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The human brain is highly sensitive to oxygen deprivation. Extensive and irreversible damage occurs within approximately 10 minutes of cardiac (and hence circulatory) arrest. For the first time, researchers from Charité - Universitätsmedizin Berlin and the University of Cincinnati have been able to study these events in humans. The results from this research, which has been published in Annals of Neurology*, may inform future treatment strategies of cardiac arrest and stroke.

Oxygen deprivation results in brain injury. For years, researchers have been studying the underlying processes in animals: within 20 to 40 seconds, the brain enters an 'energy-saving mode' - it becomes electrically inactive, and all interneuronal communication ceases. Within a few minutes, the brain's fuel reserves have become depleted that maintain the uneven distribution of ions between the inside and outside of nerve cells, and the ion gradients start to break down. This breakdown takes the form of a massive wave of electrochemical energy release in the form of heat, which is known as 'spreading depolarization'. More vividly described as a 'brain tsunami', this energy loss spreads through the cortex and other areas of the brain, triggering pathophysiological cascades which gradually poison the nerve cells. Importantly, this wave remains reversible up to a certain point in time: nerve cells will recover fully if circulation is restored before this point is reached. However, if circulation remains disrupted, the cells will die. Until now, recordings of electrical brain activity obtained from human subjects have been of limited applicability, and experts have been divided as to the transferability of results from animal-based research.

It is usually impossible to take the relevant measurements in the minutes immediately following a stroke or cardiac arrest. Under the leadership of Prof. Dr. Jens Dreier of Charité's Center for Stroke Research, and working with Prof. Jed Hartings of the Mayfield Clinic in Cincinnati, researchers have now been able to study such cases for the first time. Their research was facilitated by a very specific setup. Specialist neuromonitoring techniques, which enable the early detection and subsequent treatment of clinical complications, are becoming an increasingly common feature of modern neurocritical care. In particular, electrocorticography and invasive methods of monitoring oxygen are becoming increasingly significant. In contrast to conventional electroencephalography, electrocorticography goes beyond the process of recording epileptic seizure activity, enabling clinicians to record spreading depolarization with never-before-seen precision. Over the past few years, a number of international clinical studies have been able to confirm that, in many severe cases of acute brain injury, spreading depolarizations develop as soon as the patient's condition worsens. When this happens, treatment must target the underlying causes of this phenomenon, in order to limit its occurrence.

As part of their observational study, the researchers used state-of-the-art neuromonitoring technology. Scientific analysis of both monitoring data and each patient's clinical course showed that the event known as 'terminal spreading depolarization' also occurs in humans, beginning within minutes of circulatory arrest. "We were able to show that terminal spreading depolarization is similar in humans and animals. Unfortunately, the research community has been ignoring this essential process of central nervous system injury for decades, all because of the mistaken assumption that it does not occur in humans," explains Prof. Dreier. The reasons for this have been primarily methodological in nature. Reestablishing circulation as rapidly as possible has, until now, been the sole aim of treatment in stroke and cardiac arrest patients. "Knowledge of the processes involved in spreading depolarization is fundamental to the development of additional treatment strategies aimed at prolonging the survival of nerve cells when brain perfusion is disrupted," explains Prof. Dreier. He adds: "This of course follows from the tenet espoused by Max Planck that insight must precede application; our insights can give us hope for the future."

Spinraza, the gene therapy medication, also provides significant improvements in cases with the next most severe form of neuromuscular disease, spinal muscular atrophy (SMA), which afflicts children from 6 to 18 months of age. That is shown by a study published in the New England Journal of Medicine (NEJM).

"The effects are convincing, and this reinforces results from the earlier study," says Mar Tulinius, professor of pediatrics at Sahlgrenska Academy and chief medical officer at the Queen Silvia Children's Hospital.

In the earlier study, published in NEJM in November, Mar Tulinius also was responsible for the Swedish part. Then Spinraza was administered for the most severe form of spinal muscular atrophy, SMA type 1, which afflicts children before they are six months old.

This time the study concerned SMA type 2, in which the illness occurs when children have learned to sit by themselves but have not yet begun to walk. The muscles gradually weaken, the children never stand upright on their legs and ultimately they need respirators to survive.

Two out three children in the current study received Spinraza; one out of three received a placebo. And this time, too, it turned out that the drug with the active substance nusinersen, which partly compensates for an inherited genetic error, altered the children's condition.

Their ability to sit up straight, raise their hands, move by rolling around, etc., was improved by an average of four points on the scale used to measure changes in spinal muscular atrophy. At the same time, children in the placebo group regressed an average of 1.9 points on the scale.

"The natural progression is for the children to lose points on this scale. Although there are variations within the group, they are never destined to get better. The fact that strength and mobility increased in those who received the drug is really quite amazing," Mar Tulinius said.

People with spinal muscular atrophy lack a protein that is required for the motor nerve cells in the spinal cord to function. If both parents are carriers, the likelihood that the child will get the disease is 25 percent.

Every year 10 or so children in Sweden are diagnosed with SMA. The two most difficult variations, type 1 and 2, are covered by a recently issued recommendation from the Swedish Council for Novel Therapies (NT-rådet) of Sweden's municipalities and county councils that under certain conditions and strict control, children should be offered treatment with Spinraza.

"Often, they say no, we can't afford it, when it comes to expensive orphan drugs. But this one produces such good results that it is impossible to ignore," says Mar Tulinius.

TORONTO, Feb. 26, 2018--"Is there a doctor on board?"

Hearing this call go out at 36,000 feet can be anxiety-provoking for any physician and may trigger a dilemma of whether to respond, or wait to see if anyone else will offer their expertise.

That's why physicians at St. Michael's Hospital have developed practical recommendations for in-flight medical emergencies for healthcare professionals, published online today in the journal CMAJ.

More and more people are travelling by plane each year, with approximately 2.75 billion passengers flying on commercial airlines annually, according to the authors. In Canada, there were 133.4 million airline passengers in 2015, a 27 per cent increase from 2009, they said.

This increase in patient traffic, along with longer flights that increase the stress of flying on the body and a greater proportion of older passengers and those with pre-existing medical conditions, have led to an increase in in-flight medical emergencies in recent years, according to the authors.

"Every health-care professional is likely to hear this call at some point while flying, but for most of us, treating patients on a plane is a completely unfamiliar scenario," said Dr. Alun Ackery, an emergency physician at St. Michael's Hospital and senior author of the recommendations. "We wanted to provide a better understanding of what to expect and how to respond if you're called to assist in one of these emergencies."

The recommendations, developed in collaboration with Air Canada and WestJet, provide an overview of the available medical equipment, the environmental challenges of treating patients on a plane, the airlines' policies and procedures as well as the legal and ethical duties of physicians to respond to a call for assistance.

Every plane with at least 100 passenger seats is legally required to carry a medical kit, according to Transport Canada. Although Transport Canada also outlines the minimal requirements the medical kit must contain, individual airlines have the flexibility to enhance the contents as they see fit, the authors said.

In a video accompanying the recommendations, the authors unpacked Air Canada's medical kit to help health-care professionals further understand what resources will be available during an in-flight emergency.

"Each airline's kit is going to look different, and the contents aren't always going to be familiar, which adds another layer of complexity to an already stressful situation," said Dr. David Kodama, an emergency resident at the University of Toronto and lead author of the recommendations.

In Canada, Quebec is the only province that imposes a legal duty on physicians to come to the assistance of a person in a life-threatening emergency, the authors said. All jurisdictions, however, have legislation that protects physicians who voluntarily provide emergency medical assistance at the scene of an accident or in an emergency, they said.

The Canadian Medical Association and the Canadian Medical Protective Association both suggest physicians have an ethical obligation to provide their best assistance during an emergency, according to the authors.

"We recognize that hearing the call go out for a physician on board a flight can be unexpected, but we do have an obligation to respond," said Dr. Ackery. "We hope these recommendations will provide healthcare professionals with enough knowledge to make that call a little bit less anxiety-provoking in the future."

A new study reveals that many patients with breast cancer have misconceptions and fears about radiation therapy, but their actual experiences with modern breast radiation therapy are better than they expected. In the study published early online in CANCER, a peer-reviewed journal of the American Cancer Society, most patients agreed that their initial negative impressions were unfounded.

Over the past 20 years, there have been significant advances in how radiation therapy for breast cancer is delivered, allowing clinicians to spare critical organs, create an individual radiation plan for each patient, and deliver radiation in more convenient schedules. Nonetheless, many patients have fears and misconceptions about radiation therapy.

To get a better sense of patients' views concerning modern radiation therapy, a team led by Susan McCloskey, MD, MSHS, and Narek Shaverdian, MD, of the University of California Los Angeles, surveyed 502 patients who were treated for breast cancer between 2012 and 2016. Among the 327 patients who responded to the survey, 83 percent underwent breast conservation therapy (defined as lumpectomy and radiation therapy).

"We wanted to look at the patients' perspective of the breast cancer radiation experience, to have tangible real-world data to guide future patients and providers in their decision making," said Dr. Shaverdian.

Sixty-eight percent of surveyed patients stated that they initially had little to no knowledge about radiation therapy; however, 47 percent reported that they had heard frightening stories about it. Only 2 percent of patients agreed that the negative stories they previously heard about radiation therapy were actually true. Also, 83 percent reported that short-term radiation side effects--such as breast pain, work limitations, and family disruptions--were less than or as expected, and 84 percent of patients said this about long-term side effects.

The survey revealed that 93 percent of breast conservation patients and 81 percent of mastectomy patients agreed with the statement "If future patients knew the real truth about radiation therapy, they would be less scared about treatment."

"The word radiation itself sounds frightening and is associated with many negative news stories, but the implications of this study are that, in actuality, radiation therapy for breast cancer is a much better treatment experience than perceived," said Dr. McCloskey. "We hope these real-world data from the voices of past patients can give future patients a better understanding of modern breast radiation therapy when making treatment decisions."

A new study, published in the Addiction journal, conducted by researchers from the University of Liverpool highlights the ineffectiveness of a specific drug treatment for alcohol use disorders.

Baclofen is a medication which has been used since the 1970s as an anti-spasticity treatment. More recently it has been used as a treatment for alcohol use disorders.

Baclofen has a key advantage compared with currently licensed medications: it is excreted largely through the kidneys. It is therefore possible to give baclofen to people suffering alcohol-related liver disease, a patient population with very high needs, and who often can't tolerate licensed drug treatments.

'Wonder drug'

Many studies have found baclofen to be successful in treating alcohol use disorders, some have claimed it a wonder drug capable of curing alcoholism.

Following a number of successful clinical trials the use of use of baclofen increased massively and sales of the drug have soared in some countries.

In more recent years, there have been a growing number of studies which directly compare baclofen against placebo on a number of outcome measures. Often these outcome measures are drink-related, e.g. rate of abstinence at the end of the medication trial, or number of heavy drinking or abstinent days during the trial.

However, there are other measures, potentially related to why baclofen might work (i.e. its mechanism of action). Several possibilities have been identified; firstly baclofen may reduce craving for alcohol, secondly there are reports that baclofen reduces negative mood states, such as anxiety and depression, which are known risk factors for harmful drinking.

Abstinent rates

Researchers, Dr Abi Rose and Dr Andy Jones, from the University's Addiction Research Team conducted a meta-analysis on all 12 clinical trials comparing baclofen with placebo on at least one of the described drinking outcomes, craving, anxiety, or depression.

Meta-analysis is an advanced statistical procedure that allows the researcher to merge the results of all the studies regarding a specific topic into a quantitative measure representing the size of the overall effect of one variable on another variable. Thus, meta-analysis provides more accurate and reliable outcomes compared to the single experiment.

The researchers found that baclofen led to higher abstinent rates compared with placebo, and that eight individuals would need to be treated with baclofen for one to remain abstinent due to the medication.

However, all other outcomes failed to show an effect of baclofen: baclofen did not increase abstinent days or decrease number of heavy drinking days during treatment, neither did it reduce rates of alcohol craving, anxiety or depression.

Issues highlighted

Dr Rose, said: "Our research highlights several issues with the existing body of trials. Many of the studies only recruited a limited number of patients, so maybe too small to find an effect.

"The existing trials also differ on a number of factors, such as the dose of baclofen given and the length of treatment. Importantly, the pharmacokinetics of baclofen (how it moves in the body) are not well-understood, so there may be individual factors influencing the effectiveness of baclofen that we do not yet understand."

Dr Jones, said: "This new meta-analysis shows that baclofen is no more effective than placebo on a range of key outcome measures, suggesting that the current increasing use of baclofen as a treatment for alcohol use disorders is premature."

Philadelphia, February 26, 2018 - Researchers at Massachusetts General Hospital and Harvard Medical School have developed a new method to extract valuable symptom information from doctors' notes, allowing them to capture the complexity of psychiatric disorders that is missed by traditional sources of clinical data. The study, published in Biological Psychiatry, was led by co-senior authors Tianxi Cai, Sc.D., and Roy H. Perlis, M.D. A second study published in Biological Psychiatry, also led by Dr. Perlis, applied the new method in a proof-of-concept study to identify genes associated with psychiatric symptoms.

"Many efforts to use clinical documentation in electronic health records for research aim to identify individual symptoms, like the presence or absence of psychosis," said Thomas McCoy Jr., M.D., co-first author with Sheng Yu, Ph.D. But this approach misses the complex overlap of symptoms between different mental disorders. "My co-authors and I developed a method that instead captures symptom dimensions, or sets of symptoms, informed by the National Institute of Mental Health Research Domain Criteria," continued Dr. McCoy.

The method extracts the relevant symptoms from the wealth of information in the detailed narrative notes taken by clinicians in patients' electronic health records. Dr. McCoy and colleagues used the method to characterize 3,619 adults with psychiatric hospitalizations across a range of disorders, including schizophrenia, anxiety, major depressive disorder, and posttraumatic stress disorder.

Characterizing the patients based on symptom dimensions could predict the length of hospital stay and time to hospital readmission better than the use of more structured data alone, such as health billing information, that is based on the categorization of disorders. The symptom dimensions were also associated with scoring of notes by expert clinicians and with neurocognitive testing, validating the results.

The idea of symptom domains rather than disease categories also extends to the neurobiology of mental illness. "The recognition that the genetic basis of psychiatric illness crosses traditional boundaries has encouraged efforts to understand psychopathology according to dimensions, rather than simply presence or absence of symptoms," said Dr. McCoy.

In the second study, Dr. McCoy and colleagues demonstrated the application of this new method to examine the association between symptom dimensions and common genetic variation in psychiatric disease. They compared the information on the symptom dimensions extracted from the narrative hospital discharge notes of 4,687 adults with the patients' genomic information. The researchers identified four areas of interest, or loci, in the genome, highlighting two genes which have not previously been identified with existing methods.

"The ability to combine large DNA data sets with meaningful psychiatric information from the electronic health record is an important step in facilitating large scale medical genetics research in psychiatry," said John Krystal, M.D., Editor of Biological Psychiatry.

The authors suggest that the method offers a new approach to understand brain function in mental illness. Other researchers can apply the method to different sets of patients with hospital-linked genomic records, and identification of the same loci would strengthen the support for their role in psychiatric symptoms.

"We are making the scoring software freely available and hope this work will enable transdiagnostic dimensional phenotypes to be used in efforts to achieve precision psychiatry," said Dr. McCoy.

A new Arthritis Care & Research study found that moderate-to-vigorous physical activity levels are similarly low in older adults with symptomatic knee osteoarthritis and those from the general population without osteoarthritis or knee pain.

Because the general population is doing as little as individuals with knee pain that may hinder activity, the findings point to the need for efforts to increase physical activity for all.

"We were a little surprised to see similar low levels of physical activity in both those with and without painful knee arthritis. I think this is a wake-up call to everyone that we all need to be doing more activity," said senior author Dr. Daniel White, of the University of Delaware.

Long-term results from a BJU International study indicate that tension-free vaginal tape (TVT) may be a highly effective and safe option for certain patients with urinary incontinence.

In TVT surgery, a mesh tape is placed under the urethra to keep it in its normal position, so that when a person coughs or moves suddenly, the urethra can remain closed with no accidental release of urine.

At 17 years after surgery, 41 of 46 women (89.1%) who underwent TVT implantation declared themselves cured. Similarly, 42 of the 46 women (91.4%) were objectively cured, as determined by clinical tests.

Still's disease is a serious orphan disease manifested by high fevers, skin and joint involvement, including paralysis, as well as damage to other organs such as the liver or spleen. It is caused by a deregulation of the immune system triggering an acute inflammatory response. Under the auspices of the University of Geneva (UNIGE) and Geneva University Hospitals (HUG), an international team has successfully tested a molecule inhibitor of interleukin-18, a protein involved in immune response. These encouraging results in terms of safety and efficacy are paving the way for a new kind of treatment, not only for Still's disease, but other rare inflammatory diseases, too. Recently, a baby's life was saved after the drug was administered as a last resort. Read the study in the specialist journal Annals of the Rheumatic Diseases.

In its adult form, Still's disease affects about 1 in 100,000 people each year, with its infantile form being ten times more common. This rare condition can take different forms: monocyclic, polycyclic or chronic, leading to attacks on several organs that may threaten the quality of life - or even life - of those affected. While the cause is still unknown, genetic factors have been identified in other, similar syndromes. Cem Gabay, a professor at UNIGE's Faculty of Medicine and Head of the HUG Rheumatology Department, is one of the world's leading specialists in these complex diseases and part of a European consortium whose aim is to better understand the causes and pathology of these inflammatory conditions.

An immune system disorder

Cytokines are small proteins involved in cell-to-cell interactions, whose role in triggering certain diseases is now becoming clear. One of them, interleukin-18 (IL-18), specialises in immune and inflammatory responses. "Recently, we successfully demonstrated the key role of IL-18 in Still's disease", says Professor Gabay. Patients with the condition have a very high level of this protein, correlating with the acute phases of the disease, and this rate fluctuates according to the inflammatory activity specific to this disease. "Our idea was therefore to block the harmful action. It is also worth pointing out that the treatments currently offered to patients are very empirical, so our goal was to finally give them a safe and approved treatment", he explains.

While IL-18 is useful for protecting the body against external pathogens, too much of this protein leads to a harmful overactivation of the immune system, resulting in the various symptoms presented in patients. There is a naturally occurring inhibitor ("IL-18 binding protein"), whose function is to bind to IL-18 to form an inactive complex, but people with Still's disease produce more IL-18 than its inhibitor, which triggers their symptoms.

Reusing an existing molecule

A few years ago, a pharmaceutical company developed an injectable form of the IL-18 inhibitor, with the idea of offering treatment to combat rheumatoid arthritis and psoriasis. The tests proved inconclusive and the formula abandoned. "So we bought the rights to the drug and started working with Professor Gabay to assess its safety and efficacy in a clinical trial", explains Andrew Sleight, CEO of AB2 Bio Ltd., the Lake Geneva startup that has the World Wide license of the drug.

The main objective of this study was to verify the safety of the drug and to confirm its efficacy on the clinical manifestations of the disease. Twenty-three patients, mostly suffering from forms of the condition that are particularly refractory to the usual treatments, were enrolled and divided into two groups: one receiving 80 mg, and the other 160 mg, via three subcutaneous injections per week for 12 weeks. Professor Gabay summarises the results: "We were initially reassured by the safety profile: there were very few serious side effects, only one of which was possibly related to the drug itself. In addition, 50% of patients in both treatment groups showed a positive response to the drug after three weeks of treatment, and their symptoms decreased over the entire 12 weeks of follow-up. In contrast, patients who didn't have a positive 80 mg response did not have one with 160 mg either. These first results are extremely encouraging and mean we can plan a phase 3 trial to better evaluate the effectiveness of the drug." Researchers are currently in phase 2, which aims to ensure the safety of the product and to determine the optimal dose. Phase 3, the next step envisaged by Professor Gabay's team together with AB2 Bio Ltd., will aim to assess the actual efficacy of the drug.

Potential treatment of other orphan diseases

Patients with other orphan diseases associated with dysregulated production of IL-18 and its inhibitor, for which there is no effective treatment protocol, could also benefit from these results. In 2015, the life of a three-month-old girl was saved. Professor Gabay tells us what happened: "This child, who lives in the United States, had a rare inflammatory disease that was resistant to all treatment; she was in intensive care, and was going to die. Alerted by our American colleagues, we worked with AB2 Bio Ltd. to determine what dose she should be given. The Food and Drug Administration granted permission to use the drug in a last-ditch attempt to halt the disease. She rapidly responded to treatment and is now 3 years old, well and can lead a normal life with IL-18 inhibitor therapy. A glimmer of hope for other patients!"

A new Ultrasound in Obstetrics & Gynecology study provides evidence that pregnant women with hypertension can safely monitor their blood pressure at home instead of going into a hospital or clinic. This reduces the number of hospital visits without compromising their health of the health of their babies.

The study included 108 women who were taught how to measure and record their blood pressure using a validated machine at home. A control group of 58 women was monitored in a clinic. There were no differences in adverse maternal, fetal, or neonatal outcomes.

"It is time to use existing technology in order to improve the way we look after pregnant women. Supported by both quantitative and qualitative research data, Home Monitoring of Hypertension in Pregnancy has proven very popular and is likely to be safe and cost saving," said senior author Prof. Asma Khalil, of St. George's University Hospitals NHS Foundation Trust, in London. "It is important to acknowledge that more studies are needed to establish safety for rare pregnancy complications and various aspects of its implementation in different healthcare settings."

Home Monitoring of Hypertension in Pregnancy has been selected to join the NHS Innovation Accelerator programme, which is supported by NHS England, Academic Health Science Networks, and University College London Partners.

In 1996, California became the first US state to legalise marijuana use for medical purposes. Medical marijuana is now legal in 29 states. Opponents of medical marijuana argue that such laws increase recreational marijuana use among adolescents, while advocates contend that medical marijuana helps to address the US opioid crisis by reducing overdose deaths.

Two papers published today in the scientific journal Addiction look at the current evidence of the effects of medical marijuana laws and conclude that there is little support for either claim.

The first claim, that legalizing medical marijuana increases recreational use among adolescents, is addressed by a new meta-analysis that pooled the results of eleven separate studies of data from four large-scale US surveys dating back as far as 1991. Results of the meta-analysis indicate that no significant changes (increases or decreases) occurred in adolescent recreational use following enactment of medical marijuana laws. Far fewer studies examined the effects of medical marijuana laws among adults, although existing evidence suggests that adult recreational use may increase after medical marijuana laws are passed

Senior author Professor Deborah Hasin says, "Although we found no significant effect on adolescent marijuana use, we may find that the situation changes as commercialized markets for medical marijuana develop and expand, and as states legalize recreational marijuana use. However, for now, there appears to be no basis for the argument that legalising medical marijuana increases teens' use of the drug."

The second claim, that legalising medical marijuana reduces opioid overdose deaths by offering a less risky method of pain management, is addressed in an editorial co-authored by several members of Addiction's editorial board. Here, the evidence is clear but weak, being rooted in ecological studies whose results have not been confirmed through more rigorous methods. Although those studies show a correlation over time between the passage of medical marijuana laws and opioid overdose death rates, they do not provide any evidence that the laws caused the reduction in deaths. In fact, several recent studies have shown that chronic pain patients who use cannabis do not use lower doses of opioids. There are more plausible reasons for the reduction in opioid deaths that ought to be investigated.

INDIANAPOLIS -- Beetroot juice supplements may help enhance exercise capacity in patients with heart failure, according to a new proof-of-concept study. Exercise capacity is a key factor linked to these patients' quality of life and even survival.

The study examined the impact of dietary nitrate in the form of beetroot juice supplements on the exercise capacity of eight heart failure patients with reduced ejection fraction, a condition in which the heart muscle doesn't contract effectively and can't get enough oxygen-rich blood to the body.

Tens of millions of people suffer from heart failure. In about half of all such people, the ejection fraction of the heart is reduced.

Because of their condition, these patients exhibit labored breathing, have diminished peak oxygen uptake and use more energy while exercising than would otherwise be the case.

Researchers found that the beetroot supplement resulted in significant increases in exercise duration, peak power and peak oxygen uptake while exercising.

Those improvements were not accompanied by any changes in the breathing responses of the patients, and there was no change in their exercise efficiency, a measure of how much external work a person gets for a certain input of energy.

The study, titled "Dietary Nitrate Increases V02 peak and Performance but Does Not Alter Ventilation or Efficiency in Patients with Heart Failure with Reduced Ejection Fraction," was published in the Journal of Cardiac Failure.

"Abnormalities in aerobic exercise responses play a major role in the disability, loss of independence and reduced quality of life that accompany heart failure," said Andrew Coggan, an associate professor in the Department of Kinesiology in the School of Physical Education and Tourism Management at IUPUI and one of the researchers who conducted the study. "Perhaps more importantly, elevations in ventilatory demand and decreases in peak oxygen uptake are highly predictive of mortality in patients with heart failure."

A second important aspect of the study is there were no untoward side effects from the dietary nitrate, Coggan said: "In this case, lack of any significant changes is good news."

The data suggests that dietary supplementation may be a valuable addition to treatment for exercise intolerance among heart failure patients with reduced ejection fraction, Coggan said. Multi-center trials are needed to confirm the proof-of-concept findings and to determine whether longer-term dietary nitrate treatment improves physical activity levels, quality of life and perhaps even survival in patients with heart failure with reduced ejection fraction.

While type 2 diabetes (T2D) was once considered a disease largely confined to older people, the global epidemic of obesity and overweight has seen diagnoses rocket in young adults, adolescents and even appear in young children. New research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that the earlier a person is diagnosed with T2D, the higher their risk of death from heart disease and stroke, but, unusually, the lower their risk of death from cancer.

In almost all countries of the world, diabetes rates are increasing substantially in younger adults, aged 20-45 years. Rates are also continuing to increase in adults over 45 years old, however not as sharply as in younger adults. The increase in the younger adults means there is a steadily growing pool of diabetes patients who are exposed to diabetes for a longer period in their lives.

The study by Professor Dianna Magliano and Professor Jonathan Shaw (Baker Heart and Diabetes Institute, Melbourne, Australia) and colleagues analysed the data of 743,709 Australians with T2D who were registered on Australia's National Diabetes Services Scheme (NDSS) over a 15-year period between 1997 and 2011. All-cause mortality and mortality due to cardiovascular disease (CVD), cancer and all other causes were identified.

The average (median) age at T2D diagnosis was 59 years, and a total of 115,363 deaths occurred during the study period. The authors say: "An earlier diagnosis of type 2 diabetes -- and thus a longer duration of disease -- was associated with a higher risk of all-cause mortality, primarily driven by cardiovascular disease (CVD) mortality."

The data showed that for two people of the same age, the one with a 10-year earlier diagnosis (equivalent to 10 years' longer duration of diabetes) had a 20% to 30% increased risk of all-cause mortality and about a 60% increased risk of CVD mortality. The effects were similar in men and women.

authors say: "Evidence is accumulating to suggest that earlier onset of type 2 diabetes is associated with an increased risk of complications and comorbidities compared with later onset, and that the development and progression of complications might be more aggressive in those with earlier onset."

They add: "As such, increased clinical attention is imperative for individuals with earlier-onset type 2 diabetes. Efforts should focus on timely optimisation of individuals' self-management skills and medical treatment to prevent or reduce the onset of complications and comorbidities. Additionally, there is a need to identify and screen those at high risk of developing diabetes so that individuals can make lifestyle changes that will prevent or delay the onset of diabetes."

Other interesting findings from the study by Professors Magliano, Shaw and colleagues include that for mortality due to cancer (all cancers and colorectal and lung cancers), earlier diagnosis of type 2 diabetes was associated with lower mortality compared with diagnosis at an older age. While this may appear unusual, the authors point out that "it is possible that following a diagnosis of diabetes, people have more frequent contact with the healthcare system, which may increase the likelihood of any present but undiagnosed cancer being detected."

ORLANDO, Fla. (February 21, 2018) - Pediatric and adult cancers with one of three fusion genes responds well to a new drug, larotrectinib, according to a study published today in the New England Journal of Medicine. The drug is designed to target a specific tumor gene mutation known as tropomyosin receptor kinases (TRK) that can occur in various tumor types.

"This drug represents a changing paradigm in cancer care where we evaluate a tumor, not only by where it exists in the body, but by the genetic mutations that are driving its growth," said Ramamoorthy Nagasubramanian, MD, an author of the study and division chief of pediatric hematology-oncology at Nemours Children's Hospital.

The study integrates findings of three phases of research, including an adult phase 1, a pediatric phase 1/2, and an adolescent/adult phase 2 study, to report on the safety and efficacy of the drug. Fifty-five patients with TRK fusion-positive cancers, detected by molecular profiling as routinely performed by each site, were enrolled across the study sites. Patients ranged in age from 4 months to 76 years old and had 17 unique cancer diagnoses, including infantile fibrosarcoma, salivary gland tumors, and thyroid cancer. Each patient received two daily doses of the drug in pill or liquid form.

Overall 75 percent of patients had their tumors respond to the treatment, with 13 percent achieving a complete response and 62 percent achieving a partial response. Responding patients remained on treatment or underwent surgery with curative intent. The median time to response was 1.8 months (range 0.9 to 6.4). The median duration of response and progression-free survival had not been reached, but after one year, 71 percent of patients with a response were ongoing and 55 percent of all patients remained progression-free. The treatment was well-tolerated by patients. Clinically significant adverse events were uncommon and most frequently included inflammation in the liver and other organs (alanine or aspartate aminotransferase increase), fatigue, vomiting, and dizziness.

"This study's design, simultaneously testing the efficacy and safety in adults and children, represents a strong model to follow to help advance pediatric cancer research," said Nagasubramanian. "In an era where we are not only treating tumors by names, but by their genetic signature, this research allows us to move the field forward without leaving children behind, as is so often the case in pediatric research."

The study authors note that additional data reflecting longer follow-up and a larger patient population will provide further insight into the safety profile of the drug, as well as the durability of the response.

CORVALLIS, Ore. - Midwife-friendly laws and regulations tend to coincide with lower rates of premature births, cesarean deliveries and newborn deaths, according to a new U.S.-wide "report card" that ranks all 50 states on the quality of their maternity care.

The first-of-its-kind study found a strong connection between the role of midwives in the health care system - what the researchers call "midwifery integration" - and birth outcomes. States with high midwifery integration, like Washington and Oregon, generally had better results, while states with the least integration, primarily in the Midwest and South, tended to do worse. The findings were published today in the journal PLOS ONE.

"Our findings suggest that in states where families have greater access to midwifery care that is well integrated into the maternity system, mothers and babies tend to experience improved outcomes. The converse was also demonstrated; where integration of midwives is poorer, so are outcomes," said Melissa Cheyney, a licensed midwife, medical anthropologist and associate professor in Oregon State University's College of Liberal Arts and one of the study's co-authors.

As with most population health studies, the statistical association between the role of midwives and birth outcomes doesn't prove a cause-and-effect relationship. Other factors, especially race, loom larger, with African-Americans experiencing a disproportionate share of negative outcomes. However, almost 12 percent of the variation in neonatal death across the U.S. is attributable solely to how much of a part midwives play in each state's health care system.

"In communities in the U.S. that are underserved - where the health system is often stretched thin - this study suggests that expanding access to midwifery is a critical strategy for improving maternal and neonatal health outcomes," said Saraswathi Vedam, an associate professor in the Department of Family Practice at the University of British Columbia, who led the team of U.S. epidemiology and health policy researchers responsible for the study.

About 10 percent of U.S. births involve midwives, far behind other industrialized countries, where midwives participate in half or more of all deliveries. Each state has its own laws and regulations on midwives' credentialing, their ability to provide services at a client's home or at birth centers, their authority to prescribe medication and the degree to which they are reimbursed by Medicaid.

"A large body of cross-cultural research has actually demonstrated similar relationships between midwifery care, systems integration and improved maternity care outcomes," Cheyney said. "This study is important because it suggests that the same relationships hold true in the United States. There are significant policy implications stemming from this work."

The research team created a midwifery integration score based on 50 criteria covering those and other factors that determine midwives' availability, scope of practice and acceptance by other health care providers in each state.

Washington had the highest integration score, 61 out of a possible 100, followed by New Mexico at 59 and Oregon at 58. North Carolina had the lowest score, 17. The complete list, with links to each state's report card, is available online at http://www.birthplacelab.org/how-does-your-state-rank/.

An interactive map created by the researchers reveals two clusters of higher midwifery integration - one swath stretching from the Pacific Northwest to the Southwest, and a cluster of Northeastern states.

Vermont, Maine, Alaska and Oregon had the highest density of midwives, as measured by the number of midwives per 1,000 births. The lowest midwifery integration was in the Midwest and Deep South.

The study used higher rates of vaginal birth and breastfeeding as positive maternity care outcomes. Higher rates of caesarean birth, premature births, low birth weight and newborn deaths were indicators of poor outcomes.

The Deep South, which not only had lower integration scores, but also higher rates of African American births, had the worst rates of premature birth, low birth weight and newborn mortality. The West Coast states of California, Oregon and Washington consistently scored well on those measures.