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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."

AUGUSTA, Ga. (June 21, 2018) - Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Adoptive T cell therapy appears to reprogram the metabolism of tumor cells, increasing their level of reactive oxygen species, or ROS, and their destruction, says Dr. Gang Zhou, immunologist at the Georgia Cancer Center and Department of Medicine at the Medical College of Georgia at Augusta University.

Scientists treated mice that had large, localized colorectal tumors with adoptive T cell therapy after preconditioning them with a chemotherapy drug known to help with the expansion and persistence of these infused T cells. The T cells are a patient's own cells, but engineered to better fight cancer.

The therapy appeared to deliver a deadly double-whammy to the cancer cells, says Zhou, corresponding author of the study in the journal Cell Metabolism.

The scientists found the treatment interfered with production of glutathione, a natural antioxidant found in all cells, as it heightened production and accumulation of ROS inside tumor cells.

Results included increased production by T cells of proinflammatory cytokines - including tumor necrosis factor alpha - which regulate many functions cancer needs to control like cell proliferation, differentiation and death.

"We started by asking questions about how immunotherapy can change the metabolism of tumor cells. Our studies show tumor necrosis factor alpha can act directly on tumor cells and induce ROS inside them," Zhou says.

The bottom line of the metabolic changes include, for example, complete tumor regression in nearly all the tested mice.

The scientists found similar effects - higher ROS levels correlated with high tumor cell death - when the therapy was used in models of breast cancer and lymphoma.

Tumor necrosis factor alpha appears key to these desired results following adoptive T cell therapy, because when the scientists eliminated it from the equation, tumor cell death decreased dramatically.

Scavenging ROS had a similar effect. When they gave the antioxidant N-acetylcysteine - a precursor to glutathione - it also hampered the curative effect of adoptive T cell therapy, they report.

They also found that tumor necrosis factor alpha synergizes with chemotherapy to increase oxidative stress and cancer cell death. And, that giving pro-oxidants - drugs known to raise ROS levels - can somewhat replicate the tumor-killing benefit of adoptive T cell therapy. It's known that these drugs may increase oxidative stress in cancer cells and push them toward death, or apoptosis, Zhou says.

"Their baseline is already high and if you further disrupt their ability to deal with these free radicals, they will go toward apoptosis," Zhou says.

In fact, in an apparent failed attempt to fight off the higher ROS, the scientists found increased expression of several antioxidant genes in treated tumor cells.

The significant, cancer-lethal ROS increases they found were limited to the tumor cells, not other nearby cell types.

The scientists note that the direct killing of tumors by ROS they saw does not negate the possibility that tumor necrosis factor alpha also is working through its previously known method of killing off blood supplies to tumors.

Antioxidant therapy in patients with active cancer has drawn mixed results, but most studies indicate that it worsens cancer, particularly in smokers, according to the National Cancer Institute. Preclinical studies in mice indicate the therapy promotes tumor growth and metastasis. Studies exploring the benefit of antioxidant therapy in preventing cancer have largely shown no benefit or harm, the NCI says.

Tumors are known to impact T cells. In fact scientists have shown that the two can compete for nutrition and energy in the tumor microenvironment, remote sites tumors establish to successfully spread, the scientists write. It's T cells that usually get short shrift in the struggle.

Comparatively little focus has been on what T cells do to tumors, Zhou and his colleagues report. But better understanding of that impact should help improve immunotherapies, like adoptive T cell therapy, that seek to enable T cells to better target tumors.

Adoptive T cell therapy is still under development for treatment of colorectal cancer. This therapeutic approach was already known to essentially poke holes in cancer cells to kill them.

ROS are chemicals like peroxide and superoxide that are byproducts of necessary body functions like the use of oxygen and energy production by cell powerhouses called mitochondria. One reason cancer cells have naturally higher ROS levels is they have a high energy demand, Zhou says, constantly working to grow and spread.

Some level of ROS also benefits our healthy cells, including cell proliferation and differentiation. But, too much is also deadly to normal cells, even damaging to DNA.

Eating foods high in salt is known to contribute to high blood pressure, but does that linear relationship extend to increased risk of cardiovascular disease and death? Recent cohort studies have contested that relationship, but a new study published in the International Journal of Epidemiology by investigators from Brigham and Women's Hospital and their colleagues using multiple measurements confirms it. The study suggests that an inaccurate way of estimating sodium intake may help account for the paradoxical findings of others.

"Sodium is notoriously hard to measure," said Nancy Cook, ScD, a biostatistician in the Department of Medicine at BWH. "Sodium is hidden - you often don't know how much of it you're eating, which makes it hard to estimate how much a person has consumed from a dietary questionnaire. Sodium excretions are the best measure, but there are many ways of collecting those. In our work, we used multiple measures to get a more accurate picture."

Sodium intake can be measured using a spot test to determine how much salt has been excreted in a person's urine sample. However, sodium levels in urine can fluctuate throughout the day so an accurate measure of a person's sodium intake on a given day requires a full 24-hour sample. In addition, sodium consumption may change from day to day, meaning that the best way to get a full picture of sodium intake is to take samples on multiple days.

While previous studies have used spot samples and the Kawasaki formula, the team assessed sodium intake in multiple ways, including estimates based on that formula as well as ones based on the gold-standard method, which uses the average of multiple, non-consecutive urine samples. They assessed results for participants in the Trials of Hypertension Prevention, which included nearly 3,000 individuals with pre-hypertension.

The gold-standard method showed a direct linear relationship between increased sodium intake and increased risk of death. The team found that the Kawasaki formula suggested a J-shaped curve, which would imply that both low levels and high levels of sodium consumption were associated with increased mortality.

"Our findings indicate that inaccurate measurement of sodium intake could be an important contributor to the paradoxical J-shaped findings reported in some cohort studies. Epidemiological studies should not associate health outcomes with unreliable estimates of sodium intake," the authors wrote.

MAYWOOD, IL - A Loyola Medicine study is providing further evidence that floppy eyelids may be a sign of sleep apnea.

In a study published in the journal The Ocular Surface, corresponding author Charles Bouchard, MD, and colleagues reported that 53 percent of sleep apnea patients had upper eyelids that were lax and rubbery. The most severe cases of sleep apnea were associated with the most pronounced cases of floppy eyelids, but this association was not strong enough to be considered statistically significant.

Obstructive sleep apnea (OSA) occurs when the upper airway becomes blocked repeatedly, preventing restful sleep. Symptoms include loud snoring, excessive daytime sleepiness and fatigue. OSA affects an estimated 34 percent of men and 17 percent of women, but up to 80 percent those affected have not been diagnosed. A 2010 Harvard Medical School report estimated that moderate-to-severe sleep apnea was associated with $115 billion in healthcare costs, behind only cancer, diabetes and coronary heart disease.

Lax, rubbery eyelids are found in people who have one of three related conditions: lax eyelid condition (rubbery lids); lax eyelid syndrome (lax eyelids plus conjunctivitis); and floppy eyelid syndrome (lax eyelid syndrome in obese young men), said Dr. Bouchard, chair of Loyola Medicine's department of ophthalmology.

The Loyola study included 35 patients who were evaluated by Loyola sleep specialists for suspicion of sleep apnea. Overnight sleep studies confirmed that 32 of these patients had sleep apnea. Examinations by ophthalmologists found that 17 of the 32 sleep apnea patients (53 percent) also had lax eyelid condition.

Among the methods ophthalmologists employed to measure lax eyelids was a measuring instrument developed at Loyola called a laxometer. Researchers hypothesized that this objective measuring technique would provide a more accurate predictor of sleep apnea.

It's unclear why sleep apnea is linked to floppy eyelids. One theory suggests the condition is associated with low-grade inflammation that causes degradation of elastin, a protein that allows skin and other tissues to resume their shape after stretching or contracting.

"Obstructive sleep apnea is a severely underdiagnosed disease, and without treatment leads to increased morbidity and mortality," researchers concluded. "It is the duty of today's ophthalmologist to be diligent in making the diagnosis of lax eyelid syndrome in the ophthalmology clinic. They are in the unique position to identify patients at risk for obstructive sleep apnea and address this critical public health problem."

CHARLOTTESVILLE, VA (JUNE 19, 2018). This month marks the 50th anniversary of the assassination of Senator Robert F. Kennedy. Struck by bullets on June 5, 1968, following his victory speech at the California Democratic Party presidential primary, Kennedy died of severe brain injury on the following day, June 6.

Although much has been written about RFK's assassination--some documented and some speculative--to date there has been no detailed medical discussion of Kennedy's injuries and treatment. A new article published today in the Journal of Neurosurgery addresses this subject: "The assassination of Robert F. Kennedy: an analysis of the senator's injuries and neurosurgical care," by Jordan M. Komisarow, MD, Theodore Pappas, MD, Megan Llewellyn, MSMI, and Shivanand P. Lad, MD, PhD, from Duke University School of Medicine.

In this article, the authors "review the eyewitness reports of the mechanism of injury, the care rendered for 3 hours prior to the emergency craniotomy, the clinical course, and, ultimately, the autopsy." The discussion of autopsy findings is supplemented by an artist's depiction of the extent of Senator Kennedy's head injury.

Komisarow and colleagues provide a thorough review of clinical events from the time of the shooting until Kennedy's death. They also discuss differences and similarities between 1968 and 2018 in the care of patients with gunshot wounds to the head.

Immediately following the shooting, multiple physicians converged at the scene to render assistance. There was a delay of about 45 minutes in transporting Senator Kennedy to the hospital best equipped to treat his severe wounds, due to a transport protocol in place at the time. Diagnostic tests that are commonplace today, such as computed tomography (CT) and CT angiography and venography, were not available. The surgical procedure performed in 1968, a craniotomy, however, was similar to what would be performed today. Some postoperative monitoring techniques and preferred medications have changed over the years.

Based on their analysis of medical records and testimony, Komisarow and colleagues believe that the steps taken by physicians to care for Senator Kennedy in 1968 were in keeping with the standard medical practices of the day. An aggressive attempt was made to save him, but the outcome, given his serious head injury, was not unexpected.

Kennedy suffered "extensive injury to the right cerebellum and right occipital cortex." There was damage to the brainstem and evidence of epidural, subdural, and subarachnoid hemorrhage. Bone and bullet fragments were embedded in tissue throughout the brain. The authors point out that penetrating gunshot wounds to the head such as Kennedy's are associated with a high mortality rate--one that has not changed much in the last 100 years, since the time of Harvey Cushing's observations on penetrating head trauma conducted in 1918.

When asked whether Kennedy could have survived if he were to be treated using 2018 medical techniques, Dr. Komisarow responded, "By all accounts an aggressive and valiant effort was made to save the senator's life. Unfortunately, a similar injury would likely also be fatal, or severely debilitating, in 2018."

Dr. Lad added, "Despite numerous advances in imaging, anesthesia, and surgical technique over the last 50 years, damage to the brainstem and its associated blood vessels continues to be a devastating and catastrophic injury."

Using two experimental anti-malarial vaccines, which work in different ways, can greatly reduce the number of malaria infections in animal studies.

Experimental vaccines, which independently achieve 48% and 68% reductions in malaria cases, can achieve 91% reduction when combined.

Presently, each vaccine is at a different stage of human trials, and there have not been efforts to combine them. However, a team led by Imperial College London have now tested the effectiveness when using the two types of vaccine together.

The study, published today in the journal eLife, used genetically altered mouse parasites that express proteins expressed on the human version of the malaria parasite. The research was funded by the PATH Malaria Vaccine Initiative and the Medical Research Council (MRC), including researchers at Imperial's MRC Centre for Outbreak Analysis and Modelling.

Lead researcher Dr Andrew Blagborough, from the Department of Life Sciences at Imperial, said: "This is the first direct evidence than combining vaccines of different types significantly improves their efficacy in terms of reducing malarial burden.

"Reaching a potential 91% reduction in cases would have a huge impact on public health because the vaccines could be effective in areas where malaria is more prevalent."

Malaria is caused by a group of parasites that have a complex life cycle, spending time in the mosquito midgut and salivary glands, in the human liver, and circulating in human blood, where they cause the disease.

The team tested two types of vaccines: those that prevent mosquitoes from transferring the parasites, called transmission-blocking vaccines (TBVs), and those that prevent the parasite from infecting the liver, termed pre-erythrocytic vaccines (PEVs).

RTS,S is the world's first PEV malaria vaccine that has been shown to provide partial protection against malaria in young children by blocking infection of the liver. However, its maximum efficacy is under 50% (i.e. it reduces cases by around 50%).

There are currently several types of transmission-blocking vaccines in early trials, which are thought to reduce the number of parasites in the mosquito salivary glands. Their efficacy typically ranges from around 50-95%.

It has been assumed that combining these vaccines would increase their efficacy, but it has never been tested until now. The team found that when a partially effective PEV was combined with the most effective transmission-blocking vaccine, the efficacy was around 91%.

The team also found that combining any of the two types of vaccines improved efficacy of the mixture more than might be expected from the single efficacy of each vaccine separately.

Dr Morven Roberts, Programme Manager for parasites and neglected tropical diseases at the MRC, said: "While these findings are in the preliminary stages, they're valuable as they shed light on optimising strategies for preventing malaria. Learning that combining vaccines can dramatically boost efficacy in mice provides another potential tactic for controlling this disease. This is timely research as global health officials work towards WHO targets to eliminate malaria by 2030."

The team will next study how combined vaccines could work in more complex situations. Dr Blagborough said: "In the real world, the vaccine coverage we can achieve- how many people we can give it to - is important, as are the local levels of transmission, and how prevalent malaria currently is in that area.

"We plan to use a combination of rodent experiments and computer modelling to help us estimate effectiveness requirements for future vaccines."

The efficacy of current lead malaria vaccines is known to reduce over time after vaccines are administered, so the team will also investigate how combined vaccines perform in the long term.

Children who are exposed to hostile, escalating conflicts between parents are at increased risk for developing mental health problems. However, many children from homes marked by conflict don't experience significant psychological problems. A new longitudinal study sought to determine why some children are protected from the negative consequences of witnessing repeated hostility between their parents. It found that having a good relationship with a sibling may help buffer the distress of ongoing family conflict.

The study was done by researchers at the University of Rochester, the University of Nebraska-Lincoln, and the University of Notre Dame. It appears in Child Development, a journal of the Society for Research in Child Development.

"Most children not only grow up with a sibling but spend more time interacting with siblings than with any other family member," according to Patrick T. Davies, professor of psychology at the University of Rochester, who led the study. "We showed that having a good relationship with a brother or sister reduced heightened vulnerability for youth exposed to conflicts between their parents by decreasing their tendencies to experience distress in response to later disagreements between their parents." The study defined a good relationship as one in which there were high levels of warmth and problem-solving and low levels of conflict and detachment.

The researchers looked at 236 families, including children with at least one sibling who wasn't a twin, their mothers, and their fathers. The families, most of which were White and middle class, were assessed when the children were 12, 13, and 14 years old.

Conflict between parents was gauged by observing arguments between mothers and fathers, who were asked in the lab to discuss topics of disagreement. The quality of sibling relationships was measured by mothers' verbal responses to interview questions about siblings' closeness and conflict, which the authors acknowledge may limit accuracy. Adolescents reported on their distressed responses to family conflicts. And adolescents, mothers, and teachers completed questionnaires to assess the youth's psychological problems (e.g., aggression, depression, anxiety, hyperactivity).

Adolescents who witnessed conflict between their parents had greater distressed responses to conflicts a year later, and greater distressed responses, in turn, predicted mental health problems in the teens in the subsequent year, the study found. However, teens who had good bonds with their siblings were protected from experiencing these distressed responses when they witnessed their parents' conflict, and ultimately were protected from subsequent mental health problems. These protective effects were similar for siblings of different ages and combinations of genders.

"Relationships with siblings protected teens whether we defined a good bond as one that included warmth and problem-solving skills or one that had low levels of destructive conflict or disengagement," explains Meredith Martin, assistant professor of psychology at the University of Nebraska-Lincoln, who coauthored the study. "Strengthening sibling relationships may not only directly foster children's psychological adjustment, but also offer new approaches to counteracting the risks associated with experiencing hostility and unresolved conflicts between parents."

The study's authors caution that because the families were mostly White and middle class, the findings should not be generalized to families of other races and socioeconomic statuses.

A common ingredient in toothpaste and hand wash could be contributing to antibiotic resistance, according to University of Queensland research.

A study led by Dr Jianhua Guo from UQ's Advanced Water Management Centre focused on triclosan, a compound used in more than 2000 personal care products.

Dr Guo said while it was well-known the overuse and misuse of antibiotics could create 'superbugs', researchers were unaware that other chemicals could also induce antibiotic resistance until now.

"Wastewater from residential areas has similar or even higher levels of antibiotic resistant bacteria and antibiotic resistance genes compared to hospitals, where you would expect greater antibiotic concentrations," he said.

"We then wondered whether non-antibiotic, antimicrobial (NAAM) chemicals such as triclosan can directly induce antibiotic resistance," Dr Guo said.

"These chemicals are used in much larger quantities at an everyday level, so you end up with high residual levels in the wider environment, which can induce multi-drug resistance.

"This discovery provides strong evidence that the triclosan found in personal care products that we use daily is accelerating the spread of antibiotic resistance."

Advanced Water Management Centre Director, Professor Zhiguo Yuan, said the discovery should be a wake-up call to re-evaluate the potential impact of such chemicals.

"While the US Food and Drug Administration (FDA) has banned the use of triclosan in antibacterial soap, the previous lack of unequivocal evidence prevented such a policy being adopted in other countries," Professor Yuan said.

Antimicrobial resistance has become a major threat to public health globally with approximately 700,000 people a year dying from antimicrobial-resistant infections.

The Review on Antimicrobial Resistance report predicted this will reach 10 million deaths a year by 2050 if no action is taken now.

For every three individuals who have had a stent implanted to keep clogged arteries open and prevent a heart attack, at least one will experience restenosis--the renewed narrowing of the artery due to plaque buildup or scarring--which can lead to additional complications.

Now, a team led by UBC electrical and computer engineering professor Kenichi Takahata has developed a type of "smart stent" that monitors even subtle changes in the flow of blood through the artery, detecting the narrowing in its earliest stages and making early diagnosis and treatment possible.

"We modified a stent to function as a miniature antenna and added a special micro-sensor that we developed to continuously track blood flow. The data can then be sent wirelessly to an external reader, providing constantly updated information on the artery's condition," said Takahata.

The device uses medical-grade stainless steel and looks similar to most commercial stents. Researchers say it's the first angioplasty-ready smart stent--it can be implanted using current medical procedures without modifications.

Research collaborator Dr. York Hsiang, a UBC professor of surgery and a vascular surgeon at Vancouver General Hospital, noted that monitoring for restenosis is critical in managing heart disease.

"X-rays such as CT or diagnostic angiograms, which are the standard tools for diagnosis, can be impractical or inconvenient for the patient," said Hsiang. "Putting a smart stent in place of a standard one can enable physicians to monitor their patient's health more easily and offer treatment, if needed, in a timely manner."

The device prototype was successfully tested in the lab and in a swine model. Takahata, who holds patents for the technology, says his team is planning to establish industry partnerships to further refine the device, put it through clinical trials and eventually commercialize it.

Forty percent of deaths attributed to cardiac arrest are not sudden or unexpected, and nearly half of the remainder are not arrhythmic--the only situation in which CPR and defibrillators are effective--according to an analysis by researchers at UC San Francisco and the City and County of San Francisco Office of the Chief Medical Examiner.

In a three-year study of 20,440 deaths in San Francisco, the researchers identified 912 cases in which the individual died of an apparent out-of-hospital cardiac arrest (OHCA), and conducted autopsies and lab tests on 896 (98 percent) of those. They found that only 541 individuals--or 59 percent--actually met the criteria set by the World Health Organization (WHO) for sudden cardiac death (SCD).

Of those SCDs, 13.5 percent, or almost 1 in 7, were due to a hidden overdose, with lethal opioid levels in 61 percent of the cases, a reflection of the ongoing opioid epidemic.

The findings call into question the accuracy of aggregate mortality data, clinical trials and research studies, as well as the death certificates and emergency medical system (EMS) records on which those datasets are based. The analysis also showed substantial race and sex differences in SCD epidemiology, reinforcing the importance of investigating these deaths in women and diverse populations.

"Our findings demonstrate the poor accuracy of our current, widely adopted definitions for sudden cardiac death, which essentially are a presumption of cardiac cause," said lead author Zian H. Tseng, MD, MAS, UCSF Health cardiac electrophysiologist. "Restricting all such deaths to autopsy-confirmed cardiac causes, we found a lower prevalence of coronary disease and an increasing prevalence of causes not involving reduced blood flow to the heart."

The study appears in the June 19, 2018, special autopsy issue of the American Heart Association journal Circulation.

The WHO defines sudden deaths as nonviolent and otherwise unexplained deaths occurring less than 24 hours from the onset of symptoms. In everyday practice, the category also includes the reported impression of an EMS responder of OHCA. These variable definitions result in widely varying estimates of the annual incidence of SCDs, from 184,000-450,000 in the United States.

As more than 90 percent of these deaths occur outside the hospital and non-forensic autopsies are rarely performed, causes of death are almost always presumed.

In the POstmortem Systematic invesTigation of Sudden Cardiac Death (POST SCD) study, Tseng and his colleagues reviewed all deaths in San Francisco County between February 2011 and March 2014, and conducted autopsy, toxicology and histology tests, as well as record reviews, on patients who had been reported to have died in OHCA. A multidisciplinary committee of the assistant medical examiner, cardiac pathologist, neurologist and two cardiologists/cardiac electrophysiologists adjudicated the final cause of death.

Of the 912 identified OHCA deaths, 40 percent did not meet the WHO criteria for sudden death. Of the 525 cases that met the criteria and were autopsied, only 55.8 percent were found to be sudden arrhythmic deaths (SADs).

"Because SADs are the only type of sudden deaths rescued by defibrillators and the intended focus of clinical trials, risk studies and molecular studies of SCD, it is essential to distinguish SAD from non-arrhythmic causes," said Tseng, the Murray Davis Endowed Professor in the Cardiology Division and Cardiac Electrophysiology Service at UCSF.

The rates of WHO-defined sudden death were highest in blacks and lowest in Hispanics. However, autopsies showed that arrhythmic deaths in these populations were significantly lower than for whites, and much lower in women (45 percent) than men (61 percent).

The leading causes of death in the 525 autopsies were coronary disease (32 percent), overdose (13.5 percent), cardiomyopathy (10 percent), cardiac hypertrophy (8 percent) and neurologic (5.5 percent). Since all of these misclassified deaths were designated by EMS as cardiac arrest, overdoses and other metabolic emergencies may be under-recognized as causes of death, the authors said.

"Our methods may provide an outline for medical examiner or coroner protocols for the systematic examination of these out-of-hospital natural deaths, which are rarely investigated in the community," said senior author Ellen Moffatt, MD, assistant medical examiner in the Office of the Chief Examiner.

While this was the most comprehensive study of SCD to date, the authors cautioned that exact causes of death sometimes remain unclear and subject to interpretation.

Researchers previously showed that overweight and obese individuals with knee osteoarthritis can reduce pain by 50% and significantly improve function and mobility with a 10% or more weight loss over an 18-month period. The investigators' latest findings, which are published in Arthritis Care & Research, reveal that a 20% or more weight loss has the added benefit of continued improvement in physical health-related quality of life along with an additional 25% reduction in pain and improvement in function.

The results come from a secondary analysis of diet-only and diet plus exercise groups in the Intensive Diet and Exercise for Arthritis (IDEA) randomized controlled trial. A total of 240 overweight and obese older community-dwelling adults with pain and knee osteoarthritis were divided into four groups according to weight loss achieved over an 18-month period: less than 5% (

The researchers found that the greater the weight loss, the better participants fared in terms of pain, function, 6-minute walk distance, physical and mental health-related quality of life, knee joint compression force, and IL-6 (a marker of inflammation). Also, when comparing the two highest groups, the ?20% group had 25% less pain and better function than the ? 10% group, and significantly better health-related quality of life.

Obesity is a health issue worldwide and a major and modifiable risk factor for many of the more than 250 million adults with knee osteoarthritis. "Currently, there is no treatment that slows the progression or prevents this debilitating disease; hence, research has focused on improving clinical outcomes important to the patient," said lead author Stephen Messier, PhD, of Wake Forest University, in Winston-Salem, NC. "A 10% weight loss is the established target recommended by the National Institutes of Health as an initial weight loss for overweight and obese adults. The importance of our study is that a weight loss of 20% or greater--double the previous standard--results in better clinical outcomes, and is achievable without surgical or pharmacologic intervention."

Milan, Italy: Children who are born severely ill or who develop serious illness in the first few weeks of life are often difficult to diagnose, with considerable implications for their short and longer-term care. Whole genome sequencing*carried out quickly has the potential to provide an early diagnosis, and thus improve the clinical care of these infants as well as reducing its cost, the annual conference of the European Society of Human Genetics will hear tomorrow (Sunday).

Dr Shareef A. Nahas, Senior Director, Rady Children's Institute for Genomic Medicine, San Diego, CA, United States, will report on his team's study of rapid whole genome sequencing (rWGS) of all inpatient children under one year of age who were nominated for genetic investigation at Rady Children's Hospital. Rapid WGS is able to return results in 48 to 96 hours, whereas standard genetic testing takes six to eight weeks to provide a result. They then noted subsequent changes in medical care that occurred while the child was still in hospital. Where there was a significant change in care due to a new diagnosis, the cases were reviewed by an independent expert panel who tried to determine what they believed would have happened had the child not received rWGS.

After 12 months of testing, 363 patients had been enrolled in the study and rWGS interpreted in 340 of them. This yielded a diagnosis in 115 cases (about 34%). Diagnosis occurred quickly, on average within 96 hours. Changes in management as a result of diagnosis were identified in 77 patients, or about 67% of those diagnosed. Such changes ranged from specific changes, for example surgical interventions, to guidance in palliative care. Among the first 42 infants diagnosed, rWGS provided over $1.3million in net cost saving over the projected standard care.

"To date, our studies have shown a considerable clinical and economic benefit of sequencing children who were identified by clinicians as being suspected of having a genetic disorder. In the course of the study, one child was spared devastating neurological damage,and one had a significantly reduced risk of death. The net cost savings totalled several hundred thousand dollars, even when we included the cost of analysing the genome of the child and both parents, » says Dr Nahas.

Although many studies have shown that WGS improves the diagnosis if genetic disorders in infants and can lead to beneficial changes in their management, the new research has shown that, by implementing rapid sequencing, cost savings will also ensue. &laquo We are now in a situation where we have a technology that leads to improved diagnosis and improved outcomes but is also not a net burden on healthcare resources. This means that for large healthcare payers, there is not a logical cost barrier to implementing rWGS in neonates suspected to have a genetic disorder. There will need to be further data on who else can benefit from early use of this technology but implementation in the current cohort should not be delayed, » says Dr Nahas.

Currently, the use of WGS among sick neonates is very infrequent across the world, and there are few healthcare systems that have the ability to turn round genetic testing quickly enough to be clinically relevant, the researchers say. This is vital if medical management needs to be changed during the childrens' hospitalisation. In the course of Dr Nahas' study, one child was spared devastating neurological damage and another had a significantly reduced risk of death.

&laquo The logic for the use of rWGS in these patients, both diagnostic and economic, is totally convincing. We have demonstrated that early sequencing saves money during admission. We were surprised by the proportion of children who received a change in care during that admission - around 25% of children sequenced and 80% of those diagnosed. This rate is much higher than other published rates for neonates who received WGS. We believe that this difference is due to the fact that the children received results at a much younger age, at a point where medical decisions were yet to be made.

&laquo There is an ethical imperative to act in the best interest of neonates, but implentation will require a concerted effort across all healthcare systems, and this will need to be at government level in Europe. Consistent with many diagnostic tests in the post-natal period, rWGS has the potential to identify conditions associated with lifelong disability or shortened lifespans, » Dr Nahas will conclude.

In a second presentation, Courtney French, PhD, a research associate/bioinformatician at the University of Cambridge, Cambridge, UK, will describe how she and colleagues carried out WGS analyses on 145 severely ill babies and children with an unidentifiable disease. As a result, they were able to identify the cause of disease in more than 15% of cases.

&laquo We have developed a rapid, affordable turnaround pipeline for this sequencing within the UK National Health Service system. This means that we can feed back clinically relevant information to doctors and parents in a timescale that allows care to be affected. Because it is hard to tell from observation alone who will benefit from genomic diagnosis, we think that it should be carried out on all eligible children, rather than doctors deciding on individual cases based on previous clinical knowledge. By comparing the entire DNA sequence in children to that of their parents we can identify quickly the likely cause of disease, » says Dr French.

The researchers are using their current data to investigate how rare genetic diseases present at an earlier stage than they are usually diagnosed in newborns. &laquo Greater numbers of patients will expand our ability to do this, and we hope that our work will serve as a model for expanding the programme to other hospitals and regions, » Dr French will say. &laquo The success of this project will depend on people working together across the health research and healthcare system. The translation of this work to routine care will require significant investment of resources in achieving consent from parents, and in giving information at what is a very stressful time for them. »

Many of the conditions characterised through WGS to date can be treated more effectively once identified. In the Cambridge dataset, several epilepsies that respond better to some medications than others were found. And there were cases where the diagnosis was able to prompt better screening for the clinical consequences of a condition and enabled the creation of a properly focused care plan, for example cardiac surveillance, renal follow up, or dietary advice. Even where there is no effective treatment available, having a diagnosis can provide reassurance to families that all that could be done has been done, and it can also provide useful information to parents when they are considering the most appropriate care for their child in the future.

&laquo We were pleasantly surprised at the enthusiastic welcome parents gave to our study, with more than half of those approached wanting to take part. Despite the complications of getting samples from both parents, as well as their child, we managed to achieve this in 85% of families. We were also surprised at the huge range of clinical conditions we were able to diagnose, and particularly to find that when a child was already known to have learnng disability or developmental delay we were more likely to make a genetic diagnosis. This reflects the enormous increase in genetic knowledge over the last decade; ten years ago we would not have been able to do this even if we had sequenced the genome.

&laquo Genome sequencing is currently rare in newborns and paediatric cases, but our research has shown that it can be extremely effective in providing rapid answers in difficult to diagnose cases. It is also be cost-effective, since it can reduce the time spent as an in-patient. Early diagnosis of neonatal and paediatric disease is not only important in pointing the way to the best care and treatment, but also in reducing anxiety for parents, » Dr French will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: "Both these studies confirm the value of genome sequencing to detect the cause of unexplained disease. The study of Nahas shows that this can now even be done within four days, which is very impressive. This greatly increases the practical use of genetics in an acute clinical setting where treatment decisions can now be made based upon this powerful test. Personalised genomic medicine is becoming a reality!"

Milan, Italy: Giving personal genomic information to individuals can have a major, long-term effect on their lifestyle, researchers have found. The Finnish GeneRISK study, providing information on the risk of cardiovascular disease (CVD) based on their genome and traditional risk factors to 7,328 people inspired changes for the better in areas such as weight loss and smoking cessation. Nearly 90% of them said the information had made them take better care of their health, the annual conference of the European Society of Human Genetics will hear today (Saturday).

Although there is plenty of evidence that genomic factors have an important impact on the risk of common diseases, to date there has been little use of this information in prevention. Elisabeth Widen, MD, a senior scientist at the Institute for Molecular Medicine, University of Helsinki, Finland, and colleagues have developed a web-based tool that allows patients and doctors to see and manage genomic information based on 49,000 disease-associated genetic variants and lifestyle-associated risk factors.

&laquo Delivering the results of the tool KardioKompassi® directly to patients, they were able to see their 10-year risk for ischemic heart disease. The tool combines risk information based on traditional risk factors such as age, sex, cholesterol levels and blood pressure with a polygenic risk score. Where a patient's overall disease risk was elevated, KardioKompassi advised the participant to contact their doctor in order to discuss how best to reduce it, » Dr Widen will say.

When reassessed eighteen months later, the results were impressive. Compared with a 4% smoking cessation rate in the general population, 17% of smokers in the study had given up, and sustained weight loss had been achieved by 13.7% of participants. Overall, risk-reducing behaviour such as weight loss, giving up smoking, or visiting a doctor was 32.4% in those with a predicted CVD risk of more than 10% and 18.4% in those at lower risk.

&laquo As many as 40% of participants with a high risk of CVD were smokers at the start of the study, so these results are encouraging. We believe that giving information on their genetic profile to individuals is particularly motivating, perhaps simply because it is new information. For example, many of the participants already knew that they had high levels of cholesterol. But it was receiving information on their personal genetic risk that triggered changes, » Dr Widen says.

GeneRISK participants will be recalled for follow-up studies over the next 20 years and their health status will be closely followed. The researchers believe that those who have already made lifestyle changes are likely to continue them. &laquo Since they have managed to maintain these changes for 1.5 years, we expect them to persist, » says Dr Widen.

The general trend towards patient participation is particularly important in disease prevention, say the researchers. Empowering individuals by giving information on their personal risk of disease, as opposed to something more generalised, is clearly effective in encouraging them to follow healthier lifestyles.

&laquo Our results show that this approach to managing and interpreting genomic data for individuals is feasible and effective. We think that our study provides a model for the use of such data in healthcare that can be easily adapted to other diseases, where we believe that it is likely to be equally valuable, » Dr Widen will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: "It is impressive to see how genomic information can be used successfully to promote a healthier lifestyle in people at higher risk of developing heart disease. Clearly in the population there will also be many people with a relatively lower genetic risk of developing common diseases, and I do wonder what would happen if these people are informed about this; would they start showing an unhealthier lifestyle? This field of predictive genomic medicine is only just emerging, with lots of opportunities for further research."

The results of two studies presented today at the Annual European Congress of Rheumatology (EULAR 2018) provide insight into the role of sleep in chronic pain. The first study demonstrates a predictive role of sleep problems for chronic pain1 and the second provides insight into chronic pain and sleep in adolescents.2

"The relationship between pain and sleep is complex, as the consequences of sleep problems can affect perception to pain and, in turn, pain can interfere with sleep quality," said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. "This is why these studies are important as they help elucidate the role of sleep in chronic pain and highlight it as a potentially important modifiable risk factor for alleviating the distress in these patients."

Sleep problems predict the onset of chronic widespread pain (CWP) in 20-year prospective study1

Within the study all four parameters relating to sleep - difficulties initiating sleep, maintaining sleep, early morning waking and non-restorative sleep - as well as one related to fatigue, were found to predict the onset of CWP after five years in a model adjusted for age, gender, socio-economy and mental health. In addition, all parameters except 'problems with early awakening' predicted the onset of CWP at 18 years.

"Our results demonstrate that sleep problems are an important predictor for chronic pain prognosis and highlight the importance of the assessment of sleep quality in the clinics," said Katarina Aili, PhD, Spenshult Research and Development Center, Halmstad, Sweden.

Additional analysis showed that reporting all four sleeping problems at baseline versus no sleep problems was significantly associated with CWP at both time points using a number of models adjusted for age, gender, socio-economy as well as mental health, number of pain regions or pain severity.

Individuals included in the study had not reported CWP* at baseline or during the previous three years, 1249 entered the five-year and 791 entered the 18-year follow up analysis. Four parameters related to sleep (difficulties initiating sleep, maintaining sleep, early morning awakening and non-restorative sleep), and one parameter related to fatigue (SF-36 vitality scale) were investigated as predictors for CWP.

Sleeping problems and anxiety associated to chronic multisite musculoskeletal pain in adolescents2

One in ten students in the study was suffering with chronic multisite musculoskeletal pain (CMP). Analysis showed that, compared to other students, having CMP was associated with reporting severe sleeping problems as well as probable cases of anxiety.

"Although the relationship between sleep and pain is complex, our results clearly indicate a strong association which needs to be explored further," said Julia S. Malmborg, PhD student at The Rydberg Laboratory for Applied Sciences, Halmstad University, Sweden. "As both problems affect the physiological and psychological well-being of sufferers we hope that these results will be used by school health professionals to promote student health."

The study included 254 students from a Swedish school who completed questionnaires on chronic pain, sleeping problems, stress, anxiety and depression. The mean age of participants was 16.1 years (SD 0.6) and two thirds were girls. CMP† was identified in 9.8% of students with no difference between boys and girls. CMP was significantly associated with reporting severe sleeping problems‡ (OR 2.49, 95% CI 1.06-5.81, p=0.035) and also probable cases of anxiety§ (OR 3.06, 95% CI 1.09-8.61, p=0.034) but not possible cases of anxiety or probable/possible cases of depression.

Abstract number: OP0072 and OP0361-HPR

(WASHINGTON, June 15, 2018) -- Austrian researchers have discovered that a small number of patients taking targeted drugs known as Janus kinase (JAK) inhibitors to treat myelofibrosis may develop aggressive lymphomas.

They also speculate that screening for a preexisting B-cell clone before starting therapy may help prevent this side effect and potentially save lives, according to a study published online today in Blood, the Journal of the American Society of Hematology (ASH).

One of three disorders that falls under the umbrella of myeloproliferative neoplasms is myelofibrosis, a rare bone marrow cancer in which too many blood cells are produced, leading to scarring and hardening inside the bone marrow. The exact cause of myelofibrosis is not known, but it has been linked to the JAK2 gene, which control the production of blood cells. Doctors treat the condition with medications designed to target or inhibit the action of this gene when it is faulty.

Though not a cure, JAK inhibitors are very effective at providing symptom relief, said study coauthor Heinz Gisslinger, MD, of the Medical University of Vienna in Austria. "However, we started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment."

To test this, investigators assessed 626 patients receiving treatment for myeloproliferative neoplasms at the Medical University of Vienna and identified 69 that had myelofibrosis and were being treated with JAK inhibitors. Of those, four (5.8%) developed lymphomas. In comparison, they found that of the 557 patients who did not receive JAK inhibitors, only two (0.36%) developed lymphomas.

That amounts to a 16-fold increased risk for aggressive B-cell lymphoma in patients receiving JAK inhibitors, said study coauthor Ulrich Jäger, MD, of the Medical University of Vienna.

In samples taken from the patients with myelofibrosis, investigators found a preexisting B-cell clone in the bone marrow in three of the four patients who later developed lymphoma. Further investigation suggested that this clone was the same that later transformed into lymphoma.

The investigators also demonstrated an association between JAK inhibition and an increased frequency of aggressive B-cell lymphomas in mouse models.

"By replicating this link between this B-cell clone and aggressive lymphoma, we hope to speed the discovery of an alternative therapy for myelofibrosis," said study coauthor Veronica Sexl, MD, of the University of Veterinary Medicine, Vienna. "These findings are going to be valuable in clinical care."

"We determined that patients with this preexisting B-cell clone in their bone marrow are most at risk for developing aggressive lymphoma," said Dr. Jäger. "We also know that up to 16 percent of people with myelofibrosis have immunoglobulin gene rearrangements like this B-cell clone. Therefore, our findings suggest that all patients with myelofibrosis should be tested for such gene rearrangements before prescribing JAK inhibitors to treat their disease."