Inflammatory syndrome linked to kids with COVID only occurs in 0.3%

Inflammatory syndrome linked to kids with COVID is rare – only occurring in about 0.3% of children – but black and Latino youngsters are up to THREE TIMES more likely than whites to get it

  • A new study looked at 248 cases of MIS-C in pediatric patients with coronavirus out of more than nine million children
  • MIS-C is a condition in which different body parts become inflamed and is linked to children infected with COVID-19 
  • Researchers determined the incidence rate was 316 persons per 1,000,000 coronavirus infections, or a rate of 0.3%
  • Black children were two times more likely than white children and Hispanic almost three times more likely to be diagnosed with MIS-C
  • Rates were highest among those under age five, and higher among six-10-year-olds, than in older children 

A very small percentage of children develop the inflammatory condition linked to COVID-19, a new study suggests.

Researchers found that just 0.3 percent of youngsters under age 21 were diagnosed with multisystem inflammatory syndrome in children (MIS-C), a disorder in which different body parts become inflamed.

The complication was most common in kids under age five, and black and Hispanic children were up to three times more likely to have the condition than white youngsters.

It’s not clear why minorities are at greater risk of MIS-C, but theories include a greater prevalence of underlying conditions among communities of color and less access to healthcare compared to Caucasian neighborhoods.

The team, from the Centers for Disease Control and Prevention (CDC), says understanding which children are at the highest risk can help doctors keep a close eye on certain patients so they can be treated before they develop MIS-C. 

A new study looked at 248 cases of MIS-C, a condition in which different body parts become inflamed, in pediatric patients with coronavirus out of more than nine million. Pictured: A five- year-old child in a hospital bed at Westchester Medical Center in Valhalla, New York, May 2020

Black children were two times more likely than white children and Hispanic almost three times more likely to be diagnosed with MIS-C, a new study finds

MIS-C was originally thought to be linked with Kawasaki disease, a condition that causes inflammation in the walls of the blood vessels and affects mostly children under five years old.

Cases were first reported in Britain, Italy and Spain in April 2020 and began cropping up in the U.S. in May.

A total of 4,018 cases have been confirmed across the country and at least 36 children have died, according to the CDC.

The majority of children and adolescents develop MIS-C between two and four weeks after being infected with the coronavirus.

Not every child who has developed the condition has tested positive for coronavirus, but 98 percent have – enough for doctors to believe the conditions are linked.

For the study, published in JAMA Network Open, the team looked at data from seven states reporting cases of MIS-C to the CDC.

Between April and June 2020, there were 248 reported cases that occurred in Americans under age 21 out of more than nine million children.

Researchers determined the incidence rate was 316 persons per 1,000,000 coronavirus infections, or a rate of 0.3 percent.

MIS-C rates were highest among those under age five, and higher among six-10-year-olds, than in older children

When broken down by race, about 30.2 percent, or 75 kids, were black and 38.7 percent, 96 kids, were Hispanic.

Comparatively, just 13.7 percent – 34 kids – were white. 

That means black children were two times more likely and Hispanic almost three times more likely to be diagnosed with MIS-C.

Additionally, younger children were much more likely to have the condition than older children.

Those under five years old were the most likely at 33 percent, closely followed by those ages six to 10.

‘These estimates indicated that MIS-C was a rare complication associated with SARS-CoV-2 infection in this cohort overall,’ the authors wrote.

‘Our findings of higher incidence among younger children and among Hispanic or Latino, black, and Asian or Pacific Islander persons emphasize a need for further study of risk factors for MIS-C.’

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Drinking alcohol is linked to reduced chances of pregnancy

Drinking alcohol is linked to reduced chances of pregnancy

A study of the associations between drinking alcohol and the chances of becoming pregnant suggests that women who want to conceive should avoid heavy drinking. In the second half of menstrual cycle even moderate drinking is linked to reduced chances of pregnancy.

The study, published today in Human Reproduction, one of the world’s leading reproductive medicine journals, investigated alcohol intake and fecundability, which is defined as the probability of conceiving during a single menstrual cycle. It is the first study to look at this according to the difference phases of women’s menstrual cycles.

Researchers led by Dr. Kira Taylor, associate professor of epidemiology and population health at the University of Louisville School of Public Health and Information Sciences (Kentucky), analyzed data from the Mount Sinai Study of Women Office Workers. Women aged 19-41 years were recruited between 1990 and 1994 and followed for a maximum of 19 menstrual cycles. The women completed daily diaries reporting how much alcohol they drank and what type, and they provided urine samples on the first and second day of each menstrual cycle in order to check for pregnancy.

Heavy drinking was defined as more than six alcoholic drinks a week, moderate drinking was three to six drinks a week, and binge drinking was defined as four or more drinks on a single day. Each drink consisted of a third of a liter of beer (355 milliliters), a medium glass of wine (148 milliliters), or just under a double shot of spirits (44 milliliters). The researchers collected information on factors that could affect the results, such as age, medical history, smoking, obesity, use of birth control methods and intention to become pregnant. Data on 413 women were available for the current study.

Dr. Taylor said: “We found that heavy drinking during any phase of the menstrual cycle was significantly associated with a reduced probability of conception compared to non-drinkers. This is important because some women who are trying to conceive might believe it is ‘safe’ to drink during certain parts of the menstrual cycle.

“During the luteal phase, which is the last two weeks of the menstrual cycle before bleeding would start and when the process of implantation occurs, not only heavy drinking but also moderate drinking was significantly associated with a reduced probability of conception.

“At the time of ovulation, usually around day 14 of the cycle, consuming a lot of alcohol—either heavy or binge drinking—was significantly associated with reduced chances of conception.”

Compared to non-drinkers both moderate and heavy drinking during the luteal phase was linked to a reduction in the odds of conceiving by about 44%. Heavy drinking during the ovulatory part of the cycle was also associated with significant 61% reduced odds of becoming pregnant. However, the researchers stress these are all estimates and should be treated with caution.

“If we assume that a typical, healthy, non-drinking woman in the general population who is trying to conceive has approximately a 25% chance of conceiving during one menstrual cycle, then out of 100 women approximately 25 non-drinkers would conceive in a particular cycle, about 20 moderate drinkers would conceive and only about 11 heavy drinkers would conceive,” said Dr. Taylor. “But the effect of moderate drinking during the luteal phase is more pronounced and only about 16 moderate drinkers would conceive.

“Our study only included a few hundred women and, while we believe the results strongly suggest that heavy and even moderate alcohol intake affects the ability to conceive, the exact percentages and numbers should be viewed as rough estimates.”

Each extra day of binge drinking was associated with an approximate 19% reduction in the odds of conceiving during the luteal phase and a 41% reduction during the ovulatory phase. The researchers found no difference in their results between different types of drinks.

The study is not able to show that drinking alcohol causes the reduction in the chances of becoming pregnant, only that it is associated with it. Possible biological mechanisms that might explain the association could be that alcohol intake affects the processes involved in ovulation so that no egg is released during the ovulatory part of the cycle, and that alcohol could affect the ability of a fertilized egg to implant in the womb.

Dr. Taylor said: “This is the first study to examine the effect of alcohol on fecundability during specific phases of the menstrual cycle, using daily data on alcohol and other important factors such as smoking and unprotected intercourse over a period of up to 19 menstrual cycles.”

Limitations of the study included the fact that not all women were trying to conceive; alcohol intake has increased since the time of the study and the women in the study were leaner, on average, than women today; the study used self-reported data and women might under-report their alcohol consumption; and the influence of drinking by male partners was not assessed.

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Protein linked to sex differences in age-related dopamine neuron loss

Protein linked to sex differences in age-related dopamine neuron loss

It is not every day that scientists come across a phenomenon so fundamental that it is observed across fruit flies, rodents and humans.

In a paper published today in Aging Cell, neuroscientists from the University of Pittsburgh Schools of the Health Sciences discovered that a single protein—a glutamate transporter on the membrane of vesicles that carry dopamine in neurons—is key to regulating sex differences in the brain’s vulnerability to age-related neuron loss.

The protein—named VGLUT—was more abundant in dopamine neurons of female fruit flies, rodents and human beings than in males, correlating with females’ greater resilience to age-related neuron loss and mobility deficiencies, the researchers found. Excitingly, genetically reducing VGLUT levels in female flies diminished their protection from neurodegeneration associated with aging, suggesting that VGLUT could be a new target for prolonging dopamine neuron resilience and delaying the onset of symptoms of aging in the brain.

“From flies to rodents to human beings, we found that VGLUT levels distinguish males from females during healthy aging,” said senior author Zachary Freyberg, M.D., Ph.D., assistant professor of psychiatry and cell biology at Pitt. “The fact that this marker of dopamine neuron survival is conserved across the animal kingdom suggests that we are looking at a fundamental piece of biology. Understanding how this mechanism works can help prolong dopamine neuron resilience and delay aging.”

Neurodegenerative disorders such as Parkinson’s disease are more likely to develop as we age. Parkinson’s disease—a slow but relentless loss of dopamine neurons in the brain that impairs one’s ability to move or talk—is known to predominantly affect men. But while biological sex differences, which arise from a combination of hormonal, genetic and environmental influences, seem to explain why females are protected from early stages of Parkinson’s, the driver and regulator of these protections was, until now, unknown.

Using a combination of biochemical and genetic techniques, as well as behavioral studies where flies’ locomotion was monitored for a 24-hour period, researchers found that age-related benefits afforded to females disappeared when the levels of VGLUT gene expression were significantly reduced in dopamine neurons.

“We found that VGLUT expression increases with age, and that flies become more vulnerable to dopamine neuron degeneration when we knock down VGLUT,” said lead author Silas Buck, a Ph.D. candidate at the Pitt Center for Neuroscience. “We also found that VGLUT expression is higher in females than males, suggesting that VGLUT may play a role in regulating sex differences in vulnerability to neurodegeneration in Parkinson’s and other neurological disorders where females are more resilient than males.”

As the rates of Parkinson’s disease are rapidly rising—the number of people affected by the illness worldwide is projected to reach 20 million by 2040—Pitt scientists hope to further probe the role of VGLUT in neuroprotection in humans.

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Leisure physical activity is linked with health benefits but work activity is not

work

The first large study showing that leisure time physical activity and occupational physical activity have opposite, and independent, associations with cardiovascular disease risk and longevity is published today in European Heart Journal.

“We adjusted for multiple factors in our analysis, indicating that the relationships were not explained by lifestyle, health conditions or socioeconomic status,” said study author Professor Andreas Holtermann of the National Research Center for the Working Environment, Copenhagen, Denmark.

The World Health Organization (WHO) recommends physical activity during both recreation and work to improve health. Previous studies have suggested that occupational activity is related to an increased risk for heart disease and mortality but have been too small to fully explain whether this was due to the manual work or because employees had unhealthy lifestyles or low socioeconomic status (e.g. low level of education).

This study included 104,046 women and men aged 20-100 years from the Copenhagen General Population Study with baseline measurements in 2003-2014. Participants completed questionnaires about activity during leisure and employment and were categorized as low, moderate, high, or very high activity for each.

During a median follow-up of 10 years, there were 9,846 (9.5%) deaths from all causes and 7,913 (7.6%) major adverse cardiovascular events (MACE, defined as fatal and nonfatal myocardial infarction, fatal and non-fatal stroke, and other coronary death).

Compared to low leisure time physical activity, after adjustment for age, sex, lifestyle, health, and education, moderate, high, and very high activity were associated with 26%, 41%, and 40% reduced risks of death, respectively. In contrast, compared to low work activity, high and very high activity were associated with 13% and 27% increased risks of death, respectively.

Similarly, after adjustments, compared to low leisure activity, moderate, high, and very high levels of leisure activity were associated with 14%, 23%, and 15% reduced risks of MACE, respectively. Compared to low work activity, high and very high levels were associated with 15% and 35% increased risks of MACE, respectively.

Professor Holtermann said: “Many people with manual jobs believe they get fit and healthy by their physical activity at work and therefore can relax when they get home. Unfortunately, our results suggest that this is not the case. And while these workers could benefit from leisure physical activity, after walking 10,000 steps while cleaning or standing seven hours in a production line, people tend to feel tired so that’s a barrier.”

While the study did not investigate the reasons for the opposite associations for occupational and leisure time physical activity, Professor Holtermann said: “A brisk 30-minute walk will benefit your health by raising your heart rate and improving your cardiorespiratory fitness, while work activity often does not sufficiently increase heart rate to improve fitness. In addition, work involving lifting for several hours a day increases blood pressure for many hours, which is linked with heart disease risk, while short bursts of intense physical activity during leisure raises blood pressure only briefly.”

Professor Holtermann’s vision is to reorganize occupational activity so that it mimics the beneficial aspects of leisure exercise. Several approaches are being piloted, such as rotating between workstations on a production line so that employees do a “healthy mixture” of sitting, standing, and lifting during a shift. In another study, childcare workers play games together with children, instead of observing, so that both get their heart rate up and increase fitness. “We are trying to vary the tasks, give recovery time, or raise heart rate so there is a fitness and health benefit,” he said.

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Researchers provide complete clinical landscape for gene linked to epilepsy and autism

gene

Researchers from Children’s Hospital of Philadelphia (CHOP) affiliated with the CHOP Epilepsy Neurogenetics Initiative (ENGIN) have compiled a complete genetic and clinical analysis of more than 400 individuals with SCN2A-related disorder, which has been linked to a variety of neurodevelopmental disorders, including epilepsy and autism. By linking clinical features to genetic abnormalities in a standardized format, the researchers hope their findings lead to improved identification and clinical intervention.

The study was published online by the journal Genetics in Medicine.

Pathogenic variants in the SCN2A gene can lead to a wide range of clinical features—or phenotypes—associated with neurodevelopmental disorders. Several studies have described the genetic information collected on individuals with disease-causing changes in this gene. However, while genetic information is collected in a standardized manner, data on phenotypes is not standardized, and prior to this study, the available data on clinical features of these patients had not been thoroughly analyzed, meaning that many correlations between the genotypes and phenotypes of these patients were often anecdotal.

To properly link genetic and phenotypic data, researchers from CHOP utilized Human Phenotype Ontology (HPO), a method that standardizes a patient’s clinical features and allows that data to be translated similar to genetic data.

“Based on our previous work with HPO, we knew we had the opportunity to provide the research and clinical community with the full phenotypic landscape of SCN2A-related disorders,” said Ingo Helbig, MD, attending physician and director of the genomic and data science core of ENGIN and lead investigator of the study. “Individuals with variants of SCN2A present with a wide variety of clinical features, some of which have been difficult to easily categorize prior to our study.”

The researchers extracted phenotypic information from SCN2A-related disorders published over the course of nearly two decades, encompassing every description of the disease in medical literature between 2001 and 2019, in addition to patients followed by ENGIN. Across 413 unrelated individuals, the study team derived a total of 10,860 clinical annotations in HPO terms, with a total of 562 terms unique terms. This allowed researchers to link clinical features with specific genetic variants.

For example, protein-truncating variants, which are genetic variants that shorten the coding sequence of genes, were associated with autism and behavioral abnormalities. Missense variants, or alterations of the genetic code that result in the production of a different amino acid than what would normally be expected, were associated with neonatal onset epileptic spasms and seizures. Using a principal component analysis to simplify the complexity of the data, the researchers found that three principal components accounted for one-third of the phenotypic variability in their dataset, emphasizing that despite the complexity of the data, informative clinical groups can be derived.

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Decrease in exercise more closely linked with higher rates of depression during the pandemic

Decreases in exercise more closely linked with higher rates of depression during the pandemic

Exercise has long-been recommended as a cognitive-behavioral therapy for patients of depression, yet new evidence from the University of California of San Diego suggests that the COVID-19 pandemic changed the nature of the relationship between physical activity and mental health.

In a study of college students conducted before and during the pandemic, findings revealed the average steps of subjects declined from 10,000 to 4,600 steps per day and rates of depression increased from 32% to 61%.

The research, recently published in the Proceedings of the National Academy of Sciences, also revealed short-term restoration of exercise does not meaningfully improve mental well-being.

“This raises many possible explanations, including that the impact of physical activity may require a longer-term intervention,” said co-author Sally Sadoff, associate professor of economics and strategy at UC San Diego’s Rady School of Management. “At the same time, our results clearly show that those who maintained physical exercise throughout the pandemic were the most resilient and least likely to suffer from depression.”

Sadoff added there is a 15 to 18 percentage point difference in depression rates between participants who experienced large disruptions to their mobility, compared to those who maintained their habits.

Sadoff and coauthors from the University of Pittsburg and Carnegie Mellon University point to the alarming trend of increased depression among young adults (ages 18-24) during the pandemic, which is two-times higher than the general population.

The students in the study answered repeated surveys about their well-being and time use over the course of a semester. From March to July 2020, depression rates skyrocketed by 90%, compared to pre-pandemic levels.

Fitbit data helps fill in the gaps in understanding mobility’s role in mental health

The study enrolled multiple cohorts of hundreds of U.S. college students from February 2019 through July 2020. In addition to filling out surveys, participants received wearable devices (Fitbits) that track their activity levels. Participants in the 2020 cohort began the study in February and continued participating after their university moved all classes online in March and encouraged students not to return to campus.

Among the subjects, sleep increased by 25 to 30 minutes per night, time spent socializing declined by more than half (less than 30 minutes per day), and screen time more than doubled to five or more hours per day.

The researchers found large declines in physical activity during COVID-19 was most strongly associated with higher rates of depression. Physical activity minutes translate to about 10 minutes in which the heart rate is raised enough to burn at least 1.5 times as many calories as it does at rest.

Those who experienced declines of one to two hours of physical activity per day were most at risk for depression during the pandemic, while participants who were able to maintain their daily habits were at the lowest risk.

“This relationship is one that only emerges during the pandemic,” the authors note. “Before the pandemic, there was not a very strong connection between changes in physical activity and mental health, but our analyses suggest that disruption to physical activity is a leading risk factor for depression during this period.”

Short-term restoration of exercise habits does not provide mental health relief

In order to examine whether a policy intervention could help counteract some of the pandemic’s adverse impacts to mental health, the researchers implemented a randomized experiment.

Half of the participants were incentivized to walk at least 10,000 steps per day for two weeks. The strategy significantly increased their average steps by about 2,300 steps per day and physical activity by almost 40 minutes per day, compared to the other half of subjects. However, the impact of exercise did not translate into an improvement in mental health, nor did it encourage the students to keep up the physical activity after the two-week period ended.

“Physical activity may have important interactions with other lifestyle behaviors such as social interactions,” the authors write. “It could also be the case that the relationship between physical activity and depression is driven more by mental health than it is by lifestyle habits.”

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Lifelong discrimination linked to high blood pressure in black people

AHA news: lifelong discrimination linked to high blood pressure in black people

Enduring a lifetime of discrimination may increase the risk of high blood pressure in Black people but not in Hispanic, Chinese or white people, a new study suggests.

Previous research has linked lifelong discrimination to the development of high blood pressure, also known as hypertension, in Black people. This new study, however, is among the first to look at multiple types of discrimination in a large multi-ethnic group over a period of time.

The study included 3,297 Black, Hispanic, Chinese and white adults from 45 to 84 years old. They did not have high blood pressure at the start of the study. Participants were asked to report experiences of lifetime and everyday discrimination.

Lifetime discrimination measures included six items, such as being denied a promotion or having life made difficult by neighbors. Everyday discrimination, meanwhile, consisted of nine items, such as being treated with less respect than others or being harassed in day-to-day life.

After nearly two decades, almost half of participants developed high blood pressure. Black participants who reported lifetime discrimination had a 35% increased risk of hypertension, even after accounting for age, income, education, body mass index, physical activity and other factors. Everyday discrimination, however, did not appear to contribute to risk for hypertension.

“Discrimination impacts the health of Black Americans and it should be recognized as a major public health problem,” said Allana T. Forde, lead author of the study published last week in the Journal of the American Heart Association. In November, the American Heart Association issued a “call to action” advisory acknowledging structural racism as “a fundamental cause of poor health and disparities in cardiovascular disease.”

“Health professionals should look beyond traditional risk factors, such as diet and physical activity, and acknowledge discrimination as another risk factor,” said Forde, a researcher at the National Institutes of Health’s National Institute on Minority Health and Health Disparities.

Surprising for researchers, she said, was that lifetime discrimination did not reach the level of statistical significance for contributing to high blood pressure among Chinese and Hispanic participants, even after accounting for being born outside the United States.

Studies in other areas of the U.S. are needed to confirm the findings, researchers said, because the new study was limited to those living in five large cities and one county. In addition, the study only assessed discrimination experiences once at the start of the study, making it unclear what impact changes in discrimination exposure might have had on hypertension development during the follow-up period.

“There is always a concern that not enough subjects were included in the study to show differences in populations or that not all relevant variables were accounted for,” said Dr. Willie Lawrence, chief of cardiology at the Research Medical Center in Kansas City, Missouri. He was not involved in the study.

When measuring decades of discrimination that leads to hypertension, other social determinants of health also must be accounted for. These include health care access, transportation options and a person’s neighborhood.

“Whether communities have sidewalks and green spaces impacts health,” Lawrence said. “If we want to make people healthier, we have to not only eliminate disparities in health care delivery, but we must also seek equity in housing, neighborhoods and education.”

Overall, the study found Black people reported the highest levels of discrimination. About 65% reported lifetime discrimination compared to 42% of Hispanic people, 40% of white people and 23% of Chinese people. Black people most often attributed the unfair treatment to race, whereas white people by far attributed it to non-racial factors such as age, sex or religion. Hispanic and Chinese people were about evenly split between feeling the discrimination was motivated by race versus other factors.

For everyday discrimination, 52% of Black people, 32% of white people, 26% of Hispanic people and 20% of Chinese people reported high levels of exposure.

“Race is complicated in America. It is not genetic,” Lawrence said. “So, I’m not ready to believe that when people of other colors are treated the way Black Americans have been treated for decades that they won’t have higher rates of high blood pressure.”

Even so, he said, “it’s an important study that adds to our belief that social factors impact health.”

Certain, however, is that Black people have higher rates of high blood pressure than other racial and ethnic groups. According to AHA statistics, about 58% of Black adults in the U.S. have the condition, which increases the risk for heart attack and stroke.

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Researchers find delirium in hospitalized patients linked to mortality, disability

Researchers find delirium in hospitalized patients linked to mortality, disability

Delirium, a form of acute brain dysfunction, is widespread in critically ill patients in lower resourced hospitals, and the duration of delirium predicted both mortality and disability at six months after discharge, according to a study published in PLOS ONE.

Working with partners in Zambia, Vanderbilt University Medical Center researchers evaluated 711 hospitalized critically ill patients; delirium occurred in 48.5%. The findings shed light on the impact of delirium on a patient’s recovery—and even whether a patient is likely to live or die.

There have been limited data on the prevalence and outcomes of delirium in low- and middle-income countries, despite there being high numbers of critically ill patients. The mitigation of delirium and post-acute support of patients with delirium is a growing public health concern in the U.S. and Europe as the number of patients in intensive care units surged with the rise of COVID-19 cases.

“There is a driving unmet need to understand what happens with people’s brains in critical illness in low- and middle- income countries as well as with HIV in all settings. The necessity is now urgent because of the COVID-19 pandemic. Delirium has become the epidemic within the pandemic—and it’s the strongest predictor of long-term acquired cognitive impairment after critical illness. These are bread and butter issues people care about: will I live or die and if I live, what will I be like as a person,” said Wesley Ely, MD, MPH, co-director of the Critical Illness, Brain Dysfunction, and Survivorship Center at VUMC and senior author.

Patients with delirium had a higher six-month mortality, 44.6%, than patients without delirium who had a 20.0% six-month mortality. Compared to no delirium, presence of 1, 2 or 3 days of delirium predicted higher odds of six-month mortality of 1.43, 2.20, and 3.92, respectively. A similar relationship was found between duration of delirium and odds of worse six-month disability, assessed using the WHO Disability Assessment Schedule.

The study adjusted for age, sex, education, income, Universal Vital Assessment (UVA) severity of illness score, HIV status, and current antituberculosis treatment in adult patients who spoke English, Nyanja, or Bemba at the University Teaching Hospital, a 1,655-bed national referral hospital in Lusaka with about 17,500 acute admissions annually.

The prevalence of HIV in the study cohort was 45.4% while 27.2% of participants had a history of tuberculosis, suggesting delirium is an important clinical issue impacting the lives of hospitalized patients with HIV and tuberculosis in Sub-Saharan Africa. The high mortality and disability associated with delirium in this medically and socioeconomically vulnerable patient population spotlights an urgent global health issue.

“Acute brain dysfunction can have a variety of drivers, yet we know that delirium can itself lead to poor outcomes. In other parts of the world delirium is recognized as a major public health concern, while in lower resourced communities the magnitude of the problem has been obscured by acutely pressing issues such as HIV, malaria, and tuberculosis. Our research suggests it’s widespread and may present an opportunity to improve the lives of critically ill patients in low- and middle-income countries in the future as well as advocate for global critical care equity during the COVID-19 pandemic,” said Justin Banerdt, MD, MPH, internal medicine resident at Yale School of Medicine, and corresponding author who led the study on the ground in Zambia while a MD/MPH student at Vanderbilt University School of Medicine.

The next step is to see which interventions are effective in resource limited hospitals, said Douglas Heimburger, MD, MS, professor of Medicine and core faculty at the Vanderbilt Institute for Global Health. He leads projects with grant funding from the Fogarty International Center of the National Institutes of Health (NIH).

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Acute itching in eczema patients linked to environmental allergens

Acute itching in eczema patients linked to environmental allergens

In addition to a skin rash, many eczema sufferers also experience chronic itching, but sometimes that itching can become torturous. Worse, antihistamines—the standard treatment for itching and allergy—often don’t help.

New research from Washington University School of Medicine in St. Louis indicates that allergens in the environment often are to blame for episodes of acute itch in eczema patients, and that the itching often doesn’t respond to antihistamines because the itch signals are being carried to the brain along a previously unrecognized pathway that current drugs don’t target.

The new findings, published Jan. 14 in the journal Cell, point to a possible new target and strategy to help eczema patients cope with those episodes of acute, severe itch.

“Years ago, we used to think that itch and pain were carried along the same subway lines in the nerves to the brain, but it turned out they weren’t, and these new findings show there’s another pathway entirely that’s causing these episodes of acute itching in eczema patients,” said principal investigator Brian S. Kim, MD, a dermatologist and an associate professor of medicine. “The itch can be maddening. Patients may rate their chronic itch at around a 5 on a scale of 10, but that goes up to 10 during acute itch flares. Now that we know those acute flares are being transmitted in an entirely different way, we can target that pathway, and maybe we can help those patients.”

The typical pathway for itching in eczema patients involves cells in the skin that are activated and then release histamine, which can be inhibited with antihistamine drugs. But with this acute itching, a different type of cell in the bloodstream transmits itch signals to the nerves. Those cells produce too much of another non-histamine substance that triggers itch; therefore, antihistamines don’t work in response to such signals.

“We’ve connected acute itching in eczema to allergic reactions transmitted by an entirely different population of cells,” said Kim, also the co-director of the Center for the Study of Itch & Sensory Disorders. “In patients who experience episodes of acute itching, their bodies react in the same way as in people with acute allergy. If we can block this pathway with drugs, it might represent a strategy for treating not only itch but other problems, including perhaps hay fever and asthma.”

In recent years, several clinical studies have tested a strategy that involves blocking Immunoglobulin E (IgE), a substance produced by the immune system in response to allergens. Patients with allergies produce IgE, causing allergic reactions, but its role in itch has been unclear.

Reviewing data from clinical studies of drugs aimed at treating chronic itching, Kim found a pattern in which patients reported episodes of acute itching, often after exposure to environmental allergens. He also found that eczema patients who make IgE in response to allergens in the environment were more likely to experience those episodes of severe, acute itch.

“Environmental allergens actually promote this type of itch,” he explained. “Say a patient with eczema goes to Grandma’s house, where there’s a cat, and that person’s itching just goes crazy. It’s likely cat dander is activating IgE, and IgE is activating itch.”

Kim’s team took these observations to the laboratory, where his team made a mouse model of eczema. Studying the animals, they found that when the mice made IgE, they began to itch. But unlike standard itch signals, in which cells in the skin called mast cells release histamine, the IgE in mice with eczema activated a type of white blood cell called a basophil. Those cells then activated an entirely different set of nerve cells than the cells that carry itch signals that respond to antihistamines.

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Preemie-born parents linked to children with autism

premature

In a study of medical registry records of nearly 400,000 parent-child pairs from Denmark, a Yale School of Public Health study found that parents who were themselves born very prematurely were nearly twice as likely to have children with autism spectrum disorder.

The study, recently published in the International Journal of Epidemiology, provides solid evidence that autism spectrum disorder risk factors can span multiple generations—a new hypothesis that previously lacked much empirical evidence in humans. According to senior author Zeyan Liew, assistant professor in the Department of Environmental Health Sciences, these findings can help spark further research into the underlying mechanisms of autism risk transmission in families.

“It’s already well established that preterm birth and low birth weight of the child are risk factors for autism,” he said. “But this is the first study to show that parental preterm birth and low birth weight might carry some risk for their future offspring as well.”

For their research, Liew and his team evaluated data collected from families across Denmark from 1978 to 2017 as part of its central medical records database. Researchers linked birth records of the parents to the medical records in their offspring to investigate whether there is a link between neonatal characteristics of the parents and autism spectrum disorder risk in their children. Their results suggest that women and men who were born at less than 37 weeks or low birth weight were more likely to have children diagnosed with autism spectrum disorder than those without adverse birth characteristics. The study authors reported that some other possible multigenerational risk factors they analyzed, such as grandparents’ education, place of residence, and their age at the time of pregnancy, only contributed minimally to the observed associations.

It remains unclear how exactly autism spectrum disorder risks travel across generations, but Liew said he has some hypotheses. For one, there has been growing evidence showing that changes in gene activity in response to environmental stimuli could be inherited across generations without changing the underlying DNA sequences—a phenomenon known as epigenetic inheritance. “These adverse characteristics at birth may act as a proxy measure of possible heritable epigenetic modifications as a result of harmful prenatal exposures affecting early life growth, which could help explain the multigenerational transmission of disease risk we observed,” Liew said.

Parents who were born with unfavorable characteristics may also be more likely to encounter challenges in the physical, mental, reproductive, or social domains of health in childhood and adulthood. Liew and his group evaluated these factors and found that educational achievement and mental health status of the parents before pregnancy played a small mediating role in the observed associations.

Genetics and other environmental or household factors shared across generations could play a part as well, but the researchers did not have that information for their sample in this study.

Liew and his team plan to do more research in this area to see if the same conclusions hold in other parts of the world and in other populations, with additional considerations of potential methodological challenges of conducting multigenerational studies like this.

“From previous studies, a lot of the findings that we’ve seen in Denmark hold up in other countries as well,” he said. “We think that this is not specific to Denmark, but we need more evidence from other places.”

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