Body

CLEVELAND, Ohio (April 21, 2021)--The importance of getting a good night's sleep cannot be overstated. Lack of sleep can lead to a number of health problems and affect a woman's overall quality of life. A new study suggests that insufficient quality sleep also may lead to problems in the bedroom in the form of female sexual dysfunction. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Both sleep and sexual function problems are common in women during midlife. More than 26% of midlife women experience significant sleep symptoms that meet the criteria for insomnia, and sleep problems are reported by nearly half of women during the menopause transition. Up to 43% of women report sexual problems during this same period in their lives.

Multiple studies have been conducted to determine whether there is any association between sleep and sexual function problems. However, most of the previous studies did not consistently evaluate sexual dysfunction with validated tools, nor did they define sexual dysfunction by the presence of sex problems associated with distress.

In this study involving more than 3,400 women (mean age, 53 y), researchers evaluated potential associations between sleep quality and duration and sexual function using validated tools after accounting for factors that may influence both outcomes. They concluded that poor sleep quality, but not sleep duration, was associated with greater odds of female sexual dysfunction. Good sleep quality, in contrast, was linked with sexual activity.

Understanding this association is valuable as clinicians seek to identify potential treatment options for women affected by sleep and sexual problems. Both of these common midlife issues have been determined to adversely affect a woman's quality of life.

Results are published in the article "Associations of sleep and female sexual function: good sleep quality matters."

"This study highlights an association between poor sleep quality and sexual dysfunction. These are two common issues for midlife women and asking about and addressing each may contribute to improved quality of life," says Dr. Stephanie Faubion, NAMS medical director and senior author of the study.

Study of 30,000 adults living with HIV receiving antiretroviral therapy (ART) in Latin America and the Caribbean finds life expectancy has increased to within 10 years of the general population in these countries over the last two decades.

Disparities in life expectancy due to demographic and clinical factors at the point participants began ART (including sexual HIV transmission risk, low CD4 cell count, and history of tuberculosis) highlight an ongoing need to reach vulnerable populations in the region.

Life expectancy among adults living with HIV receiving antiretroviral therapy (ART) in Latin America and the Caribbean has increased significantly since HIV testing and treatment services became more widely available, according to research published today in The Lancet HIV journal.

The largest study of its kind indicates that life expectancy for people in the region living with HIV who receive ART is now close to that for the general population, mirroring trends seen in higher-income countries.

In 2016, the WHO launched the 'Treat All' policy recommendations to help achieve the global target of ending AIDS by 2030 by treating all people living with HIV using antiretroviral drugs. By the end of 2020, 96% of low- and middle-income countries (LMICs) were on course to adopt Treat All, compared with 40% in 2016. [1]

ART was introduced to Latin America in the 1990s and became more available during the 2000s. However, little data exists on the life expectancy of people living with HIV in LMICs. Until now, no large-scale investigations had taken place, with studies limited to single-country analyses in South Africa and Brazil. Large studies in Europe, Canada, and the USA have previously shown that ART has greatly increased life expectancy among people living with HIV.

Dr Claudia P. Cortes, from Fundación Arriarán and University of Chile School of Medicine, Chile, said: "More data on HIV in Latin America and the Caribbean is needed and there are several countries in Latin America for which there is practically no information on HIV. Latin America and the Caribbean is a large, heterogeneous, and diverse region, and HIV impacts a number of different populations. It is also, however, a region with the least resources available for HIV clinical studies and research.

"In our analysis, the greatest gains in life expectancy coincided with the period after the launch of Treat All. Since the end of the study period in 2017, more LMICs have gone on to adopt the policies, so we are hopeful that further analysis will show that Treat All is continuing to help transform the lives of people living with HIV." [2]

The authors of the new study analysed data on adults living with HIV starting ART for the first time at CCASAnet (Caribbean, Central and South America network for HIV epidemiology) sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru between 2003-2017. Life expectancy at 20 years old was estimated for three time periods (2003-2008, 2009-2012, and 2013-2017), and by demographic and clinical factors when participants began ART. Life expectancy estimates for the general population were obtained from World Health Organization data.

Among 30,688 study participants living with HIV, 17,491 (57%) were from Haiti and 13,197 (43%) were from other CCASAnet sites. There were 1,470 deaths among people in Haiti and 1,167 deaths at other sites during the study period.

The analysis reveals that life expectancy increased among all age groups over time. From 2003-2008 to 2013-2017, overall life expectancy for people living with HIV who are 20 years of age (or expected number of remaining years of life from age 20 years) increased from an additional 13.9 to 61.2 years in Haiti, and from 31.0 to 69.5 years in the other countries. This has brought life expectancy among people living with HIV on ART to within around 10 years of the general population (69.9 years in Haiti and 78.0 years at all other sites).

However, the authors identified a number of factors contributing to persistent disparities in life expectancy throughout the study. Women had greater life expectancy than men, with estimates of 65.3 years for those in Haiti, and 81.4 years for women in other countries, by the end of the study period. By comparison, estimated life expectancy was 56.0 years of age for men in Haiti, while in other countries estimates for heterosexual men and men who have sex with men were 58.8 and 67.0 years, respectively

In countries other than Haiti, life expectancy for participants with low numbers of CD4 cells (fewer than 200 cells per microlitre of blood) - a type of white blood cells that fight infection, and a marker of HIV disease severity - was 52.7 years by the end of the study. This was considerably lower than the 84.8 years for those with higher CD4 cell counts (more than 200 cells per microlitre). Similar trends were observed in Haiti, with life expectancies of 48.5 and 71.0 years, respectively.

People with a history of tuberculosis - one of the leading causes of death among people living with HIV [3] - also had a lower life expectancy than those with no history of the disease. By the end of the study, in countries other than Haiti, life expectancy was estimated at 48.0 years of age for people with a history of tuberculosis, compared with 74.1 years of age for those without. For the same groups in Haiti, life expectancy was 44.1 and 66.6 years, respectively.

Lower educational attainment was also linked with lower life expectancy. In countries other than Haiti, life expectancy was estimated at 75.5 years of age for people with upper secondary education compared with 57.0 years of age for those with lower secondary education. In Haiti, estimated life expectancies among these groups was 77.7 and 53.3, respectively.

Dr Jessica L. Castilho, from Vanderbilt University Medical Center, USA, said: "The significant gains in life expectancy that we've observed are very encouraging, and mirror reports from higher-income countries on the impact of the WHO's 'Treat All' approach to ART. Ongoing efforts should see the gap between the life expectancies of people living with HIV and the general population in low- and middle-income countries narrow yet further.

"We did, however, also observe that a number of disparities in life expectancies remain, and may in some instances be increasing, indicating a need for future investigations to help improve outcomes for these vulnerable groups." [2]

The authors acknowledge some limitations. A high number of patients were lost to follow-up and, while the authors sought to account for this in their analyses, this may have led to an overestimation of life expectancy. The analysis method used also resulted in a lack of adjustment for some confounding factors in life expectancy estimates. For instance, it was not possible to determine whether differences in life expectancy by HIV transmission risk factors and tuberculosis status were reflective of disparities in CD4+ cell counts. Most CCASAnet sites are located in major urban centres, meaning estimates may not reflect trends in rural or less populous areas.

The study focused on the life expectancy of people starting ART for the first time, so estimates are not reflective of all people with HIV receiving care. A lack of complete information on some key demographic and social factors may also have contributed to disparities in estimated life expectancy.

Writing in a linked Comment, Lara E Coelho and Paula M Luz, from Instituto Nacional de Infectologia Evandro Chagas, Brazil, who was not involved in the study, said: "The findings from the study by Smiley and colleagues suggest that, with prompt ART initiation irrespective of socioeconomic status, life expectancy for all people with HIV will reach that of the uninfected populations in Latin America and the Caribbean. Sadly, however, the old challenges linger amid the COVID-19 pandemic, such that life expectancy gains among people with HIV could wane. The region is affected by endemic income and health inequalities that have been severely aggravated by the COVID-19 pandemic, transforming a health crisis into a humanitarian one. By the end of 2020, poverty was projected to have reached 231 million people in Latin America, a level that was last seen 15 years ago. We anticipate the syndemic effects of the COVID-19 pandemic in the region will disproportionately impact the most vulnerable groups, including people with HIV."

With roughly 80% of jobs being sedentary, often requiring several hours of sitting stooped in front of a computer screen, neck pain is a growing occupational hazard. Smartphones and other devices have also caused people to bend their necks for prolonged periods. But is bad posture solely to blame?

In a recent study, researchers at Texas A&M University have found that while poor neck and head postures are indeed the primary determinants of neck pain, body mass index, age and the time of the day also influence the neck's ability to perform sustained or repeated movements.

"Neck pain is one of the leading and fastest-growing causes of disability in the world," said Xudong Zhang, professor in the Wm Michael Barnes '64 Department of Industrial and Systems Engineering. "Our study has pointed to a combination of work and personal factors that strongly influence the strength and endurance of the neck over time. More importantly, since these factors have been identified, they can then be modified so that the neck is in better health and pain is avoided or deterred."

The results of the study are published online in the journal Human Factors, a flagship journal in the field of human factors and ergonomics.

According to the Global Burden of Disease Study by the Institute for Health Metrics and Evaluation, neck pain is ranked as the fourth leading cause of global disability. One of the main reasons for neck pain has been attributed to lifestyle, particularly when people spend long durations of time with their necks bent forward. However, Zhang said a systematic, quantitative study has been lacking on how personal factors, such as sex, weight, age and work-related habits, can affect neck strength and endurance.

For their experiments, Zhang and his team recruited 20 adult men and 20 adult women with no previous neck-related issues to perform controlled head-neck exertions in a laboratory setting. Instead of asking the participants to hold a specific neck posture for a long time, similar to what might happen at a workplace, they performed "sustained-till exhaustion" head-neck exertions.

"In the laboratory, conducting experiments where subjects do long tasks with their neck can take several hours of data collection, which is not very practical for the experimenters and, of course, the participants in our study," said Zhang. "To solve this problem, our experiments were strategically designed to mimic workplace neck strains but in a shorter period of time."

In these exercises, subjects were seated and asked to put on an augmented helmet that allowed them to exert measurable force by the neck. Then, the researchers asked them to either keep their necks straight or maintain their neck tilted in a forward or backward position. In this position, a force was applied to their head and neck on an adjustable frame. This exertion was either to their maximum capacity of half of it. Before testing, the researchers noted their subjects' age, body mass index and the time of day.

When Zhang and his team analyzed their data, they found that, as expected, work-related factors like head/neck posture play a very important role in determining both neck strength and endurance. But they also observed that while there was no significant difference between male and female subjects' in neck endurance, body mass index was a significant predictor of neck endurance. Also, to their surprise, the time of day affected the neck's ability to sustain an exertion without fatigue.

"It is intuitive to think that over the course of the day, our necks get more tired since we use it more," Zhang said. "But roughly half of our participants were tested in the morning and the remaining in the afternoon. Also, some of the participants had day jobs and some worked the night shift. Despite this, we consistently found the time-of-day effect on neck endurance."

The researchers said their database of neck strength and endurance is also necessary for building advanced musculoskeletal biomechanical models of the neck, which can then be used to, for example, tease apart specific neck muscles that are more vulnerable to injury.

"Looking ahead, we might have the data to begin evaluating if patients recovering from neck injuries are ready to return to work based on whether their neck strength and endurance are within the norm," Zhang said. "Also, engineers and designers could utilize our data to make wearable devices, like helmets, that are more ergonomic and less stressful on the neck."

BOSTON - New research from Boston Medical Center identifies elevated mortality risk for women with back pain when compared to women without back pain. Back pain was not associated with mortality among men indicating long-term consequences of back pain may differ by sex. The overall findings suggest that mild back pain (pain that does not keep a person from exercising or doing daily activities) is unlikely to impact the length of one's life, but risk of mortality was increased among adults with more severe back pain. Published in the Journal of General Internal Medicine, this new study raises the question of whether better management of back-related pain and disability, over time, may extend life.

Back pain is the leading cause of disability worldwide, and disability and inactivity are generally associated with greater mortality. More than 80 percent of Americans experience back pain at some point in their lives, and older women are more likely to experience activity-limiting back pain.

Potential pathways between back pain and mortality were identified through the study including limitations in activities of daily living, and reduced physical activity that may lead to weight gain and the development or worsening of chronic conditions such as cardiovascular disease. Back pain has also been associated with poor balance and falls, which can result in fragility fractures. Such fractures are in turn associated with increased mortality.

Nonpharmacologic treatments recommended for treating back pain include acupuncture, chiropractic care, massage, and physical therapy. There is evidence that these treatments are effective for managing back pain and they are considered safe. Some treatments are known to have potentially serious side effects, such as opioids for pain management. Countless Americans have died as a result of the opioid epidemic, and low back pain is among the most common reasons why opioids are prescribed. The Centers for Diseases Control and Prevention released a report this week highlighting the continued impact of the epidemic with 87,000 Americans dying of overdose in the past year (ending September 2020), the highest number of overdose deaths ever recorded.

"I hope this study will lead to a better understanding of the long-term impacts of activity-limiting back pain on overall health and research to improve back pain treatment over the course of patients' lives," says Eric Roseen, DC, MSc, director of the Program for Integrative Medicine and Health Disparities at Boston Medical Center and an assistant professor of family medicine at Boston University School of Medicine. "Proper management of back pain is important, especially as the opioid epidemic has been exacerbated and the COVID-19 pandemic has impacted people seeking medical care, stress-levels and the environments in which many Americans are working right now."

This is the first systematic literature review on the association of back pain and mortality, and was followed by a meta-analysis of all-cause mortality in 11 studies with 81,337 middle-aged and older adults. Age did not appear to have an effect on the association between back pain and mortality in this review, an unexpected result considering past research showing the impact of back pain on disability increases with age. The highest risk of mortality associated with back pain was observed in studies that only included women, and those that identified adults with more severe back pain.

Future studies should focus on the complex relationship between back pain, back pain treatment, mental health, disability, and mortality.

Leesburg, VA, April 20, 2021--An award-winning Scientific Electronic Exhibit to be presented at the ARRS 2021 Virtual Annual Meeting found no statistically significant threshold for increased renal transplant biopsy risk based on systolic (SBP), diastolic (DBP), or mean arterial (MAP) blood pressure alone.

"When these metrics are combined," first author Winston Wang of the Mayo Clinic Arizona cautioned, "the risk of complication is significantly higher when the SBP is >= 180 mm Hg, DBP is >= 95 mm Hg, and MAP is >= 116 mm Hg."

Wang and team's review of consecutive ultrasound-guided renal transplant biopsies from August 1, 2015 to July 31, 2017 noted recordings of SBP, DBP, and MAP for each patient prior to entering the procedure room. Although no blood pressure threshold to cancel the biopsy was indicated, the development of a major bleeding complication (Common Terminology Classification for Adverse Events grade 3 and above) had been recorded in the electronic medical record.

Of the 1,689 biopsies on 958 patients (547 men, 411 women) meeting the inclusion criteria, only 10 (0.59%) had bleeding complications, and Wang et al. observed no statistically significant difference between biopsies with complication compared to those without complication for SBP (p = 0.351), DBP (p = 0.088), or MAP (p = 0.132).

Acknowledging that previous studies also showed scant correlation between major hemorrhagic complication of renal transplant biopsy and elevated SBP and DBP, compared to normotensive patients, "the data is limited, based on only 4 complications," the authors of this Cum Laude ARRS Annual Meeting Scientific Electronic Exhibit added.

Professor Bin He's team at Carnegie Mellon University, in collaboration with the Mayo Clinic, has discovered that fast oscillations in scalp-recorded electroencephalography can pinpoint brain tissues responsible for epileptic seizures. The collaborative research, recently published in the Proceedings of the National Academy of Sciences (PNAS), leverages noninvasive EEG technology along with the development of a novel machine learning algorithm to automatically identify and delineate concurrent high-frequency oscillations and epileptiform spikes, a key link related to epilepsy. In the near future, these findings may be harnessed to rethink imaging and treatment options for epilepsy patients.

More than 70 million people across the globe are affected by epilepsy, one of the most common neurological disorders. For people with epilepsy, brain activity becomes abnormal, causing seizures or unusual behavior, sensations, and sometimes loss of awareness. The incurable condition affects men and women of all ages, races, and ethnic backgrounds.

While medication is an effective treatment option for some, nearly one-third of epileptic patients do not respond well to medication. Many of these patients undergo surgical removal of the epileptic tissues to stop their seizures, if such epileptic foci can be identified in the brain and safely removed. The go-to clinical process to observe and localize epileptogenic brain activity, known as intracranial electroencephalography (iEEG), is invasive and involves drilling holes in the skull or removing a part of the skull, to place electrodes on the brain. Furthermore, iEEG recording is also time-consuming, lasting from days to weeks, until a spontaneous seizure occurs and can be monitored.

New groundbreaking research led by Bin He, professor of biomedical engineering at Carnegie Mellon University, in collaboration with the Mayo Clinic, combines clinical application and engineering innovation to present a safe, noninvasive, cost-effective, and quicker imaging option for patients with epilepsy.

Other researchers have attempted noninvasive EEG studies; however, He's work is unique in that it discovers and automatically records a novel link between high-frequency oscillations (HFOs) and epileptiform spikes. The link, in turn, identifies a unique biomarker by which the epileptogenic brain can be delineated and localized, thus offering extremely desirable means for noninvasive management of epilepsy, as well as aiding with treatment options.

"Over the years, HFOs have been identified as a promising biomarker for localizing epileptogenic brain tissues and potentially guiding neurosurgery correlated with the origin of seizures," explained He. "Challenges exist in that there are both physiological and pathological HFOs. Only pathological HFOs are tagged with epilepsy and helpful for clinical use, and unfortunately, differentiating between the two is highly-complicated using current practices and methods. Our team hypothesized and proved through morphological and source imaging evidence that pathological HFOs can be identified by the concurrence of HFOs and epileptiform spikes, all recorded noninvasively over the scalp."

He's collaborative study observed and recorded 25 patients with temporal epilepsy. Using a novel technology, the group was able to automatically identify the scalp recorded HFOs consistently cooccurring with epileptiform spikes and localize the corresponding cortical sources generating these events using source imaging techniques. In tandem, they also further validated the clinical value of using the identified pathological HFOs in determining the underlying epileptic tissues responsible for generating seizures, in comparison to clinical findings defined by epileptologists, and the surgical outcomes in the patients. He's results demonstrated significantly improved performance of the new method with comparison to the conventional spike imaging method.

Coming full circle, these findings suggest that concurrent HFOs and spikes reciprocally discriminate pathological activities, providing a translational tool for noninvasive presurgical diagnosis and postsurgical evaluation in vulnerable epileptic patients.

"This technology, if it advances to hospitals and medical centers, could be lifechanging," said He. "It is completely safe and noninvasive, and it occurs over a much shorter timeframe. It is a truly exciting development that brings with it significant societal and financial implications."

Looking ahead, the desire is to expand clinical studies and validate in more patients, with the eventual goal of having the technology adopted worldwide, across the healthcare industry.

OAK BROOK, Ill. - People living with human immunodeficiency virus (HIV) and without known cardiovascular disease have two to three times the noncalcified coronary plaque burden of non-HIV healthy volunteers, according to a study from Canada published in Radiology. Researchers said the results underscore the importance of a heart-healthy lifestyle in people living with HIV.

HIV/AIDS emerged as a major public health crisis in the 1980s. Disease-related mortality peaked in the mid-1990s and has been dropping since, thanks in large part to antiretroviral therapy, which does not cure the disease but helps control it.

Today, people with HIV infection live longer and are increasingly subject to age-related diseases, such as coronary artery disease. Studies from North America and Europe have shown a greater risk of heart attacks in people living with HIV compared with the general population, even after adjustment for risk factors. The reasons for this are not entirely known.

For the new prospective study, researchers compared the burden and CT characteristics of coronary plaque in 265 participants, including 181 asymptomatic people living with HIV without known cardiovascular disease and 84 non-HIV healthy volunteers.

All 265 participants underwent coronary artery calcium scoring, a CT-based assessment that provides information on the presence and amount of calcified plaque in the arteries of the heart. Most of the participants also had coronary CT angiography, a noninvasive imaging option capable of quantifying and characterizing coronary plaque and predicting the risk of adverse cardiovascular events like a heart attack. Image assessors who had been blinded to the clinical characteristics of the participants and their HIV status used the CT angiography results to categorize the coronary plaques as calcified, noncalcified or mixed.

There was no difference between the two groups in coronary artery calcium score and overall plaque prevalence. The median 10-year Framingham Risk Score, a commonly used measure to estimate the risk of coronary artery disease, was also similar.

However, noncalcified plaque prevalence and volume were two to three times higher at coronary CT angiography in people living with HIV compared with non-HIV healthy volunteers after adjustment for cardiovascular risk factors. Noncalcified plaque may be more prone to rupture than calcified plaque.

"Our study shows that noncalcified coronary plaque is increased in people living with HIV," said study lead author Carl Chartrand-Lefebvre, M.D., M.Sc., from the Radiology Department at the Centre hospitalier de l'Université de Montréal (CHUM) in Montreal. "And noncalcified plaque has previously been shown to be associated with worse cardiovascular outcomes than calcified or mixed plaques."

Calcified plaque frequency was reduced in people living with HIV. Treatment with protease inhibitors was associated with higher volume of overall and mixed plaque.

According to Dr. Chartrand-Lefebvre, the differences in plaque burden between the two groups are likely due to a number of factors, including the antiretroviral therapy.

"Multiple studies suggest that there is probably an impact of antiretroviral therapy that could increase the risk of coronary artery disease, although there are far more advantages for people living with HIV to be on antiretroviral therapy, instead of not taking it," he said.

The study results suggest that the adoption of a healthy lifestyle, crucial to preventing atherosclerotic disease in the general population, may be especially important for people living with HIV. Dr. Chartrand-Lefebvre recommended that people living with HIV be aware of their cardiovascular risk factors such as smoking, diabetes, high blood pressure, obesity and lack of physical exercise. They should also discuss with their physicians the best ways to prevent cardiovascular disease.

"For radiologists, these results suggest that coronary CT angiography interpretation in people living with HIV should probably include quantification of coronary plaque by subtypes to allow better cardiovascular risk stratification," Dr. Chartrand-Lefebvre said.

Chronic pain is among the most common chronic conditions in the United States, but estimates of its prevalence and impact vary widely. In 2019, the National Center for Health Statistics of the Centers for Disease Control and Prevention added a new set of questions relating to pain to its National Health Interview Survey (NHIS), a large household-based annual survey that offers valuable insights into the health statuses of U.S. adults nationwide. In an article published in Pain, researchers from Brigham and Women's Hospital and Mass Eye and Ear report that 50.2 million (20.5 percent) U.S. adults experience chronic pain based on analysis of the new NHIS data. They estimated the total value of lost productivity due to chronic pain to be nearly $300 billion annually.

"Chronic pain is a serious condition that affects millions of Americans," said corresponding author R. Jason Yong, MD, MBA, medical director of the Pain Management Center at the Brigham and associate chief of pain in the Department of Anesthesiology, Perioperative, and Pain Medicine. "Other studies have touched on this fact, but data from pain clinics, hospitals and other providers tends to only provide information on people seeking out medical attention. Having the NHIS data to validate previous studies is incredibly impactful."

The authors found that respondents with chronic pain reported missing significantly more workdays compared to those without chronic pain (10.3 days versus 2.8). They used these figures to quantify the total economic impact of chronic pain on Americans, which they estimated to be $79.9 billion in lost wages. Those with chronic pain also reported more limitations to their engagement in social activities and activities of daily living. Back, hip, knee and foot pain were the most common sources of pain reported, and physical therapy and massage therapy were most commonly sought as treatments.

"The impetus for our study arose from the day-to-day clinical finding that many of our chronic sinusitis patients also reported headache, migraine and other forms of chronic pain," said senior author Neil Bhattacharyya, MD, MA, FACS, professor of Otolaryngology--Head and Neck Surgery at Mass Eye and Ear. "We decided to look at the bigger picture of chronic pain, and we were somewhat surprised at the large-scale presence of chronic pain in the US."

The 2019 NHIS included data from 31,997 adults across the nation. When the data was first published in May, investigators decided to focus their initial analysis on ascertaining national estimates of prevalence and impact, but plan to conduct further analysis of other questions included in the survey. This may reveal more specific trends related to pain and its treatment across the U.S., especially regarding opioid use.

"Given the overall scale and impact of pain on Americans, we see that a multimodal, multidisciplinary approach to treating pain is even more important than what we have been emphasizing over the past few decades," Yong said. "Pain medicine is relatively young as a field, and it encompasses specialties including emergency medicine, anesthesia, psychiatry, neurology, physiatry and radiology. We need all of the tools in our armamentarium to treat patients suffering from chronic pain."

PHILADELPHIA-- Researchers at Penn Medicine have identified more genetic mutations that strongly predispose younger, otherwise healthy women to peripartum cardiomyopathy (PPCM), a rare condition characterized by weakness of the heart muscle that begins sometime during the final month of pregnancy through five months after delivery. PPCM can cause severe heart failure and often leads to lifelong heart failure and even death. The study is published today in Circulation.

PPCM affects women in one out of every 2,000 deliveries worldwide, with about a third of those women developing heart failure for life, and about five percent of them dying within a few years. Maternal mortality in the United States has doubled in the last 20 years, and PPCM is a leading cause of these deaths. Previously, the reasons behind why women developed PPCM remained a mystery until a 2016 study strongly suggested that some genetic mutations predispose women to the disease. Zoltan P. Arany, MD, PHD, the Samuel Bellet Professor of Cardiology in the Perelman School of Medicine at the University of Pennsylvania was also the senior author of that study. This newly released study shines a light on four more genetic variants that had not previously been associated with PPCM. It found that this genetic profile is highly similar to that found in patients with non-ischemic dilated cardiomyopathy (DCM), a very similar disease that typically impacts middle-aged men and women, and one that the medical community knows more about.

"This study provides the first extensive genetic and phenotype landscape of PPCM and has major implications for understanding how PPCM and DCM are related to each other," said Arany. "It shows that predisposition to heart failure is an important risk factor for PPCM, suggesting that approaches being developed for DCM may also apply to patients with PPCM."

For the study, Penn researchers identified nearly 470 women with PPCM, retrospectively, from several academic centers in the United States and abroad, and looked at clinical information and DNA samples. Then, they performed next-generation sequencing on 67 genes, including a gene known as TTN, which generates a large protein that controls how heart muscle cells contract and pump blood. 10.4 percent of the patients sampled showed shortened variants in the TTN gene, compared with just 1.2 percent of the reference population. Researchers also found overrepresentation of shortened variants in three other genes not previously associated with PPCM, but previously associated with DCM.

Researchers hope this will push for changes to allow physicians to follow similar, well-established genetic testing practices and counseling guidelines already used for patients with DCM, as well as gene-specific therapies.

"We believe this study shows how important genetic screening and counseling are for women who develop PPCM, something that isn't currently common practice, and perhaps even for their female family members of child-bearing age," Arany said. "As a physician, knowing you have a patient with PPCM who shows these genetic mutations would lead you to make changes in care, such as lowering the threshold for defibrillator use in the case of high-risk variants, or counseling family members on their risk of developing PPCM."

While this study shines an important light on the genes in play for women who develop PPCM, what needs further study is how pregnancy triggers it in some women with a specific genetic predisposition, as not all women with these gene variants will develop PPCM when they get pregnant.

A myriad of genetic factors can influence the onset of diseases like high blood pressure, heart diseases, and type 2 diabetes. If we were to know how the DNA influences the risk of developing such diseases, we, we could shift from reactive to more preventive care, not only improving patients' quality of living but also saving money in the health system. However, tracing the connections between the DNA and disease onset requires solid statistical models that reliably work on very large datasets of several hundred thousand patients.

Matthew Robinson, Assistant Professor at the Institute of Science and Technology (IST) Austria, together with an international team of researchers has now developed a new mathematical model that improves the predictive quality gained from large sets of patient genomic data. This method could help develop personalized predictions about health risks, similar to what a physician does when discussing a family's medical history.

Sampling from Billions

The human DNA consists of several billion base pairs that encode our biological structure and functions. In their study, the scientists selected several hundred thousand genetic markers - short parts of the DNA sequence - for their investigations. Using their statistical model, they then linked these the composition of these markers to the onset of high blood pressure, heart disease or type 2 diabetes in the patients in the database. The researchers were specifically interested in the patients' age at disease onset. With this information, they can then use their model to predict probabilities for when a disease might occur.

Yet, this statistical model cannot construct direct relations between certain genes and disease onset, but only provides an improved prediction of probabilities of disease onset. There is also an important difference between commonly used black-box models for big data studies and this method by Robinson and his colleagues: Black-box models produce predictions, but their inner workings cannot easily be understood by humans because of the many layers of abstraction they use. In contrast, the model by Robinson and his colleagues provides trackable statistical computations.

Being able to understand the inner workings of a mathematical model for producing predictions about health and disease onset is an important part of an ethical approach to using large sets of sensitive patient data. With this, the researcher can explain how the predictions were generated.

Using Patient Data

Harnessing the full potential of such predictive methods requires both effective models and the collection of large genomic datasets that comes with its own concerns of data security and privacy that both the researchers and the health care system have to address.

Strict measures of data security have to be obeyed when using patient data. Only with the permission of the respective ethics boards, the researchers were able to access anonymized patient data from state-funded biobanks - large collections of genetic patient data - in both the UK and Estonia. They used the data from the UK to build their model and the data from Estonia to test its predictive power. The latter even produced some first personalized risk assessments of disease onset. These then will be relayed through the Estonian health care system back to the patients, giving them the incentive to take preventive steps.

The new statistical model by Robinson and colleagues is just one step towards using the full potential of large genomic datasets for preventive health care. Both the models and the data infrastructure of biobanks, together with a robust and secure data protection system, are needed to fulfill the promises of personalized predictive medicine.

PORTLAND, Ore. - Policies designed to prevent the misuse of opioids may have the unintended side effect of limiting access to the pain-relieving drugs by terminally ill patients nearing the end of their life, new research led by the Oregon State University College of Pharmacy suggests.

A study of more than 2,500 hospital patients discharged to hospice care over a nine-year period showed a decreasing trend of opioid prescriptions as well as an increase in the prescribing of less powerful, non-opioid analgesics, meaning some of those patients might have been undertreated for their pain compared to similar patients in prior years.

The findings, published in the Journal of Pain and Symptom Management, are an important step toward optimizing pain management and minimizing the suffering of dying patients. Hospice care refers to treatments whose goal is to maximize comfort and quality of life as opposed to prolonging life.

Researchers at OSU, Oregon Health & Science University, the Dana Farber Cancer Institute and Ariadne Labs in Boston, the University of Massachusetts Medical School and the University of Maryland School of Pharmacy used electronic health record data to examine 2,648 discharges of adult patients to hospice care.

The discharges were from an acute care, academic hospital between Jan. 1, 2010, and Dec. 31, 2018. The average patient age was 65, more than half had cancer, and the study sought to determine the year by year frequency of patients receiving opioid prescriptions.

After adjusting for factors that could affect prescription frequency, including age, specific diagnosis and where the patient was to receive hospice care, the results showed a nearly 12% downward trend from the first year (91.2%) to the last (79.3%).

"Pain is a common end-of-life symptom and it's often debilitating," said the study's lead author, Jon Furuno, an associate professor and the interim chair of the Oregon State Department of Pharmacy Practice, who notes that more than 60% of terminal cancer patients report "very distressing pain."

Opioids, a class of drugs that block pain signals between the body and brain, are an effective pain management tool. But there are barriers, Furuno said, to the optimal prescribing of opioids.

Among the hurdles are timely and accurate pain assessments, patient and caregiver concerns regarding addiction, and caregiver concerns about making mistakes in administering the meds. Additional obstacles are policies and practices aimed at limiting opioid use in response to the opioid epidemic.

Traced to over-prescribing that began in the 1990s, the epidemic claims more than 40,000 American lives annually, according to the U.S. Department of Health and Human Services. Ten million people a year misuse prescription opioids and 2 million suffer from an opioid use disorder. Opioids can be highly addictive and they exist both as prescription painkillers like morphine, hydrocodone, fentanyl and oxycodone and street drugs such as heroin.

Five years ago, the Centers for Disease Control and Prevention produced a guideline for prescribing opioids for chronic pain, and there have been several other federal, state and local efforts over the last 10 years to curb opioid prescribing, Furuno said.

"There are some concerns, however, that indiscriminate adoption or misapplication of these initiatives may be having unintended consequences," he said. "The CDC Prescribing Guideline and the other initiatives weren't meant to negatively affect patients at the end of their lives, but few studies have really looked at whether that's happening. Our results quantify a decrease in opioids among patients who are often in pain and for whom the main goal is comfort and quality of life."

Furuno adds that the concurrent increase in non-opioid analgesic prescriptions suggests health care providers remained concerned about pain management even as they wrote fewer opioid prescriptions.

"Sometimes non-opioids alone are the best choice, or non-opioids in combination with opioids," he said. "But it's important to remember that non-opioids alone are also not without risk and that delaying the start of opioid therapy may be delaying relief from pain.

"Even among patients prescribed opioids during the last 24 hours of their inpatient hospital stay, opioid prescribing upon discharge decreased," Furuno added. "It seems unlikely that patients would merit an opioid prescription on their last day in the hospital but not on their first day in hospice care, and it's well documented that interruptions in the continuity of pain treatment on transition to hospice are associated with poor patient outcomes."

Philadelphia, April 20, 2021 - A collaborative study from the Center for Injury Research and Prevention (CIRP) and the Center for Autism Research (CAR) at Children's Hospital of Philadelphia (CHOP) identified clear strengths and a series of specific challenges autistic adolescents experience while learning to drive. The findings were recently published by the American Journal of Occupational Therapy.

Researchers conducted in-depth interviews with 17 specialized driving instructors who were trained as occupational therapists, driving rehabilitation specialists, or licensed driving instructors and who had completed additional training related to teaching autistic individuals to drive. Their insights stress the importance of providing specialized, scaffolded instruction where skills are taught one at a time, allowing students to develop mastery before adding new skills. These approaches help young autistic drivers develop driving skills over time supported by plenty of caregiver-supervised practice.

Instructors described specific behind-the-wheel challenges among young autistic drivers, including being overly rule-bound, becoming easily distracted, and having difficulty integrating what other drivers are doing with their own hand-eye-foot coordination required to drive. Instructors believed many of these challenges could be overcome through careful skill-building instruction over a prolonged period of time.

Observed strengths of young autistic drivers included carefully following the rules of the road, paying close attention to their driving environment, and limiting risk-taking. Instructors believed these clear strengths help students become competent drivers.

"Through our interviews with specialized driving instructors who worked specifically with young autistic drivers, we learned about teaching strategies perceived to be effective and recommendations to improve the learning-to-drive process for these adolescents and young adults," said Rachel K. Myers, PhD, lead author of the study and a scientist at CIRP. "Rigorous, individualized training is needed for their behind-the-wheel instruction. More research is needed to standardize best practices for autistic adolescent driver instruction."

Besides breaking down driving tasks into discrete learning goals, instructors used a variety of strategies to build driving skills, including having teens sit in the passenger seat and describe what the driver is doing, and repeated practice on the same driving routes to reduce anxiety.

Instructors also stressed that young autistic drivers should be prepared for experiences they may encounter outside the vehicle, such as changing a tire or interacting with law enforcement. After getting licensed, some instructors may recommend autistic adolescents drive only with supervision or restrictions, such as only traveling on familiar routes.

"According to the specialized driving instructors we interviewed, autistic adolescents who had limited experience with other forms of transportation or vehicle use, such as bicycling, before learning to drive had a harder time learning to control the vehicle," said Benjamin E. Yerys, PhD, study author and a clinical psychologist at CAR. "This difficulty could contribute to challenges in controlling speed, maintaining lane position, and managing oncoming traffic. Caregivers should find ways to promote these life skills and hand-eye-foot coordination skills before beginning the learning-to-drive process."

Recent research conducted at CHOP found that newly licensed young autistic drivers have similar to lower crash rates than their non-autistic peers. Additionally, young autistic drivers are much less likely to have their license suspended or to receive a traffic violation than their non-autistic peers.

Driving is an important part of leading an independent life and is one option for ensuring safe mobility for autistic adolescents and young adults. Resources for families to help with the transition to adulthood are available at TeenDriverSource.org and CAR Autism Roadmap.

A new study at Tel Aviv University found that the British variant (termed: B.1.1.7) of Covid-19 is 45% more contagious than the original virus. The researchers relied on data from about 300,000 PCR tests for Covid-19 obtained from the COVID-19 testing lab, which was established in collaboration with the Electra Group.

The new study was conducted by Prof. Ariel Munitz and Prof. Moti Gerlitz of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine, together with Dr. Dan Yamin and PhD student Matan Yechezkel from the Laboratory for Epidemic Modeling and Analysis (LEMA) at the Department of Industrial Engineering, all at Tel Aviv University. The study's results were published in the prominent scientific journal Cell Reports Medicine.

The Electra-TAU laboratory was established in March 2020, right after the outbreak of the first wave of the pandemic in Israel. To date, it has analyzed hundreds of thousands of tests from all over the country - from public drive-in test facilities, as well as programs targeting specific populations - such as 'Shield for Fathers and Mothers' which routinely ran tests in at-risk hotspots like retirement homes.

Prof. Ariel Munitz explains: "We use a kit that tests for three different viral genes. In the British variant, also known as B.1.1.7, one of these genes, the S gene, has been erased by the mutation. Consequently, we were able to track the spread of the variant even without genetic sequencing."

According to Prof. Munitz, the data from the lab shows that the spread of the British variant was very rapid: On December 24, 2020 only 5% of the positive results were attributed to the British variant. Just six weeks later, in January 2021, this variant was responsible for 90% of Covid-19 cases in Israel. The current figure is about 99.5%.

"To explain this dramatic increase, we compared the R number of the SARS-CoV-2 virus with the R of the British variant. In other words, we posed the question: How many people, on the average, contract the disease from every person who has either variant? We found that the British variant is 45% - almost 1.5 times - more contagious."

In the second stage of the study, the researchers segmented contagion by age groups. The results indicated that the turning point for the 60+ population compared to other age groups occurred two weeks after 50% of Israel's 60+ population received their first vaccine shot.

"Until January we saw a linear dependence of almost 100% between the different age groups in new cases per 1,000 people," says Dr. Dan Yamin. "Two weeks after 50% of the 60+ population received the first dose of the vaccine this graph broke sharply and significantly. During January a dramatic drop was observed in the number of new cases in the 60+ group, alongside a continued rise in the rest of the population. Simply put, since more than 90% of those who died from Covid-19 were over 60, we can say that the vaccine saved hundreds of lives - even in the short run."

Moreover, the new study proves that active monitoring of at-risk populations works. "There is a threshold value for determining whether a specific test is positive or negative for the virus - with a lower value indicating a higher viral load," says Prof. Munitz. "When we compared the threshold values of the different genes in 60+ residents of retirement homes with the values measured in 60+ persons in the general population, we saw significantly higher values in the retirement homes. This means that the viral load in retirement homes was lower compared to the rest of the population.

Since the residents of retirement homes are tested routinely, while other people are usually tested only when they don't feel well or have been in contact with someone who had tested positive for the virus, we conclude that constant monitoring of at-risk populations is a method that works. It is important to emphasize: the relatively low viral load was found in retirement homes despite the fact that the British variant had already begun to spread in all populations. Consequently, we show that monitoring retirement homes, together with vaccination that gives precedence to vulnerable populations, prevent illness and mortality."

Dr. Yemin concludes: "Due to crowded conditions, large households and age distribution in the Israeli population, the coronavirus had a more favorable environment for spreading in Israel compared to most Western countries. Our message to the world is that if with our problematic starting point a distinct decline was identified, other Western countries can certainly expect the curve to break - despite the high contagion of the British variant - with a dramatic drop in severe cases following the vaccination of 50% of the older population, alongside targeted testing at risk epicenters."

Frequent use of social media may not amount to the same as addiction, according to research at the University of Strathclyde.

The study invited 100 participants to locate specific social media apps on a simulated smartphone screen as quickly and accurately as possible, while ignoring other apps. The participants were varied in the extent and type of their social media use and engagement.

The exercise aimed to assess whether social media users who reported the greatest level of use were more likely to have their attention drawn to the apps through a process known as 'attentional bias,' which is a recognised hallmark of addiction.

It also assessed whether this bias was associated with scores on established measures of social media engagement and 'addiction'.

The findings did not indicate that users' attention was drawn more to social media apps than to any others, such as a weather app; they were also not associated with self-reported or measurable levels of addictive severity. This contrasted with other studies which have shown attentional bias related to addictions such as gambling and alcohol.

The research has been published in the Journal of Behavioural Addictions.

Dr David Robertson, a Lecturer in Psychology at Strathclyde and a partner in the research, said: "Social media use has become a ubiquitous part of society, with 3.8 billion users worldwide. While research has shown that there are positive aspects to social media engagement, such as feelings of social connectedness and wellbeing, much of the focus has been on the negative mental health outcomes which are associated with excessive use, such as higher levels of depression and anxiety.

"The evidence to support such negative associations is mixed but there is also a growing debate as to whether excessive levels of social media use should become a clinically defined addictive behaviour.

"We did not find evidence of attentional bias. People who frequently checked and posted their social media accounts were no more likely to have their attention drawn to the icon of a social media app than those who check and post less often.

"Much more research is required into the effects of social media use, both positive and negative, before definitive conclusions can be reached about the psychological effects of engagement with these platforms. Our research indicates that frequent social media use may not, at present, necessarily fit into traditional addiction frameworks."

Targeted therapy in early stages of breast cancer can pave the way for a notable higher success rate, shows a study from the University of Bergen, Norway (UiB).

PARP (Poly (ADP-ribose) polymerase) inhibitors represent an established targeted therapy for multiple cancer types, including cancers of the prostate, ovary and rare cases of breast cancer.

PARP inhibitors take advantage of defects in a central mechanism of DNA damage repair, observed in these cancers. While such compounds have been successfully applied in ovarian and prostate cancers, to this end only a small minority of patients with breast cancer (2-3%), harboring germline mutations in the BReast CAncer type-1 and -2 (BRCA1/2) genes have benefitted, and a seminal study conducted 12 years ago reveled no benefit for patients with breast cancer not harboring such mutations.

Now, a national Norwegian study headed by professors Hans Petter Eikesdal, Stian Knappskog and Per Eystein Lønning at University of Bergen and Haukeland University Hospital for the first time reveals benefit of the PARP inhibitor Olaparib in patients with early breast cancer not harboring germline mutations.

Poor prognosis - considerable results

In the PETREMAC study, unselected patients with large (>4 cm diameter) so-called triple negative breast cancers were treated upfront with Olaparib.

Triple negative breast cancers is a breast cancer subgroup often affecting young patients and is a form of breast cancer associated with a poor prognosis.

Among 32 patients treated, 18 (56%) responded with tumor regression on Olaparib monotherapy. Most importantly, 16 out of the 18 responders revealed molecular markers predicting a likely benefit (gene mutations or so-called epigenetic modifications) of genes involved in the process of DNA repair contrasting only 4 out of 14 non-responders.

These findings allow identification of individual tumors likely to benefit from PARP inhibition. Five patients harbored germline mutations (i.e. patients that may potentially be treated with a PARP inhibitor prior to this study).

However, among patients not harboring such germline mutations (i.e. patients that would normally be excluded from PARP inhibitor therapy), 14/26 patients (54%) responded to therapy. Moreover, among these 14 patients, 12 could be identified upfront as likely responders based on analyzing their tumor tissue for mutations / epimutations affecting DNA repair.

Improved personalized treatment

In conclusion, the study challenges the previous dogma that PARP inhibition may not work for patients not harboring germline mutations. Most importantly, the authors found a strong correlation between response to therapy and molecular markers easily detectable in the tumor tissue.

"While the results need confirmation in independent studies, our results point toward improved personalized treatment for many patients diagnosed with triple negative breast cancer", says professor Lønning.

Finally, the study illuminates a concept gaining increasing support in oncology: While previous studies revealed no benefit from PARP inhibition in late-stage breast cancer, this study demonstrates a therapy which was ineffective in late cancer may potentially be of great benefit in the early setting.