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4-10% of adults worldwide have a chronic cough - a cough lasting more than eight weeks.

Phase 2b clinical trial of drug to treat unexplained chronic cough, a condition that has a significant impact on quality of life, shows promising results.

Currently, no effective licensed therapies exist for this problem.

A new treatment - called gefapixant - may reduce the frequency of coughing, including in patients who have suffered from a chronic cough for more than 15 years, according to results from a phase 2b clinical trial which lasted 12 weeks and included 253 people, published in The Lancet Respiratory Medicine journal.

Between four and 10% of adults worldwide suffer from an unexplained chronic cough. Non-smokers with a chronic cough are likely to have an underlying condition such as asthma, or to have been exposed to dust or fumes in the workplace. However, not all people with conditions such as asthma report a chronic cough. This suggests that it's caused by a separate process, which may explain why it often does not respond to treatment for underlying conditions.

When a cough is unexplained and unresponsive to treatment, a patient may be described as having cough hypersensitivity syndrome. Until now, there has been no safe, long-term treatment for this. A target for treatment could be reducing hyperexcitability of the neuronal pathways involved in coughing. Gefapixant blocks a receptor involved in the cough reflex.

Previous studies found that gefapixant could reduce the frequency of coughing when given in a high dose (600mg) over two weeks, and that doses as low as 50mg could reduce coughing over a four-day trial when given twice daily. The new trial, which lasted 12 weeks, was randomised, double-blind and placebo-controlled to study how effective three different doses of gefapixant were and their associated side effects.

"Many patients with a chronic cough are driven to seek treatment because of the significant negative impact it can have on their quality of life, but at the moment physicians are unable to help," says Professor Jacky Smith from the University of Manchester, who led the study. "Ours' is the first study to report a treatment that is safe and effective over the longer term, and phase 3 trials are already underway with an even larger group of people and over a longer timeframe." [1]

In the current study, the researchers recruited 253 patients with an unexplained or untreatable cough that had persisted for an average of 14.5 years. The patients were recruited from 44 sites across the UK and US. Most (70%, or 177/253) had never smoked. The average age of patients was 60 and over three-quarters (76%, or 193/253) were women, which resembles the profile of patients who attend cough clinics.

Patients were randomly assigned to receive either a placebo (63 patients) or gefapixant twice daily, every day for 84 days. They were administered one of three doses: 7.5mg (64 patients), 20mg (63 patients) or 50mg (63 patients).

Throughout the study, patients kept a cough severity diary, including reporting how many times they coughed per hour. Cough frequency was also captured objectively, by fitting patients with a sound recording device over four 24-hour periods. During three treatment visits, participants completed a Leicester Cough Questionnaire, and during six visits they rated the severity of their cough on a scale from "no cough" to "worst possible cough". Clinicians recorded any adverse events that could be associated with treatment.

Before treatment started, patients coughed around 24-29 times per hour. After 12 weeks of treatment, the placebo group coughed 18 times per hour, but this reduced by an additional 37% to 11 coughs per hour in the 50mg group. There were also some reductions in the 7.5mg and 20mg groups, but these were not statistically significant.

The most common side effect seen in the trial was a change in patients' sense of taste (occurring in three (5%) patients given placebo, six (10%) given 7.5 mg gefapixant, 21 (33%) given 20 mg gefapixant, and 30 (48%) given 50 mg gefapixant). Dysgeusia and other taste-related adverse experiences led to 10 patients in the 50mg group discontinuing with the study, but most patients who continued to receive treatment said they would be happy to continue for at least a year. It is not yet available on prescription, while clinical testing continues.

During the trial, there was one serious adverse event (frostbite) but this was thought to be unrelated to the drug.

The authors note that a limitation of their study is that it recorded a strong placebo effect. For example, the waking frequency of coughs in the placebo group went down from an average of 28 per hour before treatment to 18 per hour after 12 weeks. Previous, smaller studies with gefapixant recorded little change in patients given placebo. The authors suggest that patients' expectations in this trial may have been affected by positive results from previous studies, as well as by the high likelihood (75%) of being assigned to a treatment group.

Writing in a linked Comment, lead author Dr Richard Irwin (who was not involved in the study) from the University of Massachusetts Medical School, USA, says: "Based on the unadjusted data shown in table 2, there was an incrementally larger decrease in cough frequency with each successively larger dose, with the cough frequency at 50 mg being the lowest, but the absolute frequency of cough is not reported as being statistically different from placebo. Because large placebo effects have been seen in other randomized, placebo-controlled cough treatment studies, the authors took this into account by analyzing cough frequency relative to placebo. When this was done, the improvement with the 50mg dose, but not other doses, did reach statistical significance compared with placebo."]

Some species of deaf moths can absorb as much as 85 per cent of the incoming sound energy from predatory bats -- who use echolocation to detect them. The findings, published in Royal Society Interface today [25 February], reveal the moths, who are unable to hear the ultrasonic calls of bats, have evolved this clever defensive strategy to help it survive.

Bats hunt at night using echolocation. The technique, which is also known as biological sonar, first evolved around 65 million years ago and enables bats to search for and find prey putting huge predation pressure on nocturnal insects. One defence that many nocturnal insects evolved is the ability to hear the ultrasonic calls of bats, which allows them to actively evade approaching bats.

Many moth species, however, cannot hear. The team of researchers from the University of Bristol wanted to investigate the alternative defences against bats that some species of deaf moths might have evolved.

Using scanning electron microscopy, the team from Bristol's School of Biological Sciences discovered that the thorax scales of the moths Antherina suraka and Callosamia promethea looked structurally similar to fibres that are used as noise insulation, so wanted to explore whether the thorax scales of moths might be acting in some way to absorb the ultrasonic clicks of bats and dampen the echoes returning to the bat, offering the moths a type of acoustic camouflage.

The team measured that the scales on the body of a moth absorb as much as 85 per cent of the incoming sound energy and that the scales can reduce the distance a bat would be able to detect a moth by almost 25 per cent, potentially offering the moth a significant increase in its survival chances.

Dr Thomas Neil, Research Associate from Bristol's School of Biological Sciences and lead author, said: "We were amazed to see that these extraordinary insects were able to achieve the same levels of sound absorption as commercially available technical sound absorbers, whilst at the same time being much thinner and lighter.

"We are now looking at ways in which we can use these biological systems to inspire new solutions to sound insulating technology and analyse the scaling on a moth's wing to explore whether they too have sound absorbing properties."

Patients with opioid use disorder (OUD) receiving treatment with opioid agonists (medications such as methadone or buprenorphine) had an 80 percent lower risk of dying from an opioid overdose compared to patients in treatment without the use of medications.

The new findings, published online February 25 in the journal Addiction, are a collaboration between researchers at NYU Grossman School of Medicine, Johns Hopkins Bloomberg School of Public Health, the Maryland Department of Health, and multiple Maryland State agencies.

The majority of research examining the effectiveness of medication treatment for OUD in population-based studies has been conducted outside of the U.S. and compares patients receiving treatment to those receiving no treatment. This is one of the first U.S. population-based studies, the researchers say, to compare overdose risk among two patient populations across an entire state—one whose treatment includes agonist medications, and a control group receiving psychosocial interventions without agonist medication.

The team of researchers additionally found that being in any kind of treatment for OUD (with or without medication) is protective against overdose compared to not being in treatment at all. However, neither treatment type offers any additional protections against lethal overdose once patients leave treatment.

Nationally, approximately 60 percent of patients entering specialty treatment for OUD do not receive medication, and many patients with access to medication treatment prematurely discontinue care. This is often due to persisting stigma around the use of medication to treat OUD along with logistical barriers involved in accessing medication treatment, which can, in turn, lead to relapse and overdose.

The researchers also found that taking medication while in treatment offered no protection against fatal opioid overdose once patients left treatment. "This lack of post-treatment protection highlights the need to promote better retention strategies so that patients can remain in treatment as long as it continues to help them," said Noa Krawczyk, PhD, assistant professor, Center for Opioid Epidemiology and Policy in the Department of Population Health at NYU Langone Health, and lead author of the study.

They also found that overdose risk was highest in the first month after leaving treatment, for both medication and non-medication treatment groups.

How the Study Was Conducted

Krawczyk and colleagues examined administrative claims records for publicly-funded outpatient specialty treatment programs in 2015 to 2016 for 48,274 patients with primary diagnosis of opioid use disorder. The research team then linked these claims to mortality data provided from Maryland's Office of the Chief Medical Examiner. Seventy-two percent of the patients in treatment received medication during the study period, while 28 percent did not (a breakdown that differs significantly from the national landscape, where less than 40 percent of patients in treatment receive medication for OUD).

Accounting for time, the researchers compared four distinct groups: people receiving non-medication treatment, people receiving treatment with medication, people no longer in treatment but who left non-medication treatment, and people who left medication treatment.

"Getting people in the door and started on medication treatment is a great first step, but retention in treatment is equally important," says Krawczyk. "Because of this, we need to remove barriers to continuation of care, adopt more harm reduction approaches and employ better strategies to encourage and enable people to stay in treatment."

Study Limitations

Krawczyk and colleagues identify a number of study limitations. Findings relied on administrative data used for payment and not research, which limits clinical information available. The investigators also clustered all types of non-medication treatment together and were unable, for example, to distinguish between specific non-medication treatment types such as counseling relative to detox. Similarly, they grouped buprenorphine and methadone together; they did not compare patients using different opioid agonists. Finally, the study focuses only on patients receiving outpatient specialty treatment and does assess overdose risk among patients receiving buprenorphine in primary care settings.

MINNEAPOLIS - Pingpong may hold promise as a possible form of physical therapy for Parkinson's disease. People with Parkinson's who participated in a pingpong exercise program once a week for six months showed improvement in their Parkinson's symptoms, according to a preliminary study released today that will be presented at the American Academy of Neurology's 72nd Annual Meeting in Toronto, Canada, April 25 to May 1, 2020.

Parkinson's disease is a movement disorder in which a chemical in the brain called dopamine is gradually reduced. This process results in slowly worsening symptoms that include tremor, stiff limbs, slowed movements, impaired posture, walking problems, poor balance and speech changes.

"Pingpong, which is also called table tennis, is a form of aerobic exercise that has been shown in the general population to improve hand-eye coordination, sharpen reflexes, and stimulate the brain," said study author Ken-ichi Inoue, M.D., of Fukuoka University in Fukuoka, Japan. "We wanted to examine if people with Parkinson's disease would see similar benefits that may in turn reduce some of their symptoms."

The study involved 12 people with an average age of 73 with mild to moderate Parkinson's disease. The people had been diagnosed with Parkinson's for an average of seven years.

The people were tested at the start of the study to see which symptoms they had and how severe the symptoms were.

Participants then played pingpong once a week for six months. During each weekly five-hour session, they performed stretching exercises followed by table tennis exercises with instruction from an experienced table tennis player. The program was developed specifically for Parkinson's disease patients by experienced table tennis players from the department of Sports Science of Fukuoka University.

Parkinson's symptoms were evaluated again after three months and at the end of the study.

The study found that at both three months and six months, study participants experienced significant improvements in speech, handwriting, getting dressed, getting out of bed and walking. For example, it took participants an average of more than two attempts to get out of bed at the beginning of the study compared to an average of one attempt at the end of the study.

Study participants also experienced significant improvements in facial expression, posture, rigidity, slowness of movement and hand tremors. For example, for neck muscle rigidity, researchers assessed symptoms and scored each participant on a scale of zero to four with a score of one representing minimal rigidity, two representing mild rigidity, three representing moderate rigidity and four representing severe rigidity. The average score for all participants at the start of the study was three compared to an average score of two at the end of the study.

Two participants experienced side effects. One person developed a backache and another person fell.

"While this study is small, the results are encouraging because they show pingpong, a relatively inexpensive form of therapy, may improve some symptoms of Parkinson's disease," said Inoue. "A much larger study is now being planned to confirm these findings."

The main limitation of the study was that the participants were not compared to a control group of people with Parkinson's disease who did not play pingpong. Another limitation was that a single specialist assessed the patients.

Boston - A new study shows that people with opioid use disorder who enter inpatient medically managed withdrawal treatment (detox) do not usually receive further treatment, including medication for opioid use disorder or additional inpatient treatment. Those who did receive further treatment with medication (methadone, buprenorphine or naltrexone) or residential treatment were more likely to survive to 12 months. Published in Addiction, this study emphasizes the importance of keeping people with opioid use disorder engaged in treatment in order to increase their chances of survival.

Inpatient medically managed withdrawal - detox - is one of the most common ways that people with opioid use disorder (OUD) seek treatment. While people enter detox with the goal of getting better, many do not engage in additional treatment specific to their OUD, including with medication, after discharge. Without ongoing medication for OUD, they leave detox with reduced opioid tolerance, which increases their risk of overdose to rates even higher than when they entered detox. Residential treatment does not typically include medications for OUD during the treatment program.

"Previous studies have shown that FDA-approved medications for opioid use disorder work by reducing opioid use, keeping people in treatment and, for methadone and buprenorphine, decreasing mortality," said Alexander Walley, MD, MPH, a physician in general internal medicine and researcher with the Grayken Center for Addiction, both at Boston Medical Center. "For this study, we looked specifically at mortality after discharge from detox based on further treatment with medication for opioid use disorder and residential treatment."

In collaboration with the Massachusetts Department of Public Health, BMC researchers examined individually-linked data sets for persons age 18 and older in Massachusetts with health insurance, focusing on individuals who had gone through detox between January 2012 and December 2014. This timeframe allowed for 12 months of observation prior to and following the first recorded detox. The researchers investigated the 12-month all-cause and opioid-related mortality rates after detox for individuals discharged who: did not get any treatment for OUD; received medication for OUD following discharge; received residential treatment (discontinuing medication); or received residential treatment and medication for OUD.

The data showed that the all-cause mortality rate for those who received no treatment after detox was high, at 2 percent per year, with overdose being the primary cause. Fifteen percent of individuals received medication for OUD in the month after detox, and for those who remained in treatment, their all-cause mortality decreased by 66 percent compared to those who received no treatment. Seventeen percent of individuals received residential treatment, and their all-cause mortality was reduced by 37 percent compared to those who received no treatment. Only three percent of those in the study received both medication for OUD and residential treatment, and their all-cause mortality was reduced by 89 percent compared to those who received no treatment.

"Opioid use disorder is a chronic condition best addressed with ongoing treatment," said Walley, also an associate professor of medicine at Boston University School of Medicine. "The data from our study shows that medication and residential treatment for opioid use disorder reduce the risk of overdose and death, but these treatments need to continue in order to be effective."

Of the individuals included in this study, less than half received further treatment after detox, and continued engagement in care in both inpatient and outpatient settings was not typically sustained. The authors note that the combination of medication and residential treatment may be especially effective for those at highest risk.

"It is important to consider the initiation of medication during detox, as well as the expansion of the care system that would enable better collaboration between residential treatment centers and MOUD programs to improve access to medication and increase the number of people remaining in treatment," added Walley.

Globally, an estimated 1.9 billion adults and 380 million children are overweight or obese. According to the World Health Organization, more people are dying from being overweight than underweight. Researchers at Concordia are urging health authorities to rethink their approach to obesity.

In their paper published in the journal Obesity Reviews, the researchers argue that obesity should be considered premature aging. They look at how obesity predisposes people to acquiring the kinds of potentially life-altering or life-threatening diseases normally seen in older individuals: compromised genomes, weakened immune systems, decreased cognition, increased chances of developing type 2 diabetes, Alzheimer's disease, cardiovascular disease, cancer and other illnesses.

The study was led by Sylvia Santosa, associate professor of health, kinesiology and applied physiology in the Faculty of Arts and Science. She and her colleagues reviewed more than 200 papers that looked at obesity's effects, from the level of the cell to tissue to the entire body. The study was co-authored by Bjorn Tam, Horizon postdoctoral fellow, and José Morais, an associate professor in the Department of Medicine at McGill University.

"We are trying to comprehensively make the argument that obesity parallels aging," explains Santosa, a Tier II Canada Research Chair in Clinical Nutrition. "Indeed, the mechanisms by which the comorbidities of obesity and aging develop are very similar."

From cells to systems

The paper looks at ways obesity ages the body from several different perspectives. Many previous studies have already linked obesity to premature death. But the researchers note that at the lowest levels inside the human body, obesity is a factor that directly accelerates the mechanisms of aging.

For instance, Santosa and her colleagues look at the processes of cell death and the maintenance of healthy cells -- apoptosis and autophagy, respectively -- that are usually associated with aging.

Studies have shown that obesity-induced apoptosis has been seen in mice hearts, livers, kidneys, neurons, inner ears and retinas. Obesity also inhibits autophagy, which can lead to cancer, cardiovascular disease, type 2 diabetes and Alzheimer's.

At the genetic level, the researchers write that obesity influences a number of alterations associated with aging. These include the shortening of protective caps found on the ends of chromosomes, called telomeres. Telomeres in patients with obesity can be more than 25 per cent shorter than those seen in control patients, for instance.

Santosa and her colleagues further point out that obesity's effects on cognitive decline, mobility, hypertension and stress are all similar to those of aging.

Pulling out from the cellular level, the researchers say obesity plays a significant role in the body's fight against age-related diseases. Obesity, they write, speeds up the aging of the immune system by targeting different immune cells, and that later weight reduction will not always reverse the process.

The effects of obesity on the immune system, in turn, affect susceptibility to diseases like influenza, which often affects patients with obesity at a higher rate than normal-weight individuals. They are also at higher risk of sarcopenia, a disease usually associated with aging that features a progressive decline in muscle mass and strength.

Finally, the paper spells out how individuals with obesity are more susceptible to diseases closely associated with later-life onset, such as type 2 diabetes, Alzheimer's and various forms of cancer.

Similarities too big to ignore

Santosa says the inspiration for this study came to her when she realized how many children with obesity were developing adult-onset conditions of diseases, such as hypertension, high cholesterol and type 2 diabetes. She also realized that the comorbidities of obesity were similar to that of aging.

"I ask people to list as many comorbidities of obesity as they can," Santosa says. "Then I ask how many of those comorbidities are associated with aging. Most people will say, all of them. There is certainly something that is happening in obesity that is accelerating our aging process.'"

She thinks this research will help people better understand how obesity works and stimulate ideas on how to treat it.

"I'm hoping that these observations will focus our approach to understanding obesity a little more, and at the same time allow us to think of obesity in different ways. We're asking different types of questions than that which have traditionally been asked."

More than just causing discomfort, regional heatwaves have been associated with a number of health risks, particularly for children and the elderly.

A new study by researchers at University of California San Diego identified another important at-risk group: people who are pregnant and their unborn infants. The study, published February 11, 2020 in Environment International, found that exposure to heatwaves during the week before birth was strongly linked to an increased risk of preterm delivery -- the hotter the temperature or the longer the heatwave, the greater the risk. In particular, longer duration heatwaves were associated with the highest risk of a preterm birth.

"We looked at acute exposure to extreme heat during the week before birth, to see if it triggered an earlier delivery," said first author Sindana Ilango, a PhD student in the Joint Doctoral Program in Public Health at UC San Diego and San Diego State University. "We found a consistent pattern: exposure to extreme heat does increase risk. And, importantly, we found that this was true for several definitions of 'heatwave.'"

"We knew from previous studies that exposure to extreme heat during the last week of pregnancy can accelerate labor," said senior author Tarik Benmarhnia, PhD, assistant professor of epidemiology at UC San Diego School of Medicine and Scripps Institution of Oceanography. "But no one had tried to figure out exactly what kinds of conditions could trigger preterm births. Is it the temperature? Is it the combination of the temperature and the humidity? Is it the duration of the heatwave? It's important to ask these questions to know when we need to intervene and inform pregnant people to stay inside and stay cool."

Preterm birth is defined as birth before 37 weeks of pregnancy, which normally lasts at least 40 weeks. While the difference might not seem significant, preterm birth can cause a variety of health problems in infants, from respiratory and cardiac ailments and difficulty controlling body temperature to increased risk for brain hemorrhages and long-term health concerns such as cerebral palsy, learning difficulties, and vision and hearing problems.

"Identifying risk factors that can contribute to increased preterm birth rates is an important piece of improving birth outcomes," Ilango said. While similar studies had previously been conducted in other countries, including Canada, China, and Australia, this is the first of its kind to be completed in the United States.

The researchers also incorporated information about ambient humidity into their data, which affects the "feels like" temperature in a region.

"In coastal California, due to climate change, we're seeing more humid heat waves," said Benmarhnia. "Humid air holds heat longer, which can keep temperatures high overnight, contributing to longer heatwaves. This could be important for the recommendations given to pregnant people -- it might not be enough to stay inside just during the day, we might have to think about what to do for night temperatures, too."

The researchers used data collected by the California Department of Public Health that included information about every single birth in the state of California between 2005 and 2013, comprising nearly 2 million live births during the summer months. Then they categorized individuals based on their zip code and compared the birth outcome data to environmental records for that area at the time the person went into labor.

"California is an interesting region for this study because it has a very diverse population spread across a wide variety of microclimates, providing a lot of variation in the data to help us tease apart the relationship between high temperatures and preterm birth rates," said Benmarhnia.

The study found that while the baseline rate of preterm birth was around 7 percent of all pregnancies, under the most conservative definition classifying a heatwave (an average maximum temperature equal to or greater than the 98th percentile, averaging 98.11 degrees and lasting at least four days), the risk of preterm birth was increased by 13 percent.

While the results were in line with the researchers' hypothesis, "it was surprising how strong the trend was," said Ilango. "It was so clear that as temperature and duration of a heatwave went up, so did the risk of preterm birth."

"We were also surprised to note that the duration of the heatwave seems to be more important than the temperature threshold," added Benmarhnia. "We thought that temperature would matter the most, but it turns out that it has more to do with how long you're stuck with the high temperatures rather than how hot it is outside."

These results could be used for directly informing recommendations for families faced with high temperatures in their region, as communities use regional weather trends to determine how they define a heatwave and when to issue warnings for pregnant people to stay in air conditioned spaces. Future research will examine the effects of other environmental conditions linked to climate change on birth outcomes, including exposure to wildfire smoke and what the researchers called the "micro heat island effect" -- the impact that green spaces like parks and gardens can have on local microclimates.

"We want to be thinking about the big picture," said Ilango. "In addition to reducing personal exposure, cities need to be considering city planning interventions that can reduce the impacts of heatwaves, as well as other plans to mitigate and adapt to climate change to protect human health."

According to a study published today in the Journal of the American Medical Association, abbreviated breast magnetic resonance imaging (MRI) detected significantly more cancers than digital breast tomosynthesis (3-D mammography) in average-risk women with dense breast tissue. The study compared the 10-minute MRI exam to 3-D mammography, in women with dense breasts, because the ability of mammography to detect breast cancer is limited in these women. The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) designed and conducted the study (EA1141) with funding from the National Cancer Institute, part of the National Institutes of Health, and Bracco Diagnostics Inc. (Monroe Township, NJ).

According to Christopher E. Comstock, MD, the publication's lead author, "When screening women at average risk with dense breasts, we found that abbreviated breast MRI detected significantly more (almost two and a half times as many) breast cancers as 3-D mammography. We also found that the abbreviated breast MRI was well tolerated by women, with very few side effects."

Dr. Comstock is Attending Radiologist and Director of Breast Imaging Clinical Trials at Memorial Sloan Kettering Cancer Center and Imaging Chair for ECOG-ACRIN's Breast Cancer Committee. Study leadership included breast cancer researchers from Memorial Sloan Kettering Cancer Center, University Hospital of RWTH Aachen, University of Chicago, University of Pennsylvania and the Department of Biostatistics and Center for Statistical Sciences at Brown University School of Public Health.

Despite current screening methods, over 40,000 women die each year from breast cancer. The ability of mammography to detect breast cancer is especially limited in women with dense breast tissue. Having dense breasts is not an abnormal condition; in fact, about half of all women over the age of 40 have dense breasts.

Breast MRI is a screening test that uses radio waves to capture images following intravenous injection of contrast dye. Because it is not limited by breast density, MRI offers the highest cancer detection rate of all breast imaging modalities. However, breast MRI is more expensive than a mammogram, takes longer to perform (45 minutes compared to about 15 minutes for a mammogram) and requires an injection.

Although most evidence exists for using MRI to screen the small proportion of women at very high risk of breast cancer, there is accumulating evidence, pioneered by Christiane K. Kuhl, MD, PhD (Chairman of Radiology at University Hospital Aachen and the publication's senior author), that the higher sensitivity of MRI is also seen in women at average risk.

As Dr. Comstock explained, "Although MRI is undoubtedly the most sensitive test for detecting breast cancer, it is not being used to screen the large number of average-risk women with dense breasts due to its high cost and time to perform. Abbreviated breast MRI is a 10-minute test that reduces the complexity and cost of MRI by shortening the time it takes to perform and interpret the exam. The EA1141 results will hopefully give far more women access to this powerful tool in the fight against breast cancer."

The EA1141 study compared the diagnostic performance of abbreviated breast MRI to 3-D mammography in screening average-risk women with dense breasts for breast cancer.

Women were eligible to participate in the study if they were between the ages of 40 and 75, had dense breasts on their prior mammogram, and did not currently have breast cancer or any clinical symptoms. This analysis pertains to 1,444 trial participants, all of whom were screened with both 3-D mammography and abbreviated MRI within 24 hours. The images were interpreted independently by two different board-certified breast radiologists who remained blinded to the results of the other modality.

Participants were screened twice in the study, first as a baseline and again after one year, and are being followed for three additional years. Enrollment took place over 11 months (December 2016 - November 2017) at 47 centers in the US and one in Germany. The US centers are a mixture of academic, community hospital, and private institutions throughout the country.

In the first year of the study, 23 women were diagnosed with breast cancer. The abbreviated MRI detected 22 out of the 23 women with breast cancer, while the 3-D mammogram detected only nine out of the 23 women. Abbreviated MRI detected all of the cancers found on 3-D mammography except for one early stage cancer. At the same time, abbreviated MRI found an additional 10 invasive breast cancers, including three high-grade cancers, which were not detected on 3-D mammography.

There were no patients with interval cancers, which are cancers detected within 12 months after a screening exam interpreted as normal. However, the abbreviated MRI led to slightly more false-positive results, including recommendations for biopsies of findings that turned out not to be cancer.

The EA1141 study looked solely at women with dense breasts. It provides promising results for abbreviated MRI, and may ultimately help better screen women with dense breasts for cancer. The study did not attempt to provide cancer mortality information.

According to Dr. Comstock, "While these early results are promising, further studies are needed to evaluate the cost-effectiveness of widespread screening with abbreviated breast MRI and its impact on reducing breast cancer mortality. Currently, only a few centers offer abbreviated breast MRI and it is not covered by insurance. Our hope is that study EA1141 will provide the impetus for more centers to provide this new test and that insurers will see its benefit to improve early detection of breast cancer."

New study findings suggest that weight gain after breast cancer is a greater problem than previously thought. The first national survey on weight after breast cancer in Australia, published in BMC Cancer journal, found close to two-thirds (63.7%) of women reported weight gain at an average of nine kilograms after a breast cancer diagnosis, and overall nearly one-in-five women (17%) added more than 20 kilograms.

Researchers from NICM Health Research Institute, Western Sydney University and ICON Cancer Centre, Sydney Adventist Hospital, Wahroonga, surveyed 309 women with breast cancer living in Australia using an anonymous, self-administered online cross-sectional survey between November 2017 and January 2018. The national sample consisted mainly of members from Breast Cancer Network Australia (BCNA).

The majority of women surveyed (77%) reported gaining weight within the first 12-18 months after diagnosis, which could be the ideal 'window of opportunity' to provide additional support for weight management among women with breast cancer says Dr Ee, lead author, general practitioner and senior research fellow at NICM Health Research Institute, Western Sydney University.

"As well as significant weight gain, we also found high levels of concern about weight among our survey participants. Timing may be the key in helping women to manage weight after a diagnosis of breast cancer," said Dr Ee.

"Cancer services and general practitioners play an important role in having early conversations with women, and referring them to a team of qualified healthcare professionals such as dieticians and exercise physiologists with experience in cancer," she said.

The survey also found:

The proportion of women who were overweight or obese increased from 48% at time of diagnosis to 67% at the time of the survey, with the proportion of women who were obese almost doubling from 17% to 32%.

The majority (69%) of women gained weight in excess of the rates reported in age-matched controls without breast cancer - an additional 2.42 kilograms over five years.

Professor John Boyages AM, co-author and radiation oncologist at Icon Cancer Centre says that all women should be prescribed exercise after being diagnosed with breast cancer, according to the Clinical Oncology Society of Australia (COSA) guidelines.

"As doctors we really need to actively think about weight, nutrition and exercise and advise about possible interventions," said Professor Boyages.

"Breast cancer is the most common cancer in women worldwide and in Australia, and weight gain is common after breast cancer treatment. Many patients assume they will lose weight. Weight gain adds to self-esteem problems, increases the risk of heart disease and other cancers and several reports suggest it may affect prognosis and also increases the risk of arm swelling (lymphoedema). Prescribing a healthy lifestyle is just as important as prescribing tablets."

Dr Ee further says that after diagnosis of breast cancer, many women experience fatigue, which can be a barrier to staying active, and studies show exercise is an effective treatment for fatigue. However, for this to be feasible and sustainable, she says supervision by an experienced exercise physiologist is invaluable.

BCNA CEO Kirsten Pilatti says many studies highlight the importance of specialists such as exercise physiologists and nutritionists for breast cancer treatment plans, however they are often an unfunded component of follow-up care.

"For many breast cancer survivors, the cost of accessing the expertise of these specialists puts them beyond their reach. We want a system that helps women and men diagnosed with breast cancer to come out and be able to move on with their life, not be crushed by the experience," said Ms Pilatti.

The researchers will next analyse the survey data to investigate reasons why women are gaining weight after breast cancer, with several risk factors reported in other studies, including the type of treatment that women receive, and whether or not they were menopausal before diagnosis and treatment.

Walter and Eliza Hall Institute researchers have revealed new details about how joint inflammation evolves in rheumatoid arthritis, and the cells that prolong the inflammatory attack.

In both laboratory models and human clinical samples, the research team pinpointed immune cells called natural killer (NK) cells as an unexpected source of the inflammatory protein GM-CSF in rheumatoid arthritis, the first clue that these cells contribute to inflammatory autoimmune diseases. The research also explained how GM-CSF signals to other immune cells to prolong joint inflammation, and how GM-CSF signalling to immune cells is kept in check in healthy joints.

These discoveries could indicate potential new therapeutic targets for reducing joint inflammation in rheumatoid arthritis, and could potentially reduce inflammation in other autoimmune disease such as multiple sclerosis.

The research was published in the Journal of Experimental Medicine by a team co-led by Professor Ian Wicks, Professor Nicholas Huntington and Dr Cynthia Louis, with Dr Fernando Souza-Fonseca-Guimaraes.

At a glance

The cell signalling protein GM-CSF causes inflammation that occurs in joints during rheumatoid arthritis.

Our researchers have identified natural killer (NK) cells as a major source of GM-CSF in rheumatoid arthritis, the first time these cells have been implicated in an autoimmune disease.

The team also identified the protein CIS as a key molecular brake that dampens GM-CSF activity and inflammation, revealing a potential new therapeutic avenue for inflammatory diseases.

A surprising source of GM-CSF

Rheumatoid arthritis is a chronic inflammatory autoimmune disease in which the immune system mistakenly attacks joints and other tissues, causing inflammation, pain and long-term joint damage.

GM-CSF was originally discovered at the Walter and Eliza Hall Institute as a growth factor for blood cells, but it is increasingly recognised as a key inflammatory mediator that drives a number of autoimmune diseases.

Professor Wicks said that his team's earlier research, together with colleagues at the University of Melbourne, had identified the signalling protein GM-CSF as an important contributor to joint inflammation in rheumatoid arthritis. "When we removed GM-CSF, we could see a reduction in inflammation. This finding underpinned the development and current clinical trials of inhibitors of GM-CSF signalling as a new approach to treating rheumatoid arthritis," he said.

"Although we knew that GM-CSF signalling was important in joint inflammation, which cells were producing GM-CSF within joints, and how this protein signalled after binding to its receptor on other immune cells, was not well understood."

Dr Louis said the team discovered that GM-CSF in inflamed arthritis joints was produced by immune cells called natural killer (NK) cells. "This was a surprise because, until now, NK cells were thought to primarily be important for clearing virus-infected or cancer cells," she said. "This is the first time NK cells have been found to contribute to tissue inflammation in autoimmune diseases such as rheumatoid arthritis.

"As well as looking at our laboratory model of arthritis, we examined cells from the joints of people with rheumatoid arthritis and confirmed that NK cells are indeed a significant source of GM-CSF in patients.

"This discovery has solved one part of the puzzle about how inflammation occurs in rheumatoid arthritis," Dr Louis said.

Filling in the gaps

The team revealed that the protein CIS is important for 'switching off' GM-CSF signalling, a critical mechanism to restrain destructive inflammation in arthritis.

"In the absence of CIS, we saw hyperactivation of GM-CSF signalling and more severe arthritis," Dr Louis said.

"This research showed that if a new drug that mimics CIS were to be developed, it may help to reduce the debilitating effects of GM-CSF in rheumatoid arthritis, but also in other inflammatory diseases driven by GM-CSF, such as multiple sclerosis."

Professor Wicks said the research revealed new aspects of cell signalling that warranted further investigation. "We're very excited to have progressed our understanding of rheumatoid arthritis and potentially other inflammatory diseases," he said.

A new infection test, made up of sheets of paper patterned by lasers, has been developed by University of Southampton researchers to allow diagnosis at the point of care - helping doctors give patients the right treatment, faster.

Laboratory tests to identify the cause of common infections like urinary tract infections (UTIs) can take up to four days, with doctors having to use broad-action antibiotics as a first line of treatment.

This may not only be less effective than using drugs specific to the infection, but also contributes to an increase in antibiotic-resistant bacteria.

Now new research, led by Dr Collin Sones from the University of Southampton and published in Biosensors and Bioelectronics, shows a paper-based device made using lasers could allow doctors to find out which antibiotic, if any, they should give.

'Cheap and easy to use'

Using similar methods to existing pregnancy tests and urine dipsticks, the new technology has the potential to be cheap to produce, easy to use and could be done by a doctor or nurse on the ward - slashing diagnosis times.

Made using lasers, the test paper has three layers - a top layer containing four common antibiotics in confined rectangular areas, an absorbent paper in the middle and an agar gel-containing base layer, all sealed in a plastic casing.

The liquid sample (e.g. urine) is added to a small paper tab, which is then covered with tape to prevent drying out or contamination.

The sample then spreads across the middle paper layer, coming into contact with the four rectangles containing the test antibiotics (amoxicillin, ciprofloxacin, gentamicin and nitrofurantoin).

If bacteria are present the paper will turn blue and if the infection can be treated with one of the antibiotics there will be a clear patch around the corresponding rectangle.

As well as giving doctors an early identification of bacterial infection, the test also directs which one of the four common antibiotics will work best - or if it is a strain untreatable with any of them.

When compared against standard lab tests done in petri dishes with agar gel, using artificial urine spiked with the bacteria E.coli, the team got comparable results.

'Fighting antibiotic resistance'

A serious threat, which opens the prospect of routine procedures and infections to small cuts once again becoming potentially life threatening, antibiotic resistant infections rose by 9% in England between 2017 and 2018, with about 61,000 cases.

It occurs when bacteria evolve defences against antibiotics, usually through being exposed to the drug for too long or at too low a dose - allowing the strongest, most drug resistant, to survive and replicate.

Cutting overuse of antibiotics, particularly broad-action drugs, is critical for preventing more resistant strains emerging, keeping the drugs effective and reducing the threat to patients.

"By enabling doctors to quickly determine if an infection is caused by bacteria, and if the bacteria are resistant to four common antibiotics, this device could cut down on unnecessary antibiotic prescriptions and help fight the growing threat of antibiotic resistance," said Dr Sones.

Dr Sones and his team will present their research, as part of the University of Southampton's Network on Antimicrobial Resistance and Infection Prevention (NAMRIP), on 25th February at a Superbugs event at the UK Parliament.

Adults do not need tetanus or diphtheria booster shots if they've already completed their childhood vaccination series against these rare, but debilitating diseases, research published in the journal Clinical Infectious Diseases indicates.

The conclusion aligns with the World Health Organization's recent recommendations to only routinely give adults tetanus and diphtheria vaccines if they didn't receive a full series of shots as children. In the U.S., the CDC's Advisory Committee on Immunization Practices still recommends all adults receive booster shots every 10 years.

Mark Slifka, Ph.D., and colleagues found no significant difference in disease rates between countries that require adults to receive tetanus and diphtheria booster shots and those that don't. The finding is the result of comparing data from millions of people from 31 North American and European countries between 2001 and 2016.

"To be clear, this study is pro-vaccine," says the study's lead researcher, Slifka, a professor at the Oregon Health & Science University School of Medicine and the Oregon National Primate Research Center. "Everyone should get their series of tetanus and diphtheria shots when they're children. But once they have done that, our data indicates they should be protected for life."

Requiring fewer vaccinations for adults could save the U.S. about $1 billion annually in unnecessary medical costs, the researchers estimate.

The paper follows research Slifka and colleagues published in 2016, which concluded the vaccine produced at least 30 years of immunity for the 546 adults in that study. As a result, the researchers recommended at that time to vaccinate adults against these diseases only every 30 years.

"Based on our new data, it turns out we were probably overly conservative back in 2016," Slifka now says. "Even though it looked like immunity could be maintained for decades, we didn't have direct evidence back then that this would translate into true protection against disease in the real world.

"However, our new data provides the final piece to the puzzle. We now have evidence showing the childhood vaccination series can provide a lifetime of protection against both tetanus and diphtheria."

Tetanus, also known as lockjaw, is a bacterial infection that causes jaw cramping, painful muscle spasms, trouble swallowing and breathing, seizures, convulsions and, in severe cases, death. It's spread by bacteria commonly found in dirt or feces, or on contaminated objects such as nails or needles. About 30 people in the U.S get tetanus annually, and one or two out of 10 cases can be fatal. Tetanus-associated deaths almost always occur among unvaccinated people, or those with incomplete or unknown vaccination history.

Diphtheria is a bacterial infection that causes a thick covering in the back of the throat, which can lead to difficulty breathing, heart failure, paralysis or death. It's spread by exposure to infected people or in rare cases, infected animals. In the past decade, less than five U.S. cases of diphtheria were reported to the CDC. In an unvaccinated population, about one in 10 cases can be fatal. But more than 99.8 percent of vaccinated people who are diagnosed with diphtheria and receive appropriate care survive.

In the pre-vaccine era, there were about 470 tetanus-associated deaths and 1,800 diphtheria-associated deaths in the U.S. each year. Tetanus- and diphtheria-related deaths have declined by more than 99% since vaccines became available to prevent them.

The number of people with chronic non-cancer pain prescribed an opioid medicine worldwide increased in the last two-and-a-half decades. But there was only a small number of studies reporting prescription data outside the United States, finds research led by the University of Sydney.

Chronic pain unrelated to cancer includes conditions such as chronic lower back pain, osteoarthritis and rheumatoid arthritis.

The researchers point to guidelines such as those from the Centres of Disease Control and Prevention in the United States that discourage the use of opioids to manage chronic non-cancer pain because of concerns about harmful effects and the lack of evidence about effectiveness. The use of opioids in the US and deaths from overdoses and addiction has been said to have reached epidemic proportions.

The systematic review of studies from across the world is the first to examine the literature about the extent opioid pain relievers are being prescribed to manage people with chronic pain conditions.

The findings are published today in the high-impact Journal of Internal Medicine.

The research spanned eight countries and evaluated 42 published studies that included 5,059,098 people with chronic pain conditions (other than cancer).

Two-thirds of the studies were from the US; one study was from Australia and the other studies were from the United Kingdom, Norway, India, Spain, Denmark and Canada.

Lead author Dr Stephanie Mathieson from the University of Sydney's Institute for Musculoskeletal Health says that in the period 1991-2015, prescribing of opioid medicines increased markedly.

In the early studies, opioid medicines were prescribed to about 20 percent of patients experiencing chronic pain but the later studies report rates of more than 40 percent.

"Over this period, on average around 30 percent of people with chronic pain were prescribed an opioid medicine," said Dr Mathieson, from the School of Public Health in the Faculty of Medicine and Health.

"We noted that a higher proportion of people were prescribed a strong opioid medicine such as oxycodone compared to weak opioid pain-relieving medicines."

The authors also discovered there was insufficient data on the dose and duration of opioids prescribed to patients with chronic non-cancer pain.

Key findings:

Opioid prescribing:

Between 1991 and 2015, the researchers found in people with chronic pain (unrelated to cancer):

Opioid prescribing increased over time from approximately 20 percent in early years to around 40 percent in later years.

On average over this period approximately one in three patients (30.7 percent) were prescribed an opioid medicine.

42 percent of patients with chronic lower back pain were prescribed an opioid.

The average age of those prescribed an opioid medicine was 55.7 years.

Prescribing was not associated with the geographical location or the clinical setting where the opioids were prescribed (such as GPs or medical specialists).

Types of opioid painkillers:

In 17 studies that described the type of opioid pain relievers prescribed:

24.1 percent were strong combination products containing opioids (eg oxycodone plus paracetamol).

18.4 percent were strong opioids (eg oxycodone, morphine, fentanyl).

8.5 percent were weak opioids (eg codeine, tramadol).

11 percent were weak combination products containing opioids (eg codeine plus paracetamol).

An 'evidence' gap in global prescription data

The study aimed to establish a baseline for how commonly opioids are prescribed for people with chronic pain conditions (other than cancer). But the authors discovered a crucial evidence gap in prescription data in countries outside of the US.

"While we have sufficient data for this purpose for the US, we have little or no data for other countries," the authors write.

Dr Mathieson says that studies in other countries, particularly low and middle-income countries, are needed in order to check whether these countries are at risk of the problems seen in the US, where there is liberal use of opioid medicines.

This research is a collaboration between the University of Sydney; the University of Warwick, UK; the University of Notre Dame; the University of New South Wales and Monash University.

ATLANTA - Today, the American College of Rheumatology (ACR) published the 2020 Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. This is the first, evidence-based, clinical practice guideline related to the management of reproductive health issues for all patients with rheumatic diseases. With 131 recommendations, the guideline offers general precepts that provide a foundation for its recommendations and good practice statements.

"This guideline is paramount, because it is the first official guidance addressing the intersection of rheumatology and obstetrics and gynecology (OB-GYN)," said Lisa Sammaritano, MD, lead author of the guideline. "Rheumatic diseases affect many younger individuals; however, little education has been provided to rheumatology professionals on current OB-GYN practices. The guideline [and more detailed online appendices] presents vital background knowledge and recommendations for addressing reproductive health issues in the full spectrum of rheumatology patients, with additional focus on specific diagnoses that require more detailed recommendations such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

The guideline provides 12 ungraded good practice statements and 131 graded recommendations that are intended to guide care for rheumatology patients except where indicated as being for patients with specific conditions or antibodies present. Good practice statements are those in which indirect evidence is compelling enough that a formal vote was considered unnecessary; these are ungraded and are presented as suggestions rather than formal recommendations. The recommendations were separated into six categories: contraception, assisted reproductive technology (fertility therapies), fertility preservation with gonadotoxic therapy, menopausal hormone replacement therapy, pregnancy assessment and management, and medication use.

While some of the recommendations are strong, many of the recommendations presented are conditional due to a lack of data. Pregnant women are not generally enrolled in clinical studies; and few maternal health studies focus on rheumatology patients. A few notable recommendations from each category include:

Contraception

Strong recommendation for women with rheumatic disease who do not have lupus or APS to use effective contraceptives with a conditional recommendation to preferentially use highly effective IUDs or a subdermal progestin implant.

Strong recommendation against using combined estrogen-progestin contraceptives in women who test positive for anti-phospholipid autoantibodies (aPL) or APS.

Assisted Reproductive Technology (Fertility Therapies)

Strong recommendation for fertility therapy in women with uncomplicated rheumatic disease who are receiving pregnancy-compatible medications, whose disease is stable, and who test negative for aPL. Specific recommendations also address patients testing positive for aPL and suggest an anti-blood clotting procedure.

Conditional recommendation against increasing prednisone dosage during fertility therapy procedures in lupus patients.

Fertility Preservation

Conditional recommendation against testosterone co-therapy in men with rheumatic disease receiving cyclophosphamide (CYC) and a good practice suggestion to cryopreserve sperm before CYC treatment in men who desire it.

Conditional recommendation for monthly gonadotropin-releasing hormone agonist co-therapy for premenopausal women with rheumatic disease who are receiving monthly CYC injections/infusions to prevent premature ovarian insufficiency.

Pregnancy Assessment and Management

Strong good practice suggestion to counsel women with rheumatic disease, who are considering pregnancy, on the improved maternal and fetal outcomes associated with entering pregnancy during low disease activity.

Conditional recommendation to treat lupus patients with low-dose aspirin daily (81 to 100 mg) starting in the first trimester. For women testing positive for aPL who do not meet the criteria for obstetric or thrombotic APS, it is conditionally recommended to preventatively treat with a daily aspirin (81 to 100 mg) starting early in pregnancy and continuing through delivery.

Menopause and Hormone Replacement Therapy

A good practice suggestion to use hormone replacement therapy in postmenopausal women with rheumatic disease who do not have lupus or have a positive aPL test; and who have severe vasomotor symptoms, have no contraindications, and desire treatment.

A conditional recommendation for hormone replacement therapy in women with lupus and without aPL.

Conditionally recommend against treating with hormone replacement therapy for women with asymptomatic aPL, and strongly recommend against hormone replacement therapy for women with any form of APS.

Medication Use (Paternal and Maternal)

Strongly recommend against use of CYC and thalidomide in men prior to attempting conception.

Strong recommendation against the use of NSAIDs in the third trimester.

Individuals involved in the development of the new guideline included rheumatologists, obstetrician/gynecologists, reproductive medicine specialists, epidemiologists, and patients with rheumatic diseases. ACR guidelines are currently developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, which creates rigorous standards for judging the quality of the literature available and assigns strengths to the recommendations that are largely based on the quality of the available evidence.

"This guideline should open avenues of communication between the rheumatologist and the patient, as well as between the rheumatologist and the OB-GYN," said Dr. Sammaritano. "A better understanding of the risks and benefits of reproductive health options will enhance patient care by providing safe and effective contraception, improving pregnancy outcomes by conceiving during inactive disease periods, and allowing for continued control of rheumatic diseases during and after pregnancy with the use of well-suited medications."

A draft of the guideline was presented during the 2018 ACR/ARP Annual Meeting in Chicago. Since that time, the guideline team has condensed the original three-part draft into a single, concise manuscript, with detailed background and discussion now available online. The guideline development team also incorporated color-coded flow charts to highlight common decision-making points to make it user friendly.

BOSTON- Researchers at Boston Medical Center have found that only a fraction of patients at risk of having their utilities shut off were identified through social determinants of health (SDOH) screening. Published in The Journal of Ambulatory Care Management, the research showed that among the patients who received a utility protection letter in 2018, 70 percent were screened for SDOH and only 16 percent screened positive for difficulty paying their utility bills.

Preventing utility shut-off is vital to maintaining patients' health, which is why most states in the U.S. have laws prohibiting or delaying utility companies from terminating service to low-income households when occupants present a medical letter confirming a household member has a chronic serious illness. These laws ensure electricity-powered medical devices continue running, and that patients have electricity to refrigerate medications. Preventing utility shutoffs may help patients pay for other necessities like food, medicine, and shelter. It is widely-documented that SDOH can greatly impact a patient's health and their ability to manage a chronic serious illness.

"Patients experiencing difficulty paying utility bills may not be detected by systems of care that screen for SDOH, and this is concerning for at-risk populations," says Karen Lasser, MD, MPH, a general internist at BMC and professor at Boston University Schools of Medicine and Public Health. "This research calls for better approaches to identify those needing assistance, to ensure better health outcomes for all patients."

In January 2018, Boston Medical Center (BMC) implemented an electronic health record-based SDOH screening and referral program, which identifies eight domains of potentially unmet SDOH needs: housing and food insecurity, inability to afford medications, utilities or transportation, need for employment or education, and difficulty taking care of children or other family members.

There are several reasons why patients may not be identified for utilities insecurity. Difficulty paying utility bills may be a seasonal phenomenon - patients screened in warmer months may not identify this need as they would in the winter when heat is a necessity, especially in Boston. Screening for SDOH also takes place at medical appointments. Patients in precarious social circumstances may be less likely to attend visits and therefore may not get screened. Patients may also feel stigmatized by SDOH screening, or may not report difficulty paying for utilities if they are already receiving assistance.

Researchers also analyzed characteristics of adult patients at BMC, a safety-net hospital, who received a utility shut-off protection letter between 2009 and 2018. During the study period, 2,973 unique adult patients received a utility letter. Looking at the demographics of those receiving the letter, two-thirds were women, most were English-speaking, and the average age of the person receiving the letter was 56 years. Two thirds of the patients were non-Hispanic black and 75 percent had government insurance. Overall, these patients had high levels of medical and behavioral health comorbidities.