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The risk of serious adverse effects on the blood status and bone marrow of patients during chemotherapy can be predicted by a model developed at Linköping University, Sweden. This research may make it possible to use genetic analysis to identify patients with a high probability of side effects. The study has been published in npj Systems Biology and Applications.

It is often difficult during cancer treatment to achieve a balance between getting rid of as many tumour cells as possible, while at the same time not causing serious side effects.

One of the common properties of tumour cells is that they grow rapidly and in an uncontrolled manner. The chemotherapy drugs that are used to treat cancer have for this reason been designed to kill rapidly growing cells. But the treatment also kills normal cells that grow rapidly. One of the more sensitive tissues is the bone marrow, where various types of blood cell are formed at a rapid rate. Approximately 25% of lung cancer patients who receive combination treatment with the drugs gemcitabine and carboplatin experience life-threatening side effects on the bone marrow during standard treatment. In many cases, the treatment must be discontinued.

We know that genetic factors play a role in the response of an individual to these treatments. Complicated interactions between many genes are probably involved. The scientists who carried out the study have therefore investigated whether genetic signatures exist that can be used to identify the patients at a high risk of experiencing severe side effects from the treatment. This would enable them to adapt treatment to the individual more accurately from the start: those with a low risk of side effects can be given higher doses, with a stronger effect on the cancer, while those with highest risk can be given another treatment.

The study, published in npj Systems Biology and Applications, is a collaboration between researchers in pharmacogenetics and bioinformatics. They determined the complete DNA sequences of 96 patients with non-small cell lung cancer who had been treated with gemcitabine/carboplatin. Sequencing of the whole genome in this way provides information about millions of genetic variants that may be interesting. The researchers wanted to see whether they could find in this huge amount of data functional groups of genes that were linked to the degree of toxicity that the treatment had had on the bone marrow of the different patients.

The researchers in a first step identified a network of 215 genes that were tightly linked to each other. This network was particularly rich in genes that have been associated with these drugs in previous studies. The next step was to reduce the number of genetic variants in the gene network to the 62 that are included in the final model. The researchers demonstrate that the model can be used to classify patients into one of two groups, with high or low probability of experiencing severe side effects.

"It's extremely interesting that the genes involved are associated with cell division, in particular in bone marrow. We managed not only to predict side effects for the patients, but also show that the model is biologically relevant", says Henrik Gréen, professor at the Department of Biomedical and Clinical Sciences, Linköping University.

The prediction model must be tested in further studies before it can be used in the clinic. Increasingly advanced methods of genetic analysis are being introduced into the Swedish medical care system, which makes it possible in the long term to introduce this type of method, built on an analysis of many genes at the same time.

"We want to work towards establishing a standard within translational bioinformatics, and show that the same type of method can be applied in several medical situations. The patient material here may appear to be small, but we have even so demonstrated that this approach can be used to predict the severity of side effects for patients", says Mika Gustafsson, senior lecturer in the Department of Physics, Chemistry and Biology at Linköping University, and, together with Henrik Gréen, leader of the study.

Bristol scientists have demonstrated a new virtual reality [VR] technique which should help in developing drugs against the SARS-CoV-2 virus - and enable researchers to share models and collaborate in new ways. The innovative tool, created by University of Bristol researchers, and published in the Journal of Chemical Information and Modeling, will help scientists around the world identify anti-viral drug leads more rapidly.

A SARS-CoV-2 enzyme known as the main protease (Mpro) is a promising target in the search for new anti-viral treatments. Molecules that stop the main protease from working - called enzyme inhibitors - stop the virus reproducing, and so could be effective drugs. Researchers across the world are working to find such molecules. A key predictor of a drug's effectiveness is how tightly it binds to its target; knowing how a drug fits into the protein helps researchers design changes to its structure to make it bind more tightly.

Professor Adrian Mulholland from Bristol's School of Chemistry and the study's lead author explained: "We've shown that interactive virtual reality can model how viral proteins and inhibitors bind to the enzyme. Researchers can use this tool to help understand how the enzyme works, and also to see how potential drugs fit into the enzyme. This should help design and test new potential drug leads. We are sharing these models with the whole community."

The Bristol team have developed a virtual framework for interactive 'molecular dynamics' simulations. It is an open source software framework, called Narupa, which uses readily available VR equipment.

In this study, the Bristol team created a 3D model structure of the SARS-CoV-2 Mpro and used interactive molecular dynamics simulations in VR (iMD-VR) to 'step inside' it and visualise molecules binding to the enzyme, in atomic detail. Results showed that users were able to show how a drug molecule fits within the enzyme.

Professor Mulholland added: "There are currently many efforts globally aimed at identifying drug leads for COVID-19. Our iMD-VR tools will be a valuable resource, enabling virtual collaboration for the international drug discovery community, helping to predict how potential drug leads bind to SARS-CoV-2 targets. An exciting aspect is that it also allows researchers to collaborate in new ways: using cloud computing, they can tackle a drug discovery problem together at the same time when in they are in different locations - potentially even in different countries - working simultaneously in the same virtual molecular environment."

"Computational modelling of how drugs bind to the SARS-CoV-2 spike protein has been critical in advancing the global fight against the pandemic. Narupa takes that modelling to an entirely new level with molecular dynamics simulations in virtual reality," said Alison Derbenwick Miller, Vice President, Oracle for Research. "We are delighted that Oracle's high-performance cloud infrastructure supported the development of this innovative framework, and is now helping to advance globally-connected efforts to defeat COVID-19. Growing a connected community of cloud-powered researchers is exactly what Oracle for Research was designed to do."

PHILADELPHIA (November 12, 2020) - Type 1 diabetes (T1D) is the third most common pediatric chronic disease in the United States, and the risk of the disease has risen sharply in non-Hispanic Black (NHB) children in the last 20 years, data show. Ironically, the significant advances in T1D therapeutics over recent years, especially new technologies, may have exacerbated racial disparities in diabetes treatment and outcomes.

In an article in the journal Pediatric Diabetes, researchers from the University of Pennsylvania School of Nursing (Penn Nursing) and the Children's Hospital of Philadelphia detail their retrospective study of more than 2,800 children with T1D. Their findings have helped quantify racial and ethnic disparities in health care use, technology application, and outcomes in pediatric diabetes treatment.

"Disparities in these treatments are of clinical significance, as both intensive insulin therapy and the incorporation of technology have been associated with improved glycemic control and, consequently, reduced long-term complications," writes Terri H. Lipman, PhD, CRNP, FAAN, Miriam Stirl Endowed Term Professor of Nutrition, Professor of Nursing of Children and Assistant Dean for Community Engagement at Penn Nursing.

The article, "Racial Disparities in Treatment and Outcomes of Children With Type 1 Diabetes," details how treatment modalities, clinical outcomes, and appointment attendance in NHB versus non-Hispanic white and Hispanic children with T1D were examined while including the contribution of insurance status (as a proxy for socioeconomic status) to these disparities. Despite similar outpatient appointment attendance rates, significant disparities in continuous glucose monitoring and insulin pump use were observed.

"Disparities in health care cannot be eliminated without a societal effort to address structural racism. The underlying etiologies of health care disparities, including the impact of patient and provider bias, should be fully investigated and strategies developed to mitigate these contributing factors," concludes Lipman.

New research from the University of Cincinnati (UC) finds that women with kidney failure have low rates of contraceptive use. The study, published in the journal Kidney Medicine, finds an overall contraceptive use rate of 5.3% among women with kidney failure undergoing dialysis in the United States.

"Although end-stage kidney disease adversely impacts fertility, conception is common among women on dialysis. Kidney failure increases the risk of adverse pregnancy outcomes, including pre-eclampsia, fetal growth restriction and preterm babies," says Silvi Shah, MD, assistant professor in the Division of Nephrology, Kidney CARE Program at UC and lead author of the study. "Unplanned pregnancies occur in women with kidney disease. It is of paramount importance that pregnancies in this high-risk population are planned and gives us the opportunity to counsel women about family planning and the impact of pregnancy on kidney disease, and the impact of kidney disease on maternal and fetal outcomes."

The study evaluated 35,732 women of childbearing age between Jan. 1, 2005 and Dec. 31, 2014. They were all between the ages of 15-44 years, on dialysis and with Medicare as the primary payer, using the United States Renal Data System. Overall, the rate of contraceptive use was 5.3%. The mean age at study entry was 30±7 years for women with any contraceptive use. The contraceptive use was highest among women aged 15-24 years (11.1%) and lowest among women aged 40-44 years (2.6%). The study showed that younger age, Native American and black race/ethnicity, kidney failure due to glomerulonephritis, hemodialysis modality, and predialysis nephrology care were associated with a higher likelihood of contraceptive use. The analysis also found that the socioeconomic status did not impact the likelihood of contraceptive use.

Shah says study unique in that it addresses a comprehensive group of women undergoing dialysis of all racial and ethnic groups in the United States from 2005-2014 to better understand the incidence of contraceptive use and factors associated with it. The study further took into account patients with complete Medicare coverage, thus avoiding the potential shortfalls of registries dependent on voluntary reporting or patient recall. This research shows for the first time that contraceptive usage rates in women with kidney failure who are undergoing dialysis remains very low in the United States.

"We were not able to account for use of natural methods or use of condoms in our study, which remains a limitation," says Shaw. "However, the results highlight that contraceptive use among women with kidney failure is extremely low which may account for higher rates of unintentional pregnancies in this high-risk population. We need to include contraceptive counselling for women of child-bearing age in routine clinical care. Additionally, the present study emphasizes the importance of formulating policies that promote awareness of reproductive health and contraception among women with kidney failure."

New Rochelle, NY, November 10, 2020--A significant number of women would consider using cannabis to treat gynecological conditions, primarily gynecological pain. Women with a history of cannabis use are reported in a study in Journal of Women's Health. Click here ( http://doi.org/10.1089/jwh.2020.8437) to read the article now.

Women who self-medicate with cannabis do so to relieve chronic pelvic pain, menstrual cramps, and pain associated with gynecological cancer or medical procedures such as abortion.

"A larger proportion of women who reported ever using cannabis were willing to use cannabis to treat conditions commonly seen in gynecological practices compared to never-users (91.6% vs. 64.6%)," states Leo Han, MD, MPH, and coauthors, from Oregon Health & Science University. This difference was statistically significant.

"Coinciding with the increased perception of cannabis safety is the increased national recognition of the dangers of opioid pain medications," says the authors.

"In this study, a large proportion of those women who had never used cannabis were willing to try it to treat gynecological pain. Fewer, but still a substantial percentage, would use it for procedural pain or other gynecological conditions," says Journal of Women's Health Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA.

SAN FRANCISCO - Nov. 12, 2020 - The COVID-19 Early Treatment Fund (CETF), today announced that JAMA, The Journal of the American Medical Association, published the results of a Washington University School of Medicine in St. Louis double-blind, randomized controlled clinical trial that investigated whether the antidepressant medication fluvoxamine, if taken within seven days of first symptoms of COVID-19, can reduce the risk for respiratory deterioration. The CETF-funded study showed that fluvoxamine was effective: none of the 80 patients who took the drug met the respiratory deterioration criteria compared to an 8.3% rate in the 72 patients who took a placebo.

Dr. Carolyn Machamer, a professor of cell biology at the Johns Hopkins School of Medicine and a member of CETF's scientific advisory board (SAB), who has studied the basic biology of coronaviruses for years noted, "The results of the fluvoxamine trial are encouraging and warrant a further evaluation in a larger study. A treatment that can prevent lung problems in people with mild symptoms of COVID-19 is desperately needed."

Under the leadership of Dr. Eric Lenze, director of the Healthy Mind Lab at Washington University School of Medicine in St. Louis, study researchers tested fluvoxamine, which is typically used to treat patients with obsessive-compulsive disorder, in coronavirus patients because it has strong anti-inflammatory properties. The researchers believed this capability could prevent cytokine storms - the body's massive, sometimes deadly, inflammatory reaction to coronavirus and other infections.

"This placebo-controlled study indicates that fluvoxamine may prevent serious breathing problems in people with mild COVID-19 illness, and is the first in this patient population to be published in a peer-reviewed journal," said Lenze. "These are promising findings, and we look forward to conducting a much larger study in the coming weeks to further evaluate the effectiveness of fluvoxamine."

The 152 trial participants, all of whom were 18 years or older, were diagnosed with mild forms of COVID-19, and lived in either Missouri or Illinois. Participants were randomly assigned (1:1) to take either fluvoxamine or a placebo. In this outpatient clinical trial, there was no face-to-face contact between participants and clinicians; study materials, including the study drug, were delivered to the participants' homes. In this trial, of the 80 participants who received the drug, zero hit the endpoint of clinical deterioration (oxygen saturation of 92% or lower along with difficulty breathing or hospitalization for pneumonia), as opposed to the six of 72 people who got the placebo and experienced deterioration. The results show that fluvoxamine has the potential to reduce the risk of hospitalization in COVID-19 patients.

"We now have evidence that an inexpensive, safe, and readily available pill can reduce deterioration and hospitalization from COVID-19," said Steve Kirsch, CETF founder. "This trial validates what we have already learned from multiple scientific studies, the greater the sigma-1 activation, the greater the protection."

The study result affirmed a large, multi-center observational study done in France that showed that SSRI drugs significantly reduced the risk of requiring a ventilator or death from COVID-19. The French study showed that the SSRIs with the highest sigma-1 receptor activation had the greatest benefit.

Unaffiliated to this study, David Seftel, M,D., Harvard-educated internist and CEO of Stanford partner lab Enable Biosciences who serves as a Principal Investigator for several NIH projects, opined: "Fluvoxamine might be considered by doctors for off-label use to treat COVID-19 patients early in their disease. Even if vaccines or other therapeutics are used as a first line of defense, fluvoxamine may dramatically decrease the odds that someone will need to be hospitalized."

Exposure to COVID-19 could pose a risk to the health and aging of individuals who aren't even born yet, according to a newly published analysis by USC researchers.

In the article, University Professors Eileen Crimmins and Caleb Finch of the USC Leonard Davis School of Gerontology and Keck School of Medicine neonatology fellow Molly Easterlin note that by the end of 2020, approximately 300,000 infants could be born to mothers infected by SARS-CoV-2, the virus that causes COVID-19. Millions more will be born into families who have experienced tremendous stress and upheaval due to the pandemic even if they haven't been infected themselves, the authors added.

While the longer-term effects of COVID-19 on infants is yet to be seen, researchers can find some insight from the past, including the 1918 flu pandemic and previous coronavirus illnesses such as SARS in 2002 and MERS in 2012, Finch said.

"The 1918 influenza pandemic had long-term impacts on the cohort exposed in utero, which experienced earlier adult mortality and more diabetes, ischemic heart disease and depression after age 50," he said. "It is possible that the COVID-19 pandemic will also have long-term impacts on the cohort that was in utero during the pandemic, from exposure to maternal infection and/or the stress of the pandemic environment."

Maternal viral infections can affect fetuses through multiple pathways, from direct transmission through the placenta to inflammatory responses that disturb in-utero metabolism and negatively affect growth. While direct maternal-fetal transmission of the virus and severe birth defects appear to have been rare during previous coronavirus outbreaks, there were increases in preterm delivery and low birth weight during both the 2002 SARS and 2009 H1N1 influenza outbreaks, which are possible consequences of increased inflammation.

While studies on COVID-19 and pregnancy are still in their early stages, there have already been some concerning results that merit a closer look in ongoing studies, the authors wrote. Increased rates of preterm birth may be linked to maternal SARS-CoV-2 infections, and other studies indicate that severe illness is correlated with a higher risk of stillbirth. Other potential dangers, including the increased risk of blood clots presented by both pregnancy and severe COVID-19, also need further study.

"We suggest that to capture the consequences of viral exposure in utero for childhood development and adult health, COVID-19 birth cohort studies consider immediate collection of data from the mother, fetus, neonate, and placenta," Easterlin said. "These initial data should be followed by analysis of child growth and development and lifelong study of health, behavioral patterns, and cognitive functioning."

In addition to the direct risks posed by infection, the COVID-19 pandemic has also increased levels of stress, unemployment, food insecurity, and domestic violence, and diminished or disrupted prenatal care. For these reasons, the researchers suggest that cohort studies also include non-infected mothers and children as well as compare the COVID-19 cohort to children born before or after the pandemic and include various socioeconomic measures.

"The inclusion of information on social and economic stresses will allow comparisons between countries taking different measures to reduce spread of the virus," Crimmins said. "These types of comparisons may give us further insights beyond the effects of COVID, such as socioeconomic and social policies that may decrease risk of preterm birth."

Early-life events, such as the exposure to air pollutants, increases the risk of chronic lung disease in young adulthood, according to new results by researchers at Karolinska Institutet, Sweden, published in the European Respiratory Journal and Thorax. The studies add to the growing evidence that chronic lung disease in adulthood can be traced back to childhood.

Chronic bronchitis and chronic obstructive pulmonary disease (COPD), with the hallmark features phlegm and irreversible airflow limitation, respectively, are lung diseases known to affect adults with a history of long-term smoking.

"To our surprise, we found the prevalence of chronic bronchitis and irreversible airflow limitation to be rather high (5.5% and 2.0%, respectively), considering the young age of the study participants." says senior author Erik Melen, professor and paediatrician , Department of Clinical Science and Education, Karolinska Institutet, Sodersjukhuset.

"Those diseases are usually diagnosed in patients older than 50 years of age", comments further co-author Anders Linden, professor and pulmonologist, Institute of Environmental Medicine.

In the present studies, the researchers used data from birth up to age 24 years from the follow-up of the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child (Barn), Allergy, Milieu, Stockholm, Epidemiological), which includes 4,089 participants from the Stockholm area recruited 1994-96.

Analyses performed by PhD student Gang Wang showed that smoking as well as early-life air pollution exposures and childhood asthma are risk factors for chronic bronchitis, whereas breast-feeding was identified as a protective factor.

In addition, the early-life risk factors for development of irreversible airflow limitation were recurrent lung infections, asthma, and exposure to air pollution.

"The levels of air pollutants in the current study mainly reflect local emissions from road traffic, which implies that this preventable risk factor may play an important role in the development of chronic lung disease in young adults." says professor Erik Melen.

Given that air pollution levels in Stockholm are comparatively low by international standards, this makes the current findings very important in a global context. And despite the young participants' age, active smoking was linked to chronic bronchitis, which underlines the negative health effects from even a limited period of exposure to tobacco smoke.

"In conclusion, our two novel studies demonstrate that chronic bronchitis and irreversible airflow limitation do exist in young adults and emphasize the importance of early-life events for maintaining lung health during adulthood. The take home-message is: If you want to prevent disease, early prevention is the key to success."

PITTSBURGH, Nov. 12, 2020 - In an analysis published today in the American Journal of Preventive Medicine, researchers from the University of Pittsburgh Graduate School of Public Health demonstrate positive effects of the Affordable Care Act (ACA) Medicaid expansion on rates of early cancer diagnosis.

The study showed that health insurance expansions increased early-stage cancer diagnoses, while rates of late-stage cancer decreased.

"We used cancer diagnosis rates as a marker of access to care," explained lead author Lauren Lin, B.S., a medical student at Pitt School of Medicine. "An increase in early-stage cancer diagnoses means that people who didn't have health care before the Medicaid expansion got a chance to see a primary care physician and get screened."

As the U.S. Supreme Court hears arguments this week that could decide the future of the ACA, results presented in the manuscript make a strong case that striking down the law would hurt the nation's health.

"Our study adds to the literature demonstrating the positive health effects of Medicaid expansion," said senior author Coleman Drake, Ph.D., assistant professor in Pitt Public Health's Department of Health Policy and Management. "This is another case where, depending on the Supreme Court's ruling, the beneficial effects of preventive care provided by Medicaid expansion could disappear."

The scientists used data collected from cancer registries to track cancer diagnoses pre- and post- Medicaid expansion across different states. They found an immediate increase in early-stage cancer diagnoses within a year of ACA expansion, and a slight reduction in late-stage cancer diagnoses after three years.

"It is important to remember that while the ACA was passed 10 years ago, the key provisions weren't implemented until 2014," said co-author Lindsay Sabik, Ph.D., associate professor of health policy and management at Pitt Public Health, and member of the UPMC Hillman Cancer Center. "Because we often don't see the effects immediately, it's important for us to keep studying the long-term consequences of health care reform."

Bottom Line: Enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research

Author: Leopoldo Segal, MD, director of the Lung Microbiome Program, associate professor of medicine at the New York University Grossman School of Medicine, and member of NYU Langone's Perlmutter Cancer Center

Background: "The lungs were long thought to be sterile, but we now know that oral commensals--microbes normally found in the mouth--frequently enter the lungs due to unconscious aspirations," said Segal. While many studies have demonstrated the impact of the gut microbiome on cancer, the impact of the lung cancer microbiome remains unclear.

Prior research from Segal and colleagues showed that the presence of microbes in the lung can activate the immune response, leading to the recruitment of immune cells and inflammatory proteins such as the cytokine IL-17, which has been shown to modulate lung cancer pathogenesis. "Given the known impact of IL-17 and inflammation on lung cancer, we were interested in determining if the enrichment of oral commensals in the lungs could drive an IL-17-type inflammation and influence lung cancer progression and prognosis," Segal explained.

How the Study was Conducted and Results: In this study, Segal and colleagues analyzed the lung microbiomes of 83 untreated adult patients with lung cancer using samples obtained from diagnostic clinical bronchoscopies. Samples were analyzed to identify microbial composition and to determine which genes were expressed in lung tissue.

The researchers found that patients who had advanced-stage lung cancer (stages 3b-4) had greater enrichment of oral commensals in the lung than those who had early-stage disease (stages 1-3a). Furthermore, the enrichment of oral commensals in the lung was associated with decreased survival, even after adjusting for tumor stage. Poor prognosis was associated with the enrichment of Veillonella, Prevotella, and Streptococcus bacteria in the lung microbiome, and tumor progression was associated with the enrichment of Veillonella, Prevotella, Streptococcus, and Rothia bacteria.

In patients with early-stage disease, enrichment of Veillonella, Prevotella, and Streptococcus was associated with activation of the p53, PI3K/PTEN, ERK, and IL-6/IL-8 signaling pathways. A Veillonella strain, found to be enriched in patients with advanced-stage lung cancer, was associated with the expression of IL-17, cell adhesion molecules, cytokines, and growth factors, as well as with the activation of the TNF, PI3K-AKT, and JAK-STAT signaling pathways.

Segal and colleagues also examined the effects of the lung microbiome in a mouse model of lung cancer. They seeded Veillonella parvula in the lungs of mice with lung cancer to model the enrichment of oral commensals. This led to decreased survival, weight loss, and increased tumor burden and was associated with increased expression of IL-17 and other inflammatory proteins, increased recruitment of immune-suppressing cells, and increased activation of inflammatory pathways. To understand the role of IL-17 in lung cancer pathogenesis, Segal and colleagues treated Veillonella parvula-enriched mice with an antibody targeted to IL-17, which resulted in a significant decrease in tumor burden compared to mice treated with a control.

Author's Comments: "Given the results of our study, it is possible that changes to the lung microbiome could be used as a biomarker to predict prognosis or to stratify patients for treatment," said Segal. "Another exciting possibility is to target the microbiome itself or the host response to microbes as a form of cancer therapy. Our results using an antibody against IL-17 suggest that this could be an effective strategy."

Study Limitations: A limitation of the study was that the sample size prevented additional stratification of patients into subgroups based on the treatments they received. Additionally, since the lung microbiome was only sampled prior to treatment, changes resulting from treatment could not be assessed.

BOSTON - The expansion of health insurance in New York City under the Affordable Care Act (ACA) resulted in a significant reduction in the dispatch of ambulances for asthma emergencies, a study by Massachusetts General Hospital (MGH) has found. In a paper published in JAMA Network Open, researchers suggested that the likely reason for this decline is improved access to outpatient management of the chronic condition. The finding has major implications for the broader public health system as it seeks to control costs and better utilize fixed resources like emergency medical services (EMS).

"Our research suggests that giving access to affordable health insurance to people with asthma can rapidly reduce the frequency and severity of asthma exacerbations and lead to significantly fewer 911 calls," says Gregory Peters, MD, an investigator in the Department of Emergency Medicine at MGH and lead author of the study. "Our analysis of the effects of a major health policy change like the Affordable Care Act on a high-volume EMS system like the one in New York City provides valuable insights for public health officials."

Emergency medical services respond to millions of calls per year nationwide, despite constraints on ambulances and personnel. Additional pressure on these systems through increased utilization, as often occurs in cities and larger communities, can result in delayed care and even increased mortality, particularly in vulnerable neighborhoods. Asthma, because it is an "ambulatory care-sensitive" condition - meaning it can typically be controlled with the help of a primary care clinician and a treatment plan - has been the subject of prior studies on the impact of disease management on emergency services use under expanded insurance coverage. Those studies, however, yielded conflicting results.

MGH investigated more than 217,000 EMS dispatches for asthma-related emergencies in New York City, one of the nation's busiest EMS systems, between 2008 and 2018. The study showed that national implementation of the Affordable Care Act in January 2014 resulted in a significant decline in asthma-related EMS calls, from 261 dispatches per 100,000 people per year before enactment to 211 dispatches afterwards, a reduction of 20 percent.

"Expanded insurance has enormous potential to reduce 911 calls by providing individuals with chronic diseases, like asthma, with a way to better control their disease and thereby lower the risk of requiring emergency care," explains Alexander Ordoobadi, MD, a resident with the Department of Surgery at Brigham and Women's Hospital and co-lead author on the study. "Improved coverage gives patients access to long-term controller therapies to prevent exacerbations, and to rescue therapies to improve breathing. More than just medications, though, expanded insurance gives them access to clinicians who can counsel them on how to avoid asthma triggers and provide an asthma action plan."

The public health impact of expanded insurance for individuals who often go without any health coverage could extend well beyond asthma, the MGH research team indicated. "Epilepsy is another ambulatory care-sensitive condition where we might be able to significantly reduce seizures - and emergency calls - by ensuring that people have access to effective medicines and neurologists," stresses Peters. "Preventing 911 calls to already hard-pressed EMS systems through improved outpatient management of a host of conditions is a discussion that public policy makers need to revisit. The upcoming challenge to the Affordable Care Act before the U.S. Supreme Court makes this issue more timely than ever."

Team sport effectively counteracts diminished vascular function in women with high blood pressure, even several years after the onset of menopause. This, according to new research from the Copenhagen Center for Team Sports and Health at Department of Nutrition, Exercise and Sports, University of Copenhagen.

Estrogen loss associated with transition into menopause increases women's risk of developing cardiovascular disease and reduces their ability to benefit from training. However, a new study from the Center for Team Sports and Health at the Department of Nutrition, Exercise and Sports, University of Copenhagen demonstrates that postmenopausal women do benefit from playing small-sided floorball twice a week.

Effect of ten weeks of floorball

In the study, a group of postmenopausal women with high blood pressure and a control group with normal blood pressure participated in bi-weekly floorball training for ten weeks.

For the women with high blood pressure, floorball training reduced vascular stiffness and lead to a decrease in blood pressure by 15 (systolic) and 9 (diastolic) mmHg in the hypertensive women. This is significant and corresponds to a 40% lower risk of death by heart attack and a 30% reduction for coronary artery disease, which is characterized by reduced oxygen supply to the heart.

The group of women with normal blood pressure had slightly elevated blood pressure at the onset of the study, which is common among inactive postmenopausal women. They too experienced a noteworthy 10 mmHg decrease in systolic blood pressure with the floorball training.

Associate Professor Thomas P. Gunnarsson of the Department of Nutrition, Exercise and Sports is enthused that just two workouts a week resulted in such a pronounced effect on women's health:

"The study demonstrates that team sport among postmenopausal women is such an effective form of exercise that, with only two workouts a week, there are significant improvements in blood pressure, vascular function and body composition."

Reduction of the dangerous fat

One of the study's other interesting outcomes was also that the postmenopausal women experienced a noteworthy 10% reduction of visceral fat mass (the 'dangerous' fat found between internal organs). Furthermore, total fat mass decreased by half-a-kilogram.

According to Professor Jens Bangsbo, head of the Copenhagen Center for Team Sports and Health, it is especially noteworthy that these results emerge from a group of women with no prior experience with floorball:

"The study supports the numerous health benefits from team sports participation and provides us with a deeper understanding of training adaptations associated with team sport, which creates high motivation among postmenopausal women. Furthermore, the lack of experience with floorball was not a limitation in the womens´ability to achieve excellent health results in a relatively short time."

The results are promising especially as it has been believed that vascular smooth muscle in postmenopausal women cannot change with exercise. The study contradicts that notion.

The new findings contribute to an increasing body of knowledge about the mechanisms involved in high blood pressure among postmenopausal women, as well as the types of exercise that can effectively counteract the negative consequences of loss of estrogen with time in the postmenopausal state.

About the study:

17 women participated in the study. All participants had their last menstrual cycle at least six years prior to enrollment in the study.

The women played bi-weekly floorball for 10 weeks. Matches from 2 vs. 2 to 5 vs. 5 were played.

Systolic and diastolic blood pressure decreased by 15 and 9 mmHg respectively in the hypertensive group of postmenopausal women, while systolic blood pressure decreased by 10 mmHg in the control group.

Deteriorated vascular function can lead to hypertension. In the study, it was observed that vascular smooth muscle cell function was reduced by 30-40% in the women with high blood pressure in comparison with the control group.

The study demonstrated that vascular function can be improved significantly in postmenopausal women after a period of playing floorball, even among women with no prior experience with the sport. After training, there was no difference in the vascular function between the groups.

Researchers analyzing blood samples from blood donors across Kenya estimate that by June 2020, when many COVID-19 deaths were expected in the country but hadn't occurred at such scale, 4.3% of Kenyans had antibodies to the virus. This suggests SARS-CoV-2 exposure has been more extensive than indicated by case-based surveillance in Kenya, the authors say. Their results will help guide the pandemic response in a region where economic effects of lockdown - including for the way it disrupts routine medical care to women and children - have proven particularly debilitating. Africa accounts for 17% of the global population but by late July 2020, despite evidence of several months of SARS-CoV-2 transmission, it accounted for only 5% of the global COVID-19 cases and 3% of the global COVID-19 deaths. In Kenya, the first case of SARS-CoV-2 was reported in mid-March 2020, followed quickly by the institution of lockdowns. By end of July, however, national surveillance recorded 20,636 cases and 341 deaths in Kenya - an increase notably slower than the epidemic in parts of China, Europe and the United States. Seeking to understand this pattern, Sophie Uyoga and colleagues conducted one of the first field-based seroprevalence surveys in Africa. They analyzed samples collected from more than 3,000 blood transfusion donors from late April to mid-June 2020. Using a highly specific assay, the authors report a crude seroprevalence of 5.6% in this group. Adjusting for the age-sex structure of Kenya, the authors estimate an overall seroprevalence of 4.3%, peaking in younger age groups, which is consistent with other studies. The authors offer several potential explanations for why Kenya has seen relatively lower cases and deaths even as SARS-CoV-2 exposure appears considerable, including the steep demographic age-pyramid in Kenya, which results in a smaller vulnerable age group. The results of their study, say the authors, support "the impression that disease may be attenuated in Africa."

The accuracy of a rapid finger-prick antibody test for SARS-CoV-2, the virus responsible for covid-19 infection, may be considerably lower than previously suggested, finds a study published by The BMJ.

The results suggest that if 10% of people given the test had previously been infected, around 1 in 5 positive test results would be incorrect (false positive results).

These conclusions contrast with an earlier (not yet peer reviewed) study suggesting that the test gives no false positive results.

The findings suggest the test can deliver a sufficient degree of accuracy for surveillance studies of the population, but laboratory confirmation of positive results is likely to be needed if these tests are to be used to provide evidence of protection from the virus.

The AbC-19TM Rapid Test uses a drop of blood from a finger-prick to see if it's likely that someone has previously been infected with SARS-CoV-2. It gives results in 20 minutes, without the need to go to a laboratory, and is approved for use by health professionals in the UK and EU.

The latest research was commissioned by the Department of Health and Social Care and conducted by scientists from Public Health England and the Universities of Bristol, Cambridge and Warwick.

Scientists tested blood samples in a laboratory from 2,847 key workers (healthcare, fire, and police staff) in England in June 2020.

Of these, 268 had a previous PCR (positive polymerase-chain reaction) positive result so were "known positives" while the remaining 2,579 had unknown previous infection status. A further 1,995 pre-pandemic blood samples were also tested as "known negatives."

Based on a series of analyses, the researchers estimated the specificity of the AbC-19 test (ability to correctly identify a true negative sample) to be 97.9%, meaning that 2.1% of people who did not have a previous SARS-Cov-2 infection incorrectly tested positive.

They estimated the sensitivity of the AbC-19 test (ability to correctly identify a true positive sample) to be 92.5% based on PCR confirmed cases but considerably lower (84.7%) in people with unknown previous infection status prior to antibody testing.

This difference is probably due to the test being more sensitive when antibody levels are higher, explain the researchers. As people with a positive PCR result tended to have more severe disease, it is likely that they would have produced more antibodies.

They say the lower figure of 84.7% is probably a more realistic estimate of test sensitivity in the real world, if people were to choose to take the test to find out their own previous infection status. This means that 15.3% of people with a previous SARS-CoV-2 infection would be missed.

Putting these findings into context, the researchers say that, if 1 million people were tested with AbC-19, of whom 10% had been previously infected with SARS-CoV-2, there would be 18,900 false positive results. Overall, about one in five positive results would be wrong.

They also found that trained laboratory staff noted the test result band was often weak and disagreed on whether the result was positive or negative for almost 4% of AbC-19 tests. This implies that test accuracy could be lower still if the test was used at home by members of the public.

This is a large study, using data from individuals with both known and unknown previous infection status, but the authors do highlight some limitations.

For example, the test was evaluated in a laboratory, rather than having participants perform the test themselves, which may have overestimated performance, and the study included few people aged over 65 years, suggesting the need for further evaluation of the test in older ages when risk of severe covid-19 is substantially higher.

It is possible that other lateral flow devices detecting antibodies to SARS-CoV-2 may also work less well at lower antibody concentrations; while this study did not investigate this, the authors note that their work "highlights the scope for overestimation of SARS-CoV-2 antibody test sensitivity in other studies in which sensitivity has been estimated only from PCR confirmed cases."

The UK Government has placed an order for one million AbC-19 tests for research purposes, to help build up a picture of how the virus has spread across the country.

In a linked editorial, Dipender Gill at Imperial College London and Mark Ponsford at Cardiff University, say this study "identifies notable limitations of the UK government's antibody test of choice and provides good evidence that its specificity in a "real life" setting is highly unlikely to be 100%."

They call for further work to clarify the relation between circulating antibody levels and immunity to SARS-Cov-2, and say "a clear message must be communicated to the public that positive results from these assays do not provide evidence of immunity."

"Apart from limited surveillance to estimate the proportion of a population that has been infected, widespread use of this assay in any other role could risk considerable harm," they conclude.

Women who stop using some forms of contraception may have to wait up to eight months before their fertility returns, suggests research published online in The BMJ.

US and Danish researchers measured the delay in return of fertility in women after use of a variety of contraceptive methods. They found that the time until fertility returned varied depending on which method was used. The return to fertility did not depend on how long the woman had been using contraceptives.

Globally, about 22% of reproductive-aged women used hormonal contraception in 2019. Male condoms and oral contraceptives are the most commonly used methods in North America and Europe, but long-acting reversible contraceptive (LARC) methods such as intrauterine devices (IUDs), implants, patches and injectable contraceptives have become increasingly popular globally.

Previous studies on the return to fertility after use of long-acting reversible contraceptives have been small and inconsistent, leaving many questions unanswered. Earlier research has focused mainly on the effects of oral contraceptives, with most studies showing short delays of approximately three months in the return of fertility after women stopped taking them.

To round out the picture, a team of Boston University School of Public Health researchers led by Jennifer Yland, in collaboration with Aarhus University in Denmark, set out to evaluate the association between pre-pregnancy use of a variety of contraceptive methods and the subsequent probability of becoming pregnant (fecundability).

For their study, the researchers pooled data from three studies that altogether involved nearly 18,000 women from Denmark and North America who planned pregnancies between 2007 and 2019.

At the start of the study, the women reported their contraceptive histories, as well as personal, medical, and lifestyle information.

Follow-up questionnaires were sent every two months for up to 12 months or until they reported they had become pregnant. More than 80% of participants completed at least one follow-up questionnaire.

Overall, there were 10,729 pregnancies recorded in these women during 66,759 menstrual cycles of observation. Approximately 56% of women conceived within 6 cycles of follow-up, and 77% within 12 cycles.

The most commonly reported method of contraception was oral contraceptives (38%), followed by barrier methods such as condoms, diaphragm and sponge (31%), and natural methods such as withdrawal, and avoiding sex when fertile (15%).

Approximately 13% of women used long-acting reversible contraceptive methods; the most frequently used of these were IUDs - 8% of women used the hormonal IUD and 4% of women used the copper IUD as their last method of contraception.

Women experienced short-term delays in a return to fertility if they had recently stopped using oral contraceptives, the contraceptive ring, and some long-acting reversible contraceptive methods, compared with users of barrier methods.

Women who used injectable contraceptives had the longest delay in return of normal fertility (five to eight cycles), followed by users of patch contraceptives (four cycles), users of oral contraceptives and vaginal rings (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles).

The study had important limitations. The authors did not have data on the date of the last injection for women who used injectable contraceptives, and instead relied upon self-reported time since discontinuation of contraception for all methods studied.

Nevertheless, the results indicate that return of normal fertility varies substantially by contraceptive method.

The authors noted that: "Our results, although imprecise, indicate little or no lasting effect of long term use of these methods on fecundability .... these findings might inform clinical recommendations on contraceptive decision making."