Body

Researchers from the Saint Louis University School of Medicine have discovered why many multiple myeloma patients experience severe pain when treated with the anticancer drug bortezomib. The study, which will be published April 27 in the Journal of Experimental Medicine, suggests that a drug already approved to treat multiple sclerosis could mitigate this effect, allowing myeloma patients to successfully complete their treatment and relieving the pain of myeloma survivors.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful side effect of many anticancer drugs that can cause patients to discontinue treatment or, because symptoms can persist for years, reduce the quality of life for cancer survivors. “This growing problem is a major unmet clinical need because the increased efficacy of cancer therapy has resulted in nearly 14 million cancer survivors in the United States, many suffering from the long-term side effects of CIPN,” says Daniela Salvemini, Professor of Pharmacology and Physiology at the Saint Louis University School of Medicine.

Bortezomib, which is widely used to treat multiple myeloma and mantle cell lymphoma, causes CIPN in over 40% of patients, but the reasons for this are unclear. Salvemini and colleagues found that bortezomib accelerates the production of a class of molecules called sphingolipids that have previously been linked to neuropathic pain. Rats treated with bortezomib began to accumulate two sphingolipid metabolites, sphingosine 1-phosphate and dihydrosphingosine 1-phosphate, in their spinal cords at the time that they began to show signs of neuropathic pain. Blocking the production of these molecules prevented the animals from developing CIPN in response to bortezomib.

Sphingosine 1-phosphate and dihydrosphingosine 1-phosphate can activate a cell surface receptor protein called S1PR1. Salvemini and colleagues determined that the two metabolites cause CIPN by activating S1PR1 on the surface of specialized nervous system support cells called astrocytes, resulting in neuroinflammation and enhanced release of the excitatory neurotransmitter glutamate.

Drugs that inhibit S1PR1 also prevented rats from developing CIPN in response to bortezomib. One such inhibitor was fingolimod, an orally administered drug approved to treat multiple sclerosis. Importantly, fingolimod did not inhibit bortezomib’s ability to kill myeloma cells. Indeed, fingolimod itself has been reported to inhibit tumor growth and enhance the effects of bortezomib. “Because fingolimod shows promising anticancer potential and is already FDA approved, we think that our findings in rats can be rapidly translated to the clinic to prevent and treat bortezomib-induced neuropathic pain,” Salvemini says.

CHICAGO --- Consumers consider online reviews important for choosing physicians, but they should be wary of using those ratings to choose plastic surgeons. The reviews tend to be polarized, and some are written by people whom consulted with the doctor but never had surgery, reports a new Northwestern Medicine study.

The study examined online ratings of doctors who performed cosmetic breast augmentation in six major U.S. cities.

In reviews by patients who had cosmetic breast augmentation, patients' treatment by the surgeon's staff was nearly as important to them as the outcome of the surgery.

The online platforms for patient reviews in the study analysis were RealSelf, Yelp and Google. The study assessed 1,077 reviews across the platforms, comprising 935 positive and 142 negative reviews.

"We found the people who write these review are either very happy or unhappy, so it's difficult for the consumer to get balanced information," said senior study author Dr. John Kim, a professor of plastic surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine plastic surgeon.

The study will be published April 26 in Plastic and Reconstructive Surgery Journal.

The finding most surprising to Kim is the importance of interactions with the doctor's support staff.

"The important thing used to be how the surgery turned out," Kim said. "Our study shows what's almost equally important are things we wouldn't have thought of like how quickly we answer the phone, how nice the staff is in their interactions, the wait time and bedside manner. Service is becoming paramount and almost as important as tangible results and outcomes."

The cost of the elective cosmetic surgery procedures, which are generally not covered by insurance, is at the bottom of patient concerns, Kim said.

The data was obtained in December of 2016 and January of 2017 from New York, Los Angeles, Chicago, Houston, Philadelphia and Miami. The first five of these cities were included because they represent the five most populous metropolitan areas in the U.S., based on 2015 U.S. Census data. Miami was included because it has the most plastic surgeons per capita of any metropolitan area in the U.S.

Other study findings:

There were significantly more 1 star and 5 star reviews than 2, 3 or 4 star reviews. Patients with more extreme views (1 star: worst surgeon ever, or 5 star: best surgeon ever) are more likely to write a review online than those with more moderate views.

"Unhappy patients take up more screen 'real estate' than happy patients, posting longer reviews, which creates a bias of dissatisfaction in online ratings," said first study author Rob Dorfman, a fourth-year student at Feinberg.

Doctors are not allowed to respond to negative reviews online due to HIPPA (the Health Insurance Portability and Accountability Act).

"That is an important point for people to understand," Kim said.

As a result of the findings, Kim has begun implementing changes, including office training for personnel to enhance the service aspect of patient care.

Google reviews were more favorable than reviews on Yelp in each major city studied. The difference was most evident in Houston, where the average Google rating was 4.7 and the average Yelp rating was 3.8 despite 60 percent overlap in surgeons reviewed.

There are many more reviews of plastic surgeons for consumers to evaluate. The number of online reviews on plastic surgeons on Yelp and Google have shot up at an average rate of 42.6 percent per year since 2011, driven predominantly by a 51.4 percent annual growth rate among Yelp reviews.

Kim cautions that online exposure can become a surrogate for experience.

"You could have been practicing quietly and humbly for 20 years, but patients think someone with 1,000 reviews, even though they have much less experience, must be better," Kim said. "So the ubiquity and quality of online reviews may increasingly substitute for experience and ability."

Kim suggests consumers do the following when vetting a plastic surgeon: 1) determine if they are board certified, 2) ask your primary care doctor, trusted friends and family for a referral, 3) meet with the surgeon and determine your comfort and confidence in them.

Taking a biopsy of a brain tumor is a complicated and invasive surgical process, but a team of researchers at Washington University in St. Louis is developing a way that allows them to detect tumor biomarkers through a simple blood test.

Hong Chen, a biomedical engineer, and Eric C. Leuthardt, MD, a neurosurgeon, led a team of engineers, physicians and researchers who have developed a groundbreaking, proof-of-concept technique that allows biomarkers from a brain tumor to pass through the tough blood-brain barrier into a patient's blood using noninvasive focused ultrasound and some tiny bubbles, potentially eliminating the need for a surgical biopsy.

Chen, assistant professor of biomedical engineering in the School of Engineering & Applied Science and of radiation oncology in the School of Medicine, said while researchers have already learned how to get a drug through the blood-brain barrier into the brain via the bloodstream, no one -- until now -- has found a way to release tumor-specific biomarkers -- in this case, messenger RNA (mRNA)-- from the brain into the blood.

"I see a clear path for the clinical translation of this technique," said Chen, an expert in ultrasound technology. "Blood-based liquid biopsies have been used in other cancers, but not in the brain. Our proposed technique may make it possible to perform a blood test for brain cancer patients."

The blood test would reveal the amount of mRNA in the blood, which gives physicians specific information about the tumor that can help with diagnosis and treatment options.

Results of the study, which blends imaging, mechanobiology, genomics, immunology, bioinformatics, oncology, radiology and neurosurgery, are published in Scientific Reports April 26, 2018.

Chen; Leuthardt, professor of neurological surgery in the School of Medicine; and researchers from the schools of Engineering and of Medicine, tested their theory in a mouse model using two different types of the deadly glioblastoma brain tumor. They targeted the tumor using focused ultrasound, a technique that uses ultrasonic energy to target tissue deep in the body without incisions or radiation. Similar to a magnifying glass that can focus sunlight to a tiny point, focused ultrasound concentrates ultrasound energy to a tiny point deep into the brain.

Once they had the target -- in this case, the brain tumor -- researchers then injected microbubbles that travel through the blood similar to red blood cells. When the microbubbles reached the target, they popped, causing tiny ruptures of the blood-brain barrier that allows the biomarkers from the brain tumor to pass through the barrier and release into the bloodstream. A blood sample can determine the biomarkers in the tumor.

This technique could lead to personalized medicine.

"In many ways this has been a holy grail for brain tumor therapy," Leuthardt said. "Having the ability to monitor the changing molecular events of the tumor in an ongoing way allows us to not only better diagnose a tumor in the brain, but to follow its response to different types of treatment."

"Once the blood-brain barrier is open, physicians can deliver drugs to the brain tumor," Chen said. "Physicians can also collect the blood and detect the expression level of biomarkers in the patient. It enables them to perform molecular characterizations of the brain tumor from a blood draw and guide the choice of treatment for individual patients."

In addition, Gavin Dunn, MD, assistant professor of neurosurgery, a co-author and leader in cancer immunobiology, plans to use the technique with immunotherapy, which offers precision treatment that targets specific biomarkers in the brain.

"This noninvasive focused ultrasound-enabled liquid biopsy technique can be useful for long-term monitoring of brain cancer treatment response, where repeated surgical tissue biopsies may not be feasible," Chen said. "Meanwhile, variations within tumors pose a significant challenge to cancer biomarker research. Focused ultrasound can precisely target different locations of the tumor, thereby causing biomarkers to be released in a spatially-localized manner and allow us to better understand the spatial variations of the tumor and develop better treatment."

The team continues to work to refine the process. The future will require integration with advanced genomic sequencing and bioinformatics to enable even more refined diagnostics. These efforts are being led by co-authors, Allegra Petti, assistant professor of medicine, and Xiaowei Wang, associate professor of radiation oncology.

"Our ongoing work is to optimize the technique and evaluate its sensitivity and safety," Chen said.

SAN DIEGO - Revised guidelines incorporating new data on discharge criteria for patients undergoing elective percutaneous coronary intervention (PCI) will allow for flexibility in length of stay while ensuring patient safety. The guidelines were published in early-view online in SCAI's official journal, Catheterization and Cardiovascular Interventions.

PCI is one of the most frequently performed medical procedures, yet there is considerable variability in the duration of hospitalization following such procedures. Traditionally, most patients undergoing elective PCI were admitted as inpatients and monitored overnight because of concerns about post-procedural complications.

Despite pressure from payers to minimize the cost of observation time, the safety of same-day and expedited discharge after PCI was not firmly established. Accordingly, in the interests of quality and patient safety, in 2009 the SCAI published an expert consensus document titled "Defining the Length of Stay (LOS) Following Percutaneous Coronary Intervention" which specified that the standard of care was an overnight stay following uncomplicated elective PCI and proposed that safeguarding patient welfare required LOS criteria be 'dictated by a level of conservatism' in the absence of definitive studies.

Since publication of the 2009 document, PCI practice has continued to evolve, and rates of post- procedural complications have declined significantly. In addition, studies have demonstrated the safety of same-day discharge in patients undergoing PCI, and that most complications occur either very early (24 hours) after PCI. Many patients prefer to recover from a PCI procedure at home rather than spend a night in the hospital. Same-day discharge has, therefore, become a reasonable, patient-centered approach for uncomplicated elective procedures.

The updated guidelines include new criteria to assess readiness for discharge after PCI along three lines including: procedural (successful procedure, adequate hemostasis, and without complications), patient (clinically stable, at their baseline mental status and vital signs, and with stable comorbidities), and programmatic (safe monitoring at home, appropriate guideline-directed medical therapy, compliance with PCI performance measures, and timely follow-up). Specific restrictions that previously precluded expedited discharge based on anatomic (i.e., multivessel disease, bifurcations) or patient factors (i.e., age, comorbidities) have been removed in the absence of evidence that overnight observation modifies the risk incurred.

Advances in practices and technologies have made discharge following PCI demonstrably safe when milestones of clinical stability, procedural success, and process measures have been achieved.

Ultimately, the duration of observation following PCI is a professional medical decision based on individual procedural and patient factors. The updated consensus recommendations support the reasonable judgment of physicians to allow expedited discharge following PCI without prescribing a specific period of observation for individual patients. As the leading professional organization of interventional cardiologists, the SCAI is the only organization to have published consensus recommendations on LOS after PCI, and these are expected to have a significant impact on clinical practice and health policy.

As chair of the consensus committee Arnold Seto, MD, MPA, chief of cardiology, Long Beach VA Medical Center stated, "This SCAI PCI LOS update reflects the most recent information on PCI outcomes, techniques, strategies and health care policy. The new document replaces the prior prescriptive recommendations with a new, more flexible paradigm whereby patients are ready for discharge when individualized clinical milestones are reached. These new recommendations provide for a patient-centered, evidence-based, and efficient process for patient care after both elective and nonelective PCI procedures."

Zika virus. Ebola virus. Influenza. SARS and MERS corona viruses. Existing and emerging viral diseases are an increasing problem, particularly in developing countries. The World Health Organization has called for better control of viral diseases, but developing drugs for this purpose can be challenging.

Now, a multinational team of scientists and clinicians led by Denis Kainov from the Norwegian University of Science and Technology (NTNU) has reviewed all approved, investigational and experimental antiviral agents that have been shown to be safe in humans to search for new uses for these substances against existing and emerging viruses The results have just been published in Antiviral Research.

Antiviral drugs and vaccines are the most powerful tools to combat viral diseases. Most drugs and vaccines, however, selectively target a single virus, thereby providing a "one drug-one bug" solution, the researchers say.

In contrast, broad-spectrum antivirals (BSAs) can cover multiple viruses and genotypes and reduce the likelihood of development of resistance.

Therefore, some BSAs can be used for the rapid management of new or drug-resistant viral strains, for a first-line treatment or for prophylaxis of acute virus infections, as well as for viral co-infections, which can reduce the complexity of treatment.

With this in mind, the team identified 59 compounds already shown to be safe in humans that targeted at least three viral diseases. The researchers then tested 55 of these compounds on eight different viruses, and found that seven showed new effects against HIV-1, Zika virus and Rift Valley Fever.

"Re-purposing these therapeutics from one viral disease to another could save resources and time needed for development of novel drugs," Kainov said.

The researchers say that their results show existing safe-in-human BSAs could be used on other viral infections. The goal is to create broad-spectrum antiviral drugs, much like the broad-spectrum antibacterial drugs that are currently available.

"Effective treatment with broad-spectrum antivirals may shortly become available, pending the results of further pre-clinical studies and clinical trials. The most effective and tolerable compounds will expand the available therapeutics for the treatment of viral diseases," said Aleksandr Ianevsky, the first author of the study and a PhD student at NTNU.

"We hope that not only broad-spectrum antibiotics but also broad-spectrum antivirals will be available in a future," said Magnar Bjørås, a professor at NTNU's Department of Molecular Medicine. "These drugs could be used as first-line therapeutics to combat emerging and re-emerging viral threats that have a global impact, improving preparedness and the protection of the general population from viral epidemics and pandemics."

BOSTON - April 25, 2018 - NovaDigm Therapeutics, a company developing innovative immuno-therapeutics and preventative vaccines for fungal and bacterial infections, today announced the publication of data from a Phase 2a study of its NDV-3A vaccine program in the journal Clinical Infectious Diseases. The data demonstrate that a single dose of NDV-3A with alum adjuvant was safe, well-tolerated, immunogenic and efficacious, leading to reduced recurrences of vaginitis in patients with recurrent vulvovaginal candidiasis (RVVC). NDV-3A is the company's lead development candidate to potentially treat or prevent diseases caused by fungal and bacterial pathogens, including antimicrobial-resistant strains.

The article, titled "A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis - A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trials," was published online in the journal Clinical Infectious Diseases . The article was published with a concurrent editorial entitled, "A Therapeutic Vaccine for Recurrent Vulvovaginal Candidiasis," by Arturo Casadevall, M.D., M.S., Ph.D., Chair, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health and Liise-anne Pirofski, M.D., Chief, Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine .

"There is a growing need for vaccines that can prevent or treat conditions caused by Candida species, such as Candida albicans, the major causative agent of RVVC," commented John Edwards, M.D., first author of the study, Emeritus Chief, Division of Infectious Disease at Harbor-UCLA Medical Center and a scientific founder of NovaDigm. "The positive results in patients with RVVC represent the first demonstration of efficacy for any antifungal vaccine. These results encourage further development of NDV-3A against life-threatening invasive Candida infections, including those by the recently emerging, highly drug-resistant Candida auris."

Nine million women in the United States (11%) report having recurrent yeast infections, with approximately seven million (9%) experiencing RVVC, which has been defined as having three or more episodes per year. Approximately 90% of patients report onset of RVVC prior to the age of 40 years . Many of these women experience frequent episodes of pain and discomfort, high rates of depression and a reduced overall quality of life . While current therapies are effective at controlling acute infections, they do not control recurrences without chronic antifungal suppression, which is not widely used due to potential adverse events.

"Women who have recurrent vulvovaginal candidiasis have limited options to maintain control of this chronic condition, which can have a significant impact on their health and overall quality of life," said Paul Nyirjesy, M.D., Professor of Obstetrics and Gynecology and of Medicine at Drexel University College of Medicine, who was a principal investigator in the Phase 2a study. "The results of this trial demonstrate increases in recurrence-free time out to 12 months for younger women based on patient symptom scores following a single dose of NDV-3A. This finding represents a potential breakthrough for an immunotherapeutic approach to treating these patients."

Top line results reported in August 2016 show the study of 188 patients met its primary endpoint of safety and tolerability. There were no significant differences between NDV-3A and placebo for injection site reactions and systemic reactions of grade 3 or greater. A single dose of NDV-3A generated rapid and robust immune responses. Exploratory efficacy measures based on patient-reported symptom scores showed a higher proportion of patients in the NDV-3A group with no recurrences at the 12-month follow-up period compared to the placebo group (p=0.10). Younger patients showed higher efficacy rates. In patients under 40 years of age (77% of the study population), 42% of NDV-3A recipients were recurrence-free at 12 months post-vaccination compared to 22% of placebo recipients (p=0.03). Patients in this age group receiving NDV-3A also showed a doubling in median time to first recurrence (210 days) compared to placebo recipients (105 days).

Doctors at the University of Illinois Hospital have cured seven adult patients of sickle cell disease, an inherited blood disorder primarily affecting the black community, using stem cells from donors previously thought to be incompatible, thanks to a new transplant treatment protocol.

The doctors report on the new technique in the journal Biology of Blood and Marrow Transplantation.

With the new protocol, patients with aggressive sickle cell disease can receive stem cells from family members if only half of their human leukocyte antigen (HLA) markers match. Previously, donors had to be a family member with a full set of matching HLA markers, or a "fully-matched" donor.

HLA markers are proteins on the surface of cells that help to regulate the immune system. The human body uses these proteins to identify which cells belong in the body and which cells do not. Because HLA markers are inherited from parents, family members are the most likely to have matching proteins. In transplants, matching HLA markers between the patient and the donor help to limit the risk that the patient's body will reject the donor cells.

While doctors always try to find a closely matched donor for patients who need a stem cell transplant, only 20 percent of sickle cell patients have a family member with a full set of matching HLA markers.

"We have made great strides curing adults with sickle cell disease with stem cell transplants, but the unfortunate truth is that the majority of these patients have, until now, been unable to benefit from this treatment because there are no fully-matched HLA-compatible donors available in their family," said corresponding author Dr. Damiano Rondelli, the Michael Reese Professor of Hematology and director of the Blood and Marrow Transplant program at the University of Illinois at Chicago.

Rondelli and his team run the largest adult sickle cell program in the Chicago area and pioneered the use of chemotherapy-free fully-matched stem cell transplants for sickle cell patients nearly six years ago.

Now, by allowing for "half-matched" donors, the new treatment protocol, which uses only a small does chemotherapy, significantly increases the number of potential donors for each patient.

The doctors screened 50 adult sickle cell patients as candidates for a half-matched stem cell transplant between January 2014 and March 2017. Ten patients received a transplant. Following two unsuccessful transplants, the doctors adopted the new treatment protocol, which included modifications to a process first developed at Johns Hopkins University.

"We modified the transplant protocol by increasing the dose of radiation used before the transplant, and by infusing growth factor-mobilized peripheral blood stem cells instead of bone marrow cells," Rondelli said. "These two modifications helped ensure the patient's body could accept the healthy donor cells."

Of the eight patients who underwent the revised transplant, one experienced chronic graft-versus-host disease following the transplant and died of unknown causes. The other seven patients are alive and maintain 95 percent or higher stable engraftment - acceptance of donor cells - with improved blood work at least 12 months following the transplant.

"These patients are cured of sickle cell disease," Rondelli said.

"The takeaway message is twofold. First, this transplant protocol may cure many more adults patients with advanced sickle cell disease," he said. "Second, despite the increasing safety of the transplant protocols and new compatibility of HLA half-matched donors, many sickle cell patients still face barriers to care - of the patients we screened, only 20 percent underwent a transplant."

Rondelli says that medical insurance denial accounted for 20 percent of the lack of access to the transplant. Other factors included personal decisions and high rates of donor-specific antigens in patients who had received frequent blood transfusions.

An investigational drug in clinical trials for rheumatoid arthritis prevents a common, life-threatening side effect of stem cell transplants, new research from Washington University School of Medicine in St. Louis shows. Studying mice, the researchers found the drug prevented what's known as graft-versus-host disease, a debilitating, sometimes lethal condition that develops when transplanted stem cells attack the body's own organs or tissues.

About half of patients receiving donor stem cells develop graft-versus-host disease, which can linger for months or years after their transplants. In some cases, patients die not from their cancer but from the complication itself. Current treatments are not effective.

The study is online in the journal Leukemia.

In past work, this research team defined the role of molecules called JAK1/2 kinases and their signaling pathways in immune cell activation and graft-vs-host disease. In the new study, these same researchers evaluated ruxolitinib and baricitinib, and found baricitinib to be the superior of the two drugs in reducing and preventing graft-versus-host-disease in mice. Both drugs belong to a class of pharmaceuticals called JAK inhibitors that are known for dialing down inflammation.

"Transplanted donor stem cells -- and more specifically, the T cells in the donor stem cell product -- are particularly good at fighting off leukemia, but these cells can go haywire, unfortunately, and attack the patient's healthy tissues, causing graft-versus-host disease," said senior author John F. DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor of Medicine in Oncology. "The typical ways we can reduce the effects of the disease also tend to weaken the T cells' ability to attack the cancer. We're looking for a treatment strategy that stops the disease without shutting down T cells' assault on the cancer."

Surprisingly, baricitinib did more than shut down graft-versus-host disease. It actually boosted the ability of the donor T cells to fight the cancer.

"We don't know yet exactly how this happens, but we're working to understand it," said first author Jaebok Choi, PhD, an assistant professor of medicine. "We think at least part of the explanation is the drug strips the leukemia cells of their immune defenses, making them more vulnerable to attack by the donor T cells. At the same time, the drug also stops the donor T cells from being able to make their way to important healthy tissues, such as the skin, liver and gastrointestinal tract, where they often do the most damage."

In other words, the drug appears to stop graft-versus-host disease by simply keeping the donor T cells circulating in the bloodstream, away from vital organs. Simultaneously, the drug makes the leukemia cells more vulnerable to immune attack from the donor T cells, which are now mostly confined to the bloodstream, where the cancer is.

The drug also appeared to boost levels of specific immune cells that put the brakes on a runaway immune response that can make graft-versus-host disease worse. These apparently independent effects are specific to baricitinib and may explain why other JAK inhibitors did not work as well, according to DiPersio, who is also deputy director of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The researchers emphasized the finding that the drug not only prevented graft-versus-host disease from developing in the mice but reversed established disease, suggesting possible options for patients already affected by it.

"We were surprised to achieve 100 percent survival of mice with the most severe model of graft-versus-host disease," Choi said. "We are now studying the multi-pronged ways this drug behaves in an effort to develop an even better version for eventual use in clinical trials."

Because of the drug's broad effectiveness in preventing inflammatory disorders, DiPersio said he and his colleagues are beginning to explore whether it could be used to prevent organ rejection in patients undergoing solid organ transplantation. Such a strategy might reduce the need to give these patients powerful immune-suppressing drugs that increase the risk of infection.

WINSTON-SALEM, N.C. - April 24, 2018 - People who are 30 pounds or more overweight may want to slim down a bit even if they don't have high blood pressure or any other heart disease risk, according to scientists at Wake Forest Baptist Medical Center.

In a study published in the May issue of the Journal of the American College of Cardiology, the researchers found that slightly less than half of the people who were considered obese - 30 pounds or more overweight - developed metabolic syndrome within 10 years, putting them at a much higher risk for cardiovascular disease and diabetes.

"Common medical wisdom has been that some people who are obese seemed to be pretty healthy and free from heart disease risks, so they haven't been advised to lose weight or take other steps to prevent future heart disease," said Morgana Mongraw-Chaffin, Ph.D., assistant professor of public health sciences at Wake Forest Baptist and lead author of the study.

"The big question has been whether these people who are metabolically healthy will stay that way or whether they will progress to metabolic syndrome over time."

Metabolic syndrome includes those risk factors - high blood pressure, high blood sugar, unhealthy cholesterol levels and abdominal fat - which double the risk of cardiovascular disease that can lead to heart attacks and strokes. In addition, these risk factors increase the risk of diabetes by five times.

The Wake Forest Baptist study included 6,809 participants from the Multi-Ethnic Study of Atherosclerosis who were recruited from six sites in the United States. Participants with cardiovascular disease were excluded.

The study was conducted to determine if metabolically healthy obesity (MHO) at baseline remained stable or led to metabolic syndrome and increased the risk of heart and vascular disease. Participants were followed for 12 years with clinical evaluation repeated every two years. MHO was defined as a body mass index of more than 30 and two or fewer risk factors.

The researchers found that compared to normal weight, baseline MHO was not significantly associated with incident cardiovascular disease, the first occurrence of a potentially life-threatening condition. However, almost half of the participants developed metabolic syndrome over the course of the study and had increased odds of cardiovascular disease compared to those with stable MHO and normal weight.

"In this paper, we specifically looked to see whether that progression was associated with a higher risk for heart disease and we found that it was," Mongraw-Chaffin said. "Metabolically healthy obesity is not a stable or reliable indicator of future risk for cardiovascular disease. Right now, there isn't any way to know which 50 percent will progress and which won't.

"Therefore we recommend that everyone with MHO work with their doctor to lose weight or at least maintain their current weight, exercise more and make other lifestyle changes so they don't develop metabolic syndrome."

Researchers at the University of Exeter have found a statistical link between pneumonia in older people and a group of medicines commonly used to neutralize stomach acid in people with heartburn or stomach ulcers. Although proton-pump inhibitors (PPIs) are still a valuable group of medicines, research is indicating that PPIs are not as completely safe for older people as previously thought.

PPIs are medicines commonly prescribed to reduce gastric (stomach) acid production and to protect the stomach. Approximately 40 percent of older adults receive PPIs, although according to some experts, up to 85 percent of people who receive PPI prescriptions may not need them.

Researchers say people should not stop using their PPI medication, but should discuss with their prescribing healthcare professional whether the PPIs are still needed. Just stopping PPIs could be dangerous as PPIs may be useful, for example, to prevent stomach bleeds in some people.

Once thought to be relatively harmless, PPIs have more recently been linked to increased rates for certain health concerns like fractures, cardiovascular disease, and some bacterial infections. The association between PPI use and pneumonia was studied because stomach acid helps to prevent infections spreading from the gut in some individuals. Since pneumonia is a major cause of death for older adults, it is important for healthcare providers to understand the links between PPIs and pneumonia.

The Exeter team designed a study to look at statistical links in medical records between long-term PPI use and pneumonia in older adults. Their study was published in the Journal of the American Geriatrics Society.

David Melzer, Professor of Epidemiology and Public Health at the University of Exeter Medical School, said: "This study shows that there was a higher rate of pneumonia in older people who received PPIs over a two year period. Caution is needed in interpreting the findings as our study is based on analyzing data from medical records, so other factors may be involved. However, our study adds to growing evidence that PPIs are not quite as safe as previously thought, although they are still a very useful class of medication for certain groups of patients."

The researchers used information from Clinical Practice Research Datalink (CPRD) for England, a large database containing records from many primary care practices in the U.K. They selected patients 60-years-old and older who had taken prescribed PPIs regularly and who also had previous regular medical records. The researchers identified more than 75,000 older adults who were treated with PPIs.

As with all prescription medications, regularly review your use of medicines like PPIs with your healthcare providers to make sure each prescription is still needed.

This summary is from "Proton-Pump Inhibitors and Long-Term Risk of Community?Acquired Pneumonia in Older Adults." It appears online ahead of print in the Journal of the American Geriatrics Society. The study authors are Jan Zirk-Sadowski, PhD; Jane A. Masoli, MBChB; Joao Delgado, PhD; Willie Hamilton, MD; W. David Strain, MD; William Henley, PhD; David Melzer MBBCh, PhD; and Alessandro Ble, MD.

BUFFALO, N.Y. -- In the largest federally funded non-drug clinical trial for irritable bowel syndrome (IBS), patients with the most severe and persistent symptoms achieved robust and sustained relief by learning to control symptoms with minimal clinician contact. Led by University at Buffalo researchers in collaboration with colleagues at New York University and Northwestern University, the study was published online before print in Gastroenterology.

The research is a product of 20 years of funding from the National Institute of Diabetes, Digestive and Kidney Diseases of the National Institutes of Health, and one of the largest, behavioral medicine trials not including a drug arm. It reflects a longtime partnership between researchers at UB and NYU, who pooled their respective expertise and talents to develop and test a novel treatment strategy.

Of 436 patients recruited at UB and Northwestern, 61 percent reported symptom improvement two weeks after home-based behavioral treatment ended compared to 55 percent in clinic-based treatment and 43 percent who received patient education. The treatment benefit also persisted for as long as six months after treatment ended.

"This is a novel, game-changing treatment approach for a public health problem that has real personal and economic costs, and for which there are few medical treatments for the full range of symptoms," said Jeffrey Lackner, PsyD, lead author, professor in the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB and director of its Behavioral Medicine Clinic. He is affiliated with UB's Clinical and Translational Science Institute.

Women are disproportionately affected

IBS is a persistent and difficult-to-treat condition that is one of the most common diseases that gastroenterologists and primary care physicians treat. It's characterized by chronic abdominal pain, diarrhea and/or constipation. Medical and dietary treatment have a disappointing track record of relief for many patients.

Afflicting between 10 and 15 percent of adults worldwide, most of whom are female, the condition creates a public health burden that causes pain, isolation and frustration, all of which impair quality of life. Beyond the personal toll, Lackner said, the economic burden of IBS in the U.S. is estimated at $28 billion annually.

"These findings will be welcomed by many women and men," he continued, "who have unfortunately been stigmatized, marginalized and too often treated as 'head cases' merely because no definitive cause for their symptoms is identified through routine medical testing."

This treatment will help address a major barrier to quality health care faced by those living in rural areas, Lackner added, because now these patients will have access to a state-of-the-art treatment once only available in metropolitan areas.

According to NYU Silver School of Social Work Professor James Jaccard, PhD, a key investigator on this research program since its inception in 2000, "The creative development of this symptom-management approach for IBS can affect millions of people, primarily women, who suffer from this often stigmatized and poorly understood condition. By integrating perspectives from medicine and the social sciences, it illustrates the power of team-oriented and multidisciplinary approaches to reducing health care disparities in vulnerable populations."

While IBS affects mostly women, Lackner said this study is noteworthy because 20 percent of the patients were male, many of whom are themselves reluctant to seek help. "These men are more likely to reach out for help if they can access treatment that is brief and home-based," he said.

Brain-gut connections

The treatment consists of a form of cognitive behavioral therapy (CBT) that teaches practical skills for controlling gastrointestinal symptoms, either during 10 clinic visits, or four clinic sessions in conjunction with self-study materials developed by Lackner in a previous NIH grant. Both CBT treatments focused on information on brain-gut interactions, self-monitoring of symptoms, triggers and consequences, worry control, muscle relaxation and flexible problem-solving.

"The treatment is based on cutting-edge research that shows that brain-gut connection is a two-way street," Lackner explained. "Our research shows that patients can learn ways to recalibrate these brain-gut interactions in a way that brings them significant symptom improvement that has eluded them through medical treatments."

Physicians and patients agree on improvement

Lackner added that the study's strength is underscored by the fact that both patients and the gastroenterologists, who evaluated patients and were unaware of which treatment patients were assigned, reported similar rates of symptom improvement as patients.

"One measure of the strength of clinical-trial findings is when two data sources report similar data about an endpoint," he explained. "In our study, there was striking similarity between the treatment response reported by patients and 'blind' assessors. This pattern of agreement from patients and physicians shows that we see very real, substantial and enduring improvement in GI symptoms immediately after treatment ends and many months later."

'Mind-based intervention'

The research holds special interest for Emeran Mayer, MD, PhD, professor in the David Geffen School of Medicine at UCLA and executive director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, an internationally known expert on the interactions between the digestive and nervous systems and women's health.

"This study clearly established the clinical value of a mind-based intervention for IBS," said Mayer. "The success of this research shows that this should be offered to patients not as a last resort but as a safe and effective first or second-line therapy. It's very different from the pharmaceutical model where you are searching for magic-bullet medications. With current medications, you cannot treat the whole patient. The medications can improve their bowel habits, but it's not a complete treatment for the patient with IBS."

Lackner oversaw the training of clinicians who work with Mayer at UCLA on the UB program. The two have been building on this work with a groundbreaking study of how the microbiome of IBS patients influences their response to cognitive behavioral therapy. The collaborative work is jointly funded by a $2.3 million NIH grant to UCLA, the lead institution, and UB. Results from that study are forthcoming.

Patients with asthma and hay fever have an increased risk of developing psychiatric disorders, finds a new study published in open-access journal Frontiers in Psychiatry. Almost 11% of patients with common allergic diseases developed a psychiatric disorder within a 15-year period, compared to only 6.7% of those without - a 1.66-fold increased risk. While previous studies have linked allergies with certain psychiatric or emotional disorders, this is the first to find a connection between common allergies and the overall risk of developing psychiatric disorders. The findings could have implications for how doctors care for and monitor patients with allergic diseases.

Asthma, allergic rhinitis (hay fever) and atopic dermatitis (eczema), are among some of the most common allergic diseases and are nicknamed the three "A"s. Dr. Nian-Sheng Tzeng , from Tri-Service General Hospital in Taiwan and lead author of the study, noticed something unexpected about these patients.

"As a clinician, I observed that some patients with the three 'A's appeared to suffer emotionally," says Tzeng. "Therefore, I wanted to clarify whether these allergic diseases are associated with psychiatric disorders."

When Tzeng and colleagues searched the literature, they found that previous studies had reported links between allergic diseases and specific psychiatric disorders or emotional problems. For example, a study in Denmark found that children with allergic diseases had more emotional and behavioral problems.

However, not all previous research supported this positive link, with one study in Taiwan suggesting that allergic rhinitis is less common among patients with schizophrenia, for example. Clearly, more extensive research was needed for a more complete picture.

Despite the previous research, no-one had studied the link between the three "A"s and the overall risk of developing psychiatric disorders. To study this in a large sample of people, the researchers used an extensive database of health insurance claims in Taiwan, covering a 15-year period.

The researchers identified 46,647 people in the database with allergic diseases and 139,941 without. Unlike previous studies, the researchers included patients of all ages. They found that over the 15-year period, 10.8% of people with allergic diseases developed a psychiatric disorder, compared with 6.7% of those with no allergic disease. This translated to a 1.66-fold increased risk of developing psychiatric disorders for people with an allergic disease.

A closer look at the data revealed that people with atopic dermatitis had a lower risk of developing a psychiatric disorder, while those with asthma and allergic rhinitis had a higher risk. Interestingly, the team discovered that using certain asthma medications was associated with a lower risk of psychiatric disorders in asthma patients.

So, why might patients with certain allergic diseases have a higher risk of psychiatric disorders? Recent research suggests that inflammation is linked to psychiatric disorders, such as depression and anxiety disorders. As allergies also involve inflammation, it is possible that it may contribute to psychiatric disorders in the same patients. The psychological stress of a psychiatric disorder might also contribute to physical symptoms.

The current study did not examine the potential cause of this phenomenon and researchers need to complete further studies to identify the precise mechanisms involved. However, knowing that there is a link between allergic diseases and psychiatric disorders could help doctors to care for their patients.

"We would like to let clinicians who care for patients with allergic diseases know that their risk for psychiatric diseases may be higher," says Tzeng. "Assessing their emotional condition and monitoring their mental health could help to avoid later psychiatric problems."

Southern and Western states have the highest rates of white firearm suicide, while Midwestern states have highest rates of black firearm homicide, according to new research from McGill University. The findings place a spotlight on states where firearm policies may help reduce homicide and suicide rates.

Gun violence has a long history in the U.S. Less understood is how homicide or suicide varies amongst black and white men across states US states and how household gun ownership influences them.

To find out, researchers from McGill University in Canada used data from death certificates to identify firearm homicides and suicides that took place in each US state between 2008 and 2016 and calculated how these differed among black and white men. Corinne Riddell, a postdoctoral fellow in the Department of Epidemiology, Biostatistics and Occupational Health, and her colleagues, also wondered if U.S. states with higher rates of gun ownership also have more gun violence. To do so, they used their data to investigate the relationship between homicide/suicide rates and state household gun ownership for both groups.

Rates of gun ownership associate to suicide/homicide among white men

Their results, published in a forthcoming study in the Annals of Internal Medicine, describe a complex relationship between suicide and homicide rates, race and levels of state gun ownership.

Southern states with high rates of gun ownership such as Mississippi, Alabama and Arkansas, had among the highest rates of both firearm homicide and firearm suicide for white men. On the other hand, states with less gun ownership (Massachusetts, New Jersey, Rhode Island, Connecticut, and New York) had the lowest rates of both homicide and suicide.

"Looking at these numbers by state offers an interesting perspective," says Jay Kaufman, professor in the Department of Epidemiology, Biostatistics and Occupational Health in McGill's Faculty of Medicine and senior author of the new study. "For white men, higher rates of gun ownership seem to be strongly associated with higher rates of suicide and homicide."

Large disparities in black homicides from state to state

In contrast, the researchers found only a modest association between rates of firearm homicide and firearm suicide for black men. Whereas Northeastern states with low gun ownership also had the lowest rates of black firearm suicide, Corinne Riddell points out that states with medium to high rates of gun ownership had both high and low rates of homicide.

"In a state like Michigan, which has relatively high gun ownership, black men experienced 49 firearm homicides per 100,000, wheras in a state like Texas, which also has relatively high gun ownership, the figure was 18," explains Riddell.

This suggests that different factors may influence rates of firearm homicide for black and white men from state to state.

"Nationwide one-size-fits-all gun control legislation might not be sufficient to eliminate racial disparities in firearm violence," said Riddell.

Prior studies have shown that in the U.S., black men are 10 times more likely to be killed by someone else, and 80% of these homicides occur with firearms. White men are 3 times more likely to commit suicide and about two thirds of these deaths involve a gun.

The greasy food being served at hockey rinks isn't really what young hockey players want, according to a study from the University of Waterloo.

The study of 25 travel team players aged 11-15 found they were more motivated by performance, recovery and marketing when making food choices - values that typically aren't represented with the unhealthy food currently served at arenas.

"The perceptions these players place around the value of healthy food choices for performance and post-exercise recovery could be leveraged to influence change," said Susan Caswell, a PhD candidate at Waterloo and author of the study. "This has implications for policies and processes relating to player training and food retail and media environments."

She added that "recreational food establishments might be missing an opportunity by not providing food that adolescent hockey players will eat before and after games."

The study, which used photographs taken by players and interviews to explore their perceptions of food in relation to playing hockey, noted that players tended to avoid arena food in favour of establishments that were perceived and marketed as being more healthy. In terms of fast food, they gravitated towards Tim Horton's and Subway, even when food from those chains wasn't necessarily healthy.

"Interestingly, we found that the Subway experiences appeared to contradict the impressions of players," said Caswell. "For example, photographs of a healthy meal experience at Subway could include fountain pop, chips and/or cookies, which we know aren't nutritious."

Caswell added that Subway and some foods, such as chocolate milk and Gatorade, obtain 'halo' status by linking themselves to either athletic performance or healthy eating through their marketing. This suggests a need to look at how food is marketed to teens.

Several Canadian provinces are considering policies to increase healthy food offerings in recreation facilities, but not yet Ontario. British Columbia, Alberta, and Nova Scotia have already instituted voluntary nutrition guidelines.

The study was published in Public Health Nutrition with Rhona Hanning from the School of Public Health and Health Systems.

Journal

Public Health Nutrition

Six in seven women with a family history of breast cancer opt out of taking tamoxifen as a preventative measure, according to a study funded by Cancer Research UK and published in Breast Cancer Research and Treatment today (Tuesday)*.

Researchers asked 258 healthy women across England who had been identified as having an increased risk of the disease whether they had agreed to take the drug to help prevent breast cancer developing, and interviewed 16 women to identify what influenced their decision to take it.

Women chose not to start taking the drug because they thought cancer was down to fate, they distrusted medication in general or they feared side effects would interfere with looking after their family.

But overall the team, based at the University of Leeds, Northwestern University, University College London and Queen Mary University of London, found women with children were more likely to take up the offer of tamoxifen.

The research, which is the first of its kind since the drug was approved to be used for prevention, also suggested that social class, educational attainment and ethnicity had no effect on uptake.

Tamoxifen is most commonly given to women who have been treated for breast cancer to lower the risk of it recurring.

But in 2013 the National Institute for Health and Care Excellence (NICE) also approved it for cancer prevention in women at increased risk of the disease due to a family history of breast or ovarian cancer, following research which showed it could lower risk by around a third**.

Dr Samuel Smith, study author from the University of Leeds, said: "While it's reassuring a woman's background doesn't seem to be a barrier to taking tamoxifen, only one in seven of those at increased risk of breast cancer are taking up the option. Therefore it's important doctors can discuss women's concerns and provide information to help them while they are considering their options.

"Further research is needed to understand if all women eligible to take tamoxifen for prevention are getting the help and support they need."

Dr Richard Roope, Cancer Research UK's senior clinical adviser and GP expert, said: "When an established drug like tamoxifen is found to work not only as a treatment for breast cancer, but is also shown to reduce the risk of the disease, it seems we're making real progress.

"It's valuable to understand why women might reject tamoxifen, and this research highlights there are a range of complex reasons behind the decision.

"It's vital more work is done to understand these barriers, improve treatments and ensure doctors are getting the support they need to help women decide whether preventative medication is right for them.

"Whatever a woman's risk of developing breast cancer, keeping a healthy weight and cutting back on alcohol are also ways of reducing it."