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Regular injections of a cholesterol-cutting drug could reduce the risk of heart attack or stroke in patients with diabetes and who have had a recent heart attack.

The findings come from a trial of almost 19,000 patients with a recent heart attack or unstable angina and who were already taking the highest doses of cholesterol-lowering medication statins.

Researchers found that patients taking an additional twice-monthly injection of another type of cholesterol-lowering drug, called alirocumab, further cut their cholesterol levels significantly and reduced their risk of having another heart attack.

The scientists behind the latest analysis - led by researchers at Imperial College London - say that alirocumab could provide more benefit to patients with diabetes, compared to those without diabetes, following a recent heart attack.

High levels of low-density lipoprotein (LDL) cholesterol (so-called 'bad' cholesterol) in the blood are a known risk factor for cardiovascular disease. But patients with diabetes are at twice the risk of cardiovascular events, such as a heart attack or stroke, due to damage to the heart and blood vessels. The researchers say that the injections reduce this risk by further lowering their levels of LDL cholesterol.

Their findings, published in the journal Lancet Diabetes & Endocrinology, could inform current guidelines for use of cholesterol-lowering medications, potentially advocating more aggressive cholesterol reduction in those with diabetes after a heart attack.

As an estimated one third of heart attack patients have diabetes, the researchers say these patients are a common and easily recognisable group who would benefit from achieving even lower cholesterol levels from this injectable treatment.

Alirocumab is a monoclonal antibody licensed for patients throughout the world. It is part of a class of cholesterol-lowering drugs called the PCSK9 inhibitors. The drug is delivered by injection every two weeks and works by blocking the action of a key enzyme in the liver to reduce LDL cholesterol levels in the blood.

Previous research has shown that alirocumab is safe and effective at reducing LDL cholesterol levels, without increasing the risk of diabetes.

However, PCSK9 inhibitors are more expensive than other cholesterol-lowering drugs, such as statins, and cost an estimated £4000 per patient per year in the UK, so their use is restricted to patients with the highest levels of LDL cholesterol. Doctors are therefore considering who would benefit most from this class of drugs.

Professor Kausik Ray, Chair in Public Health (clinical) at Imperial College London, and first author of the study, explained: "Cholesterol-lowering injections, such as alirocumab, are effective but they are expensive, so we need to consider targeting them to where they will have the most impact. Diabetes patients make up about one third of all heart attacks and these patients have roughly twice the risk as those without diabetes.

"In this study, we found that alirocumab had greater reduction in risk for patients with diabetes compared to those without. People with diabetes who have recently had a heart attack and who have high LDL cholesterol, despite statins, are an easily identifiable and cost-effective group to think about giving these treatments to."

In the latest study, 18,924 patients recruited in 57 countries were classified into three groups: having diabetes; having pre-diabetes (higher than normal blood sugar); or normoglycaemia (healthy blood sugar levels).

All patients had previously been hospitalised due to a 'cardiac event' (heart attack, unstable angina - chest pains caused by poor blood flow to the heart at rest) and all patients were randomised to receive either alirocumab or placebo every two weeks, on top of their existing high-intensity statins.

The distribution of patients in the trial was similar to earlier studies, with diabetes or prediabetes making up approximately 70 per cent of the cohort. Whether a patient had diabetes or not did not influence their LDL cholesterol levels at the start of the trial, or during the treatment period (when they received either alirocumab or placebo).

Four months into the trial, LDL cholesterol levels in patients taking alirocumab were reduced to an average of 0.8 mmol/L (for diabetes, pre-diabetes and normoglycaemia) compared to those taking placebo - who had LDL levels of 2.25 mmol/L in patients with diabetes and prediabetes, and 2.28 mmol/L in the normoglycaemia group. By comparison, the NHS advises a healthy adult should have an LDL level of 3 mmol/L and 2 mmol/L or less for those at high risk such as those who have had a heart attack.

After an average follow up period of 2.8 years, the team found that alirocumab was equally effective in reducing risk across the three groups but because people with diabetes were at highest risk they gained bigger absolute benefits. Analysis revealed that for diabetes patients, in absolute terms, treatment with alirocumab reduced their risk of further cardiovascular events by an average of 2.3 per cent.

Following a heart attack, the number of diabetes patients that needed to be treated was 43 for 2.8 years to prevent one event, versus 82 for those without diabetes.

While reducing blood cholesterol has proven benefits for cardiovascular health, there has been some uncertainty regarding whether achieving very low levels of LDL cholesterol increases the risk of diabetes. The researchers say the current study, amongst almost 19,000 patients including more than 5000 people with more than three years of follow up, shows there was no increased risk of diabetes with alirocumab.

CLEVELAND - An international collaboration of infectious disease experts has identified a large group of people who appear to have naturally mounted an immune response to TB, a bacterial infection that is the leading cause of infectious disease death worldwide. Nearly 200 people from 2500 households with active TB were clearly exposed to TB for more than 10 years but the two most reliable tests (TST and IGRA) came back negative on repeated tests.

"Further research is needed, but it seems that either the tests are not sufficiently sensitive to detect a low-level case of TB or some people are mounting a natural defense, which is what we believe is happening," said W. Henry Boom, MD, Division Chief of Infectious Disease and HIV Medicine at University Hospitals (UH) Cleveland Medical Center and Case Western Reserve University (CWRU) School of Medicine.

Boom was a co-author of the research published May 20 in Nature Medicine. He was joined in that research by Catherine M. Stein, PhD, of the Department of Population & Quantitative Health Sciences at CWRU School of Medicine. The study also included colleagues from the Uganda-CWRU Research Collaboration clinic, Makerere University in Uganda, the University of Washington, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University.

"TB remains the leading infectious cause of death worldwide, and for that reason, these findings about natural defenses by a significant sample - eight percent - of people exposed to TB over more than 10 years is eye-opening," said Dr. Boom. "This may point us to a signature among people who appear to be naturally immune that could inform vaccine development." said Dr. Boom.

"It also is possible that we need to reconsider the standard TB tests to take into consideration for very low level cases of TB," he continued. "Clearly, we need to investigate further, as the imperative to find prevention, treatment and cure for TB is pressing."

The study looked at more than 2500 households in Uganda that had individuals with active TB. The researchers found 198 individuals (8.2 percent) who lived in these households for more than 10 years but who never tested positive on the Tuberculin Skin Test (TST, developed in 1886) or the more modern blood test interferon-gamma release assay (IGRA). This meant they were either "resistant" to the Mtb infection or not being detected by the two standard tests.

"We found through molecular profiling of these individuals that they had been exposed to the bacteria," said Dr. Boom. "They had likely been infected, but did not exhibit signs or symptoms of Mtb infection and the tests were standard tests were negative. We assume that they mounted a natural immune response, but need to explore further.

A team of researchers from UCLA and the University of Toronto have identified a new biomarker found in urine that can help detect aggressive prostate cancer, potentially saving hundreds of thousands of men each year from undergoing unnecessary surgeries and radiotherapy treatments.

Prostate cancer can be easy to diagnose, but classifying patients into risk groups has been challenging. Current tools, which include PSA tests and biopsies, have high error rates and can cause severe health complications such as life-threatening infections. Testing for biomarkers in urine is noninvasive and accurately helps to distinguish slow growing cancers from potentially life-threatening ones.

Under current screening tools, about 25% to 40% of men are diagnosed with clinically insignificant disease, meaning the prostate cancer is slow growing and would most likely not have any significant damaging health effects. Yet, these men often still get treated, which leads to major costs for both the individual and the health care system. An additional 20% to 35% of men with prostate cancer diagnoses don't get enough treatment, and often suffer relapse of the disease.

"We currently do not have accurate biomarkers to help determine the aggressiveness of prostate cancer that are not invasive," said Paul Boutros, director of cancer data science for the UCLA Jonsson Comprehensive Cancer and senior author of the study.

The standard clinical care to determine whether someone has prostate cancer is to undergo a biopsy procedure. A needle is inserted into the prostate and a tiny piece of the prostate tissue, both normal and tumor cells, are removed. But that's invasive and brings all sorts of clinical risks, Boutros said. Another way to detect prostate cancer is with a blood draw, which is less invasive but not always accurate. The easiest way to evaluate the prostate is to take a sample of the urine, since the prostate will always be shedding things into the urine as part of its natural biology, Boutros said.

Through a multidisciplinary team, the researchers were able to identify a biomarker using the microRNA in urine, which may give physicians insight into how far a tumor has spread and how it may best be treated. These small pieces of RNA that were used to develop the biomarker are involved in prostate cancer development and progression; influence how men respond to treatment; and are detectable in urine, making this detection tool a promising noninvasive option.

"We developed a three-stage experimental strategy that would maximize statistical and data science considerations to give us the best chance of finding a biomarker to predict prostate cancer aggressiveness," said Boutros, who is also a professor of urology and human genetics at the David Geffen School of Medicine at UCLA.

To test the noninvasive application, the team worked with 149 men to create and validate a biomarker to show that it works well and could be used to predict the likelihood of an aggressive prostate cancer. Participants in the study were evaluated for at least three years, allowing researchers to fully understand how their cancer changed over time.

"Being able to go beyond just a snapshot in time is critical because you are able to focus in on the trends that are associated with the cancer, which is really the most important thing to distinguish in order to develop an accurate biomarker," Boutros said.

The team found the biomarker was successful in identifying high-risk individuals and it achieved similar accuracy as compared with the invasive tissue-based tests. In the study, the test accurately identified 80% of aggressive cancers. The researchers estimate that about 50% of treatments were unnecessary and could have been avoided by using the noninvasive test.

"What this test does is gives the clinician, the patient and their caregivers confidence in their treatment plan," Boutros said.

The study was published in the Journal of the National Cancer Institute.

Dr. Jouhyun Jeon from the Ontario Institute for Cancer Research is the study's first author. Nineteen other authors contributed to this study and are listed in the journal article.

ANN ARBOR--Indwelling devices like catheters cause roughly 25% of hospital infections, but ongoing efforts to reduce catheter use and misuse haven't succeeded as much as health care workers would like.

But most problems with catheter use stem from poor physician-nurse communication, according to a new University of Michigan study.

Milisa Manojlovich, a professor at the U-M School of Nursing, says the bigger picture underscores a more disturbing problem: Even routine patient care such as catheter use can cause serious problems for patients if communication breaks down among health care workers.

"Even those mundane, simple things can have unintended consequences way beyond their scope," she said. "People get catheters all the time, but meanwhile they cause lots of harm so we need to talk about them. This study found a whole host of factors that affected the ability to discuss this issue."

Manojlovich and colleagues interviewed a small group of nurses, physician assistants, nurse practitioners and physicians about problems monitoring and communicating among their teams about patients' indwelling catheters.

All respondents said poor communication delayed removal of unnecessary catheters. Communication broke down for various reasons and on many levels: poor relationships between doctors and nurses, hierarchical differences or misalignment of workflows that prevented nurses from being present for daily rounds (when surgeons and health care teams review patient care plans).

Catheters are hidden beneath blankets, so physicians don't automatically know who's using one--especially if a nurse isn't there to point it out.

Often, catheters remain in too long, which can cause infection, or they aren't necessary at all. It's estimated that 60% to 90% of intensive care patients, and 10% to 30% outside the ICU have urinary catheters, according to the study.

"Any foreign object in the body carries an infection risk, and a catheter can serve as a superhighway for bacteria to enter the bloodstream or body," Manojlovich said.

Electronic health records also cause confusion--sometimes nurses and doctors have different information, or there's a lag updating charts, or a reliance on both paper and computer records causes problems, she says.

Research shows that some patients and caregivers request catheters, believing they're preferable to getting up to use the toilet, Manojlovich said. However, they should understand that catheters bring risk of infection, and non-infection risks such as pain, trauma or bleeding, and should talk to their nurse or physician about complications.

Precision medicine represents a revolution in health care. Doctors and researchers may soon be able to use the genetic profiles of patients to predict with great accuracy which treatment and prevention protocols will work for them.

The opportunities are staggering, but for all its promise, precision, or personalized, medicine is poised to create new inequities. That's because the individuals who have contributed DNA to population biobanks for medical research are disproportionately white.

Sandra Soo-Jin Lee, an anthropologist and bioethicist who leads the newly launched Division of Ethics in the Department of Medical Humanities and Ethics at Columbia University Irving Medical Center, says that to improve medical care researchers need more data about the individual differences that make each of us unique.

Lee is the lead principal investigator of a multi-institutional study designed to understand the barriers to minority group participation and to support the creation of policies and approaches that will help build a diverse genetic database. The four-year, $2.8 million study, funded by the National Human Genome Research Institute, will analyze diversity and inclusion practices at academic medical centers located across the United States. The centers are based California, Alabama, Texas, Mississippi and in New York.

"Without engaging underrepresented communities in genetic studies, efforts to move precision science forward may recapitulate ongoing inequities in health care and limit and bias the research," Lee says. "The early stages of precision medicine offer a critical window in which to intervene before research practices and their consequences become locked in."
(Read Lee's June 7 article in Science Magazine: "Ethics on Inclusion: Cultivate Trust in Precision Medicine" science.sciencemag.org/content/364/6444/941.abstract

Precision medicine relies on the collection of biospecimens, electronic records and other sources of behavioral and environmental data, Lee says. Diseases can present differently among ethnic groups. They may, for example, appear at an earlier age, or they may progress more rapidly or respond disparately to treatment.

The Columbia study will explore how these centers recruit participants and collect, measure and share data. It will also examine how they communicate the findings of their research. "We are looking to see if there are unintended consequences that would limit researchers' ability to meet diversity recruitment goals, address social and biological causes of health disparities, and distribute the benefits of precision medicine equitably," Lee says.

One group being studied is the All of Us Research program, which includes Columbia University Irving Medical Center in partnership with Weill Cornell Medicine, NYC Health + Hospitals/Harlem and NewYork-Presbyterian. The Columbia-led program is part of an ambitious National Institutes of Health initiative that aims to recruit 1 million people throughout the United States over the next decade. Its goal is to create one of the world's most demographically diverse biobanks that would reflect the entire nation--young and old, healthy and sick, urban and rural, as well as people from all different ethnic and racial backgrounds.

Lee warns that building a diverse genetic database may prove challenging, however. "There is a long history of racial discrimination and exploitation in medical research," she says. "Questions about trust loom large."

Mistrust of the medical establishment lingers in ethnic minority communities, who remember incidents like the infamous Tuskegee Experiment, in which the U.S. Health Service infected black men with syphilis without their knowledge to study the disease. More recently, the African Americans have watched white supremacists invoke genetic research to claim racial superiority.

Lee stresses that, as a result, recruiting for diverse participation alone is not nearly enough. "An ethics of inclusion demands transparency and a culture of openness," she says. "Precision medicine studies must open themselves up to multidisciplinary teams that include social scientists, ethicists and policymakers who can identify and implement practices that respect the histories and concern of diverse populations-and recognize where reform is needed."

Aquatic organisms in marine systems and freshwaters are threatened by fungal and fungal-like diseases globally. These pathogens are especially dreaded in aquaculture. But they also pose a threat to biodiversity of amphibians. There are few approved chemical means for combating these pathogens, and many have unwanted side-effects. Scientists at the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB) now propose alternative biological concepts to control fungal disease in a more environmentally friendly way.

Some fungal and fungal-like diseases produce small infectious stages - zoospores - that swim in water to look for new hosts. They can infest fish, amphibians but also algae and seaweeds that are produced for human consumption. "The damage caused by these diseases is considerable. Few chemicals are approved for prophylaxis, but are expensive, harmful to the environment and often ineffective on the long run - which makes proper application very difficult, especially when used in species protection," says Dr. Thijs Frenken, lead author of the study, describing the problem.

80 million tons of global fish productions come from aquaculture, and its share in human protein diet is expected to increase. Diseases are the largest cause of economic losses in aquaculture. At least ten percent of all hatched salmon in the aquaculture industry succumb to zoosporic diseases. On Scottish salmon farms alone, for example, infections with this fungal disease lead to production losses of at least 6.5 million US dollars per year. Efficient and sustainable ways of controlling fish diseases are therefore paramount to the future success (and economic viability) of the aquaculture industry. "We have to go back to the basics and start applying our ecological understanding of these organisms to limit spread of infections," specifies Frenken.

The researchers propose 7 biological concepts for the protection of aquatic organisms against zoosporic diseases, which may be less harmful and more sustainable than chemical methods:

1. Prevent or reduce transmission (control of distribution pathways and vectors): Animal and plant species can spread pathogens. Close contact between different populations, for instance by migrations, can increase risk of spreading pathogens.

2. Increase the diversity of host species: The so-called monoculture effect applies - genetically homogeneous populations are more susceptible to infectious agents. Making host populations/communities more diverse can limit spread of infections.

3. Vaccination and immunisation: Vaccinating fish against viral or bacterial diseases is a common practice in aquaculture. No vaccines against fungal-like diseases currently exist, but this could be a promising avenue.

4. Stimulate defense and production of anti-fungal peptides by the host: When parasitic pathogens enter the host, host cells die and peptides are released. These signalling substances induce an increased immune defence in the neighbouring cells.

5. Probiotics: They can inhibit growth of parasitic zoospores, and also can prevent attachment of zoospores to the host by forming surface-active substances. Probiotics have already been successfully tested in fish as a treatment for zoosporic infections.

6. Hyperparasitism: Introduce another parasite that infects (and eliminates) the target parasite.

7. Use "parasite eaters": Eating parasites is very common practice in nature. Other microscopic organisms in the water (zooplankton), for example, can "graze" on parasitic fungi.

"The constantly changing environmental conditions have a great influence on the parasite-host interaction. These dynamics must also be incorporated into the planning of protection and therapy concepts. We hope that our work will stimulate the further development of alternative biological control strategies. Much more work is needed before we can safely implement these methods into natural habitats without incurring unforeseen risks," emphasizes IGB researcher and head of the study, Prof. Dr. Justyna Wolinska.

Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.

Using data from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial led by Flinders University, the new study has found a significant decrease in cases of depression after patients received CPAP treatment for their sleep apnea.

This is by far the largest trial of its type and one of very few studies reporting such an effect, says Professor Doug McEvoy from Flinders University.

From detailed analysis of the SAVE data, Flinders University experts and collaborators at the George Institute have found that CPAP for moderate-severe OSA in patients with cardiovascular disease has broader benefits in terms of preventing depression, independent of improved sleepiness.

Prior studies investigating the effect of CPAP on mood with various experimental designs and length of follow-up periods have yielded heterogenous results.

"Patients who have had a stroke or heart attack are prone to suffer from low mood and are 2 to 3 times more likely to develop clinical depression, which then further elevates their risk of future heart attacks and strokes," says SAVE principal investigator Professor McEvoy, a senior author in the paper just published by The Lancet in EClinicalMedicine.

With up to 50% of patients with CV disease likely to have OSA, the study is "welcome news that treatment of OSA substantially relieves cardiovascular patients' depressive symptoms and improves their wellbeing".

The paper's first author, Dr Danni Zheng, from the George Institute for Global Health (UNSW), says the 2687 OSA patients enrolled in the SAVE trial were based solely on their history of cardiovascular disease and not on their current mood status.

"After following them for an average of 3.7 years, we found that CPAP provided significant reductions in depression symptoms compared with those who were not treated for OSA. The improvement for depression was apparent within six months and was sustained."

As expected, those with lower mood scores to start with appeared to get the greatest benefit.

"Our additional systematic review which combined the SAVE study findings with previous work provided further support of the treatment effect of CPAP for depression," Dr Zheng says.

CHICAGO--July 1, 2019-- Primary care physicians trained in dermatoscopy can improve odds for early detection of melanoma while reducing the need for invasive biopsies, according to a study in The Journal of the American Osteopathic Association.

Researchers say non-dermatologist physicians can make earlier and more accurate diagnoses of melanomas using a dermatoscope. This would be particularly beneficial for patients who lack access to dermatologists, the authors noted, because primary care physicians typically biopsy suspicious spots or refer patients to a specialist.

"The training is available in different formats and physicians can hone their skills quickly with regular practice," says Natalia Jaimes, MD, a dermatologist and lead author on this study. "The best way to improve proficiency is by incorporating thorough skin exams in patients' annual checkups."

Melanoma is the fifth most common cancer in the U.S. and kills more than 9,000 people each year. Dr. Jaimes says that number could be significantly lowered with more widespread early detection in communities without access to specialized care.

"If detect early, Melanoma is a highly treatable disease, yet so many people die from it," she says. "The good news is the solution is relatively inexpensive."

Dermatoscopes are inexpensive instruments, costing as little as $500, that provide ×10 magni?cation and illuminate the skin in a manner that minimizes light re?ection off the skin surface. Researchers say diagnosis of specific melanomas using a dermatoscope is four times more accurate than when done with an unaided eye.

Adequate training on dermatoscopy is available in a one- or two-day course but can be as minimal as a 12-hour online program. Physicians who cannot accurately differentiate benign nevi from a malignant melanoma must rely on biopsies to make the diagnosis. Having more physicians trained in dermatoscopy would reduce the costs associated with those medical procedures as well as patient discomfort.

Dr. Jaimes says physicians trained in dermatoscopy can improve odds for early detection of melanoma, which is crucial for patients' prognoses and survival rates. Most melanomas discovered in Stage 0 or Stage 1 can be easily removed with no need for further treatment. The survival rate at this stage is around 98%.

PHILADELPHIA - Treating prostate cancer with higher doses of proton therapy over a shorter amount of time leads to similar outcomes when compared to standard dose levels and treatments and is safe for patients, according to a new study examining the risk of long-term side-effects from the treatment. Researchers in the Perelman School of Medicine at the University of Pennsylvania and the Roberts Proton Therapy Center examined data on non-metastatic prostate cancer patients treated with 28 doses of proton therapy instead of the standard 44 and found that the rates of cancer control at four years was the same in both groups, with notably low rates of urologic and gastrointestinal effects from the treatment at four-year follow up. The findings, which are the first to show patient reported outcomes for shorter courses of proton therapy in prostate cancer, were published in the International Journal of Radiation Oncology, Biology, Physics.

The shorter course of radiation is called hypofractionation, and previous studies have shown it can be effective with traditional photon radiation, but proton therapy has a few key differences. Photon radiation typically uses multiple x-ray beams to attack a tumor target but unavoidably deposits radiation in the normal tissues beyond the target, potentially damaging those tissues as the beam exits the body. Proton therapy is an FDA-approved treatment that is an alternative radiation treatment. It directs positively charged protons at the tumor target, where they deposit the bulk of the radiation dose, with minimal residual radiation delivered beyond the target, potentially reducing side effects and damage to surrounding tissue. Due to these differences, researchers point out the need for better understanding of patient outcomes for the hypofractionated approach in protons, specifically.

"Even though protons are a more targeted way to deliver radiation, we need to make sure we understand the long-term effects of giving patients a higher dose of radiation during each treatment, and our study shows it's safe," said the study's lead author Amardeep Grewal, MD, assistant chief resident in Radiation Oncology.

The study looked at data on 184 men who received hypofractionated proton therapy for prostate cancer that had not spread. At a follow up of 49 months, 96 percent (N = 179) were still alive, with none of the patient deaths related to treatment. The cumulative four-year rate of serious gastrointestinal problems was estimated at 13.6 percent, almost all of which occurred in the first two years. Of the patients who had GI effects, 79 percent experienced rectal bleeding. The cumulative four-year rate of urologic issue was 7.6 percent. The most common issue was needing to urinate frequently. All issued resolved within six months.

"This study provides some prospective evidence that the higher daily radiation dose delivered in hypofractionated proton therapy does not negatively impact patient quality of life," said senior author Neha Vapiwala, MD, an associate professor of Radiation Oncology. "These data can help guide clinicians and patients as they weigh treatment efficacy, tolerability and convenience."

The authors say more research is needed to evaluate the differences between hypofractionated radiation with photon and proton radiation.

Using blood pressure self-monitoring is an effective way to empower patients with hypertension to stick with an exercise program, according to a first-of-its-kind study conducted by a multidisciplinary team of UConn researchers in collaboration with Hartford Hospital.

The findings, recently published in the Journal of Hypertension, confirm a long-held but previously untested theory by the study's principal investigator, Linda Pescatello, a distinguished professor in UConn's Department of Kinesiology, and Dr. Paul Thompson, chief of cardiology at Hartford Hospital, that blood pressure self-monitoring can and should be used as a behavioral strategy to help keep patients with hypertension engaged in an aerobic exercise training program, a proven means of addressing the chronic condition known to be a leading risk factor for cardiovascular disease.

"We know that hypertension is the most common and costly, but modifiable, chronic condition in the U.S. and world," says Amanda Zaleski, a postdoctoral fellow in UConn's Department of Kinesiology who works as an exercise physiologist in Hartford Hospital's Department of Preventive Cardiology. Zaleski is the lead author of the study, which was her doctoral dissertation.

"We know that regular aerobic exercise lowers blood pressure on average to the order of five to seven points," she says, "and these reductions are even greater for those with higher baseline blood pressure."

The difficulty, Zaleski adds, is that hypertension causes no outward symptoms, and patients often become frustrated when they don't know or understand what their blood pressure values are and don't see results from lifestyle modifications. These frustrations can make starting and, perhaps more importantly, sticking with an exercise training program more difficult for many patients.

The research team - which included experts in kinesiology, psychology, cardiology, and statistics, among other disciplines - set out to test their long-held notion that encouraging patients to monitor their own blood pressure, especially before and after exercising, would not only show the patients that exercise had an immediate, positive effect on their blood pressure, but also would help them better adhere to an exercise training program.

Exercise, Zaleski says, lowers blood pressure immediately, an effect first established by Pescatello in a 1991 study which showed that, after one single bout of exercise, blood pressure drops about five to seven points and that this reduction persists for up to 22 hours after the exercise.

She says these blood pressure reductions serve as an objective biomarker that people can measure and see with their own eyes. "This is really powerful for someone with hypertension because it enables them to demonstrate to themselves that their blood pressure is lower on days they exercise than on days that they do not. There are very few chronic conditions that respond this way to exercise. Imagine if an individual with overweight/obesity lost five to seven pounds after a single bout of exercise?"

The researchers recruited 24 participants with hypertension and engaged them in a 12-week supervised aerobic exercise training program. Half of the study participants self-monitored their blood pressure twice a day as well as before and after exercising, and the other half did not self-monitor their blood pressure at all. Most of the participants exercised on a treadmill for 40-minute supervised sessions three times a week at moderate intensity, and they were encouraged to exercise on their own at home in addition to the training sessions.

While both groups saw their blood pressure values lowered by the end of the 12 weeks, the group engaged in self-monitoring lowered their blood pressure by about double the magnitude - about 10 points - compared to the group that was not self-monitoring, which saw an average five-point reduction.

But the study didn't end there.

Four weeks after the supervised training period ended, Zaleski and other kinesiology graduate and undergraduate students conducted telephone exit interviews with the study participants and asked whether they were still engaging in physical activity and, for those in the self-monitoring group, if they were still checking their own blood pressure.

In total, about 75 percent of the study participants were still maintaining some level of exercise, but those who were in the blood pressure self-monitoring group were engaging at an average of 70 percent of their previous exercise training volume - compared to the other group, who were only engaging in about 30 percent as much exercise as when they were supervised.

Within the self-monitoring group, 60 percent of the participants were still measuring their own blood pressure and those participants still self-monitoring were engaged in even greater physical activity - exercising for 45 minutes at least three and a half days per week. This compared to those who were not measuring their blood pressure, who were exercising for about 19 minutes one day a week.

"That was really promising to us," Zaleski says, "demonstrating that if they're out on their own in the free living world, with all of the other confounders that can come into play - like stress, family, vacations - that even without our team holding them accountable, the favorable effects of blood pressure self-monitoring still held true."

Study co-author Beth Taylor notes that blood pressure is one of the only ways to see non-invasively the effects of lifestyle modification.

Taylor, director of exercise physiology research in cardiology at Hartford Hospital and an assistant professor of kinesiology at UConn, says most clinical guidelines right now call for patients to monitor their blood pressure at home; gold-standard, accurate, and easy-to-use blood pressure monitors are available for patient use at home for less than $100. But using blood pressure monitoring before and after exercise, she says, when most patients would be able to see for themselves a notable drop in their blood pressure, would represent a new behavioral health strategy for providers to employ to help increase adherence to an exercise training program.

Both Taylor and Zaleski says that additional studies, with larger sample sizes, are needed to try to replicate the findings. Additionally, for reasons currently unknown, 10 to 20 percent of people do not demonstrate the same drop in blood pressure immediately following exercise, which could limit the effectiveness of self-monitoring as a behavioral modification strategy.

But, says Taylor, exercise is important for a host of different reasons - including body weight management, bone density, and overall health - and blood pressure self-monitoring could have lifestyle modification implications well beyond treating hypertension.

"This is a great study that shows how we might increase exercise adherence for patients with hypertension," she says. "Could this be a 'gateway drug' to getting people to exercise for an abundant variety of reasons?"

Philadelphia, July 1, 2019—Faced with a preteen boy in pain and struggling to breathe from a severe, deteriorating rare condition, researchers at Children’s Hospital of Philadelphia identified the responsible gene mutation and harnessed that knowledge to develop a novel treatment that dramatically improved the problem. The patient had been born with a complex defect that disrupted the circulation of lymphatic fluid throughout his body.

A leading geneticist and a pediatric cardiologist with expertise in lymphatic disorders co-led a team effort to translate knowledge of the affected biological pathway into an innovative treatment, repurposing an existing drug that caused the abnormal lymphatic system to remodel itself. This unexpected result may form the basis of a new therapy for this type of defective lymphatic circulation.

"This case is a dramatic example of implementing a precision medicine treatment for a life-threatening rare disease," said study leader Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at Children's Hospital of Philadelphia (CHOP). "We discovered a causative gene mutation in two patients, identified an existing drug that acts on that gene’s pathway, showed that the drug relieves the condition in lab animals, and then successfully treated the original patient."

Hakonarson collaborated with pediatric cardiologist Yoav Dori, MD, PhD, from the innovative Center for Lymphatic Imaging and Interventions, based at CHOP. “Our patient suffered from a lymphatic conduction disorder known as a central conducting lymphatic anomaly,” said Dori. “The gene mutation drove uncontrolled proliferation of abnormal lymphatic vessels, leading to leak of lymphatic fluid, edema and respiratory difficulties. Because we were able to repurpose an existing drug to block the signals causing the dysregulated growth, we caused our patient’s lymphatic channels to reshape themselves into a more normal anatomy and function, and dramatically improved his condition."

The study team published their findings online today in Nature Medicine.

"The lymphatic system is sometimes called ‘the forgotten circulation,’” said Dori, who added that the lymphatic system interacts with the cardiovascular system, absorbing and returning fluid from tissues back to the venous circulation. As lymphatic fluid circulates through the body, it has a crucial role in immune function as well as fat and protein transport. Abnormal lymphatic flow, which often goes undiagnosed, may cause fluid accumulation in the chest, abdomen or other tissues, leading to respiratory distress, abdominal swelling, and severe swelling of the limbs or tissues.

Daniel was 10 years old when he first came to his local hospital in Virginia with swelling in his lower body, shortness of breath and exercise intolerance caused by a buildup of lymphatic fluid around his heart. “This came on suddenly for Daniel,” said his mother, who added that he had been a competitive soccer player and had run a 5K course in 25 minutes without any training. Doctors drained the fluid, but it continued to accumulate, and he was transferred to CHOP for further evaluation by the lymphatics team.

At CHOP, the lymphatics team blocked the abnormal flow and used minimally invasive methods to initially stabilize the problem, but the fluid buildup reoccurred and worsened over the next two years. Daniel’s respiratory problems and swelling worsened, despite a variety of minimally invasive and surgical interventions. Sirolimus, a drug commonly used in lymphatic conditions, did not work. The care team was running out of options and Daniel’s condition continued to deteriorate.

Hakonarson, a pediatric pulmonologist in addition to his genetics and genomics expertise, consulted with the lymphatics clinical team on Daniel’s case. “All lymphatics patients are now also seen by our genomics team,” said Hakonarson, who added that based on this work, CHOP is now expanding an existing program in complex vascular anomalies that investigates the underlying genetic mutations that impair normal development of blood or lymphatic vessels.

Hakonarson’s team performed whole-exome sequencing (WES) on Daniel’s DNA with the aim of identifying a specific genetic cause for his condition. The team also did WES on DNA from an unrelated young adult patient, from another center, with a severe lymphatic condition. That DNA was stored in a patient registry. In both cases, the sequencing identified a previously undiscovered gain-of-function mutation in the ARAF gene. Unfortunately, the adult patient died from this life-threatening disease before the subsequent experimental treatment became available.

The researchers explored the function of the ARAF mutation by inserting it into the embryos of zebrafish, an animal frequently used to model genetic diseases. The zebrafish then developed similar abnormal lymphatic channels. The next step was to use a drug called an MEK inhibitor known to act on biological pathways affected by ARAF. The drug “rescued” the structural defect in the zebrafish, causing them to develop normal lymphatic vessels.

MEK inhibitors are typically approved for use in patients with the skin cancer, melanoma. Based on their zebrafish results, Hakonarson and Dori consulted with Dr. Jean Belasco from the CHOP Oncology team, who is a leading clinician in vascular anomalies, and a study co-author. Dr. Belasco obtained compassionate permission from the FDA to use an MEK inhibitor called trametinib in Daniel.

Within two months after starting the experimental treatment, Daniel’s breathing improved. Three months after starting the treatment, he had reduced fluid retention and was able to cut back on supplemental oxygen, start breathing room air, and begin more physical activity. An MRI showed that his lymphatic vessels were remodeling themselves. He was able to stop using supplemental oxygen and transition to breathing room air. The heavy swelling in Daniel’s legs gradually disappeared.

Now 14 years old, Daniel has been able to resume many normal activities, such as riding his bicycle, playing basketball, and taking up others, such as weight training and helping to coach soccer camps. His mother said, “Just over two years ago, Daniel was getting measured for a wheelchair and had to be tutored at home. Now he’s back at school full-time and is able to be active with his friends."

Dori and Hakonarson said that this research is the first real evidence for complete remodeling of an entire organ system by a drug, and offers hope for many patients with similar lymphatic flow disorders. “Our work exemplifies how genetic discoveries can impact disease classification and uncover novel biological and life-saving treatments,” they concluded in the paper.

His mother added, “As difficult as this process of discovery, experimentation and treatment has been, we are so grateful for the perseverance and skill of his medical team, in addition to Daniel’s resilience and optimism. The fact that Daniel’s case has the potential to help countless other patients is a silver lining for sure."

Wyss Center for Bio and Neuroengineering, Geneva, Switzerland - Personalized neurotechnology-aided rehabilitation of the arm could improve recovery in severe chronic stroke patients according to a new paper published today in the journal Brain.

Neurotechnology-based therapies, including brain-machine interfaces, robotics, and brain stimulation among others, will lead to largest treatment effects and success if they are tailored to the needs of individual patients, and used in combination, say the authors from the Wyss Center for Bio and Neuroengineering, Swiss Federal Institute of Technology Lausanne (EPFL), Scuola Superiore Sant'Anna, University of Geneva Faculty of Medicine and Clinique Romande de Réadaptation. The paper calls for longitudinal clinical studies to show the rehabilitation benefits of individual therapies as well as the use of multiple complementary therapies used in combination over long time periods.

Lead author Dr. Martina Coscia, Staff Engineer at the Wyss Center said: "Our findings show that neurotechnology-aided upper limb rehabilitation is promising for severe chronic stroke patients. However, we also found that the 'one size fits all' approach doesn't lead to the best outcome. We suggest a move towards a personalized combination of neurotechnology-based stroke rehabilitation therapies, ideally in a home-based environment where prolonged therapy is more feasible than in a clinic.

"We believe that by sequentially introducing stroke therapies according to individual progress, we could allow patients to continue their recovery beyond what is possible today."

Stroke is a major public health problem that causes long-term impairments in millions of people worldwide. One of the most common consequences of stroke is impaired upper arm function which has a direct impact on daily tasks and quality of life. Rehabilitation therapies generally have the largest effect in the first three months after stroke. After this time, patients are considered chronic and the likelihood of further natural recovery is limited; this is especially true for those most severely affected.

Professor Friedhelm Hummel from EPFL (Director, Defitech Chair of Clinical Neuroengineering) and the University of Geneva Medical School said: "What we would like to see in the future are long-term trials in which multiple neurotechnology-based therapies are used within the same patient. We believe that this synergistic approach could uncover previously undiscovered treatment pathways for chronic stroke patients."

The authors compared effectiveness data from 64 clinical studies on upper limb neurotechnology-aided treatments in chronic stroke patients. The interventions analyzed in the paper included robotics, functional electrical stimulation of muscles, brain stimulation and brain-computer interfaces as well as their use in combination.

The interdisciplinary research team is now starting a clinical trial to test these ideas. The trial uses a new experimental design with a personalized therapy approach using brain-computer interfaces, robotics, functional electrical stimulation and brain stimulation specifically chosen to maximize treatment effects in each individual patient. The goal is to keep incrementally improving recovery by using new personalized, neurotechnology-based therapies in combination. The trial will start in Switzerland in summer 2019.

Postmenopausal women who are "apple" shaped rather than "pear" shaped are at greater risk of heart and blood vessel problems, even if they have a normal, healthy body mass index (BMI) according to new research.

In fact, the study, which is published in the European Heart Journal [1] today (Monday), found that storing a greater proportion of body fat in the legs (pear-shaped) was linked to a significantly decreased risk of cardiovascular disease (CVD) in these women.

This is the first study to look at where fat is stored in the body and its association with risk of CVD in postmenopausal women with normal BMI (18.5 to less than 25 kg/m2). It involved 2,683 women who were part of the Women's Health Initiative in the USA, which recruited nearly 162,000 postmenopausal women between 1993 and 1998 and followed them until February 2017. They did not have CVD at the time of joining the study but, during a median (average) of nearly 18 years of follow-up, 291 CVD cases occurred.

The researchers, led by Dr Qibin Qi, an associate professor at the Albert Einstein College of Medicine, New York (USA), found that women in the top 25% of those who stored most fat round their middle or trunk (apple-shaped) had nearly double the risk of heart problems and stroke when compared to the 25% of women with the least fat stored around their middle. In contrast, the top 25% of women with the greatest proportion of fat stored in their legs had a 40% lower risk of CVD compared with women who stored the least fat in their legs.

The researchers found that the highest risk of CVD occurred in women who had the highest percentage of fat around their middle and the lowest percentage of leg fat - they had a more than three-fold increased risk compared to women at the opposite extreme with the least body fat and the most leg fat.

Dr Qi said: "Our findings suggest that postmenopausal women, despite having normal weight, could have varying risk of cardiovascular disease because of different fat distributions around either their middle or their legs. In addition to overall body weight control, people may also need to pay attention to their regional body fat, even those who have a healthy body weight and normal BMI.

"However, it is important to note that participants of our study were postmenopausal women who had relatively higher fat mass in both their trunk and leg regions. Whether the pattern of the associations could be generalisable to younger women and to men who had relatively lower regional body fat remains unknown."

The researchers calculated that, among 1000 women who kept their leg fat constant but reduced the proportion of trunk fat from more than 37% to less than 27%, approximately six CVD cases could be avoided each year, corresponding to 111 cases avoided over the 18 years of the study. Similarly, among 1000 women who kept their trunk fat constant but increased their leg fat from less than 42% to more than 49%, approximately three CVD cases could be avoided each year and 60 cases would have been avoided over the 18-year period.

Dr Qi said: "In routine clinical practice, BMI is a common approach to assessing a person's risk of cardiovascular disease. Measurement of waist circumference is also recommended by national organisation to provide additional information, but usually only in those with a BMI between 25 to 34.9 kg/m2. As such, some people who are categorised as being a normal weight may not be recognised as being at increased risk of cardiovascular disease due to the distribution of their body fat, and so may not have preventive measures recommended for them.

"Our findings highlight the need for using anthropometric measures that better reflect regional fat distribution to identify increased risk of cardiovascular disease. These are important research directions for future population studies."

In the study, the researchers measured fat mass by means of a DXA scan (Dual-energy X-ray Absorptiometry), which measures fat, muscle and bone density, and they say that at this stage it is premature to recommend DXA scans for risk screening in the normal weight population. However, measurements of waist and hip circumference and the ratio between them would provide better information than just calculating BMI. In addition, they stress that their findings do not show that the site of stored body fat causes the difference in risk of CVD, only that it is associated with it.

When women reach the menopause, they can undergo changes in their body shape and metabolism; more fat may be stored around the organs in the body rather than underneath the skin. In addition, the distribution of body fat is determined by both genetics and exposure to environmental factors, such as diet and exercise.

"While there have been some large studies of genetic determinants of upper- and lower-body fat, fewer large studies have focused on lifestyles factors, though modifiable factors such as physical activity and dietary intakes are thought to play key roles in determining an individual's fat distribution," said Dr Qi. "In the next step, our group will focus on the long-term impacts of dietary habits on fat distribution among these postmenopausal women, and evaluate whether and how dietary habits may affect multiple health risks, such as risk of cancer, cardiovascular disease and premature death, through the impacts on the distribution of body fat."

It is known already that fat stored around the organs in the abdomen increases the risk of metabolic problems, such as worse control of blood sugar levels, raised levels of insulin, inflammation and higher cholesterol levels, that can lead to cardiovascular disease. The mechanisms underlying the reason why increased leg fat may be protective are less well understood, but may be because fat stored in the legs is not causing problems elsewhere in the body.

In an accompanying editorial [2], Professor Matthias Blüher and Professor Ulrich Laufs, from the University of Leipzig, Germany, write: "The study may inspire novel concepts of how a dysbalance between 'atherogenic' and 'anti-atherogenic' fat depots may indirectly contribute to vascular damage. Importantly, the study identifies a. positive effect of leg fat on ASCVD [atherosclerotic cardiovascular disease] risk."

Washington, DC - June 18, 2019 - Researchers have now developed a new vaccine, a native outer membrane vesicle (NOMV) vaccine, for meningitis and bloodstream infections caused by "meningococcal group B" bacteria. This will allow younger people to be vaccinated and will address several limitations of the current vaccinations. The research is published this week in mBio, a journal of the American Society for Microbiology.

"We developed the improved version of the vaccine by making several genetic changes to the strain of bacteria used to produce the vaccine, resulting in a broadly protective vaccine rather than a strain-specific vaccine," said Peter Beernink, Ph.D., Scientist at the Center for Immunobiology and Vaccine Development, Benioff Children's Hospital Oakland.

There are currently only two licensed vaccines for prevention of meningitis and bloodstream infections caused by "meningococcal group B" bacteria, which are only licensed for use in people age 10 years and older. Both vaccines contain a bacterial protein known as Factor H binding protein (FHbp), which can bind to a host protein known as Factor H (FH).  The licensed vaccines have several limitations, which include lack of effectiveness against some bacterial strains and low immune responses of infant humans.

The researchers immunized infant rhesus monkeys with the NOMV-FHbp vaccine, which induced higher levels of protective serum antibodies than a licensed vaccine against five of six bacterial strains tested.  Two macaques immunized with the licensed vaccine, which contains FHbp that binds macaque FH, developed antibodies to the host FH protein whereas none of the animals given the NOMV-FHbp vaccine or a negative control vaccine developed such antibodies.

The monkey antibody responses to the vaccines were measured in the laboratory based on the ability of serum antibodies to kill the bacteria in a test that is widely considered to predict protection in humans.  The sample sizes of animals were chosen such that the results are highly statistically significant.

"The experimental NOMV vaccine extends the approach of using outer membrane vesicle vaccines, which previously have been given to millions of persons during meningitis B epidemics in Norway, Cuba and New Zealand," said Beernink.

Thus, in a relevant infant non-human primate model, the NOMV-FHbp vaccine elicited higher levels of protective antibodies than the licensed vaccine and anti-FH antibodies in fewer animals. "This shows that the vaccine has the potential to be developed into a more broadly protective vaccine for humans, to extend coverage to infants and toddlers, which are the age groups among the highest risk of developing meningococcal disease, and to increase vaccine safety," said Beernink.

A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.

Breast cancer survivor Joy Jensen said such a test would give control back to those who felt helpless about their situation.

"If an oncologist could look at test results and say, 'we don't believe you would benefit from chemotherapy', then it would have been nice to be given this choice," Ms Jensen said.

Diagnosed with high-grade invasive lobular breast cancer in June 2014, Ms Jensen underwent a mastectomy, chemotherapy, radiation and hormone therapy.

"I am a full-time worker and a mother of two teenage boys," she said.

"If I could have skipped anything in my treatment which would not have impacted my outcome, it would have been chemotherapy."

UQ Centre for Clinical Research scientist Dr Amy McCart Reed said the test could result in tailored treatment for those diagnosed with invasive lobular breast cancer.

"Using gene profiling, we can identify which patients are unlikely to need chemotherapy," Dr McCart Reed said.

"It means we could protect a significant amount of patients from enduring needless chemotherapy."

Invasive lobular breast cancer is the second most common type of breast cancer with 2000 Australian women diagnosed every year.

Although patients initially respond well to treatment, they often return years later with a terminal spread of the disease.

“It is very hard to tell at diagnosis which patients will do well from those who will not be so lucky, which means chemotherapy may be prescribed,” Dr McCart Reed said.

"In this study, we pulled together a set of 194 genes that, when working together, act as a signature to help clarify which patients are likely to have a positive outcome with their breast cancer.

"If they have a low-risk signature score, it means we might relieve them of the burden of chemotherapy.

"If they have a high-risk signature score, we could continue to recommend chemotherapy as the course of treatment.

"In our lab, we are trying to work towards precision oncology and do our best to match people to treatments that will work for them."

Joy Jenson said having a test like this available at diagnosis would bring hope and a brighter future to women like her.

"This research is a positive step forward and one which empowers oncologists and patients to have control over their treatment," Ms Jensen said.