Immune response study explains why some people don't get COVID-19

 Scientists have discovered novel immune responses that help explain how some individuals avoid getting COVID-19.

Using single-cell sequencing, researchers from the Wellcome Sanger Institute, University College London (UCL), Imperial College London, the Netherlands Cancer Institute and their collaborators, studied immune responses against SARS-CoV-2 infection in healthy adult volunteers, as part of the world's first COVID-19 human challenge study.

Not all exposed participants went on to develop a COVID-19 infection, allowing the team to uncover unique immune responses associated with resisting sustained viral infection and disease.

The findings, published in Nature, provide the most comprehensive timeline to date of how the body responds to SARS-CoV-2 exposure, or any infectious disease. The work is part of the Human Cell Atlas initiative to map every cell type in the human body.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions across the globe with Coronavirus disease 2019 (COVID-19). While it is potentially fatal, many will have come into contact with someone who has tested positive for COVID-19, but have managed to avoid getting ill themselves, whether remaining negative on PCR testing or having an asymptomatic case of the disease.

While previous studies have examined COVID-19 patients after symptom onset, in this new study researchers set out to capture immune responses right from exposure, in an immunologically-naive cohort for the first time.

As part of the UK COVID-19 Human Challenge study, led by Imperial College London, 36 healthy adult volunteers without previous history of COVID-19 were administered SARS-CoV-2 virus through the nose.

Researchers performed detailed monitoring in the blood and lining of their noses, tracking the entire infection as well as the immune cell activity prior to the infection event itself for 16 volunteers. The teams at the Wellcome Sanger Institute and UCL then used single-cell sequencing to generate a dataset of over 600,000 individual cells.

Across all participants, the team discovered previously unreported responses involved in immediate virus detection. This included activation of specialized mucosal immune cells in the blood and a reduction in inflammatory white blood cells that normally engulf and destroy pathogens.

Individuals who immediately cleared the virus did not show a typical widespread immune response but instead mounted subtle, never-seen-before innate immune responses. Researchers suggest high levels of activity of a gene called HLA-DQA2 before exposure also helped people prevent a sustained infection from taking hold.

In contrast, the six individuals who developed a sustained SARS-CoV-2 infection exhibited a rapid immune response in the blood but a slower immune response in the nose, allowing the virus to establish itself there.

The researchers further identified common patterns among activated T cell receptors, which recognize and bind to virus-infected cells. This offers insights into immune cell communication and potential for developing targeted T cell therapies against not just COVID-19, but other diseases.

Dr. Rik Lindeboom, co-first author of the study, now at the Netherlands Cancer Institute, said, "This was an incredibly unique opportunity to see what immune responses look like when encountering a new pathogen—in adults with no prior history of COVID-19, in a setting where factors such as time of infection and comorbidities could be controlled."

Dr. Marko Nikolić, senior author of the study at UCL and honorary consultant in respiratory medicine, said, "These findings shed new light on the crucial early events that either allow the virus to take hold or rapidly clear it before symptoms develop. We now have a much greater understanding of the full range of immune responses, which could provide a basis for developing potential treatments and vaccines that mimic these natural protective responses."

Dr. Sarah Teichmann, senior author of the study and co-founder of the Human Cell Atlas, formerly at the Wellcome Sanger Institute, and now based at the Cambridge Stem Cell Institute, University of Cambridge, said, "As we're building the Human Cell Atlas we can better identify which of our cells are critical for fighting infections and understand why different people respond to coronavirus in varied ways.

"Future studies can compare with our reference dataset to understand how a normal immune response to a new pathogen compares to a vaccine-induced immune response."

Shobana Balasingam, research lead in Wellcome's Infectious Disease team, said, "Human challenge models are an invaluable way to build our understanding of how the body responds to infectious disease. These studies enable us to closely monitor what happens from the moment of infection by allowing us to follow the immune response through to the development and severity of symptoms.

"These results are an exciting addition to our evidence-base of how different people might respond to, or be protected against, COVID-19 infections. We need to understand how factors like natural exposure to the disease affect the body's response to the virus or a vaccine. Therefore, it is crucial studies like this expand to low-resource settings where diseases are endemic, to ensure we are developing context-specific tools and therapeutics that work for those most vulnerable."

More information: Rik Lindeboom, Human SARS-CoV-2 challenge uncovers local and systemic response dynamics, Nature (2024). DOI: 10.1038/s41586-024-07575-x. www.nature.com/articles/s41586-024-07575-x

https://medicalxpress.com/news/2024-06-immune-response-people-dont-covid.html

Modifying homes for stroke survivors saves lives, extends independence

 Every 40 seconds, someone in the United States suffers a stroke, in which blood flow to the brain is blocked. For the survivors, the ensuing brain damage can lead to lifelong disabilities, making mundane tasks—such as using the toilet and taking a shower—risky ventures.

One in eight of those who experience a stroke die within a year of hospital discharge. But a clinical trial led by researchers at Washington University School of Medicine in St. Louis has found that modifications to stroke survivors' homes—such as grab bars, shower seats, ramps and other safety interventions—reduce the risk of death within a year or so of leaving the hospital,and allow many to keep living independently in their homes.

"The transition period is a critical time for stroke survivors who go home after weeks in inpatient rehabilitation," said senior author Susan Stark, a professor of occupational therapy, of neurology and of social work. "The home environment looks different and is more challenging than a facility outfitted with accommodations. We have found that occupational therapy can make impactful contributions by creating safe spaces that enable stroke survivors to remain independent and in their own homes."

The study appears in Archives of Physical Medicine and Rehabilitation.

The research team tested a novel program in St. Louis in which occupational therapists visited stroke survivors' homes to identify environmental barriers—such as stairs without handrails, low toilets and dark walkways—and implement accommodations to address their specific needs. The therapists also provided self-management training that involved building problem-solving skills, such as how to connect with accessible transportation.

The severity of the blockage and the speed of treatment delivery affect the recovery process after a stroke. People with minor cognitive and motor impairments typically receive outpatient rehabilitation after leaving the hospital. Severe stroke patients are more likely to be transferred to a skilled nursing facility to receive continuous care and therapy.

But another group, one that includes about 25% of stroke patients, has moderate cognitive and motor impairments. These patients—the focus of the clinical trial—typically leave the hospital for inpatient rehabilitation facilities and have the potential to live independently again, explained Stark.

Life at home looks different for such survivors, however. Pulling a shirt from a drawer challenges muscles weakened by stroke. Using the toilet tests their compromised balance. Climbing stairs may feel like navigating an obstacle course, posing a barrier to socializing and connecting with others.

There's a high rate of depression with stroke, Stark said. "People become even more depressed when they don't reengage in their community," she said.

The clinical trial enrolled 183 individuals age 50 and over, as they transitioned to their homes from inpatient rehabilitation facilities. They were randomly assigned to two groups: one that received at-home modifications and self-management skills, and one that received stroke education prevention during four occupational therapy sessions.

The researchers found that removing barriers and teaching problem-solving skills saved lives.

Compared with the control group, individuals in the intervention group had a higher survival rate; 10 people who received only education died over the course of the study, while no one from the intervention group died. Similarly, those who received the home modifications and self-management training were less likely to transfer to a skilled nursing facility.

Donna C. Jones was one of the individuals in the intervention group who benefited from the study. After suffering a stroke in summer 2021, Jones received modifications to her home that put her on a path to recovery, giving her the confidence to function independently while regaining balance and learning new abilities.

"My modified bathroom gives me hope that my life is moving in the right direction," said Jones, who completed her doctoral degree in ethical leadership and employee development just three months before suffering a stroke. "The practical tools and services I received are the foundation of my new journey. I have a new life. It's very different, and I love it."

Jones enjoys event planning, travel and community volunteerism. The stroke and a lower right leg amputation a year later have not stopped her from living her life with passion.

"Today, I'm finding creative ways to continue the quest of impacting our global society through ethical leadership development, teaching, programs and services. I am grateful for the study that provided the foundation for me to be able to approach my future with a positive outlook," Jones said.

Because the small clinical trial focused on a single geographical region, the transition program must be tested more broadly, Stark said. She also aims to perform an economic analysis to define the cost savings of implementing home modifications.

"The biggest barrier to implementing this program is getting insurance to reimburse the cost of home modifications," Stark said. "These interventions are not super expensive, but the system is not in place to cover the cost. If $500 in home modifications keeps people out of the hospital or a skilled nursing facility, that seems like a no-brainer to me. So we are doing the economic analysis to look at the health-care cost savings of such interventions."

More information: Melissa J. Krauss et al, The Community Participation Transition after Stroke (COMPASS) randomized controlled trial: Impact on adverse health events, Archives of Physical Medicine and Rehabilitation (2024). DOI: 10.1016/j.apmr.2024.05.015

https://medicalxpress.com/news/2024-06-homes-survivors-independence.html

Drugs for enlarged prostate may also protect against dementia with Lewy bodies

 A new study suggests that certain drugs commonly used to treat enlarged prostate may also decrease the risk for dementia with Lewy bodies (DLB). This observational finding may seem surprising, but it mirrors previous work by the University of Iowa Health Care team that links the drugs to a protective effect in another neurodegenerative condition—Parkinson's disease. The new findings were published online on June 19, 2024, in Neurology.

The UI researchers think that a specific side effect of the drugs targets a biological flaw shared by DLB and Parkinson's disease, as well as other neurodegenerative diseases, raising the possibility that they may have broad potential for treating a wide range of neurodegenerative conditions.

"Diseases like dementia with Lewy bodies, or Parkinson's disease, or Alzheimer's disease, are debilitating and we don't really have any good treatments that can modify the disease progression. We can treat symptoms, but we can't actually slow the disease," explains lead study author Jacob Simmering, Ph.D., UI assistant professor of internal medicine.

"One of the most exciting things about this study is that we find that same neuroprotective effect that we saw in Parkinson's disease. If there is a broadly protective mechanism, these medications could potentially be used to manage or prevent other neurodegenerative diseases."

DLB is a neurodegenerative disease that causes substantial and rapid cognitive decline and dementia. While less common than Parkinson's disease, DLB affects about one in 1,000 people per year, and accounts for 3 to 7% of all dementia cases. Because aging is a key risk factor for DLB, it is likely to become more common as our population gets older.

For the new study, the UI researchers used a large database of patient information to identify more than 643,000 men with no history of DLB who were newly starting one of six drugs used to treat benign prostatic hyperplasia (enlarged prostate).

Three of the drugs, terazosin, doxazosin, and alfuzosin (Tz/Dz/Az), have an unexpected side effect; they can boost energy production in brain cells. Preclinical studies suggest that this ability may help slow or prevent neurodegenerative diseases like PD and DLB.

The other drugs, tamsulosin and two 5-alpha-reductase inhibitors (5ARIs) called finasteride and dutasteride, do not enhance energy production in the brain and therefore provide a good comparison to test the effect of the Tz/Dz/Az drugs.

The team then followed the data on these men from when they started taking the medication until they left the database or developed dementia with Lewy bodies, whichever happened first. On average, the men were followed for about three years.

Because all the participants were selected to start a drug that treats the same condition, the researchers reasoned that the men were likely similar to each other at the outset of the treatment. The researchers also matched the men using propensity scores for characteristics like age, the year they started the medication, and other illnesses they had before staring the treatment, to further reduce the differences between the groups.

"We found that men who took Tz/Az/Dz drugs were less likely to develop a diagnosis of dementia with Lewy bodies," Simmering says. "Overall, men taking terazosin-type medications had about a 40% lower risk of developing a DLB diagnosis compared to men taking tamsulosin, and about a 37% reduction in risk compared to men taking five alpha reductase inhibitors."

Meanwhile, there wasn't a statistically significant difference in risk between men taking tamsulosin and 5-alpha reductase inhibitors.

This was an observational study and therefore the results show only an association between taking the Tz/Dz/Az drugs and a reduced risk of developing DLB rather than a causal relationship.

In addition, the study only included men because the drugs are prescribed for prostate problems, which means that the researchers don't know if the findings would apply to women. However, Simmering and his colleagues are excited by the potential of these drugs, which are already FDA approved, inexpensive, and have been used safely for decades.

"If terazosin and these similar medications can help slow this progression—if not outright preventing the disease—this would be important to preserving cognitive function and quality of life in people with DLB," Simmering says.

More information: Association of Terazosin, Doxazosin, or Alfuzosin Use and Risk of Dementia With Lewy Bodies in Men, Neurology (2024). DOI: 10.1212/WNL.0000000000209570

https://medicalxpress.com/news/2024-06-drugs-enlarged-prostate-dementia-lewy.html

Study finds one copy of protective genetic variant helps stave off early-onset Alzheimer's

 A scientific story that began with a discovery in just one extraordinary patient is now panning out. In 2019, an international team that included researchers from two Mass General Brigham hospitals—Mass Eye and Ear and Massachusetts General Hospital (MGH)—reported on the case of a patient who did not develop cognitive impairment until her late 70s, despite being part of a family at extremely high genetic risk for developing early-onset Alzheimer's disease.

In addition to having the genetic variant that causes an autosomal dominant form of Alzheimer's disease, the woman had two copies of a rare variant of the APOE3 gene, called Christchurch (APOE3Ch). Now, the research team reports on an additional 27 members of the family who carry just one copy of the variant and experienced delayed disease onset.

The study, published in The New England Journal of Medicine, represents the first evidence that having one copy of the Christchurch variant may confer some level of protection against autosomal dominant Alzheimer's disease, even if less pronounced compared to when two copies are present. The findings have important implications for drug development, suggesting the potential effects of targeting this genetic pathway.

"As a clinician, I am highly encouraged by our findings, as they suggest the potential for delaying cognitive decline and dementia in older individuals. Now we must leverage this new knowledge to develop effective treatments for dementia prevention," said co-first author Yakeel T. Quiroz, Ph.D., clinical neuropsychologist and neuroimaging researcher and director of the Familial Dementia Neuroimaging Lab in the Departments of Psychiatry and Neurology at Massachusetts General Hospital.

"As a neuroscientist, I'm thrilled by our findings because they underscore the complex relationship between APOE and a deterministic mutation for Alzheimer's disease, potentially paving the way for innovative treatment approaches for Alzheimer's disease, including targeting APOE-related pathways."

Quiroz and her team at MGH and co-senior study author Joseph Arboleda-Velasquez, MD, Ph.D., of Mass Eye and Ear, have been working with their colleagues in Colombia as part of the MGH Colombia-Boston (COLBOS) biomarker study to examine family members of the world's largest-known kindred with a genetic variant called the "Paisa" mutation (Presenilin-1 E280A).

The Paisa mutation is an autosomal dominant variant, meaning that inheriting just one copy of the mutated gene from a parent is enough to cause a genetic condition. The family consists of about 6,000 blood relatives, and about 1,200 carry the variant.

Carriers of this Paisa variant are destined to develop Alzheimer's disease; most develop mild cognitive impairment in their 40s, dementia in their 50s, and die from complications of dementia in their 60s. Francisco Lopera, MD, director of the Grupo de Neurociencias de Antioquia in Medellín, Colombia, and co-senior author of the paper, is the neurologist who discovered this family and has been following them for the last 40 years.

In addition to the 2019 case report about a family member with two copies of the Christchurch variant, molecular studies have added further biological evidence that the variant could be playing a protective role. In 2023, the research team identified another "resiliency gene variant" called Reelin-COLBOS that appeared to delay the onset of symptoms in other family members. The new study reports on a larger group of individuals from this family who carry a copy of the Christchurch variant.

"Our original study told us that protection was possible, and that was an important insight. But if a person needs two copies of a rare genetic variant, it just comes down to luck," said co-senior author Joseph F. Arboleda-Velasquez, MD, Ph.D., an associate scientist at Mass Eye and Ear.

"Our new study is significant because it increases our confidence that this target is not only protective, but druggable. We think that therapeutics inspired by protected humans are much more likely to work and to be safer."

The research team assessed 1,077 descendants of the Colombian family. They identified 27 family members who carried both the Paisa mutation and one copy of the Christchurch variant. On average, these family members began showing signs of cognitive impairment at age 52, compared to a matched group of family members who did not have the variant, who began showing signs at age 47. The family members also showed signs of dementia four years later than those who did not carry the variant.

Two of these individuals had functional brain imaging performed. Scans showed lower levels of tau and preserved metabolic activity in areas typically involved in Alzheimer's disease, even in the presence of amyloid plaques—proteins considered a hallmark of Alzheimer's disease. The team also analyzed autopsy samples from four deceased individuals that showed less pathology in blood vessels, a characteristic that appears important for the protective effects of APOE3 Christchurch.

The authors note that their study was limited to a relatively small number of people carrying both the Paisa and Christchurch variants, and to a single, extended family. They write that further studies involving larger and more ethnically diverse samples of Alzheimer's disease may shed further light on the protective effect of the Christchurch variant and help determine if findings from the family in Colombia could translate into discoveries relevant for treating sporadic forms of Alzheimer's disease.

"As a next step, we are currently focused on improving our understanding of the brain resilience among the remaining family members who carry one copy of the Christchurch variant. This involves conducting structural and functional MRI scans and cognitive evaluations, as well as analyzing blood samples to assess their protein and biomarker profiles," said Quiroz.

"The unwavering commitment to research shown by our Colombian patients with autosomal dominant Alzheimer's and their families has been indispensable in making this study possible and allowing us to continue to work toward interventions for this devastating disease."

More information: APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease, New England Journal of Medicine (2024). DOI: 10.1056/NEJMoa2308583

https://medicalxpress.com/news/2024-06-genetic-variant-stave-early-onset.html

Fauci's Inner Circle Initially Thought COVID Came From a Lab

Sen. Rand Paul explains why FOIA litigation shouldn’t have been necessary to find this out.

Did COVID-19 originate in a lab? To answer this question, let's revisit the early days of the pandemic and examine what some of Anthony Fauci's inner circle said privately about the origins of the virus—discussions that were only revealed through Freedom of Information Act (FOIA) litigation.

Evolutionary biologist Kristian Andersen wrote, "The lab escape version of this is so friggin' likely to have happened because they were already doing this type of work and the molecular data is fully consistent with that scenario."

Epidemiologist Ian Lipkin stressed the "nightmare of circumstantial evidence to assess" regarding the possibility of inadvertent release given the scale of bat coronavirus research pursued in Wuhan, China.

Virologist Bob Garry said at the time, "I really can't think of a plausible natural scenario when you get from the bat virus, or one very similar to it, COVID–19 where you insert exactly four amino acids, 12 nucleotides, and all have to be added at the exact same time to gain this function. I just can't figure out how this gets accomplished in nature." According to Garry, "it's not crackpot to suggest this could have happened, given the gain of function research we know was happening in Wuhan."

Even Ralph Baric, world-famous gain-of-function researcher and collaborator with Wuhan Institute of Virology doctor Shi Zhengli, admitted, "So [the Wuhan Institute of Virology has] a very large collection of viruses in their laboratory. And so it's—you know—proximity is a problem. It's a problem."

Federal court orders reveal that Fauci himself privately acknowledged concerns about gain-of-function research in Wuhan and "mutations in the virus that suggest it might have been engineered" just days before he commissioned the Proximal Origin paper.

Despite these private doubts, publicly, these so-called experts and their allies were dismissing the lab leak theory as a conspiracy. Within days, Andersen, Lipkin, and Garry were putting the final touches on what will be remembered as one of the most remarkable reversals in modern history.

In their Proximal Origin paper, these scientists concluded, "We do not believe that any type of laboratory-based scenario is plausible." Media pundits parroted this narrative, while social media platforms censored discussions about the lab leak, labeling it as misinformation and stifling open discourse about the virus's origins.

The cover-up went beyond public statements. Federal agencies and key officials withheld and continue to conceal crucial information from both Congress and the public.

For instance, David Morens of the National Institutes of Health (NIH) deleted emails that could have contained valuable insights into early discussions of how and where the virus originated, and the Office of the Director of National Intelligence (ODNI) failed to comply with a law passed by Congress unanimously to declassify information on the origins of COVID-19. The Department of Health and Human Services (HHS) and the NIH have not produced documents related to gain-of-function research that Senate Homeland Security Chair Gary Peters (D–Mich.) and I requested nearly a year ago. And just last week, a House committee released its findings that the HHS and the NIH engaged in a deliberate, prolonged effort to deceive the committee about certain gain-of-function research experiments the agencies funded.

Thanks to brave whistleblowers, we've learned that EcoHealth Alliance partnered with the Wuhan Institute of Virology on an NIH grant to conduct research to make viruses more dangerous. It was revealed that three scientists who worked at the Wuhan Institute fell sick with COVID-like symptoms in the fall of 2019. Additionally, a brave whistleblower revealed that in 2018, EcoHealth, the Wuhan Institute of Virology, and the University of North Carolina submitted a proposal to the military research agency DARPA to insert a furin cleavage site remarkably similar to COVID-19 into bat coronaviruses, a modification expected to make the virus more lethal.

These revelations have provided crucial evidence on the origins of COVID-19. In fact, both the FBI and the Department of Energy now conclude that COVID-19 resulted from a lab.

The American people deserve complete transparency on the origins of COVID-19. The pandemic killed millions of people and shut down global economies. Our federal and state governments used the pandemic as a justification to strip Americans of their civil liberties and freedoms. Children missed critical developmental opportunities, families lost jobs, and businesses were forced to close.

Today's full committee hearing, the first of its kind in the Senate, is a crucial step to obtaining answers for the American people on the origins of COVID-19. The next step is to have government officials testify before our committee publicly, and I look forward to working with Chairman Peters to hold that hearing.

Understanding the origin of the COVID-19 pandemic is not just about assigning blame—it's about learning from what happened so we can prevent future, more deadly pandemics and the negative societal consequences associated with them. My goal is to uncover the truth, implement necessary safeguards, and prevent a tragedy of this magnitude from happening again.

https://reason.com/2024/06/18/anthony-faucis-inner-circle-initially-thought-covid-came-from-a-lab/

Candidates Use Fearmongering to Push Abortion Agenda

 Campaigns tempted to drive this year’s elections with scare tactics instead of facts should be put on notice: voters expect a real debate about solutions.  

Just recently, State Sen. Rachel Hunt, candidate for lieutenant governor in my home state of North Carolina, claimed that without laws ensuring abortion-on-demand, doctors “leave [women] to bleed out in the parking lot.” 

This blatant falsehood infuriates me as an OBGYN who has practiced for over 25 years. These attacks on us and on prolife laws, which have not restricted our ability to treat women in emergencies, must stop. Unfortunately, as the anniversary of the Dobbs Supreme Court decision approaches in this election year, we can expect a plethora of fear-inducing comments from political candidates to surface.  

If you are a woman who is pregnant, I want to assure you that prolife protections provide you access to exceptional health care and the support you need to thrive before, during and after pregnancy. Candidates should focus on sharing the steps they will take to address how to best ensure women and their pre-born children have access to this care, not peddle unrestricted abortion on demand as a false solution. 

In truth, not a single state with pro-life laws on its books forces doctors to practice the kind of blatant negligence described by politicians seeking support from abortion activists. Pro-life laws are not the cause of pregnancy-related tragedies. Negligence, misinterpretation and misapplication of the laws are largely to blame.  

Many politicians, as evidenced by a U.S. Senate hearing this month on abortion, could benefit from a basic review of medical ethics, including the way intent guides medical care. Every day, doctors make decisions that while intended to help our patients, could also cause them harm. Chemotherapy can have horrific side effects. When prescribed, our goal is not to give our patient hair loss or nausea, rather those are unintended consequences of treating their cancer.  

The same principle applies when women experience medical emergencies during pregnancies. We may have to prematurely separate our maternal and fetal patients to save our maternal patient’s life with the unintended consequence being the death of our fetal patient. 

This is completely different from an induced abortion that is defined by the CDC as an intervention “intended” to terminate a pregnancy. It is not an induced abortion when we intervene with the intention of saving the life of the mother, but the unintended consequence is the death of our fetal patient. I have had to intervene in this way hundreds of times as an obstetrician and gynecologist, and no law in this country prevents me from doing so now. 

It is also critical that pro-life laws be properly implemented and explained by the executive branches in state governments. South Dakota Gov. Kristi Noem signed a medical education bill into law that requires her state’s Department of Health to explain its new prolife protections to medical professionals, attorneys and the public by video. This kind of educational resource empowers doctors with further understanding of their state laws and allows them to save lives and administer care with confidence and competence. 

Medical associations must likewise recommit themselves to issuing guidance on state laws post-Roe. Unfortunately, organizations such as the American College of Obstetricians and Gynecologists (ACOG) have done little to help doctors understand how they should be caring for patients under new life-affirming laws, despite the fact that ACOG’s very mission is to produce “practice guidelines for health care professionals and educational materials for patients.” The Society for Maternal-Fetal Medicine (SMFM), a group of doctors specializing in high-risk care, has likewise held back from offering any clarification or guidance to its members. In fact, SMFM members have contributed to the rampant misinformation asserting that OBGYNs can no longer treat pregnant women whose lives are at risk.  

Fortunately, the American Association of Pro-Life Obstetricians and Gynecologists (APPLOG) is already actively offering fact-based resources to its members and the public instead of promoting abortion on demand at all costs. My colleagues have participated in educational webinars and podcasts and created a glossary of medical terms designed to equip doctors with information about their states’ position on abortion. I encourage anyone with questions about new abortion laws to seek clarity from AAPLOG resources.  

Candidates who resort to scare tactics should be ashamed of the chaos and uncertainty they are inciting among women and their families, who are being led to believe that their health is at risk when the very opposite is true. It’s long past time for candidates to focus their discussions on how to truly care for the women in their communities instead of relying on fearmongering to win votes. Induced abortion does not save women’s lives. And no law can make it so.  

Susan Bane, M.D., Ph.D., is a board-certified OB/GYN and holds a certificate in Theology and Health Care from the Duke Divinity School. She is the medical director of four pregnancy centers in North Carolina and is on the board of directors of the American Association of Pro-Life Obstetricians and Gynecologists (AAPLOG) and is the chair of the board for AAPLOG Action. 

https://www.realclearhealth.com/blog/2024/06/19/candidates_use_fearmongering_to_push_abortion_agenda_1039040.html

USPSTF Recommends Behavioral Interventions for Kids With High BMI

 The U.S. Preventive Services Task Force (USPSTF) recommended that children and adolescents with a high body mass index (BMI) be referred to intensive behavioral interventions -- and not weight-loss drugs -- in a final recommendation statement.

Solidifying its previous draft statement, the USPSTF recommended "with moderate certainty" that providing or referring children and adolescents ages 6 years and older with a BMI at or over the 95th percentile for age and sex to comprehensive intensive behavioral interventions "has a moderate net benefit" (grade B recommendation).

"Comprehensive, intensive behavioral interventions with at least 26 contact hours or more that include supervised physical activity sessions for up to 1 year result in weight loss in children and adolescents," the task force wrote in JAMAopens in a new tab or window.

Since the draft statement's release in Decemberopens in a new tab or window, the task force has expanded on the harms associated with a high BMI among kids and teens, as well as the use of BMI for screening. While it acknowledged BMI is "an imperfect measure of adiposity," most children at the 95th percentile or higher have high adiposity and therefore should follow the recommended interventions. The 2017 USPSTF recommendationsopens in a new tab or window focused on screening for childhood obesity, rather than interventions.

The USPSTF kept pharmacotherapy out of the final recommendations at this time -- neither recommending for nor against weight-loss drugs, citing the small number of studies, lack of long-term maintenance data, and potential for side effects. Currently, there are four weight-management drugs approved for adolescents ages 12 and older: semaglutide (Wegovy)opens in a new tab or window, liraglutide (Saxenda)opens in a new tab or window, phentermine/topiramate (Qsymia)opens in a new tab or window, and orlistat (Xenical, Alli).

"If medications need to be used long-term to maintain weight loss, the USPSTF states that long-term studies of both efficacy and harms are essential," wrote Amy S. Shah, MD, of Cincinnati Children's Hospital Medical Center, and colleagues in an accompanying JAMA Network Openopens in a new tab or window editorial. "This sentiment is undoubtedly shared by the medical community, i.e., the need for additional data to characterize long-term safety, with a focus on outcomes in the years of prime development."

Notably, the American Academy of Pediatrics (AAP) does not share this viewopens in a new tab or window, based on its first clinical practice guideline for children and adolescents with overweight and obesity, which included recommendations for weight-loss pharmacotherapy and metabolic surgery in addition to intensive behavioral treatment.

"The differences in between USPSTF and AAP recommendations can be attributed to underlying methodology," Shah and team noted. "The AAP bases recommendations on evidence-based literature and includes expert opinion, clinical guidelines, and position statements from professional societies when necessary. The USPSTF purely uses the evidence-based literature, although USPSTF acknowledges that clinical decisions involve more considerations than evidence alone."

While kids with obesity should start with intensive lifestyle therapy as per the USPSTF recommendations, Shah's group advocated for an individualized approach.

"For many patients, [intensive lifestyle therapy] alone may not be enough to prevent serious outcomes," they wrote. "In these instances, pharmacotherapy and/or bariatric surgery may need to be considered to improve health outcomes in youth with obesity."

While authors of a JAMA editorialopens in a new tab or window agreed that there's still "many unanswered questions" about children using weight-loss drugs, they praised the AAP's guidance for considering "the well-documented harms of untreated obesity, the poor access and reimbursement for intensive, comprehensive behavioral treatment, and the FDA approved indications in formulating this recommendation."

"The evidence base related to pharmacotherapy is expected to rapidly grow," noted Thomas N. Robinson, MD, MPH, of Stanford University in Palo Alto, California, and Sarah C. Armstrong, MD, of Duke University in Chapel Hill, North Carolina.

Evidence Report

Underpinning the final USPSTF recommendations was an evidence reportopens in a new tab or window that included 58 randomized controlled trials with 10,143 participants: 50 trials on behavioral interventions and eight on pharmacotherapy.

All four medications yielded BMI reductions, with the greatest reduction seen with semaglutide (mean difference in BMI -6.0). GLP-1 receptor agonists (semaglutide, liraglutide) and phentermine/topiramate yielded larger weight reductions than behavioral interventions (~8.8 to 39.7 lb), reported Elizabeth A. O'Connor, PhD, of Kaiser Permanente Northwest in Portland, Oregon, and colleagues.

Phentermine/topiramate at the higher dose level was the only medication to demonstrate a clear blood pressure benefit (mean difference in diastolic blood pressure -4.0). Semaglutide improved low-density lipoprotein cholesterol levels (mean difference in percent change -7.1,) and phentermine/topiramate improved high-density lipoprotein cholesterol levels (mean difference in percent change 8.8).

Although serious adverse effects (AEs) were rare for all medications, gastrointestinal AEs were common with GLP-1 receptor agonists and orlistat. In the liraglutide trial, 10.4% discontinued due to AEs.

When evidence was available on weight maintenance after discontinuation, weight rebounded quickly after medication use ended, O'Connor and team concluded. "This suggests that long-term use is required for weight maintenance and underscores the need for evidence about potential harms from long-term use."

Only semaglutide and high-contact behavioral interventions were linked with a boost in quality of life (a 3.7- to 5.3-point increase on mostly 100-point scales), though only a few trials reported on this outcome.

While the AAP guidelines recommended that clinicians refer eligible patients to bariatric surgery, the USPSTF's evidence report did not include any mention of surgery

.Disclosures

The USPSTF is an independent, voluntary body. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. Two task force members reported federal grant funding.

Shah disclosed no relationships with industry. A co-author disclosed support from Rhythm Pharmaceuticals.

Robinson and Armstrong disclosed relationships with WW International, the NIH, the CDC, and the American Academy of Pediatrics.

O'Connor and co-authors reported no conflicts of interest.

Primary Source

JAMA

Source Reference: opens in a new tab or windowUS Preventive Services Task Force "Interventions for high body mass index in children and adolescents: US Preventive Services Task Force recommendation statement" JAMA 2024; DOI: 10.1001/jama.2024.11146.

Secondary Source

JAMA Network Open

Source Reference: opens in a new tab or windowKharofa RY, et al "Interventions for children and adolescents with high body mass index -- implementing the recommendations in clinical practice" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.18201.

Additional Source

JAMA

Source Reference: opens in a new tab or windowRobinson TN, Armstrong SC "Treatment interventions for child and adolescent obesity: from evidence to recommendations to action" JAMA 2024; DOI: 10.1001/jama.2024.11980.

Additional Source

JAMA

Source Reference:opens in a new tab or window O’Connor EA, et al “Interventions for weight management in children and adolescents: updated evidence report and systematic review for the US Preventive Services Task Force” JAMA 2024; DOI: 10.1001/jama.2024.6739.

https://www.medpagetoday.com/pediatrics/obesity/110700