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More from @jsm2334

Prof Jeffrey S Morris

@jsm2334

Mar 9

There is talk from HHS that fluoride in water mau lead to reduced cognitive levels in children.

There is a new published paper on a Bangladeshi study assessing links between urinary fluoride levels and cognitive performance of children at 5yrs and 10yrs that is being touted as evidence of this link.

The authors conclude links between prenatal maternal urinary fluoride levels and children's cognitive levels at 5yrs and 10yrs, between children's urinary fluoride levels at 10yrs and cognitive levels at 10yrs, and also say there is a negative association between urinary fluoride levels at 5 years and cognitive levels at 5yrs and 10yrs that is not statistically significant.

However, when looking at the data and analyses in the paper in detail, the evidence for these links are at best very weak, and the paper really shows very little evidence.

In this thread, I will explain some of the data and statistical details that lead me to that conclusion.

The primary question of this study is whether fluoride exposure from water is linked with lower cognition, which in this study involves analyzing potential associations between urinary fluoride levels at 5yrs and and cognitive scores at 5yrs and 10yrs, urinary fluoride levels at 10yrs with cognitive scores at 10yrs, and prenatal urinary fluoride levels at 8wks gestation with cognitive scores at 5yrs and 10yrs.

They propose that given fluoride's low half-life, the urinary fluoride levels should be a reasonable surrogate for fluoride levels in the water, and they measure water fluoride levels at the 10yr time point to show evidence of some correlation with the urinary levels.

While the authors confidently conclude evidence for a link, when one looks at the actual data there is little to no evidence of any link, and they have to take a series of unusual and potentially questionable statistical steps to arrive at these conclusions.

I will describe what I mean.

Given that the primary hypothesis is whether fluoride in the water leads to decreased cognitive abilities in children, I will start with the analysis of children's urinary fluoride levels and their cognitive test results at 5yrs and 10yrs.

Read 17 tweets

Prof Jeffrey S Morris

@jsm2334

Mar 8

Many people misunderstand "indirect costs" (i.e. F&A) from NIH grants, thinking these are superfluous or unnecessary costs or a "gift" to universities.

Indirect costs are actually "Facility and Administrative" (F&A) expenses that are not allowed to be included in the direct cost budget of an NIH grant, but are essential for research.

Below is a video that explains how the system works, what F&A expenses cover, how they are determined, and why they are essential, and how the proposed severe reduction of 65-80% of these expenses endangers the entire USA research enterprise that leads the world and provides great societal benefit, technologically, medically, and economically.

youtube.com/watch?v=NtqK8S…

The indirect costs, or Facilities and Administrative (F&A) expenses, are not a "tip" or "fluff" for the universities, but cover essential research costs that are not allowed to be included in the direct cost budget for an NIH grant, including:

* Laboratory and other research-specific facilities
* Utilities including electricity, gas, water, HVAC
* Shared research instruments
* Maintenance and security for research facilities
* IT and cybersecurity infrastructure
* Administrative staff needed to meet federal requirements including safety, compliance, and research operations.

Research could not be done without these expenses, and without F&A it is not clear how they can be covered.

Typically, the indirect costs from grants only partially cover these expenses, with universities and research centers having to cover 30-50% of these required expenses through other means.

As a result, universities subsidize federal research, and typically lose a substantial amount of $$ for their research enterprise.

Read 5 tweets

Prof Jeffrey S Morris

@jsm2334

Feb 16

Journal of Infection and Public Health just published a paper summarizing case fatality rate (CFR) and infection mortality rate (IFR) for all of Austria from February 2020 through May 2023.

Critically, they also split out results over time, by variant, age group, vaccination and previous infection status, sex, and nursing home residency status.

Key results were:
1. CFR was much higher in older age groups and nursing home residents
2. CFR decreased greatly with later variants, coincident with increases in population immunity levels from vaccination and previous infection.
3. Vaccinated individuals had substantially lower CFR for each variant/age group
4. Those surviving previous infection had substantially lower CFR for each variant/age group.
5. The immune protection evident in reduced CFR was similar in vaccinated and those surviving previous infection for each variant/age group.

In this thread, I will summarize and try to make sense of its key results.

Link to paper:
sciencedirect.com/science/articl…

There are other papers looking at CFR/IFR, but none as expansive or rigorous as this one.

Austria had very restrictive early mitigation measures and mass vaccination like most higher income countries, which makes its results relevant to many richer Western countries.

Also, Austria had the highest SARS-CoV-2 testing rate among non-island nations in the world, making it ideal for this study since they had fewer undocumented infections than other countries.

Most results presented in the paper are of case fatality rate (CFR), computed as:

This study also estimated infection fatality rate (IFR), imputing the estimated number of undocumented infections using a model based on testing positivity rate (TPR=% of positive tests), with the reasoning that time periods with high TPR should have higher numbers of undocumented infections.

CFR was significantly higher than IFR during 2020 when testing was more sparse, but starting 2021 less so given Austria’s extraordinarily high testing rate.

Read 16 tweets

Prof Jeffrey S Morris

@jsm2334

Dec 9, 2024

My colleagues and I just published a paper in eClinicalMedicine evaluating effects of vaccination on long COVID risks in children and adolescents during the Delta and early Omicron periods.

These data were from the RECOVER network including 21 pediatric hospital networks from all over the USA, including 112,590 adolescents during the Delta period, and 84,735 adolescents and 188,894 children during the early Omicron period.

Long COVID-19 (post-acute sequelae of SARS-CoV-2, PASC, or multi-system inflammatory syndrom, MIS) was defined using a symptom-based computable phenotype definition based on five body systems.

Our analyses utilized propensity score weighting to adjust for confounding from age, demographics, medical co-morbidities as well as healthcare utilization including past COVID-19 testing practices, and we used proximal analyses with negative control exposures and outcomes to investigate and adjust for potential residual bias from unmeasured confounders.

In adolescents 12-20yrs, we found vaccination resulted in 95.4% reduced risk of long COVID-19 during the Delta period, and 75.1% during the Omicron period.

In children 5-11yrs, we found vaccination resulted in 60.2% reduced risk of long COVID-19 during he Omicron period.

To evaluate how much of this vaccine protection was from reduced risk of infection and how much was reduced risk of long COVID-19 independent of any effect in reducing infection, we performed a causal mediation analysis to split the total vaccine effect into indirect effects, mediated through reducing risk of infection, and direct effects, independent of any reduced risk of infection.

Again, propensity score weighting was used to carefully adjust for potential confounders.

We found that the protective effect of vaccines on long COVID-19 was almost wholly mediated through its reduced risk of infection.

Various sensitivity analyses were done and included in the online supplement along with a detailed description and explanation of all methods and modeling decisions.

@chenyong1203

sciencedirect.com/science/articl…

These data were from the RECOVER network including 21 pediatric hospital networks from all over the USA, including 112,590 adolescents during the Delta period, and 84,735 adolescents and 188,894 children during the early Omicron period

Our analyses utilized propensity score weighting to adjust for confounding from age, demographics, medical co-morbidities as well as healthcare utilization including past COVID-19 testing practices, and we used proximal analyses with negative control exposures and outcomes to investigate and adjust for potential unmeasured confounders.

Read 8 tweets

Prof Jeffrey S Morris

@jsm2334

Oct 30, 2024

Earlier this month, a research group from University of Southern California published a paper studying long term (>1000 days) risk of major adverse cardiac events (MACE, including myocardial infarction, stroke, and all cause mortality) after documented COVID-19 infections from population level data from the UK Biobank.

Confirming many other studies, they found increased risk of MACE after COVID-19, 2.09x higher for all levels of severity and 3.65x higher in hospitalized COVID-19.

Notably, they found that hospitalization for COVID-19 was a coronary artery disease risk equivalent, such that a person with no history of cardiovascular disease who got hospitalized COVID-19 was higher risk than a person with history of cardiovascular disease without hospitalized infection.

This, of course, validates what has been found in many other studies -- that COVID-19 infected have increased risk of severe cardiovascular events even after recovery, especially if they had severe/hospitalized COVID-19, and explains the increased cardiac risk in the past few years.

BTW, this study covers infections in 2020, before vaccines were available.

ahajournals.org/doi/10.1161/AT…

The study was quite well designed, using n=10,005 COVID-19 cases between February 1, 2020 and December 31, 2020 in the UK Biobank, compared with population controls (n=217,730) and matched controls (n=-38,660) based on propensity scores including age, sex, ethnicity, education, diabetes, asthma, smoking status, and use of lipid-lowering or antihypertension medication.

The comparison with the propensity score-matched controls is more valid for estimating COVID-19 effects given that it adjusts for confounders.

They found that with >1000 days of followup, the risk of MACE was 3.65x higher in hospitalized COVID-19 group than matched controls.

They computed the hazard ratio of MACE in those with cardiovascular comorbidities and/or hospitalized COVID-19 infections relative to those not infected with COVID-19 and without diabetes, peripheral artery disease, or cardiovascular disease.

They found that among uninfected, diabetes increased risk by 1.88x, peripheral aterial disease by 5.08x, and existing cardiovascular disease by 5.63.

Those with hospitalized COVID-19 but no cardiovascular comorbidities had 7.04x increased risk of MACE, meaning the hospitalized COVID-19 status by itself with no prior cardiovascular comorbidities made one have an even greater risk of MACE than those with cardiovascular comorbidities but no hospitalized COVID-19.

Read 6 tweets

Prof Jeffrey S Morris

@jsm2334

Aug 27, 2024

A group of French researchers published a paper in JAMA today assessing long term cardiac outcome with 18 months after vaccine-caused myocarditis after mRNA vaccines and compared with post-covid-19 mycarditis and conventional myocarditis using a large whole-country cohort covering the entire 12-49 year old population of France.

They found 558 cases of post-vaccine myocarditis out of ~64 million doses of vaccine in this age group (376 after 2nd dose), for an incidence of 1 in 115k doses (1 in 64k after 2nd dose), and 298 with post-COVID myocarditis and 3779 with conventional myocarditis.

A total of 18/15/1 of the 558 post-vaccine myocarditis patients were rehospitalized for myocarditis, had other cardiovascular events, or all cause death, versus 12/22/4 of 298 post-covid myocarditis patients and 277/49/17 of 3779 conventional myocarditis patients.

After rigorously adjusting for confounders including age, sex, region, SES, lifestyle habits, comorbidities, vaccination history, and medications using propensity score weighting to calibrate all populatons to the conventional myocarditis group (the comparison group), they statistically compared the post-vaccine and post-covid groups to the conventional myocarditis group with respect to
(1) Rehospitalization with myocarditis
(2) Cardiac events, including heart failure, heart rhythm and conduction disorders, and cardiomyopathy
(3) All cause death
(4) Rehospitalization for any reason
(5) Composite outcomes (1)-(3)
(6) Composite outcomes (1)-(4)

From this comparison, they found the risk of all of these 6 events were all lower after post-vaccine myocarditis than conventional myocarditis by 25%/46%/47%/31%/45%/36%, respectively, while risk after post-covid myocarditis was similar to conventional myocarditis, at the higher levels.

Myocarditis is the key minority harm risk for mRNA vaccines, especially for young men and especially after 2nd dose.

Before this study, there were very little looking at moderate to long term cardiac outcomes of myocarditis, so this paper is an important addition to the literature.

More study of this important question is needed.

In this thread, I discuss a few of the details and strengths and limitations of this study.

SARS-CoV-2 vaccines have been shown by many studies to greatly reduce the morbidity and mortality from COVID-19 during the pandemic, especially during 2021-2022. mRNA vaccines have been the predominate type used in many places around the world, and has consistently shown the highest effectiveness in most studies.

However, within a few months of rollout, a key minority harm risk of myo/pericarditis was discovered to occur in a subset of individuals soon after vaccination, with rates highest in teen boys and young men, especially after 2nd dose given shortly after 1st dose, and with Moderna having the highest rate. It is important to weight this risk against the benefits, especially in young men who have lower risks of severe/fatal COVID-19.

While most cases appeared to be mild and quickly resolved, myocarditis is serious and there is always a risk of cardiovascular sequelae after myocarditis, so long term follow up studies are critical to assess potential long term cardiac damage in those experiencing post-vaccine myocarditis.

This study involves a whole-France 12-49 year old cohort, with all individuals hospitalized for myocarditis between December 27, 2020 and June 30, 2022, with extensive demographic and medical variables for these individuals analyzed in this study.

The myocarditis patients were separated into 3 groups:
(1) post-vaccine myocarditis (hospitalized within 7 days of a vaccine dose)
(2) post-covid mycarditis (hospitalized within 30 days of a documented covid infection, but not within 7 days of a vaccine dose)
(3) conventional myocarditis -- not meeting the criteria of (1) or (2).

There were a total of 558 cases of post-vaccine myocarditis out of ~64 million doses of vaccine in this age group (376 after 2nd dose), for an incidence of 1 in 115k doses (1 in 64k after 2nd dose).

There were a total of 298 with post-COVID myocarditis and 3779 with conventional myocarditis.

The post-vaccine myocarditis group was younger, more male, and fewer comorbidities than the post-covid or conventional myocarditis groups.

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