Police Killings of Unarmed Black Americans Affect Mental Health of Black Community First Study to Show Mental Health “Spillover Effects” from Deaths of Unarmed Black Americans Newswise — PHILADELPHIA — Black Americans are nearly three times more likely to be killed by police than their white counterparts, with even larger disparities among those who are unarmed. The trend is also harming the mental health of the black community, according to new research published in The Lancet from the Perelman School of Medicine at the University of Pennsylvania and the Boston University School of Public Health. “These deaths don’t just have immediate consequences for the families and friends. There’s a true mental health spillover effect for those not directly involved,” said Atheendar S. Venkataramani, MD, PhD, an assistant professor of Medical Ethics and Health Policy in Penn’s Perelman School of Medicine, and co-lead author of the study. In a national survey of nearly 40,000 black Americans who were interviewed within three months following at least one death of a black American at the hands of police in their state, the team found that police killings of unarmed black Americans were associated with worse mental health among other black Americans in the United States general population. “Addressing this problem will require interventions to reduce the prevalence of police killings as well as programs that mitigate the adverse mental health effects in communities when these events occur,” said co-lead author Jacob Bor, ScD, SM, an assistant professor at the Boston University School of Public Health. “More broadly, the findings indicate that events widely perceived to reflect structural racism cause significant harm to the mental health of black Americans. Efforts to reduce health disparities should explicitly target structural racism.” Structural racism is described as policies, laws, practices, and other norms entrenched in institutions that can harm a certain racial group and perpetuate racial inequities. The researchers combined newly released data on police killings between 2013 and 2016 from the Mapping Police Violence Project database with data from the U.S. Behavioral Risk Factor Surveillance System (BRFSS) of over 103,000 black Americans. BRFSS is a nationally-representative, telephone-based, random-digit dial survey of adults ages 18 years and older. The primary exposure was the number of police killings of unarmed black Americans occurring in the three months prior to the person being surveyed. Exposure included word of mouth and news stories in print, radio, television, and/or social media. To measure mental health outcomes, the researchers asked respondents: “Now thinking about your mental health, which includes stress, depression, and problems with emotions, for how many days during the past 30 days was your mental health not good?” Researchers then compared the number of poor mental health days experienced by black Americans surveyed after a police killing of an unarmed person to that of black Americans residing in the same state surveyed before that event. Overall, the study suggests the police killings could contribute 1.7 additional poor mental health days per person ever year, or 55 million more poor mental health days every year among black Americans in the United States. To contextualize those numbers, the authors point to diabetes, which is responsible for an estimated 75 million poor mental health days among black Americans. “Our estimates therefore suggest that the population mental health burden from police killings among black Americans is nearly as large as the mental health burden associated with diabetes,” they wrote. The study shows, for the first time, that police killings of unarmed black Americans have a “meaningful, population-level impact” on the mental health of other black Americans. “The effects are likely even larger than what we estimated,” said Venkataramani, pointing to the fact that more high-profile cases of police killings that grabbed national media attention could have exerted mental health effects among black Americans living in other states, as well. Importantly, the researchers saw no spillover mental health effects among white respondents, nor among respondents of either race in response to police killings of unarmed whites or of armed black Americans. This striking specificity points to the importance of structural racism as a key mechanism underlying the study findings, and a driver of population health, more generally, the authors said: “[P]olice killings of unarmed black Americans are perceived by many as manifestations of structural racism and as implicit signals of the lower value placed on black lives by law enforcement and legal institutions – as well as by society at large.” Co-authors of the study include David R. Williams, PhD, of the Harvard T.H. Chan School of Public Health, and Alexander C. Tsai, of Massachusetts General Hospital. ### Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise. The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year. The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided more than $500 million to benefit our community.
The Veterans Admininistration system undertakes a remarkable amount of research that helps improve lives. Here's a rundown of some of the latest findings. Nursing home quality of care linked to cost (10/10/2018) Higher quality of nursing home care was linked to higher cost, in a study of 132 VA community living centers. Researchers looked at data from two years for all community living centers in the VA system. They measured quality of care by looking at rates of adverse health events (such as falls). Fewer adverse events were linked to higher predicted cost, suggesting that greater resources allocated to quality lead to better care. However, higher costs were not driven by higher nurse staffing levels. According to the researchers, more studies are needed to determine what precisely drives the relationship between quality and cost. (PLoS One, Sept. 19, 2018) Evidence lacking on outcomes of genetic testing for statin resistance (10/10/2018) Information is lacking on patient outcomes for statin-associated muscle symptoms (SAMS) after testing for the SLCO1B1 gene, according to a VA Boston Healthcare System literature review. SAMS refers to muscle pain and weakness sometimes caused by statin medication used to treat cardiovascular disease. Previous studies have shown that people with the SLCO1B1 gene are more likely to get SAMS. The researchers looked at 37 studies for evidence that testing for SLCO1B1 could lead to treatment changes and improved cholesterol levels in statin-intolerant patients. They found very few reports of patient outcomes after SLCO1B1 testing. More studies are needed to explore whether this type of genomic testing can lead to improvements in care, say the researchers. (Clinical Pharmacology and Therapeutics, Aug. 23, 2018) Study suggests adverse health impact on sexual minorities from religious freedom law (10/10/2018) A team including a VA researcher found that “unhealthy days” increased for Indiana residents identifying as sexual minorities after that state passed a religious freedom restoration act (RFRA). Statewide religious freedom restoration laws aim to protect the free exercise of religion by ensuring that any government interference must be for “compelling” interests, and must employ the “least restrictive means” possible. Some legal scholars have argued that RFRAs could potentially expose sexual minorities to more discrimination. And past research has shown that stigma and discrimination could worsen physical and mental health for sexual minority individuals. The researchers surveyed sexual-minority individuals in 21 states with RFRAs in 2015. They found the number of people reporting more than 14 “unhealthy days” per month increased quarterly in Indiana following the passing of an RFRA there. Unhealthy days did not increase for heterosexual people. This trend did not occur in other states. Indiana was the only state to pass and enact an RFRA in the time frame of the study. Other states already had RFRAs in place or had passed an RFRA but not put it into practice. Indiana also differed from other states in that its law applies to cases between private parties, not just those involving government. (American Journal of Orthopsychiatry, Sept. 24, 2018) Telehealth a viable way to improve antimicrobial stewardship (10/04/2018) A pilot telehealth program shows promise in improving infectious disease control at rural medical centers, according to a Louis Stokes Cleveland VA Medical Center study. Staff at two rural VA medical centers used videoconferencing to work with infectious disease physicians at other facilities. These videoconference antimicrobial stewardship teams (VASTs) held weekly meetings to discuss ways to combat antimicrobial resistance on a patient-by-patient basis. After a year of the program, one site accepted VAST recommendations in 73 percent of cases presented, and the other accepted 65 percent of the recommendations. Participants felt that the sessions improved their antimicrobial stewardship efforts and patient care. (Infection Control and Hospital Epidemiology, Sept. 6, 2018) Mental health disorders linked with more unintended pregnancy (10/04/2018) Women Veterans with mental health disorders are more likely to have experienced unintended pregnancy than those without, found a study by VA Pittsburgh Health Care System researchers and colleagues. They surveyed almost 3,000 women Veterans by phone. Sixty percent of women with at least one mental health disorder reported having an unintended pregnancy, while 51 percent of women without a mental health disorder said they had had an unintended pregnancy. Mental health disorders were linked to a greater number of unintended pregnancies. Multiple mental health disorders were also connected to a greater number of unintended pregnancies. More research is needed on how to improve reproductive health outcomes for women with mental health disorders, say the researchers. (Journal of General Internal Medicine, Sept. 5, 2018) Opioids not linked to better sleep for chronic pain patients (10/04/2018) Opioid use did not improve insomnia or fatigue for patients with chronic pain, in a Minneapolis VA Health Care System study. Insomnia is a common problem related to chronic pain. Researchers studied data on medication dosage and sleep disturbance for patients taking opioids or non-opioid medication for chronic pain. Over a year of treatment, neither group showed improvements in insomnia or fatigue despite improvements in pain severity. Medication dosage increased over the course of the trial. Patients with chronic pain commonly take extra opioid medication to sleep, but this increase did not lead to improved sleep. The results suggest that patients should be encouraged to used evidence-based behavioral sleep interventions to manage their insomnia, according to the researchers. (International Association for the Study of Pain, Sept. 13, 2018) Early nonadherence to diabetes drugs leads to more heart attacks and strokes (09/27/2018) Patients who did not adhere early on to their medication treatment for type 2 diabetes were more likely to have poor health outcomes, found a study by VA Mid South Health Care Network researchers and their colleagues. Researchers looked at data for more than 159,000 Veterans with type 2 diabetes over an 11-year period. They measured patients’ adherence to oral diabetes medication by how often patients filled prescriptions in the first year of treatment. Patients who did not take their medication as prescribed were 14 percent more likely to have a heart attack in the five years after starting treatment, compared with those who took their medication. Those not regularly taking their medication were 22 percent more likely to have a stroke. The less compliant patients were to their medication regimen, the higher their chances were of having a heart attack or stroke. Those not adhering to treatment were also more likely to have died. The results underscore the need to help patients understand the importance of taking their oral antidiabetes medication regularly, say the researchers. (Diabetes Medicine, July 6, 2018) Blood test could predict effectiveness of NSAID treatment in Alzheimer’s patients (09/27/2018) Blood tests could identify which Alzheimer’s disease patients will respond to non-steroid anti-inflammatory drug (NSAID) therapy, according to a study including a VA San Diego Healthcare System study. Previous research has shown the potential of NSAIDs to improve outcomes in Alzheimer’s patients because the disease has been linked to inflammation. An earlier study treated Alzheimer’s patients with two NSAIDs, rofecoxib and naproxen. In it, some patients improved and some declined in both groups as well as in controls. For the new study, researchers tested blood samples from these patients for four specific proteins that have been identified as inflammation biomarkers. They found that they could identify which patients in the rofecoxib group had cognitive improvements with 98 percent accuracy. They also predicted improvements in the naproxen group with 97 percent accuracy. The results show that a precision-medicine approach could identify which treatments will be most effective for specific patients with Alzheimer’s, according to the researchers. (Journal of Alzheimer’s Disease, Sept. 4, 2018) Benzodiazepine prescribing higher than evidence warrants in older adults (09/27/2018) Prescribing of benzodiazepines may be higher than appropriate in older adults, according to a study that included several VA researchers. The team looked at use of the drugs across various health systems, not just in VA. Benzodiazepines are sedative drugs commonly prescribed for conditions such as insomnia, anxiety disorders, and behavioral and psychological symptoms of dementia. However, evidence suggest that these drugs could be dangerous for elderly patients. The researchers looked at 31 studies on the effects of benzodiazepines in patients over age 50 with the above three conditions. They found 21 studies that demonstrated improved insomnia outcomes. Only one study showed a benefit of the drugs for patients with anxiety disorder. They also found only a single study that showed improvements in behavioral disturbances in patients with dementia. The results suggest that benzodiazepine prescribing in older adults is higher than what is supported by evidence, according to the researchers. Studies are needed on how to reduce use of this type of drug in older patients, they say. (Harvard Review of Psychiatry, Sept/Oct 2018) Brain peptide implicated in migraine pain VA and University of Iowa researchers may have identified one of the sources of migraine pain. Researchers injected mice with calcitonin gene-relate peptide (CGRP), a substance naturally found in the brain that is believed to be related to nerve hypersensitivity and photosensitivity in migraine. They found that CGRP caused spontaneous pain in the mice, regardless of whether they were in light or darkness. When the researchers gave the mice an antibody that blocks CGRP receptors, the pain went away. They also found that the nonsteroidal anti-inflammatory drug meloxicam did not block the effects of CGRP. The antimigraine drug sumatriptan partially blocked CGRP response in male mice, but not females. (Pain, Sept. 1, 2018) Suicide risk common in patients with anxiety (09/20/2018) A high number of patients with anxiety could be at risk for suicide, found a Syracuse VA Medical Center study. Researchers surveyed 182 primary care patients who had anxiety symptoms but were not in psychotherapy specialty care. Forty percent had elevated suicide risk, based on a standard assessment. Suicide risk was more common in patients who also had depression (51 percent) than in those who had anxiety alone (27 percent). The severity of anxiety symptoms did not affect patients’ suicide risk. The results suggest that primary care providers should assess suicide risk in patients with anxiety, even when patients are not seeking mental health treatment or when their anxiety symptoms do not rise to the level of an anxiety disorder, say the researchers. (Family Practice, Sept. 14, 2018) Oxytocin fails to boost social cognition in schizophrenia trial (09/20/2018) Oxytocin did not improve social cognition in patients with schizophrenia, in a study by VA San Diego Healthcare System researchers and their colleagues. Social cognition refers to how a person deals with other people, including aspects like social knowledge and emotional processing. People with schizophrenia often have impaired social cognition. The researchers prescribed schizophrenic patients oxytocin—a drug that has been shown to improve social cognition in the general population—over 24 weeks, along with cognitive-behavioral training. Patients taking oxytocin showed no improvements in social cognition over the course of the study, compared with patients taking placebo. The results add to growing literature suggesting that oxytocin may not be effective in this population. (Psychological Medicine, Sept. 6, 2018) Herbicide-related COPD rates differ between self-report and lung tests Herbicide exposure during the Vietnam War was linked to self-reported chronic obstructive pulmonary disease (COPD), but the link was not supported by lung tests, in a study by VA's Office of Patient Care Services. Researchers surveyed more than 3,000 Veterans of the U.S. Army Chemical Corps who served in Vietnam. Those who had actively sprayed herbicides during their service were nearly twice as likely to say they had been told by a doctor that they had COPD, compared with non-sprayers. However, when the survey respondents were examined with spirometry—a common test of lung function—people in the spraying group were not more likely to have COPD than the non-spraying group. The difference may be due to physicians diagnosing COPD based on symptoms rather than spirometry, according to the researchers. Spirometry is underutilized by physicians, they say. (American Journal of Industrial Medicine, Aug. 29, 2018) PTSD may disrupt parasympathetic nervous system during sleep (09/14/2018) Patients with PTSD had blunted parasympathetic nervous system modulation during sleep, found a Durham VA Health Care System study. The parasympathetic nervous system is the part of the nervous system that regulates rest and digestion. Heart-rate variability can be used to assess how well the parasympathetic system is working. Researchers studied the sleep of 62 post-9/11 Veterans and service members. They found that, for those with PTSD, high-frequency heart rate variability was lower during the non-rapid eye movement sleep phase, compared with those without PTSD. Impaired parasympathetic nervous system function increases the risk of cardiovascular events. This parasympathetic modulation could be one reason for the increased rates of cardiovascular disease among Veterans with PTSD, suggest the researchers. Patients with PTSD had blunted parasympathetic nervous system modulation during sleep, found a Durham VA Health Care System study. The parasympathetic nervous system is the part of the nervous system that regulates rest and digestion. Heart-rate variability can be used to assess how well the parasympathetic system is working. Researchers studied the sleep of 62 post-9/11 Veterans and service members. They found that, for those with PTSD, high-frequency heart rate variability was lower during the non-rapid eye movement sleep phase, compared with those without PTSD. Impaired parasympathetic nervous system function increases the risk of cardiovascular events. This parasympathetic modulation could be one reason for the increased rates of cardiovascular disease among Veterans with PTSD, suggest the researchers. (Sleep, Aug. 29, 2018) Development of a new non-addictive pain drug (09/14/2018) A team including a researcher from the W.G. Hefner VA Medical Center in Salisbury, North Carolina, is working on a pain medication that could potentially work as well as opioids without being addictive. They developed a new compound, AT-121, that works on the mu opioid receptor, a type of neuron that opioids interact with to block pain. AT-121 also activates the nociceptin receptor, which blocks the addictive side effects of opioids. Using non-human primates, the researchers showed that AT-121 gave the same level of pain relief as opioids without the risk of addiction that comes with opioids. The results suggest that this new drug could have potential to both safely and effectively relieve pain, and also treat prescription opioid abuse. More studies will be needed before AT-121 can be tested in humans. (Science Translational Medicine, Aug. 29, 2018) Circadian rhythm disruption linked to cognitive decline in older men (09/14/2018) Disruptions in circadian rhythm are linked to greater cognitive decline in older men, according to a study including a Minneapolis VA Health Care System researcher. Circadian rhythm refers to the body's natural sleeping and waking patterns. Over multiple follow-up visits during an average period of three years, the researchers found that men with disrupted rest-activity circadian rhythm had greater cognitive decline, as measured by a standard cognition test, compared with those without disrupted circadian rhythms. Rest-activity circadian rhythm was measured using an accelerometer that recorded any time a patient's wrist moved. Aging is often associated with altered rest-activity circadian rhythm. The results add to growing evidence that age-related disruptions to sleep pattern are connected to cognitive decline, say the researchers. (Journal of the American Geriatric Society, Aug. 23, 2018) Complex relationship between alcohol consumption and psychiatric distress (09/06/2018) Hazardous drinking was linked to higher likelihood of psychiatric symptoms, while results of moderate drinking were mixed, in a study by Durham VA Health Care System researchers and colleagues. Previous studies have linked heavy drinking with increased depression and anxiety, but the it is not clear what cause-and-effect relationships, if any, may exist. The researchers collected data on alcohol use and psychiatric conditions for 3,003 Veterans. They found that hazardous drinkers were more likely to have PTSD, depression, and suicidality, compared with moderate drinkers. For men, moderate drinkers were less likely than nondrinkers to have depression and suicidality. However, this relationship disappeared when nondrinkers with past alcohol use disorder were removed from the calculations. Women moderate drinkers had lower rates of PTSD than nondrinkers and light drinkers, even when those with past AUD were removed. More research is needed on the possible protective effects of moderate drinking, say the researchers. Also, patients with a history of AUD may benefit from mental health screening and treatment, they say. (Journal of Studies on Alcohol and Drugs, July 2018) Written exposure therapy effective as PTSD treatment Written exposure therapy (WET) could be as effective as cognitive processing therapy in treating PTSD, according to a VA Boston Healthcare System study. WET involves five weekly sessions in which patients write for 30 minutes in detail about a single traumatic event associated with their PTSD. Cognitive processing therapy (CPT), a common PTSD treatment, involves learning how to evaluate and change upsetting thoughts. WET is shorter than CPT, which usually lasts for 12 sessions and includes homework between each session. Patients in both a WET and CPT group showed similar improvement of PTSD symptoms when assessed 60 weeks later. Both treatments significantly reduced depressive symptoms, although the CPT group did have a more rapid decrease in symptoms. WET takes a similar approach to prolonged exposure therapy, another common psychological PTSD treatment, in that both focus on directly confronting memories of trauma. Prolonged exposure is usually based on talking with a therapist, and generally involves more sessions than WET. The results show that WET could be a short and long-lasting treatment for PTSD. (Depression and Anxiety, Aug. 24, 2018) Study shows two genes may be linked to suicide attempts (09/06/2018) Durham VA Medical Center researchers have identified two genes that may be related to suicidal behavior. They conducted a genome-wide association study, in which they compared the genomes of a large number of Veterans to look for variations common among those with history of suicidal behavior. The researchers found an association between a gene called KCNMB2 and suicide attempts. This gene plays a key role in neuronal excitability. They also found evidence that may link another gene, ABI3BP, to both suicide attempts and suicidal thoughts. While the results are interesting, the researchers caution that they are preliminary and need replication in further studies. (Psychiatry Research, July 17, 2018) Group treatment program curbs intimate partner violence (08/29/2018) The Strength at Home program can successfully reduce intimate partner violence use, found a study by Central Texas and Boston VA health care system researchers. SAH is a 12-week cognitive-behavioral and trauma-informed group treatment designed to reduce and end IPV use among military and Veteran populations. The pilot program is part of a national program within VA to help Veterans who use or experience IPV. It was implemented at 10 VA medical centers over a year. Seventy percent of sites successfully launched the program in the first year. Results from 51 Veterans who participated in the program showed a significant reduction in the number who exhibited violence toward a partner. The participants also showed reduced PTSD symptoms. While the pilot program showed overall successful implementation, more work is needed to reduce the time between initial training and the start of group treatment, according to the researchers. (BMC Health Services Research, July 24, 2018) Repeated ketamine infusions may ease PTSD and depression (08/29/2018) Repeated ketamine infusions may improve PTSD and depression symptoms, according to a Minneapolis VA Health Care System study. Researchers gave 15 people with both PTSD and major depressive disorder six intravenous infusions of ketamine—a medication used mainly for anesthesia—over two weeks. Eighty percent had remission of PTSD symptoms immediately after treatment. The remission lasted a median of 41 days. For major depressive disorder, 93 percent experienced remission of symptoms, which lasted a median of 20 days. The results suggest that repeated ketamine treatments are safe and may be an effective treatment for people with both PTSD and major depressive disorder, say the researchers. (Journal of Clinical Psychiatry, May/June 2018)
In rare occurrences, forceful manipulation of the neck is linked to a damaging side effect: vision problems and bleeding inside the eye. For those in the habit of getting their neck adjusted by a chiropractor, the University of Michigan Kellogg Eye Center has an interesting case to know about: High velocity neck manipulation has been shown to result in stress on the eye and lead to spotty vision. The risk is rare, but one that Yannis Paulus, M.D., a retina specialist at Kellogg, reports on in the American Journal of Ophthalmology Case Reports. The energetic thrusts and rotations sometimes performed in high-velocity neck manipulation have been linked to damage to the blood vessels in the retina. Resulting abnormal bleeding inside the eye may also cause vision loss. This was the case for a 59-year-old woman who experienced a “tadpole” shaped spot in her vision while driving home from a chiropractor visit — with her sight worsening the next day. She had just received cervical spine manipulation using the high-velocity technique to help with her headaches. The woman’s vision returned to normal in about two weeks without treatment. She was referred to Kellogg Eye Center by her optometrist who co-authored the case report. Because the cells of the retina are so sensitive, even small injuries to the blood vessels can translate to vision problems. That’s why Paulus encourages patients to report their alternative medicine pursuits — and for physicians to actively listen and inform them of possible related side effects. Risks from chiropractic treatment Cardiovascular experts have been outspoken about health risks of chiropractic treatment. High-velocity neck manipulation has been associated with a certain type of stroke, or vertebral artery dissection, which led the American Heart Association to issue a warning statement in 2014. The short, rapid movements of neck manipulation may cause a small tear in the artery walls in the neck. The artery wall injury can result in a stroke if a blood clot forms at the site and later breaks free to block a blood vessel in the brain. Eye problems can follow, including double vision or central retinal artery occlusion, a blockage of the artery carrying oxygen to the nerve cells in the retina at the back of the eye. But the case at Kellogg suggests a new complication: direct damage to structures in the eye due to the force of neck adjustments. It’s the first case report of chiropractic care leading to multiple preretinal hemorrhages, authors say. Other possible complications are disrupting the vitreous humor — the clear, gel-like substance that fills the eye between the lens and the retina. The high-velocity technique may have induced a posterior vitreous detachment, or PVD, which occurs when the vitreous humor pulls away from the retina. No specific treatment is needed for PVD. Most patients no longer notice flashes in their vision after three months and “floaters” tend to improve, according to the American Society of Retina Specialists. Complications from PVD are rare but can be serious and in some cases require urgent treatment such as laser treatment to seal the retinal tear or surgery for a retinal detachment. Although the connection to chiropractic care is considered a temporal association, the timing of the patient’s eye symptoms following the chiropractic visit is hard to ignore. Paulus didn’t rule out future chiropractic visits for the patient but notes that “her chiropractor may need to modify techniques used during her visits.”
Newswise — In a proof-of-principle study, researchers at Johns Hopkins report that a certain liver immune cell called a macrophage contains only defective or inert HIV-1 copies, and aren’t likely to restart infection on their own in HIV-1-infected people on long-term antiretroviral therapy (ART). The study, the investigators say, strongly suggest that defective or inert HIV-1 can remain in the liver macrophages for up to ten years without functioning as an HIV-1 “reservoir” that can replicate the virus at high levels. A report of the findings was published online on Sept. 10 and in the Oct. issue of the Journal of Clinical Investigation. “Our study was the first, to our knowledge, in which purified liver tissue macrophages from HIV-1 infected people taking ART directly tested the idea that tissue macrophages are a long-lived active HIV-1 reservoir,” says Ashwin Balagopal, M.D., an associate professor in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine. According to the U.S. Centers for Disease Control and Prevention (CDC), 36.7 million people worldwide and 1.1 million people in the U.S. are infected with HIV-1. Commonly, ART is successfully used to suppress the replication of HIV-1 and stop or control the progression of acquired immunodeficiency syndrome (AIDS) in humans. The virus infects the body’s immune system cells, commonly forming a persistent, and reservoir in humans in so-called resting memory CD4+ T white blood cells. Macrophages work with T cells normally to envelop and clear tissues of microbes and debris. The inability to completely wipe out pools of infectious HIV-1 has for decades frustrated efforts to completely cure the infection. And it means that the interruption or discontinuation of ART at any time re-activates HIV-1 replication, spreading the virus to new cells. As a result, Balagopal says, investigators are increasingly focused more specifically on the location and biology of these HIV-1 reservoirs. To determine if liver macrophages were a true source of infection-capable HIV-1 reservoirs after ART, liver tissue samples were taken from nine HIV-1 infected persons, seven of whom underwent liver transplantation at the Johns Hopkins Hospital and would have otherwise had their livers discarded. Eight of the nine persons were on ART for periods ranging from eight to 140 months. The sample group included only adults whose demographic information is considered exempt from human subject research because all samples were obtained strictly for scientific reasons or postmortem, and would otherwise have been discarded. The Johns Hopkins School of Medicine institutional review approved this study protocol. Using lab techniques that both measure HIV-1 containing T cells and separate out the liver macrophages, the researchers found HIV-1 to be present in the macrophages even after exposure to longstanding virus-suppressing ART. However, Balagopal said that when his team tried to simulate virus “rebound” from the liver macrophages in the laboratory, they found only “fragments of HIV-1 in small quantities, without robust growth of full-length, infectious virus.” The researchers found that HIV-1 was in the liver macrophages of one subject who took ART for 11.7 years. They concluded that while liver macrophages might harbor HIV-1 for a long time, it’s unlikely these viruses could continue an infection on their own, unlikely to function as a reservoir, because the viruses were not able to replicate. Balagopal cautioned that their study results still affirm the need to address liver macrophage infection, because even if inert, these cells may be able to produce portions of viral proteins that can misdirect the immune system. “These results contribute an important piece in our efforts to understand the role of non-T cells, such as macrophages, as HIV-1 cellular reservoirs in individuals on long-term ART, but also may help the research community focus on additional cure strategies," Abraham Kandathil, Ph.D., a research associate in the Division of Infectious Diseases at Johns Hopkins University School of Medicine who performed all of the key experiments. In the future, Kandathil says, more research is needed to determine if the inert HIV-1 infected liver macrophages have any functional significance in people taking ART because expression of defective HIV-1 proteins can confuse the immune system and cause tissue inflammation. “To find a comprehensive HIV-1 cure, it’s important to identify all of the relevant HIV-1 reservoirs in the body, since it’s possible that the virus hides in the DNA of numerous cell types and each may require different strategies to get a cure,” says Balagopal. Balagopal noted that their study was limited by the small number of liver macrophages and human samples studied, as well as the small number of CD4+ T cells in the liver cell cultures that may have prevented the researchers’ ability to detect them. Other authors on this paper include Sho Sugawara, Christine M. Durand, Jeffrey Quinn, Jaiprasath Sachithanandham, Andrew M. Cameron, and Justin R. Bailey of the Johns Hopkins University School of Medicine along with Ashish Goyal and Alan S. Perelson from Los Alamos National Laboratory. This research is supported by grants from the National Institute of Allergy and Infectious Diseases (K08 AI 081544, R56 AI 118445, R01 AI024333, R01 AI116868, and P01 AI131365), the National Institute on Drug Abuse (R01 DA 016078), the National Institutes of Health Office of the Director (R01 OD 011095 and 108707-54-RKRL ) and amfAR, the Foundation for AIDS Research (108814-55-RGRL). The authors have declared that no conflict of interest exists.
More than 1 in 10 people aged 50-64 have had genetic tests ordered by a doctor or ordered directly. Many more want to – but also worry about worrying Newswise — ANN ARBOR, MI – Only a small percentage of people in their 50s and early 60s have had their DNA tested – either for medical reasons, to learn their ancestry or out of curiosity – but far more have an interest in getting such tests done, according to a new poll. One in 10 have taken genetic tests offered directly to consumers, and one in 20 have taken genetic tests ordered by a doctor, according to new findings from the National Poll on Healthy Aging. More than half expressed interest in getting DNA tests to guide medical care, understand health risks or know their ancestry. Still, the poll finds, that desire to know more about their risk of disease or heritage comes with a grain of salt. Two thirds of those polled said they thought genetic testing could lead them to worry too much about their future health. The poll of 993 adults between the ages of 50 and 64 was conducted by the University of Michigan Institute for Healthcare Policy and Innovation, and sponsored by AARP and Michigan Medicine, U-M’s academic medical center. It comes at a time when the U.S. Food and Drug Administration has approved several disease-specific tests to be marketed directly to the public, instead of requiring a physician to order them. The poll also asked respondents their interest in testing to learn their genetic risk for three later-life disorders: Alzheimer’s disease, Parkinson’s disease or macular degeneration. Around two-thirds had at least some interest in each test. Scott Roberts, Ph.D., a professor from the U-M School of Public Health who has studied use of genetic testing, including direct-to-consumer testing, worked on the poll’s design and analysis. He notes that even those who get direct-to-consumer genetic tests mainly to learn about their ancestral heritage could end up being “blindsided” by findings showing that they have a high risk of diseases such as Alzheimer’s. “Compared to previous findings in the general adult population, this age group appears to be a little more lukewarm about their views of the benefits versus the risks of genetic testing overall,” he says. “The majority said they might be interested in knowing their risk for specific conditions, but on other hand they were worried about potential psychological distress from the results.” Roberts points out that the accuracy of any genetic test is not 100 percent. He also notes that testing ordered by physicians often comes with a chance to meet with a genetic counselor – a specially trained clinician who can help patients decide whether to get tested, prepare them for handling the results, and help them understand what the results do and don’t mean. By contrast, direct-to-consumer testing often comes with none of these services, and individuals who buy DNA tests directly may encounter difficulty in interpreting them, or getting access to a genetic counselor after they receive their results. Genetic counselors are already in high demand for clinical cases, and their appointment times are prioritized for those who have a clinical reason for DNA testing, including family history of a serious genetic illness. “Patients may not think about the downstream effects of direct-to-consumer genetic testing. An unexpected positive result may lead to several additional tests that may or may not be covered by insurance,” says Preeti Malani, M.D., director of the poll and a professor of internal medicine at the U-M Medical School who has special training in geriatric medicine. Experience with testing The five percent of the poll respondents who had already had a genetic test ordered by their physician said it was done either because the physician suggested it or because they had wanted to find out more about their risk of disease or how best to manage a current condition. Ten percent had had a direct-to-consumer test. More than 70 percent of them said they were interested in learning more about their ancestry, and just under half said they were just curious about their genetic make-up. Just over one in 10 said they got tested to find out more about their health in general, or their risk of a particular disease. Combining the two types of genetic testing, 14 percent had had either kind. “We’re living in an era when advances like DNA testing are providing an amazing amount of useful health information,” says Alison Bryant, Ph.D., senior vice president of research for AARP. “As genetic testing becomes even more sophisticated and common among older adults, the challenge will be to ensure that people understand the benefits and limitations of these tests.” Future of genetic testing Roberts, who specializes in genetic testing for Alzheimer’s disease, notes that 70 percent of poll respondents had an interest in learning their Alzheimer’s risk. Newer clinical trials of drugs that aim to prevent, delay or slow progression of memory loss and other cognitive problems are actually looking to enroll people who have a higher-than-usual genetic risk of Alzheimer’s. So those who elect to buy such a test, or whose doctors order one for them because of family history, may now have an action they can take based on their results. “Before, there wasn’t much we could recommend, but now there are more research opportunities to take part in, and we know more about health behaviors earlier in life that can affect the risk of Alzheimer’s and other forms of dementia later in life,” he says. Poll respondents seemed to understand how genetic testing provides a potential window into the future, both for their own health risks (90 percent agreed with this idea) or for those of their children and grandchildren (86 percent). But 41 percent said that a genetic test wasn’t necessary if they already know what disease risks run in their family. The poll results are based on answers from a nationally representative sample of 993 people ages 50 to 64. The poll respondents answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have it. A full report of the findings and methodology is available at www.healthyagingpoll.org, along with past National Poll on Healthy Aging reports.
Highlights The blood pressure–lowering medication ramipril reduced protein excretion—or proteinuria—in children with chronic kidney disease. Greater reductions in proteinuria during the first months of treatment were linked with a lower risk of kidney disease progression. Newswise — Washington, DC (June 21, 2018) — In a study of children with chronic kidney disease (CKD), blood pressure medications reduced protein excretion in the urine, which was linked with a lower risk of disease progression. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), provide valuable information for monitoring and treating pediatric patients with CKD. The excretion of protein in the urine, or proteinuria, indicates an increased risk for kidney and heart problems, and it is known in adult patients that this risk can be lowered with medications called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Both types of drugs cause blood vessel relaxation and a decrease in blood pressure. It has not been clear, however, whether these medications benefit children with proteinuria. To investigate, Sophie van den Belt, MD, PhD (University Medical Center Groningen, in The Netherlands) and her colleagues analyzed data from the Effect of Strict Blood Pressure Control and ACE inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. This trial investigated whether intensified blood pressure control can delay the progression of chronic kidney disease (CKD) in children with the condition. In total, 280 children with CKD stage 2–4 received a fixed dose of the ACE inhibitor ramipril and were subsequently randomized to conventional or intensified blood pressure control with antihypertensive medications. The average initial proteinuria lowering was 40.2% in the conventional blood pressure control group and 46.7% in the intensified blood pressure control group. Due to the similar initial proteinuria change in the 2 study arms, the groups were combined for further analysis. The investigators found that ramipril therapy lowered proteinuria by an average of 43.5%. Also, a higher degree of proteinuria lowering during the first months of treatment was linked with a lower risk of CKD progression. “The results indicate that a higher initial proteinuria reduction with ACE inhibition is independently associated with long-term preservation of renal function in children with CKD. This finding suggests that proteinuria lowering is an important target in the management of pediatric CKD,” said Dr. van den Belt. Study co-authors include Hiddo Lambers Heerspink, PharmD, PhD, Valentina Gracchi, MD, PhD, Dick de Zeeuw, MD, PhD, Elke Wühl, MD, PhD, and Franz Schaefer, MD, PhD, for the ESCAPE trial group. Disclosures: The ESCAPE study was supported by grants of the Boehringer Ingelheim Stiftung, the European Commission (5th Framework Programme QLRT-2001-00908, the Kuratorium für Dialyse und Nierentransplantation e.V., Neu-Isenburg, and the Baxter Extramural Grant Program. The study protocol was developed exclusively by the participants. Onsite monitoring of study data collection was performed by an independent clinical research organization (Omnicare Clinical Research). Aventis Pharmaceuticals supplied ramipril and financed the GCP audit. Dr. Schaefer reports serving as a paid advisor for Abbvie, Astellas, and Bayer. No other potential conflicts of interest relevant to this article were reported. The article, entitled “Early proteinuria lowering by ACE inhibition predicts renal survival in children with chronic kidney disease,” will appear online at http://jasn.asnjournals.org/ on June 21, 2018, doi: 10.2215/ASN.2018010036. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 18,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.
MEDICAID EXPANSION HAS HELPED LOW-INCOME KIDNEY FAILURE PATIENTS GET ON THE TRANSPLANT WAITLIST BEFORE STARTING DIALYSIS
Highlights In states that expanded Medicaid under the Affordable Care Act to cover more low-income individuals, there was an increase in the number of Medicaid beneficiaries who were preemptively waitlisted to receive a kidney transplant. Medicaid expansion was associated with greater gains racial and ethnic minorities in being listed pre-emptively on the transplant waitlist compared with whites. Newswise — Washington, DC (June 21, 2018) — New research indicates that Medicaid expansion under the Affordable Care Act has helped to place many low-income individuals with chronic kidney disease (CKD) on the kidney transplant waiting list before starting dialysis. In addition, after expansion, there were larger gains in pre-emptive listing for minorities with Medicaid coverage than for whites. The findings appear in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN). Kidney transplantation is considered more cost-effective than dialysis, and preemptive wait-listing—or placing patients on the kidney transplant waiting list before they require dialysis—can help minimize the time that patients will eventually need to spend on dialysis before receiving a kidney transplant. Access to the kidney transplant waiting list is generally contingent on having health insurance coverage, however. Medicare provides a health insurance safety net once individuals develop kidney failure and require dialysis, but prior to Medicaid expansion under the Affordable Care Act, no similar safety net existed for low income individuals with advanced CKD who were not yet on dialysis. Studies are needed to determine whether Medicaid expansion under the Affordable Care Act has provided opportunities for low-income individuals with CKD to get the care they need. To investigate, Meera Nair Harhay, MD, MSCE, FASN (Drexel University College of Medicine) and her colleagues examined information from the United Network of Organ Sharing database on adults listed for kidney transplantation before dialysis dependence in 2011–2013 (pre–Medicaid expansion) and 2014–2016 (post–Medicaid expansion). “We explored whether Medicaid expansion, in offering an option for health insurance coverage for low-income individuals in the United States, would be associated with an increase in the number of Medicaid beneficiaries on the kidney transplant waiting list,” said Dr. Harhay. The team found that after states expanded Medicaid to cover more low-income individuals, there was an increase in preemptive listings of Medicaid beneficiaries. States that fully implemented Medicaid expansion on January 1, 2014 had a 59% relative increase in Medicaid-covered preemptive listings from the pre-expansion to post-expansion period, compared with an 8.8% relative increase among Medicaid non-expansion states. From the pre- to post-expansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage-points among non-expansion states and increased by 3.0 percentage-points among expansion states. Also, more of the new racial/ethnic minority listings from expansion states were Medicaid beneficiaries, as compared with the new white listings. In addition, Medicaid beneficiaries on the waiting list from Medicaid expansion states were more likely to be employed and functionally independent than Medicaid beneficiaries on the waiting list from non-expansion states. The authors noted that additional studies are needed to determine whether long-term transplant outcomes differ among candidates who were listed with expanded Medicaid coverage compared with those with other coverage options. In an accompanying editorial, Nitender Goyal, MD and Daniel Weiner, MD, MS (Tufts Medical Center) note that policies that improve access to care can have a tremendous impact on the delivery of medical care. “Harhay and colleagues elegantly quantified this by describing the effects of access to Medicaid on preemptive kidney transplant listing. Much harder to quantify but likely far more numerous are the patients who, because of earlier diagnosis and treatment of their kidney disease may never need to be listed for a kidney transplant, but rather will be able to maintain kidney health with better access to medical care,” they wrote. Study co-authors include Ryan M. McKenna, PhD, Suzanne M. Boyle, MD, Karthik Ranganna, MD, Lissa Levin Mizrahi, MD, Stephen Guy, MD, Gregory E. Malat, PharmD, Gary Xiao, MD, David J. Reich, MD, and Michael O. Harhay, PhD. Disclosures: The authors reported no financial disclosures. The article, entitled “Association Between Medicaid Expansion Under the Affordable Care Act and Preemptive Listings for Kidney Transplantation,” will appear online at http://cjasn.asnjournals.org/ on June 21, 2018, doi: 10.2215/CJN.00100118. The editorial, entitled “The Affordable Care Act, Kidney Transplant Access and Kidney Disease Care in the United States,” will appear online at http://cjasn.asnjournals.org/ on June 21, 2018. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 18,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.
Newswise — ANN ARBOR, Mich. — Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers in the University of Michigan Medical School Center for Consciousness Science are working to identify areas of the brain that help us wake up, a basic building block of everyday consciousness. In the search for what controls our overall level of consciousness, researchers have traditionally focused on structures in the lower part of the brain. These structures include the brainstem (which regulates vital functions like breathing, blood pressure and heartbeat); the hypothalamus (which is involved in sleep and controlling bodily functions); and the thalamus (which relays information from the senses). George Mashour, M.D., Ph.D., professor in the Department of Anesthesiology and director of the center, decided to look at different areas of the cortex, the upper part of the brain, for its ability to control the level of consciousness. Recent research in nonhuman primates provides evidence that the prefrontal cortex has a switchboard-like relationship with other areas of the brain, helping to ignite awareness of visual information. “There has been a debate that has recently intensified as to whether or not the prefrontal cortex — versus areas farther back — plays a role in generating conscious experience. We thought that we’d target some of these different areas in the front and back of the brain to see which ones had the ability to control the level of consciousness,” he says. The key to ignition? Because anesthesia is used to temporarily eliminate conscious experience during medical procedures, it provides the perfect opportunity to test hypotheses about consciousness. Mashour and lead-author Dinesh Pal, Ph.D., also of the Department of Anesthesiology, anesthetized rats with a common anesthetic used in humans. “We wanted to see what had the causal power to take an unconscious brain receiving ongoing anesthesia and wake it up,” says Pal. To test this, they targeted two neurotransmitters that are associated with wakefulness: acetylcholine and norepinephrine. The team exposed the anesthetized rats’ prefrontal and parietal cortex to drugs that ramped up the effect of the neurotransmitters and measured their brain activity and behavior. When exposed to an acetylcholine-receptor activator, their brain waves, normally slow during sleep and anesthesia, sped up. But rats were able to start behaving as though they were awake only with prefrontal cortex stimulation, all while continuing to receive the same level of anesthesia that is used clinically for surgery in humans. These findings were published in the journal Current Biology. Mashour says their new study “suggests that the prefrontal cortex also has the potential to play a role in coordinating the level of consciousness, possibly through the cholinergic system.” Clinically, these results could be explored for applications in people with disorders of consciousness, such as coma or vegetative states. “Let’s say you have a patient in a coma: Could the prefrontal cortex be a site that is modulated to help coordinate events to help improve level of consciousness?” Mashour asks. The implications of this possibility are significant because of the relative accessibility of the prefrontal cortex. “It’s very difficult and dangerous to directly intervene at the level of arousal centers in the brainstem because of its location, small size and nearby vital functions. Maybe the prefrontal cortex is an accessible gateway to some of those other arousal systems that could be leveraged in a clinical setting outside of anesthesia,” he says. This work was funded by the National Institutes of Health (R01GM098578), and the Department of Anesthesiology, University of Michigan Medical School, Ann Arbor. Physiology doctoral student Jon Dean was co-first author of the article.
EMBARGOED AJPH RESEARCH: PROP. 47 AND DRUG ARRESTS, TEEN SELF-INJURY, LGBQ SUBSTANCE ABUSE, WOMEN’S TOBACCO USE, PUBLIC HOUSING AND ASTHMA
American Journal of Public Health August Issue research highlights: Proposition 47 reduced racial disparities in California drug possession arrests Newswise — In the month following passage of Proposition 47 in California, absolute black–white disparities in monthly felony drug arrests decreased from 81 to 44 per 100,000 and continued to decrease over time. During the first year after enactment, felony drug arrests fell by an estimated 51,985 among whites, 15,028 among blacks, and 50,113 among Latinos. Researchers concluded that reducing criminal penalties for drug possession can reduce racial/ethnic disparities in criminal justice exposure and has implications for improving health inequalities linked to social determinants of health. The study used data on all drug arrests made in California from 2011 to 2016, comparing racial/ethnic disparities in drug arrests between whites, blacks and Latinos, immediately and 1 year after policy changes, controlling for secular and seasonal trends. [Author Contact: Alyssa C. Mooney, Department of Epidemiology and Biostatistics, San Francisco, CA. “Racial/Ethnic Disparities in Arrests for Drug Possession After California Proposition 47, 2011–2016.”]. Teenagers at high risk of self-injury; higher among girls As much as 30 percent of girls in some areas of the United States self-harm without the intention of suicide. This research found rates of boys reporting purposefully hurting themselves without wanting to die over the past 12 months ranged from 6.4 percent (in Delaware) to 14.8 percent (in Nevada). Rates for girls varied from 17.7 percent (in Delaware) to 30.8 percent (in Idaho). Rates of self-injury declined with age and varied by race and ethnicity. Depression; suicidal thoughts, plans and attempts; sexual minority status; being electronically bullied; and smoking and substance use were associated with non-suicidal self-injury. [Author Contact: Martin A. Monto, Department of Sociology and Social Work, University of Portland, Portland, OR. “Nonsuicidal Self-Injury Among a Representative Sample of US Adolescents, 2015.”]. LGBQ adolescents at substantially greater risk of substance abuse Researchers found that LGBQ adolescents were 1.12 times as likely as heterosexual adolescents to report any lifetime substance abuse and 1.27 times more likely to report past 30-day substance use. LGBQ adolescents had significantly greater risk for alcohol, tobacco and other illicit drugs. LGBQ adolescents were more than 3.5 times as likely to use methamphetamines, more than 2.7 times as likely to use hallucinogens and more than 2.6 times as likely to use steroids or ecstasy. Study authors conclude policymakers should invest in prevention and early intervention resources to address substance use risks among LGBQ adolescents. [Author Contact: John W. Ayers, Graduate School of Public Health, San Diego State University San Diego, CA. " Substance Use Among Lesbian, Gay, Bisexual, and Questioning Adolescents in the United States, 2015."]. Women’s cigarette use decreased; blunt use increased over time This analysis of data from the U.S. National Survey on Drug Use found among all women, cigarette use decreased, blunt use increased and cigar use remained stable between 2006 and 2016. Among pregnant women, smoking prevalence was highest in the first trimester. From 2006 to 2016, pregnant women were less likely to smoke cigarettes, cigars and blunts than were nonpregnant women, with declines in use occurring from first to third trimesters. Across all years, the likelihood of pregnant women having smoked cigarettes in the past 30 days (14.5 percent) was lower than in nonpregnant women (26.4 percent). Similarly, the likelihood of pregnant women having smoked cigars (1.2 percent) was lower than in nonpregnant women (3.4 percent). The likelihood of pregnant women having smoked blunts (1.8 percent) was lower than in nonpregnant women (4.0 percent). The likelihood of blunt smoking is increasing among reproductive-aged women, with use in the second and third trimesters increasing since 2013. Researchers concluded that pregnancy is an opportunity for mothers to reduce or discontinue tobacco use. [Author Contact: Victoria H. Coleman-Cowger, Battelle, Baltimore, MD." Cigar and Marijuana Blunt Use Among Pregnant and Nonpregnant Women of Reproductive Age in the United States, 2006–2016."]. Residents of public housing and rental assistance twice as likely to have asthma This research found the rate of asthma was 2.02 and 2.34 times higher among public housing development residents and rental assistance renters, respectively, than among homeowners in Boston. Researchers observed smoking-related effect modification. This heightened asthma rate remained consistent when researchers compared the rate with non-public housing renters who were eligible for subsidized housing according to income. Smoking was found to modify the association between housing status and current asthma, and the associations of public housing residents and rental assistance residents were highest in magnitude among ever-smokers. [Author Contact: Amar J. Mehta, Research and Evaluation Office, Boston Public Health Commission, Boston, MA "Subsidized Housing and Adult Asthma in Boston, 2010–2015."]. Uninsured and minorities less likely to receive smoking cessation help from health clinics Researchers found that odds of receiving counseling and medication from a health clinic to help quit smoking were lower among uninsured patients and those of a race/ethnicity other than non-Hispanic White. The odds of receiving smoking cessation help were also lower among patients with diabetes. The odds of receiving smoking cessation assistance were higher for older patients, those with comorbidity, women and those with more visits. Authors concluded that disparities in smoking cessation assistance exist in health clinic settings. [Author Contact: Steffani R. Bailey, PhD, Oregon Health & Science University, Department of Family Medicine, Portland, OR "Disparities in Smoking Cessation Assistance in US Primary Care Clinics."]. Find a full list of AJPH research papers published online below: Austerity Policies and Mortality in Spain after the Financial Crisis of 2008. Human Experimentation In Public Schools: How Schools Served As Sites Of Vaccine Trials In The Twentieth Century Did Reducing Criminal Penalties for Drug Possession in California Affect Racial Disparities in Drug Arrests? Prevention of Underage Drinking on California Indian Reservations Using Individual- And Community-Level Approaches Substance Use Among Lesbian, Gay, Bisexual And Questioning Adolescents In The United States, 2015 Community And Street-Scale Supports For Walking In The US Virgin Islands Before The 2017 Hurricanes Childhood Experiences Of Sexual Violence, Pregnancy, And Marriage Associated With Child Sex Trafficking Among Female Sex Workers In Two US-Mexico Border Cities. Industry Support Of Patient Advocacy Organizations: The Case For Sunshine Subsidized Housing And Adult Asthma: Findings From A Population-Based Health Survey In Boston Non-Suicidal Self-Injury Among A Representative Sample Of U.S. Adolescents, 2015 Cigar And Marijuana "Blunt" Use Among Pregnant And Non-Pregnant Women Of Reproductive Age In The United States, 2006-2016 Early Childhood Caries: Determinants Of Country Level Prevalence And Data Availability Disparities In Smoking Cessation Assistance In US Primary Care Clinics Homeless Children Seeking Shelter In An Urban Pediatric Emergency Department After State Housing Policy Change HPV Knowledge And Vaccine Awareness, Intention, And Uptake Among Adult Inmates In Kansas When Inclusion Excludes: Epidemiological Reframing Of Behavioral Diagnoses And Home Experiences Of Deaf Children Toward Real-Time Infoveillance Of Twitter Health Messages: Practical Considerations For Data Collection, Management, And Human Coding. Incarceration And Health Of Sexual And Gender Minority Persons Compliance In 2017 With Federal Calorie Labeling In 90 Chain Restaurants And 10 Retail Food Outlets Prior To Required Implementation The articles above will be published online June 21, 2018, at 4 p.m. ET by AJPH under “First Look.” “First Look” articles have undergone peer review, copyediting and approval by authors but have not yet been printed to paper or posted online by issue. AJPH is published by the American Public Health Association, and is available at www.ajph.org. Complimentary online access to the Journal is available to credentialed members of the media. Address inquiries to Megan Lowry at APHA, 202-777-3913, or email her. A single print issue of the Journal is available for $35 from the Journal’s Subscriptions Department. If you are not a member of the press, a member of APHA or a subscriber, online single-issue access is $30, and online single-article access is $22 at www.ajph.org. 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Newswise — BIRMINGHAM, Ala. – A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy. Paradoxically, the sending cells in this signaling are glioblastoma cells that are undergoing programmed cell death, or apoptosis, according to research by a team at institutes in the United States, Russia and South Korea. The dying cancer cells send their signals by means of extracellular vesicles induced and released during apoptosis. These vesicles — small, membrane-bound blobs known as exosomes — carry components that alter RNA splicing in the recipient glioblastoma cells, and this altered splicing promotes therapy resistance and aggressive migration. This mechanism thus becomes a possible target for new therapies to treat glioblastoma, a primary brain cancer, and the mechanism may apply to other cancer types as well. “Clinically, our data may provide the rationale to the molecular targeting of RNA splicing events or specific splicing factors for novel cancer therapies,” said Ichiro Nakano, M.D., Ph.D., leader of the international studybeing published in Cancer Cell. “This may lead to decreased acquisition of therapy resistance, as well as reduction in the migration of cancer cells.” Nakano is an academic neurosurgeon at the University of Alabama at Birmingham who conducts both brain tumor translational research and clinical brain tumor surgery. He is professor of neurosurgery in the UAB School of Medicine and a senior scientist for the UAB Comprehensive Cancer Center. Glioblastoma exhibits invasive behavior, abrupt growth and poor patient survival. As the number of the cancer cells rapidly increases, abundant apoptotic tumor cells are intermingled with neighboring proliferating tumor cells. The apoptotic cells can account for up to 70 percent of the tumor cell population. The discovery of this unusual cell-to-cell communication began with a simple experiment — injecting a combination of lethally irradiated human glioblastoma cells, which makes them apoptotic, and “healthy” glioblastoma cells into a mouse xenograft model. This combination led to much more aggressive tumor growth, as seen in brain scans, compared to “healthy” glioblastoma cells or irradiated glioblastoma cells alone. The combination was also more therapy-resistant. The UAB researchers and colleagues found that, after induction of apoptosis, glioblastoma cells shed significantly higher numbers of exosomes with larger average sizes. Those apoptotic exosomes, when combined with “healthy” glioblastoma cells, significantly increased tumor growth in the xenograft model and cell motility in bench experiments. Also, while the “healthy” glioblastoma cells alone had a clear border between the tumor and adjacent normal tissue in the xenograft, the glioblastoma cells co-injected with apoptotic exosomes invaded into adjacent brain tissue. Exosomes shed by non-apoptotic cells did not have these effects. To discover the mechanism underlying these changes, the researchers looked at what was inside the apoptotic exosomes. The vesicles were enriched with spliceosomal proteins and several U snRNAs — parts of the cellular machinery that remove introns from pre-messenger RNA. These are normally confined to the nuclei of cells; but the Nakano team found that, as the glioblastoma cells underwent apoptosis, the spliceosomal proteins were transported out of the nucleus to the cell cytoplasm, where they could be packaged into vesicles for release. Glioblastoma cell subtypes include the proneural subtypes and the mesenchymal subtype. Recent data have shown that, after therapy, glioblastoma cells shift from the less aggressive proneural subtype to the more aggressive and therapy-resistant mesenchymal subtype. The researchers found that apoptotic exosomes induced substantial alternate RNA splicing in recipient cells that resembled the splicing patterns found in the mesenchymal glioblastoma subtype. Part of this was caused by the splicing factor RBM11, which is encapsulated in the vesicles. The researchers found that exogenous RBM11 caused upregulation of endogenous RBM11 in the recipient cells and activated glycolysis. Overexpression of RBM11 increased the migration of glioblastoma cells. They also found that RBM11 altered RNA splicing to produce an isoform of the protein cyclinD1 that promotes DNA repair and an isoform of the protein MDM4 that has significantly higher anti-apoptotic activity. These changes can make the cells more therapy-resistant. Examination of the Cancer Genome Atlas database showed that elevated expression of those two isoforms is associated with poor prognoses for glioblastoma patients. Finally, the Nakano-led team looked at paired glioblastoma specimens of primary and recurrent tumors from matched patients. In most of the 43 pairs of matched samples, the RBM11 protein levels were substantially higher in the recurrent glioblastoma compared to the original, untreated tumors. In two other patient cohorts, they found that the higher RBM11 levels correlated with poor post-surgical survival for glioma patients. Beside Nakano, co-authors of the paper, “Apoptotic cell-derived extracellular vesicles promote malignancy of glioblastoma via intercellular transfer of splicing factors,” are Marat S. Pavlyukov, Hai Yu, Soniya Bastola, Mutsuko Minata, Suojun Zhang, Jia Wang, Svetlana Komarova, Jun Wang, Shinobu Yamaguchi and Heba Allah Alsheikh, UAB Department of Neurosurgery; Victoria O. Shender, Ksenia Anufrieva, Nadezhda V. Antipova, Georgij P. Arapidi, Vadim Govorun, Nikolay B. Pestov and Mikhail I. Shakhparonov, the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; Yeri Lee, Yong Jae Shin and Do-Hyun Nam, Sungkyunkwan University School of Medicine, Seoul, Korea; Ahmed Mohyeldin, Junfeng Shi and L. James Lee, Ohio State University, Columbus, Ohio; Dongquan Chen, UAB Division of Preventive Medicine; Sung-Hak Kim, Chonnam National University, Gwangju, Korea; and Evgeniy G. Evtushenko, Lomonosov Moscow State University, Moscow, Russia. This work was supported by NIH grants NS083767, NS087913, CA183991 and CA201402; Russian Foundation for Basic Research grants 16-04-01414, 16-04-01209 and 17-29-06056; and Russian Science Foundation grants 17-75-20205 and 16-14-10335; and by the Scholarships of the President of the Russian Federation SP-4811.2018.4. At UAB, Nakano surgically cares for brain tumor patients. For any questions about his clinical program, call 205-996-2098 during working hours or 205-572-9703 at night or on weekends.