Body

CLEVELAND, Ohio (September 24, 2019)--Losing weight during and after menopause is not easy, but it's not impossible, either. A new study out of Florida suggests that lifestyle coaching may be effective in reducing body mass index (BMI), body fat, and waist circumference, although the results are more easily obtained by premenopausal women. Study results will be presented during The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25 to 28, 2019.

It's a fact that most women gain body weight in the peri- and postmenopausal years with the average weight gain being just under five pounds. The bad news from a health perspective is that much of the weight gain is represented by central abdominal fat which has been proven to cause greater cardiovascular (CVD) risk than general obesity.

In this new study, researchers evaluated the effectiveness of lifestyle coaching in helping women set and maintain goals for healthy eating habits and increased physical activity. They additionally compared the results obtained in premenopausal women with peri- and postmenopausal women. Women in both groups participated in a free Health Coaching Program at a primary care clinic.

The results showed that the lifestyle coaching did effectively help decrease BMI, body fat, and waist circumference in all women; however, peri/postmenopausal women experienced smaller reductions in percentage of body fat and waist circumference. No difference in BMI or lean mass was identified among the groups.

"Our results suggest that lifestyle coaching is worth pursuing but that a longer, more aggressive, or differently tailored, program might be needed for women in peri/postmenopause to achieve maximum health benefits," says Dr. Silvina Levis, lead author of the study from the Miami Veterans Affairs Healthcare System and the University of Miami, Miller School of Medicine.

"These findings are important in helping women maintain a healthy weight and normal waist circumference, especially since the reduction of central obesity is critical in helping to reduce the risk of CVD," says Dr. Stephanie Faubion, NAMS medical director

CLEVELAND, Ohio (September 24, 2019)--The VITamin D and OmegA-3 Trial (VITAL) is the largest and most recent to test whether vitamin D or fish oil can effectively prevent cancer or cardiovascular disease. Results to date have been mixed but show promise for some outcomes, now confirmed by updated pooled (meta) analyses. The latest results from VITAL will be presented during The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25-28, 2019.

Nearly 26,000 U.S. men and women participated in the nationwide VITAL clinical trial. After more than five years of study and treatment, the results show promising signals for certain outcomes. For example, while Omega-3 fatty acids (fish oil) showed only a small, but nonsignificant, reduction in the primary cardiovascular endpoint of major CVD events, they were associated with significant reductions in heart attacks. The greatest treatment benefit was seen in people with dietary fish intake below the cohort median of 1.5 servings per week but not in those whose intake was above that level. In addition, African-Americans appeared to experience the greatest risk reductions. The heart health benefits are now confirmed by recent meta-analyses of omega-3 randomized trials.

Similarly, vitamin D supplementation did not reduce major CVD events or total cancer incidence but was associated with a statistically significant reduction in total cancer mortality among those in the trial at least two years. The effect of vitamin D in reducing cancer death is also confirmed by updated meta-analyses of vitamin D trials to date.

"The pattern of findings suggests a complex balance of benefits and risks for each intervention and points to the need for additional research to determine which individuals may be most likely to derive a net benefit from these supplements," says Dr. JoAnn Manson, lead author of the study from Brigham and Women's Hospital, an affiliate of Harvard Medical School.

"With heart disease and cancer representing the most significant health threats to women, it is imperative that we continue to study the viability of options that prevent these diseases and help women survive them," says Dr. Stephanie Faubion, NAMS medical director.

Drs. Manson and Faubion are available for interviews before the presentation at the Annual Meeting.

CLEVELAND, Ohio (September 24, 2019)--The benefits of hormone therapy (HT) on atherosclerosis relates to achieved estradiol levels among those women who initiate HT early in postmenopause. Despite the use of hormones, however, women's estradiol levels are often inconsistent. A new study identifies the various determinants of estradiol levels among healthy women using HT. Study results will be presented during The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25 to 28, 2019.

The researchers involved in the new study relied on analysis of data from the Early versus Late Intervention Trial with Estradiol (ELITE). Their work in this area previously showed that estradiol levels were higher among early compared to late postmenopausal women. The new research focused on identifying the various factors affecting estradiol levels and how this impacted a woman's risk of developing atherosclerosis (hardening of the arteries).

The research yielded a number of results. Higher estradiol levels were associated with such determinants as higher BMI, higher weight, higher creatinine, and antihypertensive medication use, among others. Current and past smoking and use of antifungal medicine were associated with lower estradiol levels. These determinants were similar between early and late postmenopausal women.

"Healthcare providers need to consider the impact of these various factors when attempting to reach desirable estradiol levels in their postmenopausal patients and understand that not all women's bodies will respond the same to hormone therapy," says Dr. Intira Sriprasert, lead author of the study from the Keck School of Medicine of the University of Southern California.

"NAMS continues to promote individualized approaches to treating women's menopause symptoms, and this study provides one more piece of evidence as to why such individualization is critical," says Dr. Stephanie Faubion, NAMS medical director.

CLEVELAND, Ohio (September 24, 2019)--Expert reports estimate that one in three breast cancer cases could be prevented by lifestyle modifications. Those modifications include such basics as weight management, physical activity, nutrition, and alcohol consumption, among others. The latest research on risk management and most current lifestyle recommendations will be presented during The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25-28, 2019.

Breast cancer remains the most common cancer in women in the United States and around the globe. Numerous studies focused on breast cancer prevention have already been completed, many of which point to the same conclusion; lifestyle modifications offer the best and easiest form of prevention.

In 2018, The World Cancer Research Fund and the American Institute for Cancer Research updated their breast cancer prevention recommendations categorized by menopause status, where possible. The recommendations included some of the more common modifiable elements of breast cancer risk with respect to exercise, diet, alcohol, and breast feeding. The collective recommendations were based on a number of proven facts, including:

For postmenopausal women there is a 1.5 to 2.0 times increased risk of breast cancer if a woman is obese.

Body fatness is suggested to increase cancer risk as a result of hyperinsulinemia, increased estradiol, and inflammation.

The Centers for Disease Control estimate that physical activity alone could prevent one in eight breast cancer cases.

Alcohol is a carcinogen attributable to 6.4% of breast cancer cases.

Any amount of alcohol increases the risk of breast cancer and the more a woman drinks, the higher her risk of breast cancer.

The Cancer Update Project from 2017 observed a significant inverse relationship between non-starch vegetable consumption and a lower risk of breast cancer.

Dr. Juliana Kling from the Mayo Clinic in Arizona will be presenting the latest recommendations, as well as highlights of the studies behind them, at the upcoming NAMS Annual Meeting.

"Given the magnitude of breast cancer occurrence and the accumulated evidence supporting prevention as the most cost-effective, long-term strategy for reducing breast cancer risk, lifestyle education centered on the American Institute for Cancer Research cancer prevention recommendations should be a core component of routine patient visits," says Dr Kling.

"This presentation should provide some valuable insights to healthcare providers who have the power to help guide women to adopt healthier lifestyles which, in turn, will decrease their risk of developing breast cancer," says Dr. Stephanie Faubion, NAMS medical director.

Drs. Kling and Faubion are available for interviews before the presentation at the Annual Meeting.

CLEVELAND, Ohio (September 24, 2019)--The Women's Health Initiative (WHI) remains one of the most highly quoted when debating the benefits and risks of hormone therapy. Now a new study based on WHI data demonstrates that, among other benefits, hormone therapy decreases a number of metabolites that are directly linked with Type 2 diabetes. Study results will be presented during The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25 to 28, 2019.

In the WHI trials, the incidence of diabetes was reduced with the use of hormone therapy, particularly combined estrogen and progestin therapy. The new study utilized data from a prior study which measured approximately 370 metabolites on 1,362 women involved in the WHI. Researchers in the current study selected nine metabolites that were previously found to be strongly associated with the development of Type 2 diabetes in other studies to see if they were affected by randomized hormone therapy.

Of the nine targeted metabolites, seven were significantly decreased with the use of hormone therapy consisting of a combination of estrogen and progestin.

"Interestingly, we found that the decreases were more pronounced with the use of estrogen and progestin combined than with estrogen alone," says Dr. Heather Hirsch, lead author of the study from The Ohio State University Medical Center. "This result parallels the findings from the WHI on the effect of hormone therapy on the incidence of type 2 diabetes."

"It's valuable for healthcare providers to better understand the full spectrum of potential risks and benefits of hormone therapy for management of menopausal symptoms, particularly given the debilitating effects of diabetes and its increased incidence in the United States, " says Dr. Stephanie Faubion, NAMS medical director.

Drs. Hirsch and Faubion are available for interviews before the presentation at the Annual Meeting.

For more information on menopause and healthy aging, visit menopause.org.

Founded in 1989, The North American Menopause Society (NAMS) is North America's leading nonprofit organization dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field--including clinical and basic science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and education--makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit http://www.menopause.org.

COLUMBUS, Ohio - A new clinical trial conducted at The Ohio State University Wexner Medical Center found a cost-effective generic medication works just as well as a more expensive drug in preserving cardiovascular function in boys with Duchenne muscular dystrophy (DMD).

Results of this multi-center trial are in today's Journal of the American Heart Association.

The researchers at The Ohio State University College of Medicine compared spironolactone and eplerenone - two potassium-sparing diuretic medications typically used to treat high blood pressure and help manage heart failure. In their previous work, the team showed that lower dose eplerenone is better than placebo in protecting the heart in boys with DMD.

"Even though it works well, the concern with eplerenone is that it's more costly and less available worldwide," said Dr. Subha Raman, a cardiologist and professor at Ohio State who led the research. "Spironolactone is more commonly available and can cost about 75% less, making it more accessible to everyone who could benefit."

To conduct their trial, researchers enrolled 52 boys with DMD between the ages of 12 and 18 at seven academic medical centers across the country. All of the boys started with preserved cardiac function. After baseline cardiac imaging, participants were randomly assigned to receive 50 mg of eplerenone or spironolactone orally once daily for one year. Neither the patients nor the researchers knew which drug they were assigned.

At the end of 12 months, cardiac function remained stable in both groups, meaning there was no change in the appearance of heart muscle tissue and in pumping capacity. The team reported that stabilization seemed better in this study using a higher dose compared to a prior low-dose study. Importantly, kidney and lung function also remained stable in both groups, and no one experienced serious side effects such as high potassium levels.

"These findings support early therapy as a safe and effective treatment to slow the progression of heart damage in patients at high genetic risk of heart muscle disease, such as those with DMD. The genetic abnormality nearly always advances to heart muscle damage that is a leading cause of death in boys with DMD. Beginning treatment before the first hint of damage, while heart function can be maintained, could have a significant impact on quality and quantity of life," Raman said.

DMD is a genetic disorder in which the body lacks dystrophin, a protein that helps keep muscle cells intact. It causes the skeletal and heart muscles to rapidly degenerate and weaken. DMD predominantly affects males. A majority of patients survive into their 20s or 30s.

"This work will advance how physicians care for young boys with DMD. Rather than simply treating the inevitable damage as it comes, we're now able to significantly delay, and maybe someday prevent, heart failure in DMD," said Dr. K. Craig Kent, dean of the College of Medicine. "Dr. Raman's passion for this work is admirable. Her team's commitment to this research is a great example of Ohio State Wexner Medical Center's mission to improve lives and help people remain productive and healthy at home."

Raman's many years of research was inspired by 32-year-old Ryan Ballou of Pittsburgh, a young man with DMD who, along with his father, started BallouSkies to raise awareness and funding for Raman's research of heart disease in muscular dystrophy patients. BallouSkies, the National Institutes of Health and Parent Project Muscular Dystrophy financially supported this study.

Charlottesville, VA (September 24, 2019). Researchers from the University of California San Francisco and Veterans Affairs Health Care System, San Francisco investigated the safety and efficacy of deep brain stimulation in the treatment of refractory severe tinnitus in a small group of patients. They found the procedure to be safe and the results to be encouraging. Detailed findings are found in the article, "Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus," by Steven W. Cheung, M.D., and colleagues, published today in the Journal of Neurosurgery.

Background

Tinnitus is the perception of sound in the ear with no external stimulus. This sound may take a variety of forms, including ringing, humming, hissing, clicking, pulsating, or roaring. Tinnitus may come and go, or it may be continuous. It is commonly associated with age-related hearing loss, damage to the ear sustained from exposure to loud noises, and an adverse reaction to medications. It can also be impacted by physical or emotional stress, mood changes, and sleep disturbance.

Approximately 15 percent of people experience tinnitus. For most, symptoms are not bothersome and require no treatment. For others whose tinnitus is intrusive, there are a variety of pharmaceutical, acoustic, and behavioral therapies that can help diminish the sound's capacity to cause mental fatigue and degrade sense of well-being. Unfortunately, some people experience tinnitus symptoms that do not respond to available treatments and are so loud and intrusive that they disrupt normal activities of life. For these people a potential new therapy for tinnitus has emerged: deep brain stimulation.

Deep brain stimulation (DBS) surgery is currently performed to treat a variety of movement disorders and some psychological disorders in select patients. During surgery, electrodes attached to the end of leads are implanted deep within the brain in areas where abnormal electrical impulses are disrupted. The leads are connected by insulated wires to an implantable pulse generator, a battery-operated micro-electronic device that is placed elsewhere in the body, just under the skin. The generator delivers electrical stimulation to the brain sites where the leads have been implanted. This stimulation helps relieve patients' rigid limbs and other symptoms.

In earlier studies of DBS as a treatment for movement disorders, researchers found that DBS delivered to the caudate nucleus effected temporary changes in tinnitus loudness in those patients who had tinnitus as a comorbidity. The goals of the present study were threefold: 1) develop a DBS therapy that could reduce the severity of tinnitus in patients in whom other treatments had been ineffective; 2) provide a long-term reduction in the loudness of tinnitus; and 3) provide a critical evaluation of the effects of DBS on tinnitus in patients with no confounding comorbidity such as a movement disorder.

Present Study

The authors report the results of a prospective, open-label, nonrandomized, phase I clinical trial of DBS in five patients (three men and two women, mean age 51 years) with severe tinnitus that had proved refractory to acoustic or behavioral treatments. Four of the patients reported tinnitus in both ears and one patient reported it in only one ear. Their tinnitus produced such a negative impact on their lives that they chose to undergo an unproved invasive procedure in the hopes that it could provide meaningful relief of their symptoms.

Each patient underwent stereotactic neurosurgery to implant DBS electrodes in the caudate nucleus on each side of the brain. The patients were awake during surgery and interacted with the surgical team, which helped the team determine the final position of the leads. There were no serious surgery-related adverse events in these patients.

After a five-week period of postoperative healing, the patients began a stimulation optimization period during which settings on the DBS internal pulse generator were periodically adjusted in the clinic and at home by the patient. The goal was to find a stimulation setting that would prove optimal for reducing the severity of tinnitus for each patient, and thus this period varied in length (5 to 13 months) according to each patient's needs.

Once a promising stimulation setting had been determined, the patients entered a 24-week-long period of constant stimulation at that setting. Minor setting adjustments were made in only one patient during that time period.

Overall, DBS proved effective in diminishing the negative experience of tinnitus, although each patient experienced the effect differently. Various tests were applied to measure the efficacy of DBS in tinnitus. A comparison of the patients' Tinnitus Functional Index scores before treatment and during constant stimulation showed significant clinical improvement in three patients (60%). A comparison of the patients' Tinnitus Handicap Inventory scores before treatment and during constant stimulation showed significant clinical improvement in four patients (80%). One patient found no relief.

In this group of five patients, there were no serious surgery- or stimulation-related adverse effects. Surgery-related adverse events included postoperative incisional pain and headache, which were expected and resolved quickly. Stimulation-related adverse events included worsening of tinnitus symptoms and, in one patient, visual phantoms that occurred briefly while the stimulation settings were being adjusted.

Given the promising outcomes of this study, the authors look forward to a phase II study. They suggest that this next trial could benefit by a refinement of the target position of the DBS leads, with the aim of shortening the stimulation optimization period and making the treatment effect more uniform.

When asked about the study, Dr. Cheung said, "Our research team from the disciplines of Neurosurgery, Neurology, Otolaryngology, and Radiology worked synergistically to tackle the challenging condition of treatment-resistant tinnitus. We are encouraged by results of this phase I trial and hope to use a personalized targeting approach to implant electrodes in a phase II trial to improve efficacy."

After a recent study showed that chronic lymphocytic leukemia patients who received ibrutinib as a frontline treatment had a 7% death rate, a new study offers a clearer picture on the reasons for the deaths.

A team of researchers utilized the VigiBase, a global database of drug complications maintained by the World Health Organization, to analyze deaths associated with ibrutinib, a targeted therapy for several blood cancers that has boosted long-term survival rates and proven superior to other therapies.

However, ibrutinib also was shown to have a death rate of 7% compared to 1% for chemotherapy during treatment or within 30 days afterward, according to a study published Dec. 27, 2018, in The New England Journal of Medicine.

The death rate, which was noted on the eighth page of that study, stood out to Javid Moslehi, MD, director of Cardio-Oncology and associate professor of Medicine at Vanderbilt University Medical Center. He is part of a team at Vanderbilt-Ingram Cancer Center focusing on toxicities associated with targeted therapies, immunotherapies and other newer treatments.

"Seven percent of people dying from a frontline treatment is not a good thing," said Moslehi, the senior author of a follow-up study published Sept. 23 in Journal of The American College of Cardiology that analyzed deaths associated with ibrutinib utilizing VigiBase.

The study identified several cardiovascular toxicities associated with ibrutinib, including supraventricular arrhythmias, central nervous system hemorrhagic events, heart failure, ventricular arrhythmias, conduction disorders, ischemic strokes and organ damage related to hypertension.

"Our study is interesting in that it allowed for detection of new signals of potentially fatal cardiovascular toxicities associated with ibrutinib, such as heart failure, conduction disorders and central nervous system hemorrhagic events. Treating physicians should be aware of these risks," said the study's lead author, Joe-Elie Salem, MD, PhD, associate professor of Cardiology and Pharmacology at Sorbonne University and adjunct professor at Vanderbilt University.

Some of the cardiovascular adverse drug reactions associated with ibrutinib are difficult to treat.

"The challenge is that from a cardiology perspective we don't always know what to do," Moslehi said. "For example, we generally treat patients with atrial fibrillation with blood thinners. The problem is that ibrutinib also thins the blood, so you already have a bleeding risk. That is a problem."

The study noted "there is a clear and pressing need to improve management of these patients." The research team is currently investigating what protein kinase within the drug mechanism is causing the atrial fibrillations and how best to reverse the effect, Moslehi said.

Two of the cardiovascular adverse drug reactions identified in the VigiBase analysis - heart failure and conduction disorder - are new findings.

The median time from start of treatment with ibrutinib to onset of supraventricular arrythmia was two to three months. The median time was four to five months for hypertension. Heart failure, brain bleeds and ventricular arrythmias had onset times of two to three months. However, the onset of conduction disorder occurred more quickly, mainly within the first month of treatment.

Moslehi and the team of oncologists who are co-authors on the manuscript, including Nishitha Reddy, MBBS, MSCI, associate professor of Medicine at Vanderbilt University, urge monitoring patients closely when prescribing ibrutinib and to consult with cardiologists with difficult patient cases.

Researchers have discovered that gene expression regulators work together to raise an individual's risk of developing schizophrenia. Schizophrenia-like gene expression changes modeled in human neurons matched changes found in patients' brains. The researchers, led by Kristen Brennand, of the Icahn School of Medicine at Mount Sinai, New York City, report on their findings in Nature Genetics. The work was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Genome-wide association studies have revealed at least 143 chromosomal sites associated with risk for schizophrenia. However, individually, each of these sites can explain only a small fraction of the risk. Even when the effects of disease-linked rare genetic variants are factored in, most of schizophrenia's known high inheritance remains unexplained. One possible clue: more than 40% of the suspect chromosomal sites contain regulators, called expression quantitative trait loci, or eQTLs, that govern the expression of multiple genes.

"Individually, these gene regulators have a modest effect on the brain. Working in concert, they exert different and more significant effects on the brain--effects that boost schizophrenia risk," explained David Panchision, chief of the Developmental Neurobiology Program at NIMH. "Learning more about the downstream cellular and molecular effects of such synergy holds hope for advances in precision psychiatry and more personalized medicine."

To explore the role of these regulators, Brennand and colleagues studied them in induced neurons using a molecular modeling technology. This induced pluripotent stem cell method makes it possible to grow a person's unique neurons in a petri dish using stem cells derived from their skin cells. The researchers used the model to take a closer look at the downstream molecular consequences of gene expression changes known to occur in schizophrenia, and compared them with changes seen in postmortem brains and similarly modeled neurons of people with the illness.

The researchers experimentally mimicked the interaction of multiple risk genes thought to contribute to schizophrenia. They used the gene editing tool CRISPR to simultaneously increase or decrease expression of four schizophrenia-implicated genes known to harbor eQTLs. The genes were selected because they were deemed most likely to confer disease risk by regulating gene expression. To trigger changes in the direction predicted to heighten risk for schizophrenia, expression was increased for three of the genes and decreased for one.

Manipulating expression of the four genes altered expression of 1,261 other genes - 665 increased and 596 decreased. This was many more than would be expected if the genes had been merely acting individually, suggesting an underlying mechanism that is synergistic rather than additive.

"This unexpected synergy between gene variants demonstrated how even subtle genetic variations can impact neuronal function," said Brennand. "These interactions emphasize the importance of considering the complex nature of schizophrenia and other psychiatric disorders, where a combination of gene variants contributes to disease."

Many of the genes affected downstream contained variants that had been linked to autism spectrum disorder or bipolar disorder, in addition to schizophrenia - consistent with other research suggesting genetic overlap across mental disorders.

The experimentally induced gene expression changes mirrored those seen in postmortem brains of people with the three mental illnesses. The same changes were also seen in induced pluripotent stem cell neurons from people with childhood-onset schizophrenia, a rare form of the illness thought to be more genetic in origin.

"Notably, all of these gene changes resulted in loss-of-brain-function effects when screened one-at-a-time in a zebrafish model," said Brennand. "We have added several of them to a list of genes worthy of further study for possible involvement in schizophrenia. There is an overwhelming need for future studies to similarly model such multi-gene interactions in complex cells and circuits."

According to recent research, even mild long-term depressive symptoms among mothers are connected with emotional problems among small children such as hyperactivity, aggressiveness and anxiety.

The study investigated how the depressive symptoms of both parents affected the child by the age of two and five.

The father's depressive symptoms affected the child's emotional problems only if the mother was depressed as well. The mother's symptoms, however, affected the child even if the father was not depressed.

Moderate depressive symptoms can be observed in over 20% of parents in Finland. Most serious symptoms are seen in less than 9% of mothers and around 2.5% of fathers.

"Depression among parents both during and after pregnancy not only affects the person suffering from depression but also has a long-term impact on the well-being of the newborn child. Even in cases of mild depression, it is important that the symptoms are identified and the parents are offered support as early as possible, if necessary already during the pregnancy," explains Visiting Researcher Johanna Pietikäinen from the Finnish Institute for Health and Welfare (THL).

"In families, depression experienced by the mother has a key impact on the child's well-being. In Finland, the maternity clinic system functions well, but attention should be paid to depressive symptoms among mothers over a longer period: from the pregnancy through to the end of the child's first year of age," she adds.

One parent's depression also puts the other at risk

The depression of one parent is a factor that can put the other parent at risk of depression as well. In addition, depressive symptoms among mothers and fathers are quite long-term: they can start already during pregnancy and continue past the child's first birthday.

"It is important to monitor the mental well-being of both parents during pregnancy and after the birth of the child, and if one parent shows symptoms of depression then the symptoms of the other parent should also be examined. Currently, however, fathers' psychological well-being is not necessarily covered by depression questionnaires in maternity clinics, for example," Pietikäinen points out.

Prior depression is the most significant risk factor

Long-term depression is an indication that the depression may have been experienced already before the pregnancy. Previous experience of depression was, in fact, one of the key risk factors for moderate or severe depressive symptoms.

Other significant risk factors included sleep deprivation during pregnancy, stress, anxiety and a bad family environment. These most prominent risk factors were predictors for depression among both mothers and fathers.

Effective diagnosis and treatment of disease draws on painstaking research, which often relies on biological samples. The avalanche of studies used to better understand illnesses and design effective therapies cost billions of dollars and potentially affects millions of lives.

So, it would seem reasonable to assume that the reliability of biological samples, on which accurate results depend, would be of paramount concern for the scientific community.

According to Chad Borges, a researcher in the Biodesign Virginia G. Piper Center for Personalized Diagnostics at Arizona State University, that assumption is quite often wrong.

"One of the major reasons that there are so many discoveries of biomarkers (early indicators of disease) in the literature, but so few positive validations that confirm those findings is the fact that in many cases during the discovery, samples were used that have a history or an integrity that's simply unknown."

Biological samples can be highly susceptible to changes over time, which often occur when they are removed from deep refrigeration. Degraded samples can produce spurious results in research. To address these concerns, Borges and his colleagues have designed a highly sensitive test that can be used to establish the integrity of blood plasma and serum, the most common biosamples used in medical research.

Ensuring such samples have been properly handled is the first step in careful research that meets the necessary high standards of reliability and reproducibility. The new test, which relies on accurate measurement of the relative proportions of two forms of the protein albumin present in blood, was recently described in the journal Molecular and Cellular Proteomics.

Houston, we have a problem

The immediacy of the issue of sample quality became apparent to Borges during the course of his own research, which involved experiments on biological samples slated for distribution by the National Institute of Health (NIH). "We got a little suspicious that something wasn't quite right about the sample set," he says. Borges applied the newly designed test to the samples, with surprising results. "Low and behold, there was a major difference between the cases and controls for this specimen integrity marker."

Further investigation revealed that the freezer in which the control samples were stored had lost power for several days during a natural disaster. "That information is really important with regard to the quality of the samples and the stability of the markers that were in them."

The implications of this discrepancy plainly went beyond his own research. "Who knows how many other markers are differentiated simply because of the way in which the cases and controls were handled," Borges says

Lurking beneath the surface

In 2018 alone, the National Institute of Health's Medline logged close to a million published papers of health-related research. Advances relying on research findings have transformed medical science, improving the quality of life and saving millions from dreaded diseases and afflictions.

But progress has not always been smooth going. In addition to formidable scientific challenges facing researchers, political considerations and career concerns also influence how science is done. The pressure to publish findings in scientific journals often weighs heavily on researchers and is considered essential to the advancement of a young scientist's career. While rooted in career pragmatism, the increasingly competitive drive to publish or perish can overshadow concerns about data reliability.

Long taken for granted, the issue of scientific reproducibility has recently moved to the forefront of discussions on the practice of science, as many studies face reexamination and increased scrutiny. Just how solid are the results of published studies? Can they be replicated? A recent book-length exposé makes the case that the issues surrounding scientific reliability are considerably more profound and alarming than once thought.

Biological samples are ground zero in the quest for dependable science, yet researchers hoping to publish their work may have a disincentive to spend the time to probe the integrity of their specimens. Should they uncover a problem, it may throw their data into question and preclude publication--a serious setback, with little for the researcher to show for it. There is a danger of an ignorance is bliss mentality.

Know your specimens!

As Borges notes, addressing the problem requires two things. First, a regulatory body like the NIH needs to issue strict guidelines that include detailed documentation of sample history and handling. Currently, some scientific journals do require documentation of specimen storage conditions prior to publication, but such records are often inadequate for ensuring a high level of sample integrity. Secondly, researchers need reliable methods for testing their samples to ensure they meet exacting standards. The technique described in the current study is an important advance in this direction.

Depending on the nature and purpose of a given blood plasma or serum sample, even minor fluctuations in the collection, processing, storage and handling can affect quality and reliability. The most important of many factors affecting such samples is the time they have spent in a thawed condition above -30o C. This is also one of the more challenging variables to track over time, in many instances.

One recent clinical example highlighting the issue of sample integrity concerns HER2, a critical biomarker used for the diagnosis of breast cancer. It has recently been discovered that this marker is highly unstable and can yield specious results when applied to sample tissue, unless it is processed within 1 hour of surgical resection.

QC for blood

The new biomarker sets cutoff values for blood plasma and serum, allowing researchers to easily assess the quality of samples and their suitability for given experiments, even if a detailed record of sample handling and storage is unavailable. For the first time, plasma and serum--the most commonly used biospecimens for medical research--can be tracked with a reliable biomarker.

The biomarker, which relies on relative proportions of two isoforms of albumin, requires only a low volume of plasma or serum and minimal sample preparation. (Different isoforms of this protein are functionally similar but an oxygen-induced modification that occurs to an abnormal extent outside of the body is used to identify mishandled samples.)

Albumin is the most abundant protein in blood plasma and serum, comprising roughly half of all protein content in these biofluids. Outside the body, the natural unmodified form of albumin becomes oxidized with time. This can be detected by observing a change in protein mass, using mass spectrometry.

By describing a chemical rate law for this protein oxidation reaction that takes place in plasma and serum, the biomarker acts as a kind of molecular stopwatch that can precisely gauge the elapsed time a particular sample has remained in a thawed state.

The biomarker described is inexpensive, easy and rapid to use and can be fully automated, making it a strong candidate to serve as the new gold standard for plasma and serum analysis. It is capable of detecting biospecimen exposure to room temperature conditions for as little as 2 hours, quickly and accurately identifying mishandled or mis-stored samples and preventing their inclusion in clinical research.

The study was carried out in collaboration with Maricopa County Hospital. Patient study samples were acquired with the help of cardiologist Dr. Christian Breburda and his staff.

In addition to more conventional clinical research, the new biomarker is poised to make inroads in a variety of health-related investigations. It has recently been incorporated into an ambitious project sponsored by the Defense Advanced Research Projects Agency or DARPA, which uses epigenetic markers in blood to identify exposure to weapons of mass destruction or their precursor chemicals. The new biomarker will be used to ensure the quality of blood samples, further establishing the power and versatility of this approach.

Research published today in the journal Circulation has found that women with high blood pressure in pregnancy, including conditions such as preeclampsia, have an increased risk of developing cardiovascular disorders later in life, including stroke and heart failure.

Led by King's College London, the team of researchers studied electronic health records from 1997 to 2016 to recreate a UK population-based cohort of 1.3 million women covering nearly 1.9 million completed pregnancies. They used statistical analysis to determine the associations between hypertensive disorders of pregnancy, such as preeclampsia with 12 cardiovascular disorders.

They found that during the 20-year study period, 18,624 cardiovascular events occurred (such as heart attacks, stroke, heart failure), of which 65% occurred in women under 40 years of age.

High blood pressure in pregnancy affects up to 10% of pregnancies often causing complications in the woman and requiring early delivery of their baby.

Women who had one or more pregnancies affected by preeclampsia or other types of pregnancy hypertension were more likely to have a stroke, heart attack, heart failure, or similar event.

Women with pregnancy high blood pressure had twice the number of deaths in this follow-up period from cardiovascular disease compared with women without pregnancy high blood pressure. These women also developed chronic hypertension 4.5 times faster than women without pregnancy high blood pressure.

The increased risk that occurred in those women with previous pregnancy high blood pressure was found as early as one year after pregnancy compared to women without pregnancy high blood pressure.

Currently in the UK, women are screened for the development of cardiovascular disease from 40 years of age. This research suggests that the age for cardiovascular screening may need to be lowered for women with a history of pregnancy hypertensive disorders as they are at higher risk of heart and blood vessel problems than women who had unaffected pregnancies. Hypertensive disorders of pregnancy could be considered as a natural screening tool for premature cardiovascular events, enabling cardiovascular risk prevention through national initiatives.

Lead author, Dr Fergus McCarthy from University College Cork, said: "This research further supports the evidence that what occurs in pregnancy has lifelong implications for a mother's health. By looking at pregnancy outcomes, we may have an excellent opportunity to identify women at high risk of cardiovascular disease and offer them early interventions after pregnancy to try and reduce this risk. It is critical now that we focus our research on potential interventions to improve the long-term health of mothers."

Professor Lucy Chappell, Department of Women & Children's Health at King's College London said: "These results clearly show that we should now look at how we share this information with women who have had pregnancy hypertension, and that we need to find out what interventions work for these women so that they can reduce their risk of heart disease later in life. It is essential that we work with women and all the healthcare professionals involved in their care so that we can tailor the interventions appropriately to this period of a woman's life."

The next steps in this research are to determine what interventions, such as diet modifications, salt reduction, exercise or medications that may protect the heart, may work in the women after pregnancy to try and reduce this risk and improve long term health.

An NHS scheme to give every patient aged 75 and over in England a named GP responsible for their care has failed to deliver hoped-for improvements, according to a study by researchers at the University of Bristol's Centre for Academic Primary Care.

The scheme, introduced by the NHS Employers and General Medical Services in April 2014, was designed to improve the care of older people and keep them healthy, independent and out of hospital.

The National Institute for Health Research funded study, published in BMJ Open, found that the named GP scheme did not lead to patients seeing the same GP more often (continuity of care) or reduce rates of emergency admission to hospital. Instead it found that continuity of care decreased after the scheme was introduced and the risk of emergency hospital admissions increased.

The team analysed the records of over 19,000 patients in 139 English GP practices, linked with hospital data, to compare their health care use in the two years before and after the scheme was introduced. Results for those aged 75-84 were compared with those aged under 65-74.

Continuity of care decreased at a similar rate in both age groups after the scheme was introduced, and emergency hospital admissions increased in both age groups. However, the increase was greater for patients aged over 75.

Dr Peter Tammes, a Senior Research Associate at the Centre for Academic Primary Care, University of Bristol and lead author of the study, said: "The named GP scheme appears not to have delivered hoped-for results in terms of improved continuity of care and reduced emergency hospital admissions for older patients. This suggests that the policy of allocating a named GP is not, in itself, effective and more sophisticated interventions are needed.

"It also raises questions about how the scheme was implemented - whether, for example, it would have made a difference if patients had been given the option to express a preference for who their named GP should be and how well they understood what having a named GP was for.

"We did not interview patients and staff about what they thought about the scheme, so our understanding of why it does not appear to have worked is therefore limited. We would urge policy makers to look at other ways of improving care for this older patient group, taking both patient and GP views into account."

Bethesda, MD (Sept. 23, 2019)-- Diagnosing patients with chronic watery diarrhea can be difficult for health care providers, since several causes with specific therapies, such as inflammatory bowel disease (IBD), microscopic colitis and chronic infection, need to be ruled out. A new clinical guideline1 (superscript 1) from the American Gastroenterological Association (AGA) published in Gastroenterology, the official journal of the AGA Institute, provides recommendations on the appropriate laboratory tests based on current evidence to exclude other diagnoses in the setting of suspected functional diarrhea or irritable bowel syndrome with diarrhea (IBS-D).

"When managing patients with chronic watery diarrhea, it is important for health care providers to determine whether it is being caused by organic disease or a functional disorder, such as functional diarrhea or irritable bowel syndrome with diarrhea," said Walter Smalley, MD, MPH, first author, Veterans Affairs Tennessee Valley Healthcare System and Vanderbilt University School of Medicine, Nashville, Tennessee. "Both functional diarrhea and IBS-D are clinical diagnoses with no defining laboratory tests. A workup to exclude all organic disease is impractical, expensive and potentially dangerous to patients if false-positive tests result in further invasive testing. The AGA guideline on evaluation of chronic diarrhea is intended to reduce practice variation and promote high-quality and high-value care for this patient population."

The AGA guideline applies to patients with properly working immune systems who have "watery" diarrhea of at least four weeks duration. It excludes patients with bloody diarrhea; diarrhea with signs of poor fat absorption; features of alarm symptoms, such as weight loss, anemia and hypoalbuminemia; a family history of IBD, colon cancer or celiac disease; and those with a travel history to regions where diarrhea-related diseases are common.

The guideline recommends considering the use of the following laboratory tests for the evaluation of functional diarrhea and IBS-D in adults:

1. In patients presenting with chronic diarrhea, AGA suggests the use of either fecal calprotectin or fecal lactoferrin, which have been proposed as markers for inflammatory conditions, such as IBD. (Conditional recommendation; low quality evidence)

2. In patients presenting with chronic diarrhea, AGA suggests against the use of erythrocyte sedimentation rate or C-reactive protein to screen for IBD. (Conditional recommendation: low evidence)

3. In patients presenting with chronic diarrhea, AGA recommends testing for Giardia, a common cause of watery diarrhea that can be readily treated. (Strong recommendation: high quality evidence)

4. In patients presenting with chronic diarrhea with no travel history to or recent immigration from high risk areas, AGA suggests against testing for ova and parasites (other than Giardia). (Conditional recommendation: low quality evidence)

5. In patients presenting with chronic diarrhea, AGA recommends testing for celiac disease with IgA tissue transglutaminase and a second test to detect celiac disease in the setting of IgA deficiency. Celiac disease is an important cause of chronic diarrhea. (Strong recommendation: moderate quality evidence)

6. In patients presenting with chronic diarrhea, AGA suggests testing for bile acid diarrhea, which may be due to excess production or decreased absorption of bile acids, which then reach the colon and can cause watery diarrhea. (Conditional recommendation: low quality evidence)

7. In patients presenting with chronic diarrhea, AGA makes no recommendation for the use of currently available serologic tests for diagnosis of IBS. (No recommendation; knowledge gap)

Read the AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D) to review the complete recommendations.

What is diarrhea and IBS-D?

Diarrhea happens when a patient has loose, watery stools three or more times a day. When diarrhea lasts four weeks or more, it is considered chronic, or long-term, diarrhea. While diarrhea is a common health problem, impacting 179 million people in the US a year, it can also be associated with a health condition called irritable bowel syndrome (IBS), a common disorder of the large intestine.

There are different types of IBS -- IBS-D: IBS with diarrhea; IBS-C: IBS with constipation; IBS-M: IBS mixed. General symptoms for all types can include belly pain, cramping in the stomach area, gas, bloating and changes in the stool, such as diarrhea, constipation or an urgent need to go. IBS impacts about 35 million Americans, physically, emotionally and socially.

Resources for health care providers

Technical review: Evaluation of functional diarrhea and IBS-D

Clinical decision support tool: IBS-D in adults

Spotlight: Laboratory evaluation of functional diarrhea and IBS-D in adults

AGA University education: Laboratory evaluation of functional diarrhea and IBS-D

Resources for patients

Patient summary: AGA clinical practice guidelines on the laboratory evaluation of functional diarrhea and IBS-D

AGA patient education: IBS

References

1 Smalley, W., Falck-Ytter, C., Carrasco-Labra, A., Wani, S., Lytvyn, L., Falck-Ytter, Y. AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D) (2019). DOI: https://doi.org/10.1053/j.gastro.2019.07.004. https://www.gastrojournal.org/article/S0016-5085(19)41083-4/fulltext

2 Carrasco-Labra, A., Lytvyn, L., Falck-Ytter, Y., Surawicz, C.M., Chey, W.D. AGA Technical Review on the Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D) (2019). DOI: https://doi.org/10.1053/j.gastro.2019.06.014. https://www.gastrojournal.org/article/S0016-5085(19)41012-3/fulltext

All print, broadcast and online journalists who receive the Obesity embargo alert agree to abide by the embargo and may not publish, post, broadcast or distribute embargoed news releases or details of the embargoed studies before the embargo date and time.

When writing about these studies, journalists are asked to attribute the source as the journal Obesity and to include the online link to the Obesity articles as provided below.

Links are active now.

About the journal - Obesity is the peer-reviewed, scientific journal of The Obesity Society.

Editors' Choice 1 - Intensive Behavioral Therapy: Protocol Now Available Online, Thomas A. Wadden, wadden@pennmedicine.upenn.edu, Adam G. Tsai, and Jena Shaw Tronieri
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22594)

See accompanying Commentary by Scott Kahan and Steven B. Heymsfield (http://onlinelibrary.wiley.com/doi/10.1002/oby.22643)

Editors' Choice 2 -Lipedema: An Under-Recognized and Poorly Understood Disease, Giacomo Buso, Michele Depairon, Didier Tomson, Wassim Raffoul, Roberto Vettor, and Lucia Mazzolai, lucia.mazzolai@chuv.ch
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22597)

Editors' Choice 3 - Obesity Found to Increase Risk of Unemployment, Illness Absence, Maja Bramming, Maja B. Jørgensen, Anne I. Christensen, Cathrine J. Lau, Kia K. Egan, and Janne S. Tolstrup, jest@sdu.dk
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22578)

Editors' Choice 4 - Self-Reported Height and Weight Consistently Taller and Lighter, Katherine M. Flegal, kmflegal@stanford.edu; katherine.flegal@gmail.com, Cynthia L. Ogden, Cheryl Fryar, Joseph Afful, Richard Klein, and David T. Huang
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22591)

Scroll down to find abstracts for each of the above papers. To request the full text of any of these studies and agree to the embargo policy, or to arrange an interview with a study's author or an obesity expert, please contact communications@obesity.org.

Editors' Choice Abstracts

Editors' Choice 1 - A Protocol to Deliver Intensive Behavioral Therapy (IBT) for Obesity in Primary Care Settings: The MODEL-IBT Program

Objective The Centers for Medicare and Medicaid Services (CMS) initiated coverage of intensive behavioral therapy (IBT) for obesity in 2011, providing beneficiaries 14 to 15 brief, individual counseling visits in 6 months. CMS offered general recommendations for delivering IBT but did not provide an evidence-based treatment protocol, which was the objective of the present research.

Methods: This review describes the evidence that CMS considered in developing its IBT benefit. It also examines weight losses produced by the intensive lifestyle intervention in the Diabetes Prevention Program (DPP), as well an adapted version of the DPP delivered (for the first 6 months) on the visit schedule recommended by CMS. This new protocol, which was evaluated in a recent randomized trial, provided 14 visits in the first 24 weeks, with 7 additional monthly visits through week 52.

Results: As reported previously, the 50 participants with obesity assigned to the new IBT protocol lost a mean of 5.4% of their initial weight at week 24; 46% of participants lost ? 5% of their baseline weight. At 1 year, the mean loss was 6.1%, and 44% of participants lost ? 5%.

Conclusions: With these generally favorable results, the IBT protocol is being posted online for practitioners and researchers to use.

Editors' Choice 2 - Lipedema: A Call to Action!

Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.

Editors' Choice 3 - BMI and Labor Market Participation: A Cohort Study of Transitions Between Work, Unemployment, and Sickness Absence

Objective This study aimed to test the hypotheses that individuals with obesity are at higher risk of unemployment and sickness absence and have a lower chance of getting employed compared with individuals with normal weight.

Methods: Data on weight and height were collected at baseline from 87,796 participants in the Danish National Health Survey 2010. Participants were then followed in national registers for 5 years. Outcome measures were transitions from employment to unemployment and sickness absence and the transitions from unemployment or sickness absence to employment. Data were analyzed by Cox proportional hazards models adjusted for potential confounders.

Results: Hazard ratios for unemployment were 1.18 (95% CI: 1.10-1.26) for individuals with obesity and 1.27 (95% CI: 1.14-1.41) for individuals with severe obesity compared with individuals with normal weight. Participants with obesity also had a higher risk of sickness absence. Additionally, participants with obesity who were unemployed at baseline had a lower chance of becoming employed compared with participants with normal weight.

Conclusions: Obesity was associated with a higher risk of unemployment and sickness absence compared with individuals with normal weight. Additionally, obesity was associated with a lower chance of employment.

Editors' Choice 4 - Comparisons of Self-Reported and Measured Height and Weight, BMI, and Obesity Prevalence from National Surveys: 1999-2016

Objective The aim of this study was to compare national estimates of self-reported and measured height and weight, BMI, and obesity prevalence among adults from US surveys.

Methods: Self-reported height and weight data came from the National Health and Nutrition Examination Survey (NHANES), the National Health Interview Survey, and the Behavioral Risk Factor Surveillance System for the years 1999 to 2016. Measured height and weight data were available from NHANES. BMI was calculated from height and weight; obesity was defined as BMI ? 30.

Results: In all three surveys, mean self-reported height was higher than mean measured height in NHANES for both men and women. Mean BMI from self-reported data was lower than mean BMI from measured data across all surveys. For women, mean self-reported weight, BMI, and obesity prevalence in the National Health Interview Survey and Behavioral Risk Factor Surveillance System were lower than self-report in NHANES. The distribution of BMI was narrower for self-reported than for measured data, leading to lower estimates of obesity prevalence.

Conclusions: Self-reported height, weight, BMI, and obesity prevalence were not identical across the three surveys, particularly for women. Patterns of misreporting of height and weight and their effects on BMI and obesity prevalence are complex.

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