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Newswise — Regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may help some patients with head and neck cancer survive the disease, according to a study led by Professor Jennifer Grandis at the University of California, San Francisco. The study, which will be published January 25 in the Journal of Experimental Medicine, indicates that NSAIDs are effective in patients with mutations in a gene called PIK3CA, and the researchers suggest this is because NSAIDs lower the levels of an inflammatory molecule called prostaglandin E2. The researchers note, however, that they are not yet able to make any specific recommendations about the type, timing, or dosage of NSAIDs such patients should take, and that their results need to be corroborated by a prospective clinical trial. Head and neck squamous cell carcinoma (HNSCC) accounts for about 4% of all cancers in the US and continues to have high rates of patient mortality. Risk factors for HNSCC include smoking, alcohol use, and human papillomavirus infection, but several studies have shown that regular use of aspirin can reduce the risk of developing the disease. However, whether aspirin or other NSAIDs can promote the survival of patients who have already developed HNSCC is unclear; studies investigating this question have so far produced conflicting results. One possibility is that NSAIDs are only effective against some types of HNSCC. Around 35% of HNSCC tumors carry mutations that activate the PIK3CA gene, which encodes the catalytic subunit of a key signaling enzyme called PI3Ka. The team of researchers led by Dr. Grandis investigated whether regular NSAID use specifically improved the survival of HNSCC patients with alterations in the PIK3CA gene. The team, which also included researchers from the University of Pittsburgh School of Medicine and the University of Arizona, analyzed a group of 266 HNSCC patients who had had their tumors surgically removed and, in most cases, were then treated with adjuvant chemotherapy and/or radiotherapy. Patients without any alterations in their PIK3CA gene were no better off if they also took NSAIDs on a regular basis (defined as taking two or more doses per week for at least six months). By contrast, regular NSAID usage dramatically enhanced the survival of patients whose PIK3CA gene was mutated and/or amplified. Among these patients, NSAIDs increased the overall five-year survival rate from 45% to 78%. NSAIDs also reduced the growth of tumors in mice injected with cancer cells harboring a mutant PIK3CAgene. By analyzing these mice, Grandis and colleagues found that NSAIDs likely inhibit tumor growth by reducing the production of prostaglandin E2. This proinflammatory molecule has been implicated in a variety of cancers and can be induced by the PI3Ka signaling pathway. NSAIDs may therefore also be effective against a variety of cancers that contain activating mutations in the PIK3CA gene. Indeed, previous studies have shown that regular aspirin usage can aid the survival of colorectal cancer patients carrying mutated PIK3CA. “The present study is the first to demonstrate that regular NSAID usage confers a significant clinical advantage in patients with PIK3CA-altered HNSCC,” Grandis says. “Inconsistencies in the type, timing, and dosages of NSAIDs taken by patients in this study limit our ability to make specific therapeutic recommendations. But the magnitude of the apparent advantage, especially given the marked morbidity and mortality of this disease, warrants further study in a prospective, randomized clinical trial.” Hedberg et al., 2019. J. Exp. Med. http://jem.rupress.org/cgi/doi/10.1084/jem.20181936?PR

Newswise — Newborn babies are born with the innate skills needed to pick out words from language, a new study published in Developmental Science reveals. Before infants can learn words, they must identify those words in continuous speech. Yet, the speech signal lacks obvious boundary markers, which poses a potential problem for language acquisition. Studies have found that by the middle of the first year, infants seem to have solved this problem, but it is unknown if segmentation abilities are present from birth, or if they only emerge after sufficient language exposure and/or brain maturation. Near-Infrared Spectroscopy An international team of researchers from the University of Liverpool, SISSA in Italy, the Neurospin Centre in France and The University of Manchester conducted experiments to find the cues crucial for the segmentation of human speech. The researchers played the infants a three-and-a-half minute audio clip in which four meaningless words, were buried in a stream of syllables. Using a painless technique called Near-Infrared Spectroscopy, which shines red light into the brain, they were able to measure how much was absorbed, telling them which parts of the brain were active. 'Key Insight' The researchers discovered two mechanisms in three-day-old infants, which give them the skills to pick out words in a stream of sounds. The first mechanism is known as prosody, the melody of language, allow us to recognise when a word starts and stops. The second is called the statistics of language, which describes how we compute the frequency of when sounds in a word come together. The discovery provides a key insight into a first step to learning language. Important tools Dr Alissa Ferry, University of Manchester, said: "We think this study highlights how sentient newborn babies really are and how much information they are absorbing. That's quite important for new parents and gives them some insight into how their baby is listening to them." Dr Perrine Brusini, University of Liverpool, said: "We then had the infants listen to individual words and found that their brains responded differently to the words that they heard than to slightly different words. "This showed that even from birth infants can pick out individual words from language." Dr Ana Flò, Neurospin, said: "Language in incredibly complicated and this study is about understanding how infants try to make sense of it when they first hear it. We often think of language as being made up of words, but words often blur together when we talk. So one of the first steps to learn language is to pick out the words. "Our study shows that at just three days old, without understanding what it means, they are able pick out individual words from speech. And we have identified two important tools that we are almost certainly born with, that gives them the ability to do this."

Newswise — Researchers from the National Institutes of Health have discovered that antibodies that may form the basis of a universal flu vaccine inhibit a second viral protein in addition to the one that they bind. The study, to be published January 25 in the Journal of Experimental Medicine, reveals that antibodies that recognize the viral surface protein hemagglutinin can also inhibit the viral neuraminidase, and that this enhances antibody neutralization of the virus and the activation of innate immune cells with anti-viral activity. Hemagglutinin and neuraminidase are yin-yang proteins present on the surface of the influenza virus. The former mediates virion attachment and fusion with host cell membranes, while the latter is an enzyme that releases budding progeny virions from the cell surface that remain attached via the hemagglutinin binding. Hemagglutinin consists of a head domain that contains the receptor binding site that attaches to host cell membranes and a stem domain that connects the head to the virion membrane.  Current flu vaccines induce antibodies that recognize the hemagglutinin head and inhibit its ability to mediate viral entry. But the hemagglutinin head undergoes rapid mutation to escape existing antibodies.  This generates vaccine–resistant strains of the influenza virus each year, necessitating the yearly mad dash to create a matched vaccine. The hemagglutinin stem domain, in contrast, is far more resistant to mutations, providing a target for universal flu vaccines, as has been shown by dozens of studies in animal models. “Hemagglutinin stem-specific antibodies are perhaps the most promising approach for improving the duration and effectiveness of influenza vaccination,” write the authors of the study, which was led by Jonathan W. Yewdell, a senior investigator at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. “It is therefore critical to better understand how anti-stem antibodies provide protection from the virus.” Stem-binding antibodies can block viral entry into host cells by inhibiting hemagglutinin cell fusion activity, but as Yewdell’s lab reports, they also inhibit the release of newly replicated virions by blocking neuraminidase molecules in close proximity to hemagglutinin on the virion.  Experiments in mice confirmed that the ability of anti-stem antibodies to inhibit neuraminidase enabled animals to better survive a severe influenza infection.  Yewdell and colleagues think that this effect may be largely due to the role that neuraminidase normally plays in preventing the activation of innate immune cells with anti-viral activity. In support of this idea, the researchers found that the FDA-approved neuraminidase inhibitor oseltamivir (Tamiflu) further boosted the ability of anti-stem antibodies to activate immune cells exposed to influenza virus. “The ability of neuraminidase inhibitors to enhance… immune cell activation [by anti-stem antibodies] bound to viruses or infected cells suggests the possible clinical synergy between neuraminidase inhibitors and [anti-stem antibodies] in humans,” the authors write. In addition, this new understanding of how anti-stem antibodies exert their protective effects should aid the design of universal flu vaccines targeting the hemagglutinin stem domain. Kosik et al., 2019. J. Exp. Med. http://jem.rupress.org/cgi/doi/10.1084/jem.20181624?PR

Implants can provide doctors with regular activity updates and are powered by the patient’s movement BINGHAMTON, N.Y. – Smart knee implants may soon be a reality thanks to research conducted by a team including faculty at Binghamton University, State University of New York. Knee replacement surgery is the most common joint replacement procedure, with the number of surgeries increasing every year. Many of those surgeries are done to replace an older implant or one that has worn out. Increasingly, this surgery is being performed for younger, more active patients who are faced with a dilemma. When they undergo the surgery, they are expected to remain physically active for their overall health, but that activity can also wear down the new implant. Often, doctors don’t know if patients are overexerting themselves until they begin to develop symptoms. By that point, the damage to the implant has already been done. For a young patient, going through knee replacement surgery every five or 10 years is a daunting task, but finding the perfect balance of activity levels to maintain the integrity of the implant has been equally daunting. Researchers decided it was time to create smarter knee implants that could monitor changes in activity as they happened. Assistant Professor Sherry Towfighian from Binghamton University served as the lead principal investigator on the study, which has been supported by the National Institutes of Health (NIH). “We are working on a knee implant that has built-in sensors that can monitor how much pressure is being put on the implant so doctors can have a clearer understanding of how much activity is negatively affecting the implant,” said Towfighian. The sensors allow doctors to tell patients when a certain movement has become too much for the implant so patients can quickly adjust and avoid further damage to the implant. It helps them find the sweet spot of activity for each particular patient. While the sensors solved one problem, they brought in another. The researchers did not want to power the sensors with a battery that might need to be replaced periodically and therefore, defeat the purpose of a smart implant. Instead, they worked on an energy harvesting mechanism that can power the knee implant from motion. Wathiq Ibrahim, a postdoc in Towfighian’s group, developed a prototype of the energy harvester and tested that under a mechanical testing machine to examine its output under equivalent body loads. They used triboelectric energy, a type of energy that is collected from friction. Once someone walks, the friction of the micro-surfaces coming into contact with each other can be used to power the load sensors. Associate Professor Emre Salman from Stony Brook University designed the circuit and determined that it would need 4.6 microwatts. The preliminary testing showed the average person’s walk will produce six microwatts of power, more than enough to power the sensors. This part of the research was complemented by Assistant Professor Ryan Willing from the University of Western Ontario, who worked on the implant design and the package of the sensor. These smart implants will not only give feedback to doctors but will help researchers in the development of future implants. “The sensors will tell us more about the demands that are placed on implants, and with that knowledge, researchers can start to improve the implants even more,” said Towfighian. Towfighian is hopeful that the combination of activity sensors and a self-powered system will increase the life span of knee implants and reduce the need for follow-up surgeries. For young patients looking at the possibility of knee replacement surgery, this development has the potential to be life-changing. This research has been supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health under award number R21AR068572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research was published in Smart Materials and Structures.

Newswise — LOS ANGELES (January 21, 2019)—Cedars-Sinai pharmacists are helping make clinical care safer and more effective as more patients with complex medical needs require a variety of increasingly complicated medication therapies.  "Frequent medical breakthroughs mean that more of the patients we see are taking a myriad of medications for a wide range of diseases," said Rita Shane, PharmD, chief pharmacy officer and professor of medicine at Cedars-Sinai. "We ensure that a patient's treatment plan is carried out the way it was intended. It's an expansion of the role of a pharmacist in a community practice that people are familiar with." Cedars-Sinai pharmacists are tasked with ensuring patients receive the medications they need safely and effectively and stick to their regimens once they return home while not taking unnecessary drugs. When patients fail to take prescribed medications—or don't use them the right way—they risk return trips to the hospital and cost the U.S. healthcare system more than $100 billion a year, according to a 2005 study in The New England Journal of Medicine. Older hospital patients are most susceptible to drug-related problems that can lead to readmissions or even death. To help these individuals get the right medications and take them correctly after discharge, Cedars-Sinai has embedded pharmacists in the care teams treating certain high-risk patients. Medication lists are double-checked by a pharmacist for errors prior to discharge, and patients are sent home with their prescription drugs after being counseled on how to take them properly. Early data show that the transitions of care pharmacy program reduced 30-day readmissions for these patients by 14.5% percent while eliminating prescription errors caused by providers. Some of the initiatives in Cedars-Sinai's innovative pharmacy practice include:    Medication Education—Pharmacists teach patients at high-risk of being readmitted to the hospital about their medications and ask patients to explain their drug regimens in their own words. Pharmacists also counsel patients at their hospital bedsides or call them within 72 hours of being discharged to check that patients are taking their medications as prescribed. Reducing Errors—Pharmacists and pharmacist technicians stationed in the medical center's Emergency Department take medication histories for high-risk patients, reducing prescribing errors. Other high-risk hospital patients also have their medication lists evaluated to help avoid unnecessary readmissions. This Cedars-Sinai innovation was tested, and research proved this approach to be effective, which led to a new California law that went into effect this year. Inpatient pharmacists evaluate all orders for medications to avoid drug-to-drug interactions and to ensure that dosages are safe based upon each patient's underlying diseases or conditions. Curbing Unnecessary Antibiotic Use—Pharmacists trained in treating infectious diseases monitor antibiotic use by accompanying physicians on patient rounds. Inpatient pharmacists routinely evaluate and monitor antibiotics to catch early signs of antibiotic resistance. Medication Delivery—Patients can request that their discharge prescription medications be delivered to their room before they leave the hospital. A pharmacist completes a comprehensive review of the patient's medical and medication history and, if needed, offers information about financial assistance. This ensures a smooth transition back home.  High-Cost Drugs—As drug costs skyrocket, Cedars-Sinai's inpatient pharmacy is reducing the amount of money spent on certain high-cost medications. Pharmacists work closely with physicians and the latest medical evidence to determine when a high-cost drug is essential or when a generic drug or an alternative approach would work equally well.

** Newswise — Researchers at the Fralin Biomedical Research Institute at VTC have identified a cellular response in mice to mild traumatic brain injuries that may lead to seizures. Traumatic brain injury is a leading cause of epilepsy, which is characterized as the repeated occurrence of seizures. No treatments currently interrupt the process that the brain undergoes after injury that can eventually lead to the chronic condition of epilepsy.  The study, published Monday (Jan. 21) in JNeurosci, suggests that the development of epilepsy triggered by mild traumatic brain injury may be related to an atypical response from brain cells known as astrocytes, which change to form scars after a severe brain injury. This process is important to protect uninjured brain areas but comes at a price, because these scars have been associated with epilepsy. The scientists found that astrocytes do not form scars after mild traumatic brain injury, but some astrocytes are altered in a different way almost immediately by these less severe types of injuries. Then, weeks later, the scientists observed spontaneous, recurrent seizures in some mice. “Our experiments show a strong relationship between changes in astrocytes and the eventual occurrence of a seizure,” said Stefanie Robel, the corresponding author of the study, who is an assistant professor with the Fralin Biomedical Research Institute and at the School of Neuroscience in Virginia Tech’s College of Science. “The findings point to a unique population of astrocytes that respond within 30 minutes of an injury being at the root of the problem where seizures may occur after a latency period of weeks or months, suggesting a therapeutic window to prevent seizure disorders after concussive injuries.” Robel, research associate Oleksii Shandra, and colleagues at the Fralin Biomedical Research Institute discovered areas of the brain where astrocytes no longer performed their usual housekeeping work to support normal nerve cell function after mild traumatic brain injury. They first assumed these pockets of nonfunctioning astrocytes were dead, because they no longer made the proteins that normally identify them as astrocytes. Later, Alex Winemiller, a research assistant at the Robel lab and one of the first authors of the study, discovered the cells were alive, but not reacting to injury in their typical manner. Researchers compared data from mice that eventually developed epilepsy with mice that never developed seizures and found a correlation between the loss of function in patches of astrocytes and the development of epilepsy. “Each of these astrocytes is connected to multiple neurons, which make hundreds of thousands of connections, which means the loss of function of even a few astrocytes can be devastating to other cells in the brain,” said Shandra, the first author of the study. “Not only have these astrocytes lost their function, but due to these altered connections, the effects can be widespread to brain cells far away. The degree of this astrocyte dysfunction might be something that defines whether epilepsy develops.” While it has been known that traumatic brain injury is a leading cause of acquired epilepsy, the precise relationship between such injuries and seizures has been elusive. This new study shows that after a latency period, some of the mice developed spontaneous recurrent seizures reminiscent of post-traumatic epilepsy in human patients with traumatic brain injuries, providing a new experimental model that could contribute to understanding of post-traumatic epilepsy. The research was supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, the Institute for Critical Technology and Applied Science at Virginia Tech, and the Fralin Biomedical Research Institute. **The cortical grey matter of a mouse is depicted in the 3-D reconstructed confocal image above. Researchers at the Fralin Biomedical Research Institute at VTC linked a subtype of atypical brain cells called astroscytes with post-traumatic genesis of epilepsy. The reactive astrocytes are characterized by proteins glutamate transporter 1 (blue) and S100 beta (green). Instead of undergoing cell death after mild traumatic brain injury, the atypical astrocytes have an enhanced expression of fluorescent protein tdTomato (red).  

Newswise — A commonly held belief among the general public is orthodontic treatment will prevent future tooth decay. Research undertaken at the University of Adelaide has found that this is not the case. Published in the journal Community Dentistry and Oral Epidemiology the study, conducted by Dr Esma J Dogramaci and co-author Professor David Brennan from the University’s Adelaide Dental School, assessed the long-term dental health of 448 people from South Australia. “The study found that people who had orthodontic treatment did not have better dental health later in life,” says Dr Dogramaci. “Patients often complain about their crooked teeth and want braces to make their teeth straight so they can avoid problems, like decay, in the future.” The study, which followed people from the age of 13 until they were 30, recorded patients’ dental health behaviours and the number of decayed, missing or filled teeth. “By the age of 30 over a third of participants had received orthodontic treatment,” says Dr Dogramaci. “There is a misconception amongst patients that orthodontic treatment prevents tooth decay, but this is not the case.” The cost of orthodontic treatment, in which crooked teeth are realigned using braces worn over several years, varies from approximately AUS$3000 to $13,000 according to the severity of the problems. Braces are becoming increasingly popular, with one in five patients being adults. The global orthodontics market is predicted to be worth more than US$6 billion by 2023. “Evidence from the research clearly shows that people cannot avoid regularly brushing their teeth, good oral hygiene and regular dental check-ups to prevent decay in later life,” says Dr Dogramaci. “Having your teeth straightened does not prevent tooth decay in later life.” The research was carried out by the Adelaide Dental School, and the Australian Research Centre for Population Oral Health (ARCOPH), the University of Adelaide.

Leading Global Experts Identify Good Practices in the Use of Evidence to Inform Decision Making for Health Technologies Newswise — Lawrenceville, NJ, USA—January 21, 2018—ISPOR—the professional society for health economics and outcomes research—announced today the publication of the first report in 20 years to comprehensively synthesize good practices in health technology assessment (HTA)—intended to support population-based decision making for pharmaceuticals, medical devices, and other health technologies. The report, “Identifying the Need for Good Practices in Health Technology Assessment: Summary of the ISPOR HTA Council Working Group Report on Good Practices in HTA,” was published in the January 2019 issue of Value in Health.   The paper is the work of prominent experts in health technology assessment (HTA) who are members of the "Overview Of Good Practices For Synthesizing And Using Evidence In Healthcare Decision Making” Working Group of the ISPOR Health Technology Assessment Council. The authors point out that while most research articles on HTA focus on research methods, HTA is defined not by its methods but by its intent, which is to inform healthcare decision making. In keeping with this focus, the Working Group members have provided important guidance for practice. They framed their report around 4 primary themes: (1) defining the HTA process, (2) synthesizing evidence (assessment), (3) using evidence (contextualization), and (4) implementing and monitoring HTA.  The primary audience for this report are those who manage, design, or seek to improve HTA processes, although it is informative to a wider audience of patients, healthcare providers, payers, academics, and industry stakeholders. Given the large scope of this work, the HTA Council Working Group created this overview report that included a summary of key references related to good practices in HTA. The report outlines where there appears to be guidance for good practices and where guidance is still emerging (or could not be identified) with a view to prioritizing next steps that may be taken by ISPOR and other interested parties.  “We identified 3 areas where few good practices in HTA have been developed or where there is no clear consensus,” noted author Don Husereau, MSc, BScPharm, University of Ottawa, Ottawa, ON, Canada. “These areas include the structure/governance/organizational aspects of HTA, the deliberative processes and other methods for integrating social values in HTA, and measuring the impact of HTA. In my opinion, the area of integrating social values is the most important and underdeveloped aspect of HTA. HTA bodies have increasingly been exploring how to best integrate social values, particularly patient values, but many fall short of standards for deliberative processes that are fair and transparent.”  The report authors are global experts in the field of HTA and include:  Co-Chairs: Finn Børlum Kristensen, MD, PhD; University of Southern Denmark; Odense, Denmark Don Husereau, MSc, BScPharm; Institute of Health Economics; Edmonton, AB, Canada; University of Ottawa, Ottawa, ON, Canada; and University of Health Sciences, Medical Informatics, and Technology, Hall in Tirol, Austria  Leadership Group: Federico Augustovski, MD, MS, PhD; Institute for Clinical Effectiveness and Health Policy; Buenos Aires, Argentina Marc L. Berger, MD; New York, NY, USA Kenneth Bond, MA; Canadian Agency for Drugs and Technologies in Health; Ottawa, ON, Canada Andrew Booth, PhD; ScHARR; The University of Sheffield; Sheffield, England, UK John F. P. Bridges, PhD; The Ohio State University, Columbus, OH, USA Michael F. Drummond, DPhil, MCom, BSc; University of York; York, England, UK Jeremy Grimshaw, MBCHB, PhD; Cochrane Canada and University of Ottawa; Ottawa, ON, Canada Mirjana Huić, MD, MSc; Agency for Quality and Accreditation in Health Care and Social Welfare; Zagreb, Croatia Maarten J. IJzerman, PhD; University of Melbourne, Melbourne, Australia; University of Twente, Enschede, The Netherlands Egon Jonsson, PhD; Institute of Health Economics; Edmonton, AB, Canada Daniel A. Ollendorf, MPH, PhD; Tufts University, Boston, MA, USA Alric Rüther, dr. med; Institute for Quality and Efficiency in Health Care; Cologne, Germany Uwe Siebert, MD, MPH, MSc, ScD; University of Health Sciences, Medical Informatics, and Technology, Hall in Tirol, Austria; ONCOTYROL - Center for Personalized Cancer Medicine, Innsbruck, Austria; Massachusetts General Hospital, and Harvard T.H. Chan School of Public Health, Boston, MA, USA Jitendar Sharma, PhD, AP MedTech Zone and Department of Health and Family Welfare; Andhra Pradesh, India Allan Wailoo, PhD, MSc, MA; ScHARR; University of Sheffield and NICE Decision Support Unit; Sheffield, England, UK  ###

Racial disparities in electroconvulsive therapy Illustration: National Institute of Mental Health (01/14/2019) Racial disparities exist in the use of electroconvulsive therapy to treat depression in older adults, found a study including a Houston VA health Care System researcher. ECT involves applying electrical current to the brain to treat mood disorders. It has proven effective in treating major depressive disorder when medication does not work. The researchers looked at nearly 700,000 patients older than 65 in a national health care database. They found that black and Hispanic patients were nearly half as likely to receive ECT, compared with white patients. While the research team acknowledges that patient preference may have played some role, they assert that efforts are needed in any case to ensure that minority groups have equal access to care. (American Journal of Geriatric Psychiatry, Nov. 29, 2018) Barriers to medication treatment for opioid use disorder (01/14/2019) VA Palo Alto Health Care System researchers explored the barriers to using medication to treat opioid use disorder within VA. Evidence shows that medications such as methadone, buprenorphine, and naltrexone care be effective at treating opioid use disorder. However, only 21 percent of patients with the disorder in VA residential treatment are on these medications. According to patient and staff surveys, barriers to this type of treatment include program philosophy against medication use, lack of coordination with other treatment settings, and perceived low patient interest. Having prescribers on staff, education and support for patients and staff, and support from leadership would help facilitate medication treatment, according to survey responses. (Journal of Studies on Alcohol and Drugs, November 2018) Survey: Most Vets OK with curbing gun access during times of high suicide risk (01/14/2019) Veterans receiving mental health care were in favor of voluntary programs to reduce firearm access during high-risk periods for suicide, in a VA Ann Arbor Health Care System survey. Veterans in mental health care have high rates of firearm-related suicide. Of Veterans surveyed receiving mental health care at one VA facility, 93 percent were in favor of health system interventions to limit firearm access. Of those, 75 percent were in favor of substantially limiting firearm access during times of crisis. While Veterans with household firearms were less likely to be in favor of interventions, 50 percent of the group that owns firearms still said they would participate in an intervention to limit firearm access during high-risk periods. The results suggest that VA and other health systems should consider more intensive efforts to voluntarily limit firearm access during high-risk periods, say the researchers. (General Hospital Psychiatry, Nov.-Dec. 2018) Risk factors for transition from suicidal thoughts to attempts (01/03/2019) A team co-led by a VA San Diego Healthcare System researcher identified characteristics that differed between service members who contemplated suicide and those who went on to make a suicide attempt. As part of the Army STARRS study, researchers surveyed more than 10,000 soldiers. They found that, compared with soldiers without suicidal thoughts, those with suicidal thoughts had higher rates of interpersonal violence, relationship problems, major depressive disorder, PTSD, and substance use disorder. Soldiers with combat trauma in the past 12 months, intermittent explosive disorder, or any college education were less likely to have suicidal thoughts. Of those with suicidal thoughts in the past 30 days, those with PTSD had higher risk of suicide attempt. Those with intermittent explosive disorder or some college education were less likely to have attempted suicide. The results show that PTSD, intermittent explosive disorder, and education should be considered when studying what makes suicidal ideation transition into suicide attempts. (Depression and Anxiety, Dec. 14, 2018) Carpal tunnel syndrome treatment varies widely in VA (01/03/2019) Nonsurgical therapy use for carpal tunnel syndrome varies widely within the Veterans Health Administration, according to a study by VA Ann Arbor and Palo Alto researchers. Of nearly 80,000 patients diagnosed with carpal tunnel syndrome, 8 percent had surgery. Across different facilities, between 0 and 93 percent of surgical patients received physical therapy, occupational therapy, or an orthotic. Between 1 and 67 percent of nonsurgical patients received these types of therapy. Between 0 and 100 percent of surgical patients had electrodiagnostic studies (such as X-rays or CT scans), while between 0 and 55 percent of nonsurgical patients had diagnostic scans. The results suggest that clinical practice guidelines are needed to improve the uniformity and efficiency of carpal tunnel care, say the researchers. (Journal of Hand Surgery, Dec. 19, 2018) Probing the evidence for probiotics (01/03/2019) Evidence suggests that several probiotics are effective to treat various conditions, found a study by an Edward Hines, Jr. VA Hospital researcher and colleagues. Probiotics are live bacteria and yeast that promote a healthy microorganism balance in the digestive tract. While many probiotics are on the market, evidence is lacking on their effectiveness. Researchers reviewed the current medical literature and consulted experts in the field about which probiotics have been shown to be effective. They found enough evidence to suggest that 22 different types of probiotics are effective at treating different conditions. Some probiotics had strong evidence for treatment of conditions such as antibiotic-associated diarrhea, pediatric acute diarrhea, and inflammatory bowel disease. The researchers stress that it is important to pick the correct strain, formulation, and dose of a probiotic to match a specific disease. (PLoS One, Dec. 26, 2018) Intimate relationships may buffer against suicide (12/26/2018) Strong intimate relationships could help protect service members from suicide, according to a VA Ann Arbor Health Care System study. Researchers surveyed 712 National Guard members after they returned home from deployment. The found that lower relationship satisfaction and more depressive symptoms at six months after deployment were linked to greater risk of suicide 12 months after deployment. Couple satisfaction was related to suicide risk for service members with PTSD, depression, and anxiety. The results show that the strength of an intimate relationship could serve as a buffer against suicide for patients who have these conditions, say the researchers. (Suicide and Life-Threatening Behavior, Dec. 3, 2018)

Survey of first-year internal medicine residents shows those in programs with longer hours, less faculty mentoring & more research focus had higher depression scores Newswise — Nearly 20,000 future doctors will graduate from U.S. medical school this spring, and embark on the residency training that launches their careers. Right now, they’re choosing which hospitals and health systems they’d most like to train at. But a new study suggests that their mental health in the crucial first year of training – called internship – may depend a lot on the nature of the program they enter. Writing in the journal Academic Medicine, a team from the University of Michigan and Medical University of South Carolina report that medical interns were more likely to suffer from depression at certain programs compared with others. The researchers documented the effect across several years’ worth of year-long surveys of 1,276 interns in 54 programs across the country, who were taking part in the larger effort known as the Intern Health Study. Internal medicine residency programs whose trainees reported the longest working hours, the least helpful feedback from faculty, and the least-valuable inpatient training rotation experiences had the highest rates of depression symptoms among their trainees. So do programs that produced doctors who tended to go on to research-focused careers, as ranked by Doximity. Disparities in depression Depression symptoms rose across the intern years, as measured on a standard survey that each intern took before their intern year began, and four times during the year. A composite ‘depression score’ rose on average from 2.3 to 5.9. That’s expected. The stress and demands of intern year have previously been shown to be associated with depression, in years of work led by Srijan Sen, M.D., Ph.D., the senior author of the new paper and leader of the Intern Health Study. Depression among medical students, residents and practicing physicians has been shown to be associated with career burnout, medical errors, lower quality care, motor vehicle crashes and suicidal thoughts. But the new paper drills down to see what factors that interns reported about their experience in a specific program, and publicly available factors about the programs, mattered most. “While most of the focus on resident depression has been on the individual resident, in this paper we show that institutions and residency programs play a critical role,” says Sen, the Eisenberg Professor of Depression and Neurosciences at U-M and member of the U-M Depression Center and the U-M Molecular and Behavioral Neuroscience Institute. “Some programs have consistently high rates of depression year after year, while others have consistently low depression. We also find four factors that explain much of the difference between programs.” Mapping the differences Sen and his colleagues, led by U-M Department of Psychiatry researcher Karina Pereira-Lima, M.Sc., looked at which factors predicted the largest rises in depression scores, and the highest percentage of interns whose scores were above 10, meaning that they met the criteria for having major depression. At least five, and as many as 101, interns from each program participated. On average, one-third of interns met the criteria for major depression – about what Sen has found in previous work. But some programs had no interns meet the criteria for depression, while in others, three-quarters of those surveyed met the criteria. Even when the researchers accounted for factors about the interns themselves that might have made them more prone to depression – such as a history of past depression, childhood stress, a tendency toward neurotic behavior and female gender – the four residency program factors still stood out as making a difference in their likelihood to develop depressive symptoms during their intern year. In all, the four factors accounted for nearly half of the variation among internship programs in the change in depression symptoms experienced by all the participating interns. Poor timeliness and appropriateness of faculty feedback stood out as the most important factor, suggesting that efforts to improve the teaching skills of the physicians who supervise and mentor interns could affect interns’ mental health. The impact of the research ranking of a residency program was noteworthy and suggests that some of our most prestigious institutions could most benefit from reform, says Sen. Doximity’s rankings are based on the quantity of research papers published by alumni of a particular program, and the number of research grants won by those alumni. The researchers found no differences between the baseline depression-prone characteristics of interns who chose research-focused residency training sites. Rather, they say, the research ranking may be a marker of residency program culture, and of the complexity of the patients that interns care for at research-intensive institutions compared with hospitals that don’t train as many future researchers. More study is needed, they say. “These findings suggest that the residency program environment plays a central role in the mental health of medical interns,” says Pereira-Lima, who is also a doctoral candidate at the Ribeirão Preto Medical School of the University of São Paulo in Brazil. “These program-level factors can inform changes to residency programs that may reduce the risk of depression in resident physicians.” Next steps Sen notes that the results of the study have been shared with groups interested in physician and trainee well-being. He and his colleagues are planning further research on residency program factors, beyond surveys and beyond internal medicine training. They’re also continuing to analyze genetic samples from thousands of participants in the study, to see if they can detect changes over time and relate them to changes in depression symptoms. Meanwhile, more than 2,050 current interns are enrolled in the Intern Health Study for 2018-2019, using Fitbit activity trackers and a mood-tracking smartphone app to monitor their sleep, work hours and depression symptoms. The team is beginning to recruit graduating medical students and others who will begin their intern year this summer at more than 80 sites across the U.S. and China in several types of residency programs. For more information visit https://www.srijan-sen-lab.com/intern-health-study In addition to Pereira-Lima and Sen, the study’s authors are U-M medical student Rahael Gupta, who has written in JAMA of her own experience with depression, and Constance Guille, M.D., Ph.D. of MUSC, who has also led research on depression and medical trainees, including a study in JAMA Internal Medicine in 2017 that found that differences in depression symptoms between male and female interns was partly explained by differences in levels of work-family conflict between the genders.   The study was funded by the National Institute of Mental Health (MH101459, MH095109) which supports the Intern Health Study, and by the Sao Paulo Research Foundation.   Reference: Academic Medicine, doi: 10.1097/ACM.0000000000002567, https://journals.lww.com/academicmedicine/Abstract/publishahead/Residency_Program_Factors_Associated_with.97753.aspx