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Pfizer and BioNTech are moving to enlarge the Phase where to buy generic aricept 3 trial of their Covid-19 vaccine by 50%, which could allow the companies to collect more safety and efficacy data and to increase the diversity of the study’s participants.The companies said in a press release that they would increase the size of the study to 44,000 participants, up from an initial recruitment goal of 30,000 individuals.The U.S. Food and Drug Administration will have to approve the change before it goes into effect.advertisement “The companies continue to expect that a conclusive readout on efficacy is likely by the end of October,” the press release said. The Pfizer and BioNTech where to buy generic aricept study is likely to be among the first in the U.S. To report efficacy data from a Phase 3 trial.

Expanding the trial will likely make it where to buy generic aricept easier for the company to demonstrate whether the vaccine is effective against SARS-CoV-2, the virus that causes Covid-19. The companies also said that the change will allow the study to include a more diverse population. The companies said the study will now include adolescents as young as 16, people with stable HIV, and those with hepatitis C or hepatitis B.advertisement The companies said that the trial is expected to reach its initial target of 30,000 patients next week where to buy generic aricept. Moderna, which started its trial on the same day as Pfizer, said on Sept.

4 that it is working to increase the diversity of trial participants in its study, “even if those efforts impact the speed of enrollment.” The Pfizer/BioNTech study could finish sooner than where to buy generic aricept Moderna’s, even though the two began on the same day, for other reasons, as well. Both vaccines require a second shot. Pfizer’s is given after three weeks, while Moderna’s is given after four where to buy generic aricept. The Pfizer trial also starts to count cases of Covid-19 sooner after participants receive their shots than the Moderna study.But the Pfizer/BioNTech vaccine could also prove to be one of the most difficult of the experimental vaccines to distribute, should they prove effective.

The vaccine must be kept at a temperature of -70 degrees Celsius.There has been political pressure to move a vaccine quickly, with President Trump saying that one could be available where to buy generic aricept before election day. Last week, several drugmakers, including Pfizer, issued a pledge not to move a vaccine forward sooner than was justified by the results of their clinical trials.A large, United Kingdom-based Phase 2/3 study testing a Covid-19 vaccine being developed by AstraZeneca has been restarted, according to a statement from the company. News that the trial is resuming comes four days after the disclosure that it had been paused because of a suspected serious adverse reaction in a participant.A spokesperson for where to buy generic aricept AstraZeneca told STAT that at this point, only the trial in the U.K. Has been resumed.

The company is also conducting Phase 2/3 or Phase 3 trials in the U.S., Brazil, and South Africa.“The Company will continue to work with health authorities across the world and be where to buy generic aricept guided as to when other clinical trials can resume to provide the vaccine broadly, equitably and at no profit during this pandemic,” the spokesperson, Michele Meixell, wrote in an email.advertisement Saturday’s statement from AstraZeneca said the independent U.K. Investigation into the event has concluded and it advised the Medicines Health Regulatory Authority, Britain’s equivalent of the Food and Drug Administration, that it was safe to resume the trial. The MHRA concurred and gave the green light for where to buy generic aricept the trial to restart. The illness that triggered the international pause, which occurred in a woman who was in the vaccine arm of the U.K.

Trial, has not been officially disclosed, though AstraZeneca CEO Pascal Soriot told a group of investors on Wednesday that where to buy generic aricept her symptoms were consistent with transverse myelitis, a serious condition involving inflammation of the spinal cord that can cause muscle weakness, paralysis, pain and bladder problems.advertisement The AstraZeneca statement said information about the illness the woman suffered cannot be disclosed. Oxford University, where the vaccine was developed, said in a separate statement that the nature of the illness cannot be revealed “for reasons of participant confidentiality.”As part of the review process, independent boards overseeing trials of a number of other Covid-19 vaccines were analyzing their own data, looking for cases. There are at least 35 vaccines in clinical where to buy generic aricept trials around the world, nine of which are in Phase 3, the final stage of testing. It’s not uncommon for clinical trials to be paused.

This is the second known hold of studies of the where to buy generic aricept AstraZeneca vaccine. A woman in the U.K. Trial was diagnosed with multiple sclerosis in July, but that event, which triggered the first pause, was deemed not to be related to the vaccine.An AstraZeneca spokesperson previously described the decision where to buy generic aricept as a “routine action which has to happen whenever there is a potentially unexplained illness” in a trial. Still, the pause drew extraordinary attention because of the urgent need for progress on Covid-19 vaccines in the midst of the pandemic.In the latest gambit by a state lawmaker to lower prescription drug costs, a Pennsylvania legislator has introduced a bill that would tie prices paid by residents to what Canadians are charged for medicines.Specifically, the legislation would require the state to create a list of the 250 costliest drugs every year.

From there, the Pennsylvania Insurance Department would where to buy generic aricept set a maximum rate paid by health insurers for each medicine on the list based on pricing in Canada’s four largest provinces. And health insurers would have to pass along lower premiums resulting from any reduced medication costs, or pay a fine. Unlock this article by subscribing to STAT Plus and enjoy your first 30 days where to buy generic aricept free!. GET STARTED Log In | Learn More What is it?.

STAT Plus where to buy generic aricept is STAT's premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. What's included? where to buy generic aricept. Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr.Making a key ruling in a long-running battle over lucrative patent rights, a government patent board has knocked down the University of California’s initial claims that its scientists turned CRISPR into a genome editor in plant and animal cells in 2012, threatening its effort to secure patents on the groundbreaking technology.The decision from the Patent Trial and Appeal Board comes in an ongoing dispute over who first invented the use of CRISPR genome editing in eukaryotic cells (animal and plant cells, not bacteria or DNA floating in a test tube).

It’s the where to buy generic aricept latest turn in a years long and at times nasty battle between the Broad Institute of Cambridge, Mass., and UC and its partners, the University of Vienna and scientist Emmanuelle Charpentier (collectively known in the case as CVC). Unlock this article by subscribing to STAT Plus and enjoy your first 30 days free!. GET STARTED Log In | Learn More What is it?. STAT Plus is STAT's premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis.

Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. What's included?. Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr..

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These results are promising, however, as the excellent commentary by Professor Sue Mason identifies, some unanswered questions remain. Whether these results can be generalised across the wider NHS, beyond the unique confines where to buy generic aricept of the capital, and in light of starkly heterogenous healthcare systems and workforces remains unknown.Moving closer to the front doorPhysician in Triage (PIT) remains a controversial topic in EM. In an interesting analysis of PIT from Israel, Schwarzfuchs and colleagues present an uncontrolled before-after analysis of the impacts of this triage strategy on a single time-critical condition, STEMI. At the EMJ, we usually discourage this type where to buy generic aricept of study.

However, here, the authors demonstrate how, with the inclusion of an appropriate logistic regression to consider confounders, this methodology may be an appropriate way to evaluate such interventions which may be difficult to do within a randomised controlled trial. €œMinutes mean myocardium” and as such the reduction in door-to-balloon time of 9 min when a senior physician was present, demonstrated here, may lend further support to the implementation of PIT. This is certainly a rich area for quality where to buy generic aricept improvement work evaluating such targeted interventions for our patients.All about the Bayes’We welcome an observational analysis from Hautz and colleagues that seeks to explain the patient, physician and contextual factors associated with diagnostic test ordering. Baye’s theorem describes the probability of an event based on the prior knowledge conditions that may relate to that event.

A key concept we should all adopt in test ordering. However, this manuscript goes further in exploring that prior knowledge by evaluating physician where to buy generic aricept experience, patient and situational context. Rather surprisingly, in this single centre analysis of 473 patients and 38 physicians, these factors seem to have a limited impact on test ordering. Rather, it where to buy generic aricept seems that, uncertainty around the patient’s condition (high acuity) and case difficulty seem to influence test ordering more.

So, uncertain pre-test probability equates to higher degrees of diagnostic test ordering. The Reverend Bayes would be turning in his grave.WellnessNow, unlike ever before, it is important to establish the need for physical and psychological recuperation among our staff. The first manuscript where to buy generic aricept within our Wellness section, from Graham and colleagues (this months Reader’s Choice) evaluates the Need For Recovery (NFR) Score in 168 emergency workers at a single site. The high NFR in this population provides a quantifiable insight into our high work intensity but further validation is required beyond a single site.

Over to you TERN….While knowing the extent of the problem is of great importance, what we do about it is perhaps a greater challenge. We would therefore encourage our readers to take home some of the top tips included in our expert practice review this month, Top Ten Evidence-Based Countermeasures for Night Shift Workers by Wallace and Haber.There’s a bug going around…We have had a record number of submissions during the COVID-19 pandemic and the extent to which the EM community has pulled together to inform where to buy generic aricept clinical practice at this time has been breath taking. We are sorry we cannot accept all your excellent work. It is a pleasure where to buy generic aricept to publish a number of Reports from the Front on this topic ranging from patient level interventions such as proning, to invaluable lessons from systems wide responses to the pandemic.

However, the importance of evidence-based medicine has never been higher and this is discussed in our excellent Concepts paper by some very eminent EM Professors.Introducing SONO case seriesLastly, this month sees the first in a series of SONO cases published in the EMJ. This will be a regular feature and is a case-based approach to demonstrate how ED Ultrasound can influence and improve patient care.As demand for healthcare in the UK rises, the challenges become those of trying to meet this demand in a patient-centred way whilst managing changes in the delivery of healthcare to enhance the effectiveness and efficiency of services. This requires an increased level of understanding and cooperation between different healthcare professionals, provider where to buy generic aricept organisations and patients. The changes mean reconsidering traditional roles and where appropriate, redefining professional roles, areas of responsibility and team structures, and renegotiating the boundaries between acute and community care.

Government policy has emphasised the need for the NHS to provide increased patient choice, ease of access and delivery of a high-quality service. This is where to buy generic aricept relevant to providers of emergency care services which need to develop new ways of meeting patient needs closer to home and work environments. In emergency care, ambulance services have had to consider new types of responses to those usually provided. Policy initiatives have meant local where to buy generic aricept NHS organisations assuming responsibility for managing and monitoring how local services respond to urgent and non-urgent 999 ambulance calls.

Alongside this, the NHS Long Term Plan emphasises the importance of integrating care through a more joined-up multidisciplinary approach that spans boundaries between primary and secondary care but aims to keep patients out of hospital.At the same time, we are facing workforce crisis across the NHS. This is especially the case in emergency medicine. Failure to seek new where to buy generic aricept opportunities to develop the workforce will only lead to further attrition. The challenge is how to do this in a sustainable, cost-effective and generalisable manner that leads to clear benefits for the workforce, services and patients.

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Patients Figure 1 how can i get aricept. Figure 1. Enrollment and Randomization how can i get aricept.

Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization. 541 were assigned to the remdesivir group and 522 how can i get aricept to the placebo group (Figure 1). Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned.

Forty-nine patients had remdesivir treatment discontinued how can i get aricept before day 10 because of an adverse event or a serious adverse event other than death (36 patients) or because the patient withdrew consent (13). Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2).

As of April 28, 2020, a total of 391 patients in the remdesivir group and how can i get aricept 340 in the placebo group had completed the trial through day 29, recovered, or died. Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. There were 132 patients in the remdesivir how can i get aricept group and 169 in the placebo group who had not recovered and had not completed the day 29 follow-up visit.

The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary analysis because no postbaseline data were available at the time of the database freeze how can i get aricept. Table 1.

Table 1 how can i get aricept. Demographic and Clinical Characteristics at Baseline. The mean age of patients was 58.9 years, and 64.3% were male (Table 1).

On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at how can i get aricept sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1). Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported. 249 (23.4%) how can i get aricept were Hispanic or Latino.

Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The median number of days between symptom onset and randomization was 9 (interquartile how can i get aricept range, 6 to 12). Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix.

272 (25.6%) patients met category 7 criteria on the ordinal scale, how can i get aricept 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4. There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group.

Primary Outcome Figure 2 how can i get aricept. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries how can i get aricept.

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 how can i get aricept 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 how can i get aricept a baseline score of 7 (receiving mechanical ventilation or ECMO. Panel E). Table 2.

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

Figure 3. Time to Recovery According how can i get aricept 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 how can i get aricept patients. Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days. Rate ratio for recovery, 1.32.

95% confidence interval [CI], 1.12 to 1.55 how can i get aricept. P<0.001. 1059 patients (Figure 2 how can i get aricept and Table 2).

Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84). Among patients with a baseline score of 4 (127 patients) and those with a baseline how can i get aricept score of 6 (197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7.

272 patients), how can i get aricept the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable 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 how can i get aricept for recovery, 1.31. 95% CI, 1.12 to 1.54. 1017 patients) how can i get aricept.

Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during how can i get aricept the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, 1.05 to 1.57. 664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81.

380 patients) (Figure how can i get aricept 3). 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, 1.50. 95% CI, 1.18 to 1.91.

P=0.001. 844 patients) (Table 2 and Fig. S5).

Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70. 95% CI, 0.47 to 1.04. 1059 patients).

The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2). The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits. An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10).

Safety Outcomes Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3). 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients).

Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators. Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4).

The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group). Acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]). Pyrexia (27 events [5.0%], as compared with 17 [3.3%]).

Hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]). And increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]). Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.Trial Population Table 1.

Table 1. Characteristics of the Participants in the mRNA-1273 Trial at Enrollment. The 45 enrolled participants received their first vaccination between March 16 and April 14, 2020 (Fig.

S1). Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one in the 25-μg group and one in the 250-μg group) who missed the second vaccination window owing to isolation for suspected Covid-19 while the test results, ultimately negative, were pending. All continued to attend scheduled trial visits.

The demographic characteristics of participants at enrollment are provided in Table 1. Vaccine Safety No serious adverse events were noted, and no prespecified trial halting rules were met. As noted above, one participant in the 25-μg group was withdrawn because of an unsolicited adverse event, transient urticaria, judged to be related to the first vaccination.

Figure 1. Figure 1. Systemic and Local Adverse Events.

The severity of solicited adverse events was graded as mild, moderate, or severe (see Table S1).After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group. All were mild or moderate in severity (Figure 1 and Table S2). Solicited systemic adverse events were more common after the second vaccination and occurred in 7 of 13 participants (54%) in the 25-μg group, all 15 in the 100-μg group, and all 14 in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events.

None of the participants had fever after the first vaccination. After the second vaccination, no participants in the 25-μg group, 6 (40%) in the 100-μg group, and 8 (57%) in the 250-μg group reported fever. One of the events (maximum temperature, 39.6°C) in the 250-μg group was graded severe.

(Additional details regarding adverse events for that participant are provided in the Supplementary Appendix.) Local adverse events, when present, were nearly all mild or moderate, and pain at the injection site was common. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Evaluation of safety clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no patterns of concern (Supplementary Appendix and Table S3).

SARS-CoV-2 Binding Antibody Responses Table 2. Table 2. Geometric Mean Humoral Immunogenicity Assay Responses to mRNA-1273 in Participants and in Convalescent Serum Specimens.

Figure 2. Figure 2. SARS-CoV-2 Antibody and Neutralization Responses.

Shown are geometric mean reciprocal end-point enzyme-linked immunosorbent assay (ELISA) IgG titers to S-2P (Panel A) and receptor-binding domain (Panel B), PsVNA ID50 responses (Panel C), and live virus PRNT80 responses (Panel D). In Panel A and Panel B, boxes and horizontal bars denote interquartile range (IQR) and median area under the curve (AUC), respectively. Whisker endpoints are equal to the maximum and minimum values below or above the median ±1.5 times the IQR.

The convalescent serum panel includes specimens from 41 participants. Red dots indicate the 3 specimens that were also tested in the PRNT assay. The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent serum panel.

In Panel C, boxes and horizontal bars denote IQR and median ID50, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. In the convalescent serum panel, red dots indicate the 3 specimens that were also tested in the PRNT assay.

The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent panel. In Panel D, boxes and horizontal bars denote IQR and median PRNT80, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR.

The three convalescent serum specimens were also tested in ELISA and PsVNA assays. Because of the time-intensive nature of the PRNT assay, for this preliminary report, PRNT results were available only for the 25-μg and 100-μg dose groups.Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15 (Table 2 and Figure 2A). Dose-dependent responses to the first and second vaccinations were evident.

Receptor-binding domain–specific antibody responses were similar in pattern and magnitude (Figure 2B). For both assays, the median magnitude of antibody responses after the first vaccination in the 100-μg and 250-μg dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens. The S-2P ELISA GMTs at day 57 (299,751 [95% confidence interval {CI}, 206,071 to 436,020] in the 25-μg group, 782,719 [95% CI, 619,310 to 989,244] in the 100-μg group, and 1,192,154 [95% CI, 924,878 to 1,536,669] in the 250-μg group) exceeded that in the convalescent serum specimens (142,140 [95% CI, 81,543 to 247,768]).

SARS-CoV-2 Neutralization Responses No participant had detectable PsVNA responses before vaccination. After the first vaccination, PsVNA responses were detected in less than half the participants, and a dose effect was seen (50% inhibitory dilution [ID50]. Figure 2C, Fig.

S8, and Table 2. 80% inhibitory dilution [ID80]. Fig.

S2 and Table S6). However, after the second vaccination, PsVNA responses were identified in serum samples from all participants. The lowest responses were in the 25-μg dose group, with a geometric mean ID50 of 112.3 (95% CI, 71.2 to 177.1) at day 43.

The higher responses in the 100-μg and 250-μg groups were similar in magnitude (geometric mean ID50, 343.8 [95% CI, 261.2 to 452.7] and 332.2 [95% CI, 266.3 to 414.5], respectively, at day 43). These responses were similar to values in the upper half of the distribution of values for convalescent serum specimens. Before vaccination, no participant had detectable 80% live-virus neutralization at the highest serum concentration tested (1:8 dilution) in the PRNT assay.

At day 43, wild-type virus–neutralizing activity capable of reducing SARS-CoV-2 infectivity by 80% or more (PRNT80) was detected in all participants, with geometric mean PRNT80 responses of 339.7 (95% CI, 184.0 to 627.1) in the 25-μg group and 654.3 (95% CI, 460.1 to 930.5) in the 100-μg group (Figure 2D). Neutralizing PRNT80 average responses were generally at or above the values of the three convalescent serum specimens tested in this assay. Good agreement was noted within and between the values from binding assays for S-2P and receptor-binding domain and neutralizing activity measured by PsVNA and PRNT (Figs.

S3 through S7), which provides orthogonal support for each assay in characterizing the humoral response induced by mRNA-1273. SARS-CoV-2 T-Cell Responses The 25-μg and 100-μg doses elicited CD4 T-cell responses (Figs. S9 and S10) that on stimulation by S-specific peptide pools were strongly biased toward expression of Th1 cytokines (tumor necrosis factor α >.

Interleukin 2 >. Interferon γ), with minimal type 2 helper T-cell (Th2) cytokine expression (interleukin 4 and interleukin 13). CD8 T-cell responses to S-2P were detected at low levels after the second vaccination in the 100-μg dose group (Fig.

S11).Trial Design and Oversight The RECOVERY trial was designed to evaluate the effects of potential treatments in patients hospitalized with Covid-19 at 176 National Health Service organizations in the United Kingdom and was supported by the National Institute for Health Research Clinical Research Network. (Details regarding this trial are provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The trial is being coordinated by the Nuffield Department of Population Health at the University of Oxford, the trial sponsor. Although the randomization of patients to receive dexamethasone, hydroxychloroquine, or lopinavir–ritonavir has now been stopped, the trial continues randomization to groups receiving azithromycin, tocilizumab, or convalescent plasma.

Hospitalized patients were eligible for the trial if they had clinically suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put patients at substantial risk if they were to participate in the trial. Initially, recruitment was limited to patients who were at least 18 years of age, but the age limit was removed starting on May 9, 2020. Pregnant or breast-feeding women were eligible.

Written informed consent was obtained from all the patients or from a legal representative if they were unable to provide consent. The trial was conducted in accordance with the principles of the Good Clinical Practice guidelines of the International Conference on Harmonisation and was approved by the U.K. Medicines and Healthcare Products Regulatory Agency and the Cambridge East Research Ethics Committee.

The protocol with its statistical analysis plan is available at NEJM.org and on the trial website at www.recoverytrial.net. The initial version of the manuscript was drafted by the first and last authors, developed by the writing committee, and approved by all members of the trial steering committee. The funders had no role in the analysis of the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication.

The first and last members of the writing committee vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan. Randomization We collected baseline data using a Web-based case-report form that included demographic data, the level of respiratory support, major coexisting illnesses, suitability of the trial treatment for a particular patient, and treatment availability at the trial site. Randomization was performed with the use of a Web-based system with concealment of the trial-group assignment.

Eligible and consenting patients were assigned in a 2:1 ratio to receive either the usual standard of care alone or the usual standard of care plus oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (or until hospital discharge if sooner) or to receive one of the other suitable and available treatments that were being evaluated in the trial. For some patients, dexamethasone was unavailable at the hospital at the time of enrollment or was considered by the managing physician to be either definitely indicated or definitely contraindicated. These patients were excluded from entry in the randomized comparison between dexamethasone and usual care and hence were not included in this report.

The randomly assigned treatment was prescribed by the treating clinician. Patients and local members of the trial staff were aware of the assigned treatments. Procedures A single online follow-up form was to be completed when the patients were discharged or had died or at 28 days after randomization, whichever occurred first.

Information was recorded regarding the patients’ adherence to the assigned treatment, receipt of other trial treatments, duration of admission, receipt of respiratory support (with duration and type), receipt of renal support, and vital status (including the cause of death). In addition, we obtained routine health care and registry data, including information on vital status (with date and cause of death), discharge from the hospital, and respiratory and renal support therapy. Outcome Measures The primary outcome was all-cause mortality within 28 days after randomization.

Further analyses were specified at 6 months. Secondary outcomes were the time until discharge from the hospital and, among patients not receiving invasive mechanical ventilation at the time of randomization, subsequent receipt of invasive mechanical ventilation (including extracorporeal membrane oxygenation) or death. Other prespecified clinical outcomes included cause-specific mortality, receipt of renal hemodialysis or hemofiltration, major cardiac arrhythmia (recorded in a subgroup), and receipt and duration of ventilation.

Statistical Analysis As stated in the protocol, appropriate sample sizes could not be estimated when the trial was being planned at the start of the Covid-19 pandemic. As the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that if 28-day mortality was 20%, then the enrollment of at least 2000 patients in the dexamethasone group and 4000 in the usual care group would provide a power of at least 90% at a two-sided P value of 0.01 to detect a clinically relevant proportional reduction of 20% (an absolute difference of 4 percentage points) between the two groups. Consequently, on June 8, 2020, the steering committee closed recruitment to the dexamethasone group, since enrollment had exceeded 2000 patients.

For the primary outcome of 28-day mortality, the hazard ratio from Cox regression was used to estimate the mortality rate ratio. Among the few patients (0.1%) who had not been followed for 28 days by the time of the data cutoff on July 6, 2020, data were censored either on that date or on day 29 if the patient had already been discharged. That is, in the absence of any information to the contrary, these patients were assumed to have survived for 28 days.

Kaplan–Meier survival curves were constructed to show cumulative mortality over the 28-day period. Cox regression was used to analyze the secondary outcome of hospital discharge within 28 days, with censoring of data on day 29 for patients who had died during hospitalization. For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among patients who were not receiving invasive mechanical ventilation at randomization), the precise date of invasive mechanical ventilation was not available, so a log-binomial regression model was used to estimate the risk ratio.

Table 1. Table 1. Characteristics of the Patients at Baseline, According to Treatment Assignment and Level of Respiratory Support.

Through the play of chance in the unstratified randomization, the mean age was 1.1 years older among patients in the dexamethasone group than among those in the usual care group (Table 1). To account for this imbalance in an important prognostic factor, estimates of rate ratios were adjusted for the baseline age in three categories (<70 years, 70 to 79 years, and ≥80 years). This adjustment was not specified in the first version of the statistical analysis plan but was added once the imbalance in age became apparent.

Results without age adjustment (corresponding to the first version of the analysis plan) are provided in the Supplementary Appendix. Prespecified analyses of the primary outcome were performed in five subgroups, as defined by characteristics at randomization. Age, sex, level of respiratory support, days since symptom onset, and predicted 28-day mortality risk.

(One further prespecified subgroup analysis regarding race will be conducted once the data collection has been completed.) In prespecified subgroups, we estimated rate ratios (or risk ratios in some analyses) and their confidence intervals using regression models that included an interaction term between the treatment assignment and the subgroup of interest. Chi-square tests for linear trend across the subgroup-specific log estimates were then performed in accordance with the prespecified plan. All P values are two-sided and are shown without adjustment for multiple testing.

All analyses were performed according to the intention-to-treat principle. The full database is held by the trial team, which collected the data from trial sites and performed the analyses at the Nuffield Department of Population Health, University of Oxford.Trial Design and Oversight We conducted a randomized, double-blind, placebo-controlled trial to evaluate postexposure prophylaxis with hydroxychloroquine after exposure to Covid-19.12 We randomly assigned participants in a 1:1 ratio to receive either hydroxychloroquine or placebo. Participants had known exposure (by participant report) to a person with laboratory-confirmed Covid-19, whether as a household contact, a health care worker, or a person with other occupational exposures.

Trial enrollment began on March 17, 2020, with an eligibility threshold to enroll within 3 days after exposure. The objective was to intervene before the median incubation period of 5 to 6 days. Because of limited access to prompt testing, health care workers could initially be enrolled on the basis of presumptive high-risk exposure to patients with pending tests.

However, on March 23, eligibility was changed to exposure to a person with a positive polymerase-chain-reaction (PCR) assay for SARS-CoV-2, with the eligibility window extended to within 4 days after exposure. This trial was approved by the institutional review board at the University of Minnesota and conducted under a Food and Drug Administration Investigational New Drug application. In Canada, the trial was approved by Health Canada.

Ethics approvals were obtained from the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta. Participants We included participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Participants were excluded if they were younger than 18 years of age, were hospitalized, or met other exclusion criteria (see the Supplementary Appendix, available with the full text of this article at NEJM.org).

Persons with symptoms of Covid-19 or with PCR-proven SARS-CoV-2 infection were excluded from this prevention trial but were separately enrolled in a companion clinical trial to treat early infection. Setting Recruitment was performed primarily with the use of social media outreach as well as traditional media platforms. Participants were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta.

Participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.13 After participants read the consent form, their comprehension of its contents was assessed. Participants provided a digitally captured signature to indicate informed consent. We sent follow-up e-mail surveys on days 1, 5, 10, and 14.

A survey at 4 to 6 weeks asked about any follow-up testing, illness, or hospitalizations. Participants who did not respond to follow-up surveys received text messages, e-mails, telephone calls, or a combination of these to ascertain their outcomes. When these methods were unsuccessful, the emergency contact provided by the enrollee was contacted to determine the participant’s illness and vital status.

When all communication methods were exhausted, Internet searches for obituaries were performed to ascertain vital status. Interventions Randomization occurred at research pharmacies in Minneapolis and Montreal. The trial statisticians generated a permuted-block randomization sequence using variably sized blocks of 2, 4, or 8, with stratification according to country.

A research pharmacist sequentially assigned participants. The assignments were concealed from investigators and participants. Only pharmacies had access to the randomization sequence.

Hydroxychloroquine sulfate or placebo was dispensed and shipped overnight to participants by commercial courier. The dosing regimen for hydroxychloroquine was 800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 hours later, then 600 mg (3 tablets) daily for 4 more days for a total course of 5 days (19 tablets total). If participants had gastrointestinal upset, they were advised to divide the daily dose into two or three doses.

We chose this hydroxychloroquine dosing regimen on the basis of pharmacokinetic simulations to achieve plasma concentrations above the SARS-CoV-2 in vitro half maximal effective concentration for 14 days.14 Placebo folate tablets, which were similar in appearance to the hydroxychloroquine tablets, were prescribed as an identical regimen for the control group. Rising Pharmaceuticals provided a donation of hydroxychloroquine, and some hydroxychloroquine was purchased. Outcomes The primary outcome was prespecified as symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19–related symptoms.

We assumed that health care workers would have access to Covid-19 testing if symptomatic. However, access to testing was limited throughout the trial period. Covid-19–related symptoms were based on U.S.

Council for State and Territorial Epidemiologists criteria for confirmed cases (positivity for SARS-Cov-2 on PCR assay), probable cases (the presence of cough, shortness of breath, or difficulty breathing, or the presence of two or more symptoms of fever, chills, rigors, myalgia, headache, sore throat, and new olfactory and taste disorders), and possible cases (the presence of one or more compatible symptoms, which could include diarrhea).15 All the participants had epidemiologic linkage,15 per trial eligibility criteria. Four infectious disease physicians who were unaware of the trial-group assignments reviewed symptomatic participants to generate a consensus with respect to whether their condition met the case definition.15 Secondary outcomes included the incidence of hospitalization for Covid-19 or death, the incidence of PCR-confirmed SARS-CoV-2 infection, the incidence of Covid-19 symptoms, the incidence of discontinuation of the trial intervention owing to any cause, and the severity of symptoms (if any) at days 5 and 14 according to a visual analogue scale (scores ranged from 0 [no symptoms] to 10 [severe symptoms]). Data on adverse events were also collected with directed questioning for common side effects along with open-ended free text.

Outcome data were measured within 14 days after trial enrollment. Outcome data including PCR testing results, possible Covid-19–related symptoms, adherence to the trial intervention, side effects, and hospitalizations were all collected through participant report. Details of trial conduct are provided in the protocol and statistical analysis plan, available at NEJM.org.

Sample Size We anticipated that illness compatible with Covid-19 would develop in 10% of close contacts exposed to Covid-19.9 Using Fisher’s exact method with a 50% relative effect size to reduce new symptomatic infections, a two-sided alpha of 0.05, and 90% power, we estimated that 621 persons would need to be enrolled in each group. With a pragmatic, Internet-based, self-referral recruitment strategy, we planned for a 20% incidence of attrition by increasing the sample size to 750 participants per group. We specified a priori that participants who were already symptomatic on day 1 before receiving hydroxychloroquine or placebo would be excluded from the prophylaxis trial and would instead be separately enrolled in the companion symptomatic treatment trial.

Because the estimates for both incident symptomatic Covid-19 after an exposure and loss to follow-up were relatively unknown in early March 2020,9 the protocol prespecified a sample-size reestimation at the second interim analysis. This reestimation, which used the incidence of new infections in the placebo group and the observed percentage of participants lost to follow-up, was aimed at maintaining the ability to detect an effect size of a 50% relative reduction in new symptomatic infections. Interim Analyses An independent data and safety monitoring board externally reviewed the data after 25% and 50% of the participants had completed 14 days of follow-up.

Stopping guidelines were provided to the data and safety monitoring board with the use of a Lan–DeMets spending function analogue of the O’Brien–Fleming boundaries for the primary outcome. A conditional power analysis was performed at the second and third interim analysis with the option of early stopping for futility. At the second interim analysis on April 22, 2020, the sample size was reduced to 956 participants who could be evaluated with 90% power on the basis of the higher-than-expected event rate of infections in the control group.

At the third interim analysis on May 6, the trial was halted on the basis of a conditional power of less than 1%, since it was deemed futile to continue. Statistical Analysis We assessed the incidence of Covid-19 disease by day 14 with Fisher’s exact test. Secondary outcomes with respect to percentage of patients were also compared with Fisher’s exact test.

Among participants in whom incident illness compatible with Covid-19 developed, we summarized the symptom severity score at day 14 with the median and interquartile range and assessed the distributions with a Kruskal–Wallis test. We conducted all analyses with SAS software, version 9.4 (SAS Institute), according to the intention-to-treat principle, with two-sided type I error with an alpha of 0.05. For participants with missing outcome data, we conducted a sensitivity analysis with their outcomes excluded or included as an event.

Subgroups that were specified a priori included type of contact (household vs. Health care), days from exposure to enrollment, age, and sex.Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. OWS is providing support to promising candidates and enabling the expeditious, parallel execution of the necessary steps toward approval or authorization of safe products by the Food and Drug Administration (FDA).The partnership grew out of an acknowledged need to fundamentally restructure the way the U.S.

Government typically supports product development and vaccine distribution. The initiative was premised on setting a “stretch goal” — one that initially seemed impossible but that is becoming increasingly achievable.The concept of an integrated structure for Covid-19 countermeasure research and development across the U.S. Government was based on experience with Zika and the Zika Leadership Group led by the National Institutes of Health (NIH) and the assistant secretary for preparedness and response (ASPR).

One of us (M.S.) serves as OWS chief advisor. We are drawing on expertise from the NIH, ASPR, the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), and the DOD, including the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and the Defense Advanced Research Projects Agency. OWS has engaged experts in all critical aspects of medical countermeasure research, development, manufacturing, and distribution to work in close coordination.The initiative set ambitious objectives.

To deliver tens of millions of doses of a SARS-CoV-2 vaccine — with demonstrated safety and efficacy, and approved or authorized by the FDA for use in the U.S. Population — beginning at the end of 2020 and to have as many as 300 million doses of such vaccines available and deployed by mid-2021. The pace and scope of such a vaccine effort are unprecedented.

The 2014 West African Ebola virus epidemic spurred rapid vaccine development, but though preclinical data existed before the outbreak, a period of 12 months was required to progress from phase 1 first-in-human trials to phase 3 efficacy trials. OWS aims to compress this time frame even further. SARS-CoV-2 vaccine development began in January, phase 1 clinical studies in March, and the first phase 3 trials in July.

Our objectives are based on advances in vaccine platform technology, improved understanding of safe and efficacious vaccine design, and similarities between the SARS-CoV-1 and SARS-CoV-2 disease mechanisms.OWS’s role is to enable, accelerate, harmonize, and advise the companies developing the selected vaccines. The companies will execute the clinical or process development and manufacturing plans, while OWS leverages the full capacity of the U.S. Government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.OWS selected vaccine candidates on the basis of four criteria.

We required candidates to have robust preclinical data or early-stage clinical trial data supporting their potential for clinical safety and efficacy. Candidates had to have the potential, with our acceleration support, to enter large phase 3 field efficacy trials this summer or fall (July to November 2020) and, assuming continued active transmission of the virus, to deliver efficacy outcomes by the end of 2020 or the first half of 2021. Candidates had to be based on vaccine-platform technologies permitting fast and effective manufacturing, and their developers had to demonstrate the industrial process scalability, yields, and consistency necessary to reliably produce more than 100 million doses by mid-2021.

Finally, candidates had to use one of four vaccine-platform technologies that we believe are the most likely to yield a safe and effective vaccine against Covid-19. The mRNA platform, the replication-defective live-vector platform, the recombinant-subunit-adjuvanted protein platform, or the attenuated replicating live-vector platform.OWS’s strategy relies on a few key principles. First, we sought to build a diverse project portfolio that includes two vaccine candidates based on each of the four platform technologies.

Such diversification mitigates the risk of failure due to safety, efficacy, industrial manufacturability, or scheduling factors and may permit selection of the best vaccine platform for each subpopulation at risk for contracting or transmitting Covid-19, including older adults, frontline and essential workers, young adults, and pediatric populations. In addition, advancing eight vaccines in parallel will increase the chances of delivering 300 million doses in the first half of 2021.Second, we must accelerate vaccine program development without compromising safety, efficacy, or product quality. Clinical development, process development, and manufacturing scale-up can be substantially accelerated by running all streams, fully resourced, in parallel.

Doing so requires taking on substantial financial risk, as compared with the conventional sequential development approach. OWS will maximize the size of phase 3 trials (30,000 to 50,000 participants each) and optimize trial-site location by consulting daily epidemiologic and disease-forecasting models to ensure the fastest path to an efficacy readout. Such large trials also increase the safety data set for each candidate vaccine.With heavy up-front investment, companies can conduct clinical operations and site preparation for these phase 3 efficacy trials even as they file their Investigational New Drug application (IND) for their phase 1 studies, thereby ensuring immediate initiation of phase 3 when they get a green light from the FDA.

To permit appropriate comparisons among the vaccine candidates and to optimize vaccine utilization after approval by the FDA, the phase 3 trial end points and assay readouts have been harmonized through a collaborative effort involving the National Institute of Allergy and Infectious Diseases (NIAID), the Coronavirus Prevention Network, OWS, and the sponsor companies.Finally, OWS is supporting the companies financially and technically to commence process development and scale up manufacturing while their vaccines are in preclinical or very early clinical stages. To ensure that industrial processes are set, running, and validated for FDA inspection when phase 3 trials end, OWS is also supporting facility building or refurbishing, equipment fitting, staff hiring and training, raw-material sourcing, technology transfer and validation, bulk product processing into vials, and acquisition of ample vials, syringes, and needles for each vaccine candidate. We aim to have stockpiled, at OWS’s expense, a few tens of millions of vaccine doses that could be swiftly deployed once FDA approval is obtained.This strategy aims to accelerate vaccine development without curtailing the critical steps required by sound science and regulatory standards.

The FDA recently reissued guidance and standards that will be used to assess each vaccine for a Biologics License Application (BLA). Alternatively, the agency could decide to issue an Emergency Use Authorization to permit vaccine administration before all BLA procedures are completed.Of the eight vaccines in OWS’s portfolio, six have been announced and partnerships executed with the companies. Moderna and Pfizer/BioNTech (both mRNA), AstraZeneca and Janssen (both replication-defective live-vector), and Novavax and Sanofi/GSK (both recombinant-subunit-adjuvanted protein).

These candidates cover three of the four platform technologies and are currently in clinical trials. The remaining two candidates will enter trials soon.Moderna developed its RNA vaccine in collaboration with the NIAID, began its phase 1 trial in March, recently published encouraging safety and immunogenicity data,1 and entered phase 3 on July 27. Pfizer and BioNTech’s RNA vaccine also produced encouraging phase 1 results2 and started its phase 3 trial on July 27.

The ChAdOx replication-defective live-vector vaccine developed by AstraZeneca and Oxford University is in phase 3 trials in the United Kingdom, Brazil, and South Africa, and it should enter U.S. Phase 3 trials in August.3 The Janssen Ad26 Covid-19 replication-defective live-vector vaccine has demonstrated excellent protection in nonhuman primate models and began its U.S. Phase 1 trial on July 27.

It should be in phase 3 trials in mid-September. Novavax completed a phase 1 trial of its recombinant-subunit-adjuvanted protein vaccine in Australia and should enter phase 3 trials in the United States by the end of September.4 Sanofi/GSK is completing preclinical development steps and plans to commence a phase 1 trial in early September and to be well into phase 3 by year’s end.5On the process-development front, the RNA vaccines are already being manufactured at scale. The other candidates are well advanced in their scale-up development, and manufacturing sites are being refurbished.While development and manufacturing proceed, the HHS–DOD partnership is laying the groundwork for vaccine distribution, subpopulation prioritization, financing, and logistic support.

We are working with bioethicists and experts from the NIH, the CDC, BARDA, and the Centers for Medicare and Medicaid Services to address these critical issues. We will receive recommendations from the CDC Advisory Committee on Immunization Practices, and we are working to ensure that the most vulnerable and at-risk persons will receive vaccine doses once they are ready. Prioritization will also depend on the relative performance of each vaccine and its suitability for particular populations.

Because some technologies have limited previous data on safety in humans, the long-term safety of these vaccines will be carefully assessed using pharmacovigilance surveillance strategies.No scientific enterprise could guarantee success by January 2021, but the strategic decisions and choices we’ve made, the support the government has provided, and the accomplishments to date make us optimistic that we will succeed in this unprecedented endeavor..

Patients Figure where to buy generic aricept 1. Figure 1. Enrollment and Randomization where to buy generic aricept.

Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization. 541 were assigned to the where to buy generic aricept remdesivir group and 522 to the placebo group (Figure 1). Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned.

Forty-nine patients had remdesivir where to buy generic aricept treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death (36 patients) or because the patient withdrew consent (13). Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2).

As of April 28, 2020, a total of 391 patients in the remdesivir group and 340 in the placebo group had completed the trial through day 29, where to buy generic aricept recovered, or died. Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. There were where to buy generic aricept 132 patients in the remdesivir group and 169 in the placebo group who had not recovered and had not completed the day 29 follow-up visit.

The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary analysis because no postbaseline data were available where to buy generic aricept at the time of the database freeze. Table 1.

Table 1 where to buy generic aricept. Demographic and Clinical Characteristics at Baseline. The mean age of patients was 58.9 years, and 64.3% were male (Table 1).

On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia where to buy generic aricept (Table S1). Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported. 249 (23.4%) where to buy generic aricept were Hispanic or Latino.

Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to where to buy generic aricept 12). Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix.

272 (25.6%) patients met category 7 criteria on the ordinal scale, where to buy generic aricept 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4. There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group.

Primary Outcome Figure 2 where to buy generic aricept. Figure 2. Kaplan–Meier Estimates of Cumulative where to buy generic aricept 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 where to buy generic aricept. Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation.

Panel D), and in where to buy generic aricept those with a baseline score of 7 (receiving mechanical ventilation or ECMO. Panel E). Table 2.

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

Figure 3. Time to Recovery According to where to buy generic aricept 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 where to buy generic aricept group were reported by the patients. Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days. Rate ratio for recovery, 1.32.

95% confidence interval where to buy generic aricept [CI], 1.12 to 1.55. P<0.001. 1059 patients (Figure 2 and where to buy generic aricept Table 2).

Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84). Among patients with a baseline score of 4 (127 patients) and those with a baseline score of 6 (197 patients), the rate ratio estimates for recovery where to buy generic aricept were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7.

272 patients), where to buy generic aricept the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable 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 where to buy generic aricept for recovery, 1.31. 95% CI, 1.12 to 1.54. 1017 patients) where to buy generic aricept.

Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, 1.05 where to buy generic aricept to 1.57. 664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81.

380 patients) (Figure where to buy generic aricept 3). 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, 1.50. 95% CI, 1.18 to 1.91.

P=0.001. 844 patients) (Table 2 and Fig. S5).

Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70. 95% CI, 0.47 to 1.04. 1059 patients).

The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2). The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits. An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10).

Safety Outcomes Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3). 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients).

Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators. Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4).

The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group). Acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]). Pyrexia (27 events [5.0%], as compared with 17 [3.3%]).

Hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]). And increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]). Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.Trial Population Table 1.

Table 1. Characteristics of the Participants in the mRNA-1273 Trial at Enrollment. The 45 enrolled participants received their first vaccination between March 16 and April 14, 2020 (Fig.

S1). Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one in the 25-μg group and one in the 250-μg group) who missed the second vaccination window owing to isolation for suspected Covid-19 while the test results, ultimately negative, were pending. All continued to attend scheduled trial visits.

The demographic characteristics of participants at enrollment are provided in Table 1. Vaccine Safety No serious adverse events were noted, and no prespecified trial halting rules were met. As noted above, one participant in the 25-μg group was withdrawn because of an unsolicited adverse event, transient urticaria, judged to be related to the first vaccination.

Figure 1. Figure 1. Systemic and Local Adverse Events.

The severity of solicited adverse events was graded as mild, moderate, or severe (see Table S1).After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group. All were mild or moderate in severity (Figure 1 and Table S2). Solicited systemic adverse events were more common after the second vaccination and occurred in 7 of 13 participants (54%) in the 25-μg group, all 15 in the 100-μg group, and all 14 in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events.

None of the participants had fever after the first vaccination. After the second vaccination, no participants in the 25-μg group, 6 (40%) in the 100-μg group, and 8 (57%) in the 250-μg group reported fever. One of the events (maximum temperature, 39.6°C) in the 250-μg group was graded severe.

(Additional details regarding adverse events for that participant are provided in the Supplementary Appendix.) Local adverse events, when present, were nearly all mild or moderate, and pain at the injection site was common. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Evaluation of safety clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no patterns of concern (Supplementary Appendix and Table S3).

SARS-CoV-2 Binding Antibody Responses Table 2. Table 2. Geometric Mean Humoral Immunogenicity Assay Responses to mRNA-1273 in Participants and in Convalescent Serum Specimens.

Figure 2. Figure 2. SARS-CoV-2 Antibody and Neutralization Responses.

Shown are geometric mean reciprocal end-point enzyme-linked immunosorbent assay (ELISA) IgG titers to S-2P (Panel A) and receptor-binding domain (Panel B), PsVNA ID50 responses (Panel C), and live virus PRNT80 responses (Panel D). In Panel A and Panel B, boxes and horizontal bars denote interquartile range (IQR) and median area under the curve (AUC), respectively. Whisker endpoints are equal to the maximum and minimum values below or above the median ±1.5 times the IQR.

The convalescent serum panel includes specimens from 41 participants. Red dots indicate the 3 specimens that were also tested in the PRNT assay. The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent serum panel.

In Panel C, boxes and horizontal bars denote IQR and median ID50, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. In the convalescent serum panel, red dots indicate the 3 specimens that were also tested in the PRNT assay.

The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent panel. In Panel D, boxes and horizontal bars denote IQR and median PRNT80, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR.

The three convalescent serum specimens were also tested in ELISA and PsVNA assays. Because of the time-intensive nature of the PRNT assay, for this preliminary report, PRNT results were available only for the 25-μg and 100-μg dose groups.Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15 (Table 2 and Figure 2A). Dose-dependent responses to the first and second vaccinations were evident.

Receptor-binding domain–specific antibody responses were similar in pattern and magnitude (Figure 2B). For both assays, the median magnitude of antibody responses after the first vaccination in the 100-μg and 250-μg dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens. The S-2P ELISA GMTs at day 57 (299,751 [95% confidence interval {CI}, 206,071 to 436,020] in the 25-μg group, 782,719 [95% CI, 619,310 to 989,244] in the 100-μg group, and 1,192,154 [95% CI, 924,878 to 1,536,669] in the 250-μg group) exceeded that in the convalescent serum specimens (142,140 [95% CI, 81,543 to 247,768]).

SARS-CoV-2 Neutralization Responses No participant had detectable PsVNA responses before vaccination. After the first vaccination, PsVNA responses were detected in less than half the participants, and a dose effect was seen (50% inhibitory dilution [ID50]. Figure 2C, Fig.

S8, and Table 2. 80% inhibitory dilution [ID80]. Fig.

S2 and Table S6). However, after the second vaccination, PsVNA responses were identified in serum samples from all participants. The lowest responses were in the 25-μg dose group, with a geometric mean ID50 of 112.3 (95% CI, 71.2 to 177.1) at day 43.

The higher responses in the 100-μg and 250-μg groups were similar in magnitude (geometric mean ID50, 343.8 [95% CI, 261.2 to 452.7] and 332.2 [95% CI, 266.3 to 414.5], respectively, at day 43). These responses were similar to values in the upper half of the distribution of values for convalescent serum specimens. Before vaccination, no participant had detectable 80% live-virus neutralization at the highest serum concentration tested (1:8 dilution) in the PRNT assay.

At day 43, wild-type virus–neutralizing activity capable of reducing SARS-CoV-2 infectivity by 80% or more (PRNT80) was detected in all participants, with geometric mean PRNT80 responses of 339.7 (95% CI, 184.0 to 627.1) in the 25-μg group and 654.3 (95% CI, 460.1 to 930.5) in the 100-μg group (Figure 2D). Neutralizing PRNT80 average responses were generally at or above the values of the three convalescent serum specimens tested in this assay. Good agreement was noted within and between the values from binding assays for S-2P and receptor-binding domain and neutralizing activity measured by PsVNA and PRNT (Figs.

S3 through S7), which provides orthogonal support for each assay in characterizing the humoral response induced by mRNA-1273. SARS-CoV-2 T-Cell Responses The 25-μg and 100-μg doses elicited CD4 T-cell responses (Figs. S9 and S10) that on stimulation by S-specific peptide pools were strongly biased toward expression of Th1 cytokines (tumor necrosis factor α >.

Interleukin 2 >. Interferon γ), with minimal type 2 helper T-cell (Th2) cytokine expression (interleukin 4 and interleukin 13). CD8 T-cell responses to S-2P were detected at low levels after the second vaccination in the 100-μg dose group (Fig.

S11).Trial Design and Oversight The RECOVERY trial was designed to evaluate the effects of potential treatments in patients hospitalized with Covid-19 at 176 National Health Service organizations in the United Kingdom and was supported by the National Institute for Health Research Clinical Research Network. (Details regarding this trial are provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The trial is being coordinated by the Nuffield Department of Population Health at the University of Oxford, the trial sponsor. Although the randomization of patients to receive dexamethasone, hydroxychloroquine, or lopinavir–ritonavir has now been stopped, the trial continues randomization to groups receiving azithromycin, tocilizumab, or convalescent plasma.

Hospitalized patients were eligible for the trial if they had clinically suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put patients at substantial risk if they were to participate in the trial. Initially, recruitment was limited to patients who were at least 18 years of age, but the age limit was removed starting on May 9, 2020. Pregnant or breast-feeding women were eligible.

Written informed consent was obtained from all the patients or from a legal representative if they were unable to provide consent. The trial was conducted in accordance with the principles of the Good Clinical Practice guidelines of the International Conference on Harmonisation and was approved by the U.K. Medicines and Healthcare Products Regulatory Agency and the Cambridge East Research Ethics Committee.

The protocol with its statistical analysis plan is available at NEJM.org and on the trial website at www.recoverytrial.net. The initial version of the manuscript was drafted by the first and last authors, developed by the writing committee, and approved by all members of the trial steering committee. The funders had no role in the analysis of the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication.

The first and last members of the writing committee vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan. Randomization We collected baseline data using a Web-based case-report form that included demographic data, the level of respiratory support, major coexisting illnesses, suitability of the trial treatment for a particular patient, and treatment availability at the trial site. Randomization was performed with the use of a Web-based system with concealment of the trial-group assignment.

Eligible and consenting patients were assigned in a 2:1 ratio to receive either the usual standard of care alone or the usual standard of care plus oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (or until hospital discharge if sooner) or to receive one of the other suitable and available treatments that were being evaluated in the trial. For some patients, dexamethasone was unavailable at the hospital at the time of enrollment or was considered by the managing physician to be either definitely indicated or definitely contraindicated. These patients were excluded from entry in the randomized comparison between dexamethasone and usual care and hence were not included in this report.

The randomly assigned treatment was prescribed by the treating clinician. Patients and local members of the trial staff were aware of the assigned treatments. Procedures A single online follow-up form was to be completed when the patients were discharged or had died or at 28 days after randomization, whichever occurred first.

Information was recorded regarding the patients’ adherence to the assigned treatment, receipt of other trial treatments, duration of admission, receipt of respiratory support (with duration and type), receipt of renal support, and vital status (including the cause of death). In addition, we obtained routine health care and registry data, including information on vital status (with date and cause of death), discharge from the hospital, and respiratory and renal support therapy. Outcome Measures The primary outcome was all-cause mortality within 28 days after randomization.

Further analyses were specified at 6 months. Secondary outcomes were the time until discharge from the hospital and, among patients not receiving invasive mechanical ventilation at the time of randomization, subsequent receipt of invasive mechanical ventilation (including extracorporeal membrane oxygenation) or death. Other prespecified clinical outcomes included cause-specific mortality, receipt of renal hemodialysis or hemofiltration, major cardiac arrhythmia (recorded in a subgroup), and receipt and duration of ventilation.

Statistical Analysis As stated in the protocol, appropriate sample sizes could not be estimated when the trial was being planned at the start of the Covid-19 pandemic. As the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that if 28-day mortality was 20%, then the enrollment of at least 2000 patients in the dexamethasone group and 4000 in the usual care group would provide a power of at least 90% at a two-sided P value of 0.01 to detect a clinically relevant proportional reduction of 20% (an absolute difference of 4 percentage points) between the two groups. Consequently, on June 8, 2020, the steering committee closed recruitment to the dexamethasone group, since enrollment had exceeded 2000 patients.

For the primary outcome of 28-day mortality, the hazard ratio from Cox regression was used to estimate the mortality rate ratio. Among the few patients (0.1%) who had not been followed for 28 days by the time of the data cutoff on July 6, 2020, data were censored either on that date or on day 29 if the patient had already been discharged. That is, in the absence of any information to the contrary, these patients were assumed to have survived for 28 days.

Kaplan–Meier survival curves were constructed to show cumulative mortality over the 28-day period. Cox regression was used to analyze the secondary outcome of hospital discharge within 28 days, with censoring of data on day 29 for patients who had died during hospitalization. For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among patients who were not receiving invasive mechanical ventilation at randomization), the precise date of invasive mechanical ventilation was not available, so a log-binomial regression model was used to estimate the risk ratio.

Table 1. Table 1. Characteristics of the Patients at Baseline, According to Treatment Assignment and Level of Respiratory Support.

Through the play of chance in the unstratified randomization, the mean age was 1.1 years older among patients in the dexamethasone group than among those in the usual care group (Table 1). To account for this imbalance in an important prognostic factor, estimates of rate ratios were adjusted for the baseline age in three categories (<70 years, 70 to 79 years, and ≥80 years). This adjustment was not specified in the first version of the statistical analysis plan but was added once the imbalance in age became apparent.

Results without age adjustment (corresponding to the first version of the analysis plan) are provided in the Supplementary Appendix. Prespecified analyses of the primary outcome were performed in five subgroups, as defined by characteristics at randomization. Age, sex, level of respiratory support, days since symptom onset, and predicted 28-day mortality risk.

(One further prespecified subgroup analysis regarding race will be conducted once the data collection has been completed.) In prespecified subgroups, we estimated rate ratios (or risk ratios in some analyses) and their confidence intervals using regression models that included an interaction term between the treatment assignment and the subgroup of interest. Chi-square tests for linear trend across the subgroup-specific log estimates were then performed in accordance with the prespecified plan. All P values are two-sided and are shown without adjustment for multiple testing.

All analyses were performed according to the intention-to-treat principle. The full database is held by the trial team, which collected the data from trial sites and performed the analyses at the Nuffield Department of Population Health, University of Oxford.Trial Design and Oversight We conducted a randomized, double-blind, placebo-controlled trial to evaluate postexposure prophylaxis with hydroxychloroquine after exposure to Covid-19.12 We randomly assigned participants in a 1:1 ratio to receive either hydroxychloroquine or placebo. Participants had known exposure (by participant report) to a person with laboratory-confirmed Covid-19, whether as a household contact, a health care worker, or a person with other occupational exposures.

Trial enrollment began on March 17, 2020, with an eligibility threshold to enroll within 3 days after exposure. The objective was to intervene before the median incubation period of 5 to 6 days. Because of limited access to prompt testing, health care workers could initially be enrolled on the basis of presumptive high-risk exposure to patients with pending tests.

However, on March 23, eligibility was changed to exposure to a person with a positive polymerase-chain-reaction (PCR) assay for SARS-CoV-2, with the eligibility window extended to within 4 days after exposure. This trial was approved by the institutional review board at the University of Minnesota and conducted under a Food and Drug Administration Investigational New Drug application. In Canada, the trial was approved by Health Canada.

Ethics approvals were obtained from the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta. Participants We included participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Participants were excluded if they were younger than 18 years of age, were hospitalized, or met other exclusion criteria (see the Supplementary Appendix, available with the full text of this article at NEJM.org).

Persons with symptoms of Covid-19 or with PCR-proven SARS-CoV-2 infection were excluded from this prevention trial but were separately enrolled in a companion clinical trial to treat early infection. Setting Recruitment was performed primarily with the use of social media outreach as well as traditional media platforms. Participants were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta.

Participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.13 After participants read the consent form, their comprehension of its contents was assessed. Participants provided a digitally captured signature to indicate informed consent. We sent follow-up e-mail surveys on days 1, 5, 10, and 14.

A survey at 4 to 6 weeks asked about any follow-up testing, illness, or hospitalizations. Participants who did not respond to follow-up surveys received text messages, e-mails, telephone calls, or a combination of these to ascertain their outcomes. When these methods were unsuccessful, the emergency contact provided by the enrollee was contacted to determine the participant’s illness and vital status.

When all communication methods were exhausted, Internet searches for obituaries were performed to ascertain vital status. Interventions Randomization occurred at research pharmacies in Minneapolis and Montreal. The trial statisticians generated a permuted-block randomization sequence using variably sized blocks of 2, 4, or 8, with stratification according to country.

A research pharmacist sequentially assigned participants. The assignments were concealed from investigators and participants. Only pharmacies had access to the randomization sequence.

Hydroxychloroquine sulfate or placebo was dispensed and shipped overnight to participants by commercial courier. The dosing regimen for hydroxychloroquine was 800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 hours later, then 600 mg (3 tablets) daily for 4 more days for a total course of 5 days (19 tablets total). If participants had gastrointestinal upset, they were advised to divide the daily dose into two or three doses.

We chose this hydroxychloroquine dosing regimen on the basis of pharmacokinetic simulations to achieve plasma concentrations above the SARS-CoV-2 in vitro half maximal effective concentration for 14 days.14 Placebo folate tablets, which were similar in appearance to the hydroxychloroquine tablets, were prescribed as an identical regimen for the control group. Rising Pharmaceuticals provided a donation of hydroxychloroquine, and some hydroxychloroquine was purchased. Outcomes The primary outcome was prespecified as symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19–related symptoms.

We assumed that health care workers would have access to Covid-19 testing if symptomatic. However, access to testing was limited throughout the trial period. Covid-19–related symptoms were based on U.S.

Council for State and Territorial Epidemiologists criteria for confirmed cases (positivity for SARS-Cov-2 on PCR assay), probable cases (the presence of cough, shortness of breath, or difficulty breathing, or the presence of two or more symptoms of fever, chills, rigors, myalgia, headache, sore throat, and new olfactory and taste disorders), and possible cases (the presence of one or more compatible symptoms, which could include diarrhea).15 All the participants had epidemiologic linkage,15 per trial eligibility criteria. Four infectious disease physicians who were unaware of the trial-group assignments reviewed symptomatic participants to generate a consensus with respect to whether their condition met the case definition.15 Secondary outcomes included the incidence of hospitalization for Covid-19 or death, the incidence of PCR-confirmed SARS-CoV-2 infection, the incidence of Covid-19 symptoms, the incidence of discontinuation of the trial intervention owing to any cause, and the severity of symptoms (if any) at days 5 and 14 according to a visual analogue scale (scores ranged from 0 [no symptoms] to 10 [severe symptoms]). Data on adverse events were also collected with directed questioning for common side effects along with open-ended free text.

Outcome data were measured within 14 days after trial enrollment. Outcome data including PCR testing results, possible Covid-19–related symptoms, adherence to the trial intervention, side effects, and hospitalizations were all collected through participant report. Details of trial conduct are provided in the protocol and statistical analysis plan, available at NEJM.org.

Sample Size We anticipated that illness compatible with Covid-19 would develop in 10% of close contacts exposed to Covid-19.9 Using Fisher’s exact method with a 50% relative effect size to reduce new symptomatic infections, a two-sided alpha of 0.05, and 90% power, we estimated that 621 persons would need to be enrolled in each group. With a pragmatic, Internet-based, self-referral recruitment strategy, we planned for a 20% incidence of attrition by increasing the sample size to 750 participants per group. We specified a priori that participants who were already symptomatic on day 1 before receiving hydroxychloroquine or placebo would be excluded from the prophylaxis trial and would instead be separately enrolled in the companion symptomatic treatment trial.

Because the estimates for both incident symptomatic Covid-19 after an exposure and loss to follow-up were relatively unknown in early March 2020,9 the protocol prespecified a sample-size reestimation at the second interim analysis. This reestimation, which used the incidence of new infections in the placebo group and the observed percentage of participants lost to follow-up, was aimed at maintaining the ability to detect an effect size of a 50% relative reduction in new symptomatic infections. Interim Analyses An independent data and safety monitoring board externally reviewed the data after 25% and 50% of the participants had completed 14 days of follow-up.

Stopping guidelines were provided to the data and safety monitoring board with the use of a Lan–DeMets spending function analogue of the O’Brien–Fleming boundaries for the primary outcome. A conditional power analysis was performed at the second and third interim analysis with the option of early stopping for futility. At the second interim analysis on April 22, 2020, the sample size was reduced to 956 participants who could be evaluated with 90% power on the basis of the higher-than-expected event rate of infections in the control group.

At the third interim analysis on May 6, the trial was halted on the basis of a conditional power of less than 1%, since it was deemed futile to continue. Statistical Analysis We assessed the incidence of Covid-19 disease by day 14 with Fisher’s exact test. Secondary outcomes with respect to percentage of patients were also compared with Fisher’s exact test.

Among participants in whom incident illness compatible with Covid-19 developed, we summarized the symptom severity score at day 14 with the median and interquartile range and assessed the distributions with a Kruskal–Wallis test. We conducted all analyses with SAS software, version 9.4 (SAS Institute), according to the intention-to-treat principle, with two-sided type I error with an alpha of 0.05. For participants with missing outcome data, we conducted a sensitivity analysis with their outcomes excluded or included as an event.

Subgroups that were specified a priori included type of contact (household vs. Health care), days from exposure to enrollment, age, and sex.Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. OWS is providing support to promising candidates and enabling the expeditious, parallel execution of the necessary steps toward approval or authorization of safe products by the Food and Drug Administration (FDA).The partnership grew out of an acknowledged need to fundamentally restructure the way the U.S.

Government typically supports product development and vaccine distribution. The initiative was premised on setting a “stretch goal” — one that initially seemed impossible but that is becoming increasingly achievable.The concept of an integrated structure for Covid-19 countermeasure research and development across the U.S. Government was based on experience with Zika and the Zika Leadership Group led by the National Institutes of Health (NIH) and the assistant secretary for preparedness and response (ASPR).

One of us (M.S.) serves as OWS chief advisor. We are drawing on expertise from the NIH, ASPR, the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), and the DOD, including the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and the Defense Advanced Research Projects Agency. OWS has engaged experts in all critical aspects of medical countermeasure research, development, manufacturing, and distribution to work in close coordination.The initiative set ambitious objectives.

To deliver tens of millions of doses of a SARS-CoV-2 vaccine — with demonstrated safety and efficacy, and approved or authorized by the FDA for use in the U.S. Population — beginning at the end of 2020 and to have as many as 300 million doses of such vaccines available and deployed by mid-2021. The pace and scope of such a vaccine effort are unprecedented.

The 2014 West African Ebola virus epidemic spurred rapid vaccine development, but though preclinical data existed before the outbreak, a period of 12 months was required to progress from phase 1 first-in-human trials to phase 3 efficacy trials. OWS aims to compress this time frame even further. SARS-CoV-2 vaccine development began in January, phase 1 clinical studies in March, and the first phase 3 trials in July.

Our objectives are based on advances in vaccine platform technology, improved understanding of safe and efficacious vaccine design, and similarities between the SARS-CoV-1 and SARS-CoV-2 disease mechanisms.OWS’s role is to enable, accelerate, harmonize, and advise the companies developing the selected vaccines. The companies will execute the clinical or process development and manufacturing plans, while OWS leverages the full capacity of the U.S. Government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.OWS selected vaccine candidates on the basis of four criteria.

We required candidates to have robust preclinical data or early-stage clinical trial data supporting their potential for clinical safety and efficacy. Candidates had to have the potential, with our acceleration support, to enter large phase 3 field efficacy trials this summer or fall (July to November 2020) and, assuming continued active transmission of the virus, to deliver efficacy outcomes by the end of 2020 or the first half of 2021. Candidates had to be based on vaccine-platform technologies permitting fast and effective manufacturing, and their developers had to demonstrate the industrial process scalability, yields, and consistency necessary to reliably produce more than 100 million doses by mid-2021.

Finally, candidates had to use one of four vaccine-platform technologies that we believe are the most likely to yield a safe and effective vaccine against Covid-19. The mRNA platform, the replication-defective live-vector platform, the recombinant-subunit-adjuvanted protein platform, or the attenuated replicating live-vector platform.OWS’s strategy relies on a few key principles. First, we sought to build a diverse project portfolio that includes two vaccine candidates based on each of the four platform technologies.

Such diversification mitigates the risk of failure due to safety, efficacy, industrial manufacturability, or scheduling factors and may permit selection of the best vaccine platform for each subpopulation at risk for contracting or transmitting Covid-19, including older adults, frontline and essential workers, young adults, and pediatric populations. In addition, advancing eight vaccines in parallel will increase the chances of delivering 300 million doses in the first half of 2021.Second, we must accelerate vaccine program development without compromising safety, efficacy, or product quality. Clinical development, process development, and manufacturing scale-up can be substantially accelerated by running all streams, fully resourced, in parallel.

Doing so requires taking on substantial financial risk, as compared with the conventional sequential development approach. OWS will maximize the size of phase 3 trials (30,000 to 50,000 participants each) and optimize trial-site location by consulting daily epidemiologic and disease-forecasting models to ensure the fastest path to an efficacy readout. Such large trials also increase the safety data set for each candidate vaccine.With heavy up-front investment, companies can conduct clinical operations and site preparation for these phase 3 efficacy trials even as they file their Investigational New Drug application (IND) for their phase 1 studies, thereby ensuring immediate initiation of phase 3 when they get a green light from the FDA.

To permit appropriate comparisons among the vaccine candidates and to optimize vaccine utilization after approval by the FDA, the phase 3 trial end points and assay readouts have been harmonized through a collaborative effort involving the National Institute of Allergy and Infectious Diseases (NIAID), the Coronavirus Prevention Network, OWS, and the sponsor companies.Finally, OWS is supporting the companies financially and technically to commence process development and scale up manufacturing while their vaccines are in preclinical or very early clinical stages. To ensure that industrial processes are set, running, and validated for FDA inspection when phase 3 trials end, OWS is also supporting facility building or refurbishing, equipment fitting, staff hiring and training, raw-material sourcing, technology transfer and validation, bulk product processing into vials, and acquisition of ample vials, syringes, and needles for each vaccine candidate. We aim to have stockpiled, at OWS’s expense, a few tens of millions of vaccine doses that could be swiftly deployed once FDA approval is obtained.This strategy aims to accelerate vaccine development without curtailing the critical steps required by sound science and regulatory standards.

The FDA recently reissued guidance and standards that will be used to assess each vaccine for a Biologics License Application (BLA). Alternatively, the agency could decide to issue an Emergency Use Authorization to permit vaccine administration before all BLA procedures are completed.Of the eight vaccines in OWS’s portfolio, six have been announced and partnerships executed with the companies. Moderna and Pfizer/BioNTech (both mRNA), AstraZeneca and Janssen (both replication-defective live-vector), and Novavax and Sanofi/GSK (both recombinant-subunit-adjuvanted protein).

These candidates cover three of the four platform technologies and are currently in clinical trials. The remaining two candidates will enter trials soon.Moderna developed its RNA vaccine in collaboration with the NIAID, began its phase 1 trial in March, recently published encouraging safety and immunogenicity data,1 and entered phase 3 on July 27. Pfizer and BioNTech’s RNA vaccine also produced encouraging phase 1 results2 and started its phase 3 trial on July 27.

The ChAdOx replication-defective live-vector vaccine developed by AstraZeneca and Oxford University is in phase 3 trials in the United Kingdom, Brazil, and South Africa, and it should enter U.S. Phase 3 trials in August.3 The Janssen Ad26 Covid-19 replication-defective live-vector vaccine has demonstrated excellent protection in nonhuman primate models and began its U.S. Phase 1 trial on July 27.

It should be in phase 3 trials in mid-September. Novavax completed a phase 1 trial of its recombinant-subunit-adjuvanted protein vaccine in Australia and should enter phase 3 trials in the United States by the end of September.4 Sanofi/GSK is completing preclinical development steps and plans to commence a phase 1 trial in early September and to be well into phase 3 by year’s end.5On the process-development front, the RNA vaccines are already being manufactured at scale. The other candidates are well advanced in their scale-up development, and manufacturing sites are being refurbished.While development and manufacturing proceed, the HHS–DOD partnership is laying the groundwork for vaccine distribution, subpopulation prioritization, financing, and logistic support.

We are working with bioethicists and experts from the NIH, the CDC, BARDA, and the Centers for Medicare and Medicaid Services to address these critical issues. We will receive recommendations from the CDC Advisory Committee on Immunization Practices, and we are working to ensure that the most vulnerable and at-risk persons will receive vaccine doses once they are ready. Prioritization will also depend on the relative performance of each vaccine and its suitability for particular populations.

Because some technologies have limited previous data on safety in humans, the long-term safety of these vaccines will be carefully assessed using pharmacovigilance surveillance strategies.No scientific enterprise could guarantee success by January 2021, but the strategic decisions and choices we’ve made, the support the government has provided, and the accomplishments to date make us optimistic that we will succeed in this unprecedented endeavor..

Aricept for

Start Preamble aricept for Centers for Medicare &. Medicaid Services (CMS), HHS. Extension of timeline for publication of final rule. This notice announces an extension of the timeline for publication of a Medicare final rule in accordance with aricept for the Social Security Act, which allows us to extend the timeline for publication of the final rule.

As of August 26, 2020, the timeline for publication of the final rule to finalize the provisions of the October 17, 2019 proposed rule (84 FR 55766) is extended until August 31, 2021. Start Further Info Lisa O. Wilson, (410) 786-8852 aricept for. End Further Info End Preamble Start Supplemental Information In the October 17, 2019 Federal Register (84 FR 55766), we published a proposed rule that addressed undue regulatory impact and burden of the physician self-referral law.

The proposed rule was issued in conjunction with the Centers for Medicare &. Medicaid Services' (CMS) Patients over Paperwork initiative and the Department of Health and Human Services' (the Department or HHS) Regulatory Sprint to Coordinated aricept for Care. In the proposed rule, we proposed exceptions to the physician self-referral law for certain value-based compensation arrangements between or among physicians, providers, and suppliers. A new exception for certain arrangements under which a physician receives limited remuneration for items or services actually provided by the physician.

A new exception for donations of aricept for cybersecurity technology and related services. And amendments to the existing exception for electronic health records (EHR) items and services. The proposed rule also provides critically necessary guidance for physicians and health care providers and suppliers whose financial relationships are governed by the physician self-referral statute and regulations. This notice announces aricept for an extension of the timeline for publication of the final rule and the continuation of effectiveness of the proposed rule.

Section 1871(a)(3)(A) of the Social Security Act (the Act) requires us to establish and publish a regular timeline for the publication of final regulations based on the previous publication of a proposed regulation. In accordance with section 1871(a)(3)(B) of the Act, the timeline may vary among different regulations based on differences in the complexity of the regulation, the number and scope of comments received, and other relevant factors, but may not be longer than 3 years except under exceptional circumstances. In addition, in accordance with section 1871(a)(3)(B) of the Act, the Secretary may extend the initial targeted publication date of the final regulation if the Secretary, no later than the regulation's previously established proposed publication date, publishes a notice aricept for with the new target date, and such notice includes a brief explanation of the justification for the variation. We announced in the Spring 2020 Unified Agenda (June 30, 2020, www.reginfo.gov) that we would issue the final rule in August 2020.

However, we are still working through the Start Printed Page 52941complexity of the issues raised by comments received on the proposed rule and therefore we are not able to meet the announced publication target date. This notice extends the timeline for publication of the final rule until August 31, aricept for 2021. Start Signature Dated. August 24, 2020.

Wilma M. Robinson, Deputy Executive Secretary to the Department, aricept for Department of Health and Human Services. End Signature End Supplemental Information [FR Doc. 2020-18867 Filed 8-26-20.

8:45 am]BILLING aricept for CODE 4120-01-PToday, the U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), announced over $117 million in quality improvement awards to 1,318 health centers across all U.S. States, territories and the District of Columbia. HRSA-funded health centers will use these funds aricept for to further strengthen quality improvement activities and expand quality primary health care service delivery.“These quality improvement awards support health centers across the country in delivering care to nearly 30 million people, providing a convenient source of quality care that has grown even more important during the COVID-19 pandemic,” said HHS Secretary Alex Azar.

€œThese awards help ensure that all patients who visit a HRSA-funded health center continue to receive the highest quality of care, including access to COVID-19 testing and treatment.”Health centers deliver comprehensive care to people who are low-income, uninsured or face other obstacles to getting health care. On top of the safety-net that they provide, health centers have been on the front lines preventing and responding to the COVID-19 public health emergency, including providing over 3 million COVID-19 tests. Health centers continue to provide essential services for our nation’s most vulnerable and medically underserved populations, including those who often do not have access to care, before, during and after the COVID-19 pandemic.HRSA’s aricept for quality improvement awards recognize the highest performing health centers nationwide as well as those health centers that have made significant quality improvements from the previous year.Health centers are recognized for achievements in various areas. Improving cost-efficient care delivery.

Increasing quality of care. Reducing health aricept for disparities. Increasing both the number of patients served. Increasing patients’ ability to access comprehensive services.

Advancing the aricept for use of health information technology. And Achieving patient-centered medical home recognition.“Nearly all HRSA-funded health centers have demonstrated improvement in their clinical quality measures reflecting HRSA’s strong commitment to providing high value health care,” said HRSA Administrator Tom Engels. €œHealth centers serve approximately 1 in 11 people nationally. These awards will support health centers as they continue to be a primary medical home for communities around the aricept for country.

Today, nearly 1,400 health centers operate nearly 13,000 service delivery sites nationwide.”For a list of today’s award recipients, visit. Https://bphc.hrsa.gov/programopportunities/fundingopportunities/qualityimprovement/index.html To locate a HRSA-funded health center, visit. Https://findahealthcenter.hrsa.gov/..

Start Preamble where to buy generic aricept Centers for Medicare &. Medicaid Services (CMS), HHS. Extension of timeline for publication of final rule. This notice announces an extension of the timeline for publication of a Medicare final rule in accordance with the Social Security where to buy generic aricept Act, which allows us to extend the timeline for publication of the final rule.

As of August 26, 2020, the timeline for publication of the final rule to finalize the provisions of the October 17, 2019 proposed rule (84 FR 55766) is extended until August 31, 2021. Start Further Info Lisa O. Wilson, (410) where to buy generic aricept 786-8852. End Further Info End Preamble Start Supplemental Information In the October 17, 2019 Federal Register (84 FR 55766), we published a proposed rule that addressed undue regulatory impact and burden of the physician self-referral law.

The proposed rule was issued in conjunction with the Centers for Medicare &. Medicaid Services' where to buy generic aricept (CMS) Patients over Paperwork initiative and the Department of Health and Human Services' (the Department or HHS) Regulatory Sprint to Coordinated Care. In the proposed rule, we proposed exceptions to the physician self-referral law for certain value-based compensation arrangements between or among physicians, providers, and suppliers. A new exception for certain arrangements under which a physician receives limited remuneration for items or services actually provided by the physician.

A new exception for donations of cybersecurity technology where to buy generic aricept and related services. And amendments to the existing exception for electronic health records (EHR) items and services. The proposed rule also provides critically necessary guidance for physicians and health care providers and suppliers whose financial relationships are governed by the physician self-referral statute and regulations. This notice announces an extension of the timeline for publication of the final rule and the continuation of effectiveness of the proposed where to buy generic aricept rule.

Section 1871(a)(3)(A) of the Social Security Act (the Act) requires us to establish and publish a regular timeline for the publication of final regulations based on the previous publication of a proposed regulation. In accordance with section 1871(a)(3)(B) of the Act, the timeline may vary among different regulations based on differences in the complexity of the regulation, the number and scope of comments received, and other relevant factors, but may not be longer than 3 years except under exceptional circumstances. In addition, in accordance with section 1871(a)(3)(B) of the Act, the Secretary may extend the initial targeted publication date of the final regulation if the Secretary, no later than the regulation's previously established proposed publication date, publishes a where to buy generic aricept notice with the new target date, and such notice includes a brief explanation of the justification for the variation. We announced in the Spring 2020 Unified Agenda (June 30, 2020, www.reginfo.gov) that we would issue the final rule in August 2020.

However, we are still working through the Start Printed Page 52941complexity of the issues raised by comments received on the proposed rule and therefore we are not able to meet the announced publication target date. This notice extends the timeline for publication of the final where to buy generic aricept rule until August 31, 2021. Start Signature Dated. August 24, 2020.

Wilma M. Robinson, Deputy Executive Secretary to where to buy generic aricept the Department, Department of Health and Human Services. End Signature End Supplemental Information [FR Doc. 2020-18867 Filed 8-26-20.

8:45 am]BILLING CODE 4120-01-PToday, the where to buy generic aricept U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), announced over $117 million in quality improvement awards to 1,318 health centers across all U.S. States, territories and the District of Columbia. HRSA-funded health centers will use these funds to further strengthen quality improvement activities and expand quality primary health care service delivery.“These quality improvement awards support health centers across the country in delivering care to nearly where to buy generic aricept 30 million people, providing a convenient source of quality care that has grown even more important during the COVID-19 pandemic,” said HHS Secretary Alex Azar.

€œThese awards help ensure that all patients who visit a HRSA-funded health center continue to receive the highest quality of care, including access to COVID-19 testing and treatment.”Health centers deliver comprehensive care to people who are low-income, uninsured or face other obstacles to getting health care. On top of the safety-net that they provide, health centers have been on the front lines preventing and responding to the COVID-19 public health emergency, including providing over 3 million COVID-19 tests. Health centers continue to provide essential services for our nation’s most vulnerable and medically underserved populations, including those who often do not have access to care, before, during and after the COVID-19 pandemic.HRSA’s quality improvement awards recognize the highest performing health centers nationwide as well where to buy generic aricept as those health centers that have made significant quality improvements from the previous year.Health centers are recognized for achievements in various areas. Improving cost-efficient care delivery.

Increasing quality of care. Reducing health where to buy generic aricept disparities. Increasing both the number of patients served. Increasing patients’ ability to access comprehensive services.

Advancing the use where to buy generic aricept of health information technology. And Achieving patient-centered medical home recognition.“Nearly all HRSA-funded health centers have demonstrated improvement in their clinical quality measures reflecting HRSA’s strong commitment to providing high value health care,” said HRSA Administrator Tom Engels. €œHealth centers serve approximately 1 in 11 people nationally. These awards will support health centers as they continue to be where to buy generic aricept a primary medical home for communities around the country.

Today, nearly 1,400 health centers operate nearly 13,000 service delivery sites nationwide.”For a list of today’s award recipients, visit. Https://bphc.hrsa.gov/programopportunities/fundingopportunities/qualityimprovement/index.html To locate a HRSA-funded health center, visit. Https://findahealthcenter.hrsa.gov/..

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Latest Mental Health mr caudill is taking aricept for which health condition News By Robin Foster and E.J. MundellHealthDay ReportersWEDNESDAY, mr caudill is taking aricept for which health condition Sept. 30, 2020 (HealthDay News)More than 60% of households with children in the United States have struggled with serious financial problems during the coronavirus pandemic, a new poll shows.Black and Hispanic households with children have borne the brunt of the hardships, which include struggles to afford medical care, depletion of household savings and difficulty paying debts, the poll found.Conducted by NPR, the Robert Wood Johnson Foundation and the Harvard T.H.

Chan School of Public Health, the poll surveyed more than 3,400 adults, 1,000 of whom were living with children under the age of 18, between July 1 mr caudill is taking aricept for which health condition and Aug. 3.Of the Hispanic households with children that responded, 86% reported these difficulties. In Black households, 66% reported mr caudill is taking aricept for which health condition them.

In white households, the number hovers around 50%.The stark racial differences were surprising, as they surfaced after federal and state governments invested heavily in programs for communities disproportionately affected by the pandemic, Robert Blendon, a director of the study behind the report and a professor at the Harvard School of Public Health in Boston, told The New York Times."So much money was spent to put a cushion under households," Blendon said. Still, "the numbers of people in trouble, that is the shock," he added.Experts worry that the financial fallout from the pandemic could be even worse than the poll depicts, as government measures to support households run out, Julie Morita, executive vice president of the Robert Wood Johnson Foundation, told the Times."It's a very large number of people who can't pay the basics," Blendon told the Times mr caudill is taking aricept for which health condition. "You have unbelievably mr caudill is taking aricept for which health condition vulnerable people over the next six months."But on Tuesday, there were also signs of hope that more government relief might be on the way.

House Speaker Nancy Pelosi and White House chief of staff Mark Meadows both said they're hopeful they can reach agreement on a new economic stimulus bill, the Washington Post reported.The new bill extends payroll support for the airline industry and includes new small business money, an additional round of $1,200 stimulus checks for individuals, an extension of expired $600 weekly unemployment benefits, around $500 billion for cities and states, support for schools and COVID-19 testing and tracing, and more. There is also money in the bill to support election mr caudill is taking aricept for which health condition security and the U.S. Postal Service, as well, the Post reported.Globally, COVID death toll passes 1 millionThe global coronavirus pandemic reached a grim new milestone on Tuesday.

One million mr caudill is taking aricept for which health condition dead.Americans made up more than 200,000 of those deaths, or one in every five, according to a running tally comprised by Johns Hopkins University."It's not just a number. It's human beings. It's people we love," Dr mr caudill is taking aricept for which health condition.

Howard Markel, a professor of medical history at the mr caudill is taking aricept for which health condition University of Michigan, told the Associated Press. He's an adviser to government officials on how best to handle the pandemic -- and he lost his 84-year-old mother to COVID-19 in February."It's people we know," Markel said. "And if mr caudill is taking aricept for which health condition you don't have that human factor right in your face, it's very easy to make it abstract."It's taken the coronavirus just eight months to reach a worldwide death toll that's meant personal and economic tragedy for billions.

Right now, more than 33.6 million people worldwide are known to have been infected with the new coronavirus, the Hopkins tally found.In the meantime, Americans struggle to stay ahead of the virus. The U.S mr caudill is taking aricept for which health condition. Government announced Monday that at least 100 million rapid COVID-19 tests will be distributed to states in the coming weeks.Who will get them first?.

The White House is urging governors to use the tests to help reopen schools, the AP reported.As an example, the Abbott Labs tests would mr caudill is taking aricept for which health condition allow teachers to be tested on a weekly basis, or for parents to know whether their symptomatic child has COVID-19, the AP reported.This batch of tests is part of a 150 million order the federal government has placed with Abbott, the wire service said. The company's rapid mr caudill is taking aricept for which health condition test, the size of a credit card, is the first that does not require special computer equipment to process. It delivers results in about 15 minutes.As the rapid tests are being sent out, new COVID-19 cases remain elevated averaging more than 40,000 a day -- while experts warn of a likely surge in the fall and winter, the AP reported.Only in the last two months has U.S.

Testing capacity begun to exceed mr caudill is taking aricept for which health condition demand, the AP reported. Adm. Brett Giroir, the nation's testing czar, told Congress last week that the United States will soon have the capacity to run 3 million tests per day.One-shot vaccine mr caudill is taking aricept for which health condition moves to larger trialsIn news that might help make vaccinating all Americans against COVID-19 easier to accomplish, the first coronavirus vaccine that only requires a single shot has entered the final stages of testing in the United States, the Post reported.The international trial will eventually recruit up to 60,000 participants.

The vaccine, made by Johnson &. Johnson, is the fourth to enter the large, Phase 3 trials mr caudill is taking aricept for which health condition that determine effectiveness and safety, the Post reported. QUESTION Laughter feels good because… See Answer Paul Stoffels, the company's chief scientific officer, predicted last week there may be enough data to have results by the end of the year and the company plans to manufacture 1 billion doses next year.Three other vaccine candidates have a head start, with mr caudill is taking aricept for which health condition U.S.

Trials that began earlier this summer, but the vaccine being developed by Johnson &. Johnson could be easier to administer and distribute if it's proven safe and effective, the mr caudill is taking aricept for which health condition Post reported.The company is initially testing a single dose, while the other vaccines require a second shot three to four weeks after the first one, the newspaper said. The Johnson &.

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National Institutes of mr caudill is taking aricept for which health condition Health. "Now, here in the U.S. With 200,000 deaths, we want to do everything we can without sacrificing safety or efficacy."Cases keep mountingBy Wednesday, the mr caudill is taking aricept for which health condition U.S.

Coronavirus case count passed 7.2 million while the death toll passed 205,800, according to a Times tally.According to the same tally, the top five states in coronavirus cases as of Wednesday were. California with mr caudill is taking aricept for which health condition over 817,800. Texas with more than 780,500.

Florida with more than 704,500 mr caudill is taking aricept for which health condition. New York with over 462,000 mr caudill is taking aricept for which health condition. And Georgia with over 300,000.Curbing the spread of the coronavirus in the rest of the world remains challenging.By Wednesday, India's coronavirus case count had passed 6.2 million, just over one month after hitting the 3 million mark, the Times reported.More than 97,000 coronavirus patients have died in India, according to the Hopkins tally, but when measured as a proportion of the population, the country has had far fewer deaths than many others.

Doctors say this reflects India's younger and leaner population.Still, the country's mr caudill is taking aricept for which health condition public health system is severely strained, and some sick patients cannot find hospital beds, the newspaper said. Only the United States has more coronavirus cases.Meanwhile, Brazil passed 4.7 million cases and nearly 143,000 deaths as of Wednesday, the Hopkins tally showed.Cases are also spiking in Russia. The country's coronavirus case count has passed mr caudill is taking aricept for which health condition 1.1 million.

As of Wednesday, the death toll in Russia was over 20,630, the Hopkins tally showed.Worldwide, the number of reported infections passed 33.7 million on Wednesday, with over 1 million deaths, according to the Hopkins tally.Copyright © 2020 HealthDay. All rights mr caudill is taking aricept for which health condition reserved. From Mental Health Resources Featured Centers Health Solutions From Our Sponsors.

Latest Mental Health News By Robin Foster where to buy generic aricept and E.J. MundellHealthDay ReportersWEDNESDAY, where to buy generic aricept Sept. 30, 2020 (HealthDay News)More than 60% of households with children in the United States have struggled with serious financial problems during the coronavirus pandemic, a new poll shows.Black and Hispanic households with children have borne the brunt of the hardships, which include struggles to afford medical care, depletion of household savings and difficulty paying debts, the poll found.Conducted by NPR, the Robert Wood Johnson Foundation and the Harvard T.H. Chan School of Public Health, the poll surveyed more than 3,400 adults, 1,000 of whom were living with children under the age where to buy generic aricept of 18, between July 1 and Aug.

3.Of the Hispanic households with children that responded, 86% reported these difficulties. In Black households, 66% reported where to buy generic aricept them. In white households, the number hovers around 50%.The stark racial differences were surprising, as they surfaced after federal and state governments invested heavily in programs for communities disproportionately affected by the pandemic, Robert Blendon, a director of the study behind the report and a professor at the Harvard School of Public Health in Boston, told The New York Times."So much money was spent to put a cushion under households," Blendon said. Still, "the numbers of people in trouble, that is the shock," he added.Experts worry that the financial fallout from the pandemic could be even worse than the poll depicts, as where to buy generic aricept government measures to support households run out, Julie Morita, executive vice president of the Robert Wood Johnson Foundation, told the Times."It's a very large number of people who can't pay the basics," Blendon told the Times.

"You have unbelievably vulnerable people over the next six months."But on Tuesday, there were also signs of hope that more government where to buy generic aricept relief might be on the way. House Speaker Nancy Pelosi and White House chief of staff Mark Meadows both said they're hopeful they can reach agreement on a new economic stimulus bill, the Washington Post reported.The new bill extends payroll support for the airline industry and includes new small business money, an additional round of $1,200 stimulus checks for individuals, an extension of expired $600 weekly unemployment benefits, around $500 billion for cities and states, support for schools and COVID-19 testing and tracing, and more. There is also money in the bill to support election security where to buy generic aricept and the U.S. Postal Service, as well, the Post reported.Globally, COVID death toll passes 1 millionThe global coronavirus pandemic reached a grim new milestone on Tuesday.

One million dead.Americans made up more than 200,000 of those deaths, where to buy generic aricept or one in every five, according to a running tally comprised by Johns Hopkins University."It's not just a number. It's human beings. It's people we love," Dr where to buy generic aricept. Howard Markel, a professor of medical history at the University of Michigan, where to buy generic aricept told the Associated Press.

He's an adviser to government officials on how best to handle the pandemic -- and he lost his 84-year-old mother to COVID-19 in February."It's people we know," Markel said. "And if you don't have that human factor where to buy generic aricept right in your face, it's very easy to make it abstract."It's taken the coronavirus just eight months to reach a worldwide death toll that's meant personal and economic tragedy for billions. Right now, more than 33.6 million people worldwide are known to have been infected with the new coronavirus, the Hopkins tally found.In the meantime, Americans struggle to stay ahead of the virus. The U.S where to buy generic aricept.

Government announced Monday that at least 100 million rapid COVID-19 tests will be distributed to states in the coming weeks.Who will get them first?. The White House is urging governors to use the tests to help reopen schools, the AP reported.As an example, the Abbott Labs tests would allow teachers to be tested on a where to buy generic aricept weekly basis, or for parents to know whether their symptomatic child has COVID-19, the AP reported.This batch of tests is part of a 150 million order the federal government has placed with Abbott, the wire service said. The company's rapid test, the size of a credit card, is the first that does not where to buy generic aricept require special computer equipment to process. It delivers results in about 15 minutes.As the rapid tests are being sent out, new COVID-19 cases remain elevated averaging more than 40,000 a day -- while experts warn of a likely surge in the fall and winter, the AP reported.Only in the last two months has U.S.

Testing capacity begun to exceed demand, where to buy generic aricept the AP reported. Adm. Brett Giroir, the nation's testing czar, told Congress where to buy generic aricept last week that the United States will soon have the capacity to run 3 million tests per day.One-shot vaccine moves to larger trialsIn news that might help make vaccinating all Americans against COVID-19 easier to accomplish, the first coronavirus vaccine that only requires a single shot has entered the final stages of testing in the United States, the Post reported.The international trial will eventually recruit up to 60,000 participants. The vaccine, made by Johnson &.

Johnson, is the fourth to where to buy generic aricept enter the large, Phase 3 trials that determine effectiveness and safety, the Post reported. QUESTION Laughter feels where to buy generic aricept good because… See Answer Paul Stoffels, the company's chief scientific officer, predicted last week there may be enough data to have results by the end of the year and the company plans to manufacture 1 billion doses next year.Three other vaccine candidates have a head start, with U.S. Trials that began earlier this summer, but the vaccine being developed by Johnson &. Johnson could be easier to administer and distribute if it's proven safe and effective, the Post reported.The company is initially testing a single dose, while the other vaccines require where to buy generic aricept a second shot three to four weeks after the first one, the newspaper said.

The Johnson &. Johnson vaccine can also be stored in liquid form at refrigerator temperatures for three months, whereas two of the three other vaccines must be frozen or kept at ultra-cold temperatures for long-term where to buy generic aricept storage, the Post reported."A single-shot vaccine, if it's safe and effective, will have substantial logistic advantages for global pandemic control," said Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, who partnered with Johnson &. Johnson to develop the vaccine."It is a really good thing that we have this diversity of platforms because this is a critical crisis in terms of our global circumstance," said Dr. Francis Collins, where to buy generic aricept director of the U.S.

National Institutes where to buy generic aricept of Health. "Now, here in the U.S. With 200,000 deaths, we want to do everything we can without sacrificing safety or efficacy."Cases keep mountingBy Wednesday, the where to buy generic aricept U.S. Coronavirus case count passed 7.2 million while the death toll passed 205,800, according to a Times tally.According to the same tally, the top five states in coronavirus cases as of Wednesday were.

California with where to buy generic aricept over 817,800. Texas with more than 780,500. Florida with where to buy generic aricept more than 704,500. New York with over 462,000 where to buy generic aricept.

And Georgia with over 300,000.Curbing the spread of the coronavirus in the rest of the world remains challenging.By Wednesday, India's coronavirus case count had passed 6.2 million, just over one month after hitting the 3 million mark, the Times reported.More than 97,000 coronavirus patients have died in India, according to the Hopkins tally, but when measured as a proportion of the population, the country has had far fewer deaths than many others. Doctors say this reflects India's younger and leaner population.Still, the country's public health where to buy generic aricept system is severely strained, and some sick patients cannot find hospital beds, the newspaper said. Only the United States has more coronavirus cases.Meanwhile, Brazil passed 4.7 million cases and nearly 143,000 deaths as of Wednesday, the Hopkins tally showed.Cases are also spiking in Russia. The country's where to buy generic aricept coronavirus case count has passed 1.1 million.

As of Wednesday, the death toll in Russia was over 20,630, the Hopkins tally showed.Worldwide, the number of reported infections passed 33.7 million on Wednesday, with over 1 million deaths, according to the Hopkins tally.Copyright © 2020 HealthDay. All rights where to buy generic aricept reserved. From Mental Health Resources Featured Centers Health Solutions From Our Sponsors.

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Paul Berg, M.D.While COVID-19 can you buy aricept without a prescription has caused significant illness and concern for millions of Americans and residents across the globe, experts at MidMichigan Health remind us not to lose sight of another potentially lethal virus - Influenza.Influenza is a seasonal virus that impacts the U.S. Population each year between late fall and early spring. Since 2015, influenza has caused between 280,000 to 810,000 hospitalizations each year in the U.S., and 23,000 to 61,000 Americans have can you buy aricept without a prescription died from the virus. Fortunately, influenza is a preventable illness because of the annual flu vaccine.

However, only about half can you buy aricept without a prescription of the U.S. Population receives the flu vaccine each year. Paul Berg M.D., president, MidMichigan can you buy aricept without a prescription Physicians Group. Courtney Pearson, M.D., infectious disease specialist, MidMichigan Physicians Group, and Lydia Watson, M.D., senior vice president and chief medical officer, MidMichigan Health, answer some of the common questions about the flu vaccine:Courtney Pearson, M.D.How does the flu vaccine work?.

The flu vaccine works by causing can you buy aricept without a prescription antibodies to form in the human body. These antibodies provide protection against infection if that individual is later exposed to the actual virus. Vaccines in the U.S can you buy aricept without a prescription. Protect against three (“trivalent”) or four (“quadrivalent”) different strains of the flu virus.

Once the flu vaccine is administered, it takes about two weeks for the body to generate the protective antibodies can you buy aricept without a prescription. These antibodies then provide protection for several months following the vaccination. The best time to receive the flu vaccination can you buy aricept without a prescription is in the fall, prior to the arrival of the seasonal virus. Most medical providers begin administering the vaccine in September but will continue to administer for the duration of the flu season.

The Centers for Disease Control and Prevention (CDC) recommends that people get a flu vaccine by the end of October.Who should be vaccinated? can you buy aricept without a prescription. With rare exception, every human older than 6 months of age should receive the flu vaccine each year. Some people may not be candidates for certain vaccine types, dependent on factors such as age, allergy history, or underlying medical conditions, so these individuals should can you buy aricept without a prescription check with their medical provider to discuss which vaccine may be best for them. However, the most important fact to remember is to receive the vaccine each year.Lydia Watson, M.D.Does the flu vaccine really work?.

Yes. The vaccine is effective, though the effectiveness can vary based on certain factors. The protection from the vaccine varies from season to season dependent on the “match” between the vaccine and the actual viruses circulating in the community. An individual’s health status can also play a role in the effectiveness of the vaccine.

In general, the vaccine is most effective in young, healthy adults and older children. Older adults may not mount as robust an antibody response to the vaccine. Even though it is not perfect, the flu vaccine remains a very helpful tool in preventing serious illness from influenza. Here are some statistics to highlight the benefits of the flu vaccine:In the 2018-2019 flu season, the vaccine prevented an estimated 4.4 million illnesses, 2.3 million flu-related medical visits, 58,000 flu-related hospitalizations, and 3,500 flu-related deaths.

It is estimated that receiving the flu vaccine reduces a person’s risk of having to go to the doctor with flu by 40-60 percent. A 2018 study showed that, from 2012 to 2015, the flu vaccine among adults reduced the risk of being admitted to an ICU with flu by 82 percent.A 2017 study showed that flu vaccination significantly reduces a child’s risk of dying from influenza.Flu vaccination is very beneficial for those with underlying medical conditions, as it has been shown to reduce rates of cardiac events in those with heart disease, and reduce hospitalization rates for those with COPD, chronic lung disease, or diabetes. Flu vaccination is beneficial for those that are pregnant, as it reduces the risk of serious flu-related lung infections by 50 percent. It is also beneficial for the infant, who will have circulating antibodies protecting them from illness for several months after birth.

Why do some people get sick with the seasonal influenza virus even though they received the vaccine?. It’s possible that some people get sick with the seasonal virus because they were exposed to the virus within two weeks of receiving the vaccine. It takes up to two weeks to develop the antibodies once vaccinated, so an exposure to the real virus during this window could still result in illness. Another reason may be that the person was exposed to a virus that was not in the seasonal vaccine.

There are many different strains of the influenza virus that circulate each year. The flu vaccine is designed to protect against three or four of the most common strains that the research suggests will be circulating in the given year.In addition, it’s possible that the person simply did not develop a good immune response to the vaccine. Some individuals, such as older adults or those with underlying health conditions, don’t develop a strong response to the vaccine. For this reason it is important that all individuals get vaccinated.

The more young, healthy people that are vaccinated, the less likelihood that they will spread the virus to more vulnerable individuals.Can the flu vaccine give me the flu?. No. The flu vaccine cannot cause flu illness. Flu vaccines that are administered with a needle (flu shots) are currently made two ways.

The vaccine is either flu viruses that have been killed (inactivated) and are therefore not infectious, or they are made with proteins from a flu virus (recombinant vaccines) and cannot cause illness. Nasal spray influenza vaccines are made with attenuated (weakened) live flu viruses, and also cannot cause flu illness. The weakened viruses used in the nasal spray vaccines are cold-adapted, which means that they are designed to only cause mild infection at the cooler temperatures found within the nose. The viruses cannot infect the lungs or other areas where warmer temperatures exist.What about side effects?.

The flu vaccines can have some side effects. Possible minor side effects include soreness or redness at the injection site, headaches, fever, muscle aches, nausea, or fatigue. Most individuals do not have these side effects. For those that do, the side effects are usually mild and short-lived.

As with any medicine, there is the remote chance that people could have a serious allergic reaction or complication. This is very rare.Shouldn’t we be more focused on COVID-19 than influenza?. We certainly need to keep our focus on COVID-19, but one way to protect our valuable health care resources is to reduce the chances of other serious infections like influenza. Ensuring that all health care workers and community members receive the flu vaccine is a great strategy to reduce the influenza disease burden in our communities.

Let’s all get vaccinated for the flu, protect ourselves and our resources from that lethal virus, so we can focus on the risks that COVID will present this coming fall and winter.How can you tell the difference between the flu and COVID-19 symptoms?. It’s going to be difficult to tell the difference between the flu and COVID-19 symptoms since both illnesses produce respiratory symptoms. In addition, it’s possible to have both infections at the same time. Testing needs to be done to determine if symptoms are due to flu or COVID-19.Those interested in more information on the flu vaccine may visit www.cdc.gov/flu/prevent/keyfacts.htmTo help smokers kick the habit, MidMichigan Health will host a virtual American Lung Association’s Freedom From Smoking® program this fall.

The free eight-week program will be held beginning Thursday, Oct. 15 through Thursday, Dec. 3, 2020. Sessions will take place from 5:30 to 7 p.m., via GoToMeeting™.Designed to help smokers gain control over their behavior, each session is led by a certified American Lung Association facilitator.

Attendees will be given support, encouragement and the tools to develop a plan for quitting and living a smoke-free life. Led in a group format, the program sessions help encourage attendees to work on the process and problems of quitting, individually and as part of a group.All program materials and login information will be mailed to registrants prior to the first meeting. Participants will join the GoToMeeting from their smart phones, computer, tablet or other device with an internet connection.Registration is required for this free program and can be completed at www.midmichigan.org/freedomfromsmoking. Those who need assistance with registration may call MidMichigan Health Line toll-free at (800) 999-3199.Freedom From Smoking® is a registered trademark of the American Lung Association.GoToMeeting is a trademark of LogMeIn..

Paul Berg, M.D.While COVID-19 has caused significant illness and concern for millions of where to buy generic aricept Americans and residents across the globe, experts at MidMichigan Health remind us not to lose sight of another potentially lethal virus - Influenza.Influenza is a seasonal virus that impacts the U.S. Population each year between late fall and early spring. Since 2015, where to buy generic aricept influenza has caused between 280,000 to 810,000 hospitalizations each year in the U.S., and 23,000 to 61,000 Americans have died from the virus. Fortunately, influenza is a preventable illness because of the annual flu vaccine. However, only about half of the where to buy generic aricept U.S.

Population receives the flu vaccine each year. Paul Berg M.D., president, where to buy generic aricept MidMichigan Physicians Group. Courtney Pearson, M.D., infectious disease specialist, MidMichigan Physicians Group, and Lydia Watson, M.D., senior vice president and chief medical officer, MidMichigan Health, answer some of the common questions about the flu vaccine:Courtney Pearson, M.D.How does the flu vaccine work?. The flu vaccine works by causing antibodies to form where to buy generic aricept in the human body. These antibodies provide protection against infection if that individual is later exposed to the actual virus.

Vaccines in where to buy generic aricept the U.S. Protect against three (“trivalent”) or four (“quadrivalent”) different strains of the flu virus. Once the flu vaccine is administered, it takes where to buy generic aricept about two weeks for the body to generate the protective antibodies. These antibodies then provide protection for several months following the vaccination. The best time to receive the flu where to buy generic aricept vaccination is in the fall, prior to the arrival of the seasonal virus.

Most medical providers begin administering the vaccine in September but will continue to administer for the duration of the flu season. The Centers for Disease Control and Prevention (CDC) recommends that people get where to buy generic aricept a flu vaccine by the end of October.Who should be vaccinated?. With rare exception, every human older than 6 months of age should receive the flu vaccine each year. Some people may not be candidates for certain vaccine types, dependent on factors such as age, allergy history, or underlying medical conditions, so these individuals should check with their medical provider where to buy generic aricept to discuss which vaccine may be best for them. However, the most important fact to remember is to receive the vaccine each year.Lydia Watson, M.D.Does the flu vaccine really work?.

Yes. The vaccine is effective, though the effectiveness can vary based on certain factors. The protection from the vaccine varies from season to season dependent on the “match” between the vaccine and the actual viruses circulating in the community. An individual’s health status can also play a role in the effectiveness of the vaccine. In general, the vaccine is most effective in young, healthy adults and older children.

Older adults may not mount as robust an antibody response to the vaccine. Even though it is not perfect, the flu vaccine remains a very helpful tool in preventing serious illness from influenza. Here are some statistics to highlight the benefits of the flu vaccine:In the 2018-2019 flu season, the vaccine prevented an estimated 4.4 million illnesses, 2.3 million flu-related medical visits, 58,000 flu-related hospitalizations, and 3,500 flu-related deaths. It is estimated that receiving the flu vaccine reduces a person’s risk of having to go to the doctor with flu by 40-60 percent. A 2018 study showed that, from 2012 to 2015, the flu vaccine among adults reduced the risk of being admitted to an ICU with flu by 82 percent.A 2017 study showed that flu vaccination significantly reduces a child’s risk of dying from influenza.Flu vaccination is very beneficial for those with underlying medical conditions, as it has been shown to reduce rates of cardiac events in those with heart disease, and reduce hospitalization rates for those with COPD, chronic lung disease, or diabetes.

Flu vaccination is beneficial for those that are pregnant, as it reduces the risk of serious flu-related lung infections by 50 percent. It is also beneficial for the infant, who will have circulating antibodies protecting them from illness for several months after birth. Why do some people get sick with the seasonal influenza virus even though they received the vaccine?. It’s possible that some people get sick with the seasonal virus because they were exposed to the virus within two weeks of receiving the vaccine. It takes up to two weeks to develop the antibodies once vaccinated, so an exposure to the real virus during this window could still result in illness.

Another reason may be that the person was exposed to a virus that was not in the seasonal vaccine. There are many different strains of the influenza virus that circulate each year. The flu vaccine is designed to protect against three or four of the most common strains that the research suggests will be circulating in the given year.In addition, it’s possible that the person simply did not develop a good immune response to the vaccine. Some individuals, such as older adults or those with underlying health conditions, don’t develop a strong response to the vaccine. For this reason it is important that all individuals get vaccinated.

The more young, healthy people that are vaccinated, the less likelihood that they will spread the virus to more vulnerable individuals.Can the flu vaccine give me the flu?. No. The flu vaccine cannot cause flu illness. Flu vaccines that are administered with a needle (flu shots) are currently made two ways. The vaccine is either flu viruses that have been killed (inactivated) and are therefore not infectious, or they are made with proteins from a flu virus (recombinant vaccines) and cannot cause illness.

Nasal spray influenza vaccines are made with attenuated (weakened) live flu viruses, and also cannot cause flu illness. The weakened viruses used in the nasal spray vaccines are cold-adapted, which means that they are designed to only cause mild infection at the cooler temperatures found within the nose. The viruses cannot infect the lungs or other areas where warmer temperatures exist.What about side effects?. The flu vaccines can have some side effects. Possible minor side effects include soreness or redness at the injection site, headaches, fever, muscle aches, nausea, or fatigue.

Most individuals do not have these side effects. For those that do, the side effects are usually mild and short-lived. As with any medicine, there is the remote chance that people could have a serious allergic reaction or complication. This is very rare.Shouldn’t we be more focused on COVID-19 than influenza?. We certainly need to keep our focus on COVID-19, but one way to protect our valuable health care resources is to reduce the chances of other serious infections like influenza.

Ensuring that all health care workers and community members receive the flu vaccine is a great strategy to reduce the influenza disease burden in our communities. Let’s all get vaccinated for the flu, protect ourselves and our resources from that lethal virus, so we can focus on the risks that COVID will present this coming fall and winter.How can you tell the difference between the flu and COVID-19 symptoms?. It’s going to be difficult to tell the difference between the flu and COVID-19 symptoms since both illnesses produce respiratory symptoms. In addition, it’s possible to have both infections at the same time. Testing needs to be done to determine if symptoms are due to flu or COVID-19.Those interested in more information on the flu vaccine may visit www.cdc.gov/flu/prevent/keyfacts.htmTo help smokers kick the habit, MidMichigan Health will host a virtual American Lung Association’s Freedom From Smoking® program this fall.

The free eight-week program will be held beginning Thursday, Oct. 15 through Thursday, Dec. 3, 2020. Sessions will take place from 5:30 to 7 p.m., via GoToMeeting™.Designed to help smokers gain control over their behavior, each session is led by a certified American Lung Association facilitator. Attendees will be given support, encouragement and the tools to develop a plan for quitting and living a smoke-free life.

Led in a group format, the program sessions help encourage attendees to work on the process and problems of quitting, individually and as part of a group.All program materials and login information will be mailed to registrants prior to the first meeting. Participants will join the GoToMeeting from their smart phones, computer, tablet or other device with an internet connection.Registration is required for this free program and can be completed at www.midmichigan.org/freedomfromsmoking. Those who need assistance with registration may call MidMichigan Health Line toll-free at (800) 999-3199.Freedom From Smoking® is a registered trademark of the American Lung Association.GoToMeeting is a trademark of LogMeIn..