Body

Washington, DC - June 25, 2020 - Due to the rapid spread of COVID-19, there is an increasing shortage of personal protective equipment (PPE) crucial to protecting health care workers from infection. N95 respirators are recommended by the CDC as the ideal protection method from COVID-19 and, although traditionally single-use, PPE shortages have necessitated the need for reuse. New research published this week in mBio an open-access journal of the American Society for Microbiology, describes an effective, standardized method of decontamination for hospitals and health care centers facing N95 respirator shortages.

The researchers, from Beth Israel Deaconess Medical Center, Harvard University and Massachusetts General Hospital, have detailed a reproducible decontamination approach that all health care workers would be able to utilize. "We identified an effective method of N95 decontamination by microwave-generated steam utilizing universally accessible materials. Our method resulted in almost complete sterilization after only 3 min of treatment and did not appear to affect the integrity of N95 filtration or fit with repeated treatment," the researchers write.

LONDON, ONTARIO - A team from Lawson Health Research Institute and Western University are the first in the world to profile the body's immune response to COVID-19. By studying blood samples from critically ill patients at London Health Sciences Centre (LHSC), the research team identified a unique pattern of six molecules that could be used as therapeutic targets to treat the virus. The study is published this week in Critical Care Explorations.

Since the pandemic's start there have been reports that the immune system can overreact to the virus and cause a cytokine storm - elevated levels of inflammatory molecules that damage healthy cells.

"Clinicians have been trying to address this hyperinflammation but without evidence of what to target," explains Dr. Douglas Fraser, lead researcher from Lawson and Western's Schulich School of Medicine & Dentistry and Critical Care Physician at LHSC. "Our study takes away the guessing by identifying potential therapeutic targets for the first time."

The study included 30 participants: 10 COVID-19 patients and 10 patients with other infections admitted to LHSC's intensive care unit (ICU), as well as 10 healthy control participants. Blood was drawn daily for the first seven days of ICU admission, processed in a lab and then analyzed using statistical methods and artificial intelligence (AI).

The research team studied 57 inflammatory molecules. They found that six molecules were uniquely elevated in COVID-19 ICU patients (tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10 and elastase 2).

The team also used AI to validate their results. They found that inflammation profiling was able to predict the presence of COVID-19 in critically ill patients with 98 per cent accuracy. They also found that one of the molecules (heat shock protein 70) was strongly associated with an increased risk of death when measured in the blood early during the illness.

"Understanding the immune response is paramount to finding the best treatments," says Dr. Fraser "Our next step is to test drugs that block the harmful effects of several of these molecules while still allowing the immune system to fight the virus."

What The Article Says: How to best treat patients with severe mental illness during the COVID-19 pandemic is detailed in this article.

Authors: Kai G. Kahl, M.D., of the Hannover Medical School in Hannover, Germany, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapsychiatry.2020.1701)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Editor's Note:

On June 24th, an error occurred and the incorrect press release was attached to the PLOS paper: The association between long term exposure to low level PM 2.5 & mortality in the state of Queensland, Australia. A Modelling study with a differences in differences approach. Please see the correct copy.

A landmark study of more than 240,000 deaths in Queensland over a 15-year period to 2013 has found even low levels of PM2.5, fine particulate matter found in air pollution, results in an increased risk of death from diseases such as cardiovascular and respiratory disease.

Importantly, the study showed that for every 1 ug/m3 increase in PM 2.5 there is a 2 percent increased risk of early death – and that these pollutants can kill even when they are at less than the current World Health Organization (WHO) annual standards.

The study, led by Professor Yuming Guo and Dr Shanshan Li from the Monash University School of Public Health and Preventive Medicine, linked death rates to postcode and satellite data on air quality.

While overall concentrations of PM2.5 were low in Queensland during the study - between 1 and 9 ug/m3 (highest in Brisbane) - it still impacted death rates. The WHO annual standard for safety is 10 mg/m3.

Air pollution containing PM2.5 was identified in 2015 as the fifth leading cause of mortality but this study is the first to link very low levels to increased mortality and to show that – as the particulate matter increases – so does the risk of disease and death.

The study, published in PLOS Medicine, looked at 242,320 deaths in 7 categories: mental and behavioural disorders, and diseases of the nervous system, circulatory system, respiratory system, digestive system and genito-urinary system, with an emphasis on respiratory and cardiovascular conditions, according to Professor Guo.

“What we found is that even very low levels of air pollution can have a serious effect on health and hasten death, and there is a potential threshold around 4.5 ug/m3 above which there is increased risk of death. When renewing the air quality standard, this threshold should be considered” he said.

Previous Animal studies have found PM2.5 can go from the lungs into the bloodstream and into specific organs, leading to oxidative stress, inflammation and plaque instability, potentially causing stroke or heart disease.

New research by a multidisciplinary collaboration between Queen Mary University of London, Asthma UK Centre for Applied Research (AUKCAR) University of Edinburgh, University of Nottingham, University of Cambridge and charity Asthma UK, published in the Journal of Medical Internet Research, looks at the characteristics of superusers who are actively engaged in the Asthma UK online community and Facebook group to help healthcare professionals better understand the role they play in supporting the management of long-term conditions.

The role of the superuser

Online health communities help people to self-manage certain aspects of their long-term conditions better through harnessing support and knowledge held by other users in the network. They are mostly run on a voluntary basis by their users. Superusers (the 1 per cent highly active users) play a central role in these communities as a result of the characteristics of their online activity and their constant engagement.

Online health communities offer high potential for cost-effectiveness in helping to manage long-term conditions. Therefore, understanding the mechanisms of online health communities' effectiveness, how they are organised and how they evolve over time is key. Previous work by the researchers looking at the Asthma UK online community has shown the presence of 20-30 superusers active on a weekly basis among 3,345 users. Removal of these superusers would make the network collapse into isolated non-connected groups. Thus, superusers are responsible for holding the communities together.

Without superusers there would be no effective spread of information and support within the community. However, up until now there has been little research into the characteristics of superusers. This study explores who they are, their motivations behind their engagement, the difficulties they face and what role they wish for healthcare professionals to play in health social media.

Highly motivated, altruistic, mostly female individuals

The researchers found that superusers in the Asthma UK online community and Facebook group are patients and mothers of children with asthma of a wide age range. They have a strong intrinsic motivation behind their engagement and their behaviour is self-endorsed, reflecting autonomy. Curiosity about asthma and its medical treatment was a main reason why they engage with the community, and engagement is often determined by availability of spare time when they were off-work due to asthma exacerbations or retired. Their engagement increased over time as participants furthered their familiarity with the online health community, their interest in community members, and their knowledge of asthma and its self-management.

Extrinsic motivation such as financial rewards was not relevant, as their reward came from helping and interacting with others. However, superusers do experience moral pressure to monitor health social media, answer any requests of help, rectify any inappropriate advice (misunderstandings about asthma and its treatment, "miracle cures" or dangerous ideas), or address users who are not seeking medical help when appropriate. These are things that superusers found difficult and stressful to deal with at times. Despite this, most healthcare professionals are not aware of their patients' engagement with health social media.

Reassuringly, superusers also show judgement about the complexity of coping with the illness and the limits of their advice, knowing when to defer to healthcare providers for appropriate medical advice and intervention.

Olivia Fulton, co-author of the paper and superuser of a large patient advocate network via WEGO Health, said: "I think no matter the condition, superuser traits are the same; I don't think it's unique for certain conditions like asthma. Superusers tend to have long-lived experience of the condition and seek out the most up-to-date information so they know where to direct people should the need arise. Many have been healthcare or allied healthcare professionals but have had to stop work due to ill health and therefore feel that by supporting an online forum, they are still doing something purposeful.

"Superusers are an underutilised ally because often we will see questions from someone newly diagnosed who has felt too embarrassed to ask their GP or nurse, but feel a forum is a faceless platform where they can ask these questions. Although, I am not sure how healthcare professionals would be able to identify superusers among their patients, as I never considered myself as one before it was pointed out to me."

Future research

This study shines a light on a particular group of superusers active in the Asthma UK online community and Facebook group. Further research should also examine whether superuser traits are shared among highly connected individuals in other health social media (eg Twitter). Given the effectiveness in helping people to self-manage their conditions, the study poses the question as to whether superusers should be formally recognised as allies of the healthcare workforce.

Lead author Dr Anna De Simoni from Queen Mary University of London said: "As a GP, I have become more inquisitive with my patients about any potential engagement with health social media and support they may need. I believe clinicians can have an important role in conveying norms and values for engaging safely and positively in health social media. During the COVID-19 lockdown, patients with asthma have likely been relying even more on peer support from superusers. Superusers' activity, at the same time, generates the 'hardware of online connections' enabling the crowdsourcing of information and support."

The global COVID-19 pandemic could significantly increase the global burden of tuberculosis (TB) due to disruptions to health services, and delays to diagnosis and treatment, according to new estimates published in the European Respiratory Journal.

Before COVID-19, over 4,000 people were dying from TB every day. In countries where health services are strained, there is a fear that TB cases and deaths could rise significantly.

Researchers from the London School of Hygiene & Tropical Medicine (LSHTM) and Lancaster University estimated additional TB deaths and cases in China, India and South Africa over the next five years. They examined the impact of various reductions in social contacts and impacts on health services due to COVID-19.

The researchers hypothesised that social distancing might reduce TB incidence as Mycobacterium tuberculosis, the bacteria which causes the disease, is transmitted via droplets in the air - similar to the coronavirus.

However, even after taking into account this potential reduced TB transmission, the most likely scenario was estimated to result in more than 110,000 additional TB deaths.

In the worst case scenario where the impact of COVID-19 on health services is severe, this number could rise to up to 200,000 additional deaths.

First author Dr Finn McQuaid, Assistant Professor in Infectious Disease Epidemiology at LSHTM, said: "There is concern that the COVID-19 pandemic is resulting in decreased TB clinic attendance, delayed diagnosis and treatment. This is especially so in low- and middle-income countries where health services, or access to them, might be substantially disrupted. Early anecdotal information from China, India and South Africa suggests that the number of people being diagnosed and treated for TB has fallen significantly."

The team measured the effect of these factors on TB incidence and deaths in China, India and South Africa, three countries which make up approximately 40% of the global TB cases. They modelled different scenarios with various implementations of social distancing measures and health service disruption lasting for six months to estimate the impact of COVID-19 on global TB burden.

They found that if there is substantial health service disruption, such as a 50% reduction in TB cases detected and successfully treated, there would be an increase in both incidence and deaths from TB over the subsequent five years, regardless of the level of social contact.

The most probable scenario, based on the current information and distancing measures, suggests 6,000 additional deaths could occur in China, 95,000 in India and 13,000 in South Africa.

However, if social distancing measures are minimal and there is substantial health care disruption - based on 80% reduction in case detection and treatment success - the model predicts an 8-14% increase in cumulative deaths from TB over the next five years.

Dr McQuaid explained: "We need to act now to ensure innovative approaches to people-centric TB care are the focus, so that the fight to end this pandemic doesn't overwrite the hard-won gains made against this disease.

"Given that health service disruption far outweighs the benefit of social distancing, it is crucial to maintain and strengthen TB-related health services during, and after, COVID-19.

"It is also important to note that the decline of health services is likely to have a greater impact on drug-resistance TB patients, as they often require longer treatment. Additionally, we examined social distancing measures over a six month period, but with the potential of subsequent waves of the virus, the impact could last longer."

The authors acknowledge limitations of their work including that it did not take into account setting-specific differences within the countries, while the effect on service delivery needs to be investigated in greater detail. It also did not incorporate external factors of the COVID-19 pandemic, including increased poverty or reduced access to antiretroviral treatments in areas of high HIV prevalence.

Further research is required to examine these factors, as well as whether TB patients are at higher risk of severe COVID-19.

A type of virus that preys on bacteria could be harnessed to combat bacterial infections in patients whose immune systems have been weakened by the SARS-CoV-2 virus that causes the COVID-19 disease, according to an expert at the University of Birmingham and the Cancer Registry of Norway.

Called bacteriophages, these viruses are harmless to humans and can be used to target and eliminate specific bacteria. They are of interest to scientists as a potential alternative to antibiotic treatments.

In a new systematic review, published in the journal Phage: Therapy, Applications and Research, two strategies are proposed, where bacteriophages could be used to treat bacterial infections in some patients with COVID-19.

In the first approach, bacteriophages would be used to target secondary bacterial infections in patients' respiratory systems. These secondary infections are a possible cause of the high mortality rate, particularly among elderly patients. The aim is to use the bacteriophages to reduce the number of bacteria and limit their spread, giving the patients' immune systems more time to produce antibodies against SARS-CoV-2.

Dr Marcin Wojewodzic, a Marie Sk?odowska-Curie Research Fellow in the School of Biosciences at the University of Birmingham and now researcher at the Cancer Registry of Norway, is the author of the study. He says: "By introducing bacteriophages, it may be possible to buy precious time for the patients' immune systems and it also offers a different, or complementary strategy to the standard antibiotic therapies."

Professor Martha R.J. Clokie, a Professor of Microbiology at the University of Leicester and Editor-in-Chief of PHAGE journal explains why this work is important: "In the same way that we are used to the concept of 'friendly bacteria' we can harness 'friendly viruses' or 'phages' to help us target and kill secondary bacterial infections caused by a weakened immune system following viral attack from viruses such as COVID-19".

Dr Antal Martinecz, an expert in computational pharmacology at the Arctic University of Norway who advised on the manuscript says: "This is not only a different strategy to the standard antibiotic therapies but, more importantly, it is exciting news relating to the problem of bacterial resistance itself."

In the second treatment strategy, the researcher suggests that synthetically altered bacteriophages could be used to manufacture antibodies against the SARS-CoV-2 virus which could then be administered to patients via a nasal or oral spray. These bacteriophage-generated antibodies could be produced rapidly and inexpensively using existing technology.

"If this strategy works, it will hopefully buy time to enable a patient to produce their own specific antibodies against the SARS-CoV-2 virus and thus reduce the damage caused by an excessive immunological reaction," says Dr Wojewodzic.

Professor Martha R.J. Clokie's research focuses on the identification and development of bacteriophages that kill pathogens in an effort to develop new antimicrobials: "We could also exploit our knowledge of phages to engineer them to generate novel and inexpensive antibodies to target COVID-19. This clearly written article covers both aspects of phage biology and outlines how we might use these friendly viruses for good purpose."

Dr Wojewodzic is calling for clinical trials to test these two approaches.

"This pandemic has shown us the power viruses have to cause harm. However, by using beneficial viruses as an indirect weapon against the SARS-CoV-2 virus and other pathogens, we can harness that power for a positive purpose and use it to save lives. The beauty of nature is that while it can kill us, it can also come to our rescue." adds Dr Wojewodzic.

"It's clear that no single intervention will eliminate COVID-19. In order to make progress we need to approach the problem from as many different angles and disciplines as possible." concludes Dr Wojewodzic.

The use of cholesterol-lowering drugs called statins is associated with a lower death rate and a lower incidence of mechanical ventilation in patients hospitalized with Coronavirus disease 2019 (COVID-19), researchers report June 24 in Cell Metabolism. The large-scale retrospective study also showed that mortality risk and other negative outcomes were not increased by combination therapy consisting of statins and blood pressure-lowering drugs called angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).

"These results support the safety and potential benefits of statin therapy in hospitalized patients with COVID-19 and provide a rationale for prospective studies to determine whether statins confer protection against COVID-19-associated mortality," says senior study author Hongliang Li of Wuhan University. "Moreover, our findings represent an important contribution to the accumulating clinical evidence regarding the beneficial or detrimental effects of prescribing ACE inhibitors or ARBs to patients with COVID-19."

Currently, there is no vaccine or specific antiviral drug approved to prevent or treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes COVID-19. Because a vaccine or drugs for COVID-19 will likely not be available for months or even years, repurposing clinically approved therapies might be a more attractive option. Statins may serve such a purpose because these drugs slow the progression of lung injury in animals, improve immune cell responses, and strongly reduce inflammation, which is likely responsible for severe COVID-19 complications such as organ damage.

Although statins generally have an excellent safety profile in humans, animal studies have shown that they increase the expression of angiotensin-converting enzyme II (ACE2)--the receptor that SARS-CoV-2 binds to and uses to enter host cells. On the other hand, animal studies have also shown that ACE2 protects organs such as the lungs against virus-induced injury. As a result, it has not been clear how clinical outcomes in patients with COVID-19 are affected by the use of statins, either alone or in combination with ACE inhibitors and ARBs, which are commonly prescribed with statins and also increase ACE2 expression in animals.

To address this gap in knowledge, Li and his collaborators carried out a retrospective study of 13,981 COVID-19 patients admitted to 21 hospitals in Hubei Province, China. Among these patients, 1,219 used statins, primarily atorvastatin at an average dose of 20 mg/day. Among patients with hypertension (i.e., high blood pressure), 319 used statins combined with ACE inhibitors or ARBs, and 603 used statins combined with other antihypertensive drugs.

The researchers analyzed mortality rates and secondary outcomes, including the incidence of invasive mechanical ventilation, admission to intensive care units, acute respiratory distress syndrome, and liver, kidney, or heart injury. Because patients on statins were older and had a higher incidence of lung lesions and chronic diseases, the researchers also performed analyses on subsets of patients that were matched for baseline characteristics such as age, disease severity, and pre-existing conditions.

Over a 28-day follow-up period, statin use was associated with a lower death rate and a lower incidence of mechanical ventilation. Statin use was associated with 5.5% mortality rate, compared to 6.8% without statin use, representing a 19% decrease. When the researchers examined the matched cohort of 861 patients in the statin group and 3,444 patients in the non-statin group, statin use was associated with a 45% decrease in the mortality rate, from 9.4% to 5.2%. In the matched cases, statin use was also associated with lower levels of three inflammation biomarkers, and a lower incidence of acute respiratory distress syndrome and admission to intensive care units.

In the unmatched sample, mortality and secondary outcomes over 28 days were not affected by the use of statins combined with ACE inhibitors or ARBs, compared to combination therapy consisting of statins and other antihypertensive drugs. But in the matched cohort with 204 patients in each group, the use of statins combined with ACE inhibitors or ARBs versus other antihypertensive drugs was associated with a 65% drop in the death rate (3.4% versus 9.8%) and a lower incidence of heart injury and acute respiratory distress syndrome.

"Although the use of an ACE inhibitor or ARB was once speculated to be potentially harmful in patients with COVID-19, several professional societies have recommended the continued use of these drugs in patients with COVID-19 and pre-existing hypertension," Li says. "To our knowledge, the results from this study are the first clinical evidence supporting the notion that the risk of COVID-19 mortality is not increased by using ACE inhibitors or ARBs in combination with statin treatment."

However, the study does not prove that the lower death rate of patients with COVID-19 is directly caused by the use of statins, either alone or in combination with ACE inhibitors or ARBs. For now, it is also unclear whether the findings apply to non-hospitalized patients with COVID-19. Moreover, the results of retrospective studies should be interpreted with caution, Li says. "Although these data do provide supportive evidence for the safety of statins or the combination of statins with ACE inhibitors or ARBs for treatment in patients with COVID-19, further randomized controlled trials to prospectively explore the efficacy of statins on COVID-19 outcomes appear justified."

PHILADELPHIA (June 24, 2020) - Sudden school closures in the United States were undertaken to reduce COVID-19 transmission this spring. Those closures were not typical, and how and when schools reopen will create a set of new norms, with unique stressors for students, families, school personnel, and communities.

The challenges of reopening are not easy, and there will be a need to maintain systematic quality control in the face of prescribed approaches changing rapidly. In an editorial in The Journal of School Nursing, Catherine C. McDonald, PhD, RN, Assistant Professor of Nursing at the University of Pennsylvania School of Nursing (Penn Nursing) and a Senior Fellow with the Center for Injury Research and Prevention at Children's Hospital of Philadelphia, addresses a number of challenges that will likely need to be met and how school nurses are positioned to keep children healthy, safe, and ready to learn.

"There is hope that in fall 2020, schools will be well on their way to reopening. No matter the scenario, we know that school nurses will be ready to lead in the steps to keep their schools healthy," writes McDonald. "School nurses will take on COVID-19 specific roles in advising, planning, and implementation. They are key to student health, safety, and success, and at this time, their role could not be more important."

The editorial, "Reopening Schools in the Time of Pandemic: Look to the School Nurses," has been published online first and is set for publication in the upcoming August issue as well.

June 24, 2020 - Regions with an early interest in face masks had milder COVID-19 epidemics, according to a new letter-to-the-editor published in the American Journal of Respiratory and Critical Care Medicine.

In "COVID-19 and Public Interest in Face Mask Use," researchers from the Chinese University of Hong Kong shared findings from their analysis of how public interest in face masks may have affected the severity of COVID-19 epidemics and potentially contained the outbreak in 42 countries in 6 continents.

The authors noted that "In many Asian countries like China and Japan, the use of face masks in this pandemic is ubiquitous and is considered as a hygiene etiquette, whereas in many western countries, its use in the public is less common."

There was a clear negative correlation between the awareness or general acceptance of wearing a face mask and its infection rates. "One classic example is seen in Hong Kong," said Sunny Wong, MD, associate professor, Department of Medicine and Therapeutics, The Chinese University of Hong Kong.

"Despite [Hong Kong's] proximity to mainland China, its infection rate of COVID-19 is generally modest with only 1,110 cases to-date. This correlates with an almost ubiquitous use of face masks in the city (up to 98.8 percent by respondents in a survey). Similar patterns are seen in other Asian areas, such as Taiwan, Thailand and Malaysia. To date, there are more than two million cases in the U.S. and more than one million cases in Brazil.

While, the authors acknowledge that face masks are seen as important in slowing the rise of COVID-19 infections, it is difficult to assess whether it is more effective than handwashing or social distancing alone.

As cities in the U.S. and elsewhere put re-opening plans into effect, Dr. Wong said the use of face masks should be encouraged: "Face masks can help slow the spread of COVID-19, and have a relatively low cost compared to the health resources and death toll associated with the pandemic".

He added, "We believe that face mask use, hand washing and social distancing are all important components of the non-pharmaceutical measures against COVID-19."

CLEVELAND, Ohio (June 24, 2020)--Women with premature ovarian insufficiency (POI) become estrogen deficient at an early age, which makes them more vulnerable to the loss of bone mineral density. A new study suggests that use of continuous combined oral contraceptives may be especially effective in reducing bone mass loss. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Premature ovarian insufficiency occurs when a woman's ovaries stop working before the age of 40. This results in estrogen deficiency well before the age of natural menopause, which leads to a number of potential problems, including not only hot flashes but also sexual dysfunction, mood disorders, and increased risk for cardiovascular disease and dementia. Bone mineral density is also affected, most notably in the lumbar spine. Bone mass typically continues to increase up to age 30, although 90% of peak bone mass is acquired by age 18. The lack of estrogen accelerates the loss of bone mass, which for women with POI is especially problematic because it begins at a much earlier age than average.

The condition is typically treated with the prolonged use of hormone therapy (HT) to provide the estrogen a woman normally would have produced and to minimize the effect of its early loss. Two types of hormones are most often used for treatment in women with POI--a postmenopause estrogen-based HT regimen or an estrogen-containing contraceptive, often taken orally in what is known as a combined oral contraceptive.

The benefits of combined oral contraceptives have been evaluated in previous studies but focused primarily on women with normal ovarian function. In this new study, researchers sought to evaluate the association between the use of continuous combined oral contraceptives and the bone mass variation in women with POI compared with the low-dose and high-dose HT regimens typically used for symptom management in menopausal women.

The study found that the use of continuous combined oral contraceptives is a viable option for HT in women with POI because it resulted in the least amount of bone mass loss, especially when measured at the lumbar spine. The bone effects with combined oral contraceptives were similar in women using high-dose HT regimens and superior to those seen in women on low-dose HT regimens.

Study results appear in the article "Bone mass in women with premature ovarian insufficiency: a comprehensive study between hormone therapy and combined oral contraceptives."

"The results of this study support the use of combined oral contraceptives taken in a continuous fashion without a pill-free interval as an option for the treatment of women with POI--a regimen that may be particularly appealing for women who wish to avoid the chance of pregnancy. These results also show similar bone protection with high-dose hormone therapy regimens but not with low-dose regimens, lending further credence to the recommendation to use hormone therapy doses aimed at achieving physiologic levels for a premenopausal woman," says Dr. Stephanie Faubion, NAMS medical director.

Following a major clinical trial, clinicians find the drug allopurinol does not prevent worsening of kidney disease.

The Australasian Kidney Trials Network led a large, two-year study, known as CKD-FIX, to assess the effectiveness of allopurinol, in slowing the rate of decline in kidney function.

They found the drug is ineffective in treating the condition, despite up to 20 per cent of kidney disease patients being prescribed the medication.

Queensland Renal Transplant Service Medical Director and University of Queensland Professor of Medicine based at the Translational Research Institute, David Johnson, said until now there had been little robust evidence to demonstrate allopurinol's benefit in slowing the rate of decline in kidney function.

"We felt it was important to gather evidence of allopurinol's impact on patients with kidney disease who have never had gout," said Professor Johnson.

"In the CKD-FIX study, we compared the use of allopurinol to a placebo and found, to our surprise, that it made no difference to the rate of kidney function decline," he said.

"Based on these results we believe there is no benefit in prescribing this medication, unless there is an additional specific medical reason, such as gout. This much awaited, high-quality evidence will inform global clinical guidelines for patient treatment.

"It is important, though, that people with kidney disease who are already taking a medication like allopurinol to lower blood urate levels don't abruptly stop this treatment. They should discuss their kidney care management with their doctor first."

Lead Investigator-New Zealand, Dr Janak de Zoysa from the University of Auckland and Waitemata District Health Board said trials like CKD-FIX were very important as they allowed doctors to optimise clinical practice.

"Trials which show existing treatments to be not as effective as anticipated, allow for those medications to be stopped or not started in the first place, reducing unnecessary healthcare costs," said Dr de Zoysa.

Commercially available since the late 1960s, allopurinol helps the body reduce urate in the blood. High levels of the chemical are common among patients with chronic kidney disease, where it is associated with a higher risk of developing chronic kidney disease and its progression.

The George Institute for Global Health Senior Research Fellow and St George Hospital nephrologist, Associate Professor Sunil Badve said the widely held view that elevated blood urate levels were responsible for rapid decline of kidney function was probably wrong.

"Based on our study results, it appears that elevated blood urate levels are most likely an indicator of reduced kidney function rather than a cause of reduced kidney function," said A/Prof Badve.

The CKD-FIX study ran across 31 hospitals in Australia and New Zealand, with more than 369 patients -with stage 3 or 4 chronic kidney disease who were at increased risk of further progression - taking part in the trial.

The results from the study were published in The New England Journal of Medicine.

In the paper, the study authors reported a 35% reduction in blood urate levels, which was maintained throughout the two-year study period for patients prescribed allopurinol. Kidney function, however, declined at similar rates for two treatment groups; allopurinol -3.33 mL/min/1.73 m2/year (95% CI -4·11 to -2·55) and control -3.23 mL/min/1.73 m2/year (95% CI -3·98 to -2·47). There was no difference in the quantity of protein in the urine and blood pressure between the groups.

Approximately 1.7 million Australians and 400,000 New Zealanders aged 18 years and over have chronic kidney disease.

The adverse side effects of the social isolation measures implemented to combat COVID-19 include an increase in sedentary behavior and physical inactivity, which can contribute to a deterioration in cardiovascular health even in the short term. Older people and people with chronic diseases tend to be most affected.

The warning comes from a review article published in the American Journal of Physiology by researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil. According to the authors, the slogan “Stay at home” broadcast by governments and chief medical officers is unquestionably valid under the present circumstances but should be coupled with another: “Don’t stay still.”

“You need at least 150 minutes of moderate to vigorous physical activity per week to be considered active by the World Health Organization [WHO] and medical associations. Gyms, fitness centers and sports facilities will be open to a limited extent in the months ahead, even after confinement and quarantine measures are lifted. Physical activity in the home is a worthwhile alternative,” said Tiago Peçanha, first author of the article. Peçanha has a postdoctoral research scholarship from FAPESP.

The article reviews the scientific literature to compile evidence for the effects of short periods of physical inactivity on the cardiovascular system. Some of the studies cited show that between one and four weeks of bed rest can lead to cardiac atrophy and significant narrowing of peripheral blood vessels. Peçanha stressed that this is an aggressive model and does not reflect what happens during social confinement or quarantine. “However, other experiments reviewed in the article are a good match,” he said.

In one of these experiments, volunteers were asked to reduce their physical activity so that they took less than 5,000 steps in a week instead of more than 10,000 steps as usual. At the end of the period, the researchers observed a reduction in the diameter of the brachial artery (the main blood vessel in the arm), loss of blood vessel elasticity, and damage to the endothelium (the inner cell lining of all veins and arteries).

In other experiments, volunteers stayed seated for periods varying between three and six hours. This amount of inactivity was sufficient to cause vascular alterations, an increase in inflammation markers, and a rise in postprandial blood sugar.

“This first group of alterations observed in the studies have to do with functionality. In healthy volunteers, the heart and blood vessels function differently in response to inactivity,” Peçanha said. “In an extended period of inactivity, the alterations tend to become structural and are harder to reverse.”

Prolonged inactivity is particularly harmful for people with cardiovascular diseases and other chronic health problems, such as diabetes, hypertension, obesity or cancer. In older people, it can also aggravate loss of muscle mass (sarcopenia) and increase the risk of falls, fractures and other injuries. The FM-USP group recently published an article on this topic in the Journal of the American Geriatrics Society.

“These groups that are more vulnerable to the effects of inactivity are also high-risk groups for COVID-19 and will be staying at home for months. Ideally, they should find ways of staying active, such as doing housework, going up and down stairs, taking short walks, playing with children, or dancing in the living room,” Peçanha said. “The scientific evidence shows that getting exercise in the home is safe and effectively helps control blood pressure, reduces blood lipids, and improves body composition, quality of life and sleep.”

For high-risk groups, especially people who are not habitually active, Peçanha recommends supervision by health professionals, which can be performed remotely using cameras, smartphone apps and other electronic devices. “Studies show that an online environment favoring social support and interaction tends to motivate people to keep fit,” he said.

Fresh evidence

Data published in recent months by companies that sell smartwatches and exercise tracking apps suggest that the number of daily steps taken by users since the start of confinement has fallen.

“For example, Fitbit’s blog presents data for 30 million users showing a 7%-38% decline in daily step counts during the week ending March 22,” Peçanha said. “In Brazil, an internet survey by Raphael Ritti-Dias involving over 2,000 volunteers showed more than 60% saying they reduced their physical activity after the start of confinement or lockdown. All this evidence is preliminary, but studies are in progress to measure the effects on health of physical inactivity during social restrictions.”

One of these studies is being conducted at FM-USP as part of the Thematic Project “Reducing sedentary time in clinical populations: the Take A Stand For Health Study”. The principal investigator is Bruno Gualano, a co-author of the American Journal of Physiology article.

“We’re working with clinical groups associated with the Thematic Project, such as women with rheumatoid arthritis, patients submitted to bariatric surgery, and elderly subjects with mild cognitive impairment. They’re encouraged to take more exercise in the form of daily activities such as walking the dog or getting off the bus two stops prior to their destination. The effects on their health are being studied,” Peçanha said.

Since the implementation of social restrictions to contain the pandemic, the researchers have monitored a group of female rheumatoid arthritis patients more closely to measure their level of physical activity and compare it with the pre-pandemic level. “The patients are wearing accelerometers [electronic devices that measure physical activity and distance covered in a set period] at home,” Peçanha said. “We call them frequently to ask about quality of life and diet. A few researchers visit them at home to measure body weight, body composition and blood pressure and to take blood samples.”

Half of the volunteers will be encouraged to exercise at home. “We’ll send daily targets, instructions and text messages. At the end, we’ll compare the two groups and analyze the differences,” he said.

The article “Social isolation during the COVID-19 pandemic can increase physical inactivity and the global burden of cardiovascular disease” (doi: 10.1152/ajpheart.00268.2020) is available at: journals.physiology.org/doi/full/10.1152/ajpheart.00268.2020.

Journal

The Journal of Physiology

DOI

10.1152/ajpheart.00268.2020

First-of-its-kind study finds that black cancer survivors on these plans are far more likely to struggle to afford health care and medicine than their white counterparts, while black and white cancer survivors on other types of plans are equally unlikely to face these challenges.

The growing Black Lives Matter movement has brought more attention to the myriad structures that reinforce racial inequities, in everything from policing to hiring to maternal mortality. Now, a new Boston University School of Public Health (BUSPH) study points to a previously-unidentified factor widening the racial health gap: high deductible health plans.

Published in JAMA Network Open, the first-of-its-kind study finds that black cancer survivors on high deductible health plans face more cost-related barriers to care than white cancer survivors on the same plan, including needing to skip a medication or delay a refill to save money, and not being able to see a specialist.

For example, 22.8% of black versus 8.0% of white cancer survivors on high deductible plans skipped medication to save money. But among cancer survivors on other kinds of plans, 7.7% of black versus 5.4% of white patients skipped medication.

"As enrollment in high deductible health plans continues to rise, this has really concerning implications for racial equity among cancer survivors," says study lead author Dr. Megan B. Cole, assistant professor of health law, policy & management at BUSPH. High deductible plans now cover nearly a third of all people who have employer-sponsored health insurance, and half of cancer survivors with private insurance.

"Enrollment in HDHPs may compound the many structural inequities that black cancer survivors are already facing, which may further drive disparities in health outcomes for survivors," Cole says. "Policies that limit deductible sizes and extend cost-sharing subsidies to high-risk groups, while limiting the types of services to which a deductible applies, may help to mitigate observed effects.

"But more broadly, we need policies that really tackle the structural inequities and institutional racism that lie at the root of these disparities."

Cole and colleagues used National Health Interview Survey data from 2013 through 2018 on 3,713 adults with a past or current cancer diagnosis, and analyzed the relationships between race, health plan type, and eight common indicators of difficulty accessing care and medicine.

In addition to skipping medication, the researchers found major disparities in other areas:

Took less medication to save money: 24.6% of black versus 8.6% of white patients on high deductible plans (compared to 8.5% of black and 5.4% of white patients on other types of plans).

Delayed filling a prescription: 28.1% of black versus 7.7% of white patients on high deductible plans (compared to 16.2% of black and 7.1% of white patients on other types of plans).

Unable to afford to see a specialist: 14.9% of black versus 6.2% of white patients on high deductible plans (compared to 4.9% of black and 2.9% of white patients on other plans).

Overall, the researchers also found that the percentage of privately-insured cancer survivors on high deductible plans rose from 37% in 2013 to 50% in 2018.

NEW YORK, NY (June 24, 2020) -- The first-ever cardiac study of elite female basketball players in the United States shows how their hearts adapt to intense physical training.

The study of 140 WNBA players also provides physicians with a frame of reference when screening for cardiac problems in female athletes.

The research is the result of a long-standing collaboration among cardiologists and researchers at Columbia University Irving Medical Center and NewYork-Presbyterian, the National Basketball Association and Women's National Basketball Association, and the National Basketball and Women's National Basketball Players Associations that has also created a screening and monitoring program for the leagues and guidelines for NBA and WNBA team physicians. The research team has previously reported similar data on male NBA players.

The new research, published in JAMA Cardiology, also suggests that similar studies of female athletes are needed for other sports, which affect the heart in different ways.

Why study WNBA players?

Intense physical exercise increases the size, mass, and thickness of the walls of the heart.

"We call this 'athlete's heart,' and we've recognized this remodeling process for decades," says David J. Engel, MD, a sports cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center and senior author of the paper. "But nearly all published data on this describes athletic changes in the hearts of male athletes, and there is very little data on what an athletic heart looks like in elite female athletes and absolutely no data on the athletic heart in women who are professional basketball players."

Team physicians and physicians who care for athletes need to know what a healthy heart in elite athletes looks like, so that healthy hearts can be distinguished from those with signs of cardiac problems, including hypertrophic cardiomyopathy, an enlargement and thickening of the heart that can lead to life-threatening arrhythmias.

Among U.S. athletes, basketball players have been shown in epidemiologic studies to have the highest incidence of exercise-induced sudden cardiac death, though the incidence is lower for female athletes than for males.

In 2006, the NBA was the first professional sports league to implement a standardized preseason screening program that tests all of its players for heart disease.

"But without normative data on how training for professional basketball affects heart structure compared with non-athletes or athletes from other sports, it isn't easy to identify who is at risk," says Sofia Shames, MD, a cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center and the study's lead author.

Basketball strengthens heart

In the study, the researchers analyzed cardiac ultrasound data from the 2017 season in 140 WNBA athletes, all of whom had similar training.

The researchers found that the WNBA players generally have larger and thicker (more muscular) hearts than most women who are not athletes, and the differences can be attributed to a combination of the larger height of WNBA players and their physical conditioning.

According to heart disease screening guidelines, which are based on data from the general population, approximately 16% of the WNBA players could be inappropriately classified as having left ventricular enlargement.

"The general population is not particularly athletic, and a physician who sees a heart the size of many WNBA players' hearts would do further testing," Shames says. "But in this group of women, these larger hearts are within the normal range for the athletes' size and conditioning."

"Evaluating the WNBA players on a large scale allows us to have comparison data for the future. Up until this research, some players were being sidelined until further tests could be done," says Marci Goolsby, MD, team physician for the WNBA New York Liberty team, sports medicine physician at the Women's Sports Medicine Center of the Hospital for Special Surgery, and a co-author of the paper. "We now have a much clearer picture of how to interpret data from preseason echocardiograms, and we can better determine who requires further testing."

The hearts of the WNBA players had also strengthened in different ways than the hearts of other female athletes. More than half of the WNBA players had heart walls greater than 1 cm in thickness, compared with less than 10% of Italian female athletes from a variety of sports. The scans also showed that an important index of heart geometry -- the thickness of the heart muscle in relation to diameter -- was more prominent in the WNBA players compared to other female athletes.

"That's why we need reference data for players in each specific sport," Engel adds. "If WNBA team physicians relied on the data from the European studies to screen players for heart disease, they would still be left with clinical questions. Our research can hopefully serve as a stimulus for more studies of female athletes in other sports."