventolin the Federal eRulemaking Portal. Http://www.regulations.gov. Follow the instructions for submitting comments.

SBA will post all novo salbutamol vs ventolin comments on www.regulations.gov. If you wish to submit confidential business information (CBI) as defined in the User Notice at www.regulations.gov, please send an email to ppp-ifr@sba.gov. All other comments must be submitted through the Federal novo salbutamol vs ventolin eRulemaking Portal described above.

Highlight the information that you consider to be CBI and explain why you believe SBA should hold this information as confidential. SBA will review the information and make the final determination whether it will publish the information. Start Further Info A Call Center Representative at novo salbutamol vs ventolin 833-572-0502 or the local SBA Field Office.

The list of offices can be found at https://www.sba.gov/​tools/​local-assistance/​districtoffices. If you use a telecommunications device for the deaf (TDD) or a text telephone (TTY), call the Federal Relay Service (FRS), toll free, at 1-800-877-8339. Individuals with disabilities can obtain this document in an accessible format that may be provided in Rich Text Format (RTF) or text format (txt), a thumb drive, an mp3 file, Braille, novo salbutamol vs ventolin large print, audiotape, or compact disc, or other accessible formats.

End Further Info End Preamble Start Supplemental Information I. Background Information On March 27, 2020, the asthma Aid, Relief, novo salbutamol vs ventolin and Economic Security Act (CARES Act) (Pub. L.

116-136) was enacted to provide emergency assistance and health care response for individuals, families, and businesses affected by the asthma Disease 2019 (asthma treatment) ventolin. Section 1102 of the CARES Act temporarily permitted the Small Business Administration (SBA) to guarantee 100 percent of 7(a) loans novo salbutamol vs ventolin under a new program titled the “Paycheck Protection Program,” pursuant to section 7(a)(36) of the Small Business Act (15 U.S.C. 636(a)(36)) (First Draw PPP Loans).

Section 1106 of the CARES Act novo salbutamol vs ventolin provided for forgiveness of up to the full principal amount of qualifying loans guaranteed under the Paycheck Protection Program (PPP). On April 24, 2020, the Paycheck Protection Program and Health Care Enhancement Act (Pub. L.

116-139) was enacted, which novo salbutamol vs ventolin provided additional funding and authority for the PPP Program. On June 5, the Paycheck Protection Program Flexibility Act of 2020 (PPP Flexibility Act) (Pub. L.

116-142) was enacted, which changed provisions of the novo salbutamol vs ventolin PPP relating to the maturity of PPP loans, the deferral of PPP loan payments, and the forgiveness of PPP loans. On July 4, 2020, Public Law 116-147 extended the authority to guarantee PPP loans to August 8, 2020. On December 27, 2020, the Economic Aid to Hard-Hit Small novo salbutamol vs ventolin Businesses, Nonprofits and Venues Act (Economic Aid Act) (Pub.

L. 116-260) was enacted. The Economic Aid Act reauthorized lending under the PPP through novo salbutamol vs ventolin March 31, 2021.

The Economic Aid Act added a new temporary section 7(a)(37) to the Small Business Act, which authorizes SBA to guarantee additional PPP loans (Second Draw PPP Loans) to certain eligible borrowers that previously received a First Draw PPP Loan under generally the same terms and conditions available under section 7(a)(36) of the Small Business Act. Among other things, to be eligible for a Second Draw PPP Loan, the borrower must have experienced a revenue reduction of not less than 25% in at least one quarter of 2020 compared to novo salbutamol vs ventolin the same quarter in 2019. The Economic Aid Act also redesignated section 1106 of the CARES Act as section 7A of the Small Business Act, to appear after section 7 of the Small Business Act.

Additionally, the Economic Aid Act provided for a simplified forgiveness application process for PPP loans of $150,000 or less. On March novo salbutamol vs ventolin 11, 2021, the American Rescue Plan Act (ARPA) (Pub. L.

117-2) was enacted, and among other things, expanded eligibility for First Draw PPP Loans and Second Draw PPP Loans and revised exclusions from payroll costs for purposes of forgiveness. On March 30, 2021, the novo salbutamol vs ventolin PPP Extension Act of 2021 (Pub. L.

117-6) was enacted, extending SBA's PPP program authority through novo salbutamol vs ventolin June 30, 2021. From April 3, 2020, through August 8, 2020, when the 2020 round of PPP expired, SBA guaranteed over 5.2 million PPP loans made by over 5,000 PPP lenders under delegated authority. From January 11, 2021, when the PPP reopened, through June 30, 2021, when the PPP program authority expired, SBA guaranteed over 6.6 million additional PPP loans.

Thus, the total number of PPP loans novo salbutamol vs ventolin guaranteed by SBA exceeds 11.8 million.[] The total dollar amount of Start Printed Page 40922the PPP loans guaranteed by SBA exceeds $806 billion. SBA posted the first interim final rule implementing the PPP on SBA's website on April 2, 2020, and published the rule in the Federal Register on April 15, 2020 (85 FR 20811). SBA subsequently issued numerous novo salbutamol vs ventolin additional interim final rules.

On June 1, 2020, SBA published an interim final rule on loan forgiveness requirements (85 FR 33004) and an interim final rule on loan review procedures (85 FR 33010). Prior to the publication of the loan forgiveness and loan review interim final rules, on May 15, 2020, SBA issued SBA Form 3508, which was a loan forgiveness application to be used by all PPP borrowers. On June 26, 2020, SBA published an interim final rule revising the loan forgiveness and loan review procedures to conform to the key forgiveness changes made by the novo salbutamol vs ventolin PPP Flexibility Act (85 FR 38304).

In conjunction with the rule, SBA issued a second loan forgiveness application form, SBA Form 3508EZ, which is a streamlined form that incorporates the forgiveness safe harbors established under the PPP Flexibility Act. SBA's 2020 PPP program authority expired on August 8, 2020. On August novo salbutamol vs ventolin 10, 2020, SBA began accepting PPP lender decisions on PPP borrower loan forgiveness applications through SBA's Paycheck Protection Platform (Platform) (forgiveness.sba.gov).

PPP borrowers were required to submit their loan forgiveness applications to their PPP lenders, and as required by section 1106 of the CARES Act (now section 7A of the Small Business Act), lenders were required to issue a decision to SBA on the borrower's loan forgiveness application within 60 days of receipt of the application. On August 27, 2020, SBA issued an novo salbutamol vs ventolin interim final rule on Appeals of SBA Loan Review Decisions under the Paycheck Protection Program (85 FR 52883). On October 2, 2020, SBA began remitting forgiveness payments to PPP lenders that submitted forgiveness decisions to SBA through the Platform.

SBA continues to remit forgiveness payments to PPP lenders, and as of July 12, 2021, SBA has remitted over 4.3 million forgiveness payments to lenders.[] On October 19, 2020, in response to borrower and lender concerns about the complexity of the loan forgiveness process for the smallest of borrowers, SBA and the Department of the Treasury (Treasury) jointly issued an interim final rule revising the loan forgiveness and loan review procedures to simplify the forgiveness process for PPP loans of $50,000 or less. Among other things, the rule exempted borrowers with loans of $50,000 or less from the full-time equivalent employee (FTE) and salary/wage reduction penalties included in section 1106 of the CARES Act, under the joint SBA/Treasury statutory novo salbutamol vs ventolin authority to make de minimis exemptions to those penalties. In conjunction with the rule, SBA issued a third loan forgiveness application, SBA Form 3508S, which was a further streamlined loan forgiveness application available for use by borrowers with loans of $50,000 or less.

On January 14, 2021, SBA published interim final rules implementing the Economic Aid Act amendments to the PPP. The first interim final rule implemented Economic Aid Act changes to, among other things, PPP eligibility, and novo salbutamol vs ventolin consolidated numerous prior interim final rules on PPP (86 FR 3692) (Consolidated Eligibility IFR). The second interim final rule implemented the Second Draw PPP Loan program authorized by the Economic Aid Act under section 7(a)(37) of the Small Business Act (86 FR 3712) (Second Draw IFR).

On February 5, 2021, SBA published a third interim final rule implementing Economic novo salbutamol vs ventolin Aid Act changes related to the forgiveness and review of PPP loans (86 FR 8283) (Consolidated Forgiveness and Loan Review IFR). Among other things, the Consolidated Forgiveness and Loan Review IFR implemented the simplified forgiveness application process for loans of $150,000 or less required by the Economic Aid Act. In conjunction with this rule, on January 19, 2021, SBA issued a revised SBA Form 3508S, which increased the loan amount for which the form could be used from $50,000 to $150,000.[] The new SBA Form 3508S was also shortened to one page, as required by the Economic Aid Act, and no longer requires the submission of supporting forgiveness documentation, as mandated by the Economic Aid Act.

Following the publication of the interim final rules implementing the Economic Aid Act, SBA published another interim final rule on March novo salbutamol vs ventolin 8, 2021, revising certain loan amount calculation and eligibility provisions for PPP (86 FR 13149). On March 22, 2021, SBA published an interim final rule implementing the PPP provisions of ARPA (86 FR 15083). As described below, this interim final rule further streamlines the forgiveness process for PPP loans of $150,000 or less by (a) allowing lenders to use a asthma treatment Revenue Reduction Score at the time of loan forgiveness to document the required revenue reduction for Second Draw PPP loans of $150,000 or less, and (b) establishing novo salbutamol vs ventolin a direct borrower forgiveness process for lenders that choose to opt-in as an alternative method of processing loan forgiveness applications for PPP Loans of $150,000 or less.

This interim final rule also extends the loan deferment period for those PPP loans where the borrower timely files an appeal of a final SBA loan review decision with the SBA Office of Hearings and Appeals. II. Comments and novo salbutamol vs ventolin Immediate Effective Date This interim final rule is being issued without advance notice and public comment because section 1114 of the CARES Act and section 303 of the Economic Aid Act authorize SBA to issue regulations to implement the Paycheck Protection Program without regard to notice requirements.

Even otherwise, SBA finds good cause for setting aside the advance notice-and-public-comment procedure because that procedure would be impracticable and contrary to the public interest. The intent of the CARES Act and the Economic Aid Act is to afford SBA the flexibility to provide relief to America's small businesses and nonprofit organizations expeditiously. Given the urgent need to provide borrowers with timely relief, the purpose of the rule is to minimize the burdens of the current loan novo salbutamol vs ventolin forgiveness process that, without modification, could result in borrowers unnecessarily having to make principal and interest payments on loans that should be forgiven.

If SBA were to follow the advance notice-and-public-comment process, that would delay issuance of the rule by at least three months. SBA understands—based on its expertise and consistent portfolio analysis—that a significant number of borrowers novo salbutamol vs ventolin will have to apply for loan forgiveness in the next three months. Therefore, if the proposed rule is still undergoing notice and comment during that time, these borrowers will be applying under the current process, which (as noted above) would mean these borrowers could unnecessarily have to make principal and interest payments on loans that should be forgiven and would not be positively Start Printed Page 40923impacted by a later rule change.

Providing for notice and comment would render the rule effectively moot and useless for millions of intended beneficiaries. For these same novo salbutamol vs ventolin reasons, SBA has determined that it is impractical and not in the public interest to provide a 30-day delayed effective date. An immediate effective date will allow SBA to expedite loan forgiveness to small businesses and nonprofit organizations and remit forgiveness payments to lenders.

This good cause justification also supports waiver of the 60-day delayed effective date for major rules under Subtitle E of the Small Business Regulatory Enforcement Fairness Act of 1996 (also known as the novo salbutamol vs ventolin Congressional Review Act) at 5 U.S.C. 808(2). Although this interim final rule is effective immediately, comments are solicited from interested members of the public on all aspects of the interim final rule.

These comments novo salbutamol vs ventolin must be submitted on or before August 30, 2021. SBA will consider these comments and the need for making any revisions as a result of these comments. III.

Paycheck Protection Program—asthma treatment Revenue Reduction Score, Direct Borrower Forgiveness Process, and Appeals Deferment Overview A novo salbutamol vs ventolin. Further Streamlining Forgiveness for PPP Loans of $150,000 or Less A key feature of the PPP is that a borrower may obtain forgiveness of up to the full amount of its PPP loan provided that the borrower complied with PPP requirements. Since SBA issued the first loan forgiveness application form (SBA Form 3508) in May 2020 and novo salbutamol vs ventolin published the first loan forgiveness and loan review rules in June 2020, SBA has received comments from borrowers and lenders that the loan forgiveness process is overwhelming and difficult to manage and requesting simplification of the process.

In response to borrower and lender requests for simplification of the loan forgiveness process, Congress enacted the PPP Flexibility Act in June 2020, which created safe harbors from the FTE and salary/wage reduction penalties of section 1106 of the CARES Act, and in response, SBA issued a new streamlined loan forgiveness application (SBA Form 3508EZ) implementing those changes. In October 2020, SBA and Treasury exempted borrowers with loans of $50,000 or less from the FTE and salary/wage reduction penalties and issued a second new streamlined loan forgiveness application (SBA Form 3508S) implementing those changes. Borrowers and lenders continued to express concerns about the complexity of the loan forgiveness process, and in December 2020, Congress enacted the Economic Aid Act, which provides for a simplified loan forgiveness application process novo salbutamol vs ventolin for borrowers with loans of $150,000 or less.

SBA implemented this requirement by revising the second streamlined loan forgiveness application (SBA Form 3508S) to allow all borrowers with loans of $150,000 or less to use the form. Loans of $150,000 or less represent novo salbutamol vs ventolin 93 percent of the outstanding PPP loans. Despite the implementation of the streamlined loan forgiveness application for borrowers with loans of $150,000 or less, many smaller PPP lenders continue to express concerns to SBA that they do not have the technology or human resources to develop efficient electronic loan forgiveness platforms to process the new streamlined loan forgiveness application.[] SBA has also become aware that because lenders are overwhelmed by the volume of PPP loans and are mindful of the statutory 60-day requirement for lenders to issue a forgiveness decision to SBA from receipt of the borrower's loan forgiveness application, lenders are limiting when loan forgiveness applications are accepted from borrowers, creating uncertainty among borrowers that they are going to have to start making payments on their PPP loans while they are waiting for their lenders to accept and process their loan forgiveness applications.

Additionally, SBA has heard concerns from PPP lenders of all sizes that the requirement for borrowers to submit and lenders to review at the time of forgiveness the revenue reduction documentation for Second Draw PPP Loans of $150,000 or less is delaying the forgiveness process for these borrowers. To further simplify and streamline the forgiveness process for loans $150,000 or less, SBA is making two changes under this interim final rule novo salbutamol vs ventolin. First, for Second Draw PPP Loans of $150,000 or less, where the borrower is required to provide revenue reduction documentation at the time of loan forgiveness, SBA is allowing lenders to use a asthma treatment Revenue Reduction Score developed by SBA's contractor as an optional method to document the borrower's revenue reduction.

Second, SBA is making available a direct borrower forgiveness process for lenders that choose to opt-in as an alternative method for processing borrower loan forgiveness applications for all PPP loans of $150,000 or less. 1. asthma treatment Revenue Reduction Score Among other things, to be eligible for a Second Draw PPP Loan, a PPP borrower is required to have experienced a revenue reduction of not less than 25% during one quarter of 2020 compared to the same quarter in 2019.

Under section 7(a)(37)(I) of the Small Business Act, when a borrower applies for a Second Draw PPP Loan of $150,000 or less, the borrower can submit a certification that the borrower meets the revenue reduction standard, provided that on or before the date on which the borrower submits an application for loan forgiveness, the borrower produces adequate documentation that the borrower has met the revenue reduction standard. All Second Draw PPP Loan borrowers were required to certify on their loan applications (SBA Forms 2483-SD and 2483-SD-C) that they realized a reduction in gross receipts in excess of 25% relative to the relevant comparison time period. The Second Draw PPP Loan IFR and the Loan Forgiveness and Loan Review IFR implementing the Economic Aid Act provide that if a borrower with a Second Draw PPP Loan of $150,000 or less did not produce documentation of revenue reduction at the time of application, the borrower must, on or before the date the borrower applies for loan forgiveness, submit to the lender documentation adequate to establish that the borrower experienced a revenue reduction of 25% or greater in 2020 relative to 2019, and such documentation may include relevant tax forms, including annual tax forms, or if relevant tax forms are not available, quarterly financial statements or bank statements.

The rules also provide that where a borrower with a Second Draw PPP Loan of $150,000 or less does not provide documentation of revenue reduction with its loan application, the lender must perform a good faith review of the documents provided by the borrower at or before forgiveness, including the borrower's calculations and supporting documents.[] Start Printed Page 40924 To streamline forgiveness of Second Draw PPP Loans of $150,000 or less where the borrower did not submit documentation of revenue reduction at the time of the loan application, SBA has determined that an alternative form of revenue reduction confirmation is warranted to document the borrower's revenue reduction. An independent third-party SBA contractor has developed a asthma treatment Revenue Reduction Score (score) based on a variety of inputs including industry, geography, and business size. The score uses current data on economic recovery and return of businesses to operational status.[] Each Second Draw PPP Loan of $150,000 or less will be assigned a score, which will be maintained in the Platform and will be visible to lenders to use on an optional basis as an alternative to document revenue reduction.

Additionally, the score will be visible to those borrowers that submit their loan forgiveness applications through the Platform using the direct borrower forgiveness process. When the score meets or exceeds the value required for validation of the borrower's revenue reduction, use of the score will satisfy the requirement for the borrower to document revenue reduction. When the score does not meet the value required for validation of the borrower's revenue reduction, and if the borrower has not already provided documentation to the lender that validates the borrower's revenue reduction, the borrower must provide documentation either directly to the lender (for those lenders that do not opt-in to the direct borrower forgiveness process) or provide documentation to the lender by uploading it to the Platform.

Shortly after issuance of this rule, SBA will be providing additional guidance regarding the procedures for lenders and borrowers to use the asthma treatment Revenue Reduction Score, including when a score meets or exceeds the value required for validation of the required reductions in gross receipts and thus is considered adequate documentation of the borrower's revenue reduction. 2. Direct Borrower Forgiveness Process In response to PPP lender and borrower concerns, SBA is implementing a direct borrower forgiveness process.

The direct borrower forgiveness process is an optional technology solution that SBA is providing to PPP lenders that will leverage SBA's existing and proven Platform and align with and seamlessly integrate the streamlined forgiveness application for loans of $150,000 or less mandated by the Economic Aid Act. When a PPP lender opts-in to the direct borrower forgiveness process, the Platform will provide a single secure location for all of its borrowers with loans of $150,000 or less to apply for loan forgiveness through the Platform using the electronic equivalent of SBA Form 3508S. Upon receipt of notice that a borrower has applied for forgiveness through the Platform, lenders will review the loan forgiveness application in the Platform and issue a forgiveness decision to SBA inside the Platform.

SBA believes that lenders that opt-in to using the direct borrower forgiveness process will benefit with reduced costs, increased efficiency, and more timely remittance of forgiveness payments from SBA, while borrowers will benefit from the ability to submit loan forgiveness applications directly through the Platform and reduce the wait time and uncertainty associated with submission through their lender. Shortly after issuance of this rule, SBA will be issuing more detailed procedural guidance regarding (1) the process for lenders to opt-in to the direct borrower forgiveness process, (2) the process for borrowers with loans of $150,000 or less to access the Platform and submit their loan forgiveness applications directly through the Platform, and (3) the process for lenders to access the forgiveness applications in the Platform to perform reviews of their borrowers' applications, issue forgiveness decisions to SBA, and request forgiveness payments from SBA. During the transition period after the launch of the direct borrower forgiveness process, lenders that opt-in will be expected to complete the processing of any loan forgiveness applications that have already been submitted by borrowers to the lender and should inform such borrowers not to submit a duplicate loan forgiveness application through the Platform.

After the launch of the direct borrower forgiveness process, borrowers will continue to submit loan forgiveness applications to their lenders, rather than through the Platform, under the following circumstances. The PPP lender does not opt-in to use the direct borrower forgiveness process. The borrower's PPP loan amount is greater than $150,000.

The borrower does not agree with the data as provided by the SBA system of record, or cannot validate their identity in the Platform (for example, if there is an unreported change of ownership). Or For any other reason where the Platform rejects the borrower's submission. In such circumstances, borrowers must follow instructions from their lender regarding how the lender expects the borrower to submit a forgiveness application for its PPP loan.

B. Deferment Extension for OHA Appeals Currently, the rule for appeals of final SBA loan review decisions on PPP loans provides that because a PPP borrower must begin making payments of principal and interest on the remaining balance of its PPP loan when SBA remits the loan forgiveness amount to the PPP lender (or notifies the lender that no loan forgiveness is allowed), an appeal by a PPP borrower of any final SBA loan review decision does not extend the deferment period of the PPP loan. SBA is amending the appeals rule to, among other things, provide that a borrower's timely appeal of a final SBA loan review decision will extend the deferment period for the PPP loan until SBA's Office of Hearings and Appeals (OHA) issues a final decision on the appeal.

The revised OHA rule will provide that the borrower should notify the lender of the appeal so that the lender can extend the deferment period. Under the revised OHA rule, an appeal petition must be filed with OHA within 30 calendar days after the appellant's receipt of the final SBA loan review decision. SBA has determined that, in order to avoid the potential administrative burden of having to reverse implementation of the final SBA loan review decision, including the refund of borrower payments by the lender and the processing of forgiveness payments by SBA, a timely appeal by a PPP borrower of a final SBA loan review decision should extend the deferment period of the PPP loan.

SBA believes Start Printed Page 40925that allowing for continued deferment is in the best interest of the borrower. For these reasons, SBA is conforming the applicable PPP rules to provide that a timely appeal by a PPP borrower of a final SBA loan review decision extends the deferment period of the PPP loan until OHA's decision becomes final under 13 CFR 134.1211. IV.

Revisions to Prior PPP Rules Therefore, the following changes are made to PPP rules. 1st Revision. The first sentence of Part IV.2.a.

Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8287) is revised to read as follows. 2. Loan Forgiveness Process a.

What is the general process to obtain loan forgiveness?. To receive loan forgiveness on either a First Draw PPP Loan or a Second Draw PPP Loan, a borrower must complete and submit the Loan Forgiveness Application [] to its lender (or to the lender servicing its loan), or for loans of $150,000 or less if directed by its lender, through the Paycheck Protection Platform (forgiveness.sba.gov). * * * * * * * * 2nd Revision.

Part IV.2.b. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8288) is revised by adding a sentence to the end of the paragraph to read as follows. B.

When must a borrower apply for loan forgiveness or start making payments on a loan?. €‰[] * * * Notwithstanding the foregoing, a borrower's timely appeal of a final SBA loan review decision extends the deferment period on the PPP loan until SBA's Office of Hearings and Appeals issues a final decision on the appeal under 13 CFR 134.1211. 3rd Revision.

Part IV.6.a. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8293) is revised by adding a sentence to the end of the first paragraph to read as follows. 6.

Documentation Requirements a. What must borrowers submit for forgiveness of their PPP loans?. * * * If a Second Draw PPP Loan borrower's asthma treatment Revenue Reduction Score in the Paycheck Protection Platform meets or exceeds the value required to validate the borrower's revenue reduction, no additional documentation is required to be submitted by the borrower.

* * * * * 4th Revision. The first sentence of Part IV.6.b. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8293) is revised to read as follows.

B. What documentation are borrowers who are individuals with self-employment income who file a Form 1040, Schedule C or F required to submit to their lender with their request for loan forgiveness?. For borrowers that received loans of $150,000 or less that use the SBA Form 3508S, the borrower must submit the certification and information required by section 7A(l)(1)(A) of the Small Business Act and, for a Second Draw PPP Loan, revenue reduction documentation (which could be the asthma treatment Revenue Reduction Score, if applicable) if such documentation was not provided at the time of application.[] * * * * * * * * 5th Revision.

Part IV.6.c. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8293) is revised by adding a sentence to the end of the third paragraph to read as follows. C.

What additional documentation must a borrower submit when the President of the United States, Vice President of the United States, the head of an Executive department, or a Member of Congress, or the spouse of any of the preceding, directly or indirectly holds a controlling interest in the borrower?. * * * * * * * * If a borrower with a First Draw PPP Loan of $150,000 or less submits its loan forgiveness application through the Paycheck Protection Platform (Platform), the borrower must submit any required SBA Form 3508D through the Platform not later than 30 days after submitting its application through the Platform. * * * * * 6th Revision.

Footnote 82 in Part V.1.f. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8295) is revised to read as follows. See 85 FR 52833 (Aug.

27, 2020), as amended. 7th Revision. The SBA Form 3508S subsection of Part V.2.a.

Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8296) is revised to read as follows. 2. The Loan Forgiveness Process for Lenders a.

What should a lender review?. * * * * * When a borrower submits SBA Form 3508S or lender's equivalent form, the lender shall. I.

Confirm receipt of the borrower certifications contained in the SBA Form 3508S or lender's equivalent form. Ii. In the case of a Second Draw PPP Loan of $150,000 or less for which the borrower did not provide documentation of revenue reduction with its application and the lender did not conduct a review of the documentation at the time of application.

If the borrower submits its loan forgiveness application to the lender, the lender may review the borrower's asthma treatment Revenue Reduction Score (score) in the Platform to confirm that it meets or exceeds the value required to validate the required reduction in gross receipts. If the borrower's score does not meet or exceed the required value, the lender must confirm the dollar amount and percentage of the borrower's revenue reduction by performing a good faith review, in a reasonable time, of the borrower's calculations and supporting documents concerning the borrower's revenue reduction.[] If the borrower submits its loan forgiveness application through the Paycheck Protection Platform (Platform), the lender must review the borrower's score in the Platform to confirm that it meets or exceeds the value required to validate the required reduction in gross receipts. If the borrower's score does not meet or exceed the required value, the lender must review the revenue reduction documentation uploaded by the borrower into the Platform and confirm the dollar amount and percentage of the borrower's revenue reduction by performing a good faith review, in a reasonable time, of the borrower's calculations and supporting documents concerning the borrower's revenue reduction.

For those borrowers that are required to submit documentation regarding revenue reduction (other than a asthma treatment Revenue Reduction Score), if the lender identifies errors in the borrower's calculation or material lack of substantiation in the borrower's supporting documents regarding revenue reduction, the lender should work with the borrower to remedy the issue. Providing an accurate calculation Start Printed Page 40926of the loan forgiveness amount is the responsibility of the borrower, and the borrower attests to the accuracy of its reported information and calculations on the Loan Forgiveness Application. The borrower shall not receive forgiveness without submitting all required documentation to the lender.

As the First Interim Final Rule [] and section IV.7 above indicate, lenders may rely on borrower representations. As stated in paragraph III.3.c of the First Interim Final Rule, the lender does not need to independently verify the borrower's reported information if the borrower submits documentation supporting its request for loan forgiveness (if required) and attests that it accurately verified the payments for eligible costs. 8th Revision.

The first sentence of the first paragraph of Part V.2.b. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8296) is revised to read as follows. B.

What is the timeline for the lender's decision on a loan forgiveness application?. The lender must issue a decision to SBA on a loan forgiveness application not later than 60 days after receipt of a complete loan forgiveness application from the borrower or, if applicable, notification by the Paycheck Protection Platform (Platform) that the borrower has submitted a loan forgiveness application into the Platform. * * * * * * * * 9th Revision.

Part III.B.9. Of the Consolidated Eligibility IFR (86 FR 3692, 3703) is revised to add a fourth paragraph at the end that reads as follows. 9.

When will I have to begin paying principal and interest on my PPP loan?. * * * * * Notwithstanding the foregoing, a borrower's timely appeal of a final SBA loan review decision extends the deferment period on the PPP loan until SBA's Office of Hearings and Appeals issues a final decision on the appeal under 13 CFR 134.1211. 10th Revision.

Part IV.(g)(2)(v) of the Second Draw IFR (86 FR 3712, 3721) is revised to read as follows. (g) How do I submit an application for a Second Draw PPP Loan and what documentation must I provide to demonstrate eligibility?. * * * * * (2) * * * (v) For loans with a principal amount of $150,000 or less, the applicant must submit documentation sufficient to establish that the applicant experienced a reduction in revenue as provided in subsection (c)(1)(i) of this section at the time of application, on or before the date the borrower submits an application for loan forgiveness, or, if the borrower does not apply for loan forgiveness, at SBA's request.

Such documentation may include relevant tax forms, including annual tax forms, or, if relevant tax forms are not available, a copy of the applicant's quarterly income statements or bank statements. A asthma treatment Revenue Reduction Score that meets or exceeds the value required to validate the required reduction in gross receipts will be considered adequate documentation of the borrower's revenue reduction. 11th Revision.

Part IV.(h)(2)(D) of the Second Draw IFR (86 FR 3712, 3721) is revised to read as follows. (h) What do lenders need to know and do?. (2) * * * (D) For a Second Draw PPP Loan greater than $150,000 or a loan of $150,000 or less where the borrower provides documentation of revenue reduction, confirm the dollar amount and percentage of the borrower's revenue reduction by performing a good faith review, in a reasonable time, of the borrower's calculations and supporting documents concerning the borrower's revenue reduction.

For a loan of $150,000 or less where the borrower does not provide documentation of revenue reduction with its application, the lender shall perform this review when the borrower provides such documentation. If the lender identifies errors in the borrower's calculation or material lack of substantiation in the borrower's supporting documents, the lender should work with the borrower to remedy the issue. For loans of $150,000 or less where the lender elects to use the asthma treatment Revenue Reduction Score (score) in the Paycheck Protection Platform (Platform) or where the lender has opted-in to the direct borrower forgiveness process and the borrower submits a loan forgiveness application to the lender through the Platform, the lender must review the borrower's score to confirm that it meets or exceeds the value required to validate the required reduction in gross receipts, otherwise the lender must review the borrower's supporting documentation in accordance with the foregoing requirements.

* * * * * 12th Revision. Part IV.(j) of the Second Draw IFR (86 FR 3712, 3722) is revised to read as follows. (j) Are Second Draw PPP Loans eligible for loan forgiveness?.

Second Draw PPP Loans are eligible for loan forgiveness on the same terms and conditions as First Draw PPP Loans, except that Second Draw PPP Loan borrowers with a principal amount of $150,000 or less are required to provide documentation of revenue reduction if such documentation was not provided at the time of the loan application as specified in subsections (g)(2)(iv) and (v) of this section. If a lender elects to use the asthma treatment Revenue Reduction Score (score) in the Paycheck Protection Platform (Platform) or where the lender has opted-in to the direct borrower forgiveness process and the borrower submits a loan forgiveness application to the lender through the Platform, a score that meets or exceeds the value required to validate the required reduction in gross receipts will be considered adequate documentation of the borrower's revenue reduction. V.

Additional Information SBA may provide further guidance, if needed, through SBA notices that will be posted on SBA's website at www.sba.gov. Questions on the Paycheck Protection Program may be directed to the Lender Relations Specialist in the local SBA Field Office. The local SBA Field Office may be found at https://www.sba.gov/​tools/​local-assistance/​districtoffices.

Compliance With Executive Orders 12866, 12988, 13132 and 13563, the Congressional Review Act, the Administrative Procedure Act, the Paperwork Reduction Act (44 U.S.C. Ch. 35), and the Regulatory Flexibility Act (5 U.S.C.

601-612). Executive Orders 12866 and 13563 OMB's Office of Information and Regulatory Affairs (OIRA) has determined that this interim final rule is economically significant for the purposes of Executive Orders 12866 and 13563. SBA, however, is proceeding under the emergency provision at Executive Order 12866 section 6(a)(3)(D) based on the need to move expeditiously to mitigate the current economic conditions arising from the asthma treatment emergency.

This rule is necessary to provide economic relief to small businesses and nonprofit organizations nationwide adversely impacted under the asthma treatment Emergency Declaration. We anticipate that this rule will result in substantial benefits to small businesses, nonprofit organizations, their employees, and the communities they serve. However, we lack data to estimate the effects of this rule.Start Printed Page 40927 Congressional Review Act and Administrative Procedure Act OIRA has determined that this is a major rule for purposes of Subtitle E of the Small Business Regulatory Enforcement and Fairness Act of 1996 (also known as the Congressional Review Act or CRA) (5 U.S.C.

804(2) et seq.). Under the CRA, a major rule takes effect 60 days after the rule is published in the Federal Register. 5 U.S.C.

801(a)(3). Notwithstanding this requirement, the CRA allows agencies to dispense with the requirements of section 801 when the agency for good cause finds that such procedure would be impracticable, unnecessary, or contrary to the public interest and the rule shall take effect at such time as the agency promulgating the rule determines. 5 U.S.C.

808(2). Pursuant to section 808(2), SBA for good cause finds that a 60-day delay to provide public notice is impracticable and contrary to the public interest. Likewise, for the same reasons, SBA for good cause finds that there are grounds to waive the 30-day effective date delay under the Administrative Procedure Act.

5 U.S.C. 553(d)(3). As discussed elsewhere in this interim final rule, given the urgent need to provide borrowers with timely relief and the short period of time before certain borrowers will be required to begin making principal and interest payments if they have not yet applied for forgiveness with their lenders, SBA has determined that it is impractical and not in the public interest to provide a delayed effective date.

An immediate effective date will allow SBA to expedite loan forgiveness to small businesses and nonprofit organizations and remit forgiveness payments to lenders. Executive Order 12988 SBA has drafted this rule, to the extent practicable, in accordance with the standards set forth in section 3(a) and 3(b)(2) of Executive Order 12988, to minimize litigation, eliminate ambiguity, and reduce burden. The rule has no preemptive or retroactive effect.

Executive Order 13132 SBA has determined that this rule will not have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various layers of government. Therefore, SBA has determined that this rule has no federalism implications warranting preparation of a federalism assessment. Paperwork Reduction Act, 44 U.S.C.

Chapter 35 SBA has determined that this rule will require revisions to existing recordkeeping or reporting requirements of the Paycheck Protection Program (PPP) information collection, OMB Control Number 3245-0407. The revisions will affect SBA Forms 3508S and 3508D. SBA Form 3508S will be revised to incorporate the direct borrower forgiveness process and the asthma treatment Revenue Reduction Score.

SBA Form 3508D will be revised to incorporate the direct borrower forgiveness process. SBA has requested Office of Management and Budget (OMB) emergency approval of the revisions to the information collections to give small businesses and nonprofits affected by this interim final rule the maximum amount of time to apply for loan forgiveness under the new procedures. Regulatory Flexibility Act (RFA) The Regulatory Flexibility Act (RFA) generally requires that when an agency issues a proposed rule, or a final rule pursuant to section 553(b) of the Administrative Procedure Act or another law, the agency must prepare a regulatory flexibility analysis that meets the requirements of the RFA and publish such analysis in the Federal Register.

5 U.S.C. 603, 604. Rules that are exempt from notice and comment are also exempt from the RFA requirements, including conducting a regulatory flexibility analysis, when among other things the agency for good cause finds that notice and public procedure are impracticable, unnecessary, or contrary to the public interest.

SBA Office of Advocacy guide. How to Comply with the Regulatory Flexibility Act, Ch.1. P.9.

Since this rule is exempt from notice and comment, SBA is not required to conduct a regulatory flexibility analysis. Start Authority 15 U.S.C. 636(a)(36).

636m. asthma Aid, Relief, and Economic Security Act, Pub. L.

116-136, section 1114, and Economic Aid to Hard-Hit Small Businesses, Nonprofits, and Venues Act, Pub. L. 116-260, section 303.

End Authority Start Signature Isabella Casillas Guzman, Administrator. End Signature End Supplemental Information [FR Doc. 2021-16358 Filed 7-28-21.

4:15 pm]BILLING CODE 8026-03-PExplore full-page version of the map The number of new asthma treatment s has increased significantly for the fourth consecutive week, according to a Daily Yonder analysis. The death rate remained relatively unchanged last week compared to two weeks ago. New s in rural counties climbed 60% last week to a total of 46,141.

The rate of new s has more than tripled since the last week of June. The number of asthma treatment-related deaths recorded in rural counties last week declined by 11 to 343. The rate of new s was virtually identical in rural and metropolitan counties last week, 100 new cases per 100,000 in rural counties vs.

104 new cases per 100,000 in metropolitan counties. This week’s analysis covers Sunday, July 15, through Saturday, July 24. The data is from USA Facts.

An Increase in Red-Zone Counties The map above highlights “red-zone” counties – localities where new s total at least 100 new cases for every 100,000 in population over one week. The White House asthma Response Group recommends that counties in the red zone take additional steps to contain the ventolin. Like this story?.

Sign up for our newsletter. The growth in new s is climbing fastest in the Deep South and in states adjacent to Missouri and Arkansas, the epicenter of the resurgence caused by the delta variant of the asthma.Mississippi had a four-fold increase in red-zone counties last week, climbing from 15 to 67. Forty-one of the new red-zone counties were in rural areas.

Nearly 80% of Mississippi’s 65 rural counties are in the red zone. Just one month ago, Mississippi had no red-zone counties.Alabama’s red-zone counties jumped from 20 two weeks ago to 54 last week. Nearly 80% of the state’s 38 rural counties are on the red-zone list.The number of red-zone counties in Texas more than doubled, from 59 two weeks ago to 137 last week.All but one of Arkansas’ 75 counties is in the red zone.Other states seeing significant increases in red-zone counties were Kentucky (from 21 red-zone counties two weeks ago to 56 red-zone counties last week), Kansas (from 30 to 45 red-zone counties), Tennessee (from one to 33 red-zone counties), Oklahoma (from 11 to 32 red-zone counties), and Illinois (from 26 to 39 red-zone counties).

Iowa, with Higher Vaccination Rate, Resists Surge To the north of Missouri, Iowa saw a decline in red-zone counties, from 13 two weeks ago to five last week. In the latest Daily Yonder vaccination analysis, Iowa ranked 15th in its rural vaccination rate (43.8% of the population completely vaccinated). Missouri ranked 42nd (27.7%).Arkansas, where the rate of new rural s doubled last week, ranked 41st for rural vaccinations (29.5%)Other states in the region with below-average rural vaccination rates and large numbers of red-zone counties were Louisiana (27.1% of rural population fully vaccinated), Tennessee (30.6%), Florida (31%), Oklahoma (31.8%), Mississippi (32.2%), Texas (32.2%), Kansas (35.2%).

Start Preamble Start Printed can u buy ventolin over the counter Page 40921 U.S. Small Business Administration. Interim final rule can u buy ventolin over the counter.

This interim final rule implements changes related to the forgiveness of loans made under the Paycheck Protection Program (PPP), which was originally established under the asthma Aid, Relief, and Economic Security Act (CARES Act) to provide economic relief to small businesses nationwide adversely impacted by the asthma Disease 2019 (asthma treatment), as amended. SBA has issued a number of interim final rules implementing the PPP Program. This interim final rule further streamlines the forgiveness process for PPP loans of $150,000 or less by allowing lenders to use a asthma treatment Revenue Reduction Score at the time of forgiveness to document the required revenue reduction for Second Draw PPP Loans, and establishing a direct borrower forgiveness process for lenders that choose to opt-in as an alternative method of processing loan can u buy ventolin over the counter forgiveness applications.

This interim final rule also extends the loan deferment period for those PPP loans where the borrower timely files an appeal of a final SBA loan review decision with the SBA Office of Hearings and Appeals. Effective can u buy ventolin over the counter date. The provisions of this interim final rule are effective July 28, 2021.

Applicability date. The asthma treatment Revenue Reduction Score portion of this interim final rule applies to all Second Draw PPP Loans for which the lender has not yet issued a loan forgiveness decision to SBA as of the effective date of this can u buy ventolin over the counter rule. The direct borrower forgiveness process portion of this rule applies to all PPP loans for which a loan forgiveness application has not been submitted by the borrower to the lender as of the effective date of this rule.

The deferment portion of the rule applies to PPP appeals filed after the effective date of this rule and to those PPP appeals filed before the effective date of this rule for which a Notice and Order has not been issued. Comment can u buy ventolin over the counter date. Comments must be received on or before August 30, 2021.

You may submit comments, identified by docket can u buy ventolin over the counter number SBA-2021-0015 through the Federal eRulemaking Portal. Http://www.regulations.gov. Follow the instructions for submitting comments.

SBA will can u buy ventolin over the counter post all comments on www.regulations.gov. If you wish to submit confidential business information (CBI) as defined in the User Notice at www.regulations.gov, please send an email to ppp-ifr@sba.gov. All other can u buy ventolin over the counter comments must be submitted through the Federal eRulemaking Portal described above.

Highlight the information that you consider to be CBI and explain why you believe SBA should hold this information as confidential. SBA will review the information and make the final determination whether it will publish the information. Start Further Info A Call Center Representative at 833-572-0502 or the can u buy ventolin over the counter local SBA Field Office.

The list of offices can be found at https://www.sba.gov/​tools/​local-assistance/​districtoffices. If you use a telecommunications device for the deaf (TDD) or a text telephone (TTY), call the Federal Relay Service (FRS), toll free, at 1-800-877-8339. Individuals with disabilities can obtain this document in an accessible format that may be provided in Rich Text Format (RTF) or text format (txt), a thumb drive, an mp3 file, Braille, large print, audiotape, can u buy ventolin over the counter or compact disc, or other accessible formats.

End Further Info End Preamble Start Supplemental Information I. Background Information On March 27, can u buy ventolin over the counter 2020, the asthma Aid, Relief, and Economic Security Act (CARES Act) (Pub. L.

116-136) was enacted to provide emergency assistance and health care response for individuals, families, and businesses affected by the asthma Disease 2019 (asthma treatment) ventolin. Section 1102 of the CARES Act temporarily permitted the Small Business can u buy ventolin over the counter Administration (SBA) to guarantee 100 percent of 7(a) loans under a new program titled the “Paycheck Protection Program,” pursuant to section 7(a)(36) of the Small Business Act (15 U.S.C. 636(a)(36)) (First Draw PPP Loans).

Section 1106 of the CARES Act provided for forgiveness of can u buy ventolin over the counter up to the full principal amount of qualifying loans guaranteed under the Paycheck Protection Program (PPP). On April 24, 2020, the Paycheck Protection Program and Health Care Enhancement Act (Pub. L.

116-139) was enacted, which can u buy ventolin over the counter provided additional funding and authority for the PPP Program. On June 5, the Paycheck Protection Program Flexibility Act of 2020 (PPP Flexibility Act) (Pub. L.

116-142) was enacted, which changed provisions of the PPP relating to the maturity of PPP loans, the can u buy ventolin over the counter deferral of PPP loan payments, and the forgiveness of PPP loans. On July 4, 2020, Public Law 116-147 extended the authority to guarantee PPP loans to August 8, 2020. On December 27, 2020, can u buy ventolin over the counter the Economic Aid to Hard-Hit Small Businesses, Nonprofits and Venues Act (Economic Aid Act) (Pub.

L. 116-260) was enacted. The Economic Aid Act reauthorized lending under the PPP through March 31, can u buy ventolin over the counter 2021.

The Economic Aid Act added a new temporary section 7(a)(37) to the Small Business Act, which authorizes SBA to guarantee additional PPP loans (Second Draw PPP Loans) to certain eligible borrowers that previously received a First Draw PPP Loan under generally the same terms and conditions available under section 7(a)(36) of the Small Business Act. Among other things, to be eligible for a Second Draw PPP Loan, the can u buy ventolin over the counter borrower must have experienced a revenue reduction of not less than 25% in at least one quarter of 2020 compared to the same quarter in 2019. The Economic Aid Act also redesignated section 1106 of the CARES Act as section 7A of the Small Business Act, to appear after section 7 of the Small Business Act.

Additionally, the Economic Aid Act provided for a simplified forgiveness application process for PPP loans of $150,000 or less. On March can u buy ventolin over the counter 11, 2021, the American Rescue Plan Act (ARPA) (Pub. L.

117-2) was enacted, and among other things, expanded eligibility for First Draw PPP Loans and Second Draw PPP Loans and revised exclusions from payroll costs for purposes of forgiveness. On March 30, 2021, the PPP can u buy ventolin over the counter Extension Act of 2021 (Pub. L.

117-6) was enacted, extending SBA's PPP program authority through June can u buy ventolin over the counter 30, 2021. From April 3, 2020, through August 8, 2020, when the 2020 round of PPP expired, SBA guaranteed over 5.2 million PPP loans made by over 5,000 PPP lenders under delegated authority. From January 11, 2021, when the PPP reopened, through June 30, 2021, when the PPP program authority expired, SBA guaranteed over 6.6 million additional PPP loans.

Thus, the total number of PPP loans guaranteed by SBA exceeds 11.8 million.[] The total dollar amount of Start Printed Page 40922the PPP loans guaranteed by SBA exceeds $806 can u buy ventolin over the counter billion. SBA posted the first interim final rule implementing the PPP on SBA's website on April 2, 2020, and published the rule in the Federal Register on April 15, 2020 (85 FR 20811). SBA subsequently can u buy ventolin over the counter issued numerous additional interim final rules.

On June 1, 2020, SBA published an interim final rule on loan forgiveness requirements (85 FR 33004) and an interim final rule on loan review procedures (85 FR 33010). Prior to the publication of the loan forgiveness and loan review interim final rules, on May 15, 2020, SBA issued SBA Form 3508, which was a loan forgiveness application to be used by all PPP borrowers. On June 26, 2020, SBA published an interim final rule revising the loan forgiveness and loan review procedures to conform to the key forgiveness changes made by can u buy ventolin over the counter the PPP Flexibility Act (85 FR 38304).

In conjunction with the rule, SBA issued a second loan forgiveness application form, SBA Form 3508EZ, which is a streamlined form that incorporates the forgiveness safe harbors established under the PPP Flexibility Act. SBA's 2020 PPP program authority expired on August 8, 2020. On August 10, 2020, SBA began accepting PPP lender decisions on PPP borrower loan forgiveness applications through SBA's Paycheck Protection Platform (Platform) (forgiveness.sba.gov) can u buy ventolin over the counter.

PPP borrowers were required to submit their loan forgiveness applications to their PPP lenders, and as required by section 1106 of the CARES Act (now section 7A of the Small Business Act), lenders were required to issue a decision to SBA on the borrower's loan forgiveness application within 60 days of receipt of the application. On August 27, 2020, can u buy ventolin over the counter SBA issued an interim final rule on Appeals of SBA Loan Review Decisions under the Paycheck Protection Program (85 FR 52883). On October 2, 2020, SBA began remitting forgiveness payments to PPP lenders that submitted forgiveness decisions to SBA through the Platform.

SBA continues to remit forgiveness payments to PPP lenders, and as of July 12, 2021, SBA has remitted over 4.3 million forgiveness payments to lenders.[] On October 19, 2020, in response to borrower and lender concerns about the complexity of the loan forgiveness process for the smallest of borrowers, SBA and the Department of the Treasury (Treasury) jointly issued an interim final rule revising the loan forgiveness and loan review procedures to simplify the forgiveness process for PPP loans of $50,000 or less. Among other things, the rule exempted borrowers with loans of $50,000 or less from the full-time equivalent employee (FTE) and salary/wage reduction penalties included in section 1106 of the CARES Act, under the joint SBA/Treasury statutory can u buy ventolin over the counter authority to make de minimis exemptions to those penalties. In conjunction with the rule, SBA issued a third loan forgiveness application, SBA Form 3508S, which was a further streamlined loan forgiveness application available for use by borrowers with loans of $50,000 or less.

On January 14, 2021, SBA published interim final rules implementing the Economic Aid Act amendments to the PPP. The first interim final rule implemented Economic Aid Act changes to, among other things, PPP eligibility, and consolidated numerous prior interim final can u buy ventolin over the counter rules on PPP (86 FR 3692) (Consolidated Eligibility IFR). The second interim final rule implemented the Second Draw PPP Loan program authorized by the Economic Aid Act under section 7(a)(37) of the Small Business Act (86 FR 3712) (Second Draw IFR).

On February 5, 2021, SBA published a third interim final rule implementing Economic Aid Act changes related to the forgiveness can u buy ventolin over the counter and review of PPP loans (86 FR 8283) (Consolidated Forgiveness and Loan Review IFR). Among other things, the Consolidated Forgiveness and Loan Review IFR implemented the simplified forgiveness application process for loans of $150,000 or less required by the Economic Aid Act. In conjunction with this rule, on January 19, 2021, SBA issued a revised SBA Form 3508S, which increased the loan amount for which the form could be used from $50,000 to $150,000.[] The new SBA Form 3508S was also shortened to one page, as required by the Economic Aid Act, and no longer requires the submission of supporting forgiveness documentation, as mandated by the Economic Aid Act.

Following the publication of the interim final rules implementing can u buy ventolin over the counter the Economic Aid Act, SBA published another interim final rule on March 8, 2021, revising certain loan amount calculation and eligibility provisions for PPP (86 FR 13149). On March 22, 2021, SBA published an interim final rule implementing the PPP provisions of ARPA (86 FR 15083). As described below, this interim final rule further streamlines the forgiveness process for PPP loans of $150,000 or less by (a) allowing lenders to use a asthma treatment Revenue Reduction Score at the time of loan forgiveness to document the required revenue can u buy ventolin over the counter reduction for Second Draw PPP loans of $150,000 or less, and (b) establishing a direct borrower forgiveness process for lenders that choose to opt-in as an alternative method of processing loan forgiveness applications for PPP Loans of $150,000 or less.

This interim final rule also extends the loan deferment period for those PPP loans where the borrower timely files an appeal of a final SBA loan review decision with the SBA Office of Hearings and Appeals. II. Comments and Immediate Effective Date This interim final rule is being issued without advance notice and public comment because section 1114 of the CARES Act and section 303 of the Economic Aid Act authorize SBA to issue regulations to implement the Paycheck Protection can u buy ventolin over the counter Program without regard to notice requirements.

Even otherwise, SBA finds good cause for setting aside the advance notice-and-public-comment procedure because that procedure would be impracticable and contrary to the public interest. The intent of the CARES Act and the Economic Aid Act is to afford SBA the flexibility to provide relief to America's small businesses and nonprofit organizations expeditiously. Given the urgent need to provide borrowers with timely relief, the purpose of the rule is to minimize the burdens of the current loan forgiveness process that, without modification, could result can u buy ventolin over the counter in borrowers unnecessarily having to make principal and interest payments on loans that should be forgiven.

If SBA were to follow the advance notice-and-public-comment process, that would delay issuance of the rule by at least three months. SBA understands—based on its expertise and consistent portfolio can u buy ventolin over the counter analysis—that a significant number of borrowers will have to apply for loan forgiveness in the next three months. Therefore, if the proposed rule is still undergoing notice and comment during that time, these borrowers will be applying under the current process, which (as noted above) would mean these borrowers could unnecessarily have to make principal and interest payments on loans that should be forgiven and would not be positively Start Printed Page 40923impacted by a later rule change.

Providing for notice and comment would render the rule effectively moot and useless for millions of intended beneficiaries. For these same reasons, can u buy ventolin over the counter SBA has determined that it is impractical and not in the public interest to provide a 30-day delayed effective date. An immediate effective date will allow SBA to expedite loan forgiveness to small businesses and nonprofit organizations and remit forgiveness payments to lenders.

This good can u buy ventolin over the counter cause justification also supports waiver of the 60-day delayed effective date for major rules under Subtitle E of the Small Business Regulatory Enforcement Fairness Act of 1996 (also known as the Congressional Review Act) at 5 U.S.C. 808(2). Although this interim final rule is effective immediately, comments are solicited from interested members of the public on all aspects of the interim final rule.

These comments can u buy ventolin over the counter must be submitted on or before August 30, 2021. SBA will consider these comments and the need for making any revisions as a result of these comments. III.

Paycheck Protection Program—asthma treatment Revenue Reduction Score, Direct Borrower Forgiveness Process, and can u buy ventolin over the counter Appeals Deferment Overview A. Further Streamlining Forgiveness for PPP Loans of $150,000 or Less A key feature of the PPP is that a borrower may obtain forgiveness of up to the full amount of its PPP loan provided that the borrower complied with PPP requirements. Since SBA issued the first loan forgiveness application form (SBA Form 3508) in May 2020 and published the first can u buy ventolin over the counter loan forgiveness and loan review rules in June 2020, SBA has received comments from borrowers and lenders that the loan forgiveness process is overwhelming and difficult to manage and requesting simplification of the process.

In response to borrower and lender requests for simplification of the loan forgiveness process, Congress enacted the PPP Flexibility Act in June 2020, which created safe harbors from the FTE and salary/wage reduction penalties of section 1106 of the CARES Act, and in response, SBA issued a new streamlined loan forgiveness application (SBA Form 3508EZ) implementing those changes. In October 2020, SBA and Treasury exempted borrowers with loans of $50,000 or less from the FTE and salary/wage reduction penalties and issued a second new streamlined loan forgiveness application (SBA Form 3508S) implementing those changes. Borrowers and lenders continued to express concerns about the complexity can u buy ventolin over the counter of the loan forgiveness process, and in December 2020, Congress enacted the Economic Aid Act, which provides for a simplified loan forgiveness application process for borrowers with loans of $150,000 or less.

SBA implemented this requirement by revising the second streamlined loan forgiveness application (SBA Form 3508S) to allow all borrowers with loans of $150,000 or less to use the form. Loans of $150,000 or less represent can u buy ventolin over the counter 93 percent of the outstanding PPP loans. Despite the implementation of the streamlined loan forgiveness application for borrowers with loans of $150,000 or less, many smaller PPP lenders continue to express concerns to SBA that they do not have the technology or human resources to develop efficient electronic loan forgiveness platforms to process the new streamlined loan forgiveness application.[] SBA has also become aware that because lenders are overwhelmed by the volume of PPP loans and are mindful of the statutory 60-day requirement for lenders to issue a forgiveness decision to SBA from receipt of the borrower's loan forgiveness application, lenders are limiting when loan forgiveness applications are accepted from borrowers, creating uncertainty among borrowers that they are going to have to start making payments on their PPP loans while they are waiting for their lenders to accept and process their loan forgiveness applications.

Additionally, SBA has heard concerns from PPP lenders of all sizes that the requirement for borrowers to submit and lenders to review at the time of forgiveness the revenue reduction documentation for Second Draw PPP Loans of $150,000 or less is delaying the forgiveness process for these borrowers. To further simplify and streamline the forgiveness process for loans $150,000 or less, SBA is making two changes under this interim final can u buy ventolin over the counter rule. First, for Second Draw PPP Loans of $150,000 or less, where the borrower is required to provide revenue reduction documentation at the time of loan forgiveness, SBA is allowing lenders to use a asthma treatment Revenue Reduction Score developed by SBA's contractor as an optional method to document the borrower's revenue reduction.

Second, SBA is making available a direct borrower forgiveness process for lenders that choose to opt-in as an alternative method for processing borrower loan forgiveness applications for all PPP loans of $150,000 or less. 1. asthma treatment Revenue Reduction Score Among other things, to be eligible for a Second Draw PPP Loan, a PPP borrower is required to have experienced a revenue reduction of not less than 25% during one quarter of 2020 compared to the same quarter in 2019.

Under section 7(a)(37)(I) of the Small Business Act, when a borrower applies for a Second Draw PPP Loan of $150,000 or less, the borrower can submit a certification that the borrower meets the revenue reduction standard, provided that on or before the date on which the borrower submits an application for loan forgiveness, the borrower produces adequate documentation that the borrower has met the revenue reduction standard. All Second Draw PPP Loan borrowers were required to certify on their loan applications (SBA Forms 2483-SD and 2483-SD-C) that they realized a reduction in gross receipts in excess of 25% relative to the relevant comparison time period. The Second Draw PPP Loan IFR and the Loan Forgiveness and Loan Review IFR implementing the Economic Aid Act provide that if a borrower with a Second Draw PPP Loan of $150,000 or less did not produce documentation of revenue reduction at the time of application, the borrower must, on or before the date the borrower applies for loan forgiveness, submit to the lender documentation adequate to establish that the borrower experienced a revenue reduction of 25% or greater in 2020 relative to 2019, and such documentation may include relevant tax forms, including annual tax forms, or if relevant tax forms are not available, quarterly financial statements or bank statements.

The rules also provide that where a borrower with a Second Draw PPP Loan of $150,000 or less does not provide documentation of revenue reduction with its loan application, the lender must perform a good faith review of the documents provided by the borrower at or before forgiveness, including the borrower's calculations and supporting documents.[] Start Printed Page 40924 To streamline forgiveness of Second Draw PPP Loans of $150,000 or less where the borrower did not submit documentation of revenue reduction at the time of the loan application, SBA has determined that an alternative form of revenue reduction confirmation is warranted to document the borrower's revenue reduction. An independent third-party SBA contractor has developed a asthma treatment Revenue Reduction Score (score) based on a variety of inputs including industry, geography, and business size. The score uses current data on economic recovery and return of businesses to operational status.[] Each Second Draw PPP Loan of $150,000 or less will be assigned a score, which will be maintained in the Platform and will be visible to lenders to use on an optional basis as an alternative to document revenue reduction.

Additionally, the score will be visible to those borrowers that submit their loan forgiveness applications through the Platform using the direct borrower forgiveness process. When the score meets or exceeds the value required for validation of the borrower's revenue reduction, use of the score will satisfy the requirement for the borrower to document revenue reduction. When the score does not meet the value required for validation of the borrower's revenue reduction, and if the borrower has not already provided documentation to the lender that validates the borrower's revenue reduction, the borrower must provide documentation either directly to the lender (for those lenders that do not opt-in to the direct borrower forgiveness process) or provide documentation to the lender by uploading it to the Platform.

Shortly after issuance of this rule, SBA will be providing additional guidance regarding the procedures for lenders and borrowers to use the asthma treatment Revenue Reduction Score, including when a score meets or exceeds the value required for validation of the required reductions in gross receipts and thus is considered adequate documentation of the borrower's revenue reduction. 2. Direct Borrower Forgiveness Process In response to PPP lender and borrower concerns, SBA is implementing a direct borrower forgiveness process.

The direct borrower forgiveness process is an optional technology solution that SBA is providing to PPP lenders that will leverage SBA's existing and proven Platform and align with and seamlessly integrate the streamlined forgiveness application for loans of $150,000 or less mandated by the Economic Aid Act. When a PPP lender opts-in to the direct borrower forgiveness process, the Platform will provide a single secure location for all of its borrowers with loans of $150,000 or less to apply for loan forgiveness through the Platform using the electronic equivalent of SBA Form 3508S. Upon receipt of notice that a borrower has applied for forgiveness through the Platform, lenders will review the loan forgiveness application in the Platform and issue a forgiveness decision to SBA inside the Platform.

SBA believes that lenders that opt-in to using the direct borrower forgiveness process will benefit with reduced costs, increased efficiency, and more timely remittance of forgiveness payments from SBA, while borrowers will benefit from the ability to submit loan forgiveness applications directly through the Platform and reduce the wait time and uncertainty associated with submission through their lender. Shortly after issuance of this rule, SBA will be issuing more detailed procedural guidance regarding (1) the process for lenders to opt-in to the direct borrower forgiveness process, (2) the process for borrowers with loans of $150,000 or less to access the Platform and submit their loan forgiveness applications directly through the Platform, and (3) the process for lenders to access the forgiveness applications in the Platform to perform reviews of their borrowers' applications, issue forgiveness decisions to SBA, and request forgiveness payments from SBA. During the transition period after the launch of the direct borrower forgiveness process, lenders that opt-in will be expected to complete the processing of any loan forgiveness applications that have already been submitted by borrowers to the lender and should inform such borrowers not to submit a duplicate loan forgiveness application through the Platform.

After the launch of the direct borrower forgiveness process, borrowers will continue to submit loan forgiveness applications to their lenders, rather than through the Platform, under the following circumstances. The PPP lender does not opt-in to use the direct borrower forgiveness process. The borrower's PPP loan amount is greater than $150,000.

The borrower does not agree with the data as provided by the SBA system of record, or cannot validate their identity in the Platform (for example, if there is an unreported change of ownership). Or For any other reason where the Platform rejects the borrower's submission. In such circumstances, borrowers must follow instructions from their lender regarding how the lender expects the borrower to submit a forgiveness application for its PPP loan.

B. Deferment Extension for OHA Appeals Currently, the rule for appeals of final SBA loan review decisions on PPP loans provides that because a PPP borrower must begin making payments of principal and interest on the remaining balance of its PPP loan when SBA remits the loan forgiveness amount to the PPP lender (or notifies the lender that no loan forgiveness is allowed), an appeal by a PPP borrower of any final SBA loan review decision does not extend the deferment period of the PPP loan. SBA is amending the appeals rule to, among other things, provide that a borrower's timely appeal of a final SBA loan review decision will extend the deferment period for the PPP loan until SBA's Office of Hearings and Appeals (OHA) issues a final decision on the appeal.

The revised OHA rule will provide that the borrower should notify the lender of the appeal so that the lender can extend the deferment period. Under the revised OHA rule, an appeal petition must be filed with OHA within 30 calendar days after the appellant's receipt of the final SBA loan review decision. SBA has determined that, in order to avoid the potential administrative burden of having to reverse implementation of the final SBA loan review decision, including the refund of borrower payments by the lender and the processing of forgiveness payments by SBA, a timely appeal by a PPP borrower of a final SBA loan review decision should extend the deferment period of the PPP loan.

SBA believes Start Printed Page 40925that allowing for continued deferment is in the best interest of the borrower. For these reasons, SBA is conforming the applicable PPP rules to provide that a timely appeal by a PPP borrower of a final SBA loan review decision extends the deferment period of the PPP loan until OHA's decision becomes final under 13 CFR 134.1211. IV.

Revisions to Prior PPP Rules Therefore, the following changes are made to PPP rules. 1st Revision. The first sentence of Part IV.2.a.

Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8287) is revised to read as follows. 2. Loan Forgiveness Process a.

What is the general process to obtain loan forgiveness?. To receive loan forgiveness on either a First Draw PPP Loan or a Second Draw PPP Loan, a borrower must complete and submit the Loan Forgiveness Application [] to its lender (or to the lender servicing its loan), or for loans of $150,000 or less if directed by its lender, through the Paycheck Protection Platform (forgiveness.sba.gov). * * * * * * * * 2nd Revision.

Part IV.2.b. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8288) is revised by adding a sentence to the end of the paragraph to read as follows. B.

When must a borrower apply for loan forgiveness or start making payments on a loan?. €‰[] * * * Notwithstanding the foregoing, a borrower's timely appeal of a final SBA loan review decision extends the deferment period on the PPP loan until SBA's Office of Hearings and Appeals issues a final decision on the appeal under 13 CFR 134.1211. 3rd Revision.

Part IV.6.a. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8293) is revised by adding a sentence to the end of the first paragraph to read as follows. 6.

Documentation Requirements a. What must borrowers submit for forgiveness of their PPP loans?. * * * If a Second Draw PPP Loan borrower's asthma treatment Revenue Reduction Score in the Paycheck Protection Platform meets or exceeds the value required to validate the borrower's revenue reduction, no additional documentation is required to be submitted by the borrower.

* * * * * 4th Revision. The first sentence of Part IV.6.b. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8293) is revised to read as follows.

B. What documentation are borrowers who are individuals with self-employment income who file a Form 1040, Schedule C or F required to submit to their lender with their request for loan forgiveness?. For borrowers that received loans of $150,000 or less that use the SBA Form 3508S, the borrower must submit the certification and information required by section 7A(l)(1)(A) of the Small Business Act and, for a Second Draw PPP Loan, revenue reduction documentation (which could be the asthma treatment Revenue Reduction Score, if applicable) if such documentation was not provided at the time of application.[] * * * * * * * * 5th Revision.

Part IV.6.c. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8293) is revised by adding a sentence to the end of the third paragraph to read as follows. C.

What additional documentation must a borrower submit when the President of the United States, Vice President of the United States, the head of an Executive department, or a Member of Congress, or the spouse of any of the preceding, directly or indirectly holds a controlling interest in the borrower?. * * * * * * * * If a borrower with a First Draw PPP Loan of $150,000 or less submits its loan forgiveness application through the Paycheck Protection Platform (Platform), the borrower must submit any required SBA Form 3508D through the Platform not later than 30 days after submitting its application through the Platform. * * * * * 6th Revision.

Footnote 82 in Part V.1.f. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8295) is revised to read as follows. See 85 FR 52833 (Aug.

27, 2020), as amended. 7th Revision. The SBA Form 3508S subsection of Part V.2.a.

Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8296) is revised to read as follows. 2. The Loan Forgiveness Process for Lenders a.

What should a lender review?. * * * * * When a borrower submits SBA Form 3508S or lender's equivalent form, the lender shall. I.

Confirm receipt of the borrower certifications contained in the SBA Form 3508S or lender's equivalent form. Ii. In the case of a Second Draw PPP Loan of $150,000 or less for which the borrower did not provide documentation of revenue reduction with its application and the lender did not conduct a review of the documentation at the time of application.

If the borrower submits its loan forgiveness application to the lender, the lender may review the borrower's asthma treatment Revenue Reduction Score (score) in the Platform to confirm that it meets or exceeds the value required to validate the required reduction in gross receipts. If the borrower's score does not meet or exceed the required value, the lender must confirm the dollar amount and percentage of the borrower's revenue reduction by performing a good faith review, in a reasonable time, of the borrower's calculations and supporting documents concerning the borrower's revenue reduction.[] If the borrower submits its loan forgiveness application through the Paycheck Protection Platform (Platform), the lender must review the borrower's score in the Platform to confirm that it meets or exceeds the value required to validate the required reduction in gross receipts. If the borrower's score does not meet or exceed the required value, the lender must review the revenue reduction documentation uploaded by the borrower into the Platform and confirm the dollar amount and percentage of the borrower's revenue reduction by performing a good faith review, in a reasonable time, of the borrower's calculations and supporting documents concerning the borrower's revenue reduction.

For those borrowers that are required to submit documentation regarding revenue reduction (other than a asthma treatment Revenue Reduction Score), if the lender identifies errors in the borrower's calculation or material lack of substantiation in the borrower's supporting documents regarding revenue reduction, the lender should work with the borrower to remedy the issue. Providing an accurate calculation Start Printed Page 40926of the loan forgiveness amount is the responsibility of the borrower, and the borrower attests to the accuracy of its reported information and calculations on the Loan Forgiveness Application. The borrower shall not receive forgiveness without submitting all required documentation to the lender.

As the First Interim Final Rule [] and section IV.7 above indicate, lenders may rely on borrower representations. As stated in paragraph III.3.c of the First Interim Final Rule, the lender does not need to independently verify the borrower's reported information if the borrower submits documentation supporting its request for loan forgiveness (if required) and attests that it accurately verified the payments for eligible costs. 8th Revision.

The first sentence of the first paragraph of Part V.2.b. Of the Consolidated Forgiveness and Loan Review IFR (86 FR 8283, 8296) is revised to read as follows. B.

What is the timeline for the lender's decision on a loan forgiveness application?. The lender must issue a decision to SBA on a loan forgiveness application not later than 60 days after receipt of a complete loan forgiveness application from the borrower or, if applicable, notification by the Paycheck Protection Platform (Platform) that the borrower has submitted a loan forgiveness application into the Platform. * * * * * * * * 9th Revision.

Part III.B.9. Of the Consolidated Eligibility IFR (86 FR 3692, 3703) is revised to add a fourth paragraph at the end that reads as follows. 9.

When will I have to begin paying principal and interest on my PPP loan?. * * * * * Notwithstanding the foregoing, a borrower's timely appeal of a final SBA loan review decision extends the deferment period on the PPP loan until SBA's Office of Hearings and Appeals issues a final decision on the appeal under 13 CFR 134.1211. 10th Revision.

Part IV.(g)(2)(v) of the Second Draw IFR (86 FR 3712, 3721) is revised to read as follows. (g) How do I submit an application for a Second Draw PPP Loan and what documentation must I provide to demonstrate eligibility?. * * * * * (2) * * * (v) For loans with a principal amount of $150,000 or less, the applicant must submit documentation sufficient to establish that the applicant experienced a reduction in revenue as provided in subsection (c)(1)(i) of this section at the time of application, on or before the date the borrower submits an application for loan forgiveness, or, if the borrower does not apply for loan forgiveness, at SBA's request.

Such documentation may include relevant tax forms, including annual tax forms, or, if relevant tax forms are not available, a copy of the applicant's quarterly income statements or bank statements. A asthma treatment Revenue Reduction Score that meets or exceeds the value required to validate the required reduction in gross receipts will be considered adequate documentation of the borrower's revenue reduction. 11th Revision.

Part IV.(h)(2)(D) of the Second Draw IFR (86 FR 3712, 3721) is revised to read as follows. (h) What do lenders need to know and do?. (2) * * * (D) For a Second Draw PPP Loan greater than $150,000 or a loan of $150,000 or less where the borrower provides documentation of revenue reduction, confirm the dollar amount and percentage of the borrower's revenue reduction by performing a good faith review, in a reasonable time, of the borrower's calculations and supporting documents concerning the borrower's revenue reduction.

For a loan of $150,000 or less where the borrower does not provide documentation of revenue reduction with its application, the lender shall perform this review when the borrower provides such documentation. If the lender identifies errors in the borrower's calculation or material lack of substantiation in the borrower's supporting documents, the lender should work with the borrower to remedy the issue. For loans of $150,000 or less where the lender elects to use the asthma treatment Revenue Reduction Score (score) in the Paycheck Protection Platform (Platform) or where the lender has opted-in to the direct borrower forgiveness process and the borrower submits a loan forgiveness application to the lender through the Platform, the lender must review the borrower's score to confirm that it meets or exceeds the value required to validate the required reduction in gross receipts, otherwise the lender must review the borrower's supporting documentation in accordance with the foregoing requirements.

* * * * * 12th Revision. Part IV.(j) of the Second Draw IFR (86 FR 3712, 3722) is revised to read as follows. (j) Are Second Draw PPP Loans eligible for loan forgiveness?.

Second Draw PPP Loans are eligible for loan forgiveness on the same terms and conditions as First Draw PPP Loans, except that Second Draw PPP Loan borrowers with a principal amount of $150,000 or less are required to provide documentation of revenue reduction if such documentation was not provided at the time of the loan application as specified in subsections (g)(2)(iv) and (v) of this section. If a lender elects to use the asthma treatment Revenue Reduction Score (score) in the Paycheck Protection Platform (Platform) or where the lender has opted-in to the direct borrower forgiveness process and the borrower submits a loan forgiveness application to the lender through the Platform, a score that meets or exceeds the value required to validate the required reduction in gross receipts will be considered adequate documentation of the borrower's revenue reduction. V.

Additional Information SBA may provide further guidance, if needed, through SBA notices that will be posted on SBA's website at www.sba.gov. Questions on the Paycheck Protection Program may be directed to the Lender Relations Specialist in the local SBA Field Office. The local SBA Field Office may be found at https://www.sba.gov/​tools/​local-assistance/​districtoffices.

Compliance With Executive Orders 12866, 12988, 13132 and 13563, the Congressional Review Act, the Administrative Procedure Act, the Paperwork Reduction Act (44 U.S.C. Ch. 35), and the Regulatory Flexibility Act (5 U.S.C.

601-612). Executive Orders 12866 and 13563 OMB's Office of Information and Regulatory Affairs (OIRA) has determined that this interim final rule is economically significant for the purposes of Executive Orders 12866 and 13563. SBA, however, is proceeding under the emergency provision at Executive Order 12866 section 6(a)(3)(D) based on the need to move expeditiously to mitigate the current economic conditions arising from the asthma treatment emergency.

This rule is necessary to provide economic relief to small businesses and nonprofit organizations nationwide adversely impacted under the asthma treatment Emergency Declaration. We anticipate that this rule will result in substantial benefits to small businesses, nonprofit organizations, their employees, and the communities they serve. However, we lack data to estimate the effects of this rule.Start Printed Page 40927 Congressional Review Act and Administrative Procedure Act OIRA has determined that this is a major rule for purposes of Subtitle E of the Small Business Regulatory Enforcement and Fairness Act of 1996 (also known as the Congressional Review Act or CRA) (5 U.S.C.

804(2) et seq.). Under the CRA, a major rule takes effect 60 days after the rule is published in the Federal Register. 5 U.S.C.

801(a)(3). Notwithstanding this requirement, the CRA allows agencies to dispense with the requirements of section 801 when the agency for good cause finds that such procedure would be impracticable, unnecessary, or contrary to the public interest and the rule shall take effect at such time as the agency promulgating the rule determines. 5 U.S.C.

808(2). Pursuant to section 808(2), SBA for good cause finds that a 60-day delay to provide public notice is impracticable and contrary to the public interest. Likewise, for the same reasons, SBA for good cause finds that there are grounds to waive the 30-day effective date delay under the Administrative Procedure Act.

5 U.S.C. 553(d)(3). As discussed elsewhere in this interim final rule, given the urgent need to provide borrowers with timely relief and the short period of time before certain borrowers will be required to begin making principal and interest payments if they have not yet applied for forgiveness with their lenders, SBA has determined that it is impractical and not in the public interest to provide a delayed effective date.

An immediate effective date will allow SBA to expedite loan forgiveness to small businesses and nonprofit organizations and remit forgiveness payments to lenders. Executive Order 12988 SBA has drafted this rule, to the extent practicable, in accordance with the standards set forth in section 3(a) and 3(b)(2) of Executive Order 12988, to minimize litigation, eliminate ambiguity, and reduce burden. The rule has no preemptive or retroactive effect.

Executive Order 13132 SBA has determined that this rule will not have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various layers of government. Therefore, SBA has determined that this rule has no federalism implications warranting preparation of a federalism assessment. Paperwork Reduction Act, 44 U.S.C.

Chapter 35 SBA has determined that this rule will require revisions to existing recordkeeping or reporting requirements of the Paycheck Protection Program (PPP) information collection, OMB Control Number 3245-0407. The revisions will affect SBA Forms 3508S and 3508D. SBA Form 3508S will be revised to incorporate the direct borrower forgiveness process and the asthma treatment Revenue Reduction Score.

SBA Form 3508D will be revised to incorporate the direct borrower forgiveness process. SBA has requested Office of Management and Budget (OMB) emergency approval of the revisions to the information collections to give small businesses and nonprofits affected by this interim final rule the maximum amount of time to apply for loan forgiveness under the new procedures. Regulatory Flexibility Act (RFA) The Regulatory Flexibility Act (RFA) generally requires that when an agency issues a proposed rule, or a final rule pursuant to section 553(b) of the Administrative Procedure Act or another law, the agency must prepare a regulatory flexibility analysis that meets the requirements of the RFA and publish such analysis in the Federal Register.

5 U.S.C. 603, 604. Rules that are exempt from notice and comment are also exempt from the RFA requirements, including conducting a regulatory flexibility analysis, when among other things the agency for good cause finds that notice and public procedure are impracticable, unnecessary, or contrary to the public interest.

SBA Office of Advocacy guide. How to Comply with the Regulatory Flexibility Act, Ch.1. P.9.

Since this rule is exempt from notice and comment, SBA is not required to conduct a regulatory flexibility analysis. Start Authority 15 U.S.C. 636(a)(36).

636m. asthma Aid, Relief, and Economic Security Act, Pub. L.

116-136, section 1114, and Economic Aid to Hard-Hit Small Businesses, Nonprofits, and Venues Act, Pub. L. 116-260, section 303.

End Authority Start Signature Isabella Casillas Guzman, Administrator. End Signature End Supplemental Information [FR Doc. 2021-16358 Filed 7-28-21.

4:15 pm]BILLING CODE 8026-03-PExplore full-page version of the map The number of new asthma treatment s has increased significantly for the fourth consecutive week, according to a Daily Yonder analysis. The death rate remained relatively unchanged last week compared to two weeks ago. New s in rural counties climbed 60% last week to a total of 46,141.

The rate of new s has more than tripled since the last week of June. The number of asthma treatment-related deaths recorded in rural counties last week declined by 11 to 343. The rate of new s was virtually identical in rural and metropolitan counties last week, 100 new cases per 100,000 in rural counties vs.

104 new cases per 100,000 in metropolitan counties. This week’s analysis covers Sunday, July 15, through Saturday, July 24. The data is from USA Facts.

An Increase in Red-Zone Counties The map above highlights “red-zone” counties – localities where new s total at least 100 new cases for every 100,000 in population over one week. The White House asthma Response Group recommends that counties in the red zone take additional steps to contain the ventolin. Like this story?.

Sign up for our newsletter. The growth in new s is climbing fastest in the Deep South and in states adjacent to Missouri and Arkansas, the epicenter of the resurgence caused by the delta variant of the asthma.Mississippi had a four-fold increase in red-zone counties last week, climbing from 15 to 67. Forty-one of the new red-zone counties were in rural areas.

Nearly 80% of Mississippi’s 65 rural counties are in the red zone. Just one month ago, Mississippi had no red-zone counties.Alabama’s red-zone counties jumped from 20 two weeks ago to 54 last week. Nearly 80% of the state’s 38 rural counties are on the red-zone list.The number of red-zone counties in Texas more than doubled, from 59 two weeks ago to 137 last week.All but one of Arkansas’ 75 counties is in the red zone.Other states seeing significant increases in red-zone counties were Kentucky (from 21 red-zone counties two weeks ago to 56 red-zone counties last week), Kansas (from 30 to 45 red-zone counties), Tennessee (from one to 33 red-zone counties), Oklahoma (from 11 to 32 red-zone counties), and Illinois (from 26 to 39 red-zone counties).

Iowa, with Higher Vaccination Rate, Resists Surge To the north of Missouri, Iowa saw a decline in red-zone counties, from 13 two weeks ago to five last week. In the latest Daily Yonder vaccination analysis, Iowa ranked 15th in its rural vaccination rate (43.8% of the population completely vaccinated). Missouri ranked 42nd (27.7%).Arkansas, where the rate of new rural s doubled last week, ranked 41st for rural vaccinations (29.5%)Other states in the region with below-average rural vaccination rates and large numbers of red-zone counties were Louisiana (27.1% of rural population fully vaccinated), Tennessee (30.6%), Florida (31%), Oklahoma (31.8%), Mississippi (32.2%), Texas (32.2%), Kansas (35.2%).

Page updated: 01.06.2010 21:00