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.
Newswise — A summer undergraduate research fellowship has helped South Dakota State University sophomore Caroline Kincade figure out her career path. Through the Future Agriculture and Science Taskforce Research and Extension Experiences for Undergraduates (FAST REEU) fellowship program, Kincade worked on a project to understand how cells gain resistance to antibiotics under the supervision of Assistant Professor Nicholas Butzin. She was among the first group of students to participate in the U.S. Department of Agriculture-funded program, which provided qualifying students a 10-week summer laboratory experience at SDSU. In summer 2019, each student will do an industry internship. Associate Professor of Biology and Microbiology Madhav Nepal, who coordinates the program, said “We want to get our students excited about science and agriculture.” Students interested in FAST REEU fellowship can find more information at https://www.sdstate.edu/biology-and-microbiology/fast-reeu-fellowships. Applications are due March 15. “FAST made me realize I need to figure out what I am doing after graduation,” said Kincade, a microbiology major with a chemistry minor and a member of the Van D. and Barbara B. Fishback Honors College. The Otsego, Minnesota, native transferred to SDSU in fall 2017 after earning an associate degree in veterinary technology at Ridgewater College in Minnesota. “I am very impressed by Caroline,” said Butzin, who is faculty researcher in the Department of Biology and Microbiology in the College of Natural Sciences. He also does research through the South Dakota Agricultural Experiment Station. “She’s been a great help in the lab this summer,” added doctoral student Heather Deter, who is studying how changes in the genome allow cells, known as persisters, to gain resistance to antibiotics. “Antibiotic resistance happens because of a change in DNA.” “Persister cells hide out but also get DNA from other organisms that can give them resistance,” Butzin said. “They’re like sleeper cells—they wait until the antibiotics are gone and start growing again.” To study this phenomenon, the researchers use bacteria called Mycoplasma mycoides, which have a small genome. “Life is generally complex, so we want to start with something simple,” Butzin explained. The researchers begin with cells that cannot survive exposure to antibiotics and “add synthetic circuits that will allow us to test what actually causes persistence and how.” As part of the research team, Kincade helped figure out how to grow the cells, including what type of media and buffer to use. “Doing research taught me a lot of patience,” she said. E coli cells, for instance, grow in 24 hours. “These minimal genome cells take a lot longer to grow. “In a lab class, we have a procedure. If the experiment does not work, we go to the next one,” Kincade explained. “In research, we have to figure out why it did not work and redo it until it works” Once cells are treated, the researchers count the persister cells on each plate. Kincade scanned the plates and then used a computer program Deter created to count the persister cells. “This produces highly accurate quantitative data to understand what’s going on,” said Butzin, whose goal has been to challenge Kincade and thus increase her research skills. “I’ve learned a lot about techniques, plus the computer stuff,” Kincade said. As she contemplated her career path, Kincade said, “Always in the back of my head I kept thinking that what I am most passionate about is animal anatomy and parasitology.” Though she has decided to combine microbiology with veterinary medicine, Kincade will continue to use the skills she learned last summer. “The experience set me up for success,” she added.
Researchers have found that neighbour-cells can take over functions of damaged or missing insulin-producing cells; the discovery may lead to new treatments for diabetes Newswise — Diabetes is caused by damaged or non-existing insulin cells inability to produce insulin, a hormone that is necessary in regulating blood sugar levels. Many diabetes patients take insulin supplements to regulate these levels. In collaboration with other international researchers, researchers at the University of Bergen have, discovered that glucagon.producing cells in the pancreas, can change identity and adapt so that they do the job for their neighbouring damaged or missing insulin cells. "We are possibly facing the start of a totally new form of treatment for diabetes, where the body can produce its own insulin, with some start-up help," says Researcher Luiza Ghila at the Raeder Research Lab, Department of Clinical Science, University of Bergen (UiB). Cells can change identity The researchers discovered that only about 2 per cent the neighbouring cells in the pancreas could change identity. However, event that amount makes the researchers are optimistic about potential new treatment approaches. For the first time in history, researchers were able to describe the mechanisms behind the process of cell identity. It turns out that this is not at passive process, but is a result of signals from the surrounding cells. In the study, researchers were able to increase the number of insulin producing cells to 5 per cent, by using a drug that influenced the inter-cell signalling process. Thus far, the results have only been shown in animal models. "If we gain more knowledge about the mechanisms behind this cell flexibility, then we could possibly be able to control the process and change more cells' identities so that more insulin can be produced, " Ghila explains. Possible new treatment against cell death According to the researchers, the new discoveries is not only good news for diabetes treatment. "The cells´ ability to change identity and function, may be a decisive discovery in treating other diseases caused by cell death, such as Alzheimer´s disease and cellular damage due to heart attacks", says Luiza Ghila. Facts: Pancreas There are three different types of cells in the pancreas: alpha-cells, beta-cells and delta-cells. These produce different kinds of hormones for blood sugar regulation. The cells make clusters. Alpha-cells produce glucagon, which increases the blood sugar levels. Beta-cells produce insulin, which decreases glucagon levels. Delta-cells produce somatostatin, which controls the regulation of the Alpha and Beta Cells. Persons with diabetes have a damaged beta-cell function, and therefore have constant high blood sugar levels.
Newswise — Light pollution is on everyone’s minds in Reno, Nevada, a city famous for its bright lights and nightlife. Nighttime light pollution is a growing concern for cities worldwide. Artificial light at night has been found to cause serious health effects including disrupting our sleep-wake cycle –our circadian rhythm. Our local wildlife and their circadian rhythms are affected by light pollution just like humans. Valentina Alaasam, a graduate student in Dr. Jenny Ouyang’s lab at University of Nevada, Reno, is studying a small bird, the zebra finch, to better understand how cities affect the biology of urban wildlife. Their findings suggest that light pollution changes everything from the bird’s behavior to its underlying physiology. In the most scientifically precise meaning of the term, the birds are stressed out. Their results of their research will be presented at the annual meeting of the Society for Integrative and Comparative Biology in Tampa, FL. Take a step back from birds for a moment and imaging yourself in the lighting isle of your local hardware store. There is a plethora of lights of different sizes, brightness, and “temperatures,” or whiteness to choose from. Because of their lower energy requirements and longevity, LED bulbs are filling more shelf space than they once did. With such a selection there is much to learn about the ways different lighting options affect wildlife. Alaasam’s study found that different temperatures of commercially available LEDs affect wildlife differently – cooler temperature lights, those that best replicate natural light, are more stressful to birds. Nighttime exposure to cooler temperature LEDs caused birds to have increased levels of nighttime activity and trigged their physiological stress response, raising levels stress hormones in their blood. Precise regulation of stress hormones is critical for an animal’s survival. When a bird is captured, its stress hormones rapidly increase to give them energy to attempt escape – the famous fight-or-flight response. Stress hormones normally follow a circadian rhythm and only peak during active periods of the day. Thus, excess stress hormones in birds indicate that their normal schedule is disrupted and may affect their metabolism and behavior. The long-term physiological and behavioral effects of these elevated stress hormones on wildlife is not fully understood. However, in humans elevated stress hormones can challenge fundamental physiological process such as blood sugar regulation, inflammation, and fatigue. Analyzing the effects of light on the stress response of urban birds required an interdisciplinary experiment that brought together members of Dr. Ouyang’s lab, an electrical engineer to design and build new instruments, a neuroscientist who played a role in analyzing bird behavior, and a team of students that helped care for the birds. Such diversity in experiences led to unexpected challenges throughout the experiments. The birds behavior was to be recorded using specially designed perches. However, the researchers quickly realized that the bird’s weight, – about as much as a pencil– was not enough to activate the perch correctly. They had to adjust each perch to work for its intended bird’s weight. Relying on new technology is never an easy task. Alaasam remarked that there were several sleepless nights troubleshooting glitches, “I always joke about how my circadian rhythm and stress hormones were off the charts doing this experiment on circadian rhythms and stress on birds.” “Understanding how populations can acclimate to urban areas and whether or not that is genetically controlled – who can acclimate the best and who can’t – is a really interesting question.” Alaasam notes. Her findings could improve out understanding of the way wildlife are challenged in today’s cities. Over time, research like Alaasam’s could inform the way environmentally conscious urban planners light their cities. When talking to the citizens of Reno about her research, Alaasam described the potential the benefit of changing out cooler temperature LED’s in outdoor lights to warmer LED’s Alaasam also wants the public to know that “we might be experiencing the same stressors birds are experiencing in a less obvious way. Bird behavior has obvious changes, humans are complicated. The more we ameliorate stressors for our wildlife, the better our conservation and policies will be in the long run.”
Newswise — ROCHESTER, Minn. — The percentage of women who are screened for cervical cancer may be far lower than national data suggests, according to a Mayo Clinic study recently published in the Journal of Women’s Health. Less than two-thirds of women ages 30 to 65 were up-to-date with cervical cancer screenings in 2016. The percentage is even lower for women ages 21 to 29, with just over half current on screenings. Those figures are well below the 81 percent screening compliance rate self-reported in the 2015 National Health Interview Survey. “These cervical cancer rates are unacceptably low,” says Mayo Clinic family medicine specialist Kathy MacLaughlin, M.D., the study’s lead author. “Routine screening every three years with a Pap test or every five years with a Pap-HPV co-test ensures precancerous changes are caught early and may be followed more closely or treated.” In addition to lower-than-expected screening rates, Mayo Clinic researchers also found racial inequities in terms of who is getting screened. “African-American women were 50 percent less likely to be up-to-date on cervical cancer screening than white woman in 2016,” says Dr. MacLaughlin. “Asian women were nearly 30 percent less likely than white women to be current on screening. These racial disparities are especially concerning.” Mayo Clinic researchers reviewed medical records using the Rochester Epidemiology Project database to determine cervical cancer screening rates for more than 47,000 women living in Olmsted County, Minn., from 2005 to 2016. An estimated 13,240 new cases of invasive cervical cancer were diagnosed in the U.S. in 2018, according to the American Cancer Society. Another 4,170 women died from cervical cancer last year. January is Cervical Health Awareness Month. Dr. MacLaughlin says these study results should prompt health care providers to start considering new ways of reaching out to patients to help ensure they get screened. Ideas could include setting up Pap clinics with evening and Saturday hours, or offering cervical cancer screenings at urgent care clinics. For women who qualify for the newest screening option of primary HPV screening, clinics could explore the option of giving patients at-home testing kits. “We, as clinicians, must start thinking outside the box on how best to reach these women and ensure they are receiving these effective and potentially life-saving screening tests,” she says. Cervical cancer death rates have dropped dramatically in recent decades thanks to the development of the Pap test in the 1950s. That test involves collecting cells from a woman’s cervix and examining them under a microscope to look for precancerous and cancerous cells. A second type of cervical cancer screening — called the HPV test — detects the presence of high-risk HPV, which can lead to precancerous changes and cervical cancer. In 2012, national cervical cancer screening guidelines were updated to recommend Pap testing every three years for women ages 21 to 65 or Pap-HPV co-testing every five years for women ages 30 to 65. The study results show high rates of adoption by Olmsted County health providers of the 2012 guidelines in regards to appropriate use of co-testing and in appropriately not screening women under 21 or over 65. A limitation of this study is that Olmsted County is less ethnically and racially diverse than the U.S. population, but the county’s demographic makeup is reflective of the Upper Midwest. The study’s findings related to racial disparities in screening are consistent with several other studies from across the country. Another limitation is the potential for over counting young women as not screened who are insured by their parents and have an Olmsted County address but may have gone to healthcare providers outside of Olmsted County for screening. The research was supported by the Rochester Epidemiology Project, Mayo Clinic, the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, the National Institute on Aging and the National Institutes of Health. Co-authors of the study were Robert Jacobson, M.D., Carmen Radecki Breitkopf, Ph.D., Patrick Wilson, Debra Jacobson, Chun Fan, Jennifer St. Sauver, Ph.D., and Lila Rutten, Ph.D.