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Saturday, December 5, 2020

In the End, States Determine Who Will Get COVID Vaccines First

 Vaccines against COVID-19 have arrived with unprecedented speed. At least three candidates appear to be extremely effective and are likely to be approved in the U.S. in coming weeks. By the end of December, the U.S. Centers for Disease Control and Prevention (CDC) estimates the U.S. will have enough vaccines to treat 20 million people. Britain this week approved the vaccine made by Pfizer and BioNTech.

But for the first time in modern U.S. history, not everyone who wants a vaccine will be able to get one immediately. Figuring out who gets the first shots in that country and who has to wait is the job of an obscure CDC panel known as the Advisory Committee on Immunization Practices (ACIP). This week they announced their first official COVID vaccine distribution guidelines.

The committee makes such plans for all newly approved vaccines, but never before has ACIP had to work so fast. In its December 1 meeting, the committee voted 13 to one that the approximately 21 million health care workers in the country should be the first to receive any new COVID vaccine, along with residents of long-term care facilities like nursing homes. But deciding who comes second, and third, and even further back in the priority line, is trickier, as health experts weigh factors such as vulnerabilities of specific groups and whether immunizing others can have an outsize effect in stopping the harm to larger society caused by the disease.

Public health specialists who have worked on vaccine plans say the immense effects that COVID has had on the country make these decisions challenging. “We don't have everything in place, because we've just never faced this before,” says physician Helene Gayle, president and CEO of the Chicago Community Trust, who co-chaired a committee evaluating COVID vaccine priorities for the U.S. National Academies of Sciences, Engineering, and Medicine. “In my lifetime, there's never been such a huge challenge to major swathes of the population that also has such societal impact.”

Lawrence Gostin, a health law expert at George Washington University, says there is virtually universal agreement that health care workers should get the vaccine first. This group is one of the most likely to acquire the virus because of their exposure to infected patients. Health care workers have put themselves at the front lines and their well-being ensures that other patients are treated. This follows the recommendations of an October report from Gayle’s committee.

Still, when Britain approved the Pfizer/BioNTech vaccine, the country’s Joint Committee on Vaccination and Immunisation did not give health care workers the highest priority. Instead, it recommended that long-term care residents receive the very first vaccines. The committee cited this population’s very high risk of infection and death; in one study of four nursing homes, more than a quarter of residents died over the course of two months.

In the U.S., nursing homes account for nearly half of all COVID deaths. Still, including long-term care facility residents in the first group, known as phase 1a, was a more contentious point of discussion at the recent ACIP meeting. Committee members questioned whether this population, which tends to have weaker immune systems, might not respond as well to a vaccine. The lone dissenting vote on the initial distribution plan, infectious disease expert Helen Keipp Talbot of Vanderbilt University, said she felt there was not enough data on the vaccine’s safety and efficacy in this group, and was concerned that U.S. federal agencies’ surveillance systems weren’t sufficient to track these people’s outcomes.

Choosing the second group—people who could begin receiving vaccines in about a month—will present even more difficulties. Current plans put forward by the CDC suggest essential workers—a population of about 87 million—will be in this category, known as phase 1b. The following phase, 1c, which could start in about three months, would include the approximately 153 million people who have high-risk medical conditions and those over age 65.

But those plans are not final, and ACIP will continue to meet and hammer out details after the FDA approves each new vaccine and as more doses become available. For now, the committee has to consider several factors, says Jeffrey Duchin, a former ACIP member who now directs public health efforts in Seattle and King County in Washington State. Foremost is the scientific evidence about which populations are most likely to spread the disease and who is most likely to have severe effects. Epidemiological models suggest there is little difference in spread whether a vaccine is first given to high-risk adults, essential workers or people over the age of 65.

Deciding among these groups, therefore, may come down to factors such as logistics and ethical principles like access to health care. People from racial minority groups, for instance, comprise a high percentage of essential workers with a high chance of exposure. Because these groups have historically had less access to health care and because COVID is far more likely to be fatal in nonwhite Americans, ethical principles might suggest such underserved populations be prioritized, Duchin says.

Others have argued that vaccines be specifically targeted to minority ethnic groups, regardless of whether they are essential workers, in order to make up for historical inequities. “I think there is a very strong ethical justification for giving considerable advantage to people who are socially vulnerable, and I would go further and give explicit priority to racial minorities,” Gostin says. “COVID has really amplified public concerns about racial and social injustice.”

But Gostin concedes that such a strategy would face political and legal risks. Surveys have shown that Black Americans, for instance, are already skeptical about receiving a new COVID vaccine, reflecting a broader distrust of experimental treatments among minority populations. And a conservative-leaning U.S. Supreme Court would be likely to strike down any plan based explicitly on race, if that plan were challenged in a lawsuit. Targeting the vaccine to essential workers and people in underserved communities, Gostin says, might be a more viable strategy.

One question that should be relatively easy to resolve is determining which health conditions put people in a high-risk group. The CDC has amassed a large amount of data on conditions like diabetes and morbid obesity that increase the risk of severe COVID complications, and conditions like asthma that only slightly increase the risk. This list, Gayle says, will allow public health officials to prioritize the people whose preexisting conditions put them at most risk.

Logistical issues may dictate some of the allocation as well. The Pfizer vaccine, for instance need to be stored at –70 degrees Celsius, a temperature generally only achievable at health care centers. So getting this vaccine to rural populations could prove challenging.

Ultimately, the implementation of allocation decisions is not done by ACIP. It comes down to state and local jurisdictions. The federal advisory committee can recommend a vaccination triage scheme, but the CDC can’t force states to follow it. Still, Sara Rosenbaum, a legal expert at George Washington University, expects that states will accept the plans. “I’d be surprised if they fought prioritization,” she says, noting that, historically, local public health agencies have always followed federal vaccination guidelines. 

But the CDC plans will need to allow local public health officials some flexibility in determining who is part of a particular group, for instance who qualifies as an essential worker or member of a disadvantaged population. Gostin agrees that flexibility is necessary, but is concerned that “it’s a recipe for hundred different responses across America.” He notes that during this year many state and local governments have failed to follow federal guidelines on COVID testing and mask requirements: “We’ve seen American federalism fail spectacularly.”

For that reason, Duchin says that ACIP will need to carefully word its recommendations in order to ensure consistency. “If vaccination strategies differ in big ways, it will lead to confusion and potentially undermine confidence in the process,” he says.

https://www.scientificamerican.com/article/who-will-get-covid-vaccines-first-and-who-will-have-to-wait1/

Moscow rolls out Sputnik V COVID-19 vaccine to most exposed groups

 Moscow began distributing the Sputnik V COVID-19 shot via 70 clinics on Saturday to the most exposed groups, marking Russia’s first large-scale vaccination against the disease, the city’s coronavirus task force said.

The Russian-made vaccine will first be made available to doctors and other medical workers, teachers and social workers because they run the highest risk of exposure to the disease.

“You are working at an educational institution and have top-priority for the COVID-19 vaccine, free of charge,” read a phone text message received by one Muscovite, an elementary school teacher, early on Saturday and seen by Reuters.

President Vladimir Putin has ordered a nationwide voluntary vaccination programme to begin next week. He said Russia will have produced 2 million vaccine doses within the next few days.

The head of the Russian Direct Investment Fund (RDIF), Kirill Dmitriev, said in an interview with the BBC on Friday that Russia expects to give the vaccine to about 2 million people this month.

“Over the first five hours, 5,000 people signed up for the jab - teachers, doctors, social workers, those who are today risking their health and lives the most,” Mayor Sergei Sobyanin wrote on his personal website on Friday.

Russia has already vaccinated more than 100,000 high-risk people, Health Minister Mikhail Murashko said earlier this week during a separate presentation to the United Nations about Sputnik V.

Among the first people signing up to the Moscow roll-out, Nadezhda Ragulina, an administrator at a Moscow clinic, said she wanted the vaccine as she had witnessed many COVID-19 patients.

“This is my decision... Some people close to me also have had an experience (of COVID-19). That’s why I want to protect myself, my relatives, to obtain the immunity,” she told Rossiya-24 state TV channel.

Moscow, a city of around 13 million people, has been the epicentre of Russia’s coronavirus outbreak. It reported 7,993 new cases on Saturday , up from 6,868 the day before and well above the daily tallies of around 700 seen in early September.

The age for those receiving shots is capped at 60. People with certain underlying health conditions, pregnant women and those who have had a respiratory illness for the past two weeks are barred from vaccination.

Russia has developed two COVID-19 vaccines, Sputnik V which is backed by the Russian Direct Investment Fund and another developed by Siberia’s Vector Institute, with final trials for the both yet to be completed.

Scientists have raised concerns about the speed at which Russia has worked, giving the regulatory go-ahead for its vaccines and launching mass vaccinations before full trials to test its safety and efficacy had been completed.

The Sputnik V vaccine is administered in two injections, with the second dose is expected to be given 21 days after the first.

Deputy Prime Minister Tatiana Golikova said on Friday that the vaccinated should avoid public places and reduce their intake of medicine and alcohol, which could suppress the immune system, within the first 42 days after the first jab.

Moscow closed down all public places including parks and cafes, with exception for delivery, in late March, with police patrolling the streets looking for whose violating the rules. Restrictions were eased from mid-June, however.

Russia as a whole reported 28,782 new infections on Saturday, its highest daily tally, pushing the national total to 2,431,731, the fourth-highest in the world.

In October, certain restrictions such as remote learning for some secondary school children and a 30% limit on the number of workers allowed in offices were introduced again.

https://www.reuters.com/article/us-health-coronavirus-russia-vaccination/moscow-rolls-out-sputnik-v-covid-19-vaccine-to-most-exposed-groups-idUSKBN28F09O

Moderna CEO confident of producing 500M COVID-19 vaccine doses in 2021

 

Friday, December 4, 2020

UK Exempts Sports Stars, Actors, 'High-Value' Biz Travelers Returning To England From Quarantine

 Grant Shapps has revealed “high-value" business travellers are part of a new group of people who will not have to quarantine when they return to England after traveling to countries outside of coronavirus travel corridors.

The transport secretary said recently signed sports stars, performing arts professionals, TV production staff and journalists will also be exempt from the 14-day self-isolation period even if they have visited a destination where people are required to quarantine on return.

The move, which will come into force from 4am on Saturday, was recommended by the Government’s Global Travel Taskforce, which warned that business travel would be particularly slow to recover. 

Announcing the news on Twitter, Mr Shapps wrote: “New Business Traveller exemption: From 4am on Sat 5th Dec high-value business travellers will no longer need to self-isolate when returning to ENGLAND from a country NOT in a travel corridor, allowing more travel to support the economy and jobs. Conditions apply.

“From 4am on Sat 5th Dec certain performing arts professionals, TV production staff, journalists and recently signed elite sportspersons will also be exempt, subject to specific criteria being met.”

https://www.politicshome.com/news/article/sports-stars-actors-and-highvalue-business-travellers-returning-to-england-will-no-longer-have-to-selfisolate

Metformin and risk of mortality in patients hospitalised with COVID-19

 


PDF: https://www.thelancet.com/action/showPdf?pii=S2666-7568%2820%2930033-7

Summary

Background

Type 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist.

Methods

In this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use.

Findings

6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52·8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0·887 [95% CI 0·782–1·008]) or propensity matching (odds ratio [OR] 0·912 [95% CI 0·777–1·071], p=0·15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650–0·951) and propensity matching (OR 0·759, 95% CI 0·601–0·960, p=0·021). There was no significant reduction in mortality among men (HR 0·957, 95% CI 0·82–1·14; p=0·689 by Cox proportional hazards).

Interpretation

Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive.

Funding

National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.

Get Ready for False Side Effects

 By Derek Lowe 

We’re in the beginning of the vaccine endgame now: regulatory approval and actual distribution/rollout into the population. The data for the Pfizer/BioNTech and Moderna vaccines continue to look good (here’s a new report on the longevity of immune response after the Moderna one), with the J&J and Novavax efforts still to report. The AZ/Oxford candidate is more of a puzzle, thanks to some very poor communication about their clinical work (which suffered from some fundamental problems itself).

Now we have to get people to take them. Surveys continue to show a good number of people who are (at the very least) in the “why don’t you take it first” category. I tend to think that as vaccine dosing becomes reality that more people will get in line for a shot, but that remains to be seen. I wanted to highlight something that we’ll all need to keep in mind, though.

Bob Wachter of UCSF had a very good thread on Twitter about vaccine rollouts the other day, and one of the good points he made was this one. We’re talking about treating very, very large populations, which means that you’re going to see the usual run of mortality and morbidity that you see across large samples. Specifically, if you take 10 million people and just wave your hand back and forth over their upper arms, in the next two months you would expect to see about 4,000 heart attacks. About 4,000 strokes. Over 9,000 new diagnoses of cancer. And about 14,000 of that ten million will die, out of usual all-causes mortality. No one would notice. That’s how many people die and get sick anyway.

But if you took those ten million people and gave them a new vaccine instead, there’s a real danger that those heart attacks, cancer diagnoses, and deaths will be attributed to the vaccine. I mean, if you reach a large enough population, you are literally going to have cases where someone gets the vaccine and drops dead the next day (just as they would have if they *didn’t* get the vaccine). It could prove difficult to convince that person’s friends and relatives of that lack of connection, though. Post hoc ergo propter hoc is one of the most powerful fallacies of human logic, and we’re not going to get rid of it any time soon. Especially when it comes to vaccines. The best we can do, I think, is to try to get the word out in advance. Let people know that such things are going to happen, because people get sick and die constantly in this world. The key will be whether they are getting sick or dying at a noticeably higher rate once they have been vaccinated.

No such safety signals have appeared for the first vaccines to roll out (Moderna and Pfizer/BioNTech). In fact, we should be seeing the exact opposite effects on mortality and morbidity as more and more people get vaccinated. The excess-death figures so far in the coronavirus pandemic have been appalling (well over 300,000 in the US), and I certainly think mass vaccination is the most powerful method we have to knock that back down to normal.

That’s going to be harder to do, though, if we get screaming headlines about people falling over due to heart attacks after getting their vaccine shots. Be braced.

https://blogs.sciencemag.org/pipeline/archives/2020/12/04/get-ready-for-false-side-effects

OTC 'Brain Boosters' May Pose Serious Risks

 Over-the-counter supplements advertised to improve memory and cognitive function may contain unapproved pharmaceutical drugs in potentially dangerous combinations and dosages, new research shows.

"Americans spend more than $600 million on over-the-counter smart pills every year, but we know very little about what is actually in these products," Pieter A. Cohen, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

"Finding new combinations of drugs [that have] never been tested in humans in over-the-counter brain-boosting supplements is alarming," said Cohen.

The study was published online September 23 in Neurology Clinical Practice, a journal of the American Academy of Neurology (AAN).

Buyer Beware

In a search of the National Institutes of Health (NIH) Dietary Supplement Label Database and the Natural Medicines Database, Cohen and colleagues identified 10 supplements labeled as containing omberacetam, aniracetam, phenylpiracetam, or oxiracetam — four analogs of piracetam that are not approved for human use in the US. Piracetam is also not approved in the US.

In these 10 products, five unapproved drugs were discovered — omberacetam and aniracetam along with three others (phenibut, vinpocetine and picamilon).

By consuming the recommended serving size of these products, consumers could be exposed to pharmaceutical-level dosages of drugs including a maximum of 40.6 mg omberacetam (typical pharmacologic dose 10 mg), 502 mg of aniracetam (typical pharmacologic dose 200-750 mg), 15.4 mg of phenibut (typical dose 250-500 mg), 4.3 mg of vinpocetine (typical dose 5-40 mg), and 90.1 mg of picamilon (typical  dose 50-200 mg), the study team reports.

Several drugs detected in these "smart" pills were not declared on the label, and several declared drugs were not detected in the products. For those products with drug quantities provided on the labels, three quarters of declared quantities were inaccurate.

Consumers who use these cognitive enhancers could be exposed to amounts of these unapproved drugs that are fourfold greater than pharmaceutical dosages and combinations never tested in humans, the study team says. One product combined three different unapproved drugs and another product contained four different drugs.

"We have previously shown that these products may contain individual foreign drugs, but in our new study we found complex combinations of foreign drugs, up to four different drugs in a single product," Cohen told Medscape Medical News.

The presence of these unapproved drugs in supplements, including at supratherapeutic dosages, suggests "serious risks to consumers and weaknesses in the regulatory framework under which supplements are permitted to be introduced in the US," Cohen and colleagues write.

"We should counsel our patients to avoid over-the-counter 'smart pills' until we can be assured as to the safety and efficacy of these products," said Cohen.

Concerning Findings

Reached for comment, Glen R. Finney, MD, fellow of the American Academy of Neurology, said two findings are very concerning: the lack of listed ingredients and especially the presence of unlisted drugs at active levels.

"What if a person has a sensitivity or allergy to one of the unlisted drugs? This is a safety issue and a consumer issue," Finney told Medscape Medical News.

Despite being widely promoted on television, "over-the-counter supplements are not regulated, so there is no guarantee that they contain what they claim, and there is very little evidence that they help memory and thinking even when they do have the ingredients they claim in the supplement," said Finney, who directs the memory and cognition program, Neuroscience Institute, Geisinger Health System, Wilkes-Barre, Pennsylvania.

"The best way to stay safe and help memory and thinking is to speak with your health providers about proven treatments that have good safety regulation, so you know what you’re getting, and what you’re getting from it," Finney advised.

The study had no targeted funding. Cohen has collaborated in research with NSF International, received compensation from UptoDate, and received research support from Consumers Union and PEW Charitable Trusts. Finney has no relevant disclosures.

Neurol Clin Pract. Published online September 23, 2020. Full text

https://www.medscape.com/viewarticle/938017