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Newswise — PITTSBURGH, Aug. 26, 2019 – New, more effective antibiotics are being prescribed in only about a quarter of infections by carbapenem-resistant Enterobacteriaceae (CRE), a family of the world’s most intractable drug-resistant bacteria, according to an analysis by infectious disease and pharmaceutical scientists at the University of Pittsburgh School of Medicine and published today by the journal Open Forum Infectious Diseases.  This sluggish uptake of such high-priority antibiotics prompted the researchers to call for an examination of clinical and pharmaceutical stewardship practices across U.S. hospitals, as well as behavioral and economic factors, to see if the trend can be reversed before lackluster sales lead the pharmaceutical industry to stop developing much-needed antibiotics.  “The infectious diseases community spent the past decade saying, ‘We need new antibiotics, this is a top priority,’ and now we’re at risk of sounding like the boy who cried wolf,” said lead author Cornelius J. Clancy, M.D., associate professor of medicine and director of the mycology program and XDR Pathogen Laboratory in Pitt’s Division of Infectious Diseases. “We have a responsibility to learn why it takes so long for antibiotics to be adopted into practice and figure out what we need to do to ensure the best antibiotics quickly reach the patients who desperately need them.”  The U.S. Centers for Disease Control and Prevention has classified CRE as urgent threat pathogens and calls them the “nightmare bacteria.” The World Health Organization and Infectious Disease Society of America have designated CRE as highest priority pathogens for development of new antibiotics. At the time of those declarations, polymyxins were the first-line antibiotics against CRE, even though they failed to work in about half the cases and carried a significant risk of damaging the kidneys.  Since 2015, five antibiotics against CRE have gained U.S. Food and Drug Administration (FDA) approval: ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, eravacycline and imipenem-relebactam. Studies, including those conducted at UPMC, have shown that the first three of these antibiotics are significantly more effective at fighting CRE and less toxic than polymyxins (eravacycline and imipenem-relebactam are still too new for conclusive data).  Clancy and his colleagues surveyed hospital-based pharmacists in the U.S. to gauge their knowledge of the new antibiotics and their willingness to use them. The drugs were classified as the “first-line” choice against CRE blood infections by 90% of the pharmacists, pneumonia by 87%, intra-abdominal infections by 83% and urinary tract infections by 56%.  “Clearly hospital-based pharmacists are aware of these antibiotics and believe they are the best choice for the vast majority of CRE infections,” said Clancy.  But when the team estimated the number of CRE infections nationwide and used national prescription data to calculate the proportions of old vs. new antibiotics used to treat those infections, they found that from February 2018 through January 2019, the new antibiotics were used only about 23% of the time. Their use likely started to exceed that of polymyxins only in December 2018, nearly four years after the first of the new antibiotics was approved by the FDA. Even after accounting for CRE infections in which new antibiotics might not be first-choice agents, the team found that use was only about 35% of what was expected based on positioning by hospital-based pharmacists.  Allergan and The Medicines Company, developers of two of the new antibiotics, have sought to exit the antimicrobial field since introducing their drugs because of insufficient returns on investment. Achaogen declared bankruptcy months after attaining FDA approval for a third new antibiotic.  The researchers suggest several reasons for the slow uptake of the new antibiotics, starting with cost. A 14-day course of the new antibiotics costs between $13,230 and $15,070, compared to $305 to $784 for the old drugs.  “Cost is a limitation, but I’m not convinced it is the sole cause of our findings,” said Clancy. “Clinicians may not be prescribing the new drugs due to concerns about accelerating antibiotic-resistance or because initial studies on their effectiveness were relatively small. We need to get at the root causes of the disconnect between what the doctors prescribe and what the pharmacists we surveyed believe they should be prescribing, and then find a solution.”  Additional authors on this study are M. Hong Nguyen, M.D., and Brian A. Potoski, Pharm.D., of Pitt; and Deanna Buehrle, Pharm.D., of the VA Pittsburgh Healthcare System.  There was no funding for this study. Clancy and Nguyen report unrelated research funded by various pharmaceutical and medical device companies, detailed in the study manuscript. 
Newswise — Researchers from Queen’s University Belfast have developed a test that may be able to detect ovarian cancer up to two years earlier than current approaches. The researchers discovered that the presence of four proteins together, known as a biomarker panel, indicates the likelihood of Epithelial Ovarian Cancer (EOC), a type of ovarian cancer. Using these biomarkers the researchers then developed a screening test that initial studies suggest may be able to detect ovarian cancer up to two years before current detection tests. The research was carried out in partnership with the University of New South Wales Australia, University of Milan, University of Manchester and University College London. The study, published in British Journal of Cancer as part of Nature Group publication, involved the analysis of blood samples from 80 individuals across a seven-year period. Dr Bobby Graham from the School of Biological Sciences at Queen’s University Belfast and lead author of the study explains: “Firstly, we discovered that the presence of the biomarker panel will enable us to detect EOC. We then developed a screening test to detect this biomarker panel, making this a relatively simple diagnostic test. “The algorithm designed will screen the blood sample and flag any abnormal levels of the proteins associated with the cancer. The screening test identifies ovarian cancer up to two years before the current tests allow.” Most ovarian cancers are epithelial ovarian cancers, which is a cancer that forms in the tissue covering the ovary. In females in the UK, ovarian cancer is the sixth most common cancer. In 2016, 4227 deaths were reported as a result of EOC. If diagnosed at stage one of EOC, there is a 90% chance of five-year survival compared to 22% if diagnosed at a stage three or four. Dr Graham added: “The results of this study are encouraging, however, we now want to focus on testing it in a wider sample set so that we can use the data to advocate for an ovarian cancer screening programme.” Dr Rachel Shaw, Research Information Manager at Cancer Research UK, said: “Around half of ovarian cancer cases are picked up at a late stage, when treatment is less likely to be successful. So developing simple tests like these that could help detect the disease sooner is essential. "At Cancer Research UK, we’re working hard to find new ways to detect cancer early and improve the tests already available. It’s really exciting to see these encouraging results for this type of ovarian cancer.” Athena, CEO of the Eve Appeal says, “We are extremely proud to have part funded the PROMISE programme, which brought together experts for a 7 year project to try and diagnose ovarian cancer at an earlier stage. “Sadly, so many women are diagnosed late, to devastating effect. We are hopeful the outcomes of this project will have a positive affect on women in the future.” The project was jointly funded by the Eve Appeal charity and Cancer Research UK.
Credit: Michigan Medicine A new study from the University of Michigan finds people who have mild cognitive impairment (MCI), which lies on the continuum of cognitive decline between normal cognition and dementia, are less likely to receive proven heart attack treatment in the hospital. Newswise — A new study finds people who have mild cognitive impairment (MCI), which lies on the continuum of cognitive decline between normal cognition and dementia, are less likely to receive proven heart attack treatment in the hospital. Researchers found no evidence that those with MCI would derive less benefit from evidence-based treatment that’s offered to their cognitively normal peers who have heart attacks, says lead author Deborah Levine, M.D., MPH. “Patients should get the treatments they would want if they were properly informed,” says Levine, an associate professor of internal medicine and neurology at Michigan Medicine, the academic medical center of the University of Michigan. Some people with thinking, memory and language problems have MCI. Unlike dementia, which severely interferes with daily functioning and worsens over time, MCI does not severely interfere with daily functioning and might not worsen over time. Although people with MCI have an increased risk of developing dementia, it’s not an inevitable next step, Levine says. “While some may progress to dementia, many will persist in having MCI, and a few will actually improve and revert to normal cognition,” says Levine, also a member of the University of Michigan Institute for Healthcare Policy and Innovation. “Many older adults with MCI live years with good quality of life, and so face common health risks of aging like heart attack and stroke. “Clinicians, patients and families might be overestimating the risk of dementia after a mild cognitive impairment diagnosis even without realizing it. These older adults with MCI should still receive evidence-based treatments when indicated.” The research, published in the Journal of General Internal Medicine, found pre-existing MCI was associated with significantly lower use of guideline-concordant care after a heart attack, whether catheter-based or open surgery. The study measured 609 adults ages 65 and older who were hospitalized for a heart attack between 2000 and 2011. Levine notes both cardiac catheterization (35% less likely in patients with pre-existing MCI) and coronary revascularization (45% less likely in patients with pre-existing MCI) have been shown to be highly effective at reducing deaths and improving physical functioning after heart attack in multiple large clinical trials. ‘A timely issue’ Physicians must weigh the competing risks of all health problems that increase with age, Levine says, including heart disease and cognitive decline. Many families are dealing with both concerns at once in their older loved ones. “This is a timely issue because as the population ages, the number of seniors 85 years old and older has become the fastest-growing segment of the U.S. population,” Levine says. “Seniors 85 and older are most likely to have MCI, and their incidence of heart attack has surged.” However, cardiovascular disease, including heart attack and stroke, is still the leading cause of death and serious morbidity in older adults, whether they have MCI or normal cognitive functioning. Up to 1 in 5 adults ages 65 and older has MCI, although many may be undiagnosed, Levine says. Since the Affordable Care Act mandated coverage of cognitive impairment assessments for Medicare beneficiaries, MCI diagnoses are expected to increase, she adds. The need to question decision-making Although much recent medical literature addresses overtreatment, Levine says this research shows undertreatment with high-value therapies can also be a problem. Her team’s ongoing research finds physicians might not be recommending invasive treatments as often after an older patient with some memory and thinking problems has a heart attack. She encourages clinicians to reflect on the influence of MCI in their decision-making. “It’s important for providers to consider whether they are recommending against treating a patient just because they have MCI,” Levine says. “Physicians can think about offering treatments to all patients when clinically indicated.” Invasive treatments may not be indicated in those with advanced dementia or a limited life expectancy, she says, but MCI does not fall in that category. This potential disconnect in provider recommendations provides an opportunity for patients and families to empower themselves by having conversations about the care they’d want if they become ill, she says. People with MCI can still participate in these types of discussions, and families don’t need to wait until an event happens to start the conversation. “In these discussions, patients and families often think about catastrophic illnesses where life support measures may be used, but heart attacks and stroke are much more common, and they’re treatable,” Levine says. “Because dementia is so feared among older adults and their families, it’s understandable and appropriate that it may weigh heavily on the decisions for all types of care, including heart attack care,” adds co-author Kenneth Langa, M.D., Ph.D., a professor of internal medicine at Michigan Medicine and a member of the Institute for Healthcare Policy and Innovation. “Our study emphasizes the importance of differentiating between MCI and dementia and of educating patients, families and clinicians on the relative risks of further cognitive decline versus common cardiovascular conditions for people with MCI.” An ongoing effort Levine and colleagues used data from the Health and Retirement Study, a nationally representative longitudinal study of older Americans that’s based at U-M. Heart attack, or acute myocardial infarction, was an appealing lens to research whether patients with MCI receive guideline-based treatment, Levine says. Heart attacks are acute, emergent medical problems that are common in seniors and have robust evidence of effective treatment, she adds. Levine’s team is also studying the effect of pre-existing MCI on treatment for acute ischemic stroke, and the reasons physician recommendations and patient preferences for effective treatment after stroke or heart attack might be different if the patient already has MCI. “Studies like this are an important first step in raising awareness on MCI so that providers, like cardiologists, can make sure they offer the best therapies available during heart attacks,” says senior author Brahmajee Nallamothu, M.D., MPH, an interventional cardiologist and professor of internal medicine at Michigan Medicine. Story from Michigan Health Lab
Newswise — ATLANTA – Today, the American College of Rheumatology (ACR), in partnership with the Spondylitis Association of America (SAA) and the Spondyloarthritis Research and Treatment Network (SPARTAN), released the 2019 Update of the Recommendations for the Treatment of Ankylosing Spondylitis (AS) and Nonradiographic Axial Spondyloarthritis (nr-axSpA). The guideline includes 86 recommendations that provide updated and new guidance for the management of patients with AS and nr-axSpA in the areas of pharmacologic and non-pharmacologic treatment options; AS-related comorbidities; and disease activity assessment, imaging, and screening. “SAA is proud to be a co-sponsor of these updated guidelines. SAA is committed to expanding treatment options and ensuring that both spondyloarthritis patients and the medical practitioners that are entrusted with their care have the best resources to aid in their decision-making,” said Cassie Shafer, chief executive officer of the SAA. Axial SpA, which is comprised of AS and nr-axSpA, is the main form of chronic inflammatory arthritis affecting the axial skeleton. This condition is characterized by back and hip pain, peripheral joint pain, and fatigue, all of which can vary in severity. According to the SAA, as much as 1 percent of the adult United States population may have axial SpA. This means that as many as 2.7 million adults may be affected by the disease. The ACR’s previous guideline, published in 2015, provided recommendations for pharmacological treatments, management of selected comorbidities, disease monitoring, and preventive care. The 2019 update builds on these recommendations by adding information on new medications, managing biologic and biosimilars usage in patients, and best practices for utilizing imaging (MRI and radiographs). “Based on the literature, we felt it was important to address topics such as sequencing biologics for patients with active AS despite NSAID usage, whether to taper or discontinue biologics in the setting of remission, and clearer guidelines on when to obtain images – particularly in instances when results would likely lead to a change in treatment,” said Michael Ward, MD, MPH, researcher at the National Institute of Arthritis and Musculoskeletal and Skin Diseases and principal investigator of the guideline. “We hope this new information will help get patients on an effective treatment faster and ultimately improve patients’ health status and quality of life.” To update the guideline, a team of experts conducted a systematic literature review for 20 clinical questions on pharmacological treatment addressed in the 2015 guidelines along with 26 new questions on pharmacological treatment, treat-to-target strategy, and the use of imaging. The results of this review were then discussed by a separate voting panel and crafted into recommendations that were labeled conditional or strong based on the evidence available. A few of the recommendations from the guideline include: A strong recommendation to treat adults with active AS despite treatment with NSAIDs with a TNFi (no preferred choice) over no treatment with a TNFi. A conditional recommendation to treat with a TNFi over treatment with secukinumab, ixekizumab or tofacitinib, and a conditional recommendation to treat with seukinumab or ixekizumab over tofacitinib. A strong recommendation to continue treatment with the originator biologic over mandated switching to its biosimilar for adults with stable AS. A conditional recommendation against obtaining repeat spine radiographs at a scheduled interval as a standard approach for adults with active or stable nr-axSpA on any treatment. “These guidelines update those from four years ago by consolidating the expert thought around the use of the newest therapeutic agents and modifying a number of recommendations from the 2015 guideline to reflect recent evidence. They provide patients and the medical community with clear recommendations for spondyloarthritis management using a rigorous approach, and SPARTAN is proud to endorse them,” said Dr. Liron Caplan, chair of SPARTAN. ACR guidelines are currently developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, which creates rigorous standards for judging the quality of the literature available and assigns strengths to the recommendations. Due to limited data in some areas, the quality of evidence was most often low, very low or occasionally moderate. This led to nearly all recommendations being conditional, with only a few strong recommendations in cases in which there was sufficient evidence. The updated and expanded recommendations, supporting PICO questions and evidence report are available on the ACR website.
New research shows link between high chili intake and dementia. Newswise — Think twice before adding that extra kick of chili sauce or chopped jalapeno to your meal. New research involving the University of South Australia shows a spicy diet could be linked to dementia.  A 15-year study of 4582 Chinese adults aged over 55 found evidence of faster cognitive decline in those who consistently ate more than 50 grams of chili a day. Memory decline was even more significant if the chili lovers were slim. The study, led by Dr Zumin Shi from Qatar University, showed that those who consumed in excess of 50 grams of chili a day had almost double the risk of memory decline and poor cognition.  “Chili consumption was found to be beneficial for body weight and blood pressure in our previous studies. However, in this study, we found adverse effects on cognition among older adults,” Dr Zumin says.  UniSA epidemiologist Dr Ming Li, one of five researchers involved in the study, says chili intake included both fresh and dried chili peppers but not sweet capsicum or black pepper.  “Chili is one of the most commonly used spices in the world and particularly popular in Asia compared to European countries,” Dr Li says. “In certain regions of China, such as Sichuan and Hunan, almost one in three adults consume spicy food every day.”  Capsaicin is the active component in chili which reportedly speeds up metabolism, fat loss and inhibits vascular disorders but this is the first longitudinal study to investigate the association between chili intake and cognitive function.  Those who ate a lot of chili had a lower income and body mass index (BMI) and were more physically active compared to non-consumers. Researchers say people of normal body weight may be more sensitive to chili intake than overweight people, hence the impact on memory and weight. Education levels may also play a role in cognitive decline and this link requires further research. 
Credit: Rong Li and Hung-Ji Tsai Aneuploid yeast cells on the left have difficulty drawing in fluorescent molecules. Whereas, the normal yeast cells on the right are able to rapidly draw them in. Newswise — In a study using yeast cells and data from cancer cell lines, Johns Hopkins University scientists report they have found a potential weak spot among cancer cells that have extra sets of chromosomes, the structures that carry genetic material. The vulnerability, they say, is rooted in a common feature among cancer cells — their high intracellular protein concentrations — that make them appear bloated and overstuffed, and which could be used as possible new targets for cancer treatments. “Scientists are now thinking more about targeting the biophysical properties of cancer cells to make them self-destruct,” says Rong Li, Ph.D., Bloomberg Distinguished Professor of Cell biology and Oncology at the Johns Hopkins University School of Medicine and of Chemical and Biomolecular Engineering at the Johns Hopkins Whiting School of Engineering. Further research is planned to confirm the findings in animal and human cancer cells, says Li. A report on the research, led by Li, is published in the June 6 issue of Nature. The new experiments focused on a chromosome number abnormality known as aneuploidy. Normal human cells, for example, have a balanced number of chromosomes: 46 in all, or 23 pairs of different chromosomes. A cell with chromosomes that have extra or fewer copies is called aneuploid. Li says, “aneuploidy is the #1 hallmark of cancer,” and is found in more than 90% of solid tumor cancer types. When cells gain chromosomes, Li says, they also get an extra set of genes that produce more than the normal amount of protein that a cell makes. This excess can give cells growth abilities they normally wouldn’t have, sometimes allowing them to overgrow and develop into a tumor. Because aneuploid cells have unbalanced protein production, they have too many free-floating proteins that are not organized into a complex. This increases the concentration inside of the cell compared to outside. To compensate for the increased concentration, the cells draw in water, a phenomenon that leads to hypo-osmotic stress. “Aneuploid cells tend to be bigger and more swollen than cells with a balanced number of chromosomes,” says Li. Li, who is a member of the Johns Hopkins Kimmel Cancer Center, says she and her team set out to see if there was a common Achilles’ heel among aneuploid cancer cells, one that would make a powerful strategic target for cancer treatment. For the study, which took nearly five years to complete, Li and her colleagues, including first author and Johns Hopkins postdoctoral fellow Hung-Ji Tsai, Ph.D., looked at yeast cells, which have 16 chromosomes. In stressful environments, such as those with cold temperatures or inadequate nutrients, yeast cells adapt by altering the number of chromosomes, which allows them to survive better due to changes in the relative amounts of various proteins. Li and Tsai looked at gene expression levels of thousands of aneuploid yeast cells compared with normal ones. Specifically, the scientists looked for gene expression changes that were shared among the aneuploid cells despite their differences in chromosome copy number. Among the aneuploid cells, the scientists found that gene expression was altered in about 4% of the genome compared with normal cells. Next, the scientists compared the aneuploidy-associated gene expression with information from a database at Stanford University that contains changes in gene expression among normal yeast cells exposed to different stressful environments. They found that both the aneuploid cells and normal cells under hypo-osmotic stress share certain gene expression characteristics. They also share the problem of being bloated, affecting their ability to internalize proteins located on the cell membrane that regulate nutrient uptake. Li’s team continued its work to see if it could exploit aneuploid cells’ vulnerability in properly controlling the intake of nutrients. They screened the yeast genome and found a molecular pathway involving two proteins called ART1 and Rsp5 that regulate the cells’ ability to draw in nutrients such as glucose and amino acids. When the scientists inactivated these proteins in the aneuploid yeast cells, they lacked the proper intracellular nutrient levels and were less able to grow. The human equivalent of the molecular pathway involves proteins called arrestins and Nedd4. “It’s possible that we could find a treatment that targets this or another pathway that exploits the vulnerability common to aneuploid cancer cells,” says Li. Funding for the research was provided by the National Institutes of Health (R35-GM118172, R01-HG006677, R01-GM114675 and U54-CA210173), the Prostate Cancer Foundation (16YOUN21) and the National Science Foundation. In addition to Tsai and Li, scientists who contributed to the research include Anjali Nelliat, Mohammad Choudhury, Andrei Kucharavy, Jisoo Kim, Devin Mair, Sean Sun, and Michael Schatz from Johns Hopkins and William Bradford and Malcolm Cook from the Stowers Institute for Medical Research.
Carrie Esopenko   Newswise — Data on every consenting Rutgers athlete who experiences a concussion is helping to inform a large-scale, nationwide study aimed at making sports safer for student-athletes. Rutgers is part of the Big Ten-Ivy League Traumatic Brain Injury (TBI) Research Collaboration, comprised of the nation’s most elite athletic and academic universities, and is participating in its Big Ten-Ivy League Epidemiology of Concussions study. Rutgers School of Health Professions researcher Carrie Esopenko, assistant professor in the Department of Rehabilitation and Movement Sciences and an expert on head trauma, enrolled the university in the groundbreaking study. “This provides an invaluable opportunity for ongoing collaboration between physicians, athletic trainers, researchers, and administrators to understand who’s at a higher risk of injury, and how we can reduce that risk,” Esopenko said. The multi-institutional effort broadens the sports concussion data registry to all documented concussions sustained by athletes in varsity sports at 18 participating Ivy League and Big Ten schools. At Rutgers, that has meant creating a form for every concussion sustained by a Division One athlete. “We want to know the mechanisms of how it occurred. Was it contact to a helmet? Was it an elbow to the head? Was it during practice, a scrimmage? What type of play was it? What position was the athlete playing? Was a foul called?” said Kyle Brostrand, Rutgers assistant athletic trainer and coordinator of concussion management and research. Within the TBI collaboration, Esopenko is the principal investigator for Rutgers, while Brostrand manages data collection. The partnership of research and sports medicine is what makes the TBI Collaboration unique in its approach to studying the effects of sports-related concussions and how to better prevent, detect and treat them, according to Martha Cooper, assistant director of the Big Ten Academic Alliance. Its work has literally been a game changer. When data from the Epidemiology of Concussions study showed that a disproportionately high number of concussions occurred on kickoffs, the Ivy League athletic conference implemented a change in rules on kickoffs and touchbacks. The change led to a 68 percent drop in concussion rates, according to findings released in October, and those findings sparked new NCAA kickoff rules. Now in its sixth year of data collection, the study has produced “a robust database yielding novel opportunities to better understand the epidemiology of concussion among university student-athletes participating in a variety of sports,” according to a report on methods and findings published in April in the American Journal of Sports Medicine. “These findings add to our understanding of SRC (sports-related concussions) and are the first of many that will be generated over the coming years.” This week Esopenko and Brostrand are taking part in a two-day annual Traumatic Brain Injury Summit in Rosemont, Illinois. Researchers, clinicians, and administrators from the 22 member universities are discussing their research and clinical practice as it relates to concussion. The annual summits provide a platform for Big Ten and Ivy League affiliates to present their work, identify best practices and develop research partnerships within and across the conferences that will ultimately lead to improved health and safety for student-athletes.  “Through this collaboration, we are at the forefront of understanding what increases risks of concussions and reducing the risks and prevalence of concussion,” said Esopenko.  “We have a duty to the student-athlete to make the sport safer,” adds Brostrand. "The more universities work together, the better for all of our athletes."
Newswise — PITTSBURGH – Death rates from sepsis fell faster in New York than expected—and faster than in peer states—following the introduction of the nation’s first state-mandated sepsis regulation, according to an analysis led by University of Pittsburgh researchers and published today in JAMA. The policy requires all New York hospitals to quickly implement certain protocols when the deadly condition is suspected.  The finding is good news for the nearly dozen other states in varying stages of adopting similar policies to reduce deaths from sepsis, the leading cause of death in hospitalized patients. Sepsis is a life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs.  “Rarely in the U.S. do we force hospitals to implement specific clinical protocols. Typically, quality improvement is achieved through financial incentives and public reporting,” said lead author Jeremy Kahn, M.D., M.S., professor in the Department of Critical Care Medicine at Pitt’s School of Medicine and the Department of Health Policy and Management at Pitt’s Graduate School of Public Health. “For the first time, state officials are enshrining in regulations that hospitals must follow certain evidence-based protocols when it comes to sepsis. And our study finds that, at least in New York, it seemed to work.”  Rory’s Regulations were issued by the New York State Department of Health in 2013 after 12-year-old Rory Staunton died of undiagnosed sepsis. The regulations require that hospitals in New York follow protocols for sepsis that include giving antibiotics within three hours and intravenous fluids within six hours of hospitalization. The hospitals also are required to regularly train staff in the protocols and to report adherence and clinical outcomes to the state.  Kahn and his team analyzed records of more than a million sepsis admissions in 509 hospitals in New York and four control states without a sepsis regulation: Florida, Maryland, Massachusetts and New Jersey. The team looked at dates from two years before Rory’s Regulations were adopted, and two years after.  In the years before the regulations went into place, 26.3% of the people diagnosed with sepsis in New York died while hospitalized, compared to a rate of 22% in the control states. Following the regulations, New York’s sepsis mortality rate dropped 4.3% to 22%, but the death rate only fell 2.9% to 19.1% in the control states.  After accounting for patient and hospital characteristics, as well as pre-existing sepsis trends in the states, New York’s sepsis death rate was 3.2% lower following the regulation than would have been expected, relative to the control states. This comparison was crucial to estimating the improvement and sets this study apart from prior work. Sepsis outcomes are known to improve over time—a study just looking in New York would not be able to differentiate the effects of the regulations from underlying trends. Because these improvements occurred more quickly in New York compared to other states, the researchers are more confident that the regulations are the source of the improvement.  “Sepsis is a tremendous global health burden, so developing proven ways to quickly recognize and treat people who have it is a top public health priority,” said senior author Derek Angus, M.D., M.P.H., professor and chair of Pitt’s Department of Critical Care Medicine and director of Pitt’s Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center. “While every state should consider their specific population and needs when developing regulations, our analysis reveals that policies enforcing evidence-based clinical protocols for the timely recognition and treatment of sepsis saves lives.”  Additional authors on this research are Billie S. Davis, Ph.D., Jonathan G. Yabes, Ph.D., Chung-Chou H. Chang, Ph.D., and Tina Batra Hershey, J.D., M.P.H., all of Pitt; David H. Chong, M.D., of the Columbia University Irving Medical Center; and Grant R. Martsolf, Ph.D., M.P.H., R.N., of Pitt and the RAND Corporation.  This research was funded by Agency for Healthcare Research and Quality grant R01HS025146.  To read this release online or share it, visit http://www.upmc.com/media/news/071619-kahn-ny-sepsis
Newswise — DURHAM, N.C. -- Efforts by the FDA and some cities to limit the availability and appeal of e-cigarettes to young users could drive some existing users to smoke more tobacco cigarettes to get their fix, according to new research from Duke Health. The findings, from a survey of 240 young U.S. adults who use both e-cigarettes and traditional tobacco cigarettes, are scheduled to be published July 15 in the journal Substance Use & Misuse.  “The FDA now has regulatory authority over all tobacco products, including e-cigarettes and we know that some communities have taken action to ban flavored e-cigarette products,” said Lauren Pacek, Ph.D., the study’s lead author and an assistant professor in psychiatry and behavioral sciences at Duke. “We wanted to take a first pass at seeing what users’ anticipated responses to new regulations might be,” Pacek said. “Our findings suggest that while some regulations, such as banning certain flavors to limit appeal to adolescents, might improve outcomes for those young users, the new regulations might have unintended consequences with other portions of the population.” The online survey asked participants aged 18 to 29 to predict their use of two products they already used -- e-cigarettes and traditional tobacco cigarettes -- in response to hypothetical regulations to limit e-cigarette flavors, limit the customizability of e-cigarettes or eliminate the nicotine in e-cigarettes. About 47 percent of respondents said if regulations eliminated the nicotine in e-cigarettes, they wouldn’t use e-cigs as much and would increase their use of traditional cigarettes. About 22 percent said if regulations limited the customizability of devices, such as features allowing users to adjust nicotine dose or vapor temperature, they would use e-cigs less and smoke more tobacco cigarettes. About 17 percent said if e-cigarettes were to be limited to tobacco and menthol flavors, they wouldn’t use e-cigs as much and they would smoke more tobacco cigarettes. According to other research on e-cigarette use, about a third of people who use e-cigarettes also use other tobacco products, Pacek said. For instance, some smokers might use an e-cigarette where tobacco smoking is not allowed, such as at work or a restaurant. The survey was small and not designed to predict the behavior of e-cigarette users across the U.S., Pacek said. However, the data suggest that when considering changes to e-cigarettes, such as limiting fruity flavors proven to appeal to youth, that regulators also consider the downstream effects of new regulations on other users. “It’s likely some potential new regulations on e-cigarettes will result in a net good for the whole population, such as limiting flavors that might entice young users, improving safety standards, or mandating that liquids come in child-proof containers,” Pacek said. “However, our findings suggest that there should also be thoughtful consideration to potential unintended consequences that could affect other subsets of users of e-cigarettes and other tobacco products.”  Pacek and other researchers at the Duke University Center for Addiction Science and Technology are continuing research on e-cigarette use, including an in-depth study tracking participants’ use of various tobacco products in response to potential regulations such as those posed by the online survey. In addition to Pacek, study authors include Olga Rass, Maggie M. Sweitzer, Jason A. Oliver, and F. Joseph McClernon. The research was supported by the National Institutes of Health (K01DA043413, K23DA039294 and K23DA042898). The authors did not disclose any potential conflicts of interest.
Newswise — NEW YORK/GENEVA, 15 July 2019 – 20 million children worldwide – more than 1 in 10 – missed out on lifesaving vaccines such as measles, diphtheria and tetanus in 2018, according to new data from WHO and UNICEF.Globally, since 2010, vaccination coverage with three doses of diphtheria, tetanus and pertussis (DTP3) and one dose of the measles vaccine has stalled at around 86 percent. While high, this is not sufficient. 95 percent coverage is needed – globally, across countries, and communities - to protect against outbreaks of vaccine-preventable diseases. “Vaccines are one of our most important tools for preventing outbreaks and keeping the world safe,” said Dr Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization. “While most children today are being vaccinated, far too many are left behind. Unacceptably, it’s often those who are most at risk– the poorest, the most marginalized, those touched by conflict or forced from their homes - who are persistently missed.” Most unvaccinated children live in the poorest countries, and are disproportionately in fragile or conflict-affected states. Almost half are in just 16 countries - Afghanistan, the Central African Republic, Chad, Democratic Republic of the Congo (DRC), Ethiopia, Haiti, Iraq, Mali, Niger, Nigeria, Pakistan, Somalia, South Sudan, Sudan, Syria and Yemen.If these children do get sick, they are at risk of the severest health consequences, and least likely to access lifesaving treatment and care. Measles outbreaks reveal entrenched gaps in coverage, often over many years. Stark disparities in vaccine access persist across and within countries of all income levels. This has resulted in devastating measles outbreaks in many parts of the world – including countries that have high overall vaccination rates.In 2018, almost 350,000 measles cases were reported globally, more than doubling from 2017.“Measles is a real time indicator of where we have more work to do to fight preventable diseases,” said Henrietta Fore, UNICEF’s Executive Director. “Because measles is so contagious, an outbreak points to communities that are missing out on vaccines due to access, costs or, in some places, complacency. We have to exhaust every effort to immunize every child.”  Ukraine leads a varied list of countries with the highest reported incidence rate of measles in 2018. While the country has now managed to vaccinate over 90 percent of its infants, coverage had been low for several years, leaving a large number of older children and adults at risk.Several other countries with high incidence and high coverage have significant groups of people who have missed the measles vaccine in the past. This shows how low coverage over time or discrete communities of unvaccinated people can spark deadly outbreaks. Human papillomavirus (HPV) vaccine coverage data available for the first timeFor the first time, there is also data on the coverage of human papillomavirus (HPV) vaccine, which protects girls against cervical cancer later in life. As of 2018, 90 countries – home to 1 in 3 girls worldwide - had introduced the HPV vaccine into their national programmes. Just 13 of these are lower-income countries. This leaves those most at risk of the devastating impacts of cervical cancer still least likely to have access to the vaccine.Together with partners like Gavi, the Vaccine Alliance, WHO and UNICEF are supporting countries to strengthen their immunization systems and outbreak response, including by vaccinating all children with routine immunization, conducting emergency campaigns, and training and equipping health workers as an essential part of quality primary healthcare.