Wednesday, May 03, 2023

Meta-Analyses of School Closures by University of Oxford

New research out of the United Kingdom points to heightened levels of harm associated with COVID-19 lockdowns and school closures, with an emphasis on the particularly adverse impacts of the latter. Led by Professor Kamal R. Mahtani, and colleagues at University of Oxford, the findings were telling. After a systematic review, the team had their findings published in the British Medical Journal drilling into the actual positive and negative impacts of school closures. The team finds a lot of problems with school closures (mental health, learning, etc.) as well as some positive outcomes (reduce transmission, etc.). But in-school mitigation also can help. The quality of the evidence associated with the underlying systematic reviews was low to very low. The point here is that with any pandemic, evidence-based approaches should be taken, not just what public health authorities decide on a whim.

Employing use of a critical appraisal tool for systematic reviews that include both randomized and non-randomized studies involving healthcare interventions (or both) called AMSTAR 2, the UK-based researchers sought to evaluate confidence in the included systematic reviews. They also used GRADE to assess the certainty of evidence associated with the studies looking into the impacts of school lockdowns. GRADE, or “Grading of Recommendations, Assessment, Development, and Evaluations,” is a transparent framework for developing and presenting summaries of evidence, thus contributing to a more systematic approach for making clinical practice recommendations.

Key study questions pursued by the Oxford-based investigators included:

(1) What is the impact of school closures on COVID-19 transmission, morbidity or mortality in the community?

(2) What is the impact of COVID-19 school closures on mental health (e.g., anxiety), physical health (e.g., obesity, domestic violence, sleep) and learning/achievement of primary and secondary pupils?

(3) What is the impact of mitigations in schools on COVID-19 transmission, morbidity or mortality in the community?

(4) What is the impact of COVID-19 mitigations in schools on mental health, physical health and learning/achievement of primary and secondary pupils?

The findings

Out of 578 reports, the team included only 26 based on the application of rigorous inclusion/exclusion criteria.

In this study, the team identified a total of 132 unique primary studies involving the effects of school closures on transmission of COVID, morbidity and mortality; 123 on learning; 164 on mental health, 22 on physical health; 16 on sleep with 7 concerning domestic violence. Finally, 69 of the individual studies focused on the effects of in-school mitigations on transmission/morbidity/mortality report the study authors.

The authors communicate in The BMJ:

“Both school closures and in-school mitigations were associated with reduced COVID-19 transmission, morbidity and mortality in the community. School closures were also associated with reduced learning, increased anxiety and increased obesity in pupils. We found no SRs that assessed potential drawbacks of in-school mitigations on pupils. The certainty of evidence according to GRADE was mostly very low.”

Overall, the Oxford academic researchers considered the whole body of evidence as weak when considered holistically. However, this doesn’t take away from numerous concerns in the form of negative effects on children involving school closures.

The study authors concluded that while school closures lead to both positive and negative impacts, the overall level of evidence confidence is mostly very low. Importantly they could not find any systematic reviews investigating the potential drawbacks of in-school mitigations on children, which should be studied.


Singapore Academic Medical Research Climate Healthier and More Open Than America: At Least When It Comes to COVID-19 mRNA Vaccines

While Singapore is known as somewhat of an authoritarian place, albeit free and relatively open for business and some labor, when it comes to an open discussion about the problem of COVID-19 vaccine injuries, its press is far more open and freer than that of the United States. Two well-known COVID-19 researchers, part of elite Singapore-based academic medical centers, bring real talk to the COVID-19 vaccine topic. They want to see highly efficacious vaccines that have less side effects—implicitly acknowledging problems with the current mRNA-based products. Delving into the risk-benefit analyses, they are free to speak their mind in Singapore, while Americans peers generally cower in economic fear. Some commonsense talks now come out of Singapore, the type that is sadly lacking in most top American academic medical/research circles.

During the COVID-19 pandemic, the City-State implemented “circuit breakers and lockdowns” in a bid to control the spread of the pandemic—much like other Asian nations and even Australia—they also implemented mass vaccination schemes to reduce the risk of severe symptomatic COVID, also part of the quest to transition out of the pandemic. Of course, the scale and magnitude of the mass vaccination program was but a fraction of the effort in the United States, given that over 270 million people in America received their primary series vaccination out of a population of 330 million.

Singapore, with its population at 5.5 million, through a combination of mandates and incentives, saw over 92% of the City-State’s population vaccinated against COVID-19. By the late summer of 2021, they were classified by the German press as the world’s most vaccinated place against COVID-19.

The press there have been open about two tragic deaths associated with the COVID-19 vaccines. As reported by the Singapore news outlet CNA and covered by TrialSite as well, a 43-year-old Filipino woman died just four days after vaccination with the Pfizer-BioNTech mRNA jab (BNT162b2), while at the end of 2021, a 28-year-old Bangladeshi man died three weeks after the first dose of the mRNA-based Moderna COVID-19 vaccine known as mRNA-1273 or Spikevax.

In a commentary from Ooi Eng Eong of Duke-NUS Medical School, and Paul Ananth from NUS Yong Loo Lin School of Medicine, they point out that:

“There is no vaccine or medication in the world without the risk of rare severe adverse events, so their use must always be guided by risk-benefit analyses.”

It’s interesting, the timing and topic of this opinion piece in the prominent Singapore multi-channel media. This isn’t the fringe, some politically charged platform, but rather the mainstream in the heart of a very orthodox and mainstream place at this point .

While both Drs Eong and Ananth remind all that a known potentially dangerous side effect associated with the mRNA COVID-19 vaccines—myocarditis, can also occur directly as a result of SARS-CoV-2 infection, the two absolutely mainstream medical research professionals remind us of all to learn from both smallpox and poliomyelitis.

With a refresher on the history of these vaccines, and a reminder that on very rare occasions risks of serious side effects can and do occur. In fact, in Singapore, the risks associated with the vaccine became unacceptably high:

“With poliomyelitis having been eliminated in most parts of the world, the risk of vaccine-associated paralysis became unacceptably high. Singapore, like many countries, has switched fully to the injected form, which is composed of killed polioviruses and has no risk of paralysis.”

Overall, the Singapore-based academic medical researchers are pleased with the COVID-19 vaccination outcomes, but they believe more can be done to make these and other vaccines even safer.

Arguing that unfortunately, COVID-19 won’t be the least pandemic likely in the next decades, they point out that “in just the first 23 years of the 21st century, the world has witnessed nine major outbreaks that spread rapidly across national borders.” So obviously, they point out, “For public health authorities, the next pandemic is not a question of “if” but “when.”

What’s recommended?
While Ooi Eng Eong and Paul Ananth don’t go too far in the critique—this wouldn’t be publishable—they do hint that perhaps, the COVID-19 vaccines were expedited a bit too fast. For example, the two note, “For any vaccine to be licensed, including the COVID-19 vaccines developed in record time, it will have to be tested in preclinical animal models as well as tens of thousands of human volunteers for safety and efficacy.”

Importantly, both Pfizer-BioNTech and Moderna’s mRNA vaccines included some limited animal research and Phase 3 trials with 30,000+ participants.

TrialSite has access to numerous data, documents and testimony that these studies were overly rushed, with glaring problems that were covered up. Accessing some of the documentation in the Brook Jackson lawsuit (now dismissed), it’s clear that one major investigator site network’s quality track record was unacceptable, and in normal times this alone would have paused the clinical trial.

Other findings from the disclosed Pfizer regulatory documentation (See Sonia Elijah articles) or how the company cut some corners not conducting any controlled IND-enabling preclinical studies are further glaring examples that the compressed research during the pandemic was far from optimal.

Both Eong and Ananth know this, but of course, cannot articulate such points in mainstream media or for that matter, in their respected academic medical departments.

But they both do emphasize the importance of safety for any licensed medicinal products, including vaccines, noting that “Vaccines that produce side effects that are not well tolerated will fail clinical development and will not be marketed.” They continued pointing to the current situation with Pfizer and Moderna:

“However, despite clinical trials involving tens of thousands of volunteers, rare side effects that occur in the region of 1 in 100,000 vaccinations or less will likely be missed for simple statistical reasons.”

Yet they pair point out that clinical trials programs needing hundreds of thousands of volunteers just would not be viable.

Instead, the two Singapore-based COVID-19 experts point out that the key is to better understand what’s causing vaccine side effects. Why? “So that we can reduce them while maintaining the benefits of vaccination.”

Critically important, Eong and Ananth point out the logic that seemed so apparent in America—that “side effects do not indicate and are not required for good immunity, contrary to some popular views.”

Their point is that according to their research, “Vaccinated individuals who experience side effects do not develop better or higher levels of protection against COVID-19 than those who do not.”

Those healthy clinical trials volunteers with a healthier immune system during vaccination would be more likely to experience mild COVID-19 after mRNA vaccination. Yet an “Over-activation of a specific gene and low-level chronic inflammation contributed to the development of cardiac complication after booster COVID-19 mRNA vaccination,” the authors report in their research published in Cell Press journal.

They point to the need for the development of a “a detailed map of the molecular processes that lead to side effects and rare severe adverse events will lay the foundation for the development of safer vaccines, including potentially for the next emerging infectious disease.”

With ongoing research, the authors point out in their CNA editorial what are the next steps to both building protection via vaccination, while improving pandemic control hopefully done in a more responsible way.

Some common sense talks out of Singapore, the type that is sadly lacking in most top American academic medical/research circles.




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