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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The Lancet: More nurses lead to fewer patient deaths&readmissions, shorter hospital stays, and savings

The Lancet: More nurses lead to fewer patient deaths&readmissions, shorter hospital stays, and savings

A study across 55 hospitals in Queensland, Australia suggests that a recent state policy to introduce a minimum ratio of one nurse to four patients for day shifts has successfully improved patient care, with a 7% drop in the chance of death and readmission, and 3% reduction in length of stay for every one less patient a nurse has on their workload.

The study of more than 400,000 patients and 17,000 nurses in 27 hospitals that implemented the policy and 28 comparison hospitals is published in The Lancet. It is the first prospective evaluation of the health policy aimed at boosting nurse numbers in hospitals to ensure a minimum safe standard and suggests that savings made from shorter hospital stays and fewer readmissions were double the cost of hiring more staff.

Despite some evidence that more nurses in hospitals could benefit patient safety, similar policies have not been widely implemented across the globe, partly due to an absence of data on the long-term effects and costs, as well as limited resources. In recent years, Scotland, Wales, and Ireland have mandated numbers of patients per nurse, but strategies to improve nursing levels remains debated worldwide.

“Our findings plug a crucial data gap that has delayed a widespread roll-out of nurse staffing mandates. Opponents of these policies often raise concerns that there is no clear evaluation of policy, so we hope that our data convinces people of the need for minimum nurse-to-patient ratios by clearly demonstrating that quality nursing is vital to patient safety and care”, says lead author, Professor Matthew McHugh of the University of Pennsylvania School of Nursing, USA.

In 2016, 27 public hospitals in Queensland were required to instate a minimum of one dedicated nurse for every four patients during day shifts and one for every seven patients for night shifts on medical-surgical wards.

The research team collected data from those 27 Queensland hospitals that instated ratios and from 28 other hospitals in the state that did not, at baseline in 2016 and at follow-up in 2018 (two years after the policy was implemented). Only nurses in direct contact with adult patients in medical-surgical wards were included—data from patients in birthing suites and psychiatric units were not assessed in the study.

Researchers used patient data to assess demographics, diagnoses, and discharge details for patients, as well as length of hospital stay. These data were then linked to death records for 30 days following discharge, and to readmissions within seven days of discharge.

The researchers sent an email survey to nurses in each hospital to ask about the numbers of bedside nurses and patients on their most recent shift. The responses were used to establish the numbers of nurses per patient and then averaged across wards and hospitals. Responses were received from 8,732 nurses (of a possible 26,871) at baseline in 2016, and 8,278 (of a possible 30,658) in 2018.

The study includes baseline data for 231,902 patients (142,986 in hospitals that implemented the policy and 88,916 in comparison hospitals), and for 257,253 patients (160,167 in hospitals that implemented the policy and 97,086 in comparison hospitals) after the policy was brought in.

Comparison hospitals had no change in staffing, with six patients per nurse in 2016 and the same ratio (1:6) in the follow-up period in 2018. Intervention hospitals averaged five patients per nurse at baseline in 2016, with a reduction to four per nurse after the policy implementation.

To compare the changes in outcomes in the intervention and comparison hospitals over time, the researchers estimated the odds of dying within 30 days of admission and of being readmitted within seven days of discharge, and the additional length of stay, after adjusting for factors such as patient age, sex, existing health conditions and hospital size. They found that the chance of death rose between 2016 and 2018 by 7% in hospitals that did not implement the policy, and fell by 11% in hospitals that did implement the policy.

The chances of being readmitted increased by 6% in the comparison hospitals over time, but stayed the same in hospitals that implemented the policy. Between 2016 and 2018, the length of stay fell by 5% in the hospitals that did not implement the policy, and by 9% in hospitals that did.

Further analyses found that when nurse workloads improved by one less patient per nurse, the chance of death and readmissions fell by 7%, and the length of hospital stay dropped by 3%.

Using their modelling to predict figures that would have been expected without the policy in place, the researchers estimated that there could have been 145 more deaths, 255 more readmissions and 29,222 additional days in hospital in the 27 hospitals that implemented the policy between 2016 and 2018.

To calculate the financial impact of the staffing policy, the researchers used state data to estimate the cost of funding the 167 extra staff needed to reduce workload by one patient per nurse at approximately $33,000,000 (AUD) in the first two years. Based on Australian health economic data, they further estimated that preventing readmissions and reducing lengths of stay resulted in an approximate saving of $69,150,858 in the 27 hospitals across the two years following the mandate.

“Part of the reluctance to bring in a minimum nurse-patient ratio mandate from some policy-makers is the expected rise in costs from increased staffing. Our findings suggest that this is short-sighted and that the savings created by preventing readmissions and reducing length of stay were more than twice the cost of employing the additional nurses needed to meet the required staffing levels—a clear return on investment. Often, policy-makers are concerned about whether they can afford to implement such a policy. We would encourage governments to look at these figures and consider if they can afford not to,” says Professor Patsy Yates of the Queensland University of Technology School of Nursing, Australia. [1]

The authors note that there are a number of limitations associated with the study. Hospitals in the research were not randomly assigned to comparison or intervention groups, as only 27 hospitals in the state were mandated to follow the policy. Furthermore, the hospitals included in both groups were not matched for size or patient demographics and health conditions, although this is accounted for in adjusted analyses.

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New theory may revolutionize treatment of endometriosis

uterus

Endometriosis, a disease found in up to 10 percent of women, has been enigmatic since it was first described. A new theory developed by researchers at Simon Fraser University suggests a previously overlooked hormone—testosterone—has a critical role in its development. The research could have direct impacts on diagnosis and treatment of the disease, signaling hope for women with endometriosis worldwide.

The disease is caused by endometrial tissue growing outside of the uterus, usually in the pelvic area, where it contributes to pain, inflammation, and infertility. But why some women get it, and others do not, has remained unclear.

The new research is based on recent findings that women with endometriosis developed, as fetuses in their mother’s wombs, under conditions of relatively low testosterone, compared to women without endometriosis.

According to the researchers’ theory, this low testosterone “programs” the developing reproductive system of women to exhibit the unique suite of traits that is linked with endometriosis, including early menarche, short menstrual cycles, high pain sensitivity, high inflammation, and altered levels of the hormones that control ovulation and the menstrual cycle.

The researchers found their theory to be supported by a remarkable range of data in the literature, from genetics and development to endocrinology, morphology, life history, and evolutionary biology, thus providing the first comprehensive explanation for the traits associated with endometriosis.

The theory can explain almost all symptoms of endometriosis as downstream effects of low early-life testosterone. The findings are presented in two recent papers published in Evolution, Medicine and Public Health, and Evolutionary Applications.

“Low testosterone in early development is the strongest known correlate of endometriosis, and its effects can explain the majority of endometriosis symptoms,” says SFU biological sciences professor Bernard Crespi, a Canada Research Chair and co-author of the work with graduate student Natalie Dinsdale. “What’s more, the new theory has direct implications for endometriosis diagnosis and treatment.”

Crespi notes that testosterone has apparently been overlooked in studies of endometriosis because it is usually regarded as a “male” hormone, even though it is known to have key effects in females as well.

“It is very common for researchers to focus on estrogen as a female hormone, and testosterone as a male hormone, but in reality, these are both critically important hormones in all humans,” says Ben Trumble, an assistant professor at the School of Human Evolution and Social Change at Arizona State University, who was not associated with these studies. “I applaud the authors for moving beyond this binary hormonal blind spot, and studying the full range of steroids that can impact women’s health.”

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A Psychiatrist Explains What to Do If You or Someone You Know Has Suicidal Thoughts

Any safety concerns since last time? I ask my patients that question, or a longer version, Are you having any thoughts about wanting to hurt yourself or wanting to die? Part of my work as a psychiatrist is identifying those who are at highest risk for suicide and then doing my best to prevent it.

There aren’t concrete statistics for how many men are thinking thoughts like that at this very moment, but I can tell you it’s not a small number. One survey by the CDC conducted last June suggested that twice as many people in the U. S. reported serious consideration of suicide in the previous 30 days as felt that way in 2018—and Hispanic and Black respondents were more likely to report it than people who are white or Asian. Essential workers and unpaid caregivers also reported elevated rates of these thoughts.

That’s why I ask my patients about suicidal thoughts, also known as suicidal ideation. I was recently caught off guard when a longtime patient of mine, whom I’ll call Peter, reluctantly admitted, “To be completely honest, yeah, I’ve had thoughts like that off and on for years.”

Many of us at some point have speculated about the what-ifs of life, or death. Usually, when men are talking about this type of inclination, what they’re looking for most is to feel supported. Only after I sat and listened to Peter’s thoughts did I ask the next questions. Questions like “How long have the thoughts been going on? Have you considered a plan?”

It became clear that he was experiencing passive suicidal thoughts—he wasn’t actually planning to hurt himself, and he didn’t want to, but every once in a while, he would think to himself: What if I weren’t here? When I asked him why he hadn’t told me about them before, he said, “They’re just thoughts.” But they’re really important to discuss.

Lots of people don’t want to say anything about suicidal thoughts, believing they make you seem “crazy” or “off.” Sometimes my patients are afraid that if they tell me, I’m going to admit them to a psychiatric hospital against their will. This is far from the first step; it’s for urgent mental-health crises, and usually men choose to go voluntarily. They’re also worried that friends and family would feel uncomfortable if they said anything, or would start to avoid them or act differently toward them. It’s never comfortable talking about suicidal thoughts, and that’s okay, because conversations about suicide aren’t supposed to be comfortable.

Staying silent is really what makes suicidal thoughts dangerous—that’s when they could potentially gain traction and cause people to consider acting on them. Talking helps you learn how to make sense of what you’re thinking so that you can develop healthy ways to move beyond it.

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Novel agent shows promise in treating the most aggressive type of breast cancer

breast cancer

A unique antibody drug conjugate (ADC), which delivers a high dose of a cancer-killing drug to tumor cells through a targeted antibody, has been found in a global phase 3 clinical study to nearly double the survival time of patients with refractory metastatic triple-negative breast cancer. The study of the ADC drug sacituzumab govitecan (SG), for which Massachusetts General Hospital (MGH) was a lead clinical research site after serving as the lead site for the pivotal phase 1/2 trial, reported superior outcomes compared to single-agent chemotherapy, the standard for treating metastatic triple-negative breast cancer. The phase 3 results of the study, known as ASCENT, were published in the New England Journal of Medicine.

“Favorable results with SG versus chemotherapy were observed in terms of progression-free survival (the length of time the cancer was kept from spreading); the amount of time between the start of treatment and cancer progression; and overall survival—the length of time before death from any cause,” says global principal investigator Aditya Bardia, MD, MPH, an attending physician in the Department of Medical Oncology at Mass General Cancer Center. “These statistically significant findings give patients with this devastating disease new cause for hope. We need to build on that progress and accelerate further development of antibody drug conjugates and combination therapies for patients with breast cancer.”

Metastatic triple-negative breast cancer is the most aggressive type of breast cancer with a poor prognosis. Chemotherapy has remained the only standard treatment option, but it is associated with low response rates and short progression-free survival. SG, which was developed and is manufactured by Immunomedics, a subsidiary of Gilead Sciences, received accelerated approval by the U.S. Food and Drug Administration in April 2020 on the basis of favorable phase 1/2 clinical trials, with full approval contingent on the confirmatory phase 3 results.

ASCENT is a global study to evaluate the safety and efficacy of the antibody drug conjugate compared to chemotherapy in 529 patients with metastatic triple-negative breast cancer whose cancer had relapsed or was resistant to at least two other forms of therapy. The investigators found that median progression-free survival with the ADC agent was 5.6 months compared to 1.7 months with chemotherapy, and that median overall survival was 12.1 months with the ADC agent compared to 6.7 months with chemotherapy. The study also found that the response rate— that is, shrinkage in the size of the metastatic tumor sites—was 35% after administration of ADC compared to 5% with chemotherapy.

ADCs are complex molecules that combine the targeting capabilities of monoclonal antibodies with the cancer-killing strength of cytotoxic drugs. In the case of sacituzumab govitecan, the monoclonal antibody seeks out the antigen (or protein), known as Trop-2 that is overexpressed on the surface of tumor cells, and delivers the anti-cancer drug SN-38 in a highly concentrated dose that destroys cancerous cells while sparing normal ones. ADCs have been established as a treatment option for HER2-positive breast cancer.

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A small T cell switch with a big impact

T cells play a key role in the human immune system. They are capable of distinguishing diseased or foreign tissue from the body’s own, healthy tissue with great accuracy; they are capable of triggering the actions necessary to fight off the troublemakers. The details of this immune response are manifold and the individual steps are not yet fully understood.

Scientists of the universities of Würzburg and Mainz have now figured out new details of these processes, showing that tiny point mutations in a gene can modify T cells to be less aggressive. This could be an advantage after stem cell transplantation which includes T-cell transfusion in order to keep a number of severe side effects in check. The researchers have now published the results of their study in the Journal of Experimental Medicine. The study is led by Dr. Friederike Berberich-Siebelt, head of the “Molecular and cellular immunology” research group at the Institute of Pathology of the University of Würzburg.

A protein family with multiple tasks

When T cells detect foreign or altered tissue, such as an infected or tumor tissue, this usually happens through the receptors on their cell surface. These T-cell receptors then send signals into the cell interior, initiating a response. In a first step, they activate a special family of transcription factors—scientifically called NFAT for nuclear factor of activated T-cells. The NFATs then bind to the DNA in the cell nucleus and trigger also the production of cytokines such as interleukin-2.

NFAT is composed of many family members which may have overlapping tasks or assume completely different functions. But that’s not all: Like many other proteins in the cell, they can still be modified after their synthesis to customize their function. The recently published study focuses on one specific modification of the NFATc1 “family member” which is called sumoylation.

Advantageous point mutations

“Sumoylation plays a role in different cellular processes such as nuclear transport, programmed cell death or as an antiviral mechanism,” Friederike Berberich-Siebelt explains. Sumoylation defects have also been observed in various diseases such as cancer and herpesvirus infections.

In the study now published, the scientists worked with laboratory animals that had two actually insignificant point mutations in the NFATc1 gene which, however, prevent sumoylation. This is not necessarily a disadvantage: “The offspring of these animals is perfectly healthy. The modified NFATc1 even mediates specific signals that reduce the clinical symptoms of multiple sclerosis at least in the animal model,” Berberich-Siebelt explains. When using T cells that carry these mutations in stem cell transplantation, they are much less aggressive against the tissues of the host animals than “normal” cells.

Fascinating fundamental research

This effect is due to an increase in interleukin-2 at the beginning of the immune response at the biomolecular level. Interleukin-2 counteracts the differentiation into inflammatory T-cell subtypes and at the same time supports so-called regulatory T cells according to the authors of the study. It is quite possible that this discovery will have consequences for future stem cell transplantation which includes T-cell infusion. When using T cells in which NFATc1 is not sumoylated, this might prevent severe side effects, making the point mutation “a small modification with a big impact” according to Berberich-Siebelt.

To investigate this in more detail, Berberich-Siebelt and her team will continue to research the possibilities of therapeutic implementation within the framework of the Collaborative Research Center/Transregio “Control of graft-versus-host and graft-versus-leukemia immune responses after allogeneic stem cell transplantation” funded by the German Research Foundation (DFG). “We want to find out whether CRISPR/Cas9 gene editing can be applied to human T cells to exhibit just the right amount of activity during hematopoietic stem cell transplantation,” the scientist says.

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