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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
New Jersey’s second annual Maternal Health Awareness Day on January 23 brings attention to Rutgers’ Stop.Look.Listen campaign, which one grieving father hopes to take national Newswise — Shortly after giving birth to her son Brandon in 2011, Tara Hansen – while still in the hospital – told healthcare providers her body didn’t feel right. But they considered her a healthy post-partum patient and sent her home. Six days later, she died from an infection that had occurred during the birth. “Tara was the only person who knew something was wrong, and her complaints just kept falling on deaf ears,” her husband, Ryan, said. “Everyone assumed that the pain she described was to be expected because she just had a baby.” Maternal deaths are declining worldwide, but are on the rise in the United States. The U.S. Centers for Disease Control and Prevention reported 18 pregnancy-related deaths for every 100,000 live births nationwide in 2014, up from a low of 7.2 in 1987. In New Jersey, the most recent state data shows that from 2006 to 2008, the average maternal mortality rate was 14.4 deaths per 100,000 births, with higher rates reported for black women. Vowing to make an impact in his wife’s honor, Ryan, a Rutgers alumnus, launched the Tara Hansen Foundation in 2012 and forged a partnership with Rutgers Robert Wood Johnson Medical School, where his mother, Patricia Hansen, is director of communications and public affairs. With assistance from the medical school and Robert Wood Johnson University Hospital, the foundation developed the “Stop. Look. Listen!” campaign. Its goals are to increase public and professional awareness of pregnancy-related deaths, empower women to report pregnancy-related medical issues, and increase awareness and responsiveness among healthcare practitioners.  The campaign prompted a New Jersey law establishing January 23 of each year as Maternal Health Awareness Day – the first of its kind nationwide. “Pregnancy is considered a happy time in a woman’s life, and families don’t want to think about anything negative, like hypertension or diabetes,” said Gloria Bachmann, director of the Women’s Health Institute at Robert Wood Johnson Medical School, who helped create the campaign. “Our goal is to empower women and families to advocate if they feel something is wrong and understand that no question about the mother-to-be or new mom’s health is inconsequential. For example, itchy skin could mean a liver or gall bladder problem, which was caused by the pregnancy. With ‘Stop. Look. Listen!’ clinicians need to stop whatever they are doing, look at the woman and conduct a full medical evaluation and, of course, listen carefully to what she and her family are saying about her concerns and how she is feeling,” Bachmann said. The campaign seeks to educate all healthcare providers – not just OB-GYNs, nurses and certified nurse midwives – as well as family members and emergency room physicians, who may be the first to recognize something might be wrong with a woman who has just given birth. “Many women have a history of good health but suffer from pregnancy-related issues during or just after delivery, such as cardiovascular diseases, blood clots, pneumonia and stroke, which can result in death,” said Bachmann. Ryan Hansen looks forward to promoting “Stop. Look. Listen!” nationwide. “It’s frightening that most people in the United States do not consider a healthy, postpartum woman at risk for death since we are in a developed country,” he said. “This day of awareness shows that Tara’s death has meaning – to save other women’s lives.” More information about Maternal Health Awareness Day, #123forMoms may be found here:  http://go.rutgers.edu/hbq3qwmi
Newswise — HOUSTON ― Researchers have identified a new potential immunotherapy target in pancreatic cancer, which so far has been notoriously resistant to treatment with immune checkpoint blockade drugs effective against a variety of other cancers. The University of Texas MD Anderson Cancer Center research team found overexpression of the immune checkpoint VISTA on immune cells, especially macrophages, that infiltrated pancreatic tumors. Their paper will be published online Friday at the Proceedings of the National Academy of Sciences. “VISTA is a potential therapeutic target in pancreatic cancer, and there are several antibodies to block VISTA under clinical development,” said co-senior author Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology. “Additional research also needs to be done to see if we can come up with other targets for these VISTA-positive cells as well.” Present immune checkpoint inhibitors that unleash an immune attack on cancer by blocking PD-1 and CTLA-4 brakes on T cells have been ineffective against pancreatic cancer, one of the most lethal cancers.  The five-year survival rate for patients with pancreatic cancer is 7 percent or less. The team, led by Sharma and 2018 Nobel Laureate Jim Allison, Ph.D., professor and chair of Immunology, set out to shed light on infiltration of immune cells and expression of immunity-inhibiting checkpoints in pancreatic cancer by comparing those tumors to melanoma, the cancer that is most vulnerable to immune checkpoint blockade. They first analyzed expression of nine immune inhibitory genes in 23 untreated, surgically removed pancreatic cancer tumors and found the results separated the patients into two groups, 11 with high-expression of inhibitory genes and 12 with low expression. Those with low-expression of immune inhibitors had a median survival of 37 months versus 20 months for the high-expression group, indicating potential immune impact on overall survival. Tumor architecture: Stroma and malignant cells Pancreatic cancer tumors include a high density of stroma, non-malignant supportive cells, while melanoma is at the other end of the spectrum with minimal stroma. These differences came into play in the team’s analyses. The pancreatic tumors were composed of 30 percent malignant cells and 70 percent stroma, while those proportions were flipped in melanoma tumors. In addition to the vastly different ratio of stromal cells, the architecture of the tumor types also diverges, Sharma notes. “In melanoma, you have a large area of malignant cells surrounded by a thin layer of stroma. With pancreatic cancer, it’s more like cancer cells, stroma, cancer cells, stroma ― blended.” Analysis of 29 untreated pancreatic cancer tumors and 44 untreated melanomas found heavier penetration of attacking immune T cells in melanoma as well as higher levels of cells expressing the inhibitory checkpoint molecules PD-1 and its activating ligand PD-L1, which are successfully targeted by inhibitors to treat melanoma. However, pancreatic tumors had much higher expression of VISTA. About a third of the pancreatic tumors had T cell penetration roughly equal to that found in melanoma, but the T cells were concentrated mainly in the stroma of the tumors, rather than the malignant cells, while they were evenly distributed between cancer cells and stroma in melanoma. To the researchers, that makes sense. “In pancreatic cancer, you have much more stroma than malignant cells in the tumor. Why is that? I think it’s how the tumor is growing,” Sharma said. Allison noted the stromal cells might be keeping the T cells out of the cancer cells. VISTA and macrophages VISTA is predominantly expressed on macrophages – “big eater” immune cells that engulf and digest microbes, cellular debris, and tumor cells as part of immune response.  VISTA is known to deactivate T cells. While the researchers found roughly equal density of CD68-positive macrophages in both tumor types, in pancreatic cancer they were again concentrated in the stroma. Macrophages in the pancreatic tumors had much higher expression of VISTA. A separate comparison of three types of pancreatic tumor – untreated primary, treated metastatic and primary tumors pretreated before surgery – found low penetration of T cells in the metastatic tumors and elevated levels of VISTA in the untreated primary and metastatic tumors. Analysis of seven pancreatic samples found that CD68-positive macrophages had distinct PD-L1 and VISTA pathways that inhibit immune response separately. Experiments with T cells taken from tumors of three patients with metastatic pancreatic cancer showed that an active VISTA pathway decreased active T cell responses in the tumor to a greater degree than PD-L1 inhibition. This suggests treatment with PD-1/PD-L1 inhibition might fail because an untreated VISTA pathway still suppresses immune response. Moon Shots Program collaboration Future research will include exploration of combination therapy strategies to increase T cell infiltration, possibly using anti-CTLA-4 checkpoint inhibition, plus a VISTA antibody to target macrophages, Sharma said. Allison and Sharma lead MD Anderson’s immunotherapy platform, which thoroughly characterizes immune response to tumors and to treatment via immune monitoring of tumor samples before, during and after treatment. The platform team worked with MD Anderson’s Pancreatic Cancer Moon Shot™ and Melanoma Moon Shot™, part of the institution’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives. Co-authors with Allison and Sharma are co-first authors Jorge Blando, Ph.D., and Anu Sharma, Ph.D., and Maria Gisela Higa, M.D., Hao Zhao, Ph.D., Luis Vence, Ph.D., Shalini Yadav, Ph.D., Jiseong Kim, and Sreyashi Basu, Ph.D., all of the Immunotherapy Platform; Anirban Maitra, M.B.B.S., Michael Tetzlaff, M.D., Ph.D., Russell Broaddus, M.D., Ph.D., and Huamin Wang, M.D., Ph.D., of the department of Pathology; Jennifer Wargo, M.D., and Matthew Katz, M.D., of Surgical Oncology; Gauri Varadhachary, M.B.B.S., M.D., and Michael Overman, M.D., of GI Medical Oncology; Cassian Yee, M.D., and Chantale Bernatchez, Ph.D., of Melanoma Medical Oncology; Christine Iacobuzio-Donahue, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center, New York; Alejandro Sepulveda, Ph.D., and Michael Sharp of Janssen Research and Development, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA.  Kim is a doctoral student in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. This research was funded by the immunotherapy platform, the Pancreatic Cancer Moon Shot, a grant from the National Cancer Institute (RO1 CA1633793) and the Parker Institute for Cancer Immunotherapy (PICI). Allison, Sharma, Wargo and Yee are members of PICI.
Penn study shows 41 percent increase in opioids for small animals over past 10 years; findings indicate another avenue of potential risk for human access to opioids Newswise — PHILADELPHIA—The increase in opioid prescriptions for people over the past decade may have been paralleled by an increase in opioid prescriptions for pets, according to a study from researchers at the University of Pennsylvania’s Perelman School of Medicine and the School of Veterinary Medicine. The findings, in this first-ever study of veterinary opioid prescriptions, suggest that there is also an increased demand for veterinary opioids, driven by complex procedures performed in veterinary medicine, as well as a heightened awareness of the importance of pain management. Given that opioid prescribing in veterinary medicine is not as heavily regulated as medical prescriptions for humans, it is possible that misused veterinary prescriptions could contribute to the ongoing opioid epidemic. The results are published today in JAMA Network Open. In the study, researchers reviewed all opioid pills and patches dispensed or prescribed for dogs, cats, and other small animals at the University of Pennsylvania’s School of Veterinary Medicine (Penn Vet) from January 2007 through December 2017. The results show that the quantity of these prescriptions, as measured in morphine milligram equivalents (MME), rose by 41 percent during the period annually, while the annual number of visits rose by only about 13 percent. As a veterinary tertiary care facility, Penn Vet’s unique caseload requires particular attention to and treatment of pain in veterinary species, which may account for increased opioid utilization in the study. “As we are seeing the opioid epidemic press on, we are identifying other avenues of possible human consumption and misuse,” said study senior author Jeanmarie Perrone, MD, a professor of Emergency Medicine and the director of Medical Toxicology at Penn Medicine. “Even where the increase in prescribed veterinary opioids is well intended by the veterinarian, it can mean an increased chance of leftover pills being misused later by household members, sold or diverted, or endangering young children through unintentional exposure. The results of this study suggest that by assessing the rate of veterinary opioid prescriptions, we can develop strategies to reduce both human and animal health risks associated with increasing use.” The current opioid crisis in the United States causes tens of thousands of overdose deaths every year—roughly 50,000 in 2017, according to the Centers for Disease Control and Prevention. The crisis began in the late 1990s and was fueled largely by a steep increase in prescriptions for opioid pain relievers. Tightening regulations including prescription drug monitoring programs have helped reduce the number of opioid prescriptions from their peak in 2011. Although prescription opioid overdose deaths are now exceeded by those due to illegally obtained heroin and fentanyl, the former still account for nearly 20,000 fatalities annually. Since opioid prescribing in veterinary medicine is not as comparatively regulated, concerns are raised that opioids prescribed for pets could be misused by humans.  The researchers reviewed pharmacy records at the Penn Vet’s Ryan Hospital during the 10-year study window, and analyzed trends for the four opioids prescribed or dispensed to animal patients — tramadol, hydrocodone, and codeine tablets, and fentanyl patches. The animals in the study included dogs (73.0 percent), cats (22.5 percent), and assorted others including rabbits, snakes, and birds (4.5 percent). “We found that the increased quantity of opioids prescribed by our hospital was not due to increased patient volume alone. It is likely that our goal of ensuring our patients are pain-free post-operatively, particularly for those requiring complex and invasive procedures, has driven our increased prescribing practices during this period,” said lead author Dana Clarke, VMD, an assistant professor of Interventional Radiology at the University of Pennsylvania’s School of Veterinary Medicine “At the national level, we don’t know the potential or extent of prescription diversion from animals to humans, and what impact this could have on the human opioid crisis.” Anecdotes about veterinarian-prescribed opioids being used by people have already prompted some states to add restrictions to veterinary prescribing. In Pennsylvania, state legislators are working with the Pennsylvania Veterinary Medical Association (PVMA) to determine the most effective course of action for opioid dispensing by the state’s practicing veterinarians. Two states, Maine and Colorado, now require background checks on animal owners’ opioid prescription histories before a veterinarian can write an opioid prescription. Alaska, Connecticut, and Virginia now limit the amount of opioids any one veterinarian can prescribe to a single patient/animal. Twenty states now require veterinarians to report their opioid prescriptions to a central database, just as medical doctors do. At Penn Vet, efforts currently in practice to reduce opioid prescribing include preference of local anesthetics for post-operative pain, pain scores to guide administration of opioids, and monitoring of patients requiring long-term opioid use, such as dogs with chronic coughing requiring hydrocodone. The authors say it is important that the potential problem of diverted veterinary opioids be studied further to determine its scale, and should be addressed by extending the opioid stewardship measures that already affect medical physicians to veterinary doctors, in all states. Co-authors on the study include Kenneth Drobatz, DVM, of Penn Vet, Chloe Korzekwa, of Trinity College in Dublin, and Lewis S. Nelson, MD, of Rutgers New Jersey Medical School.