Body

Exercise can only improve strength in muscle-degenerating diseases when a specific type of muscle cell ages, report a Hokkaido University researcher and colleagues with Sapporo Medical University in Japan. Their findings utilizing mice models were published in the journal Nature Communications.

Idiopathic inflammatory myopathies are rare diseases that cause muscle weakness, inflammation, and fibrosis. In addition to drugs, exercise can be powerful therapy for some patients. But in cases of chronic inflammatory myopathy, exercise can actually induce inflammation and fibrosis in muscles. Scientists have been wanting to understand why exercise benefits some myopathies but not others.

Takako S. Chikenji of Hokkaido University collaborated with Yuki Saito and Mineko Fujimiya of Sapporo Medical University in Japan to investigate why a type of muscle cell, called fibro-adipogenic progenitors (FAPs), responds differently to physical exercise depending on the type of myopathy. These cells are a key regulator of the muscle stem cells needed for regeneration.

They investigated what happens when mice with myopathy exercise. In mice with acute muscle injury which simulates idiopathic inflammatory myopathy, they found FAPs initially increased but then returned to pre-damage levels after seven days. These FAPs eventually died and were cleared by cell-eating immune cells called phagocytes. In mice with chronic inflammatory myopathy, FAPs continued to proliferate for 14 days and were resistant to cell death and clearance by immune cells.

Investigating further, the team found that FAPs in mice with acute muscle injury showed strong signs of aging after exercise while FAPs in mice with chronic inflammatory myopathy didn't. They also found that normal FAPs induced regeneration of muscle cells after acute muscle injury while FAPs lacking a cellular aging-inducing factor didn't. These results together showed the aging of FAPs after exercise is necessary to establish a state of regenerative inflammation that induces muscle regeneration.

Moreover, the combination of exercise and administrating drugs which induce cellular aging restored FAP aging and improved muscle function and regeneration in mice with chronic inflammatory myopathy.

"Our findings demonstrate that exercise leads to muscle degeneration in chronic inflammatory myopathy because FAPs accumulate when they fail to age," says Takako S. Chikenji. "Pharmacological induction of FAP senescence dramatically improved the therapeutic effects of exercise in mice with chronic myopathy. Further research is needed to investigate whether this strategy could be used to treat this condition in humans."

The factors associated with men ending treatment for erectile dysfunction have been reviewed in a study published in IJIR: Your Sexual Medicine Journal. The most influential factors reported were treatment ineffectiveness, side effects, the quality of one's intimate relationship and cost of treatment. The review also highlights the importance of men's beliefs with regards to erectile dysfunction and its treatment and suggests that these beliefs are potentially modifiable.

Erectile dysfunction, the persistent inability to develop or maintain a penile erection during sexual activity, is thought to affect up to 10% of men under 40 years and 70% of men over 70 years. Treatment includes medications delivered orally. Where these fail or are contraindicated, treatments are available which are administered via injection, or via suppositories. Finally, penile implants are available where all other treatments have failed.

The lead author; Mr Paul Williams said: "Erectile dysfunction can have a negative effect on men's quality of life. However, this can potentially be improved with successful treatment for the condition. The findings from our research indicate that rates of discontinuation for treatment are high. Understanding the reasons for discontinuation of treatment is essential with regards to improving treatment use and subsequently quality of life in this patient population".

Reviewing data on 14,371 men from 50 previous studies, researchers at City, University of London and East London NHS Foundation Trust, UK assessed the rates of discontinuation of erectile dysfunction treatment and the factors associated with it. Results indicated that discontinuation rates varied across treatments and that adherence to erectile dysfunction treatment is suboptimal.

The authors found that 12.1% of men taking oral medication, 15.2% of men taking injected medication and 31.5% of men taking suppositories reported inadequate or inconsistent erectile responses as their reason for discontinuing treatment. 2.5% of men taking oral medication, 8.1% of men injecting medication and 15% of men taking suppositories stated that they stopped treatment due to side effects including headaches, Peyronie's disease (a build-up of scar tissue in the penis) or urethral pain.

Regarding the quality of sexual relationships, the most commonly reported factors influencing whether men continued with erectile dysfunction treatment were loss of interest in a sexual relationship. This was reported by 6.6% of men taking oral medication, 8.8% of injecting medication, 8.9% of men taking suppositories and 6.9% of men with penile implants. 5.5% of men taking oral medication reported stopping treatment due their partner's perceived lack of interest in the sexual relationship, 5.5% of men described not being emotionally ready for sexual activity and 4.1% discontinued treatment because of conflict within their relationship. The findings appear to highlight the influence of the quality of a couple's sexual relationship on treatment use.

Mr. Paul Williams said: "Men's perceptions of their sexual relationships and their emotional readiness for sexual activity are important when considering the most appropriate treatment for a man and his partner."

The authors caution that due to an under-reporting of data on duration and severity of erectile dysfunction and relationship status in the majority of the included studies, the influence of these factors on treatment use could not be fully explored in this study. Further research should explore how beliefs affecting treatment adherence can be addressed during treatment to improve the quality of life of men and their partners, according to the authors.

The review also highlights the importance of men's beliefs with regards to erectile dysfunction and its treatment, with a potential effect on treatment continuation.

Mr Williams said: "Perceived ineffectiveness of treatment has a subjective element based on, for example, treatment expectations prior to treatment. We found that men who reported treatment side effects to a healthcare professional were more likely to continue with treatment. Exploring any misconceptions patients may have in relation to their treatment could potentially be beneficial to increasing treatment utilisation and therefore something that could help health care professionals when faced with treatment failure."

The authors suggest that future research would benefit from using psychological theory to explore barriers and enablers to treatment utilisation, as well as from measuring how treatment is utilised by patients. Taking such steps may lead to interventions aimed at improving treatment utilisation in this patient population, according to the authors.

Travel restrictions imposed to curb the spread of COVID-19 are making it more difficult for some heart failure patients who have artificial heart pumps to participate in follow-up care at implantation centers far from their homes. But a new study suggests there may be a viable alternative.

According to University of Utah Health researchers, local doctors in rural areas who receive specialized training in managing the devices and who work in conjunction with cardiovascular experts at a major medical center can care for these patients safely and effectively. This collaborative effort, known as shared care, not only eliminates the need for extensive travel but also eases the financial and emotional strains on many patients.

"The risk of death and adverse events for patients living remotely was almost identical to that of patients with the same devices who came in for follow-up care at our implantation center in Salt Lake City," says Michael Yaoyao Yin, M.D., lead author of the study and a U of U Health cardiology fellow. "That tells us that shared medical care can successfully deliver vital care to patients with left ventricular assist devices who are living in remote locations."

The study appears in the April issue of the Journal of the American College of Cardiology: Heart Failure.

About 6.5 million Americans have heart failure, a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body's needs for blood and oxygen. Left ventricular assist devices (LVADs), which are electrically powered pumps implanted surgically between the left ventricle and the aorta, can help keep some patients alive while they wait for a heart transplant. But more and more often, LVADs are being implanted permanently.

"People who have permanent LVADs can do everything you and I do except swim," says Erin Davis, BSN, LVAD and cardiothoracic transplant manager at U of U Health. "They can hike, they can fly, they can go on cruises, they can golf, and even camp."

But what many of them can't do is return to an implantation center for follow-up care. "Most LVAD patients need to return every three months for a checkup," Davis says. "That isn't always practical given that they may live far away. The emotional and financial burdens on patients in rural communities who are very ill and who need to travel long distances for specialized care are tremendous. Yet they worry that if they don't go, they won't receive the same level of care available to others."

To address this health care disparity, U of U Health, which serves an area that encompasses 10% of the U.S., including Idaho, Wyoming, Montana, and much of Nevada, began offering doctors throughout the region specialized training in LVAD care, either in person or via online webinars. For instance, some LVAD patients do not have a pulse because of the continuous blood flow through the machine.

This, Davis says, may be disconcerting for local doctors. "We help demystify the LVAD so the providers are not scared of it and are comfortable having the patient live and receive care in their community," she says.

To evaluate the effectiveness of these training sessions, Yin, Davis, and colleagues retrospectively analyzed the medical records of 336 LVAD patients, including 255 who were treated at shared care facilities in the U of U Health service area. On average, these patients lived 423 miles from the University of Utah. The researchers divided the shared-care facilities into three groups:

Level 1- Primary care physicians and/or general cardiologists provided basic outpatient treatment but received little or no specialized LVAD training.

Level 2 - Physicians, including cardiologists, and nurses received initial LVAD training and repeat training every six months, including how to manage blood clots and infections and maintain normal blood pressure in LVAD patients. Outpatient treatment only.

Level 3 - Physicians, including cardiologists, and nurses received advanced LVAD training and/or had access to regularly scheduled heart failure clinics conducted by U of U Health LVAD experts every one to two months. Inpatient and outpatient care available.

After following the patients for two years, the researchers concluded that level 2 and 3 shared-care facilities had similar survival and LVAD-related complication rates compared to patients receiving care at the U of U Health LVAD implantation center. Patients at level 1 facilities, which provided only rudimentary LVAD care, had a significantly higher risk of infections, blood clots and death than at other shared care medical facilities or the implantation center.

"LVAD patients who live remotely can be successfully managed with specialized training and cooperation between local physicians and medical centers, such as University of Utah Health, that provide expert heart failure care," Davis says. "LVAD is like dialysis for the heart. Kidney dialysis is available anywhere. LVAD care should be, too."

WASHINGTON, March 24, 2020 -- In the U.S., those who consume alcohol and drive are often subjected to roadside stops, breathalyzer tests and stiff penalties if their blood alcohol content exceeds certain limits. Currently, no such test exists for cannabis intoxication, although the substance is known to impair driving, among other activities. Scientists now report that they are one step closer to a convenient saliva test for measuring cannabis levels at roadside stops.

The researchers are presenting their results through the American Chemical Society (ACS) SciMeetings online platform.

A brand-new video on the research is available at http://www.acs.org/philly-2020-thc.

"People have the perception that driving after smoking marijuana is safer than driving drunk, but both substances can have similar effects, such as slowed reaction time, diminished alertness and reduced self-awareness," says Shalini Prasad, Ph.D., who led the study. However, unlike alcohol, the blood level of the psychoactive compound in marijuana, tetrahydrocannabinol (THC), that constitutes impairment has not been well characterized. "This is an emerging field, but preliminary clinical reports suggest that anywhere above 1 to 15 nanograms of THC per milliliter of blood is considered a level of impairment," Prasad says.

As more U.S. states decriminalize marijuana, law enforcement agencies are grappling with how to keep the roads safe from drivers who are high. Blood tests for THC, while accurate, are time-consuming and invasive, and many police officers lack the skills to perform such tests at roadside stops. Some researchers are working on devices that measure THC levels in breath (similar to a breathalyzer for alcohol), but according to Prasad, levels of the substance are low in breath, requiring extensive, error-prone data processing to filter out effects of other compounds. Because THC in saliva correlates closely with that in blood, Prasad and colleagues wanted to develop a simple, quick and accurate saliva test for the compound.

To do so, the researchers, who are at the University of Texas at Dallas, engineered THC sensor strips and an electronic reader. The sensor strips, which contained two electrodes, were coated with an antibody that binds THC so that the substance could be isolated from the many other compounds in saliva. "We used the antibody so that we could really only look at the needle in the haystack," Prasad says. To perform the test, the researchers added a tiny drop of human saliva spiked with THC to the strip and inserted it into the electronic reader, which applied a specific voltage. When THC attached to the antibody, the electrical current changed because of polarization that occurred between the interacting antibody and THC surfaces. The e-reader converted these data into THC concentration.

The researchers found that the device was accurate for THC levels ranging from 100 picograms per milliliter to 100 nanograms per milliliter. "This is the first demonstration of a prototype device that can report both low and high concentrations of THC in a noninvasive, highly sensitive and specific manner," Prasad says. The new test is also fast, requiring less than five minutes to complete from start to finish. In contrast, other saliva tests for cannabis must be performed in a lab, requiring trained personnel and time-consuming sample processing steps, such as dilution and buffer adjustments.

Because cannabis is illegal in Texas, the researchers haven't been able to analyze saliva from people who have actually smoked marijuana. Instead, they've used saliva samples spiked with THC. But Prasad says she has seen a lot of interest from researchers in states where cannabis is legal who want to collaborate, as well as from local law enforcement agencies.

Now, the researchers are taking the saliva test out of the lab. They've made a field-deployable version of the device that is similar in size to the glucose monitors diabetics use. In preliminary testing, they've shown that they can obtain saliva from human volunteers through a simple cheek swab, spike the saliva with different concentrations of THC and perform the test in a setting similar to a roadside stop.

Prasad says that the new test is also likely to find applications outside of law enforcement. For example, the medical marijuana community has shown interest, as well as companies that develop lifestyle devices to help people manage their cannabis consumption. In addition, lawmakers and regulatory groups are interested in using data generated by the device to develop effective laws.

The cholesterol drug alirocumab reduced low-density lipoprotein (LDL) cholesterol by 35.6% compared to placebo in adult patients with homozygous familial hypercholesterolemia (HoFH), according to a phase three clinical trial presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

HoFH is a genetic condition that causes dangerously high levels of LDL cholesterol that are difficult to control with existing medications. Patients with HoFH have two copies of the faulty gene that causes familial hypercholesterolemia (FH) and often respond poorly to conventional treatment. Uncontrolled LDL cholesterol leads to plaque building up in the arteries and FH patients face a high risk of coronary artery disease beginning as early as childhood.

Alirocumab is a monoclonal antibody approved by the U.S. Food and Drug Administration for treating high LDL cholesterol levels in adults alone or in combination with other lipid-lowering therapies. It boosts the body's ability to remove LDL cholesterol from circulation by blocking PCSK9, a protein that keeps LDL cholesterol circulating in the body. Alirocumab has been tested for use in a wide range of patients with high cholesterol, but the new placebo-controlled trial is the first to assess the efficacy and safety of the drug for patients with HoFH.

"This trial is the largest randomized controlled interventional trial in adults with HoFH to date and offers important insights into the disease," said Dirk Blom, MD, PhD, head of the Division of Lipidology in the Department of Medicine at the University of Cape Town in Cape Town, South Africa and the study's lead author. "Alirocumab is a potential new therapy that should be considered in appropriate patients with HoFH."

The trial enrolled 69 patients with HoFH. Forty-five patients were randomly assigned to receive alirocumab via subcutaneous injection every two weeks for 12 weeks. The rest received placebo injections. All patients maintained their regular cholesterol medications and treatments, such as statins, ezetimibe, lomitapide and apheresis, but did not take any other PCSK9 inhibitors.

At 12 weeks, average LDL cholesterol levels among those receiving alirocumab were 26.9% lower than at the trial's start while LDL cholesterol levels among those receiving placebo rose by 8.6%, resulting in an average relative reduction of 35.6% among those receiving alirocumab, meeting the trial's primary endpoint. The average absolute reduction in LDL cholesterol in the patients receiving alirocumab was 62.8 mg/dL.

Alirocumab also substantially reduced other harmful lipids that are typically elevated in people with FH. On average, apolipoprotein B dropped by 29.8%, lipoprotein(a) dropped by 28.4%, non-high-density cholesterol dropped by 32.9% and total cholesterol dropped by 26.5% among those taking alirocumab compared to placebo.

The trial found alirocumab to be well-tolerated and no treatment-related serious adverse events occurred.

"This is a worthwhile potential treatment that helps to lower the LDL cholesterol, though a lot of patients still require additional therapy because the LDL cholesterol is so high at baseline. Unfortunately, there are also a small number of patients with specific mutations who do not respond, or only respond very poorly, to alirocumab," Blom said.

In the U.S., it is estimated that 1 in 250 adults have heterozygous FH and approximately 1 in 300,000 may have HoFH.

Patients who experience chest pain and have abnormal results on a cardiac stress test but who do not have blocked arteries often experience changes in their symptoms and stress test results over time, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

"Even though these patients had very abnormal stress test results, symptoms and stress test findings often changed over time, and the change in the stress test and the change in the symptoms did not necessarily go together," said Harmony R. Reynolds, MD, director of the Sarah Ross Soter Center for Women's Cardiovascular Disease at NYU Langone Health, New York and the study's lead author. "The results suggest the disease activity ebbs and flows--there may be periods of time when symptoms are more active and times when they are absent."

The study, called CIAO, enrolled 208 people who were screened for the ISCHEMIA trial but did not have a blockage of more than 50% on a coronary angiogram, making them ineligible for the large international trial. ISCHEMIA assessed treatments for coronary artery disease (CAD), a buildup of plaque in the heart's arteries.

The problem of blood flow limitation or heart symptoms in the absence of 50% or more artery narrowing is known as ischemia with no obstructive CAD, commonly referred to as INOCA. All patients had experienced chest pain or other heart-related symptoms (angina) and had abnormal results on a stress echocardiogram, a test in which a doctor uses ultrasound to image the heart before and after a patient exercises on a treadmill or stationary bike.

The researchers assessed participants' symptoms and stress test results at one year and compared CIAO patients' baseline findings to those of 1,079 patients who were enrolled in ISCHEMIA and had the same type of stress test used in CIAO, a stress echocardiogram. At baseline, they found that patients in CIAO and ISCHEMIA had similar amounts of ischemia on their stress tests despite patients not having obstructive CAD in CIAO. CIAO participants with INOCA had more frequent angina; 17% of these patients had angina weekly or more often, compared to 4% among those in ISCHEMIA with CAD. CIAO patients were also more likely to have angina in the last month; 41% of CIAO patients with INOCA reported no angina in the last month compared to 62% of ISCHEMIA patients with CAD.

At one year, half of CIAO patients' stress echocardiograms became normal and 45% were the same as at baseline or worse. Angina symptoms improved in 42% and worsened in 14% and the number of medications to control angina on average remained the same. The change in stress test findings over one year and the change in symptoms over one year were not related to one another.

One notable difference from the ISCHEMIA trial was that 66% of patients enrolled in CIAO were female, a much larger proportion than in ISCHEMIA, in which only 26% of enrolled patients were female. That finding fits with previous studies that have found women are more likely to experience chest pain symptoms and have abnormal stress test results than men despite showing less extensive plaque buildup in the arteries.

"This could relate to fundamental differences in how heart disease develops in women and men," Reynolds said. For example, prior studies have suggested women are more likely to experience small vessel disease, in which the smaller blood vessels restrict blood flow to the heart even if the main arteries are clear.

"The worry is that patients with INOCA will get the brush-off from doctors, who might believe patients are fine because their arteries are open," Reynolds said. "However, they cannot be ignored. Prior studies show that these patients are at higher risk than people without angina, although they are generally at lower risk than those with obstructive CAD."

In addition to small vessel disease, intermittent chest pain and ischemia could be caused by episodes of muscle spasms in the coronary arteries, Reynolds said. Further research is needed to determine the factors that contribute to such symptoms in the absence of CAD and determine appropriate treatment approaches, she said. The researchers plan to compare different heart disease assessment strategies to clarify how less invasive tests can be used to identify patients at higher risk.

CHICAGO (March 30, 2020): As patients with Coronavirus Disease 2019 (COVID-19) flood hospitals, the health care system must not only determine how to redeploy limited resources and staff to care for them but must also make well-calculated decisions to provide other types of critical care. For surgeons, this type of critical care involves performing an emergency operation to treat a ruptured appendix or perforated colon--to both virus-exposed and non-exposed patients--while keeping both hospital personnel and non-exposed patients safe.

To help guide hospital surgery departments through this crisis, the acute surgery division at Atrium Health's Carolinas Medical Center in Charlotte, N.C., has developed a tiered plan for marshaling limited resources, which the authors have published as an "article in press" on the American College of Surgeons website ahead of print publication in the Journal of the American College of Surgeons. Atrium Health consists of more than 7,500 beds at 50 hospitals in North Carolina, South Carolina, and Georgia.

"The principles we address--such as triage criteria, beneficence, and justice--are ethical principles that we all learn as physicians, but it's also looking at the scenarios that are unfolding around the world, in China and Italy, and how health care providers are having to deal with this crisis on the fly," said lead author Samuel Wade Ross, MD, MPH, an assistant professor of surgery in the division of acute care surgery at Atrium Health Carolinas Medical Center. "We felt it would be better to have thought about this before the tsunami of COVID-19 patients is upon us."

The Atrium Health recommendations came about when acute care surgery team members approached the department of surgery leadership with the concept, drawing upon their different areas of expertise in disaster management. In addition to Dr. Ross's background in public health, coauthor Cynthia W. Lauer, MD, FACS, was a military surgeon who served two tours in Afghanistan; William S. Miles, MD, FACS, FCCM, brought extensive experience in surgical critical care management; and Ashley Britton Christmas, MD, FACS, is president of the Eastern Association for the Surgery of Trauma.

Key steps include reassigning acute care surgeons to care for COVID-19 patients, creating principles for triaging surgical cases, deferring non-emergency operations or sending these procedures to less-strained centers, and considering "battlefield promotion" for senior surgical residents. The suggestions employ recommendations included in the American College of Surgeons (ACS) recently released guidance for triage of non-emergent operations and recommendations for elective surgeries during the COVID-19 outbreak, Dr. Ross said.

The ACS triage recommendations, incorporating expertise from Allan Kirk, MD, PhD, FACS, of Duke University Medical Center, and the Elective Surgery Acuity Scale (ESAS) developed by Sameer Siddiqui, MD, FACS, of St. Louis University, provide guidance to determine the need for surgery in a hospital dealing with a COVID-19 surge. ESAS recommends that only essential operations, such as those for acute symptoms and most types of cancers, be performed in a hospital with a high COVID-19 population; all other operations should be postponed or sent to an outpatient facility or a hospital with a no-to-low COVID-19 population.

"Those acuity levels would help you decide if a surgery was emergent, urgent, or if it was completely elective; we actually started using those levels here at Atrium Health," Dr. Ross said.

The Atrium Health model uses an operating room case screening board that reviews the day's scheduled cases and determines if these procedures really must be done based on the hospital's response level. Response levels range from "Alert," when disaster preparedness must begin and non-time sensitive elective cases and even high-risk cases should be avoided, to "Condition Zero," which Dr. Ross described as "wartime footing," and only the most pressing emergency operations would be done. "Most centers in the country now are probably beyond the Alert status," he said. Atrium Health is following the guidance of both the Surgeon General and ACS to reschedule all non-essential operations, procedures, and ambulatory appointments.

The recommendations can be used in any type of hospital setting, Dr. Ross said, and have been adopted by all surgical subspecialties systemwide at Atrium Health. "It's really important to plan now so that when a COVID-19 patient surge occurs, there's a blueprint in place," he said.

The most comprehensive recommendations involve personnel. "As the hospital is getting more and more COVID-19 patients and as acute care surgeons are going to have to flex to do more intensive care unit (ICU) critical care, our plan is to shift away from doing the emergency surgery and trauma in order to shift toward focusing on the ICU and pulling more resources from the medical intensivists that cover those patients," Dr. Ross said.

Older health care providers, at higher risk of contracting COVID-19, could be assigned lower-risk roles, such as telemedicine and virtual critical care triage. Fellows and senior medical residents can be advanced to attending status to free up general surgeons for emergency surgery and trauma. "Acute care surgeons are integrated within the emergency department, the operating room, and the ICU," Dr. Ross said. "We're really the Swiss Army Knife of the hospital."

Attrition is also a consideration as staff may become exposed to the virus. The recommendations state that agreements should be in place to shift surgical services among different facilities, and large health systems or regional cooperatives could use a pool of surgeons to deploy at satellite hospitals that run short of staff.

Researchers at Cranfield University are working on a new test to detect SARS-CoV-2 in the wastewater of communities infected with the virus.

The wastewater-based epidemiology (WBE) approach could provide an effective and rapid way to predict the potential spread of novel coronavirus pneumonia (COVID-19) by picking up on biomarkers in faeces and urine from disease carriers that enter the sewer system.

Rapid testing kits using paper-based devices could be used on-site at wastewater treatment plants to trace sources and determine whether there are potential COVID-19 carriers in local areas.

Dr Zhugen Yang, Lecturer in Sensor Technology at Cranfield Water Science Institute, said: "In the case of asymptomatic infections in the community or when people are not sure whether they are infected or not, real-time community sewage detection through paper analytical devices could determine whether there are COVID-19 carriers in an area to enable rapid screening, quarantine and prevention.

"If COVID-19 can be monitored in a community at an early stage through WBE, e?ective intervention can be taken as early as possible to restrict the movements of that local population, working to minimise the pathogen spread and threat to public health."

Recent studies have shown that live SARS-CoV-2 can be isolated from the faeces and urine of infected people and the virus can typically survive for up to several days in an appropriate environment after exiting the human body.

The paper device is folded and unfolded in steps to filter the nucleic acids of pathogens from wastewater samples, then a biochemical reaction with preloaded reagents detects whether the nucleic acid of SARS-CoV-2 infection is present. Results are visible to the naked eye: a green circle indicating positive and a blue circle negative.

"We have already developed a paper device for testing genetic material in wastewater for proof-of-concept, and this provides clear potential to test for infection with adaption," added Dr Yang. "This device is cheap (costing less than £1) and will be easy to use for non-experts after further improvement.

"We foresee that the device will be able to offer a complete and immediate picture of population health once this sensor can be deployed in the near future."

WBE is already recognised as an effective way to trace illicit drugs and obtain information on health, disease, and pathogens. Dr Yang has developed a similar paper-based device to successfully conduct tests for rapid veterinary diagnosis in India and for malaria in blood among rural populations in Uganda.

Paper analytical devices are easy to stack, store and transport because they are thin and lightweight, and can also be incinerated after use, reducing the risk of further contamination.

Patients with atrial fibrillation who took oral anticoagulants alone after undergoing transcatheter aortic valve replacement (TAVR) had a lower rate of bleeding complications without an increased risk of clotting-related complications compared to patients who took antiplatelet medication in addition to oral anticoagulants, in a trial presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

TAVR, a procedure in which operators thread surgical equipment to the aorta through an artery to replace a patient's malfunctioning valve with an artificial one, has become increasingly popular as a less invasive alternative to open heart valve replacement surgery. An estimated one-third of patients undergoing TAVR have atrial fibrillation, a heart rhythm disorder that leads to a high risk of stroke. The new study, antiplatelet therapy for Patients undergoing Transcatheter Aortic Valve Implantation (POPular-TAVI), is the first randomized trial designed to assess the safety of oral anticoagulants alone as compared to using antiplatelet drugs alongside oral anticoagulants for managing TAVR complication risks in these patients. Anticoagulants work by interfering with proteins involved in the formation of blood clots, while antiplatelet drugs prevent platelets, a type of blood cell, from clumping together.

"The rates of complications for TAVR--especially complications related to bleeding--remain high," said Vincent Nijenhuis, MD, from the cardiology department at St. Antonius Hospital in Nieuwegein, Netherlands, and the study's lead author. "This study helps physicians to better understand the risks of adding antiplatelet therapy to oral anticoagulants--namely, that doing so leads to more bleeding without reducing the rate of ischemic events. I think once physicians are aware of this, they will not treat patients undergoing TAVR so aggressively, leading to better outcomes."

Both bleeding and clotting-related complications (such as stroke and heart attack) can be life threatening, especially among patients undergoing TAVR, who are generally older, have multiple comorbid conditions and are frailer than those who undergo open heart valve replacement. In focusing on patients with atrial fibrillation, who typically take oral anticoagulants for many years, the trial sought to address how best to balance the risk of clots against the increased risk of bleeding that comes with any anticoagulant or antiplatelet therapy.

Researchers enrolled 313 patients with atrial fibrillation undergoing TAVR at 17 sites in four European countries. Half were assigned to take oral anticoagulants alone and half took the antiplatelet drug clopidogrel for three months after TAVR in addition to oral anticoagulants.

At 12 months, those taking oral anticoagulants alone were significantly less likely to suffer bleeding complications than those who took oral anticoagulants plus clopidogrel, meeting the trial's prespecified composite primary endpoint. The first component of the composite primary endpoint, all bleeding as assessed with the Valve Academic Research Consortium (VARC) definition, occurred in 21.7% of those receiving only oral anticoagulants and 34.6% of those receiving clopidogrel. The second component, non-procedural bleeding as assessed with the Bleeding Academic Research Consortium (BARC) criteria, occurred in 21.7% of those receiving only oral anticoagulants and 34% of those receiving clopidogrel. This reflects a 43% reduction in the rate of bleeding complications among those taking oral anticoagulants alone.

In a secondary analysis, patients taking oral anticoagulants alone did not show an increased risk of clotting-related complications, meeting the trial's prespecified secondary endpoint for non-inferiority. A composite of cardiovascular death, ischemic stroke and heart attack occurred in 13.4% of those receiving only oral anticoagulants and 17.3% of those receiving clopidogrel, while a composite of those outcomes plus non-procedural bleeding occurred in 31.2% of patients receiving only oral anticoagulants and 45.5% of patients receiving clopidogrel.

"The results suggest it would be beneficial to not give clopidogrel--in fact, it's safer because it does not lead to as many bleeding events," Nijenhuis said.

The study is limited by its open label design, which means patients and doctors were aware of which patients had been randomized to receive clopidogrel versus oral anticoagulants alone, although outcomes were adjudicated by independent evaluators who were blinded to patients' treatment status. In addition, Nijenhuis said that the study's findings are only applicable to patients with atrial fibrillation. The researchers are assessing antiplatelet management in patients without atrial fibrillation in a separate cohort of the ongoing POPular TAVI study. Other studies are underway to assess other types of anticoagulation medications such as direct oral anticoagulants.

Patients undergoing transcatheter aortic valve replacement (TAVR) fared equally well compared with those undergoing open heart valve replacement surgery in terms of the combined risk of death, stroke or rehospitalization at two years, the primary endpoint of the PARTNER 3 trial being presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

TAVR is a procedure in which operators thread an artificial heart valve through an artery in the leg to replace a patient's malfunctioning valve. The procedure is approved by the U.S. Food and Drug Administration (FDA) for the treatment of severe aortic valve stenosis, a condition in which the heart's main valve doesn't open fully, in all patient risk groups for complications associated with surgery.

The PARTNER 3 trial focuses on patients for whom surgery poses a low risk, who are typically younger and who have fewer health problems than higher-risk patients. Last year, researchers reported that TAVR showed superior outcomes compared with surgery at one year among PARTNER 3 participants. The new findings indicate both approaches are equivalent to each other in this low-risk population in terms of outcomes occurring up to two years later.

"The one-year outcomes were only the first look at how these patients do, and this is the second look," said Michael J. Mack, MD, a cardiothoracic surgeon at Baylor Scott and White Health and the study's lead presenter. "On the basis of one-year data, many physicians were counseling patients that TAVR outcomes were better than surgery. Now, we see that the outcomes are roughly the same at two years."

PARTNER 3 enrolled 1,000 patients with severe aortic stenosis and a Society of Thoracic Surgeons risk score of less than 4%. All patients had a tricuspid (three leaflets) aortic valve. Half of the participants were randomly assigned to undergo TAVR with the SAPIEN 3 valve and half underwent surgery.

At two years, 11.5% of patients receiving TAVR and 17.4% of those receiving surgery died, suffered a stroke or were rehospitalized for cardiovascular problems, a difference in the composite primary endpoint that researchers reported as showing non-inferiority, meaning neither treatment was superior to the other.

In a secondary analysis, rates of death and stroke were found to be not significantly different between the two groups. Death occurred in 2.4% of those receiving TAVR and 3.2% of those receiving surgery, while stroke occurred in 2.4% of those receiving TAVR and 3.6% of those receiving surgery. Rehospitalization rates showed a significant difference in favor of TAVR; 8.5% of those receiving TAVR and 12.5% of those receiving surgery were rehospitalized for cardiovascular reasons during the study period.

The two-year outcomes also indicate patients undergoing TAVR had a significantly higher rate of valve thrombosis, the formation of blood clots on the valve, which occurred in 2.7% of patients in the TAVR group and 0.7% of those who received surgery at two years. However, there was no significant deterioration in the functioning of the valve itself between years one and two in either study group.

Researchers will continue to track patient outcomes for up to 10 years. "Longer-term outcomes are particularly important for this patient population because younger, low-risk patients have longer to live with this valve than patients that have been previously studied," Mack said. "Therefore, the durability of the valve is of utmost importance."

About 80% of patients in the U.S. who need valve replacement for severe aortic stenosis fall into the low-risk category studied in PARTNER 3. While TAVR is appealing to many patients because it is a less invasive procedure than open heart surgery and has a shorter recovery time, the PARTNER 3 trial and other ongoing studies provide valuable data to help inform shared decision-making among doctors and patients, researchers said.

Mack said that the trial's findings are limited to patients with severe, symptomatic aortic stenosis with a tricuspid valve and the same inclusion criteria as patients who were enrolled in the study. The trial is also limited by a reduced follow-up rate among patients who received surgery compared with those who underwent TAVR.

DARIEN, IL – Physician burnout is a significantly underappreciated public safety issue, and sleep loss is often overlooked as a contributing factor, according to a new position statement published by the American Academy of Sleep Medicine.

Sleep is essential to health, and sleep deprivation due to shift-work schedules, high workload, long hours, sleep interruptions, and insufficient recovery sleep have been implicated in the genesis and perpetuation of physician burnout. The risk for burnout is especially high due to the novel coronavirus (COVID-19) pandemic, which is requiring physicians and other health care personnel to work long hours under stressful conditions.

“Physicians tend to reside in a culture of working hard at the expense of self-care, including adequate sleep. We need a major culture shift to allow physicians to get the sleep they need,” said senior author Dr. Indira Gurubhagavatula, associate professor of medicine at the Veteran’s Administration Medical Center at the University of Pennsylvania and chair of the AASM Public Safety Committee, which developed the position statement on behalf of the AASM board of directors.

The position statement, published online as an accepted paper in the Journal of Clinical Sleep Medicine, calls for more research exploring sleep disruption, sleep deprivation and circadian misalignment in physician burnout, as well as examining efforts to address sleep problems among doctors. It notes that the physicians most at-risk are at the peak of their careers, and burnout may cause them to seek early retirement, which could negatively impact the physician workforce needed to care for a growing and aging patient population.

While the position statement was developed before the current public health emergency, Gurubhagavatula said it’s even more important now for health care workers to address sleep.

“Insomnia related to stress and anxiety about the pandemic may compound the physical, emotional and cognitive demands of working in high-stress environments,” she said. “Some coping habits, such as the use of alcohol or excessive caffeine, can worsen sleep quality and quantity, which may in turn impact the ability to function at high levels. Healthy sleep is one of the major restorative activities that will help health care workers cope and perform well.”

She noted that heath care employers should consider creating opportunities for rest breaks, including designated nap areas; providing counseling services for those dealing with stress-related insomnia; and distributing education about sleep health and sleep hygiene to help maximize productivity and well-being.

The position statement and a detailed companion paper on the role of sleep in physician burnout are available on the Journal of Clinical Sleep Medicine website.

Patients with diabetes who stopped taking aspirin three months after the insertion of a coronary stent and then took the anti-platelet medication ticagrelor alone for a year had fewer episodes of bleeding and no increase in heart attacks, stroke or other adverse events caused by blockages in the arteries, compared with patients who took both aspirin and ticagrelor for a year. The research was presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

"In patients with diabetes, treatment with ticagrelor alone significantly reduced clinically relevant bleeding compared with ticagrelor plus aspirin, without increasing the risk for additional heart attacks, strokes or death," said Dominick J. Angiolillo, MD, PhD, professor of medicine at the University of Florida College of Medicine in Jacksonville, Florida and first author of the study. The present study was a planned analysis of the TWILIGHT trial, he added, the results of which were published in the New England Journal of Medicine in November 2019. "These findings are consistent with the overall results of the TWILIGHT trial and were seen across all types of diabetes patients, irrespective of their clinical presentation and the treatment they were receiving for their diabetes."

Most heart attacks and strokes are caused by a blood clot in an artery that's been narrowed by a buildup of fatty deposits or plaque. Blood cells known as platelets help the blood to clot, and both ticagrelor and aspirin stop platelets from forming a clot that can block blood flow. Aspirin, however, also heightens the risk of bleeding, particularly in the gastrointestinal tract. The TWILIGHT trial tested whether ticagrelor alone or ticagrelor plus aspirin more effectively reduced bleeding without increasing the risk for heart attacks, stroke, death or other adverse events caused by arterial blockages in patients who had received at least one stent and were at high risk for adverse events.

Stenting, also known as coronary angioplasty or percutaneous coronary intervention, is a minimally invasive procedure in which a flexible tube (catheter) is threaded through an artery under local anesthesia. At the site of the blockage, a tiny balloon at the tip of the catheter is inflated to unblock the artery and a stent, a tiny mesh tube coated with medication, is inserted to prop it open.

The TWILIGHT trial enrolled 9,006 patients at 187 medical centers in 11 countries, including the United States, Canada, the United Kingdom, India, Israel, China and five European countries, who had received at least one stent and were at high risk for bleeding or another arterial blockage. Results showed that ticagrelor alone reduced clinically relevant bleeding more than ticagrelor plus aspirin without increasing the risk of death, heart attack or stroke.

The current study looked just at the subgroup of randomly assigned patients in the TWILIGHT trial who had diabetes (2,620 patients or 37% of all the randomly assigned patients). In this subgroup, patients who received ticagrelor plus a placebo were less likely to have clinically significant bleeding compared with those who received ticagrelor plus aspirin, 4.5% vs. 6.7%, respectively.

On the secondary endpoint, 4.6% of the patients treated with ticagrelor plus a placebo died or had a heart attack or stroke, compared with 5.9% of those who received ticagrelor plus aspirin. Although this reduction was not statistically significant, it offered some reassurance that patients were not harmed by the elimination of aspirin, Angiolillo said.

"Our primary goal was to ensure that dropping aspirin would reduce bleeding without increasing deaths, heart attacks or strokes," he said. "That goal was met."

The findings have some limitations. Patients' treating physicians made the diagnosis of diabetes, which was not confirmed by laboratory testing. Also, patients with the most severe type of heart attack, known as an ST-elevation myocardial infarction (STEMI), were excluded from the trial, so the results do not apply to them. In a STEMI heart attack, an artery to the heart is generally completely blocked, causing the death of some heart tissue. The patients enrolled in TWILIGHT had had either a non-ST-elevation myocardial infarction (NSTEMI) heart attack, in which a sudden arterial blockage due to blood clots partially stops blood flow to the heart, or stable angina, in which blood flow to the heart is interrupted by chronic arterial blockages.

Further research is needed to identify the best treatment for patients like those treated in the TWILIGHT trial after they have completed a year on ticagrelor monotherapy, Angiolillo said.

"What should we do after one year? Should patients continue on a lower dose of ticagrelor?" he said. "This is currently an unanswered question."

Patients undergoing heart bypass surgery lived longer and had better outcomes when surgeons used a segment of an artery from their arm, called the radial artery, instead of a vein from their leg, called the saphenous vein, to create a second bypass, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

After 10 years of follow-up, data showed that using the radial artery rather than the saphenous vein was associated with a statistically significant decrease in the combined rate of deaths, heart attacks and repeat revascularization procedures, said Mario Gaudino, MD, professor of cardiothoracic surgery at Weill Cornell Medicine in New York and principal investigator for the study. There was also a significantly lower incidence of the combined endpoint of deaths and heart attacks.

"The choice of an artery or a vein to create the second bypass is one of the most important unresolved questions in contemporary bypass surgery," Gaudino said. "This study offers the first evidence from randomized trials to show that patients live longer and have better outcomes when surgeons use the radial artery instead of the saphenous vein to create the second bypass."

Bypass surgery, also known as coronary artery bypass graft surgery or CABG, is the most frequently performed heart operation in adults, accounting for about 60% of all heart surgeries performed annually in adults in the U.S. A section of an artery in the chest is used to create a "detour" for blood to flow around a blocked coronary artery (one that carries blood to the heart).

When multiple bypasses are needed, most heart surgeons use the saphenous vein from the leg to create most of them, Gaudino said. Yet consensus guidelines in both the U.S. and Europe recommend using arteries instead of the saphenous vein. Findings from observational studies have suggested that patients do better and that bypasses created using the radial artery last longer than those that use the saphenous vein. Most heart surgeons, however, have resisted switching to the radial or other arteries because doing so would add some time and complexity to the heart bypass operation, Gaudino said. Until now, no clinical trials have definitively shown that patient outcomes are better when the radial artery is used, he added.

For the RADIAL study, Gaudino and his team combined the results from five trials in which patients receiving bypass surgery were randomly assigned to get a second bypass from either the radial artery or the saphenous vein. The trials enrolled a total of 1,036 patients whose average age at the time of their surgery was 67 years, and 70% were men. The trials were performed in five countries: Australia, Korea, Italy, Serbia and the United Kingdom. The primary endpoint was the combined rate of death, heart attack or need for a second procedure to treat the same artery. The co-primary endpoint was the combined rate of death or a heart attack.

In results reported in the New England Journal of Medicine in 2018, Gaudino and his team found that after an average of five years of follow-up, patients who received radial artery vs. saphenous vein bypasses had significantly fewer heart attacks and repeat procedures to open a blocked artery, but the death rate was similar in the two groups.

The current study includes an additional five years of follow-up from patients enrolled in the original trials. After a median of 10 years, patients who received radial artery vs. saphenous vein bypasses had about a 23% reduced risk of experiencing the primary or secondary endpoint event. Use of the radial artery was associated with about a 27% reduction in deaths, a 26% reduction in heart attacks and a 38% reduction in repeat procedures. Women appear to benefit the most from the use of the radial artery.

The study is limited in that the results are from a pooled analysis of several small trials rather than one large trial, and the number of patients was relatively small, Gaudino said.

"Our overall sample size of just over 1,000 patients is fairly small, especially considering that bypass surgery is such a widely performed operation," he said. "These results are important, but they do not give us a final answer. We need a large randomized trial to confirm these findings."

Gaudino said he hopes that this confirmation will come from the ongoing ROMA trial, of which he is the lead investigator. This international trial aims to enroll 4,300 patients undergoing bypass surgery in centers all around the world. It will test whether outcomes are better for patients who receive two or more arterial bypasses compared with patients who receive just one. Initial results are expected in about five years.

Patients with complex heart disease who stopped taking aspirin three months after the insertion of one or more coronary stents and then took the anti-platelet medication ticagrelor alone for a year had fewer episodes of bleeding and no increase in heart attacks, stroke or other adverse events caused by blockages in the arteries, compared with patients who took both aspirin and ticagrelor over the same period. The research, a subanalysis of the TWILIGHT trial, was presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

"Among patients with complex coronary artery disease who completed three months of ticagrelor plus aspirin, ticagrelor monotherapy significantly reduced the incidence of clinically relevant bleeding without increasing the risk of additional heart attacks, strokes or death, compared with those who received ticagrelor plus aspirin," said George Dangas, MD, PhD, professor of medicine, cardiology and surgery at Mount Sinai School of Medicine in New York and lead author of the study.

Most heart attacks and strokes are caused by a blood clot in an artery that's been narrowed by a buildup of fatty deposits or plaque. Blood cells known as platelets help the blood to clot. Both ticagrelor and aspirin stop platelets from forming a clot that can block blood flow. Aspirin, however, also heightens the risk of bleeding, particularly in the gastrointestinal tract. The TWILIGHT trial tested whether ticagrelor alone or ticagrelor plus aspirin more effectively reduced bleeding without increasing the risk for heart attacks, stroke, death or other adverse events caused by arterial blockages in patients who had received at least one stent and were at high risk for adverse events.

Stenting, also known as coronary angioplasty or percutaneous coronary intervention, is a minimally invasive procedure in which a flexible tube (catheter) is threaded through an artery under local anesthesia. At the site of the blockage, a tiny balloon at the tip of the catheter is inflated to unblock the artery and a stent, a tiny mesh tube coated with medication, is inserted to prop it open.

The TWILIGHT trial enrolled 9,006 patients at 187 medical centers in 11 countries, including the United States, Canada, the United Kingdom, India, Israel, China and five European countries, who had received at least one stent and were at high risk for bleeding or another arterial blockage. Results showed that ticagrelor alone reduced clinically relevant bleeding more than ticagrelor plus aspirin without increasing the risk of death, heart attack or stroke.

The current study looked just at the subgroup of randomly assigned patients who had complex coronary artery disease (CAD; 2,342 patients or 33% of all the randomly assigned patients) and were at high risk for adverse events caused by arterial blockages. Patients were deemed to have complex CAD if they had blockages in three or more arteries or other complications that resulted in them receiving multiple stents. In this subgroup, patients who received ticagrelor plus a placebo were less likely to have clinically significant bleeding compared with those who received ticagrelor plus aspirin, 4.2% vs. 7.7%, respectively. Severe or fatal bleeding occurred in 1.1% of patients receiving ticagrelor monotherapy compared with 2.6% of those treated with ticagrelor plus aspirin.

"In this patient subset with complex heart disease, we found that it was okay to withdraw aspirin and that doing so reduced bleeding without increasing heart attacks or other complications," Dangas said.

Rates of stent thrombosis (a blood clot inside a stent) were similar in the two groups of patients, Dangas said, which indicates that stopping aspirin did not cause an increase in this complication. While stent thrombosis is rare, he said, it is a complication that cardiologists worry about and do everything they can to avoid.

"It is reassuring that we saw no difference between the groups for this complication," he said.

A subanalysis of TWILIGHT patients with a type of heart disease known as acute coronary syndrome (ACS), presented at the American Heart Association annual scientific meeting in November 2019, also found that ticagrelor monotherapy lowered bleeding risk without increasing heart attacks, strokes or death, said Dangas. The current findings for patients with complex heart disease are consistent with those for patients with ACS, he said, indicating that in both subgroups of patients it is safe to withdraw aspirin after three months.

A limitation of the study is that patients with the most severe type of heart attack, known as ST-elevation myocardial infarction (STEMI), were excluded from the TWILIGHT trial, so the results do not apply to them. In a STEMI heart attack, an artery to the heart is generally completely blocked, causing the death of some heart tissue. The patients enrolled in TWILIGHT had either a non-ST-elevation myocardial infarction (NSTEMI) heart attack, in which a sudden arterial blockage due to blood clots more commonly partially stops blood flow to the heart, unstable angina or stable angina, in which blood flow to the heart is interrupted by chronic arterial blockages.

New studies highlighting the chronic health burden of oversized breasts outline the long-term benefits of breast reduction surgery to health, levels of wellbeing, and quality of life.

The 12-year study compared feedback from more than 200 Australian women before and after having breast reduction surgery for the painful condition of breast hypertrophy - calling to task private and public health system funding for the surgery.

One paper, published online in BMJ Open, outlines improvements in all levels of both physical and mental health after surgery compared to women in the general female population.

When compared to the health benefits of other common surgical operations, the degree of improvement in physical health approached that of major joint replacement and exceeded that of coronary artery and gall bladder surgery.

The improvement in mental wellbeing was greater than any of the other comparative surgeries, says Flinders University researcher Tamara Crittenden.

"Women with oversized breasts were found to have much more pain and physical disability compared to the normal population, as well as reduced mental wellbeing," she says.

"When measured again after surgery, the women were found to improve to the same levels as the normal population.

"This represents a huge improvement in pain levels, physical function and mental health, which was found to be sustained for at least a year after surgery."

Another major finding of the study was that women of all shapes and sizes seeking breast reduction surgery had major benefit - notably overweight or obese women who in some jurisdictions would be barred from the surgery.

"In the study, we found that those women may even benefit more than those who are slim," says Flinders University Associate Professor Nicola Dean.

"They may have had some minor complications but had a good long-term outcome."

In a separate BREAST-Q patient study, the researchers looked in more detail about how women feel about their breasts before and after surgery, and at their overall wellbeing.

Again it found that women with a higher BMI benefited as much as those who weighed less, as well as significant improvements in physical, psycho-social and sexual wellbeing.

"These (SF-36 and BREAST-Q) studies did not support withholding breast reduction surgery from obese women," says PhD candidate Ms Crittenden.

"We found obese participants gain a similar, if not better, improvement in quality of life after breast reduction, despite a slightly higher rate of minor complications."

Both of the studies indicate breast reduction surgery is undervalued by health systems, significantly improving health-related quality of life to levels comparable to those in the general population," adds Associate Professor Dean, from Flinders University, and Department of Plastic and Reconstructive Surgery at Flinders Medical Centre (FMC).

However, in an era of limited health budgets and increased demands for surgery, health care funders and third-party providers place arbitrary restrictions on access to surgery in many jurisdictions including the UK, Australia and the USA."

"Some health providers even place a body mass index (BMI) limit on whom can be offered breast reduction."