Publisher Health

Mandates designed to decrease opioid prescriptions in the U.S. have worked, but they also have had an unintended and undesirable public health outcome, according to a recent study from a researcher at The University of Texas at Dallas.
The study, published online July 2 in Production and Operations Management, focused on mandated use of Prescription Drug Monitoring Programs (PDMPs). Many states have implemented policies that require prescribers to check a patient’s prescription history prior to initiating or refilling prescriptions for controlled substances.
Dr. Tongil “TI” Kim, assistant professor of marketing in the Naveen Jindal School of Management, and the study’s co-authors found that in states that mandated PDMP use, opioid prescriptions decreased as intended. The mandates, however, had the unintended effect of driving existing opioid users toward more lethal illicit substitutes, such as heroin.
“There are currently more than 2 million individuals with opioid-use disorder, characterized by chronic abuse of prescription opiates,” Kim said. “With more than 130 people dying from opioid overdose every day, this has become a serious social issue in America.”
Addressing the Epidemic
The overprescribing of opioids by physicians is considered a primary driver of the nationwide epidemic, Kim said. Many patients who are introduced to prescription opioids, usually for pain management, go on to display a pattern of increasing usage or they begin using more dangerous drugs instead.

Women with a breast cancer diagnosis undergoing procedures for fertility preservation are not at increased risk of recurrence of the disease or disease-specific mortality. This has been shown in a study by Karolinska Institutet in Sweden that followed the participants for five years on average. The results, published in the journal JAMA Oncology, could in the future provide safety and new hope to women who want to preserve their fertility after cancer treatment with chemotherapy.
Almost one in ten women affected by breast cancer are of childbearing age and are at risk of becoming infertile from chemotherapy treatment. With the hope of being able to have children after completing cancer treatment, many women choose to undergo procedures for fertility preservation with or without hormonal stimulation. These methods include cryopreservation, the freezing of embryos, female gametes (oocytes) and ovarian tissue.
“It is not unusual that women with hormone-positive breast cancer or their treating doctors opt out of the procedures for fertility preservation because of the fear that these procedures will increase the risk of cancer recurrence or death. In some cases, women are also advised to wait 5-10 years before trying to conceive, and with increasing age, fecundity in all women decreases. More knowledge is therefore needed about the safety of procedures for fertility preservation at the time of a breast cancer diagnosis,” says the study’s first author Anna Marklund, researcher at the Department of Oncology-Pathology, Karolinska Institutet.
In this study, researchers at Karolinska Institutet and Karolinska University Hospital have investigated whether procedures for fertility preservation in connection with a breast cancer diagnosis entail an increased risk of disease recurrence or death. The study followed the women for five years on average.
The registry study covers 1,275 women of childbearing age who were treated for breast cancer between 1994-2017 in Sweden. Of these, 425 underwent procedures for fertility preservation with or without hormonal stimulation. The control group of 850 women were treated for breast cancer but did not undergo procedures for fertility preservation.
The women who underwent procedures for fertility preservation and the women in the control group were matched on age at diagnosis, calendar period at diagnosis and healthcare region. The statistical data were taken from both nationwide healthcare registers and population registers with data on outcomes, disease- and treatment-related variables and socio-economic characteristics.
The proportion of women without relapse over the five years was 89 per cent among those that underwent hormonal stimulation of the ovaries, 83 per cent among women with ovarian tissue freezing, and 82 per cent among women who did not undergo procedures for fertility preservation.
Five years after treatment for breast cancer, the survival rate was 96 per cent in the group that underwent hormonal stimulation to freeze eggs or embryos, 93 per cent in the group that underwent procedures for fertility preservation who did not undergo hormone stimulation and 90 per cent in the group that did not undergo procedures for fertility preservation.
“We did not see any increased risk of relapse or mortality when procedures for fertility preservation were undertaken, compared to the women who did not undergo procedures for fertility preservation. This is valuable information that can contribute to changed care routines when it comes to young women with breast cancer who want to preserve their fertility,” says the study’s last author Kenny Rodriguez-Wallberg, adjunct professor and research group leader at the Department of Oncology-Pathology, Karolinska Institutet, and chief physician at Karolinska University Hospital.
The researchers now plan to follow up on the results after another five years.
The study was funded by the Swedish Cancer Society, Radiumhemmet’s Research Funds, the Breast Cancer Association, Region Stockholm, and Karolinska Institutet. There are no reported conflicts of interest.
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The risk of canine cognitive dysfunction, a.k.a. “doggy dementia,” is far greater in dogs who don’t get enough exercise, researchers found. Their risk factors echo some in humans, whose homes they share.Around the time Dante turned 8, he started to seem a little off. The 70-pound Bernese mountain dog would pace his family’s home in Interlaken, N.Y., like a caged bear. Then he might stand stock still, staring trance-like at the pedals of the family’s organ. Or at a corner of a room. In the middle of the night, he would wake up and begin barking incessantly, for no obvious reason.Then the indoor incontinence began.A brain scan confirmed that Dante had canine cognitive dysfunction, colloquially known as doggy dementia. It is often described as the dog’s analog to Alzheimer’s disease. Some studies have found it can occur in at least 14 to 35 percent of older dogs. But because the symptoms resemble those in other diseases, its true prevalence is difficult to confirm.A large new study of 15,019 dogs enrolled in the Dog Aging Project, an ongoing investigation into canine illness and aging, published Thursday in the journal Scientific Reports, identifies the top factors associated with a dog’s risk of getting the disease.A key finding: Exercise may play a significant preventive role. The odds of a cognitive dysfunction diagnosis were 6.47 times higher in dogs reported as not active compared with those reported to be very active, researchers at the University of Washington found. But they also said that the disease itself could lead to lack of exercise, emphasizing that the study results, which are based on observations by owners, suggest correlation, not causation.Odds of getting the disease also appear to increase in dogs that have neurological disorders, or impaired hearing or sight. Annette Fitzpatrick, a co-author of the study and a University of Washington research professor with expertise in dementia in people as well as canines, commented, “When you don’t get stimulation from the outside world, it seems to increase the risk of our not even being able to use our brains as well.”The study, she said, “shows that there may be other things we can be aware of, to try to reduce the onset of cognitive dysfunction.”And certainly age matters. A dog’s life expectancy often depends on breed, size and body mass: think mastiff (six to 12 years) versus Chihuahua (12 to 20 years). During the later years of a dog’s projected life span, each successive year contributed to the potential for disease onset, the study found.In fact, the researchers noted, risk factors that correlate with canine cognitive dysfunction mirror some of the factors for humans with dementia, including Alzheimer’s disease.Earlier studies of canine cognitive dysfunction often drew from veterinary assessments in smaller populations of older dogs; this one is culled from dogs who range in age from puppyhood to mid-20s. In the coming years, as these dogs grow older, the project, which has enrolled more than 40,000 dogs and hopes to reach 100,000, will issue more complex findings on cognitive dysfunction and other diseases.In this study, the prevalence of canine cognitive dysfunction among all the dogs, young and old, was 1.4 percent. But the average age of the dogs was just 6.9 years, and only 19.5 percent of the dogs analyzed were in the last quarter of their life span.“This study compares dogs with cognitive dysfunction to those that don’t have it,” Dr. Fitzpatrick said. “But as the years progress, we can look at the same dog who maybe had great cognitive function but then declined.”Matt Kaeberlein, a co-director of the Dog Aging Project, with Dobby, his 12-year-old German shepherd, in their Seattle backyard.Grant Hindsley for The New York TimesDobby and Dr. Kaeberlein’s late dog Chloe keep inspiring him to research causes of canine aging.Grant Hindsley for The New York TimesThe results were derived from just one baseline accounting by owners of their dog’s health and lifestyle experience between 2019 and 2020, and a particularly high-threshold cognitive function questionnaire.Among the questions:How often does your dog pace up and down, walk in circles and/or wander with no direction or purpose?How often does your dog get stuck behind objects and is unable to get around?How often does your dog walk into walls or doors?How often does your dog have difficulty finding food dropped on the floor?If the study findings have a familiar, even intuitive ring, that may be because the Dog Aging Project, which receives funding from the National Institute on Aging, a branch of the federal National Institutes of Health, may shed insight into factors that affect the life span of humans well as the dogs who share their homes.Unlike laboratory animal subjects such as fruit flies and mice, companion dogs are affected by their owners’ environmental and social factors, such as secondhand cigarette smoke, lawn pesticides and access to health care.“Estimates of human longevity say that about 75 percent is due to environment and 25 percent is genetic,” said Matt Kaeberlein, a biogerontologist at the University of Washington who is a co-director of the Dog Aging Project. “So companion dogs give us the opportunity to really understand the role of that environmental variability in the biological aging process.”Moreover, because dogs age much more rapidly than humans, the studies underway within the project provide opportunities along an expedited timeline for insights into human and canine aging.Dr. Kaeberlein’s motivation derives not only from his professional background but also from his many years as a dog owner. He shared stories of Chloe, his lively, loving, now-deceased keeshond, who began to stare blankly and get tangled in furniture, stricken with canine cognitive dysfunction. Or Dobby, his current inspiration, the family’s longhaired German shepherd who “is just a special dog,” but who, at 12 years old, has already beat back cancer once and can no longer cavort in the backyard to chase wand soap bubbles.“I would really like it if my dogs could live longer,” Dr. Kaeberlein said. “And I would really like it if I could help other people’s dogs live longer.”The trials now underway within the project, which began in 2014 and has researchers from the University of Washington and Texas A&M, as well as from the Cornell University College of Veterinary Medicine and other universities, includes those for potentially life-expanding drugs and a biobank of tissue donated by owners of deceased dogs. It released a study that is shaking the dog world, because of its finding that better health in dogs is correlated with a single daily feeding.(As Dr. Kaeberlein discussed that association during a phone interview, two small, highly food-motivated canines who had been snoozing at this reporter’s side sat up abruptly, whining and howling in protest. Dr. Kaeberlein hastened to add that the study’s observation is more likely a comment on obesity and morbidity than it is a prescription for feeding frequency, which is in keeping with the latest study’s positive correlation with exercise.)Dante with his owner Lisa Mitchell, who worked with one of her other dogs, Rook, on obedience at Cass Park in Ithaca.Heather Ainsworth for The New York TimesCanine cognitive dysfunction is difficult to pinpoint. A dog’s seeming ignorance of a commonplace command could indicate deafness or old-age stubbornness rather than an atrophying brain. Symptoms that look like cognitive dysfunction could actually be from stroke, brain inflammation, diabetes or Cushing’s disease, said Dr. Nicole Ehrhart, a veterinarian and director of the Columbine Health Systems Center for Healthy Aging at Colorado State University. Veterinarians rely initially on keen owner observation, she said, and then perform diagnostic tests.“Look at your dog looking into your eyes and see how long they hold your gaze, especially if you have a treat by your face,” she said. “Because as dogs get dementia, they can’t focus on things they would normally focus on.”Dr. Ehrhart, who was not involved in the Dog Aging Project study, called the new research “wonderful confirmation of something that we know across all species: that exercise is good for healthy aging and that lifelong habits of exercise can be preventive for Alzheimer’s disease and other cognitive issues.”In fact the average life expectancy for Bernese mountain dogs is six to eight years; Dante is now 11. But he had been particularly active in his younger years: He had the physical and mental acuity to gleefully navigate complex obstacle course competitions and leap imperviously off top stairs at a single bound.But now, the typically love-seeking Berner shies away from his household pack — three Golden retrievers and two doting, worried humans. Instead, he prefers to plop down under his favorite lilac bush, even in the pouring rain.“I used to try to make him come inside to be with us,” said Lisa Mitchell, his owner. “But after a year I thought, ‘Tomorrow might be his last day and maybe he’s more comfortable there.’ So we’ve just given over to letting him stay outside alone, if that’s where he wants to be.Although there are medicines and diets that can ameliorate the dog’s cognitive dysfunction for a time, Dr. Ehrhart said, owners needed to be sensitive to their dog’s increasing disorientation. Don’t disrupt their routines. Don’t move around furniture. Secure your yard, so the dog can’t wander away and get lost. If you want to host a loud dinner party with unfamiliar humans, put the dog in a comforting environment that is not so stimulating.And know that dogs, like older humans, can get “sundowner syndrome”: increased anxiety and disorientation as the day comes to a close.“It turns out that probably the best model for human aging has been aging alongside of us for hundreds and hundreds of years,” Dr. Ehrhart said. “This is a two-way street: Anything we’re going to be doing to improve our dogs’ health and life span is likely to improve ours, and anything we’re doing for humans is very likely to improve our dogs’. And who doesn’t want that?”

Stopping statin treatment early could substantially reduce lifetime protection against heart disease since a large share of the benefit occurs later in life. That’s the finding of a modelling study presented at ESC Congress 2022.1
Lead author Dr. Runguo Wu of Queen Mary University of London, UK said: “The study indicates that people in their 40s with a high likelihood of developing cardiovascular disease, and people of all ages with existing heart disease, should be considered for immediate initiation of cholesterol lowering treatment. Stopping treatment, unless advised by a doctor, does not appear to be a wise choice.”
Cardiovascular disease is the most common cause of ill-health and death worldwide, and high cholesterol is a key modifiable risk factor.2 Strong evidence shows that reducing low-density lipoprotein cholesterol by 1 mmol/L with statins reduces the risks of ischaemic heart disease and stroke by 24%-25%.3 Statins are the most commonly used lipid-modifying drug — it is estimated that in 2018, they were taken by more than 145 million people.4 However, delayed treatment initiation and poor adherence are common.5,6 Exaggerated claims about side-effects of statins may also be responsible for under-use among individuals at increased risk of cardiovascular events.7
There is some uncertainty about when to start and how long to persist with statin therapy to optimise the effects. This study estimated the accumulation of benefit with statins according to age at therapy initiation using a microsimulation model that was developed using data on 118,000 participants of large international statin trials from the Cholesterol Treatment Trialists’ (CTT) Collaboration and 500,000 individuals in the UK Biobank population cohort.
The model used individual characteristics (e.g. age, sex) and disease histories to simulate the annual risk of heart attack, stroke, coronary revascularisation, diabetes, cancer, vascular death and nonvascular death for each participant. Treatment with a standard dose of statin (40 mg daily) was used to estimate the effect of therapy versus no therapy in these scenarios: (1) lifelong therapy (used until death or 110 years of age if earlier), (2) therapy stopped at 80 years of age, and (3) delayed initiation of therapy by five years in participants under 45 years of age.
The benefit of statins was measured in quality-adjusted life years (QALYs), which is the length of life adjusted by health to reflect quality of life. One QALY is equal to one year of life in perfect health. Benefits were also reported separately according to baseline cardiovascular risk, which refers to the likelihood of having a heart attack or stroke in the next 10 years, and is based on age, blood pressure, cholesterol levels, smoking status, and medical conditions.8
The researchers found that a large part of QALYs gained with statin therapy accrued later in life. The higher the participants’ 10-year cardiovascular risk, the larger and earlier the statin benefit accrued. Compared with lifelong statins, stopping therapy at 80 years of age erased a large share of the potential benefit, especially for people with relatively low cardiovascular risk.

Smokers have weaker hearts than non-smokers,according to research presented at ESC Congress 2022. The study found that the more people smoked, the worse their heart function became. Some function was restored when people kicked the habit.
“It is well known that smoking causes blocked arteries, leading to coronary heart disease and stroke,” said study author Dr. Eva Holt of Herlev and Gentofte Hospital, Copenhagen, Denmark. “Our study shows that smoking also leads to thicker, weaker hearts. It means that smokers have a smaller volume of blood in the left heart chamber and less power to pump it out to the rest of the body. The more you smoke, the worse your heart function becomes. The heart can recuperate to some degree with smoking cessation, so it is never too late to quit.”
According to the World Health Organization, tobacco kills more than eight million people each year. Cigarette smoking is responsible for 50% of all avoidable deaths in smokers, with half of these due to atherosclerotic cardiovascular diseases such as heart attack and stroke. The detrimental effects of smoking on the arteries and arterial diseases such as heart attack and stroke are well established.
Studies have also shown that smoking is associated with a higher risk of heart failure, where the heart muscle does not pump blood around the body as well as it should, usually because it is too weak or stiff. This means that the body does not receive the oxygen and nutrients it needs to work normally. The link between smoking and heart structure and function has not been fully examined. This study therefore explored whether smoking was related to changes in the structure and function of the heart in people without cardiovascular disease, and the effect of changing smoking habits.
The study used data from the 5th Copenhagen City Heart Study which investigated cardiovascular risk factors and diseases in the general population. A total of 3,874 participants aged 20 to 99 years without heart disease were enrolled. A self-administered questionnaire was used to obtain information on smoking history and to estimate pack-years, which is the number of cigarettes smoked through life. One pack-year is defined as 20 cigarettes smoked every day for one year.
Participants had an ultrasound of the heart, called echocardiography, which provides information about its structure and how well it is working. The researchers compared the echocardiography measures of current smokers versus never smokers after adjusting for age, sex, body mass index, hypertension, high cholesterol, diabetes and lung function.
The average age of participants was 56 years and 43% were women. Nearly one in five participants were current smokers (18.6%), while 40.9% were former smokers and 40.5% had never smoked. Compared to never smokers, current smokers had thicker, weaker and heavier hearts. Increasing pack-years were associated with pumping less blood. Dr. Holt explained: “We found that current smoking and accumulated pack-years were associated with worsening of the structure and function of the left heart chamber — the most important part of the heart. Furthermore, we found that over a 10-year period, those who continued smoking developed thicker, heavier and weaker hearts that were less able to pump blood compared to never smokers and those who quit during that time.”
She concluded: “Our study indicates that smoking not only damages the blood vessels but also directly harms the heart. The good news is that some of the damage is reversible by giving up.”
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Materials provided by European Society of Cardiology. Note: Content may be edited for style and length.

If bacteria enter the body, it often takes just a few minutes for the innate immune system to recognise them as foreign and set the immune defence in motion. Receptors of the immune system that recognise bacterial cell wall components play a central role in this process. An important immune stimulatory cell wall component is the molecule muramyl dipeptide (MDP), which is recognised by the receptor NOD2. A team led by LMU immunologist Veit Hornung has now discovered a previously unknown crucial intermediate step in this important process, as the scientists report in the journal Nature.
The receptor NOD2 is mainly produced by immune cells and cells of the intestinal mucosa. When activated by the molecule MDP, it triggers inflammatory responses that, among other things, prevent bacteria from entering the intestinal wall. To investigate which genes are involved in this signalling pathway, the researchers conducted an extensive genetic screen in cultured human cells. To their surprise, they found that a gene for the enzyme NAGK plays a crucial role. NAGK is a so-called kinase, an enzyme that can transfer a phosphoryl group to other molecules.
“For NOD2 to identify its target molecule MDP, it must first be converted by NAGK into its phosphorylated form, as we were able to show through subsequent molecular biological and biochemical investigations,” says Veit Hornung. “This was totally unexpected.” This role of NAGK was previously unknown and is independent of the enzyme’s function in sugar metabolism already described in the literature. However, the researchers are convinced that it corresponds well with the enzyme’s original function in bacteria, where it plays an important role in recycling the bacterial cell wall. Throughout evolution, NAGK has been preserved in organisms that lack a cell wall, therefore pointing towards its role in other functions.
The new findings could also be relevant to the mechanisms of inflammatory bowel disease, as mutations in the NOD2 gene are particularly frequently associated with Crohn’s disease. “This work leads to the exciting question, does the absent or inactivation of NAGK lead to inflammatory bowel disease?” says Che Stafford, first author of the study.
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Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length.

Throughout the COVID-19 pandemic and when maximum protection is needed against air-born infections, the N95 respirator has remained the gold standard of personal protective equipment. However, it is also much more difficult to produce and obtain than a standard surgical mask.
But a recent study published in PLOS ONE demonstrates that a simple modification to a surgical mask using rubber bands can improve its protective seal against particle exposure to the level of an N95 respirator.
To achieve N95-level protection, the respirators should demonstrate a minimum score of 100 on a standardized battery of tests — the Occupational Safety and Health Administration’s passing threshold — against the passage of particles that would potentially expose an individual to disease. Standard surgical masks are not as protective because they don’t seal around the wearer’s face, allowing particles to bypass the filter peripherally.
A research team led by a Michigan Medicine surgeon worked with 40 health care workers to test standard surgical masks modified with two 8-inch rubber bands over the crown of the subject’s head, bridge of the nose, around the cheeks and under the chin within the boundaries of the mask.
Thirty-one of the subjects, or 78%, had modified masks that passed a fit test with a score of greater than 100. The passing masks scored an average of 151, a significantly better fit than an unmodified surgical mask score of 3.8 but lower than a properly fitted N95 mask’s score of 199. By the last day of investigation, all of the modified masks passed the N95 threshold, suggesting that greater experience with the banding improved fit and performance.
This easy modification could address N95 respirator shortages worldwide and provide health care workers and individuals in under-resourced regions — or even in a resourced area like the U.S. when production demands can’t properly meet needs in a pandemic — a practical means for increased personal protection, said Jaimo Ahn, M.D., Ph.D., FACS, senior author of the paper and professor of orthopaedic surgery at University of Michigan Medical School.
“While not a vaccine, this approach emphasizes prevention rather than treatment,” Ahn said. “While not sophisticated, it has the potential to save lives and preserve wellness. Its effect will last as long as there are respiratory diseases and PPE demand exceeds supply. It is immediately impactful and sustainable, yet simple and cheap.”
Additional authors include Agnes Z. Dardas, M.D., Viviana M. Serra Lopez, M.D., Lauren M. Boden, M.D., Taras Grosh, M.D., Daniel J. Gittings, M.D., Kevin Heym, and Emily Koerber, all of the University of Pennsylvania at the time the study was performed.
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Materials provided by Michigan Medicine – University of Michigan. Original written by Noah Fromson. Note: Content may be edited for style and length.

Do you love those sugary-sweet beverages, reconstituted meat products and packaged snacks? You may want to reconsider based on a new study that explored whether individuals who consume higher amounts of ultra-processed food have more adverse mental health symptoms.
Although ultra-processed foods are convenient, low cost, quick to prepare or ready-to-eat, these industrial formulations of processed food substances (oils, fats, sugars, starch, protein isolates) contain little or no whole food. They result from extensive ‘physical, biological, and chemical processes’ that create food products that are deficient in original and natural food. Ultra-processed foods typically include flavorings, colorings, emulsifiers and other cosmetic additives.
While there is some evidence regarding ultra-processed food consumption and depression, data are sparse regarding other adverse mental health symptoms including anxiety and mentally unhealthy days.
Researchers from Florida Atlantic University’s Schmidt College of Medicine and collaborators explored a nationally representative sample of the United States population to determine if individuals who consume high amounts of ultra-processed foods report significantly more adverse mental health symptoms including depression, anxiety and mentally unhealthy days.
They measured mild depression, number of mental unhealthy days and number of anxious days in 10,359 adults 18 and older from the U.S. National Health and Nutrition Examination Survey.
Results of the study, published in the journal Public Health Nutrition, showed that individuals who consumed the most ultra-processed foods as compared with those who consumed the least amount had statistically significant increases in the adverse mental health symptoms of mild depression, “mentally unhealthy days” and “anxious days.” They also had significantly lower rates of reporting zero “mentally unhealthy days” and zero “anxious days.” Findings from this study are generalizable to the entire U.S. as well as other Western countries with similar ultra-processed food intakes.
“The ultra-processing of food depletes its nutritional value and also increases the number of calories, as ultra-processed foods tend to be high in added sugar, saturated fat and salt, while low in protein, fiber, vitamins, minerals and phytochemicals,” said Eric Hecht, M.D., Ph.D., corresponding author and an affiliate associate professor in FAU’s Schmidt College of Medicine. “More than 70 percent of packaged foods in the U.S. are classified as ultra-processed food and represent about 60 percent of all calories consumed by Americans. Given the magnitude of exposure to and effects of ultra-processed food consumption, our study has significant clinical and public health implications.”
Researchers used the NOVA food classification for the study, which is a widely used system recently adopted by the Food and Agricultural Organization of the United Nations. NOVA considers the nature, extent and purpose of food processing in order to categorize foods and beverages into four groups: unprocessed or minimally processed foods, processed culinary ingredients, processed foods and ultra-processed foods.
“Data from this study add important and relevant information to a growing body of evidence concerning the adverse effects of ultra-processed consumption on mental health symptoms,” said Charles H. Hennekens, M.D., Dr.PH, co-author, the first Sir Richard Doll Professor of Medicine, and senior academic advisor, FAU Schmidt College of Medicine. “Analytic epidemiologic research is needed to test the many hypotheses formulated from these descriptive data.”
According to the National Institute of Mental Health, nearly 1 in 5 adults live with a mental illness. Mental illnesses, including depression and anxiety, are leading causes of morbidity, disability and mortality.
Co-authors of this original research are Anna Rabil, Institute of Etiological Research; Euridice Martinez Steele, Ph.D., University of Sao Paolo; Gary A. Abrams, M.D., University of South Carolina School of Medicine; Deanna Ware, M.P.H., Georgetown University Medical Center and Institute of Etiological Research; and David C. Landy, M.D., Ph.D., University of Kentucky College of Medicine.
This research was funded in part by the Bertarelli Foundation.

Researchers at the National Institutes of Health have found that a novel blood test can be used to easily evaluate disease severity in patients with pulmonary arterial hypertension (PAH) and predict survivability. PAH is a rare, life-threatening condition that causes unexplained high blood pressure in the lungs. In early clinical studies, the researchers showed the test to significantly improve upon conventional tests, some of which use invasive tools.
The new blood test measures DNA fragments shed by damaged cells. Researchers found that these fragments, called cell-free DNA, were elevated in the blood of patients with PAH and increase with disease severity. If future studies confirm the findings, this first-of-its-kind blood test for PAH patients could allow doctors to intervene faster to prevent or delay progression of the disease and possibly save lives. Cell-free DNA is a relatively new analytical technique that is growing in its potential medical uses, which include the early detection of heart- and lung-transplant rejection as well as early detection of cancer.
The study was funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Clinical Center, both part of NIH. The findings will appear online in the journal Circulation, a publication of the American Heart Association.
PAH is a rare form of pulmonary hypertension that can cause difficulty breathing, chest pain, and fatigue. The disease, whose exact cause is unknown, is estimated to affect less than 50,000 people in the United States, according to the NIH’s Genetic and Rare Diseases Information Center. It is characterized by progressive narrowing and blockage of the small pulmonary arteries of the lungs, strain on the right side of the heart, and eventual death from heart failure. The damage to the lung in severe cases can require lung transplantation. Patients with PAH have a high death rate, and the condition mostly affects women. Despite treatment advances, it currently has no cure.
Current tests used to monitor PAH severity rely on established risk prediction scores based on clinical symptoms and on the use of an invasive catheter to measure pressure in the lungs. Doctors sometimes use echocardiography, or heart imaging, to measure pressures in the heart as an indirect measurement of lung pressure, but these tests tend to lack reliability and sensitivity.
“Researchers have been actively searching for novel, less-invasive approaches to evaluate PAH severity, disease progression, and response to therapy for more than a decade. These cell-free DNA analyses represent progress toward that goal,” said study co-author Michael A. Solomon, M.D., M.B.A., who is part of the NHLBI Cardiovascular Branch and co-director of the NIH Clinical Center Pulmonary Arterial Hypertension Section.
Sean Agbor-Enoh, M.D., Ph.D., study co-author and chief of the NHLBI’s Laboratory of Applied Precision Omics, agreed. “Here we’re proposing a one-time test where you collect a vial of blood from a patient and use that to predict survival. We’re very encouraged by the early results.”
In the current study, the research team analyzed cell-free DNA from blood samples taken from 209 adult patients, predominately women, diagnosed with PAH at two large U.S. medical centers. The researchers compared the results to cell-free DNA measured from a control group of 48 healthy volunteers without PAH at the NIH Clinical Center.
They found that cell-free DNA was elevated in patients with PAH, and also found that cell-free DNA concentrations increased in proportion to the severity of the disease. Patients with the highest level of cell-free DNA had a 3.8 times greater risk of either death or a need for lung transplantation compared to those with the lowest level of cell-free DNA, the researchers said.
Further analyses of cell-free DNA samples revealed that multiple tissue types — including the heart, blood vessels, fat tissue, and inflammatory cells circulating in the blood — were affected by PAH. The new blood test will allow researchers to better pinpoint the specific tissues involved in the PAH disease process. This knowledge may lead to new drug interventions for PAH, whose current treatment options may slow but not halt or reverse disease progression.
In addition to funding from the Intramural Research Program of the NHLBI, this research is supported by the NIH Clinical Center Research Award for Staff Clinicians Program, the NIH Distinguished Scholar Award, the Lasker Clinical Research Scholars Program, and the Intramural Research Programs of the NIH Clinical Center.

Published23 hours agoSharecloseShare pageCopy linkAbout sharingImage source, AFPSouth Korea has again recorded the world’s lowest fertility rate with the number sinking to a new low.The rate in the country first dropped lower than one child per woman in 2018.But on Wednesday, figures released by the government showed the figure had dropped to 0.81 – down from 0.84 the previous year, and a sixth consecutive decline.In comparison, the average rate across the world’s most advanced economies is 1.6 children.Countries need at least two children per couple – a 2.1 rate – to keep their population at the same size, without migration.Fertility rates have “declined markedly” in the past six decades says the OECD – Organisation for Economic Co-operation and Development.Alarm as South Korea sees more deaths than birthsFrom Seoul: ‘Why I never want babies’But the trend has been particularly pronounced in South Korea, where family sizes have reduced in the span of a few generations. At the start of the 1970s women had four children on average.A declining population can put a country under immense strain. Apart from increased pressure on public spending as demand for healthcare systems and pensions rise, a declining youth population also leads to labour shortages that impact the economy. In 2020 there was widespread alarm in South Korea when it recorded more deaths than births for the first time.In recent years, economic pressures and career factors have been key considerations for people deciding on children, experts say.For the 2021 figures, experts cited higher living costs, a spike in house prices and the impact of the Covid pandemic as factors discouraging them from having children.A crisis is brewing. If South Korea’s population continues to shrink, there won’t be enough people to grow its economy, look after its aging population, and conscript into its army. Politicians have known for years this is coming but have been unable to fix it. They have thrown billions of dollars at trying to convince people to have children and are still scratching their heads as to why this hasn’t worked. Money of course is a factor. Raising children in South Korea is expensive, and many young people are sinking under astronomical housing costs. But this is also about opportunity.Women in South Korea are highly educated, yet far from equal in the workplace. The country has the highest gender pay gap of any rich country. Most of the housework and childcare in South Korea still falls to women and it is common for women to stop work after having children or for their careers to stagnate. Essentially, many women here are still forced to choose between having a career and having a family. Increasingly they are deciding they don’t want to sacrifice their careers. As one woman put it to me: “we are on a baby-making strike”.More on this story’Why I never want babies’16 August 2018Alarm as South Korea sees more deaths than births4 January 2021