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SAN ANTONIO, TX (October 1, 2018)­­-Hospital readmissions, cost hospitals about $26 billion annually. Systems like the Hospital Readmission Reduction Program (HRRP) within the Affordable Care Act penalize hospitals with higher readmission rates for targeted diagnoses. Healthcare data reveals that healthcare facilities located in rural Southern Appalachia show readmission rates that are above the national average, which results in penalties to hospitals within this region. In order to assess and prevent the causes of these frequent hospital readmission, researchers performed a retrospective review of rural Southern Appalachia.

Researchers reviewed 15,500 patients admitted to rural Southern Appalachia hospitals from January 1, 2014 to October 31, 2017. In order to determine associations with readmission, univariate analyses and regression modeling were conducted on potential associated variables such as length of stay, age, gender, healthcare payor, discharge month/day/time, tobacco use, smoking cessation education, medication reconciliation upon discharge, and presence of comorbid diagnoses like diabetes mellitus, hypertension chronic renal failure, and psychiatric disorders.

The authors found that every day spent in the hospital, readmission likelihood increases by 2.9%. Individuals discharged between 0100 - 1300 were less likely to be readmitted compared to those discharged between 1300 - 0100 (p

"Primary causes of hospital readmissions in rural Southern Appalachia are increased length of stay, discharges after 1300, history of smoking, and presence of comorbid COPD, diabetes mellitus, hypertension, chronic renal failure, and psychiatric disorders," says Dr. Michael Zhang, researcher. "Some methods to prevent readmissions are decreasing length of stay, discharging patients before 1300, providing smoking cessation education, and controlling comorbid diagnoses."

Further results from these two studies will be shared at CHEST Annual Meeting 2018 in San Antonio on Monday, October 8, 5:00 PM to 5:15 PM at the Henry B. Gonzalez Convention Center, Room 206B. The study abstracts can be viewed on the journal CHEST® website.

SAN ANTONIO, TX (October 1, 2018)­­-Critical care ultrasound (CCUS) is an important skill for all critical care physicians to understand. However, currently there is no standard approach to how to teach CCUS. Researchers aimed to investigate the feasibility of implementing a CCUS curriculum via a social platform in order to evaluate the impact it has on fellow's self-perceived competency. Results found that utilizing a social media platform, like Facebook, provides benefits such as spaced learning, active participation, and an informal and personal learning environment.

Fellows from the University of Southern California pulmonary and critical care department voluntarily enrolled in the study in which they were provided with the typical CCUS curriculum they receive and a pre-knowledge and skills assessment. After the assessment, fellows participated in a 2-day hands-on bootcamp. Once the boot camp was completed, fellows were invited to join a private CCUS Facebook group that provided them with 41 core skills divided into 5 systems delivered over 20 weeks. These posts included a wide variety of content including quizzes, cases, images, movies, and management-type questions along with links to web pages and articles. Researchers measured analytics on the platform including the traffic, number of views, and usage over time.

The authors found that 47.6% of fellows participated in the Facebook group, with 3 first year (30%), 4 second year (40%), and 2 third year (20%) fellows. The mean number of posts viewed by a fellow was 24 (out of 41 posts). Almost all (90%) of the fellows responded to the post-intervention survey; 44% shared that they would participate in a Facebook education group again; 56% responded that the Facebook group enhanced their CCUS education and 44% stated that it motivated them to learn more.

"We believe that Facebook is a viable method for implementing a CCUS curriculum," says Dr Shiqian Li, lead researcher. "The fact that most of the fellows stated that the content was useful and had enhanced their education and some of the fellows stated that it motivated them to learn more further shows that Facebook and social media may be a beneficial adjunct for different types of learners."

Further results from these two studies will be shared at CHEST Annual Meeting 2018 in San Antonio on Monday, October 8, 1:45 PM - 2:00 PM at the Henry B. Gonzalez Convention Center, Room 216B. The study abstracts can be viewed on the journal CHEST® website.

NEW YORK -- Treatment with a HER2-targeted therapeutic cancer vaccine provided clinical benefit to several patients with metastatic HER2-positive cancers who had not previously been treated with a HER2-targeted therapeutic, according to data from a phase I clinical trial presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held Sept. 30-Oct. 3.

Among 11 evaluable patients who had received more than the lowest dose of the vaccine, six (54 percent) had clinical benefit. One patient with ovarian cancer had a complete response that lasted 89 weeks, one patient with gastroesophageal cancer had a partial response that lasted 16 weeks, and four patients (two with colon cancer, one with prostate cancer, and one with ovarian cancer) had stable disease.

"Immunotherapy marshals the exquisite specificity of the immune system to destroy cancer, and some types may have potentially fewer side effects than traditional chemotherapy," said Jay A. Berzofsky, MD, PhD, chief of the Vaccine Branch at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. "We are using a vaccine approach to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers.

"Our results suggest that we have a very promising vaccine for HER2-overexpressing cancers," continued Berzofsky. "We hope that one day the vaccine will provide a new treatment option for patients with these cancers."

The patients' vaccines are individually customized by Berzofsky and colleagues using their own immune cells isolated from their blood. The blood-derived immune cells are modified in several ways in the laboratory. The final product, which is administered intradermally (between the layers of the skin), comprises patient-derived dendritic cells genetically modified with an adenovirus to produce parts of the HER2 protein.

Preclinical studies, which were previously published in the AACR journal Cancer Research, showed that this type of vaccine could eradicate large, established tumors as well as lung metastases in mice.

In the dose escalation portion of the phase I clinical trial, patients were injected with the vaccine on weeks 0, 4, 8, 16, and 24 after enrollment in the study. Among the six patients who received the lowest dose of the vaccine, 5 million dendritic cells per injection, no clinical benefit was seen. Among the 11 patients who received either 10 million or 20 million dendritic cells per injection, six had clinical benefit.

Adverse reactions were predominantly injection-site reactions that did not require treatment. No cardiotoxicity was seen.

"Based on the current safety and clinical benefit data, the dose of the vaccine was increased to 40 million dendritic cells per injection and the trial opened to patients who have previously been treated with a HER2-targeted therapeutic, including patients with breast cancer," said Berzofsky.

"Moving forward, we would like to investigate whether we can increase the proportion of people who benefit from treatment with the vaccine by combining it with checkpoint inhibitor therapy," he added.

According to Berzofsky, the main scientific limitation of the study is that it is a relatively small, phase I clinical trial with no placebo control. However, the approach is sufficiently promising to warrant additional trials.

NEW YORK -- Angiosarcoma Project, a patient-partnered genomics study, identified immune checkpoint inhibition as a potential treatment option for patients with angiosarcomas of the head, face, neck, or scalp (HFNS), according to data presented at the fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held Sept. 30-Oct. 3.

"Angiosarcoma is an exceedingly rare cancer affecting about 300 patients a year in the United States, has a high mortality rate, and has no standard of care; because of its rarity, there is a dearth of scientific discoveries that can lead to clinical impact," said Corrie A. Painter, PhD, associate director of Operations and Scientific Outreach at Broad Institute of MIT and Harvard. "It is important to develop novel approaches for working with patients who are geographically dispersed and who may never have the opportunity to participate in a large-scale research effort because they have such a rare disease."

The Angiosarcoma Project, launched by the Broad Institute in March 2017 in collaboration with Dana-Farber Cancer Institute, partners with patients throughout the duration of the project, including design, build, launch, and accrual, to develop a comprehensive resource to enable discoveries about this rare cancer, Painter said. Researchers in this project collect patient-reported data, medical records, archival tumor tissue, saliva, and blood samples from patients across the United States and Canada who choose to sign remotely and contribute to this study.

The team performs whole exome sequencing of about 20,000 genes on tumor and matched germline DNA. The genomic data are combined with the clinical data, including diagnosis, treatments, and responses, to generate a clinically annotated genomic database that is shared publicly with the goal of identifying the genomic drivers of the disease and mechanisms of response and resistance to treatments.

Painter and colleagues identified several genes in the samples known to be altered in angiosarcoma, including KDR and TP53. Among the 321 patients with angiosarcoma registered so far, 21 percent had angiosarcomas of HFNS.

All three patients with angiosarcoma of HFNS from the initial cohort of 12 patients in the first data release had tumors with a high tumor mutational burden (more than 150 mutations/kb) and dominant UV light signature, similar to melanoma. Recent studies have shown that patients with tumors bearing a high mutational burden are more likely to respond to immune checkpoint inhibitors targeting PD-1/PD-L1. This class of immunotherapeutics has been approved by the U.S. Food and Drug Administration to treat several different cancer types, including melanoma.

"Our work suggests that patients with angiosarcoma of HFNS, which comprises the largest demographic of people affected by angiosarcoma, have a high mutational burden and UV light signature, and therefore may respond to checkpoint inhibition. This could have a major impact on clinical advances for this subset of patients, so we searched through the patient-reported data to identify additional patients," Painter said.

Through their patient portal, the researchers identified an additional 56 patients with angiosarcoma of HFNS who shared the details of their treatments. Two of them had received the anti-PD1 antibody pembrolizumab (Keytruda) off-label, one in 2015 and the other in 2016, to treat metastatic disease. Both had complete and durable responses to this treatment and remained without evidence of disease at the time of this reporting, Painter noted.

"This study is driven by a group of patients who already found each other in a single online support group. Because the patients were already in a network we could engage, and because of the tremendous effort within the community of sarcoma oncologists to alert their patients as well, we have been able to produce data in an unprecedented manner for such an exceedingly rare disease," Painter said.

"We believe that patient-partnered research such as this can serve as a model for rare cancers and outliers in common cancers in order to greatly accelerate the pace of discovery," she added.

Limitations of the study include small sample size. "We are currently able to enroll patients from the United States and Canada. Because this disease is so rare, we would benefit greatly from a global effort," Painter said. Patients are recruited through social media, which could introduce biases in who is participating, Painter noted.

DURHAM, N.C. - Up to two years following elective, arthroscopic hip surgery, a substantial proportion of patients reported troubling new health issues ranging from sleep problems, to arthritis to cardiovascular disease.

While such problems can be transient and diminish as full mobility returns, the findings suggest that patients and doctors should be prepared to manage a variety of complications over time, even as the surgeries themselves are considered a success.

"Our study focused on a younger group -- current and former military personnel ages 18-50 -- and compared their medical records both before and after surgery," said Daniel Rhon, D.Sc., an adjunct professor at the Duke Clinical Research Institute and lead author of a study published online Sept. 28 in the British Journal of Sports Medicine.

"Even among this younger group, the number and frequency of these hidden complications that arose after elective hip surgery suggests we should be taking a more wholistic approach, proactively assessing patients for risks other than the standard surgical complications we more commonly look for," Rhon said.

Rhon and colleague -- including senior author Chad Cook, Ph.D., program director of Duke's Doctor of Physical Therapy Program -- conducted the observational study by examining Military Health System records of 1,870 former and current service members undergoing arthroscopic hip surgery between 2004-2013. Patient records were collected for the 12 months prior to and 24 months after surgery.

In their analysis, they identified incidences of mental health disorders, chronic pain, substance abuse issues, cardiovascular ailments, metabolic syndrome, arthritis and sleep problems that were noted in the patients' medical records both before and after their elective hip surgeries.

Post-surgery incidences of all comorbidities after the procedure rose dramatically: mental health disorder increased 84 percent; chronic pain diagnoses soared 166 percent; substance abuse ticked up 57 percent; cardiovascular disorders rose 71 percent; metabolic syndrome cases rose 86 percent; arthritis spiked 132 percent; and sleep disorders jumped 111 percent.

"Hip arthoscopy is becoming more common even among younger people, and it can be quite successful in resolving chronic, painful conditions," Cook said. "But it's important to be prepared for a lengthy recovery. These are surgeries where people are prohibited from fully bearing weight for several weeks, so they can't exercise, they can't sleep comfortably, they are in pain."

Rhon said disruptions in sleep can be particularly problematic. Without proper rest, the sense of pain escalates, leading to a negative spiral of fatigue and pain that then depresses mood, energy levels and general health.

"These issues are compounding on each other," Rhon said. "Our study serves as an important alert to both doctors and patients. Armed with this knowledge, we can be vigilant in addressing these problems earlier and potentially stopping others from developing."

Sept. 25, 2018--A commonly used biomarker of kidney disease may also indicate lung problems, particularly COPD, or chronic obstructive pulmonary disease, according to new research published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Albuminuria, Lung Function Decline, and Risk of Incident COPD: the NHLBI Pooled Cohorts Study," Elizabeth C. Oelsner, MD, MPH, and coauthors report a link between albuminuria, the amount of the protein albumin in urine, and COPD. The researchers conducted their study by pooling information from 31,877 participants (average age: 60 years) from six cohort studies funded mainly by the National Heart, Lung, and Blood Institute.

Albuminuria indicates damage to the single layer of cells lining blood vessels, known as the endothelium, in the kidney. Previous studies have shown that this damage is associated with microvascular (small vessel) dysfunction throughout the body, including the lungs. However, according to the authors of the current study, no large-scale, prospective study has tested whether albuminuria is associated with the development of COPD.

"The pulmonary microvasculature is critical to gas exchange and known to be impaired in patients with COPD, especially those with emphysema," said Dr. Oelsner, Herbert Irving Assistant Professor of Medicine at Columbia University. "We wanted to test whether albuminuria, a non-invasive and commonly used clinical test, could serve as a marker for increased risk of developing chronic lower respiratory diseases, such as COPD and asthma."

The researchers excluded participants who had been diagnosed with COPD or asthma upon enrollment in the studies. Participants were followed for changes in lung function over a median of 6 years and for respiratory hospitalizations and mortality over a median of 15 years.

The study found for each standard deviation increase in albuminuria, there was a:

15 percent increase in those who developed moderate-to-severe COPD;

26 percent increase in COPD hospitalizations and deaths; and

3 percent greater decline in FEV1 (the amount of air that can be forcibly exhaled in one second) and an 11 percent greater decline in the ratio between FEV1 and FVC (the total amount of air that can be forcibly exhaled after taking the deepest breath possible). Both FEV1 and FEV1/FVC are important measures of lung function.

The researchers found that these associations remained significant even after taking into account smoking history, diabetes, hypertension and cardiovascular disease. Interestingly, while smoking is known to cause both endothelial damage and COPD, the results were found to be similar in never-smokers.The study did not find a significant association between albuminuria and asthma.

The authors said that their findings suggest that endothelial damage in the lungs may play an important role in the development and progression of COPD. They added that the mechanisms behind that damage and behind microvascular dysfunction may present promising targets for new therapies designed to prevent or treat COPD.

Dr. Oelsner noted that a clinical trial is currently being conducted to test whether angiotensin II receptor blockers (ARBs), which have been shown to prevent progression in kidney disease, may also slow progression of emphysema.

"Our study helps to explain why COPD patients often have a constellation of vascular problems, including heart and kidney disease," Dr. Oelsner said. "This makes it all the more important for clinicians to encourage avoidance of exposures like smoking and treatment of diseases like hypertension and diabetes that cause endothelial dysfunction."

Bangkok, Thailand, 28 September 2018: The incidence of stroke is rising in Taiwan contrary to falls in Western countries, according to a nationwide study presented at the ASEAN Federation of Cardiology Congress 2018 (AFCC 2018).

AFCC 2018 is being held 28 September to 1 October in Bangkok, Thailand. The meeting is hosted by The Heart Association of Thailand and organised by the ASEAN Federation of Cardiology. Visiting experts from the European Society of Cardiology (ESC) will present key messages from ESC guidelines.1

Stroke is the third leading cause of death and most common cause of complex disability in Taiwan, a country of about 23 million people. The burden of stroke, particularly ischaemic stroke, is greater in East Asia compared to Western countries. Stroke occurrence has declined in several Western nations due to better management of risk factors, but much less is known about patterns in East Asia in the last decade.

This study examined the incidence of stroke over a 13-year period in Taiwan. For this nationwide cohort study, researchers reviewed the records of all hospitalised patients with a primary diagnosis of stroke between 2001 and 2013 from the Taiwan National Health Insurance Research Database.

They also recorded the type of stroke: ischaemic (caused by clots which cut off blood supply to parts of the brain), intracerebral haemorrhage (bleeding within the brain), and subarachnoid haemorrhage (bleeding on the surface of the brain).

A total of 23,023 first-ever strokes were identified. Of those, 66.9% were ischaemic stroke, 21.1% were intracerebral haemorrhage, 2.9% were subarachnoid haemorrhage, and 9.1% were of undetermined type.

After adjusting for the rising age of the population, the researchers found that the incidence of ischaemic stroke increased from 110 to 122 per 100,000 person-years, intracerebral haemorrhage increased from 30 to 38 per 100,000 person-years, and the rate of subarachnoid haemorrhage was stable.

Study author Dr Yuan-Horng Yan, of Kuang Tien General Hospital, and associate professor of Hung Kuang University, Taichung, Taiwan, said: "Many strokes could be prevented with a healthy lifestyle, which includes not smoking, being physically active, eating healthily, keeping body weight down, and limiting alcohol consumption. Adopting behaviours that are good for you help to prevent high blood pressure, high cholesterol, and type 2 diabetes, which contribute to strokes. People who already have these conditions should consult their doctor about taking medication."

Dr Rungroj Krittayaphong, scientific chairperson of AFCC 2018, said: "Cardiovascular disease remains the major cause of death in Asian populations, particularly in ASEAN countries.2 Many previous reports have shown that strokes are more common in Asian than Western populations and the prevalence is increasing. We do not have data on the extent to which genetic factors contribute to the greater occurrence of stroke in Asian patients. Every effort should be made to develop regional strategies to explore the factors leading to stroke and establish management guidelines to tackle this issue."

Professor Jose Zamorano, course director of the ESC programme in Bangkok, said: "Cardiovascular diseases, including stroke, are a principal cause of death today. Adequate control of cardiovascular risk factors, such as hypertension, is crucial for reducing the burden of disease. The 2018 ESC guidelines on hypertension show the best way of treating this risk factor."3

Around one in three stillbirths occur before 28 weeks of pregnancy but are not officially recognised.

The burden of stillbirth has been underestimated by at least a third because of recommendations to report only stillbirths from 28 weeks' gestation in international comparisons, according to an observational study of 2.5 million babies in 19 European countries published in The Lancet.

The findings underscore the importance of accurate and consistent reporting of fetal deaths as early as 22 weeks so that the true burden of stillbirth can be understood and the impact on families acknowledged.

"There are major and serious gaps in our knowledge of the burden of stillbirth which will have significant unforeseen impacts on families," says Dr Lucy Smith, University of Leicester, UK, who led the research. "To a mother or father, a second trimester stillbirth is no less tragic than a stillbirth at 28 weeks of pregnancy or later. These parents also deserve recognition of their loss and accurate reporting of their child's death to improve care and policy." [1]

A Lancet stillbirth Series published in 2016 found that half of the 2.6 million stillbirths that occur worldwide every year (98% in developing countries) could be prevented, and estimated that, in high-income countries, for every 1000 births around 3.5 babies are born stillborn [2]. However, the true burden could be substantially higher. WHO recommends that international comparisons use a cut-off of 28 weeks of gestational age. However, at a country level, WHO identifies 22 weeks of gestation as a threshold for identifying stillbirth, and there are also major differences between countries in their registration legislation (in part due to differences in the perception of viability of babies born early), as well as differing policies on termination of pregnancy being reported as stillbirths.

The authors used data from 19 European countries on pregnancy outcomes from 22 weeks of gestation between 2004 and 2015, to calculate overall rates of stillbirth and changes in rates between 2004 and 2015 by gestational age and country [3].

In 2015, more than 9300 babies were stillborn from 2.5 million births in Europe, and out of these a third were stillborn between 22 and less than 28 weeks of gestation, and would have been excluded from WHO's threshold for international comparison.

Between 2004 and 2015, the overall stillbirth rate between 24 and less than 28 weeks of gestation declined from nearly 10 to 7 per 10,000 total births, a reduction of 25% (figure 1B). This is similar to global figures of stillbirths over 28 weeks of gestation which fell 25.5% worldwide (from 247 to 184 per 10,000 births) and 24.5% in developed regions (from 45 to 34 per 10,000 births) between 2000 and 2015--suggesting consistent improvements in the reduction of stillbirths from 24 weeks of gestation over time [4].

Nevertheless, the variation across countries in stillbirths from 24 to less than 28 weeks in Europe ranged between 4 and 8 per 10,000 total births (when excluding terminations of pregnancy) implying that a large proportion of stillbirths are still preventable. These results are consistent with the variation in stillbirth rates at later gestation observed in many previous studies in high-income countries. The authors point out that the consistency in reporting of these earlier stillbirths suggests that these deaths should be routinely included in international comparisons to help inform clinical practice and policy.

In contrast, the overall rate of stillbirth between 22 and less than 24 weeks has remained unchanged since 2004, at around 5 per 10,000 births in 2015. The authors speculate that this is likely to be due to improvements in the reporting of deaths at these gestations. In 2015, rates of stillbirth (22 to

According to Dr Smith: "Wide variation in the number of stillbirths occurring between 22 weeks and 24 weeks is likely to highlight differences in the collection of data across European countries rather than variation in underlying stillbirth risk. To ensure that the true magnitude and burden of stillbirth is understood, and to improve routine data collection for monitoring the outcomes and management of extremely preterm births from 22 weeks gestation, WHO's threshold for high-income country comparisons should be lowered." [1]

"Only through international studies, such as the Euro-Peristat project, that collect data with a standardised protocol, can reliable cross-country comparisons of stillbirth rates be made. This standardisation allows for consistent international reporting practices for terminations of pregnancy and agreed definitions for reporting of stillbirths and livebirths" says senior author Professor Jennifer Zeitlin, Inserm, Paris who coordinated the Euro-Peristat project. [1]

The authors note some limitations including that late terminations of pregnancy could not be excluded in a few countries, and the omission of some countries because of lack of comparable data for the study period, may have influenced the results--although sensitivity analyses supported the generalisability of the results as proportions of early stillbirths in these countries were very similar.

Writing in a linked Comment, Professor Marleen Temmerman from Aga Khan University in Kenya says: "In the Sustainable Development Goals, there is still no target for stillbirths, despite inclusion of a neonatal mortality target for the first time. This gap is a missed opportunity to count and drive change for stillbirths which are mostly preventable, but also a missed opportunity to count major impact that is coming from other investments for example in antenatal care and quality of care at childbirth."

She concludes: "Now is the time to count, and act on this burden, with good reporting from all countries above 28 weeks and all to collect data from 22 weeks. When countries meet data quality criteria, the 22-28 week stillbirth rates will be included in global reports. We also call for total births, livebirths, and stillbirths to be included in the denominators of key indices, such as maternal mortality, skilled attendance at birth, and Caesarean section rates, and for more innovation and investment in stillbirth data collection and use, including in surveys in low and middle income countries."

Another study published simultaneously in The Lancet finds that a reduced fetal movement (RFM) care package for pregnant women does not appear to reduce the risk of babies being born stillborn. The AFFIRM study is a randomised controlled trial of over 409,000 pregnancies from 33 hospitals across the UK and Ireland. However, the authors stress that their advice to pregnant women remains the same--if they notice any change in their babies' movements in the womb, they should contact their midwife or maternity unit immediately.

A care package aimed at reducing the risk of babies being stillborn may offer marginal benefit, research suggests.

Findings from a major study were inconclusive, but experts stress that advice for pregnant women remains the same.

Women who notice a change in their baby's movements in the womb should seek advice from their midwife or local maternity unit immediately.

Previous research had suggested that encouraging women to pay attention to their babies' movements, combined with additional checks and early delivery of babies at risk, might help cut rates of stillbirth by 30 per cent.

Researchers led by the University of Edinburgh investigated whether a similar care package could help to reduce rates of stillbirths in a large randomised controlled trial.

The study - called AFFIRM - analysed outcomes from more than 400,000 pregnancies from 33 hospitals around the UK and Ireland.

It is the largest study of fetal movement awareness to date and the first in the world to investigate fetal movement combined with an intervention designed to reduce stillbirth.

Results indicated a marginal drop in the stillbirth rate, from 44 in 10,000 births after standard care to around 41 in 10,000 births with the intervention.

Further analysis suggested the intervention might prevent five stillbirths for every 10,000 babies born. The effects were too small to prove that the care package had been beneficial, however. The team say further research will be needed.

Study lead Professor Jane Norman, Director of the Edinburgh Tommy's Centre at the University of Edinburgh, said: "The study was designed to detect an effect of 30 per cent or greater. The results suggest that if there is a beneficial effect, it is much smaller than this. It is not possible to say with certainty that the intervention has any effect on reducing rates of stillbirth.

"The research adds further evidence to suggest that being aware of baby movements may help to marginally reduce risks of stillbirth, but it is unlikely that this strategy alone will be reliable for monitoring the wellbeing of babies in the womb. Other interventions will likely be needed to reduce stillbirth rates worldwide."

In the group that received the care package, more women were induced early and there were higher rates of caesarean section deliveries, the study found.

Researchers say an economic analysis of these data will help policy makers assess whether this approach might fit into a stillbirth reduction strategy.

Professor Alexander Heazell, co-investigator on the study and Director of the Tommy's Stillbirth Research Centre at the University of Manchester, said: "There are a number of other ongoing fetal movement awareness studies. Results from the AFFIRM trial should be analysed in conjunction with those studies before recommendations can be made on wider implementation of this approach."

An estimated 2.6 million babies are stillborn each year around the world. In the UK, around one in 200 pregnancies end in stillbirth, around nine babies every day.

Up to a half of women whose pregnancy ends in stillbirth report reduced movements of their babies in the womb in the previous week.

Jane Brewin, Chief Executive of Tommy's, said: "We know that reduced baby movements is associated with the placenta not working so well and the baby's health being compromised. The advice for mums-to-be remains the same - if your baby's movements change please consult your midwife or local maternity unit immediately."

The study, published in The Lancet, was initiated and funded by the Scottish Government's Chief Scientist Office. It was also funded by Tommy's, the baby charity, and Sands, the Stillbirth and Neonatal Death Charity.

Dr Clea Harmer, Chief Executive at Sands (the Stillbirth And Neonatal Death charity), said: "Women's awareness of their baby's movements remains a key part of public health information during pregnancy. At least one in three of the parents Sands supports tells us that their baby's movements had slowed down or changed in the womb before they died. Getting the message out that women need to report any concerns straightaway remains vital to routine antenatal care."

Highlights

Among patients with kidney failure on dialysis, use of proton pump inhibitors was associated with a 19% higher risk of hip fracture. The association remained within subgroups of low, moderate, and high use, yielding of 16%, 21%, and 19% greater risks, respectively.

Histamine-2 receptor antagonists were not associated with hip fracture events.

Washington, DC (September 27, 2018) -- Certain medications commonly used to treat heartburn, acid reflux, and ulcers are linked with higher bone fracture risks among patients on dialysis, according to a new study. Almost three-quarters of patients who had a hip fracture had used the medications in the 3 years preceding their event. The findings appear in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN).

Among patients who have end-stage kidney disease, or kidney failure, and are on hemodialysis, hip fracture risk is estimated to be 4 times higher than in the general population. Many patients with kidney failure take medications called proton pump inhibitors (PPIs), which reduce stomach acid production and have been linked with hip fractures in the general population. Theoretically, histamine-2 receptor antagonists, which also reduce gastric acid production, would yield a similar association with hip fracture events if the mechanism of proposed risk involved acid suppression alone. Yet, studies in the general population conflict on whether these drugs are also linked with fractures.

To examine potential associations in patients with kidney failure, a team led by Chandan Vangala, MD and Wolfgang Winkelmayer, MD, PhD, ScD (Baylor College of Medicine) analyzed information from the US Renal Data System (USRDS) to identify all hip fracture events recorded between 2009 and 2014 among hemodialysis-dependent patients. All cases were matched with 10 patients on dialysis who did not experience hip fractures. Prescription drug information for the preceding 3 years was gathered from Medicare Part D claims.

In the analysis of 4551 hip fracture cases and 45,510 controls, a larger proportion of cases had any prior use of PPIs (70% vs. 63%) or histamine-2 receptor antagonists (25% vs. 23%). After adjustments, use of PPIs was associated with a 19% higher risk of hip fracture. The association remained within subgroups of low, moderate, and high PPI use, yielding of 16%, 21%, and 19% greater risks, respectively. Histamine-2 receptor antagonists were not associated with hip fracture events.

"Proton pump inhibitors are the sixth most common type of medication prescribed among patients who are dependent on dialysis; however, their use is associated with increased hip fracture risk. Therefore, we recommend interval assessment of continued PPI use in hemodialysis-dependent patients, who already experience tremendous medication burden," said Dr. Vangala.

In an accompanying editorial, Benjamin Lazarus, MBBS and Morgan Grams, MD, PhD (Johns Hopkins Bloomberg School of Public Health) noted that the association between PPI use and hip fracture is biologically plausible, but the observational study cannot definitively assert that PPI use causes hip fracture. "However, a randomized controlled trial to address risks of PPI use in patients receiving hemodialysis is probably not practicable," they wrote. "Based on the available data, we suggest that PPI use in hemodialysis patients be individualized, with discontinuation as soon as medically indicated, and that patients are counseled about possible adverse effects, including the possibility of heightened risk of hip fracture."

Study co-authors include Jingbo Niu, MD, DSc, Colin Lenihan, MB BCh BAO, PhD, William Mitch, MD, and Sankar Navaneethan, MD, MS, MPH.

Disclosures: Dr. Winkelmayer reports having served as an advisor or consultant, unrelated to the topic of this manuscript, to Akebia, Amgen, Astra-Zeneca, Bayer, Daichii-Sankyo, Relypsa, Vifor-Fresenius Medical Care Renal Pharma, and ZS Pharma. Dr. Navaneethan serves on the independent event adjudication committee for clinical trials sponsored by Bayer and Boehringer Ingelheim (unrelated to the topic of this manuscript). All other authors have no financial disclosures to report.

Rutgers researchers have developed a tool to help neurologists screen for obstructive sleep apnea in people with epilepsy whose seizures can be magnified by sleep disorders.

The study appears in the journal Neurology Clinical Practice.

Although detection and treatment of obstructive sleep apnea (OSA) can improve seizure control in some patients with epilepsy, providers have not regularly assessed patients for those risk factors. The researchers developed an electronic health record alert for neurologists to evaluate a patient's need for a sleep study.

This study can determine the necessity for treatment, which can result in improved seizure control, reduction in antiepileptic medications and reduce the risk of sudden unexpected death in epilepsy.

OSA occurs when breathing is interrupted during sleep. The Epilepsy Foundation estimates that approximately 40 percent of people living with epilepsy have a higher prevalence of OSA that contributes to poor seizure control.

"Sleep disorders are common among people living with epilepsy and are under-diagnosed," said lead author Martha A. Mulvey, a nurse practitioner at University Hospital's department of neurosciences. "Sleep and epilepsy have a complex reciprocal relationship. Seizures can often be triggered by low oxygen levels that occur during OSA. Sleep deprivation and the interruption of sleep can therefore increase seizure frequency."

The researchers developed an assessment for identifying OSA consisting of 12 recognized risk factors, which are embedded in the electronic health record. If a patient has at least two risk factors, they are referred for a sleep study. The risk factors include: body mass index greater than 30 kg/m2; snoring; choking or gasping in sleep; unexplained nighttime awakenings; morning headaches; dry mouth, sore throat or chest tightness upon awakening; undue nighttime urination; decreased memory and concentration; neck circumference greater than 17 inches; excessive daytime sleepiness; undersized or backward displacement of the jaw; and an assessment of the distance from the tongue base to the roof of the mouth.

"It was found that placing this mandatory alert for providers to screen for OSA in the EHR markedly increased the detection of at-risk epilepsy patients who should be referred for a sleep study," said co-author Xue Ming, professor of neurology at Rutgers New Jersey Medical School. "Such screening can lead to early detection and treatment, which will improve the quality of life of patients with epilepsy and OSA."

In cases that were reviewed prior to the alert being placed in the electronic health record, only 7 percent with epilepsy were referred for sleep studies. Of those who were referred, 56 percent were diagnosed with sleep apnea. Of the 405 patients who were screened for OSA after the alert was placed in the electronic health record, 33 percent had at least two risk factors and were referred for a sleep study. Of the 82 patients who completed a sleep study, 87 percent showed at least mild sleep apnea.

In the wake of media and public reports about increased mortality linked to a new drug for treating Parkinson's disease psychosis (PDP) -- a symptom of the progressive nervous system disorder in which patients experience hallucinations and delusions -- researchers at University of California San Diego School of Medicine conducted a retrospective study of qualifying patients in the UC San Diego Health system, concluding that the new drug, pimavanserin (marketed as Nuplazid), did not pose a statistically significant greater risk of death.

The findings are published in the September 26 online issue of Neurology.

"This paper is important because pimavanserin has been in the news, and there is considerable debate and concern about its safety," said Fatta B. Nahab, MD, associate professor in the Department of Neurosciences at UC San Diego School of Medicine and the study's corresponding author. "We wanted to better understand and assess the risks of using pimavanserin within our own patient community, either alone or in combination with other commonly prescribed medications."

Parkinson's disease (PD) is a complex neurodegenerative disorder. Symptoms generally develop slowly over years, and typically affect movement, balance and walking. However, cognitive dysfunction, such as PDP, often appears in the latter stages of the disease and is a leading contributor to patients being placed in nursing homes.

PD itself is not fatal, but it is associated with serious disease complications, making the condition the 14th leading cause of death in the United States, according to the Centers for Disease Control and Prevention.

Using anonymized medical records of 4,478 UC San Diego Health patients with a diagnosis of Parkinson's disease, Nahab and colleagues singled out 676 cases that met the study criteria of having a PD diagnosis and being prescribed pimavanserin, quetiapine (an antipsychotic drug marketed as Seroquel) or both medications between April 29, 2016 and April 29, 2018. The Food and Drug Administration approved Nuplazid for PDP in April 2016 after designating it a "breakthrough therapy." The expedited approval followed a single, six-week clinical trial of 199 participants. The drug is marketed by Acadia Pharmaceuticals, Inc., based in San Diego.

As the first drug approved to treat hallucinations and delusions associated with PDP, Nuplazid was immediately popular, with sales exceeding $100 million in 2017. But lingering concerns about limited clinical testing were exacerbated by reports of increased adverse effects in patients using pimavanserin, "including deaths, life-threatening incidents, falls, insomnia, nausea and fatigue," according to an April 9, 2018 story by CNN.

In their review of the 676 qualifying patient cases, UC San Diego researchers found a lower mortality percentage for those using pimavanserin compared to those using only quetiapine or those using both drugs. "But the differences were not significant," said Nahab.

The researchers did note a significant increased risk of mortality -- 74 percent -- in the quetiapine-only group compared with individuals not on these medications and a trend toward increased risk in the combination therapy group. "It's reasonable to assume, however, that individuals requiring these medications have greater disease severity and are at a higher risk of complications and death," said Nahab.

"Our findings provide the largest comparative report of mortality risk in PDP to date," said Nahab, "but there were limitations to our study based on its design and nature. We did not find any new or unexpected concerns about the use of pimavanserin in the treatment of PDP, which may provide some reassurance to clinicians, patients and families. But more work is needed to better evaluate factors like disease severity and cause of death to improve our understanding of the potential risks of treating PDP."

There is an increasing need to prevent obesity because of the consequences for mental as well as physical health, new research by academics at the University of Bristol has found.

The study, published today [Wednesday 26 September] in the BMJ, explored the impact of aspects of physical health, such as body weight, heart health and blood pressure, to see whether a wide age range of individuals with poorer physical health went on to be less happy and less satisfied with their lives.

Previous studies have shown that individuals who are happier and more satisfied with their lives tend to have better physical health and live longer than those who have lower mental wellbeing. But these studies leave the classic chicken and egg question - which comes first?

Using a technique called Mendelian randomization, the researchers asked whether poorer physical health causes lower mental wellbeing, or whether individuals with lower mental wellbeing are more likely to go on to have later problems with their physical health. This technique provides evidence of the direction of causation by using genetic variants that have been associated with physical health and mental wellbeing. Unlike previous methods, this technique helps to rule out the influence of other factors that might be causing both physical health and mental wellbeing.

The research team were able to test 11 measures of physical health including coronary artery disease, heart attack, cholesterol, blood pressure, body fat and Body Mass Index (BMI).

Results suggested a consistent causal effect of higher BMI on lower mental wellbeing. There was little evidence that the other physical health traits were leading to less happiness and life satisfaction. The same pattern of results was seen in a follow-up analysis using the UK Biobank cohort of over 300,000 individuals aged 40 to 70 years old. Here the authors were able to look at different aspects of life satisfaction and found that the key impact of higher BMI was on lower satisfaction with health. They were also able to show that the effect is present from age 40 through to age 70, and in both men and women.

When testing whether mental wellbeing caused any of these physical health traits, the authors found little evidence for a causal impact in that direction, but this analysis is limited because there are so far fewer genetic variants for mental wellbeing. As research uncovers more of the genetic variants associated with mental health traits, researchers will be able to test this direction of effects more thoroughly.

Dr Robyn Wootton, Research Associate from the Medical Research Council Integrative Epidemiology Unit (MRC IEU) at the University of Bristol and the study's lead author, said: "The next question is why we find this link. We are keen to explore the role of body satisfaction and self-esteem, which could help practitioners know how best to support individuals to remain physically and mentally healthy."

Dr Claire Haworth, Reader in Behavioural Genetics in the MRC IEU at the University of Bristol, and senior author on the study, added: "Results so far highlight the pressing need to tackle the obesity crisis because higher BMI is causing the population to be less happy and less satisfied with their lives. This information could be immediately useful to clinicians encouraging patients to maintain a healthy weight.

"Frequently individuals are encouraged to lose weight because this will lead to better physical health, but for many this is not motivating enough. Becoming happier and more satisfied with their lives might be the extra motivation needed to encourage more people to maintain a healthy weight."

BUFFALO, N.Y. - There's little question about the value of breast milk as a source of infant nutrition, but a University at Buffalo sociologist is part of a research team whose new study is adding critical nuance toward better understanding the association between breastfeeding and infant health in the first year of life.

The researchers found that mothers who while pregnant said they intended to exclusively breastfeed, but then used formula once the baby was born, had children with health outcomes similar to exclusively breastfed infants. Only about half of mothers who intend to breastfeed are able to do so, and often their ability to breastfeed is beyond their control and not known until their baby is actually born.

The findings suggest that the benefits of breastfeeding reported in the vast majority of prior research could be influenced by the mother's characteristics, such as what they know about health and nutrition. The results from the study could help guide policy makers and health care professionals when it comes to providing critical information to expectant mothers about feeding their newborns.

"It's important to understand that we are not trying to imply that just intending to breastfeed is what's leading to these health outcomes," says Jessica Su, an assistant professor in UB's Department of Sociology and co-author of the study led by Kerri Raissian, an assistant professor in the University of Connecticut's Department of Public Policy. "What we found is that intending mothers had more information about nutrition and diet; they more frequently consulted their physicians; and had better access to information related to infant health than those moms who did not intend to breastfeed."

"This access to health care is an important policy focus. By sinking so much energy into getting moms to breastfeed, we miss something very important: that access to health care and the ability to take medical advice is critically important to a mother and her infant," said Raissian. "By exploring factors influencing better infant health outcomes, information from the study helps contextualize the tradeoffs that a lot of mothers have to make when deciding how to feed their children."

The findings, based on data from more than 1,000 participants in the Infant Feeding Practices Study II, designed by the Centers for Disease Control and Prevention and the Food and Drug Administration, appear in the journal Social Science & Medicine: Population Health.

The World Health Organization and the American Academy of Pediatrics both recommend exclusively breastfeeding a child for six months. That message used to be presented as a healthy lifestyle choice, but today these agencies communicate the benefits of breastfeeding as a matter of public health.

"We don't have the social support to facilitate the recommendations being put forth. The U.S. is the only developed country with no federal paid parental leave, and only about 12 percent of mothers in the private sector have access to paid leave," says Su. "Paid maternity leave likely increases breastfeeding success, and also seems to have additional health benefits for mothers and infants. If we have concerns about disparities in infant health we need social policies that support these recommendations and also go beyond simply encouraging breastfeeding over formula."

Breastfeeding is not always practical and may not produce the health benefits mothers hope for, yet the "breast is best" message is so strong that it can create undue stress and feelings of inadequacy for mothers who are unable to breastfeed. There is a high cost to this message, especially if the benefits of breastfeeding are overstated.

"It's important to more carefully quantify the trade-offs between breast milk and formula given the strong breastfeeding recommendations and the realistic challenges that many mothers face, particularly among working mothers," Su says.

A new study by scientists at the University of Liverpool highlights how a clinically-approved lung cancer drug could potentially be 'repurposed' to design new treatments for future cancer therapies.

The research, published in Science Signaling, focuses on a protein called TRIB2, which is linked to promoting survival and drug resistance in solid tumours and blood cancers and is therefore of particular interest as a therapeutic target.

The study was led by Professor Pat Eyers and colleagues in the Department of Biochemistry at the University's Institute of Integrative Biology, where BBSRC Doctoral Training Programme student Dan Foulkes worked in collaboration with scientists at the Universities of Georgia and North Carolina, Chapel Hill, in the USA.

TRIB2 is part of the Tribbles (TRIB) family of pseudokinase proteins - sometimes described as 'zombie' enzymes, due to their inability to catalyse chemical reactions. Tribbles were named after the small, round, fictional organisms from Star Trek, whose major role in life is to eat and reproduce. Consistently, Tribble proteins play many diverse roles in cell signalling, development and cancer.

In particular, TRIB2 proteins have the ability to promote cell survival, a hallmark of cancer cells, and TRIB2 is a potential new drug target for acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), which are both in urgent need of targeted therapeutics.

Using a biochemical drug repurposing approach, the researchers discovered that a family of drugs currently approved to treat lung cancer can also degrade TRIB2 at higher concentrations in human acute myeloid leukaemia (AML) cancer cells in vitro, leading to cancer cell death.

This family of drugs, called protein kinase inhibitors, were originally designed to block a different protein called Epidermal Growth Factor Receptor (EGFR) from working in lung cancer cells, where it can help stop or slow tumour growth in some patient populations.

The approved lung cancer drug afatinib is one of a number of EGFR inhibitor compounds identified by the study as a potential drug lead for the development of TRIB2-targeted cancer therapies.

Professor Eyers commented: "A long-standing goal in cancer research is drug-induced degradation of oncogenic proteins. Our study highlights how information obtained with 'off-target' effects of known drugs is potentially useful because it might be exploited in the future to help eliminate a protein that is involved in a completely different type of cancer."

The research is one of two studies featured in the latest issue of Science Signaling that explores the structures and protein interactions of TRIB pseudokinases, a focus of work in Professor Eyers' laboratory.