Regeneration in the digestive tract / Antibiotics leave permanent traces in the gut

Public Release: 6-Nov-2018

 

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

The human gut is teeming with billions of beneficial bacteria. Therapies that use antibiotics often destroy most of them. Whether and how the intestinal flora will subsequently recover has been investigated by a research team that included scientists from the MDC. The results have been published in the scientific journal Nature Microbiology.

The human digestive tract houses a universe of tiny organisms. There are roughly as many bacteria in the gut as there are people living on earth. These microorganisms almost always serve the well-being of their host. They help to digest food, produce vitamins, and train the immune system. In addition, their very presence helps stem the spread of pathogens.

But the intestinal microcosm, also known as the microbiome, is sensitive to disruptions. “When thrown out of balance, there is a risk of infection, excess weight, and diabetes, as well as inflammatory and neurological diseases,” says Dr. Sofia Forslund, who in May this year switched from the European Molecular Biology Lab (EMBL) in Heidelberg to the Max Delbrück Center for Molecular Medicine (MDC) in Berlin to study the complex interactions between humans and microbiomes.

Antibiotics leave permanent traces in the gut

In a study published recently in Nature Microbiology, Forslund, together with colleagues from Denmark, Germany, and China, investigated how broad-spectrum antibiotic therapy affects the interaction of gut bacteria. “We were able to show that the microbiome had almost completely recovered six months after drug administration,” says the Swedish researcher. But only “almost”: “Some sensitive bacterial species disappeared completely,” says Forslund.

In the four-day study, the team led by MDC researchers and two scientists from the University of Copenhagen administered a cocktail of three antibiotics (meropenem, gentamicin, and vancomycin) to twelve healthy young men who had agreed to participate. These drugs are mainly used when more common antibiotics no longer work, due to the bacteria already having become resistant to them.

Some types of bacteria survived the drug administration

The researchers then studied their subjects’ microbiomes for six months. By means of DNA sequencing – a method used to determine the structure of the genetic material – they determined which bacterial species were present in the men’s guts, and which genes were present in the bacteria. The team also paid particular attention to resistance genes, with which the microbes defend themselves against drugs. “Our study is probably the first to investigate the influence of antibiotics on bacterial gene activity,” says Forslund.

It was first shown that the gut had not become completely sterile despite the administration of three potent antibiotics, reports the researcher. Among the remaining bacteria, the team even discovered some previously unknown species that have not yet been characterized. Other microbes shrank and turned into spores – a life form in which bacteria can persist for many years in precarious conditions without losing their original properties.

More and more disease-causing pathogens initially appeared

The subsequent repopulation of the gut was gradual. “Similar to when a forest slowly recovers after a fire,” says Forslund. However, according to the researcher, bacteria with disease-causing properties, such as Enterococcus faecalis and Fusobacterium nucleatum, initially appeared more frequently. At the same time, the team was able to identify many virulence factors in the microorganisms – structures and metabolites that are more harmful to humans. “This observation explains why most antibiotics cause gastrointestinal disturbances,” says Forslund.

Over time, however, the intestinal flora normalized again. Bad microbes were increasingly replaced by good bacteria such as the lactic acid-producing bifidobacteria that are instrumental in keeping pathogens away. After six months, the subjects’ microbiome was nearly the same as before. However, more than a few of the earlier bacterial varieties were missing. “As expected, the number of resistance genes in the bacteria also increased,” reports Forslund. Surprisingly, it was not the case that the bacterial species that reappeared most rapidly after antibiotic administration also had the most resistance genes. “This genetic material seems more likely to play a long-term role in gut repopulation,” says the researcher.

The lung microbiome will also be investigated further

“Given the apparently permanent loss of individual species and the increased number of resistance genes, the study shows once again how important it is to administer antibiotics with care,” Forslund emphasizes, adding: “It must also be further explored how to increase future success rates in protecting the sensitive microbiome from damage caused by antibiotics.”

The scientist plans to contribute to this research. For example, the MDC is currently running an observational study through which Forslund wants to find out how longer-term antibiotic treatments affect gut biodiversity – and whether a greater depletion of species increases the risk of obesity and metabolic diseases. She would also like to investigate how often gut bacteria exchange their resistance genes during antibiotic administration. A study investigating the influence of these drugs on the lung microbiome is already in the planning stage.

###

Albert Palleja et al. (2018): “Recovery of gut microbiota of healthy adults following antibiotic exposure.” Nature Microbiology 3. doi:10.1038/s41564-018-0257-9 (Publication available upon request.)

The Max Delbrück Center for Molecular Medicine (MDC)

The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrück, who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC’s mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent, and fight it better and more effectively. In these efforts the MDC cooperates with the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just under 1,300 of them in scientific research. The MDC is funded by the German Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent), and is a member of the Helmholtz Association of German Research Centers. http://www.mdc-berlin.de

Higher levels of urinary fluoride associated with ADHD in children

Public Release: 10-Oct-2018

University of Toronto

Higher levels of urinary fluoride associated with Attention Deficit Hyperactivity Disorder (ADHD) in children

Higher levels of urinary fluoride during pregnancy are associated with more ADHD-like symptoms in school-age children, according to University of Toronto and York University researchers.

“Our findings are consistent with a growing body of evidence suggesting that the growing fetal nervous system may be negatively affected by higher levels of fluoride exposure,” said Dr. Morteza Bashash, the study’s lead author and researcher at the Dalla Lana School of Public Health.

The study, “Prenatal Fluoride Exposure and Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Children at 6-12 Years of Age in Mexico City,” published today in Environment International, analyzed data from 213 mother-child pairs in Mexico City that were part of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project, which recruited pregnant women from 1994 to 2005 and has continued to follow the women and their children ever since.

Tap water and dental products have been fluoridated in communities in Canada and the United States (as well as milk and table salt in some other countries) by varying amounts for more than 60 years to prevent cavities. In recent years, fierce debate over the safety of water fluoridation — particularly for children’s developing brains — has fueled researchers to explore the issue and provide evidence to inform national drinking water standards.

The research team — including experts from the University of Toronto, York University, the National Institute of Public Health of Mexico, University of Michigan, Indiana University, the University of Washington and Harvard School of Public Health — analyzed urine samples that had been obtained from mothers during pregnancy and from their children between six and 12 years of age to reconstruct personal measures of fluoride exposure for both mother and child.

The researchers then analyzed how levels of fluoride in urine related to the child’s performance on a variety of tests and questionnaires that measure inattention and hyperactivity, and provide overall scores related to ADHD. Analyses were adjusted for other factors known to impact neurodevelopment, such as gestational age at birth, birthweight, birth order, sex, maternal marital status, smoking history, age at delivery, education, socioeconomic status and lead exposure.

“Our findings show that children with elevated prenatal exposure to fluoride were more likely to show symptoms of ADHD as reported by parents. Prenatal fluoride exposure was more strongly associated with inattentive behaviours and cognitive problems, but not with hyperactivity,” said Bashash.

This work builds off of previous research the team published on this population demonstrating that higher levels of urine fluoride during pregnancy are associated with lower scores on tests of IQ and cognition in the school-age children.

ADHD is the most common psychiatric disorder diagnosed in childhood, affecting between five and nine per cent of all school-aged children.

“The symptoms of ADHD often persist into adulthood and can be impairing in daily life,” said Christine Till, Associate Professor of Psychology at York University and co-author on the study.

“If we can understand the reasons behind this association, we can then begin to develop preventive strategies to mitigate the risk,” said Till, who is also the principal investigator of another National Institutes of Health-funded grant examining fluoride exposure in a large Canadian sample of pregnant women.

###

The National Institute of Environmental Health Sciences, part of the National Institutes of Health (NIH), funded this study.

Changes in bacterial mix linked to antibiotics increase risk for type 1 diabetes

Public Release: 24-Jul-2018

NYU Langone Health / NYU School of Medicine

A single course of antibiotics early in childhood may increase risk for Type 1 diabetes. This is the finding of a study in mice led by researchers from NYU Medical School and published online July 24 in the journal eLife.

The study centered on the intestinal microbiome, the mix of bacterial species that live in the digestive tract, and that co-evolved with humans to play roles in nutrition and immunity. As rates of children’s exposure to antibiotics has increased in recent decades – with each child receiving nearly three courses on average in the first two years of life – the number of patients with type 1 diabetes has doubled, say the study authors.

In prior work, and using mice that have an unusually high rate of type 1 diabetes, the research team had found that exposure to multiple courses of antibiotics accelerated onset of this disease. The current study finds that even a single antibiotic course significantly increased risk and severity.

The normal mix of inherited microbes is thought to “educate” the founding immune system, with evolution choosing microbes that decrease the sensitivity of immune cells, making them less likely to mistakenly attack the body’s own cells, say the authors. In autoimmune diseases like type 1 diabetes, immune cells that normally control invading microbes instead destroy insulin-producing cells in the pancreas.

Patients with type 1 diabetes produce little or no insulin, the hormone that controls the level of sugar in the blood. In the current study, the onset of disease was determined by measuring blood sugar, and by marking when levels rose to extremely high levels due to the lack of insulin.

“Our findings confirm earlier work showing that antibiotics can increase risk for type 1 diabetes,” says lead study author Xuesong Zhang, PhD, assistant professor of Medicine at NYU School of Medicine. “Even a single early life course may perturb the intestinal microbiome in ways that lead to long-term consequences in the intestinal wall, including immune cell changes and damage to the pancreas.”

Senior study investigator Martin Blaser, M.D., director of the Human Microbiome Program at NYU School of Medicine, said the results “are a model of the pervasive effects that antibiotic courses may have on children, causing immune systems to develop abnormally on the way to serious illness.”

The research team used genomic and statistical techniques to analyze the millions of pieces of bacterial DNA in samples taken from the study mice. Past studies had already matched key DNA sequences to known bacterial species, enabling the team to define each mouse’s microbiome, and to watch the effect of antibiotics on each.

Specifically, the study found that four bacterial species groups (taxa) – Enterococcus, Blautia, Enterobacteriaceae, and Akkermansia – were significantly more abundant in the guts of mice treated with the single course of antibiotics, and likely involved in driving progression of type 1 diabetes. While normally harmless, such species, called pathobionts, cause disease when environmental factors like antibiotics alter the normal balance. Past studies had found that human children who later developed type 1 diabetes were more likely to have had altered gut microbiota representation of Blautia and Akkermansia mucinophila early in life, with corresponding changes to their immune systems.

The shift in dominant species seen with antibiotics was accompanied by a shift in active bacterial genes and in chemical compounds produced by the bacteria. This in turn caused changes in gene expression patterns in the intestinal wall, say the authors. Many of these genes are known to influence the type of immune cell activation that damages pancreatic islets.

In addition, populations of four different taxa – S24-7, Clostridiales, Oscillospira, and Ruminococcus – were significantly smaller in mice treated with antibiotics in comparisons with normal mice during the developmental post-birth time window previously shown to be critical to educating the immune system. The results suggest that these taxa may be protective against Type 1 diabetes, and could be a focus of future development of probiotics, for instance, that seek to restore healthy species in newborns.

The current study focused on male mice simply because it examined mechanisms found to be important in the autoimmune development regardless of gender.

The authors say their findings support the hypothesis that, by diminishing particular beneficial bacteria, one early exposure to antibiotics permits the emergence of other species that change immunological development and worsen pancreatic damage.

###

Along with Blaser and Zhang, study authors from the NYU School of Medicine departments of Medicine and Microbiology were Jackie Li, Michelle Badri, Thomas Battaglia, Timothy Borbet, Sandy Ng, Rachel Sibley, Shawn Jindal, Victoria Ruiz, Alexandra Livanos, and Kelly Ruggles. Other NYU authors were Hyunwook Koh and Huilin Li from the Department of Population Health at NYU School of Medicine, as well as Richard Bonneau of New York University’s Center for Data Science.

Authors from other institutions were Kimberly Krautkramer and John Denu from the Department of Biomolecular Chemistry at the University of Wisconsin School of Medicine and Public Health; Yuanyuan Li, Wimal Pathmasiri. and Susan Jenkins Sumner of the Nutrition Research Institute at the University of North Carolina at Chapel Hill School of Public Health; Robin Shields-Cutler, Ben Hillmann, Gabriel Al-Ghalith, and Dan Knights of the BioTechnology Institute, Computer Science and Engineering, University of Minnesota, St. Paul; Arlin Rogers Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, and Angelique Wout, Nabeetha Nagalingam, Anthony Williamson, and Marcus Rauch of the Janssen Prevention Center London, London, UK.

These study was supported by National Institute of Health grants 5T35DK007421, R37GM059785, F30 DK108494, T32GM008692, and R01DK110014, as well as by Janssen Labs London (15-A0-00-00-0039-29-01), the TransAtlantic Networks of Excellence Program of Fondation Leducq, and by the C & D fund.

Anticonvulsant drugs ineffective for low back pain and can cause harm, despite increased prescribing

Public Release: 3-Jul-2018

Canadian Medical Association Journal

Anticonvulsant drugs are increasingly being used to treat low back pain, but a new study in CMAJ (Canadian Medical Association Journal) finds they are ineffective and can have adverse effects.

“Clinically, the prescription of anticonvulsants for back and neck pain, including radicular pain in primary care, has increased by 535% in the last 10 years,” writes Dr. Oliver Enke, University of Sydney, Sydney Medical School Nepean, Kingswood, Australia, with coauthors, citing data from a recent study on prescribing trends for back pain.

Low back pain affects millions of people and is the number one cause of disability. Clinical practice guidelines usually recommend nonpharmacologic treatments and nonopioid pain relievers rather than stronger analgesics such as anticonvulsants.

The study findings are based on high and moderate-quality evidence from 9 placebo-controlled randomized trials that found a lack of evidence of benefit from anticonvulsants and more adverse events from some of these drugs.

“We have shown, with mostly high- and moderate-quality evidence, that common anticonvulsants are ineffective for chronic low back pain and lumbar radicular pain, and are accompanied by increased risk of adverse events,” write the authors.

These findings support recent guidelines from the United States and the United Kingdom that do not recommend the use of anticonvulsants.

“Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis” is published July 3, 2018.

Antidepressants may increase risk of death by 20 percent for those COPD

Public Release: 26-Jun-2018

 

Serotonergic antidepressants increase respiratory-related adverse events for those with chronic obstructive pulmonary disease, study suggests

St. Michael’s Hospital

TORONTO, June 26, 2018 – Antidepressant use in people with chronic obstructive pulmonary disease (COPD) is associated with a 20 per cent increase in likelihood of death and a 15 per cent increase in likelihood of hospitalization due to related symptoms, finds a new study led by researchers at St. Michael’s Hospital.

Published today in the European Respiratory Journal, the research suggests that amongst adults with COPD, new users of serotonergic antidepressants – a specific class of the medication – have higher rates of hospitalization, emergency room visits, and mortality related to respiratory conditions, as well as death overall versus non-users of the medications. While the study does not show cause and effect, it suggests strong association.

“We were not surprised by these findings, as there are biological reasons why antidepressants could lead to respiratory issues,” said Dr. Nicholas Vozoris, a scientist in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital and the lead author. “These drugs can cause sleepiness, vomiting and can negatively impact immune system cells. This increases the likelihood of infections, breathing issues, and other respiratory adverse events, especially in patients with COPD.”

COPD is a progressive lung disease that causes increasing breathlessness. It affects more than 10 per cent of those aged 40 and older worldwide. Because of the nature of the disease, upwards of 70 per cent of those with COPD also struggle with symptoms of low mood and anxiety, said Dr. Vozoris, who is also an assistant professor in the Department of Medicine at the University of Toronto and a respirologist at St. Michael’s.

Using health administrative databases from the Institute of Clinical Evaluative Sciences (ICES), Dr. Vozoris and his team studied 28,360 new users of serotonergic antidepressants with COPD aged 66 and older and matched them to an equivalent amount of non-users. The analysis revealed that among older adults with COPD, new users of this class of medication have modest, but significant, increases in rates of breathing-related death and all causes of death. The research showed a strong association, but not a definite cause and effect.

“The study results should not cause alarm among those who use these medications, but rather increase caution among patients and physicians,” Dr. Vozoris said. “I hope our study encourages increased awareness when prescribing these medications and monitoring for adverse side effects. Also, because there is this association, we as physicians should give thought to psychotherapy and pulmonary rehabilitation as non-drug related treatment.”

Dr. Vozoris plans to continue to study other classes of medications used for treatment of psychological issues in patients with COPD to build a more complete picture of medication risks.

###

This research was funded by the University of Toronto and supported by the Institute of Clinical Evaluative Sciences.

About St. Michael’s Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael’s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.

Media contact

For more information or for an interview with Dr. Vozoris, please contact:

Ana Gajic
Senior Communications Advisor
St. Michael’s Hospital
Phone: 416-864-5960 or 416 458 0629
Gajica@smh.ca
Inspired Care. Inspiring Science.
http://www.stmichaelshospital.com
Follow us on Twitter: http://www.twitter.com/stmikeshospital

One-third of US adults may unknowingly use medications that can cause depression

Public Release: 12-Jun-2018

 

Polypharmacy on the rise

University of Illinois at Chicago

IMAGE

IMAGE: This is Dima Qato.

Credit: UIC/Jenny Fontaine

A new study from University of Illinois at Chicago researchers suggests that more than one-third of U.S. adults may be using prescription medications that have the potential to cause depression or increase the risk of suicide, and that because these medications are common and often have nothing to do with depression, patients and health care providers may be unaware of the risk.

The researchers retrospectively analyzed medication use patterns of more than 26,000 adults from 2005 to 2014, which were collected as part of the National Health and Nutrition Examination Survey. They found that more than 200 commonly used prescription drugs — including hormonal birth control medications, blood pressure and heart medications, proton pump inhibitors, antacids and painkillers — have depression or suicide listed as potential side effects.

Published in the Journal of the American Medical Association, the study is the first to demonstrate that these drugs were often used concurrently and that concurrent use, called polypharmacy, was associated with a greater likelihood of experiencing depression. Approximately 15 percent of adults who simultaneously used three or more of these medications experienced depression while taking the drugs, compared with just 5 percent for those not using any of the drugs, 7 percent for those using one medication and 9 percent for those taking two drugs simultaneously.

The researchers observed similar results for drugs that listed suicide as a potential side effect. These findings persisted when the researchers excluded anyone using psychotropic medications, considered an indicator of underlying depression unrelated to medication use.

“The take away message of this study is that polypharmacy can lead to depressive symptoms and that patients and health care providers need to be aware of the risk of depression that comes with all kinds of common prescription drugs — many of which are also available over the counter,” said lead author Dima Qato, assistant professor of pharmacy systems, outcomes and policy in the UIC College of Pharmacy. “Many may be surprised to learn that their medications, despite having nothing to do with mood or anxiety or any other condition normally associated with depression, can increase their risk of experiencing depressive symptoms, and may lead to a depression diagnosis.”

Qato notes that the study also shows an important trend of increasing polypharmacy for medications with depression, particularly suicidal symptoms, as a potential adverse effect. This makes the need for awareness of depression as a potential side effect even more pressing.

The researchers found use of any prescription medication with a potential depression adverse effect increased from 35 percent in the 2005 to 2006 period to 38 percent in the 2013 to 2014 period. Approximate use of antacids with potential depression adverse effects, like proton pump inhibitors and H2 antagonists, increased from 5 percent to 10 percent in the same period. Use of three or more drugs concurrently increased from 7 percent to 10 percent, approximately.

For prescription drugs with suicide listed as a potential side effect, usage increased from 17 percent to 24 percent, and use of three or more drugs concurrently increased from 2 percent to 3 percent.

“People are not only increasingly using these medicines alone, but are increasingly using them simultaneously, yet very few of these drugs have warning labels, so until we have public or system-level solutions, it is left up to patients and health care professionals to be aware of the risks,” Qato said.

Qato says that solutions worth further study may include updating drug safety software to recognize depression as a potential drug-drug interaction, so that health care professionals, including pharmacists, are more likely to notice if a patient is using multiple medications that may increase risk. Or, including evaluation of medication use in the depression screening and diagnostic tools used by doctors and nurses and recommended by the U.S. Preventive Services Task Force, especially when it comes to persistent or treatment-resistant depression.

“With depression as one of the leading causes of disability and increasing national suicide rates, we need to think innovatively about depression as a public health issue, and this study provides evidence that patterns of medication use should be considered in strategies that seek to eliminate, reduce or minimize the impact of depression in our daily lives,” Qato said.

Co-authors on the study are Katharine Ozenberger of UIC and Columbia University’s Mark Olfson. Qato and Olfson both noted financial disclosures potentially relevant to the study

Millions could have incorrect statin, aspirin and blood pressure prescriptions

Public Release: 4-Jun-2018

Stanford Medicine

More than 11 million Americans may have incorrect prescriptions for aspirin, statins and blood pressure medications, according to a study led by researchers at the Stanford University School of Medicine.

Their findings are based on an updated set of calculations — known as pooled cohort equations, or PCEs — that are used to determine the risk of a heart attack or stroke.

The PCEs are the foundation for cardiovascular-disease-prevention guidelines in the United States. They help physicians decide whether to prescribe aspirin, blood pressure or statin medications, or some combination of these, by estimating the risk a patient may have for a heart attack or stroke. Most physicians calculate a patient’s risk using a PCE web calculator or a smartphone app; the equations are also built into many electronic health records so that a patient’s risk is automatically calculated during an office visit.

But there has been debate over whether the PCEs are based on outdated data and therefore putting some patients at risk for over- or under-medication.

“We found that there are probably at least two major ways to improve the 2013 equations,” said Sanjay Basu, MD, PhD, assistant professor of primary care outcomes research at the School of Medicine and a core faculty member at Stanford Health Policy. “The first was well-known: that the data used to derive the equations could be updated.”

Old equations

For example, he said, one of the main data sets used to derive the original equations had information from people who were 30-62 years old in 1948, and who would therefore be 100 to 132 years old in 2018 — that is, likely dead. The older equations were often estimating people’s risk as too high, possibly by an average of 20 percent across risk groups.

“A lot has changed in terms of diets, environments and medical treatment since the 1940s,” Basu said. “So, relying on our grandparents’ data to make our treatment choices is probably not the best idea.”

Basu is the senior author of the study, which will be published June 5 in the Annals of Internal Medicine. The lead author is Steve Yadlowsky, a graduate student in electrical engineering at Stanford.

Furthermore, the researchers found that the old data may not have had a sufficient sample of African-Americans. For many African-Americans, physicians may have been estimating the risks of heart attacks or strokes as too low.

“So while many Americans were being recommended aggressive treatments that they may not have needed according to current guidelines, some Americans — particularly African-Americans — may have been given false reassurance and probably need to start treatment given our findings,” Basu said.

The researchers have updated the PCEs with newer data in an effort to substantially improve the accuracy of the cardiovascular risk estimates. The National Institutes of Health, which maintains and updates the cohort data, approved the updated equations.

Updating statistical methods

A second improvement to the equations, the authors found, was to update the statistical methods used to derive the equations.

“We found that by revising the PCEs with new data and statistical methods, we could substantially improve the accuracy of cardiovascular disease risk estimates,” the authors wrote.

The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

###

Basu is a member of Stanford Bio-X and the Child Health Research Institute.

Researchers from the University of Michigan, University of Washington and University of Mississippi also contributed to the study.

The study was supported by the National Institutes of Health (grants DP2MD010478, U54MD010724, K08HL121056 and P30DK092926) and a Stanford University graduate fellowship.

Stanford’s Department of Medicine also supported the work.

The Stanford University School of Medicine consistently ranks among the nation’s top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Stanford Children’s Health. For information about all three, please visit http://med.stanford.edu.

Oral antibiotics linked to increased kidney stone risk for several years after use

PUBLIC RELEASE: 10-MAY-2018

Risk appears to be highest among children

AMERICAN SOCIETY OF NEPHROLOGY

Highlights

  • Use of oral antibiotics was linked with an increased risk of developing kidney stones.
  • Risk decreased over time but was still elevated several years after antibiotic use.
  • Risk was highest for young patients.

Washington, DC May 10, 2018) — The potential to promote antibiotic resistance in bacteria isn’t the only reason to avoid using antibiotics when possible. A new study reveals that antibiotics are also linked with an increased risk of developing kidney stones, with the greatest risk among children. The findings appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

For reasons that are unclear, the prevalence of kidney stones–or nephrolithiasis–has increased 70% over the last 30 years, with the most disproportionate increase experienced by children and adolescents. Because perturbations in bacterial communities residing in the intestines and urinary tract have been associated with nephrolithiasis, a team led by Gregory Tasian MD, MSc, MSCE and Michelle Denburg MD, MSCE (The Children’s Hospital of Philadelphia) examined whether the use of antibiotics might affect individuals’ risk of developing the condition.

For their study, the investigators determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based study within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. The team matched 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at the date of diagnosis (termed the index date).

Exposure to any one of five different antibiotic classes 3-12 months before the index date was associated with nephrolithiasis. Risks were increased 2.3-times, 1.9-times, 1.7-times, 1.7-times, and 1.3-times for sulfas, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine, and broad-spectrum penicillins, respectively. The risk of nephrolithiasis decreased over time, but it remained elevated at 3-5 years after the antibiotic prescription. Also, the risk was greatest for exposures at younger ages. Previous research has shown that children receive more antibiotics than any other age group, and 30% of antibiotics prescribed during ambulatory care visits are inappropriate.

“These findings demonstrate that exposure to certain antibiotics is a novel risk factor for kidney stones and that the risk may be greatest when exposure to these antibiotics occurs at younger ages,” said Dr. Tasian. “Consequently, these results suggest that the risk of nephrolithiasis may be decreased by reducing inappropriate antibiotic exposure and choosing alternative antibiotics, particularly for those patients who are at increased risk of stone formation.”

###

Study co-authors include Thomas Jemielita, PhD, David S. Goldfarb, MD, Lawrence Copelovitch, MD, Jeffrey Gerber MD, PhD, MSCE, and Qufei Wu, MS.

Disclosures: The authors have no conflicts of interest to declare.

The article, entitled “Oral Antibiotic Exposure and Kidney Stone Disease,” will appear online at http://jasn.asnjournals.org/ on May 10, 2018, doi: 10.2215/ASN.2017111213.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 18,000 members representing 112 countries. For more information, please visit http://www.asn-online.org or contact the society at 202-640-4660.

Noise throws the heart out of rhythm

Public Release: 3-May-2018

 

Mainz University Medical Center publishes new results on noise pollution from the Gutenberg Health Study

Johannes Gutenberg Universitaet Mainz

IMAGE

IMAGE: Noise throws the heart out of rhythm.

Credit: Photomontage realized by Peter Pulkowski, Mainz University Medical Center

With an increasing level of noise, the incidence of atrial fibrillation also increases dramatically. Scientists from the Department of Cardiology at the Mainz University Medical Center were able to prove this with data from the Gutenberg Health Study. They found that the incidence of atrial fibrillation in subjects with extreme noise annoyance reactions increases to 23 percent, compared to just 15 percent without this environmental impact. Looking at the proportion of sources of extreme noise pollution, aircraft noise came first with 84 percent during the day and 69 percent during sleep. These results from the Gutenberg Health Study were published recently in the renowned International Journal of Cardiology.

Noise annoyance is a very important indicator in order to decide which noise levels may be considered significant or unacceptable and may be even harmful for our health. Anger, disturbed sleep, exhaustion, and stress symptoms due to noise permanently impair wellbeing, health, and the quality of life. “We have already been able to prove the connection between noise and vascular disease in several studies in healthy volunteers and patients with established coronary artery disease as well as in in preclinical studies. To date, there has been no explicit study being published which addresses to what extent noise annoyance can cause cardiac arrhythmia,” emphasized Professor Thomas Münzel, Director of Cardiology I at the Department of Cardiology at the Mainz University Medical Center and senior author of the study.

The effects of noise pollution have been a subject of research within the framework of the Gutenberg Health Study (GHS). The GHS is one of the world’s largest studies of its kind, including more than 15.000 men and women aged 35 to 74 from the state capital of Rhineland-Palatinate and the district of Mainz-Bingen.

The researchers investigated the relationship between different noise sources during the day and at night during sleep and the most common arrhythmia in the general population, i.e., atrial fibrillation. The study found that increasing annoyance is associated with a significant increase in the frequency of atrial fibrillation. This grew up to 23 percent in subjects experiencing extreme noise annoyance, while only 15 percent experienced no noise annoyance at all. In this context, it has been shown that aircraft noise accounts for the largest share of extreme noise pollution: 84 percent during the day and 69 percent during sleep. The aircraft noise annoyance affected 60 percent of the population, more than every second in the Mainz-Bingen region. Thus, it clearly outperformed other noise sources such as road, rail, or neighborhood noise.

“The study shows for the first time that noise annoyance caused by various noise sources during the day and night is associated with an increased risk of atrial fibrillation,” concluded study leader Omar Hahad, research associate at the Deparment Cardiology, Cardiology I. “Overall, we were able to demonstrate a stronger influence of annoyance caused by nocturnal noise on the heart rhythm.”

The study leaders, however, point out that noise annoyance was measured, not physical noise. Since this is a cross-sectional study, no statements can be made with respect to a causal relationship.

Participants in the GHS study were asked to rate how much they had been harassed in recent years by road, rail, construction, trade, neighborhood noise and aircraft noise, both day and night. Noise annoyance was recorded using internationally accepted, standardized questionnaires. Atrial fibrillation was diagnosed on the basis of the medical history (anamnestic) and / or on the study ECG.

“The relationship between noise annoyance and atrial fibrillation is an important finding that may also explain why noise can lead to more strokes. However, one must not forget that noise also leads to damage to health without the need for an anger reaction,” said Professor Thomas Münzel.

In addition, the impact of the night-time ban introduced by Frankfurt am Main airport (11 p.m. to 5 a.m.) in October 2011 on the aircraft noise reported by the participants was examined. “Interestingly, there was a significant increase in aircraft noise after the introduction of the no-fly ban, both during the day and at night,” commented Münzel. “This could be due to the fact that in spite of the ban on night flights altogether the number of flight movements has not decreased and the flight movements have been concentrated more in the marginal hours of 10 p.m. to 11 p.m. and 5 a.m. to 6 a.m.” The authors conclude that, for example, the total ban on scheduled aircraft movements at the Frankfurt Airport has to be expanded from 11 p.m. to 5 a.m. to 10 p.m. to 6 a.m., in accordance with the definition of nighttime in Germany.

Daily aspirin doubles the risk of melanoma in men

Public Release: 3-May-2018

Daily aspirin linked to higher risk in men

Women taking daily aspirin do not have higher risk in the same population

Northwestern University

  • Results surprising because aspirin is often reported to decrease risk of certain cancers
  • Men who take daily aspirin may benefit from periodic skin exams by the dermatologist
  • ‘This does not mean men should stop aspirin therapy’

CHICAGO — Men who take once-daily aspirin have nearly double the risk of melanoma compared to men who are not exposed to daily aspirin, reports a new Northwestern Medicine study.

Women, however, do not have an increased risk in this large patient population.

“Given the widespread use of aspirin and the potential clinical impact of the link to melanoma, patients and health care providers need to be aware of the possibility of increased risk for men,” said senior study author Dr. Beatrice Nardone, research assistant professor of dermatology at Northwestern University Feinberg School of Medicine.

She suggested increasing patient education about sun exposure, avoiding tanning beds and getting skin checks by a dermatologist, particularly for individuals who are already at high risk for skin cancers.

“This does not mean men should stop aspirin therapy to lower the risk of heart attack,” she stressed.

Almost half of people age 65 and over reported taking aspirin daily or every other day, according to a 2005 study. In 2015, about half of a nationwide survey of U.S. adults reported regular aspirin use.

The study was published April 27 in the Journal of the American Academy of Dermatology.

Nardone was surprised at the results because aspirin is reported to reduce risk of gastric, colon, prostate and breast cancer. And some previous studies have reported a reduced risk in aspirin-exposed men and an increased risk in aspirin-exposed women. Nardone attributed this to variability of the research methods used in studies that look for associations and risks for cancers.

Among the numerous possibilities, one reason men may be more vulnerable could be related to males (human and animal species) expressing a lower amount of protective enzymes, like superoxide dismutase and catalase, compared to females, Nardone speculated.

“These lower levels of protective enzymes suggest that a higher level of resulting oxidative cellular damage in men might contribute to the possibility of developing melanoma,” said Nardone, who is an investigator for the Research on Adverse Drug Events and Reports Program at Northwestern.

The study collected medical record data comprising almost 200,000 patients who were aspirin-exposed or aspirin-unexposed (control group), ages 18-89, with no prior history of melanoma and with a follow-up time of at least five years.

For the aspirin-exposed patient population, the study included only patients who had at least one year of once-daily aspirin exposure at a dose of 81 or 325 mg occurring between January 2005 and December 2006 in order to allow for at least five years of follow-up data to detect if melanoma occurred over time. Out of a total of 195,140 patients, 1,187 were aspirin exposed. Of these 1,187 patients, 26 (2.19 percent) (both men and women) had a subsequent diagnosis for melanoma compared to 1,676 (0.86 percent) in aspirin-unexposed (men and women) patients.

When the groups were separated into men and women, men exposed to aspirin had almost twice the risk for diagnosis of melanoma (adjusted relative risk: 1.83) compared to men in the same population who were not exposed to aspirin.

###

Other Northwestern authors include Kelsey Orrell, Ahuva D. Cices, Nicholas Guido, Sara Majewski, Erin Ibler, Thy Huynh, Stephanie Rangel, Anne Laumann, Mary Martini, Alfred Rademaker and Dennis West.

The Northwestern Medicine Enterprise Data Warehouse (NMEDW) was used as a data source. The NMEDW, is supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, Grant Number UL1TR001422.

Kids exposed to general anesthestic have poorer development, literacy and numeracy scores

Public Release: 26-Apr-2018

 

University of Sydney

The new finding published today in Pediatric Anesthesia, is based on a data-linkage study of over 210,000 children in New South Wales, Australia.

The 211,978 children included in the study were born in New South Wales at 37-plus weeks’ gestation without major congenital anomalies or neurodevelopmental disability. Of these, researchers had data on their school entry developmental assessment in 2009, 2012, or their Grade-3 school test results in 2008-2014.

The researchers compared the developmental and school results of children exposed to general anaesthesia during hospital procedures (37,880) up to 48 months of age to same-aged children with no exposure to general anaesthesia or hospitalisation (197,301).

Key findings

Compared to children unexposed to general anaesthesia, those exposed to general anaesthesia had a:

  • 17 per cent increased risk of poor child development
  • 34 per cent increased risk of lower numeracy scores on school tests
  • 23 per cent increased risk of lower reading scores on school tests.

When the researchers restricted their analyses to children who’d had only one hospitalisation involving a procedure requiring general anaesthesia, they found no increased risk for poor development or reduced reading scores, however the risk of poor numeracy scores remained.

“There are many reasons why a child requires surgery or investigation, and, in some cases, this may be lifesaving or unavoidable,” said the study’s senior author, Professor Natasha Nassar of the University of Sydney.

“For these children, our findings suggest that it is important to follow-up and monitor their literacy and numeracy skills when they reach school, and ensure early intervention, if required.”

Co-author Dr Justin Skowno, a clinical lecturer at the University of Sydney and senior staff specialist in Paediatric Anaesthesia at the Children’s Hospital, Westmead said:

“Determining exactly what is causing this effect is not easy.

“The children receiving a general anaesthetic in this study also had surgery, and often had other associated medical conditions.

“There are some procedures where alternative approaches or management may be possible, but the majority of surgeries in young infants and children cannot easily be postponed.”

“Parents can certainly discuss with their doctor and explore whether these procedures can be avoided, combined with other procedures, delayed to older ages or treated with alternatives to surgery, or other methods of sedation,” said Dr Skowno.

The researchers say further investigation of the specific effects of general anaesthesia on numeracy skills, underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to previous or long duration of general anaesthesia or with repeated hospitalisations.

Measures of development, literacy and numeracy

Child development was obtained from the Australian version of the Early Development Instrument (AvEDI), a nationwide triennial assessment of child development. It includes results from teachers’ assessment of five developmental domains: physical health and well-being, emotional maturity, communication skills and general knowledge, language, and cognitive skills (numeracy and literacy) and social competence.

Based on national percentiles, children with domain scores in the bottom 10 percent are classified as developmentally vulnerable in that domain. Children who are vulnerable in 2 or more domains are classified as developmentally high risk.

###

Children’s Grade 3 school performance was ascertained from the NSW Department of Education National Assessment Program-Literacy and Numeracy (NAPLAN) conducted in public schools in 2009- 2014. NAPLAN tests cover 5 domains: reading, writing, spelling, grammar and punctuation, and numeracy.

One in every six deaths in young adults is opioid-related: Study

 

Rate of opioid-related deaths in Ontario has tripled in past fifteen years, with most significant increase in young adults

St. Michael’s Hospital

IMAGE

IMAGE: Dr. Tara Gomes is a researcher at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital and the Institute for Clinical Evaluative Sciences (ICES).

Credit: St. Michael’s Hospital

TORONTO, April 26, 2018 – One out of every six deaths among young adults in Ontario is related to opioids, suggests a study led by researchers at St. Michael’s Hospital and the Institute for Clinical Evaluative Sciences (ICES).

The study, published today in the Journal of Addiction Medicine, found that the rate of opioid-related deaths nearly tripled in Ontario from 2000 to 2015, with one in every 133 deaths in Ontario related to opioid use by 2015. However, this number varied importantly by age group. The study expands on earlier research from Dr. Tara Gomes, which showed that one in 170 deaths in Ontario was related to opioid use in 2010.

“It is striking to see that despite the efforts put into harm reduction, proper prescribing practices, and education around opioid use, the number of opioid-related deaths continues to rise,” said Dr. Gomes, a scientist in the Li Ka Shing Knowledge Institute of St. Michael’s. “The other alarming fact is how this crisis is increasingly impacting our youth and young adults.”

Researchers reviewed all deaths in Ontario where prescribed or illicit opioids were determined to be a contributing factor between 2000 and 2015. In the last five years examined in this study (2010 to 2015), the most dramatic increase in opioid-related deaths occurred among those aged 15 to 24 years. By 2015, more than 1 in 9 deaths in this age group were opioid-related – up from 1 in 15 deaths five years earlier.

Dr. Gomes, who is also an ICES scientist, and her team found that a total of 29,410 years of potential life were lost prematurely due to opioid-related causes in 2015, which exceeds the years of life lost prematurely annually from diseases such as pneumonia, HIV/AIDS and influenza in the most recent data available.

“These shifting patterns show us that we have to better understand the dynamics of drug use in younger populations who are succumbing to opioid-related deaths,” Dr. Gomes said. “We can only truly understand this by talking directly to affected communities to learn what they need to create a safer environment in which to live.”

###

This study was funded by grants from the Ontario Ministry of Health and Long-Term Care and the Ontario Strategy for Patient-Oriented Research Support Unit, and was supported by ICES.

About St. Michael’s Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael’s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.

About the Institute for Clinical Evaluative Sciences

The Institute for Clinical Evaluative Sciences (ICES) is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting health care needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy. For the latest ICES news, follow us on Twitter: @ICESOntario

Media contacts:

Ana Gajic
Senior Communications Advisor | Communications and Public Affairs
GajicA@smh.ca
(o) 416-864-5960 or (c) 416-458-0629

Deborah Creatura
Media Advisor, ICES
deborah.creatura@ices.on.ca
(o) 416-480-4780 or (c) 647-406-5996

Common class of drugs linked to dementia even when taken 20 years before diagnosis

Public Release: 25-Apr-2018

 

Regenstrief Institute

INDIANAPOLIS – The largest and most detailed study of the long-term impact of anticholinergic drugs, a class of drugs commonly prescribed in the United States and United Kingdom as antidepressants and incontinence medications, has found that their use is associated with increased risk of dementia, even when taken 20 years before diagnosis of cognitive impairment.

An international research team from the US, UK and Ireland analyzed more than 27 million prescriptions as recorded in the medical records of 40,770 patients over age 65 diagnosed with dementia compared to the records of 283,933 older adults without dementia.

The researchers found greater incidence of dementia among patients prescribed anticholinergic antidepressants, anticholinergic bladder medications and anticholinergic Parkinson’s disease medications than among older adults who were not prescribed these drugs.

Dementia increased with greater exposure to anticholinergic medications.

“Anticholinergic Medication and Risk of Dementia: Case-control Study” is published in BMJ (formerly the British Medical Journal) an international peer-reviewed medical journal.

“Anticholinergics, medications that block acetylcholine, a nervous system neurotransmitter, have previously been implicated as a potential cause of cognitive impairment,” said Regenstrief Institute and Indiana University Center for Aging Research investigator Noll Campbell, PharmD, MS, a co-author of the new BMJ study. “This study is large enough to evaluate the long-term effect and determine that harm may be experienced years before a diagnosis of dementia is made.” Dr. Campbell is also an assistant professor of pharmacy practice at Purdue University College of Pharmacy.

“These findings make it clear that clinicians need to carefully consider the anticholinergic burden of their patients and weigh other options,” said study co-author Malaz Boustani, M.D., MPH, a Regenstrief Institute and IU Center for Aging Research investigator. Dr. Boustani is the founder of the Indiana Clinical and Translational Science Institute’s IU Center for Health Innovation and Implementation Science and the Richard M. Fairbanks Professor of Aging Research at IU School of Medicine.

“Physicians should review all the anticholinergic medications – including over-the-counter drugs – that patients of all ages are taking and determine safe ways to take individuals off anticholinergic medications in the interest of preserving brain health,” Dr. Boustani said.

The study, which was led by the University of East Anglia and funded by the Alzheimer’s Society, both in the UK, utilized data from the Clinical Practice Research Datalink which includes anonymized diagnosis, referral and prescription records for more than 11 million patients from 674 primary care practices across the UK. The data is broadly representative of the UK population in terms of age, sex and ethnicity.

“This research is really important because there are an estimated 350 million people affected globally by depression. Bladder conditions requiring treatment are estimated to affect over 13 percent of men and 30 percent of women in the UK and US,” said study lead researcher George Savva, PhD, visiting researcher at University of East Anglia’s School of Health Sciences.

“We don’t know exactly how anticholinergics might cause dementia,” said study co-author Chris Fox, MD, professor of clinical psychiatry at UEA’s Norwich Medical School and a consultant psychiatrist. “Further research is needed to understand possible reasons for this link. In the meantime, I strongly advise patients with any concerns to continue taking their medicines until they have consulted their doctor or pharmacist.”

Study co-author Ian Maidment, PhD, senior lecturer in clinical pharmacy at Aston University in the UK, said: “With many medicines having some anticholinergic activity, one key focus should be de-prescribing. Clinical staff, patients and carers need to work together collaboratively to limit the potential harm associated with anticholinergics.”

###

In addition to Regenstrief Institute, IU, Purdue, University of East Anglia and Aston University investigators, collaborators included researchers from the University of Aberdeen, the Royal College of Surgeons in Ireland, Newcastle University, and the University of Cambridge.

Commonly prescribed heartburn drug linked to pneumonia in older adults

Public Release: 24-Apr-2018

American Geriatrics Society

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.

###

About the Health in Aging Foundation

This research summary was developed as a public education tool by the Health in Aging Foundation. The Foundation is a national non-profit established in 1999 by the American Geriatrics Society to bring the knowledge and expertise of geriatrics healthcare professionals to the public. We are committed to ensuring that people are empowered to advocate for high-quality care by providing them with trustworthy information and reliable resources. Last year, we reached nearly 1 million people with our resources through HealthinAging.org. We also help nurture current and future geriatrics leaders by supporting opportunities to attend educational events and increase exposure to principles of excellence on caring for older adults. For more information or to support the Foundation’s work, visit http://www.HealthinAgingFoundation.org.

About the Journal of the American Geriatrics Society

Included in more than 9,000 library collections around the world, the Journal of the American Geriatrics Society (JAGS) highlights emerging insights on principles of aging, approaches to older patients, geriatric syndromes, geriatric psychiatry, and geriatric diseases and disorders. First published in 1953, JAGS is now one of the oldest and most impactful publications on gerontology and geriatrics, according to ISI Journal Citation Reports®. Visit wileyonlinelibrary.com/journal/JGS for more details.

About the American Geriatrics Society

Founded in 1942, the American Geriatrics Society (AGS) is a nationwide, not-for-profit society of geriatrics healthcare professionals that has–for 75 years–worked to improve the health, independence, and quality of life of older people. Its nearly 6,000 members include geriatricians, geriatric nurses, social workers, family practitioners, physician assistants, pharmacists, and internists. The Society provides leadership to healthcare professionals, policymakers, and the public by implementing and advocating for programs in patient care, research, professional and public education, and public policy. For more information, visit AmericanGeriatrics.org.

Post-surgical opioids can, paradoxically, lead to chronic pain

Public Release: 16-Apr-2018

 

Rats given morphine experienced pain-reactivity for three weeks longer, inflammatory changes in spinal cord

University of Colorado at Boulder

Giving opioids to animals to quell pain after surgery prolongs pain for more than three weeks and primes specialized immune cells in the spinal cord to be more reactive to pain, according to a new study by the University of Colorado Boulder.

The authors say the paradoxical findings, if replicated in humans, could have far-reaching implications for patient pain management and add a new wrinkle to the conversation about the national opioid epidemic.

“This indicates that there is another dark side of opiates that many people don’t suspect,” said senior author Linda Watkins, a professor in the Department of Psychology and Neuroscience. “It shows that trauma, including surgery, in combination with opiates can lead to chronic pain.”

For the study, Watkins and co-author Peter Grace, then an assistant research professor at CU Boulder, performed exploratory abdominal surgery, or laparotomy, on male rats. A similar procedure is done tens of thousands of times annually in the United States in humans, and opiates are routinely used after surgery.

“Opiates are really effective for acute pain relief. There is no drug that works better. But very little research has been done to look at what it is doing in the weeks to months after it’s withdrawn,” said Grace, now an assistant professor at MD Anderson Cancer Center in Houston.

In one experiment, half the rats were given the equivalent of what would be a “moderate” dose of morphine in people for seven days postsurgery. Half were given a saline solution.

In another experiment, the rats were given morphine for eight days and then tapered off by day 10. In a third, the animals were given morphine until day 10 and then it was abruptly withdrawn.

Before and after the treatments, the researchers measured the animal’s sensitivity to touch as well as activity of genes that express inflammatory proteins in the spinal cord.

They found that rats given morphine experienced postoperative pain for more than three weeks longer. The longer they received morphine, the longer their pain lasted. And gradual tapering made no difference.

“This tells us that this is not a phenomenon related to opioid withdrawal, which we know can cause pain. Something else is going on here,” Grace said.

Watkins describes that something as a “one-two hit” on specialized immune system cells called glial cells in the central nervous system. The first hit, the surgery, stimulates what she calls the “not me, not right, not OK” receptor, Toll-like receptor 4 on the cells, igniting the release of a cascade of inflammatory proteins and “priming” them to be on guard for a second hit.

Morphine, which also stimulates that receptor, is the second hit.

“With that second hit, the primed glial cells respond faster, stronger and longer than before, creating a much more enduring state of inflammation and sometimes local tissue damage,” she said.

In a previous study, published in the Proceedings of the National Academy of Sciences in 2016, the researchers showed that just a few days of treatment with opiates to treat peripheral nerve pain, such as sciatica, could exacerbate and prolong pain for months in animals, in part by increasing expression of inflammatory genes.

A few small studies in humans have associated postsurgical opioid administration with chronic pain as much as one year later.

“An unusually high number of people end up with postoperative chronic pain. This new study lends insight into one explanation for that,” Watkins said.

The researchers, acknowledging that animal studies cannot directly translate to humans, are now calling for more clinical studies on opioids and chronic pain.

More than 50 million U.S. adults experience chronic pain, according to the National Institutes of Health.

Watkins is also studying novel compounds that could be given with opioids to mute the exaggerated immune response they are believed to trigger, as well as alternative painkillers, including cannabinoids, for pain.

“There is surely a dark side in terms of addiction when it comes to opioids, but this is a very different idea–that we think we are treating the pain with these drugs and we may actually be prolonging it,” she said.

###

Lisa Marshall, CU Boulder media relations
lisa.marshall@colorado.edu
303-492-3115

Reflux medications linked to chronic kidney disease and kidney failure

Public Release: 4-Nov-2017

American Society of Nephrology

Highlights

  • In an analysis of published studies, individuals who used proton pump inhibitors had a 33% increased relative risk of developing chronic kidney disease or kidney failure when compared with non-users.
  • Results from the analysis will be presented at ASN Kidney Week 2017 October 31-November 5 at the Ernest N. Morial Convention Center in New Orleans, LA.

New Orleans, LA (November 4, 2017) — A recent analysis has linked certain medications commonly used to treat heartburn, acid reflux, and ulcers with the development of kidney disease. The findings will be presented at ASN Kidney Week 2017 October 31-November 5 at the Ernest N. Morial Convention Center in New Orleans, LA.

Proton pump inhibitors (PPIs), which reduce gastric acid production, are one of the most commonly prescribed medications worldwide. Recent studies have raised concerns over a potential increased risk of kidney problems among PPIs users but the results of those studies were inconsistent.

To investigate, Charat Thongprayoon, MD (Bassett Medical Center), and his colleagues conducted an analysis of published studies that reported the risk of chronic kidney disease or kidney failure among PPI users compared with non-users.

Five studies with 536,902 participants met the eligibility criteria and were included in the meta-analysis. Individuals who used PPIs had a 33% increased relative risk of CKD or kidney failure when compared with non-users.

“This study demonstrates a significant association between the use of PPIs and increased risks of chronic kidney disease and kidney failure,” said Dr. Thongprayoon. “Although no causal relationship has been proven, providers should consider whether PPI therapy is indicated for patients. Chronic use of PPIs should be avoided if not really indicated.” 

###

Study: “Proton Pump Inhibitors and Risk of Chronic Kidney Diseases: A Meta-Analysis” (Abstract 2763180)

ASN Kidney Week 2017, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2017 will take place October 31-November 5, 2017 in New Orleans, LA.

Since 1966, the American Society of Nephrology (ASN) has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 17,000 members representing 112 countries. For more information, please visit http://www.asn-online.org or contact us at 202-640-4660.

How a chemo drug can help cancer spread from the breast to the lungs

Public Release: 7-Aug-2017

 

Mouse study helps explain the paradoxical pro-cancer effects of paclitaxel

Ohio State University

 

COLUMBUS, Ohio -The very same treatment that thwarts breast cancer has a dark side — it can fuel the spread of the disease to the lungs.

Researchers at The Ohio State University studied the cascade of events that lead to metastatic cancer and found clues to why it happens, opening up the possibility of one day interfering with the medication’s downsides while preserving its cancer-fighting properties in breast tissue.

The front-line chemotherapy drug paclitaxel sets off a variety of molecular-level changes that allow breast cancer cells to escape from the tumor. At the same time, it creates an environment in the lung that is more hospitable to the cancer cells, facilitating the spread of the disease, the researchers found in a mouse model of breast cancer.

The study, which appears in the journal Proceedings of the National Academy of Sciences, includes an analysis of data from women with breast cancer that suggest the findings from mouse models could be relevant to breast cancer metastasis in humans.

“That chemotherapy can paradoxically promote cancer progression is an emerging revelation in cancer research. However, a molecular-level understanding of this devastating effect is not clear,” said Tsonwin Hai, the study’s senior author and a professor of biological chemistry and pharmacology.

The changes in both the tumor and the lung documented in the study depend on a gene called Atf3, which is turned on by stress. In human data, the researchers found higher Atf3 gene expression in patients who had chemotherapy than those who did not.

“This gene seems to do two things at once: essentially help distribute the ‘seeds’ (cancer cells) and fertilize the ‘soil’ (the lung),” Hai said.

First, the chemo appears to send signals to increase the number of molecular doors through which the cancer cells can escape from the primary tumor into the bloodstream, freeing them to travel to other organs, the researchers found.

“I think it’s an active process — a biological change in which the cancer cells are beckoned to escape into the blood — rather than a passive process in which the cancer cells get into the bloodstream because of leaky vessels,” said Hai, a member of The Ohio State University Comprehensive Cancer Center.

This finding is bolstered by another recent study conducted at the Albert Einstein College of Medicine and published in Science Translational Medicine, which showed a similar result using imaging techniques to observe the tumor in mice, Hai said.

Second, the Ohio State researchers found that, beyond aiding cancer cell escape, paclitaxel creates a cascade of events that makes the tissue environment in the lung fertile ground for circulating cancer cells. “There are signals that help cancer cells enter the lungs and set up shop, that make the environment more immunologically tolerant to cancer cells,” Hai said.

A molecular-level understanding of why chemotherapy sometimes increases risk of metastatic cancer is in the early stages, Hai said.

She said it’s important to recognize that the cancer cells in the study’s mouse model are very aggressive and that it would be interesting to test whether paclitaxel also enhances the escape of cancer cells at earlier stages in cancer progression.

Hai cautioned that much more work is required before extrapolating the findings in mice to human cancer treatment.

“At this point, what our study and the recent literature on chemotherapy taught us is that it is prudent to keep our mind open, realizing that chemo can help treat cancer, but at the same time may increase the possibility of the spread of that cancer,” she said.

What set their study apart from other research in this area is the identification of the stress gene Atf3. They showed that paclitaxel — a stressor — exerts its pro-cancer effect at least in part by turning on Atf3.

“It’s possible there could be a treatment given in conjunction with the chemo that would inhibit this problem by dampening the effect of the stress gene Atf3,” Hai said.

And that will be a focus of Hai’s work in this area going forward, she said.

###

The U.S. Department of Defense supported this study.

Other Ohio State researchers who worked on the study were Yi Seok Chang, Swati Jalgaonkar and Justin Middleton.

CONTACT: Tsonwin Hai, 614-292-2910; Hai.2@osu.edu

Sunscreen creams break down into dangerous chemical compounds under the sunlight

Public Release: 27-Jun-2017

 

Scientists of Moscow State University have found out that avobenzone decomposes into harmful chemical compounds

Lomonosov Moscow State University

 

IMAGE

Caption

Scientists from the Faculty of Chemistry of the Lomonosov Moscow State University have demonstrated in their research the nature of hazardous chemical compounds formed as a result of the breakdown of avobenzone, a component of many sunscreen products, when it interacts with chlorinated water and ultraviolet radiation.

Credit: Albert Lebedev

Scientists from the Faculty of Chemistry of the Lomonosov Moscow State University have demonstrated in their research the nature of hazardous chemical compounds formed as a result of the breakdown of avobenzone, a component of many sunscreen products, when it interacts with chlorinated water and ultraviolet radiation. The chemists have presented the results in the Chemosphere journal.

The chemists from the Lomonosov Moscow State University have chosen avobenzone as an object of research. Avobenzone is a derivative of a chemical compound, named dibenzoylmethane. This choice has been conditioned by the fact that this is the most popular UV filter in the world. Avobenzone was patented in 1973 and in 1988 approved by FDA (the Food and Drug Administration, a federal agency of the United States Department of Health and Human Services), dealing with control and supervision of food products, pharmaceutical drugs, cosmetics, tobacco products and some other categories of products. The ability of avobenzone to absorb ultraviolet light in a wide range of wave lengths has ended in its widespread use in the following products: lipsticks, creams and other cosmetics.

Sunscreen products, containing avobenzone, are applied by millions of people all over the world. Chemical UV filters like avobenzone absorb ultraviolet light due to the peculiarities of their structures. Absorbing ultraviolet radiation avobenzone translates it into waves with other length, which aren’t harmful for the skin (in other words, it translates energy of light into thermal energy). Thus the substance in itself is safe, however, the Russian scientists have managed to prove that in water solution it’s capable of breaking down into hazardous chemical compounds.

The scientists from the Lomonosov Moscow State University have defined the products forming as a result of the breakdown of avobenzone in chlorinated water and under the sunlight. These experiments simulated the real situation, when a sunscreen, applied on the skin of swimming people, gets into contact with the water in swimming pools. The breakdown of avobenzone may take place right on the wet human skin, on which a sunscreen is spread.

The chemists have revealed that avobenzone breaks down in the water, forming various organic compounds, belonging to the classes of aromatic acids and aldehydes, phenols and acetyl benzenes. Phenols and chlorinated acetyl benzenes have turned out to be the most toxic products. The latter ones and, in particular chloracetophenone, enter into the composition of lachrymatory mixtures, used by police for disrupting meetings.

Albert Lebedev, Doctor of Chemistry, one of the project authors says: “On the basis of the experiments one could make a conclusion that a generally safe compound transforms in the water and forms more dangerous products. In spite of the fact that there are no precise toxicological profiles for the most established products, it’s known that acetyl benzenes and phenols, especially chorinated ones, are quite toxic.”

Chromatomass spectrometry became the basic research method. This reliable and effective method allows conducting qualitative and quantitative analysis of the most complex mixtures of chemical compounds.

Albert Lebedev continues: “Studying the products of transformation of any popular cosmetics is very important as very often they turn out to be much more toxic and dangerous than their predecessors. In principle, basing on such researches, one could obtain results, which could restrict or even put under a ban the usage of one or another product, and preserve health of millions of people.”

At the moment the scientists are studying the transformation of avobenzone under conditions of chlorination and bromination of fresh and sea water. During chlorination or bromination of sea water the number of the breakdown products of avobenzone will be even wider. And if water contains copper salts (which are added into many swimming pools for getting nice light-blue color), then bromoform is formed in large quantities. This substance could provoke dysfunctions of liver and kidneys, along with nervous system disorder.

Paracetamol during pregnancy can inhibit masculinity

Public Release: 22-Jun-2017

 

Paracetamol during pregnancy can inhibit the development of ‘male behavior’ in mice; new research from the University of Copenhagen shows that it can reduce sex drive and aggressive behavior

University of Copenhagen The Faculty of Health and Medical Sciences

 

Paracetamol is popular for relieving pain. But if you are pregnant, you should think twice before popping these pills according to the researchers in a new study. In an animal model, Paracetamol, which is the pain-relieving substance found in the pills, actually damages the development of male behaviours.

Previous studies have shown the paracetamol can inhibit the development of the male sex hormone testosterone in male foetuses, thus increasing the risk of malformation of the testicles in infants. But a reduced level of testosterone at the foetal stage is also significant for the behaviours of adult males, says Ph.D. David Møbjerg Kristensen, a researcher employed during the studies at the Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Protein Research at the Faculty of Health and Medical Sciences.

“We have demonstrated that a reduced level of testosterone means that male characteristics do not develop as they should. This also affects sex drive. In a trial, mice exposed to paracetamol at the foetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their foetal development and this could be seen long afterwards in their adult life. It is very worrying,” says David Møbjerg Kristensen.

The dosage administered to the mice was very close to the recommended dosage for pregnant women. Because the trials are restricted to mice, the results cannot be transferred directly to humans. However, the researchers’ certainty about the harmful effects of paracetamol means it would be improper to undertake the same trials on humans, explains David Møbjerg Kristensen.

Markedly reduced male behaviour

Testosterone is the primary male sex hormone that helps develop the male body and male programming of the brain. The masculine behaviours in mice observed by the researchers involved aggressiveness to other male mice, ability to copulate and the need for territorial marking. The mice reacted significantly more passively than normal for all three parameters. They did not attack other males, they were unable to copulate and behaved more like female mice when it come to urinary territorial marking.

After observing the changed behavioural patterns, Prof. Anders Hay-Schmidt, who was employed at the then Department of Neuroscience and Pharmacology during his studies at the University of Copenhagen, investigated the specific effects of a lack of testosterone on the brain. The results showed up clearly here, too.

“The area of the brain that controls sex drive – the sexual dimorphic nucleus – had half as many neurons in the mice that had received paracetamol as the control mice. The inhibition of testosterone also led to a halving of the activity in an area of the brain that is significant for male characteristics,” he explains.

Also affects female fertility

This study focused on the effect of paracetamol on masculine characteristics but paracetamol during pregnancy also has the potential to influence the subsequent lives of female mice. In 2016, the researchers published a study showing that female mice had fewer eggs in their ovaries if their mothers had had paracetamol during pregnancy. This led to the mice becoming infertile more quickly. But even if paracetamol is harmful, that does not mean it should never be taken, even when pregnant.

“I personally think that people should think carefully before taking medicine. These days it has become so common to take paracetamol that we forget it is a medicine And all medicine has side effects. If you are ill, you should naturally take the medicine you need. After all, having a sick mother is more harmful for the foetus,” says David Møbjerg Kristensen.

He emphasizes that pregnant women should continue to follow the guidelines given by their country’s health authorities and recommends people to contact their GP if in doubt about the use of paracetamol.

###

The study, “Prenatal exposures to paracetamol/acetaminophen and precursor aniline impair masculinisation of male brain and behaviour,” has just been published in the scientific journal Reproduction.

Contact:

David Møbjerg Kristensen, a researcher associated with IRSET in France, employed by the Department of Biomedical Sciences during his studies and the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen

E: louisasch@hotmail.com

T: (+45) 5091 5988

Associate Professor Anders Hay-Schmidt, Department of Veterinary Disease Biology

E: amanda.rohde@sund.ku.dk

T: (+45) 2875 7260

Amanda Nybroe Rohde, Communication Officer

E: annie.fjeldsted@dib.ku.dk

T: (+45) 2364 9425

Study finds 1 in 5 hospitalized adults suffer side effects from prescribed antibiotics

Public Release: 14-Jun-2017

 

Infectious disease experts say nearly a fifth of prescriptions were unnecessary

Johns Hopkins Medicine

A study examining the impact of antibiotics prescribed for nearly 1500 adult patients admitted to The Johns Hopkins Hospital found that adverse side effects occurred in a fifth of them, and that nearly a fifth of those side effects occurred in patients who didn’t need antibiotics in the first place.

Their report, published June 12, 2017 in JAMA Internal Medicine, adds to growing evidence that antibiotics are not benign and that clinicians often fail to weigh both the risks and benefits of antibiotics before prescribing them.

“Too often, clinicians prescribe antibiotics even if they have a low suspicion for a bacterial infection, thinking that even if antibiotics may not be necessary, they are probably not harmful,” says Pranita Tamma, M.D., M.H.S., assistant professor of pediatrics and director of the Pediatric Antimicrobial Stewardship Program at The Johns Hopkins Hospital. “But that is not always the case. Antibiotics have the potential to cause real harm to patients. Each time we think to prescribe an antibiotic, we need to pause and ask ourselves, Does this patient really need an antibiotic?” And, she adds, “If the patient develops an antibiotic-associated adverse reaction, even though that is, of course, unfortunate, we should be able to take some comfort in knowing that at least the antibiotic was truly necessary.”

In the study, the researchers evaluated the electronic medical records of 1488 adults admitted to the general medicine services at The Johns Hopkins Hospital between September 2013 and June 2014. The patients were admitted for reasons ranging from trauma to chronic disease, but all received at least 24 hours of antibiotic treatment.

The researchers followed patients for 30 days after hospital discharge to determine the likelihood of an adverse reaction to antibiotics and to identify how many adverse reactions could be avoided by eliminating unnecessary antibiotic use.

They concluded that overall, 20 percent of patients who received antibiotics experienced one or more adverse effects, noting that for each additional 10 days of antibiotics, the risk of side effects increased by 3 percent. Gastrointestinal, kidney and blood abnormalities were the most common side effects experienced, accounting for 42 percent, 24 percent and 15 percent of adverse effects experienced, respectively.

Patients were observed for up to 90 days for the development of Clostridium difficile infection — a bacterial cause of diarrhea that can become severe — and for the development of new multidrug-resistant infections, as these often take longer to become apparent. A total of 4 percent and 6 percent of patients developed C. difficile infections and potential multidrug-resistant organism infections, respectively.

While no deaths were attributed to any antibiotic side effects in this study, the researchers say, 24 percent of patients had prolonged hospital stays as a result of adverse effects; 3 percent of patients experienced additional hospital admissions; 9 percent of patients required additional emergency department or clinic visits; and 61 percent of patients needed additional diagnostic tests.

Beyond the emotional and financial costs of dealing with the side effects, researchers also concluded that 19 percent of antibiotics prescribed to patients were clinically unnecessary, meaning that two reviewing infectious disease experts found no indication of bacterial infections in these patients. The rate of adverse effects in this group was the same as in the overall group – 20 percent, according to Tamma.

The Johns Hopkins team cautioned that their study may actually be underestimating the number of antibiotic-associated adverse effects that occur in the general population because The Johns Hopkins Hospital has a robust Antibiotic Stewardship Program that guides clinicians through making wise antibiotic choices.

“In general, we would expect our hospital to have lower numbers of antibiotic-associated side effects than at hospitals without antibiotic stewardship programs because our stewardship team assists health care providers with optimizing the administration of antibiotics, and we tend to recommend targeted therapies for shorter periods of time,” says Sara Cosgrove, M.D., M.S., professor of medicine and director of the Antimicrobial Stewardship Program at The Johns Hopkins Hospital.

Tamma says the absence of universal electronic records in all clinics may also contribute to underestimation of harmful effects associated with antibiotics: “There may have been more visits for adverse effects that we were unable to track.”

In addition to raising further awareness about unnecessary prescribing among physicians, Tamma says the new study results should also encourage patients to ask questions and understand the risks. “I think it’s good for patients to ask their doctors about potential side effects and how to recognize them,” she says. “That alone could reduce a large portion of unnecessary antibiotic prescribing.”

###

Other researchers involved in this study include Edina Avdic, David X. Li and Kathryn Dzintars of the Johns Hopkins Medical Institutions.

This study was funded by a grant from Pfizer Independent Grants for Learning & Change and The Joint Commission.

Unpublished trial data show side effects of a key MS drug increase secondary autoimmune diseases by 50%

Public Release: 12-Jun-2017

Previously unpublished trial data explain effects and side effects of key MS drug

Through a Freedom of Information request to the European Medicines Agency, researchers from Queen Mary University of London gained access to the phase III trial datasets of Alemtuzumab

Queen Mary University of London

Alemtuzumab is a highly effective drug for multiple sclerosis, approved in more than 60 countries and used by more than 12,000 patients worldwide. However, there is an almost 50 per cent risk of secondary autoimmune diseases, some of which are life-threatening, such as platelet and kidney diseases.

Although knowledge about these adverse effects was included in conference presentations and licensing submissions to European and US regulators, critical data to explain secondary autoimmune disease had not been scrutinised and published following peer review.

Through a Freedom of Information request to the European Medicines Agency (EMA) researchers from Queen Mary University of London (QMUL) gained access to the phase III trial datasets of Alemtuzumab.

Their analysis and interpretation, results of which are published in JAMA Neurology, provides new insights into the drastic responses of the immune system in people with MS taking Alemtuzumab.

The researchers discovered a massive and rapid re-population of a subset of B cells in the absence of effective T cell regulation, which they say helps create an environment for secondary autoimmune disease. This also allows a marked anti-drug response that can become problematic in some people taking the drug.

According to the researchers, controlling this B cell subset “overshoot” after Alemtuzumab administration until T cell regulation recovers, may limit the risk of secondary autoimmune disease and make it an even better medicine.

Additionally, whilst they saw a long term suppression of T cells believed by many to be the cause of the problem. They also saw loss of memory B cells, which they say offers a new explanation on why Alemtuzumab is effective in people with MS. Indeed it may provide insight of how all other drugs work in MS and ties aspects of the potential cause and treatments together.

Lead author Dr Klaus Schmierer from QMUL said: “We were very surprised to find such important information on B cell dynamics were only partially described and remained unpublished, even though they were observed and analysed several years ago following the pivotal phase III trials.

“Interrogating the original data from a different perspective opened our minds to alternative explanations. This made us discard the science dogma that we think is leading people to look in the wrong place for solutions.

“This new information will help contribute to the effective management of people with MS, firstly during the decision process about disease modifying treatment, and secondly in people who have been treated with Alemtuzumab, to ensure the risks associated with dangerous side effects are minimised.

“There remain some unanswered questions, based on what we saw. This shows us why it is important for total transparency and total access to all anonymous trial data.

“Whilst we appreciate release of data is part of the drug-marketing process, it is in the public interest that all information collected is made unconditionally available, within a reasonable time frame.”

Common antibiotics linked to increased risk of miscarriage

Public Release: 1-May-2017

 

Canadian Medical Association Journal

 

Many classes of common antibiotics, such as macrolides, quinolones, tetracyclines, sulfonamides and metronidazole, were associated with an increased risk of miscarriage in early pregnancy, according to a new study published in CMAJ (Canadian Medical Association Journal).

Erythromycin was not associated with increased risk nor was nitrofurantoin, often used to treat urinary tract infections in pregnant women.

“Infections are prevalent during pregnancy,” says Dr. Anick Bérard, Faculty of Pharmacy, Université de Montréal, Montréal, Quebec. “Although antibiotic use to treat infections has been linked to a decreased risk of prematurity and low birth weight in other studies, our investigation shows that certain types of antibiotics are increasing the risk of spontaneous abortion, with a 60% to two-fold increased risk.”

Bérard and her team looked at data from the Quebec Pregnancy Cohort between 1998 and 2009. For this study, 8702 cases, defined as clinically detected spontaneous abortions, were matched with 87 020 controls; mean gestational age at the time of miscarriage was 14 weeks of pregnancy. A total of 1428 (16.4%) cases were exposed to antibiotics during early pregnancy compared to 11 018 (12.6%) in controls.

Participants were between the ages of 15 and 45 years and covered under Quebec’s drug insurance plan. Women who miscarried were more likely to be older, living alone and to have multiple health issues and infections, all of which were taken into account in the analyses.

Study strengths include a large sample, valid information on filled prescriptions and routinely collected information on diagnosis of spontaneous abortion or related procedures. The authors note that infection severity could be a confounder, that is, contribute to pregnancy loss and explain some of the increased risk, although they did adjust for this variable in the analysis.

“Given that the baseline risk of spontaneous abortion can go as high as 30%, this is significant. Nevertheless, the increased risk was not seen for all antibiotics, which is reassuring for users, prescribers and policy-makers,” states Dr. Bérard.

The authors hope that these findings may be useful for policy-makers to update guidelines for the treatment of infections during pregnancy.

###

Monosodium glutamate (MSG) damages memory and coordination, exercise can help recover

Public Release: 26-Apr-2017

Resistance exercises recover motor and memory impairment caused by flavor enhancer

The Physiological Society

A study in rats, published in Experimental Physiology, showed that resistance exercise recovers memory and motor impairment caused by the flavour enhancer monosodium glutamate.

Monosodium glutamate (MSG) is an additive that mimics umami flavour, the fifth taste aside from sweet, sour, salty and bitter. Some studies have shown MSG to have adverse effects in humans, making it important to understand how it works in the body. Giving MSG to new-born rats has previously been shown to cause motor and memory impairment.

The team of researchers at the Federal University of Santa Maria in Brazil gave the experimental group of new-born rats a dose of MSG. This dose is not comparable to the dose humans eat.

Of the rats that were given MSG, half began a resistance exercise regimen at two months of age. The exercise consisted of climbing a ladder at an 80 degree angle. The rats performed these exercises five times per week for seven weeks.

After resistance exercise, researchers tested the rats’ motor coordination and memory. Within the group injected with MSG, motor coordination was less impaired in both male and female rats that performed resistance exercise. Memory also improved in both male and female rats, but it was a different type of memory in the two sexes. Recognition memory improved in male rats, whereas female rats had improved location memory.

To test both types of memory, researchers present rats with two objects. To test recognition memory, one object is replaced with a new one. To test location memory, one object is moved to a new location.

The next question that Cristina Wayne Nogueira, lead investigator, and her team will explore is the mechanism of memory improvement.

Commenting on the study, Nogueira said: ‘This study highlights that resistance-based exercise improves cognitive deficit induced by a flavour enhancer. Our next goal is to understand how this is happening.’

‘Alarmingly high’ risk of death for people with opioid use disorder in general medical care

Public Release: 24-Apr-2017

Wolters Kluwer Health

April 24, 2017 – Almost one-fifth of patients with opioid use disorder (OUD) in a large healthcare system died during a four-year follow-up period, reports a study in the Journal of Addiction Medicine, the official journal of the American Society of Addiction Medicine (ASAM). The journal is published by Wolters Kluwer.

The results suggest very high rates of serious illness and death among patients with OUD in general medical care settings–much higher than for those in addiction specialty clinics, according to by Yih-Ing Hser, PhD, of University of California, Los Angeles, and colleagues. They write, “The alarmingly high morbidity and mortality among OUD patients revealed in the present study challenge healthcare systems to find new and innovative ways to expand evidence-based strategies for OUD in a variety of settings.”

Late Diagnosis and High Rates of Medical Problems for OUD Patients in Healthcare Network

Using electronic health records from their university healthcare system, the researchers identified 2,576 adults with OUD. The patients, average age 41 years at first OUD diagnosis, had high rates of physical and mental health conditions and other types of substance use disorder.

At four years of follow-up, 465 of the patients had died–a rate of 18.1 percent. Mortality in this group of patients with OUD was more than 10 times higher than in the general population, adjusted for age and sex.

About 19 percent of deaths were due to causes directly related to OUD and drug overdose. But most patients died of other causes: especially cardiovascular disease, cancer, and infectious diseases. The most common infection-related cause of death was hepatitis C virus (HCV). Because of injection drug use and other risky behaviors, people with OUD are at high risk of HCV infection.

Risk of death was even higher–twice as high for OUD patients with HCV infection. Patients with alcohol use disorder also had increased mortality.

Risk of death from cardiovascular disease was higher for patients with tobacco use disorder. Mortality from cancer was increased for patients with HCV infection, while death from liver disease was more common for patients with HCV infection and alcohol use disorder.

Previous studies have found a high risk of death among people with OUD, most commonly from drug overdose. However, most of these studies have focused on patients being treated in addiction specialty clinics or programs. One recent study found that the risk of death among patients receiving treatment for OUD was four times higher than in the general population, increasing to six times higher after they were out of treatment.

The new findings suggest a much higher risk of death for patients with OUD in general medical care. Dr. Hser and coauthors note that the patients identified in their healthcare network were older when first diagnosed with OUD, and had high rates of other physical health disorders.

Their high mortality may reflect issues with identifying and addressing OUD in the healthcare system. “It is likely that patients seen in this health system became progressively sicker, as their OUD problem was not identified until very late in its course and after physical health complications had already ensued,” the researchers write.

Within the study limitations, the results may have important implications for healthcare amid the ongoing opioid epidemic. “In the United States, healthcare providers outside specialty substance use disorders treatment settings have not traditionally been adequately equipped to identify and address patients [with] addictions,” Dr. Hser and coauthors note.

Of note, the findings do not imply that addiction treatment has worse outcomes in general health settings; the higher mortality is likely due to not receiving adequate care. The authors believe that earlier intervention might be able to reduce some of the high rates of complications and death among patients with OUD in general medical care. The authors conclude: “Further research is much needed to better engage the entire spectrum of healthcare services, with the goal of developing and delivering efficient and effective chronic care management approaches and services for OUD.”

###

Click here to read “High Mortality Among Patients With Opioid Use Disorder in a Large Healthcare System.”

Article: “High Mortality Among Patients With Opioid Use Disorder in a Large Healthcare System.” (doi: 10.1097/ADM.0000000000000312)

About Journal of Addiction Medicine

The mission of Journal of Addiction Medicine, the official journal of the American Society of Addiction Medicine, is to promote excellence in the practice of addiction medicine and in clinical research as well as to support Addiction Medicine as a mainstream medical specialty. Published six times a year, the Journal is designed for all physicians and other mental health professionals who need to keep up-to-date with the treatment of addiction disorders. Under the guidance of an esteemed Editorial Board, peer-reviewed articles published in the Journal focus on developments in addiction medicine as well as on treatment innovations and ethical, economic, forensic, and social topics.

About The American Society of Addiction Medicine

The American Society of Addiction Medicine (ASAM) is a professional society representing over 4,300 physicians, clinicians, and associated professionals in the field of addiction medicine. ASAM is dedicated to increasing access and improving the quality of addiction treatment, educating physicians and the public, supporting research and prevention, and promoting the appropriate role of physicians in the care of patients with addiction. Visit us on the web at http://www.ASAM.org; follow @ASAMorg on Twitter.

About Wolters Kluwer

Wolters Kluwer N.V. (AEX: WKL) is a global leader in information services and solutions for professionals in the health, tax and accounting, risk and compliance, finance and legal sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with specialized technology and services.

Wolters Kluwer reported 2016 annual revenues of €4.3 billion. The company, headquartered in Alphen aan den Rijn, the Netherlands, serves customers in over 180 countries, maintains operations in over 40 countries and employs 19,000 people worldwide.

Wolters Kluwer shares are listed on Euronext Amsterdam (WKL) and are included in the AEX and Euronext 100 indices. Wolters Kluwer has a sponsored Level 1 American Depositary Receipt program. The ADRs are traded on the over-the-counter market in the U.S. (WTKWY).

For more information about our solutions and organization, visit http://www.wolterskluwer.com, follow us on Twitter, Facebook, LinkedIn, and YouTube.

‘Harmless’ painkillers associated with up to 50% increased risk of cardiac arrest

Public Release: 15-Mar-2017

Researchers advise avoiding diclofenac and limiting ibuprofen to 1200 mg per day

European Society of Cardiology

Sophia Antipolis, 15 March 2017: Painkillers considered harmless by the general public are associated with increased risk of cardiac arrest, according to research published today in the March issue of European Heart Journal – Cardiovascular Pharmacotherapy.1

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide and some, including ibuprofen, are available over the counter.

“Allowing these drugs to be purchased without a prescription, and without any advice or restrictions, sends a message to the public that they must be safe,” said author Professor Gunnar H. Gislason, professor of cardiology at Copenhagen University Hospital Gentofte, Denmark. “Previous studies have shown that NSAIDs are related to increased cardiovascular risk which is a concern because they are widely used.”

The current study investigated the link between NSAID use and cardiac arrest. All patients who had an out-of-hospital cardiac arrest in Denmark between 2001 and 2010 were identified from the nationwide Danish Cardiac Arrest Registry. Data was collected on all redeemed prescriptions for NSAIDs from Danish pharmacies since 1995. These included the non-selective NSAIDs (diclofenac, naproxen, ibuprofen), and COX-2 selective inhibitors (rofecoxib, celecoxib).

A case-time-control design was used to examine the association between NSAID use and cardiac arrest. Each patient served as both case and control in two different time periods, eliminating the confounding effect of chronic comorbidities. Use of NSAIDs during the 30 days before cardiac arrest (case period) was compared to used of NSAIDs during a preceding 30 day period without cardiac arrest (control period).

Information was not obtained on over-the-counter drugs. Ibuprofen is the only over-the-counter NSAID in Denmark and is limited to small packages of 200 mg dosages. As patients were their own control, any underestimation of ibuprofen use should be equally distributed between the case and control periods.

A total of 28 947 patients had an out-of-hospital cardiac arrest in Denmark during the ten year period. Of these, 3 376 were treated with an NSAID up to 30 days before the event. Ibuprofen and diclofenac were the most commonly used NSAIDs, making up 51% and 22% of total NSAID use, respectively.

Use of any NSAID was associated with a 31% increased risk of cardiac arrest. Diclofenac and ibuprofen were associated with a 50% and 31% increased risk, respectively. Naproxen, celecoxib and rofecoxib were not associated with the occurrence of cardiac arrest, probably due to a low number of events.

“The findings are a stark reminder that NSAIDs are not harmless,” said Professor Gislason. “Diclofenac and ibuprofen, both commonly used drugs, were associated with significantly increased risk of cardiac arrest. NSAIDs should be used with caution and for a valid indication. They should probably be avoided in patients with cardiovascular disease or many cardiovascular risk factors.”

NSAIDs exert numerous effects on the cardiovascular system which could explain the link with cardiac arrest. These include influencing platelet aggregation and causing blood clots, causing the arteries to constrict, increasing fluid retention, and raising blood pressure.

Professor Gislason said: “I don’t think these drugs should be sold in supermarkets or petrol stations where there is no professional advice on how to use them. Over-the-counter NSAIDs should only be available at pharmacies, in limited quantities, and in low doses.”

“Do not take more than 1200 mg of ibuprofen per day,” he continued. “Naproxen is probably the safest NSAID and we can take up to 500 mg a day. Diclofenac is the riskiest NSAID and should be avoided by patients with cardiovascular disease and the general population. Safer drugs are available that have similar painkilling effects so there is no reason to use diclofenac.”

Professor Gislason concluded: “The current message being sent to the public about NSAIDs is wrong. If you can buy these drugs in a convenience store then you probably think ‘they must be safe for me’. Our study adds to the evidence about the adverse cardiovascular effects of NSAIDs and confirms that they should be taken seriously, and used only after consulting a healthcare professional.”

Popular heartburn drugs linked to gradual yet ‘silent’ kidney damage

Public Release: 22-Feb-2017

 

Most patients don’t experience acute kidney problems beforehand

Washington University in St. Louis

 

IMAGE

Caption

Taking popular heartburn medication for prolonged periods may lead to serious kidney damage, even in people who show no signs of kidney problems, according to researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System. The drugs are sold under brand names such as Prevacid, Prilosec, Nexium and Protonix.

Credit: Michael Worful/Washington University School of Medicine in St. Louis

Taking popular heartburn drugs for prolonged periods has been linked to serious kidney problems, including kidney failure. The sudden onset of kidney problems often serves as a red flag for doctors to discontinue their patients’ use of so-called proton pump inhibitors (PPIs), which are sold under the brand names Prevacid, Prilosec, Nexium and Protonix, among others.

But a new study evaluating the use of PPIs in 125,000 patients indicates that more than half of patients who develop chronic kidney damage while taking the drugs don’t experience acute kidney problems beforehand, meaning patients may not be aware of a decline in kidney function, according to researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System. Therefore, people who take PPIs, and their doctors, should be more vigilant in monitoring use of these medications.

The study is published Feb. 22 in Kidney International.

The onset of acute kidney problems is not a reliable warning sign for clinicians to detect a decline in kidney function among patients taking proton pump inhibitors, said Ziyad Al-Aly, MD, the study’s senior author and an assistant professor of medicine at Washington University School of Medicine. “Our results indicate kidney problems can develop silently and gradually over time, eroding kidney function and leading to long-term kidney damage or even renal failure. Patients should be cautioned to tell their doctors if they’re taking PPIs and only use the drugs when necessary.”

More than 15 million Americans suffering from heartburn, ulcers and acid reflux have prescriptions for PPIs, which bring relief by reducing gastric acid. Many millions more purchase the drugs over-the-counter and take them without being under a doctor’s care.

The researchers — including first author Yan Xie, a biostatistician at the St. Louis VA — analyzed data from the Department of Veterans Affairs databases on 125,596 new users of PPIs and 18,436 new users of other heartburn drugs referred to as H2 blockers. The latter are much less likely to cause kidney problems but often aren’t as effective.

Over five years of follow up, the researchers found that more than 80 percent of PPI users did not develop acute kidney problems, which often are reversible and are characterized by too little urine leaving the body, fatigue and swelling in the legs and ankles.

However, more than half of the cases of chronic kidney damage and end-stage renal disease associated with PPI use occurred in people without acute kidney problems.

In contrast, among new users of H2 blockers, 7.67 percent developed chronic kidney disease in the absence of acute kidney problems, and 1.27 percent developed end-stage renal disease.

End-stage renal disease occurs when the kidneys can no longer effectively remove waste from the body. In such cases, dialysis or a kidney transplant is needed to keep patients alive.

“Doctors must pay careful attention to kidney function in their patients who use PPIs, even when there are no signs of problems,” cautioned Al-Aly, who also is the VA’s associate chief of staff for research and education and co-director of the VA’s Clinical Epidemiology Center. “In general, we always advise clinicians to evaluate whether PPI use is medically necessary in the first place because the drugs carry significant risks, including a deterioration of kidney function.”

Antibiotics shown to stimulate bad bacteria growth by 300%

Public Release: 30-Jan-2017

 

University of Exeter

IMAGE

IMAGE: These are two types of lab E. coli smeared across an agar plate. The green ones are drug resistant and the blue ones are not.

Credit: The University of Exeter

The growth of bacteria can be stimulated by antibiotics, scientists at the University of Exeter have discovered.

The EPSRC-funded researchers exposed E.coli bacteria to eight rounds of antibiotic treatment over four days and found the bug – which can cause severe stomach pain, diarrhoea and kidney failure in humans – had increased antibiotic resistance with each treatment.

This had been expected, but researchers were surprised to find mutated E.coli reproduced faster than before encountering the drugs and formed populations that were three times larger because of the mutations.

This was only seen in bacteria exposed to antibiotics – and when researchers took the drug away, the evolutionary changes were not undone and the new-found abilities remained.

“Our research suggests there could be added benefits for E.coli bacteria when they evolve resistance to clinical levels of antibiotics,” said lead author Professor Robert Beardmore, of the University of Exeter.

“It’s often said that Darwinian evolution is slow, but nothing could be further from the truth, particularly when bacteria are exposed to antibiotics.

“Bacteria have a remarkable ability to rearrange their DNA and this can stop drugs working, sometimes in a matter of days.

“While rapid DNA change can be dangerous to a human cell, to a bacterium like E.coli it can have multiple benefits, provided they hit on the right changes.”

The researchers tested the effects of the antibiotic doxycycline on E.coli as part of a study of DNA changes brought about by antibiotics.

The E.coli “uber-bug” that subsequently evolved was safely frozen at -80C and the scientists used genetic sequencing to find out which DNA changes were responsible for its unusual evolution.

Some changes are well known and have been seen in clinical patients, like E.coli producing more antibiotic pumps that bacteria exploit to push antibiotics out of the cell.

Another change saw the loss of DNA that is known to describe a dormant virus.

“Our best guess is that losing viral DNA stops the E.coli destroying itself, so we see more bacterial cells growing once the increase in pump DNA allows them to resist the antibiotic in the first place,” said Dr Carlos Reding, who was part of the study.

“This creates an evolutionary force for change on two regions of the E.coli genome.

“Normally, self-destruction can help bacteria colonise surfaces through the production of biofilms. You see biofilms in a dirty sink when you look down the plughole.

“But our study used liquid conditions, a bit like the bloodstream, so the E.coli could give up on its biofilm lifestyle in favour of increasing cell production.”

Dr Mark Hewlett, also of the University of Exeter, added: “It is said by some that drug resistance evolution doesn’t take place at high dosages but our paper shows that it can and that bacteria can change in ways that would not be beneficial for the treatment of certain types of infection.

“This shows it’s important to use the right antibiotic on patients as soon as possible so we don’t see adaptations like these in the clinic.”

###

The paper, published in the journal Nature Ecology & Evolution , is entitled: “The unconstrained evolution of fast and efficient antibiotic-resistant bacterial genomes.”

Antibiotics, not dirty hospitals, the main cause of C. difficile epidemic

Public Release: 24-Jan-2017

 

University of Oxford

 

The study concluded that overuse of antibiotics like ciprofloxacin led to the outbreak of severe diarrhoea caused by C. difficile that hit headlines from 2006 onwards. The outbreak was stopped by substantially reducing use of ciprofloxacin and related antibiotics.

Inappropriate use and widespread over prescribing of fluoroquinolone antibiotics such as ciprofloxacin in fact allowed C. difficile bugs that were resistant to the drug to thrive, because non-resistant bugs in the gut were killed off by the antibiotic, leaving the way clear for rapid growth of resistant C. difficile.

Concerns about hospital “superbugs” which had become resistant to common antibiotics resulted in the announcement of a programme of “deep cleaning” and other infection control measures in the NHS in 2007.

The study, by the University of Oxford, University of Leeds and Public Health England and published today in The Lancet Infectious Diseases, found that cases of C. difficile fell only when fluoroquinolone use was restricted and used in a more targeted way as one part of many efforts to control the outbreak.

The restriction of fluoroquinolones resulted in the disappearance in the vast majority of cases of the infections caused by the antibiotic-resistant C. difficile, leading to around an 80% fall in the number of these infections in the UK (in Oxfordshire approximately 67% of C. difficile bugs were antibiotic-resistant in September 2006, compared to only approximately 3% in February 2013).

In contrast, the smaller number of cases caused by C. difficile bugs that were not resistant to fluoroquinolone antibiotics stayed the same. Incidence of these non-resistant bugs did not increase due to patients being given the antibiotic, and so were not affected when it was restricted.

At the same time, the number of bugs that were transmitted between people in hospitals did not change. This was despite the implementation of comprehensive infection prevention and control measures, like better handwashing and hospital cleaning in this case.

The study’s authors therefore conclude that ensuring antibiotics are used appropriately is the most important way to control the C. difficile superbug. The authors note that it is important that good hand hygiene and infection control continues to be practiced to control the spread of other infections.

The study, analysed data on the numbers of C. diff infections and amounts of antibiotics used in hospitals and by GPs in the UK.

More than 4,000 C. diff bugs also underwent genetic analysis using a technique called whole genome sequencing, to work out which antibiotics each bug was resistant to.

Co-author Derrick Crook, Professor of Microbiology, University of Oxford said: “Alarming increases in UK hospital infections and fatalities caused by C. difficile made headline news during the mid-2000s and led to accusations of serious failings in infection control.

“Emergency measures such as ‘deep cleaning’ and careful antibiotic prescribing were introduced and numbers of C. difficile infections gradually fell by 80% but no-one was sure precisely why.

“Our study shows that the C. difficile epidemic was an unintended consequence of intensive use of an antibiotic class, fluoroquinolones, and control was achieved by specifically reducing use of this antibiotic class, because only the C. difficile bugs that were resistant to fluoroquinolones went away.

“Reducing the type of antibiotics like ciprofloxacin was, therefore, the best way of stopping this national epidemic of

C. difficile and routine, expensive deep cleaning was unnecessary. However it is important that good hand hygiene continues to be practiced to control the spread of other infections.

“These findings are of international importance because other regions such as North America, where fluoroquinolone prescribing remains unrestricted, still suffer from epidemic numbers of C. difficile infections.”

Co-author Prof Mark Wilcox, Professor of Microbiology, University of Leeds, said: “Our results mean that we now understand much more about what really drove the UK epidemic of C. diff infection in the mid-2000s.

“Crucially, part of the reason why some C. diff strains cause so many infections is because they find a way to exploit modern medical practice.

Similar C. diff bugs that affected the UK have spread around the world, and so it is plausible that targeted antibiotic control could help achieve large reductions in C. diff infections in other countries.”

The funding for the study came from the UK Clinical Research Collaboration, (Medical Research Council, Wellcome Trust, National Institute for Health Research); NIHR Oxford Biomedical Research Centre; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antibiotic Resistance, University of Oxford in partnership with Leeds University and Public Health England; NIHR Health Protection Research Unit in Modelling Methodology, Imperial College London in partnership with Public Health England; and the Health Innovation Challenge Fund.

###

NOTES TO EDITORS:

EMBARGOED to 2330 GMT Tuesday 24 January 2017

For more information contact Oliver Evans, Communications Manager (Research and Development), Oxford University Hospitals NHS Foundation Trust, Tel: 01865 223070, Mobile: 07747 456443, Email: oliver.evans@ouh.nhs.uk

The paper will be available from 2330 GMT on 24 January 2017 at: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30514-X/fulltext

Clostridium difficile is a bacterium that can infect the bowel and cause diarrhoea.

The infection most commonly affects people who have recently been treated with antibiotics, but can spread easily to others.

In some cases, serious complications can develop, such as damage to the bowel or severe dehydration, which may cause drowsiness, confusion, a rapid heart rate and death.

Oxford University Hospitals NHS Foundation Trust (OUH) is one of the largest acute teaching trusts in the UK, with a national and international reputation for the excellence of its services and its role in patient care, teaching and research. The Trust supports world-leading research programmes in cardiovascular diseases, musculoskeletal disorders, neurological disorders such as Parkinson’s and Alzheimer’s through its designation as one of the UK’s five comprehensive biomedical centres and units. It works in close partnership with the University of Oxford and is a leading centre for cancer, neurosciences, diabetes, genetics and many other fields. Research themes of particular strength are: cancer, cardiovascular science, diabetes, endocrinology & metabolism, infection and immunology, musculoskeletal science, neuroscience and reproduction and development. As of October 1 2015, the Trust was awarded Foundation Trust status. This decision comes after the Care Quality Commission gave OUH an overall rating of ‘Good’ in May 2014, and after scrutiny of the Trust’s quality, finances, service delivery and governance arrangements by the NHS Trust Development Authority and Monitor. The Trust has been designated as a major trauma centre and is one of four UK centres for craniofacial surgery and The Trust employs over 12,000 staff and consists of four hospitals: the Churchill Hospital, John Radcliffe Hospital and Nuffield Orthopaedic Centre in Oxford and the Horton General Hospital in Banbury. http://www.ouh.nhs.uk

The University of Oxford’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school. From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery. A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

The NIHR Oxford Biomedical Research Centre is funded by the National Institute for Health Research, and is a partnership between the Oxford University Hospitals NHS Foundation Trust and the University of Oxford. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world class facilities (both NHS and university), and conducting leading edge research focused on the needs of patients.

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. The NIHR is the research arm of the NHS. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.

New data show heightened risk of birth defects with antidepressants

Public Release: 18-Jan-2017

 

University of Montreal

 

MONTREAL, January 18, 2017 – A new Université de Montréal study in the British Medical Journal reveals that antidepressants prescribed to pregnant women could increase the chance of having a baby with birth defects.

The risk – 6 to 10 %, versus 3 to 5 % in women who do not take the drugs – is high enough to merit caution in their use, especially since, in most cases, they are only marginally effective, the study says.

“In pregnancy, you’re treating the mother but you’re worried about the unborn child, and the benefit needs to outweigh the risk,” said the study’s senior author, Anick Bérard, a professor at UdeM’s Faculty of Pharmacy and researcher at its affiliated children’s hospital, CHU Sainte-Justine.

A well-known expert in pregnancy and depression, Bérard has previously established links between antidepressants and low birth weight, gestational hypertension, miscarriages and autism. Her new study is among the first to examine the link to birth defects among depressed women.

Every year, about 135,000 Quebec women get pregnant, and of those, about 7 % show some signs of depression, mostly mild to moderate. A much smaller percentage – less than one per cent – suffers from severe depression.

In her study, Bérard looked at 18,487 depressed women in the Quebec Pregnancy Cohort, a longitudinal, population-based grouping of 289,688 pregnancies recorded between 1998 to 2009. Of the women studied, 3,640 – about 20 per cent – took antidepressants in the first three months.

“We only looked at the first trimester, because this is where all the organ systems are developing,” said Bérard. “At 12 weeks of gestation, the baby is formed.”

Antidepressant use during this critical time-window has the potential to interfere with serotonin intake by the fetus, which can result in malformations.

“Serotonin during early pregnancy is essential for the development of all embryonic cells, and thus any insult that disturbs the serotonin signaling process has the potential to result in a wide variety of malformations,” the study says.

For example, when Celexa (the brand name for citalopram) was taken in the first trimester, the risk of major birth defects jumped from 5 per cent to 8 per cent, Bérard found. In all, 88 cases of malformations were linked to use of the drug.

Similarly, use of Paxil (paroxetine) was associated with an increased risk of heart defects; venlafaxine (Effexor), with lung defects; and tricyclic antidepressants (such as Elavil), with increased eye, ear, face and neck defects.

Depression is on the rise across the globe and is a leading cause of death, according to the World Health Organization. Depression is particularly serious during pregnancy, and doctors – especially psychiatrists, obstetricians and other specialists – are prescribing more antidepressants than ever to expectant mothers.

Over the decade or so that Bérard studied her cohort, the proportion of expectant mothers on antidepressants in Quebec doubled, from 21 users per 1,000 pregnancies in 1998 to 43 per 1,000 in 2009.

Those using the drugs tend to be older, live alone or be on welfare; they also may have other ailments such as diabetes, hypertension and asthma, the new study shows. The women generally don’t have the financial means, leisure time or support to seek other solutions, such as exercising regularly or consulting with a psychotherapist.

“There are a multitude of ways to get mild to moderate depression treated, but you need to have the time and money and also the encouragement to take advantage of them,” Bérard said.

“Given that an increasing number of women are diagnosed with depression during pregnancy, (the new) results have direct implications on their clinical management,” the study concludes.

“This is even more important given that the effectiveness of antidepressants during pregnancy for the treatment of the majority of cases of depression (mild to moderate depression) have been shown to be marginal.

“Hence, the need for caution with antidepressant use during pregnancy is warranted and alternative non-drug options should be considered.”

###

About this study:

“Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: An updated analysis of the Quebec Pregnancy Cohort,” by Anick Bérard, Jinping Zhao and Odile Sheehy, published in BMJ Open on January 12, 2017. doi:10.1136/bmjopen-2016-01337 Anick Bérard, PhD, is a professor at Université de Montréal’s Faculty of Pharmacy and a researcher at the CHU Sainte-Justine Research Centre.

This study was supported by the Canadian Institutes of Health Reseach (CIHR), and the Fonds de la recherche du Québec – Santé (FRQ-S).

Dr. Bérard is the recipient of a FRQ-S Research Chair on Medications and Pregnancy. She is a consultant for plaintiffs in litigations involving antidepressants and birth defects.

Gastric acid suppressants linked to hospitalization

Public Release: 11-Jan-2017

 

Sax Institute

 

New research has found a link between popular heartburn drugs and an increase in the risk of infectious gastroenteritis — an illness that results in 13.1 million lost days of work in Australia a year.

The study led by The Australian National University (ANU) and based on data from the Sax Institute’s 45 and Up Study, found people who take proton pump inhibitors (PPIs), had a 70 per cent increase in the risk of being admitted to hospital with infectious gastroenteritis.

Lead author Dr Yingxi Chen from the ANU National Centre for Epidemiology and Population Health said the research examined data from the study to look at cases of infectious gastroenteritis in Australians older than 45.

“We found that taking PPIs increased the risk of hospitalisation with infectious gastroenteritis by up to 70 per cent because they significantly reduce the amount of acid made by stomach, which increases risk of infectious gastro,” Dr Chen said.

PPIs are one of the world’s most commonly used gastric acid suppressants, with more than 19 million scripts prescribed annually in Australia.

The research builds on a report by the ANU National Centre for Epidemiology and Population Health which found 15.1 million gastro cases in Australia in 2010.

“There is no doubt that PPIs are an effective treatment for reflux and heartburn. However, clinicians and the patients using them should be fully aware of the side effects when considering PPI use and dosage,” Dr Chen said.

“The elderly and those with chronic bowel problems are most at risk. These patients should be having a conversation with their doctor to ensure that they are on right dose and that these drugs are the right fit for them.”

Dr Martin McNamara, Head of Research Assets at the Sax Institute said these findings demonstrated the value of the 45 and Up Study as a national research resource.

“The 45 and Up Study is the largest ongoing study of healthy ageing in the Southern Hemisphere, allowing hundreds of Australia’s world class researchers to investigate big and complex issues and deliver answers in ways that are easily accessible to policy makers,” he said.

###

About the 45 and Up Study:

The Sax Institute’s 45 and Up Study is the largest ongoing study of healthy ageing in the Southern Hemisphere, involving a quarter of a million people – one in every 10 men and women aged 45 and over in NSW.

Medications for heartburn and gastric issues could lower possibility of survival and recovery for cancer patients

Public Release: 15-Dec-2016

Avoiding over-the-counter heartburn meds could save cancer patients’ lives

 

University of Alberta Faculty of Medicine & Dentistry

 

IMAGE

IMAGE: Proton pump inhibitors (PPIs), which are very common medications for heartburn and gastrointestinal bleeding, decrease effects of capecitabine, a type of chemotherapy usually prescribed to gastric cancer patients.

Credit: Melissa Fabrizio

Something as seemingly harmless as a heartburn pill could lead cancer patients to take a turn for the worse. A University of Alberta study published in journal JAMA Oncology discovered that proton pump inhibitors (PPIs), which are very common medications for heartburn and gastrointestinal bleeding, decrease effects of capecitabine, a type of chemotherapy usually prescribed to gastric cancer patients.

The study by Department of Oncology’s Michael Sawyer, Michael Chu and their team included more than 500 patients and the results were conclusive: PPIs affected progression-free survival by more than a month; the overall survival in cancer patients was reduced by more than two months, and the disease control rate decreased by 11 per cent.

Although this research was focused on gastric cancer patients, Sawyer’s team has followed up with another study in early stage colorectal cancer and discovered that those who took PPIs and capecitabine were also at risk for decreased cancer treatment efficacy. In that study, patients who took PPIs while on capecitabine had a decreased chance of being cured of their colorectal cancer.

PPIs are very popular for their efficacy and many of them are over-the-counter drugs (some common brands are Nexium, Prevacid and Protonix). Sawyer explains the risk of this interaction is high as some cancer patients may not even have these medications prescribed by a physician, but could obtain them easily over-the-counter at a pharmacy and accidentally alter their chemotherapy treatment without knowing it: “This could be a very common and underappreciated side effect. One study estimated that at 20 per cent of cancer patients in general take proton pump inhibitors.”

The explanation for the negative outcome may be in gastric pH levels. Previous studies had been done on the interaction of this type of chemo with the antacid medication Maalox, without obtaining any alarming results; but unlike Maalox, PPI’s are able to raise pH to a point where they could affect disintegration of capecitabine tablets. “Given that PPIs are much more potent and can essentially abolish gastric acidity there may be a significant interaction between capecitabine and PPIs,” says Sawyer.

Sawyer, a clinical pharmacologist and medical oncologist and member of the U of A’s Faculty of Medicine & Dentistry since 2001, is currently conducting more research on this topic to unveil more about the interaction of chemotherapy with other medications.

This discovery may lead to change the usual procedures for prescription of PPIs. Some cancer patients cannot discontinue these medications in order to treat bleedings or other gastric conditions that must be kept under control. “In that case, there are alternatives for oncologists or family doctors that become aware of this risk,” says Sawyer. “Physicians should use caution in prescribing PPIs to patients on capecitabine and, if they must use PPIs due to gastrointestinal bleeding issues, maybe they should consider using other types of chemotherapy that don’t present this interaction.”

Aspartame may prevent, not promote, weight loss by blocking intestinal enzyme’s activity

Public Release: 22-Nov-2016

 

Mass. General study identifies possible mechanism behind sugar substitute’s lack of effectiveness

Massachusetts General Hospital

A team of Massachusetts General Hospital (MGH) investigators has found a possible mechanism explaining why use of the sugar substitute aspartame might not promote weight loss. In their report published online in Applied Physiology, Nutrition and Metabolism, the researchers show how the aspartame breakdown product phenylalanine interferes with the action of an enzyme previously shown to prevent metabolic syndrome – a group of symptoms associated with type 2 diabetes and cardiovascular disease. They also showed that mice receiving aspartame in their drinking water gained more weight and developed other symptoms of metabolic syndrome than animals fed similar diets lacking aspartame.

“Sugar substitutes like aspartame are designed to promote weight loss and decrease the incidence of metabolic syndrome, but a number of clinical and epidemiologic studies have suggested that these products don’t work very well and may actually make things worse,” says Richard Hodin, MD, of the MGH Department of Surgery, the study’s senior author. “We found that aspartame blocks a gut enzyme called intestinal alkaline phosphatase (IAP) that we previously showed can prevent obesity, diabetes and metabolic syndrome; so we think that aspartame might not work because, even as it is substituting for sugar, it blocks the beneficial aspects of IAP.”

In a 2013 study published in Proceedings of the National Academy of Sciences, Hodin’s team found that feeding IAP to mice kept on a high-fat diet could prevent the development of metabolic syndrome and reduce symptoms in animals that already had the condition. Phenylalanine is known to inhibit the action of IAP, and the fact that phenylalanine is produced when aspartame is digested led the researchers to investigate whether its inhibitory properties could explain aspartame’s lack of a weight-loss effect.

In a series of experiments the team first found that the activity of IAP was reduced when the enzyme was added to a solution containing an aspartame-sweetened soft drink but remained unchanged if added to a solution with a sugar-sweetened beverage. IAP is primarily produced in the small intestine, and the researchers found that injecting an aspartame solution into segments of the small intestines of mice significantly reduced the enzyme’s activity. In contrast, IAP activity remained unchanged in bowel segments injected with a saline solution.

To better represent the effects of consuming beverages or other products containing aspartame, the researchers followed four groups of mice for 18 weeks. Two groups were fed a normal diet, one receiving drinking water with aspartame, the other receiving plain water. The other two groups were fed a high-fat diet, along with either aspartame-infused or plain water. Animals in the normal diet group that received aspartame consumed an amount equivalent to an adult human’s drinking about three and a half cans of diet soda daily, and aspartame-receiving animals in the high-fat group consumed the equivalent of almost two cans.

At the end of the study period, while there was little difference between the weights of the two groups fed a normal diet, mice on a high-fat diet that received aspartame gained more weight than did those on the same diet that received plain water. Aspartame-receiving mice in both diet groups had higher blood sugar levels than did those fed the same diets without aspartame, which indicates glucose intolerance, and both aspartame-receiving groups had higher levels of the inflammatory protein TNF-alpha in their blood, which suggests the kind of systemic inflammation associated with metabolic syndrome.

“People do not really understand why these artificial sweeteners don’t work. There has been some evidence that they actually can make you more hungry and may be associated with increased calorie consumption. Our findings regarding aspartame’s inhibition of IAP may help explain why the use of aspartame is counterproductive,” says Hodin, who is a professor of Surgery at Harvard Medical School. “While we can’t rule out other contributing mechanisms, our experiments clearly show that aspartame blocks IAP activity, independent of other effects.”

###

The co-lead authors of the paper are Sarah Gul and Anna Hamilton, MGH Department of Surgery. Additional co-authors are Alexander Munoz, Tanit Phupitakphol, Wei Liu, MD, Sanjiv Hyoju, Konstantinos Economopoulos, MD, Sara Morrison, MD, Dong Hu, Weifeng Zhang, Mohammad Hadi Gharedaghi, MD, Haizhong Huo, and Sulaiman Hamarneh, MBBS, all MGH Surgery.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of “America’s Best Hospitals.”

Vaccinating against dengue may increase Zika outbreaks

Public Release: 31-Oct-2016

 

York University

 

TORONTO, Monday, October 31, 2016 — Vaccinating against dengue fever could increase outbreaks of Zika, suggests new research out of York University and Xi’an Jiaotong University in China.

The research identifies a potentially serious public health concern. More than a third of the world’s population lives in areas where dengue is endemic and cases of co-infection with Zika have already been reported.

Conducted at York University’s Laboratory for Industrial and Applied Mathematics using mathematical modelling, the research was led by Biao Tang, an exchange PhD student from Xi’an Jiaotong University, in collaboration with York Professor Jianhong Wu and Tang’s supervisor, Professor Yanni Xiao at Xi’an Jiaotong University. As dengue and Zika are both part of the Flaviviridae family transmitted through a common mosquito host, the researchers wanted to know how vaccinating for one would affect the incidence of the other.

“Vaccinating against one virus could not only affect the control of another virus, it could in fact make it easier for the other to spread,” says Wu. “Recent evidence suggests that dengue virus antibodies can enhance the Zika virus infection. For that reason, we developed a new math model to investigate the effect of dengue vaccination on Zika outbreaks.”

The paper, “Implication of vaccination against dengue for Zika outbreak,” was published in Scientific Reports.

The team’s model shows that vaccinations for dengue increase the number of people contracting Zika. It also shows that the more people in a particular population that are vaccinated against dengue, the earlier and larger the Zika outbreak. The research also found that the most effective way to minimize the unintended effect of dengue vaccinations on Zika outbreaks is through an integrated strategy that includes mosquito control.

“We concluded that vaccination against dengue among humans can significantly boost Zika transmission among the population and hence call for further study on integrated control measures on controlling dengue and Zika outbreak,” says Xiao.

The researchers note their findings do not discourage the development and promotion of dengue vaccine products, however, more work needs to be done to understand how to optimize dengue vaccination programs and minimize the risk of Zika outbreaks.

According to the World Health Organization, the global incidence of dengue has grown dramatically in recent decades, with about half of the world’s population now at risk. In some Asian and Latin American countries, severe dengue is a leading cause of serious illness and death among children. Whereas the outbreaks of Zika have occurred in Africa, the Americas, Asia and the Pacific, and has been linked to microcephaly and Guillain-Barré syndrome. Although vaccines for dengue have been developed and are in use, there is no vaccine for Zika.

###

York University is known for championing new ways of thinking that drive teaching and research excellence. Our students receive the education they need to create big ideas that make an impact on the world. Meaningful and sometimes unexpected careers result from cross-discipline programming, innovative course design and diverse experiential learning opportunities. York students and graduates push limits, achieve goals and find solutions to the world’s most pressing social challenges, empowered by a strong community that opens minds. York U is an internationally recognized research university – our 11 faculties and 26 research centres have partnerships with 200+ leading universities worldwide. Located in Toronto, York is the third largest university in Canada, with a strong community of 53,000 students, 7,000 faculty and administrative staff, and more than 295,000 alumni. York U’s fully bilingual Glendon campus is home to Southern Ontario’s Centre of Excellence for French Language and Bilingual Postsecondary Education

Yearly exposure to chemicals dangerous to hormone function burdens Americans with hundreds of billions in health care costs and lost earnings

Public Release: 17-Oct-2016

 

NYU Langone Medical Center / New York University School of Medicine

 

EDC COST

Caption

Annual health care costs and lost earnings in the United States from low-level but daily exposure to hazardous chemicals commonly found in plastic bottles, metal food cans, detergents, flame retardants, toys, cosmetics, and pesticides, exceeds $340 billion, according to a detailed economic analysis by researchers at NYU Langone Medical Center.

Credit: NYU Langone Medical Center

Annual health care costs and lost earnings in the United States from low-level but daily exposure to hazardous chemicals commonly found in plastic bottles, metal food cans, detergents, flame retardants, toys, cosmetics, and pesticides, exceeds $340 billion, according to a detailed economic analysis by researchers at NYU Langone Medical Center.

The investigators who performed the calculations say the massive toll from everyday contact with endocrine- disrupting chemicals amounts to more than 2.3 percent of the country’s gross domestic product.

Included in the team’s analysis, described in the The Lancet Diabetes & Endocrinology online Oct. 17, are estimated costs from more than 15 medical conditions linked by previous research to toxic levels of these chemicals. Scientists say chemical exposure occurs through gradual ingestion and buildup of these toxins as consumer products are used and break down.

According to researchers, endocrine-disrupting chemicals have for decades been known to pose a danger to human health because the compounds can interfere with natural hormone function. Such chemicals include bisphenol A (BPA), commonly used to line tin food cans; phthalates, used in the manufacture of plastic food containers and many cosmetics; PCB-like polybrominated diphenyl ethers, or PBDEs, found in flame retardants in furniture and packaging; and pesticides, such as chlorpyrifos and organophosphates.

However, the researchers say their new analysis, which took three years to complete, is the first U.S. assessment of the costs associated with routine endocrine-disrupting chemical exposure and resulting increases not only in rates of neurological and behavioral disorders, but also in rates of male infertility, birth defects, endometriosis, obesity, diabetes, and some cancers, as well as diminished IQ scores.

“Our research adds to the growing evidence on the tremendous economic as well as human health costs of endocrine-disrupting chemicals,” says study lead investigator and health epidemiologist Leonardo Trasande, MD, MPP, an associate professor at NYU Langone.

For the new study, the NYU team reviewed blood sample and urine analyses for documentation on the presence of endocrine disrupting chemicals in participants in the National Health and Nutrition Examination Survey. Since 1999, NHANES, as it is known, has gathered information about the prevalence of and risk factors for major diseases by annually surveying 5,000 volunteers. Advanced computer models were then used to project disease totals attributable to chemical exposure and to calculate the estimated health costs and lost income for each disease.

According to Trasande, their analysis shows that yearly exposure to highly toxic fire-resisting PBDE chemicals and pesticides accounted for nearly two-thirds of the total endocrine-disrupting chemical disease burden, and mostly from neurological damage these chemicals cause in the unborn. Specifically, he says, annual PBDE exposure was estimated to account for 11 million lost IQ points in children, an additional 43,000 cases of “intellectual disability,” and an associated disease burden of some $266 billion. Meanwhile, pesticide exposure was estimated to cost 1.8 million lost IQ points and lead to 7,500 more disability cases each year, with total health costs of $44.7 billion.

Trasande says such PCB-like chemicals are more widely available in the U.S. than in Europe, where the chemicals are more tightly regulated, and whose data were studied by the same NYU Langone team last year. The team estimated the chemicals’ disease impact there at more than $100 billion.

“Based on our analyses, stronger regulatory oversight of endocrine-disrupting chemicals is needed, not just in Europe, but in the U.S.,” says Trasande. “This oversight should include not only safety tests on the chemicals’ use in the manufacture of commercial products before the chemicals receive government approval, but also studies of their health impact over time once they are used in consumer products,” he adds.

Among the other key diseases attributed to endocrine-disrupting chemical exposure and factored into the team’s calculations were over 1,500 estimated cases of autism and more than 4,400 cases of attention-deficit/hyperactivity disorder, or ADHD.

More specifically, phthalate exposure was estimated to contribute to some 5,900 adults developing obesity; 1,300 cases of diabetes; 86,000 cases of endometriosis, which cost more than $47 billion; as well as 10,700 early deaths from heart and other vascular diseases, such as stroke.

Trasande cautions that the statistical modeling used in the analysis significantly discounted disease numbers to account for likely as opposed to actual people with any particular condition. He says his team’s calculations are on the “low end of the scale” and that if total disease numbers were fully included, then cost estimates for the actual economic burden of EDCs would be much higher.

Senior study investigator Teresa M. Attina, MD, PhD, also of NYU Langone, says there are “safe and simple” steps families can take to limit exposure to endocrine-disrupting chemicals. These include not microwaving food in plastic containers or covered by plastic wrap, and washing plastic food containers by hand instead of putting them in the dishwasher. She says people can also avoid using plastic containers labeled on the bottom with the numbers 3, 6 or 7 (inside the recycle symbol), in which chemicals such as phthalates are used. Switching to “all natural” or “fragrance-free” cosmetics is also an option.

###

Funding for the latest economic analysis was provided by National Institutes of Health grant R01ES022972, the Endocrine Society, and the Broad Reach Foundation.

Media Inquiries:

David March
212-404-3528
david.march@nyumc.org

Men born to in vitro fertilization likely to be infertile themselves

Public Release: 5-Oct-2016

First results on semen quality from the world’s oldest group of ICSI men

European Society of Human Reproduction and Embryology

First results from the world’s oldest group of young men conceived by means of intracytoplasmic sperm injection (ICSI) fertility treatment because of their fathers’ infertility have shown that they have lower sperm quantity and quality than men who were spontaneously conceived.

The study, which is published today (Thursday) in Human Reproduction [1], one of the world’s leading reproductive medicine journals, has found that these men, who were aged between 18 to 22, had almost half the sperm concentration and a two-fold lower total sperm count [2] and total count of motile sperm (sperm that could swim well) than did naturally conceived men of a similar age.

In addition, compared to men born after spontaneous conception, ICSI men were nearly three times more likely to have sperm concentrations below 15 million per millilitre of semen, which is the World Health Organisation’s definition of “normal”, and four times more likely to have total sperm counts below 39 million.

ICSI was pioneered at the Centre for Reproductive Medicine at the Vrije Universiteit Brussel (VUB), Brussels, Belgium, which was headed by Professor André Van Steirteghem, one of the co-authors of this study. The first ICSI baby was born on 14 January 1992. The current study reports on 54 men, born in the early years of ICSI between 1992-1996, when ICSI was only used to treat male infertility.

ICSI is a procedure by which sperm from the father is injected directly into the mother’s egg in the laboratory, and then the fertilised egg is placed in her womb. For men who have very few, viable sperm, this means that the fertility experts can choose the best quality sperm and ensure it fertilises the egg by injecting the sperm rather than leaving it to swim to the egg unaided.

Professor Van Steirteghem and his colleagues always knew that the problems that had caused the father’s infertility, usually genetic factors, might be inherited by these men’s offspring. However, until now, questions about the fertility of the ICSI offspring could not be answered because of their young age.

“These findings are not unexpected,” said Professor Van Steirteghem, who is now emeritus professor at VUB and a consultant at the University Hospital (UZBrussel). “Before ICSI was carried out, prospective parents were informed that it may well be that their sons may have impaired sperm and semen like their fathers. For all the parents this information was not a reason to abstain from ICSI because, as they said: ‘if this happens ICSI can then also be a solution for our sons’.

“These first results from the oldest group of ICSI-conceived adults worldwide indicate that a degree of ‘sub-fertility’ has, indeed, been passed on to sons of fathers who underwent ICSI because of impaired semen characteristics.”

The study was carried out at UZBrussel between March 2013 and April 2016. It is part of a larger project that is following the health of young adults, male and female, born as a result of ICSI. The young men were approached via their parents in case the parents had not disclosed to their children the method of conception. Fifty-four out of a total of 215 young ICSI men on the UZBrussel database agreed to take part in the study and they were matched with a control group of men of a similar age who had been conceived naturally. They were asked to provide a semen sample for analysis; blood samples were also taken and other health checks performed. The participants were offered genetic testing in cases where sperm concentrations fell below 5 million/ml, and they were offered written feedback, appropriate counselling, investigation and follow-up.

ICSI had been carried out for the fathers of 50 out of 54 of the young men because of male-factor infertility (48 for male infertility only, two for combined male and female infertility), while the remaining four sets of parents suffered from infertility with unknown cause.

The researchers adjusted their results for factors that could affect semen quality, such as age, body mass index (BMI), genital malformations, time from ejaculation to analysis, and abstinence period.

Although sperm concentrations and counts were lower in the ICSI men than in their spontaneously conceived peers, the researchers found that a low sperm concentration and total motile sperm count in fathers did not correlate with corresponding values in their sons.

“The study shows that semen characteristics of ICSI fathers do not predict semen values in their sons. It is well established that genetic factors play a role in male infertility, but many other factors may also interfere. Furthermore, correlation is not the same thing as causation,” said Prof Van Steirteghem.

“These results highlight the need to continue and expand other follow-up studies on children conceived by assisted reproduction techniques. For instance, paired analysis of samples from fathers and sons should be carried out, and we need to look at larger numbers of offspring. This remains a challenging project for the VUB. However, health authorities and funding agencies should provide the means to answer questions concerning the effects of genetics, mode of conception, foetal growth patterns and birth weights on the fertility of ICSI men,” he said.

Since the early days of ICSI, the technique has been used increasingly to treat infertility, even when male infertility is not suspected. In some countries ICSI is used in nearly 100% of all in vitro fertilisation (IVF) procedures. Therefore, the authors warn that the findings from this study cannot be extrapolated to all offspring born after ICSI since nowadays ICSI is increasingly used even when there is no evidence that a couple’s infertility is due to abnormal semen measurements in the man.

###

[1] “Semen quality of young adult ICSI offspring: the first results,” by F. Belva et al. Human Reproduction journal. doi:10.1093/humrep/dew245.

[2] Total sperm count is semen volume x semen concentration.

New Research indicates its the amount of gluten that triggers celiac disease not the timing

Public Release: 3-Oct-2016

New research delimits the possible causes of celiac disease

Lund University

The amount of gluten could be a more important clue than breast-feeding or the timing of the introduction of gluten for continued research into the causes of celiac disease (gluten intolerance). This is one of the findings from several extensive studies of children with an increased genetic risk of celiac disease conducted by researchers at Lund University in Sweden.

Sweden is a high-risk country for the development of celiac disease in early life. Currently, the only known and effective treatment for the disease is for patients to follow a gluten-free diet for the rest of their lives. It is still unclear why gluten intolerance occurs, but researchers all over the world have long focused their efforts on factors such as breast-feeding, dietary habits, the timing of the introduction of gluten and geographical origin. A new doctoral thesis from Lund University includes studies covering all these aspects.

“Our findings indicate that the amount of gluten triggers the disease. We have also observed that the dietary habits among the children we studied vary from one country to another, and that there are reasons to analyse the significance of this variation more closely. More in-depth studies could perhaps contribute to explaining why Swedish children develop celiac disease earlier than children in other countries”, says Carin Andrén Aronsson, a dietician and doctoral student at Lund University, continuing:

“The timing of the introduction of gluten, on the other hand, does not seem to be of great significance. We conducted a very extensive study which confirms similar conclusions from previous, smaller studies.”

All the research in the doctoral thesis is based on small children born with an increased genetic risk of developing celiac disease. Some of the most important conclusions are:

Swedish children whose reported daily intake of gluten was high (more than five grams) up to the age of two years had twice the risk of developing coeliac disease compared to children who consumed a smaller amount. The results from the same sub-study also show that children with celiac disease ate more gluten. The risk of developing the autoimmunity which gives rise to celiac disease was highest in Sweden compared to the other countries in the study (Finland, Germany and USA). The result held after adjustment for some of the most important causes of celiac disease (carrying the risk gene, previous diagnosis in the family and gender). Breast-feeding (starting point/duration), the timing of the first introduction of solid foods and the type of diet varied among the countries studied. European children were first introduced to potatoes and root vegetables while American children were first given rice and root vegetables. There was no apparent connection between the duration of the period of breast-feeding and the risk of developing celiac disease. The timing alone of the introduction of gluten in the diet is not an independent risk factor for subsequent development of gluten intolerance.

The issues surrounding gluten intolerance will continue to occupy Carin Andrén Aronsson after the public defence of her thesis.

“We will investigate the significance of the amount of gluten in a large new study. Is the gluten intake of Swedish children different from that of children in other countries? We will expand the study with children from the other participant countries and increase the follow-up period in comparison with our previous studies, from two to five years. We will also investigate whether the addition of probiotics (beneficial bacteria) to the diet has any effect on the risk of developing celiac disease”, explains Carin Andrén Aronsson, before adding:

“With more knowledge about the significance of diet, I hope it will become possible to personalise the diet instead of having general dietary guidelines as we have today.”

The basis for the studies in the doctoral thesis is a cohort of up to 8 700 children in four countries: Sweden, Finland, Germany and the USA. The children are part of an international research project, TEDDY (The Environmental Determinants of Diabetes in the Young), whose aim is to determine the reasons why children get type 1 diabetes and/or coeliac disease. The principal funding body behind the study is the National Institutes of Health,(NIH) in the US.

“It is a very major and resource-intensive endeavour to determine the causes of celiac disease. Thanks to the children in the TEDDY study, we can conduct several studies of significance to research”, explains Carin Andrén Aronsson.

Prescription sleep aids carry a rare suicide risk, review finds

Public Release: 3-Oct-2016

 

Medical College of Georgia at Augusta University

AUGUSTA, Ga. (Oct. 3, 2016) – Prescription sleep aids appear to carry a rare risk of suicide, most typically when they cause the unexpected response of stimulating rather than quietening patients, researchers say.

“These medications can have a rare paradoxical effect like alcohol where people start behaving completely out of character,” said Dr. W. Vaughn McCall, chair of the Department of Psychiatry and Health Behavior and Case Distinguished Chair at the Medical College of Georgia at Augusta University. “Instead of calming, they may hyperstimulate; instead of being relaxed, patients become fearful; so it goes the opposite way.

“We don’t know why, and we can’t pick these people out in advance,” McCall said, which is why he encourages patients’ physicians and family members to keep a close eye out for any unusual behavior particularly in the first 7-10 days of taking a hypnotic.

The Food and Drug Administration mandates a warning of suicidal thoughts and/or actions be included in the often-discarded package insert that comes with modern hypnotics. “It got me wondering, what is really the evidence behind that, and how often does it happen?” said McCall, an expert in the trifecta of depression, insomnia and suicide.

He is corresponding author on a review article in The American Journal of Psychiatry that examined published studies as well as reports on file with the FDA, which associated modern hypnotics prescribed as a sleep aid with suicidal thoughts and actions.

Researchers looked at 11 hypnotics currently prescribed to adults for the primary complaint of insomnia, including flurazepam, the first to receive FDA approval. They looked at FDA-approved labeling on all the drugs then did a literature search for any published studies linking the drugs to suicide or suicidal thoughts. They searched the FDA website for safety reviews and commentaries on the drugs. Under the Freedom of Information Act, they asked the FDA for detailed reports of hypnotic-related suicide deaths reported to the agency’s Adverse Event Reporting System, specifically cases and drugs that had not been reported in the scientific literature. They examined reports dating back to the 1970s.

The main new finding of their extensive review is that the first few days taking the medications is when a rare and unintended response is most likely to arise. He encourages his colleagues to tell patients and their families that there is a small chance that they will feel worse – not better – taking the medication, particularly early on. If there are any instances of sleepwalking or suicidal thoughts, patients should immediately stop taking the medication and call their doctor.

“I would not wait to see what happens,” McCall said.

He shared one story uncovered in the review of an apparently otherwise healthy 39 year old who took a hypnotic for the first time and on the third night his wife found him sleep walking with no memory of it. The next morning he told his wife he could not focus, walked into the woods and shot himself. The researchers found about a dozen of these unusual responses; they found significantly more suicide cases in which the patient already had suicidal thoughts.

The use of sleeping pills as a method to commit suicide is well-known, and McCall recommends as another cautionary measure giving only a small supply of the drug to patients just starting out.

Modern hypnotics tend to work, similar to valium, by enhancing efficiency of the inhibitory neurotransmitter GABA, which tends to quiet down overall brain activity, so patients feel more relaxed, McCall said.

While insomnia and mental health problems such as depression, which also carries an increased suicide risk, often go hand in hand, modern antidepressants are not reliable as a sleep aid. “Modern antidepressants reliably help just about every other symptoms except sleep, so it’s not uncommon for someone who is depressed to take a combination,” McCall said.

“Although the jury is still out, my bet is it’s better in most cases to treat the insomnia,” said McCall, principal investigator on a four-year National Institute of Mental Health-funded study that should help answer that question. McCall reported in the Journal of Clinical Sleep Medicine in 2013 that lost hope over ever getting another good night’s sleep is itself a high risk for suicide.

“Now we are adding a new twist that is: Do the pills themselves make you suicidal when you would not think about it otherwise?” he said. He reemphasized that the review showed the answer is “In rare cases, yes.”

More commonly, it appears that a good night’s sleep can reduce suicidal thinking in a depressed individual. But his reviews found that those who committed suicide that appeared associated with hypnotic use – as a sleep aid, not as a suicide means – typically had no previous history of mental health concerns other than the fact that they could not get a good night’s sleep.

The review found only one hypnotic medication toxicology study in the United States, a look at 187 consecutive suicide victims from the San Diego coroner’s office in the early 1980s that found no direct cause and relationship between hypnotics and suicide, although in this and subsequent studies, hypnotics were sometimes used to commit suicide. A large survey of 5,692 adults in the early 2000s found 5.8 percent saying they had used a sleeping pill in the last 12 months; 2.6 percent of those reported suicidal thoughts, and .4 percent a suicide attempt. However, it was unclear in the large study how many of the individuals had other established suicide risks such as depression.

Other steps for decreasing suicide risk in adults starting to take hypnotics include prescribing the lowest dose possible and providing the standard warning about avoiding alcohol use and taking the drugs with other medicines that also have sedative or similar effects, the researchers write. Patients should also go to bed within 15 minutes of taking the drug and stay in bed long enough for the medicine to run its course.

About 3 percent of adults report using a hypnotic, and up to 10 percent use over-the-counter sleep aids, the researchers write. It’s unknown whether more commonly used over-the-counter sleep aids have a suicide risk, although the FDA currently does not require a warning on their package information, McCall said. Like their more powerful prescribed counterparts, those drugs are sometimes used to commit suicide.

Options for insomnia treatment include psychotherapy, which McCall recommends before taking any medication. Exercise can help as can sticking to a regular sleep routine where patients go to bed and arise about the same time and avoid staying in bed more than eight hours. Melatonin may help, but is not very powerful, he said. Anxiety is another cause of insomnia along with Type A personalities who can’t quieten their thoughts about what has occurred and what happens next in their lives.

###

The research was supported by the National Institute of Mental Health and the American Foundation for Suicide Prevention. Collaborators include researchers at the University of California, Irvine; Wake Forest University School of Medicine; the University of Wisconsin; and Duke University School of Medicine.

Codeine too risky for kids, experts say, urging restrictions on use

 

Date:

September 19, 2016

Source:

American Academy of Pediatrics

Summary:

Experts are urging parents and health providers to stop giving codeine to children, calling for more education about its risks and restrictions on its use in patients under age 18. They say that there is a continued use of the drug in pediatric settings despite growing evidence linking the common painkiller to life-threatening or fatal breathing reactions.

 

FULL STORY


An opioid drug used for decades in prescription pain medicines and over-the-counter cough formulas, codeine is converted by the liver into morphine.

Credit: © dimasobko / Fotolia

 

The American Academy of Pediatrics is urging parents and health providers to stop giving codeine to children, calling for more education about its risks and restrictions on its use in patients under age 18. A new AAP clinical report in the October 2016 issue of Pediatrics, “Codeine: Time to Say `No,'” cites continued use of the drug in pediatric settings despite growing evidence linking the common painkiller to life-threatening or fatal breathing reactions.

An opioid drug used for decades in prescription pain medicines and over-the-counter cough formulas, codeine is converted by the liver into morphine. Because of genetic variability in how quickly an individual’s body breaks down the drug, it provides inadequate relief for some patients while having too strong an effect on others. Certain individuals, especially children and those with obstructive sleep apnea, are “ultra-rapid metabolizers” and may experience severely slowed breathing rates or even die after taking standard doses of codeine.

Despite these well-documented risks and with concerns expressed by groups including the AAP, the U.S. Food & Drug Administration and the World Health Organization, the drug still is available without a prescription in over-the-counter cough formulas from outpatient pharmacies in 28 states and the District of Columbia. In addition, according to the AAP report, it still is commonly prescribed to children after surgical procedures such as tonsil and adenoid removal. More than 800,000 patients under age 11 were prescribed codeine between 2007 and 2011, according to one study cited in the AAP report. Otolaryngologists were the most frequent prescribers of codeine/acetaminophen liquid formulations (19.6 percent), followed by dentists (13.3 percent), pediatricians (12.7 percent) and general practice/family physicians (10.1 percent).

The new clinical report outlines potential alternatives to provide pain relief in children but acknowledges that relatively few safe and effective drugs are available for pediatric use.

“Effective pain management for children remains challenging,” said the report’s lead author, Joseph D. Tobias, MD, FAAP, “because children’s bodies process drugs differently than adults do.”

The AAP report, published online Sept. 19, calls for improved education of parents and health providers about the risks of codeine use in children and formal restrictions of its use in children, as well as further research on safe and effect pain treatment in children.


Story Source:

The above post is reprinted from materials provided by American Academy of Pediatrics. Note: Content may be edited for style and length.


Journal Reference:

  1. J. D. Tobias, T. P. Green, C. J. Cote. Codeine: Time To Say “No”. PEDIATRICS, 2016; DOI: 10.1542/peds.2016-2396

Dengue vaccine makes dengue infection far worse not better

“If someone has never been exposed to dengue, the vaccine seems to act like a silent infection. The initial exposure to the virus from the vaccine primes the immune system, so when they are infected again, the symptoms are more likely to be severe.”

Public Release: 1-Sep-2016

Dengue vaccine may increase risk of severe disease if used in areas with low rates of infection

Imperial College London

These infections are also more likely to need hospitalisation, suggests the study, by scientists from Imperial College London, John Hopkins Bloomberg School of Public Health and the University of Florida.

The research, published in the journal Science, analysed all publicly available clinical trial data for the vaccine. The results suggest that in people who have never been exposed to dengue before, the vaccine primes the immune system so that if they are subsequently infected, the infection is more severe.

However in people who are have been exposed to the virus before vaccination, the vaccine reduces the severity of future infections.

The researchers recommend testing people before they receive the vaccine, to establish if they have previously been exposed to the dengue virus. This would help avoid triggering an increase in serious cases of the disease.

Dengue is a viral infection that causes just under 400 million cases per year. According to the latest estimates, around half of the world’s population are thought to be at risk. The virus is spread by mosquitoes, and causes fever, headache, muscle and joint pain. In some cases, it can lead to a life-threatening condition called haemorrhagic fever which is a leading cause of death and serious illness among children in some Asian and Latin American countries.

Unlike most infectious diseases, the second time a person is infected with dengue is usually far more serious than the first. This may be why the vaccine appears to amplify the illness in some individuals, particularly young children.

Normally, when a person is infected with a virus their immune system builds defences against it. This means when they are infected a second time, the virus is destroyed before triggering symptoms. However, with dengue, the virus primes the immune system to work against the body. So when a person is infected a second time, a component of the immune system – called antibodies – help the virus infect the cells, leading to a more severe infection.

This has serious implications for the vaccine, explains Professor Neil Ferguson, co-lead author, who is the Director of the MRC Centre for Outbreak Analysis and Modelling at Imperial College London: “If someone has never been exposed to dengue, the vaccine seems to act like a silent infection. The initial exposure to the virus from the vaccine primes the immune system, so when they are infected again, the symptoms are more likely to be severe.”

The vaccine, produced by the company Sanofi-Pasteur, is available in six countries and has been trialled on around 30,000 people from ten countries.

After analysing the data, the research team formulated a computer model to predict the effectiveness of the vaccine if used more widely.

Professor Neil Ferguson said: “Having a licensed dengue vaccine available is a significant step forward for dengue control. However, we should be careful in considering where and how to use this vaccine as there is still uncertainty about the impact.”

The team stress the vaccine stills holds benefits – but only if used in areas heavily affected by dengue, where individuals being vaccinated are likely to have encountered the virus before.

Derek Cummings, Professor of Biology at the University of Florida and co-author of the study added: “In places with high transmission intensity, most people have been already exposed to dengue at the time of vaccination, and the vaccine has higher efficacy on average. However, in places with lower transmission intensity, were individuals haven’t been previously exposed, the vaccine can place people at risk of severe disease and overall, increase the number of hospitalized cases.”

Dr Isabel Rodriguez-Barraquer, joint first author of the research from Johns Hopkins Bloomberg School of Public Health, explained: “Our results indicate that screening potential vaccine recipients could maximize the benefits and minimise the risk of negative outcomes.”

The World Health Organization recommends that countries consider introduction of the dengue vaccine only in geographic settings (national or subnational) where data suggests a high burden of disease.

Professor Ferguson added: “Our model refines estimates of which places would see a decline in dengue incidence with large scale vaccination programmes, and which places should not implement programmes at this point in time. These results present the first published, independent predictions of the potential impact of vaccination that take account of recent data showing that the vaccine can increase the risk of severe dengue disease in young children.”

The authors hope their analysis can help inform policy-makers in evaluating this and other candidate dengue vaccines.

###

The work was funded by the UK Medical Research Council, the NIHR UK National Institute of Health Research Health Protection Research Unit (HPRU) in Healthcare Associated Infections and Antimicrobial Resistance under the Health Protection Research Unit initiative, National Institute of Allergy and Infectious Diseases and National Institute of General Medical Sciences (NIH) under the MIDAS initiative, and the Bill and Melinda Gates Foundation.

Caroline Brogan
Research Media Officer (Research)
Imperial College London
caroline.brogan1@imperial.ac.uk
+44(0)20 7594 2412
Duty press officer mobile: +44 (0)7803 886 248

1. “Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment” by Neil M. Ferguson et al is published in Science, 1 September 2016.

2. About Imperial College London

Imperial College London is one of the world’s leading universities. The College’s 16,000 students and 8,000 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.

Founded in 1907, Imperial builds on a distinguished past – having pioneered penicillin, holography and fibre optics – to shape the future. Imperial researchers work across disciplines to improve health and wellbeing, understand the natural world, engineer novel solutions and lead the data revolution. This blend of academic excellence and its real-world application feeds into Imperial’s exceptional learning environment, where students participate in research to push the limits of their degrees.

Imperial collaborates widely to achieve greater impact. It works with the NHS to improve healthcare in west London, is a leading partner in research and education within the European Union, and is the UK’s number one research collaborator with China.

Imperial has nine London campuses, including its White City Campus: a research and innovation centre that is in its initial stages of development in west London. At White City, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale. http://www.imperial.ac.uk

3. National Institute for Health Research

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. The NIHR is the research arm of the NHS. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (http://www.nihr.ac.uk).

4. MRC

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.mrc.ac.uk

Five-year study reveals patients operated on at night twice as likely to die as patients who have daytime operations

Public Release: 29-Aug-2016

 

World Federation of Societies of Anaesthesiologists

New research presented at this year’s World Congress of Anaesthesiologists (WCA) in Hong Kong (28 Aug – 2 Sept) shows that patients who have surgery during the night are twice as likely to die as patients operated on during regular working hours. Patients operated on later in the working day or in the early evening also have a higher mortality risk, concludes the study by Dr Michael Tessler, Associate Professor of Anesthesiology, and Dr Ning Nan Wang, Chief Resident, Department of Anesthesia at McGill University Health Centre, Montreal, Canada, and colleagues.

Postoperative mortality risk factors have been previously extensively studied. Previously identified risk factors include the patient age (1,2); the American Society of Anaesthesiologists (ASA) overall risk score (2) and emergency status (1,2). Research studies analysing the time of surgery and postoperative mortality have had ambiguous results. The aim of this study was to investigate relationship between postoperative mortality and the time of the day of surgery at a Canadian hospital – the Jewish General Hospital in Montreal, Canada.

After obtaining institutional ethics review board approval, a retrospective review of 30 day postoperative in hospital mortality was carried out at the hospital, which is also a teaching hospital. The study evaluated all surgical procedures for the past 5 years, starting from April 1, 2010 to March 31, 2015. A database was constructed collecting variables about surgical interventions. All elective and emergent surgical cases were included except ophthalmic and local anaesthesia cases (since the vast majority of ophthalmic cases are performed under local rather than general anesthesia, and not in the regular operating theatre).

The working day was divided into three time blocks (Daytime 07:30-15:29, Evening 15:30-23:29 and night time 23:30-07:29). The start time of the anaesthetic recorded by the circulating nurse was used to determine in which time block the operation began.

There were 41,716 elective and emergency surgeries performed on 33,942 patients in 40,044 hospitalizations. Of these, 10,480 were emergency procedures; there were 3,445; 4,951; and 2,084 emergency procedures with anaesthesia starting between day, evening and night respectively. There were 226, 97 and 29 deaths of all cases during day, evening and night surgery (79, 95, 29 mortalities for emergency surgery in the same time periods) respectively.

The researchers found that after adjustment for age and ASA scores, the patients operated in the night were 2.17 times more likely to die than those operating on during regular daytime working hours, and patients operated on in the late day were 1.43 times more likely to die than those operated on during regular daytime working hours.

The researchers say: “This study demonstrates that late day and night emergency surgery are associated with higher mortality when factoring in ASA score and patient age. Postoperative 30-day in-hospital mortality rate should include start time of anaesthesia, along with other known variables, as a risk factor.”

They say that theoretical possible causes include, but are not limited to, provider fatigue during anaesthesia and surgery, overnight hospital staffing issues, delays in treatment (for example how many operating rooms are available), or the patient being too sick to be postponed prior to treatment. The authors say: “Analysis of each of these possibilities is important to understand the reasons for this increased mortality and to direct any remedial action in an effort to reduce postoperative mortality.”

How do antidepressants trigger fear and anxiety?

Public Release: 24-Aug-2016

 

UNC School of Medicine researchers map the anxiety circuit in the brain and use a compound to limit fearful behavior — an acute side effect of commonly prescribed SSRI antidepressants

University of North Carolina Health Care

CHAPEL HILL, NC – More than 100 million people worldwide take selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Zoloft, to treat depression, anxiety and related conditions, but these drugs have a common and mysterious side effect: they can worsen anxiety in the first few weeks of use, which leads many patients to stop treatment. Scientists at the University of North Carolina (UNC) School of Medicine have mapped out a serotonin-driven anxiety circuit that may explain this side effect and lead to treatments to eliminate it.

“The hope is that we’ll be able to identify a drug that inhibits this circuit and that people could take for just the first few weeks of SSRI use to get over that hump,” said senior investigator Thomas L. Kash, PhD, the John Andrews Distinguished Professor of Alcohol Studies in the UNC School of Medicine’s department of pharmacology. “More generally, this finding gives us a deeper understanding of the brain networks that drive anxiety and fear behavior in mammals.”

The new study, published in Nature, counters the popular view of serotonin as a neurotransmitter that promotes only good feelings. SSRIs, which are taken by about one in 10 people in the United States and about one in four women in their 40s and 50s, are thought to improve mood by boosting serotonin activity in the brain. There are brain circuits through which serotonin does seem to improve mood, and some studies have linked depression to abnormally low levels of serotonin. But the short-lived promotion of anxiety in many patients on SSRIs – even suicidal thinking, particularly in younger people – has long hinted that serotonin can have negative effects on mood, depending on the precise brain circuit where it acts.

In the Nature study, for which co-authors were UNC postdoctoral researcher Catherine A. Marcinkiewcz, PhD, and UNC graduate student Christopher M. Mazzone, the researchers used an array of sophisticated methods, including advanced optogenetic and chemogenetic tools, to trace a serotonin-activated pathway in the brains of mice, a pathway that drives anxious behavior.

The team first demonstrated that a mild shock to the paws of mice – a standard method for evoking fear and anxiety behaviors – activates serotonin-producing neurons in the dorsal raphe nucleus (DRN), a brainstem region known to be involved in mood and depression. These DRN serotonin neurons project to a brain region that is called the bed nucleus of the stria terminalis (BNST) and has been shown in previous studies to have a role in serotonin’s negative mood effects in rodents. Artificially increasing the activity of the DRN-to-BNST neurons enhanced anxiety-like behaviors in the mice.

UNC scientists found that the serotonin output from the DRN neurons activates their target neurons in the BNST through a specific subset of serotonin receptors, known as 2C receptors. These serotonin-activated BNST neurons then tamp down the activity of another family of BNST neurons, which, in turn, project to the ventral tegmental area (VTA) and lateral hypothalamus (LH) – key nodes in the brain’s reward, motivation and alertness networks.

The pathways from BNST to VTA and LH have been reported in previous studies to improve mood and relieve anxiety. Researchers confirmed that artificially driving the activity of these pathways has the effect of reducing foot-shock-induced fear and anxiety behaviors in the mice. By contrast, the silencing of these pathways by serotonin-activated BNST neurons effectively allows the anxiety level to rise.

Examining the impact of SSRIs, the scientists exposed 2C-receptor BNST neurons to fluoxetine (Prozac), which like other SSRIs gives a boost to serotonin levels wherever the neurotransmitter is at work. This turned out to increase the 2C-receptor neurons’ inhibitory effect on the neighboring VTA- and LH-projecting neurons, worsening fear and anxiety behavior in mice.

How can this effect be blocked? Kash and his team observed that the anxiety-mediating BNST neurons expressed the stress-signaling molecule corticotropin releasing factor (CRF). When they added a compound to block CRF activity, they witnessed that fearful behaviors – which had been triggered by fluoxetine – were greatly reduced.

One of the next steps is to confirm that this serotonin-sensitive DRN-to-BNST anxiety circuit exists in humans as well. “It’s logical that it would,” Kash said, “since we know SSRIs can induce anxiety in people, and the pathways in these brain regions tend to be very similar in mice and humans.”

Another next step will be to test drugs – ideally FDA-approved for various conditions – for their ability to alter this anxiety circuit and thereby block SSRIs’ anxiety-inducing effect. In principle, a CRF-blocker might work. For years, pharmaceutical companies have been trying to develop CRF blockers to treat depression, anxiety and addiction. In practice, Kash said, CRF blockers haven’t yet had success in clinical trials, so an FDA-approved one is probably still years away at least.

“Other researchers are working to develop better CRF-inhibiting compounds, so that’s one potential direction to take, but there are others,” Kash said. “We’re now looking at the various proteins expressed by these BNST neurons, and we’re hoping to identify a receptor that is already targeted by established drugs. One of them might be useful for people as they start taking SSRIs.”

###

Other authors of the study were Giuseppe D’Agostino, PhD, research fellow at the University of Aberdeen; Lindsay R. Halladay, PhD, research fellow at the National Institutes of Health; J. Andrew Hardaway, postdoctoral fellow in the Kash Lab; Jeffrey F. DiBerto, research technician in the Kash Lab; Todd E. Thiele, PhD, professor of psychology at UNC; Montserrat Navarro, PhD, associate research professor of psychology and neuroscience at UNC; Nathan Burnham, graduate student in the Thiele Lab; Lora K. Heisler, PhD, chair of human nutrition at the University of Aberdeen; Claudia Cristiano, PhD, research fellow in the Heisler Lab; Cayce E. Dorrier, undergraduate research assistant in the Kash Lab; Gregory J. Tipton, research specialist at the UNC Center for Alcohol Studies; Charu Ramakrishnan, lab manager for Deisseroth Lab; Tamas Kozicz, MD, PhD, associate professor of anatomy at Tulane University; Karl Deisseroth, MD, PhD, professor of bioengineering, and psychiatry and behavioral sciences at Stanford University; Zoe A. McElligott, PhD, assistant professor of psychiatry at UNC; and Andrew Holmes, PhD, senior investigator at the National Institute on Alcohol Abuse and Alcoholism.

Prenatal exposure to paracetamol (acetaminophen), may increase autism spectrum symptoms by 30%

Public Release: 1-Jul-2016

 

Oxford University Press

A new study has found that paracetamol (acetaminophen), which is used extensively during pregnancy, has a strong association with autism spectrum symptoms in boys and for both genders in relation to attention-related and hyperactivity symptoms.

The findings were published this week in the International Journal of Epidemiology. This is the first study of its kind to report an independent association between the use of this drug in pregnancy and autism spectrum symptoms in children. It is also the first study to report different effects on boys and girls. Comparing persistently to nonexposed children, the study has found an increase of 30 per cent in the risk of detriment to some attention functions, and an increase of two clinical symptoms of autism spectrum symptoms in boys.

Researchers in Spain recruited 2644 mother-child pairs in a birth cohort study during pregnancy. 88 per cent were evaluated when the child was one year old, and 79.9 per cent were evaluated when they were five years old. Mothers were asked about their use of paracetamol during pregnancy and the frequency of use was classified as never, sporadic, or persistent. Exact doses could not be noted due to mothers being unable to recall them exactly. 43 per cent of children evaluated at age one and 41 per cent assessed at age five were exposed to any paracetamol at some point during the first 32 weeks of pregnancy. When assessed at age five, exposed children were at higher risk of hyperactivity or impulsivity symptoms. Persistently exposed children in particular showed poorer performance on a computerised test measuring inattention, impulsivity and visual speed processing.

Boys also showed more autism spectrum symptoms when persistently exposed to paracetamol. Lead author Claudia Avella-Garcia, researcher at CREAL, an ISGlobal allied centre in Barcelona, explained that, “although we measured symptoms and not diagnoses, an increase in the number of symptoms that a child has, can affect him or her, even if they are not severe enough to warrant a clinical diagnosis of a neurodevelopmental disorder.”

Co-author Dr. Jordi Júlvez, also a researcher at CREAL, commented on the possible reasoning for the effects of paracetamol on neurodevelopment: “Paracetamol could be harmful to neurodevelopment for several reasons. First of all, it relieves pain by acting on cannabinoid receptors in the brain. Since these receptors normally help determine how neurons mature and connect with one another, paracetamol could alter these important processes. It can also affect the development of the immune system, or be directly toxic to some fetuses that may not have the same capacity as an adult to metabolize this drug, or by creating oxidative stress.”

There could also be an explanation for why boys are more likely to have autism spectrum symptoms: “The male brain may be more vulnerable to harmful influences during early life”, said Claudia Avella-Garcia. “Our differing gender results suggest that androgenic endocrine disruption, to which male brains could be more sensitive, may explain the association.”

The study concluded that the widespread exposure of infants to paracetamol in utero could increase the number of children with ADHD or autism spectrum symptoms. However, they stressed further studies should be conducted with more precise dosage measurements, and that the risks versus benefits of paracetamol use during pregnancy and early life should be assessed before treatment recommendations are made.

Deceiving the public about Fosamax side effects, was it the FDA or Merck?

Merck Fights Broken-Leg Claims in 3rd Circuit

By NICK RUMMELL 

 

     NEWARK, N.J. (CN) — Remaining class-action lawsuits claiming one of Merck’s drugs caused weakened bones and eventual femur fractures should not go to a jury trial, the pharmaceutical company’s attorney argued Thursday before the Third Circuit.
     A federal judge in 2014 dismissed more than 1,000 so-called Fosamax Femur cases, tossing the allegations that Merck had failed to adequately warn consumers about osteoporosis drug Fosamax’s risks because the U.S. Food and Drug Administration had not officially approved or rejected the label’s language.
     In arguments today before the Third Circuit, Skadden Arps attorney John Beisner said the massive class-action lawsuit should be dismissed because Merck is protected by the “impossibility preemption” doctrine, which in this case means that Merck should not be liable because the FDA had not determined whether its label language was acceptable.
     Merck argued in court filings that the FDA had prohibited the company from warning consumers about certain health risks of Fosamax due to concerns about the language used. The company also said that the FDA had wanted to wait to gather information to issue an industry-wide stance on Fosamax..
     Beisner argued that now the Third Circuit — and not a jury — must now rule on whether Merck is protected under the preemption doctrine.
     “This is not a jury issue,” he said, noting the preemption issue was a question of law akin to deciding federal jurisdiction, and not subject to the whims of a jury, which might give different answers. “Either an issue is preempted or it isn’t.”
     But David Frederick, attorney for the consumers, argued that the case should move forward.
     “We’re talking about throwing these people out of court,” he said.
     In making his case, Frederick pointed to a 2009 U.S. Supreme Court ruling, in which the high court decided 6-3 against the preemption doctrine in a separate product liability case, Wyeth v. Levine, finding that state law had not been preempted in that case.
     In the Fosamax case, Frederick said the Third Circuit should allow the case to move forward to determine whether there is “clear evidence” that the FDA had any disputes with Merck’s labeling.
     During questioning, Judge Julio Fuentes said the issue of clear evidence has not been adequately defined by the Supreme Court, but that it seems to “stem from clear and convincing evidence without the word ‘convincing.'”
     Frederick argued that a 2009 memo from the FDA shows that the agency had problems with how Merck defined the possibility of atypical fractures — the pharmaceutical company used the term “stress fractures,” which are typically caused by exercise and heal normally.
     Fosamax, a drug used primarily by women with osteoporosis, has been linked to necrotic “jaw death,” as well as fractured bones due to bone decay.

http://www.courthousenews.com/2016/06/30/merck-fights-broken-leg-claims-in-3rd-circuit.htm

Low doses of common cancer drug may promote cancer spread

Public Release: 22-Jun-2016

 

Wiley

New research indicates that paclitaxel, which is the most commonly used chemotherapy for breast cancer, suppresses tumors when given at a certain dosage, but at low doses, it actually promotes cancer spread to the liver.

The findings suggest that lowering the dose of paclitaxel to reduce toxic side-effects is not a safe strategy.

“Paclitaxel and its analogous compounds are the first line agents widely used in clinical cancer chemotherapy. However, potential risks and reasonable treatment strategies of paclitaxel continue to be widely investigated,” wrote the authors of The FEBS Journal study.

Brief exposure to opioids may be a contributor to chronic pain

Public Release: 30-May-2016

Narcotic painkillers prolong pain in rats, says CU-Boulder study

Findings may have far-reaching implications for humans

University of Colorado at Boulder

The dark side of painkillers – their dramatic increase in use and ability to trigger abuse, addiction and thousands of fatal overdoses annually in the United States is in the news virtually every day.

Brace for another shot across the bow: Opioids like morphine have now been shown to paradoxically cause an increase in chronic pain in lab rats, findings that could have far-reaching implications for humans, says a new study led by the University of Colorado Boulder.

Led by CU-Boulder Assistant Research Professor Peter Grace and Distinguished Professor Linda Watkins, the study showed that just a few days of morphine treatment caused chronic pain that went on for several months by exacerbating the release of pain signals from specific immune cells in the spinal cord. The results suggest that the recent escalation of opioid prescriptions in humans may be a contributor to chronic pain, said Grace.

“We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain,” said Grace, who is a faculty member along with Watkins in CU-Boulder’s Department of Psychology and Neuroscience. “We found the treatment was contributing to the problem.”

A paper on the study was published May 30 in the Proceedings of the National Academy of Sciences.

The study showed that a peripheral nerve injury in rats sends a message from damaged nerve cells to spinal cord immune cells known as glial cells, which normally act as “housekeepers” to clear out unwanted debris and microorganisms. The first signal of pain sends glial cells into an alert mode, priming them for further action.

“I look at it like turning up a dimmer switch on the spinal cord,” said Grace.

When the injury was treated with just five days of opioids the glial cells went into overdrive, triggering a cascade of actions, including spinal cord inflammation. Watkins said the initial pain signals to the spinal cord and the subsequent morphine-induced treatment is a two-hit process, which she likened to slapping a person’s face.

“You might get away with the first slap, but not the second,” she said. “This one-two hit causes the glial cells to explode into action, making pain neurons go wild.”

The team discovered that the pain signals from a peripheral injury combined with subsequent morphine treatment worked together to cause a glial cell signaling cascade. The cascade produces a cell signal from a protein called interleukin-1beta (IL-1b), which increases the activity of pain-responsive nerve cells in the spinal cord and brain. That can cause increases in pain duration lasting several months.

“The implications for people taking opioids like morphine, oxycodone and methadone are great, since we show the short-term decision to take such opioids can have devastating consequences of making pain worse and longer lasting,” said Watkins. “This is a very ugly side to opioids that had not been recognized before.”

Roughly 20,000 Americans died in 2015 from overdoses of prescription opioid pain relievers, according to the National Institute on Drug Abuse.

On the up side, the researchers have found ways to block specific receptors on glial cells that recognize opioids. This could allow for some pain relief while potentially preventing chronic pain. The team used a designer drug technology known as DREADD to selectively turn off targeted glial cells, something that has not been done before, said Grace.

###

The study also involves Professor Hubert Yin of CU-Boulder’s BioFrontiers Institute as well as researchers from the University of Adelaide in Australia, the University of North Carolina, the Chinese Academy of Sciences, the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and Tsinghua University in Beijing.

The study was funded in part by the American Pain Society, Australia’s National Health and Medical Research Council, the National Natural Science Foundation in China, the National Institute on Drug Abuse, the National Institute of Dental and Craniofacial Research and the National Institute of Alcohol Abuse and Alcoholism.

Contact:
Peter Grace, 303-810-4589
peter.grace@colorado.edu
Linda Watkins, 303-492-7034
linda.watkins@colorado.edu
Jim Scott, CU-Boulder media relations, 303-492-3114
jim.scott@colorado.edu

Antibiotics may stop the growth of new brain cells in the hippocampus

Public Release: 19-May-2016

Mouse study finds link between gut bacteria and neurogenesis

Cell Press

 

IMAGE

Caption

This visual abstract depicts the findings of Möhle et al., which show the impact of prolonged antibiotic treatment on brain cell plasticity and cognitive function. They were able to rescue the decrease in neurogenesis by probiotic treatment, physical exercise, or transfer of Ly6Cpos monocytes. They propose that the Ly6Chi population is crucial for brain homeostasis and plasticity.

Credit: Möhle et al./Cell Reports 2016

Antibiotics strong enough to kill off gut bacteria can also stop the growth of new brain cells in the hippocampus, a section of the brain associated with memory, reports a study in mice published May 19 in Cell Reports. Researchers also uncovered a clue to why– a type of white blood cell seems to act as a communicator between the brain, the immune system, and the gut.

“We found prolonged antibiotic treatment might impact brain function,” says senior author Susanne Asu Wolf of the Max-Delbrueck-Center for Molecular Medicine in Berlin, Germany. “But probiotics and exercise can balance brain plasticity and should be considered as a real treatment option.”

Wolf first saw clues that the immune system could influence the health and growth of brain cells through research into T cells nearly 10 years ago. But there were few studies that found a link from the brain to the immune system and back to the gut.

In the new study, the researchers gave a group of mice enough antibiotics for them to become nearly free of intestinal microbes. Compared to untreated mice, the mice who lost their healthy gut bacteria performed worse in memory tests and showed a loss of neurogenesis (new brain cells) in a section of their hippocampus that typically produces new brain cells throughout an individual’s lifetime. At the same time that the mice experienced memory and neurogenesis loss, the research team detected a lower level of white blood cells (specifically monocytes) marked with Ly6Chi in the brain, blood, and bone marrow. So researchers tested whether it was indeed the Ly6Chi monocytes behind the changes in neurogenesis and memory.

In another experiment, the research team compared untreated mice to mice that had healthy gut bacteria levels but low levels of Ly6Chi either due to genetics or due to treatment with antibodies that target Ly6Chi cells. In both cases, mice with low Ly6Chi levels showed the same memory and neurogenesis deficits as mice in the other experiment who had lost gut bacteria. Furthermore, if the researchers replaced the Ly6Chi levels in mice treated with antibiotics, then memory and neurogenesis improved.

“For us it was impressive to find these Ly6Chi cells that travel from the periphery to the brain, and if there’s something wrong in the microbiome, Ly6Chi acts as a communicating cell,” says Wolf.

Luckily, the adverse side effects of the antibiotics could be reversed. Mice who received probiotics or who exercised on a wheel after receiving antibiotics regained memory and neurogenesis. “The magnitude of the action of probiotics on Ly6Chi cells, neurogenesis, and cognition impressed me,” she says.

But one result in the experiment raised more questions about the gut’s bacteria and the link between Ly6Chi and the brain. While probiotics helped the mice regain memory, fecal transplants to restore a healthy gut bacteria did not have an effect.

“It was surprising that the normal fecal transplant recovered the broad gut bacteria, but did not recover neurogenesis,” says Wolf. “This might be a hint towards direct effects of antibiotics on neurogenesis without using the detour through the gut. To decipher this we might treat germ free mice without gut flora with antibiotics and see what is different.”

In the future, researchers also hope to see more clinical trials investigating whether probiotic treatments will improve symptoms in patients with neurodegenerative and psychiatric disorders.”We could measure the outcome in mood, psychiatric symptoms, microbiome composition and immune cell function before and after probiotic treatment,” says Wolf.

###

This project was funded by the German Research Council

Cell Reports, Möhle, Mattei, and Heimesaat et al.: “Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis” http://www.cell.com/cell-reports/fulltext/S2211-1247(16)30518-6

Cell Reports (@CellReports), published by Cell Press, is a weekly open-access journal that publishes high-quality papers across the entire life sciences spectrum. The journal features reports, articles, and resources that provide new biological insights, are thought-provoking, and/or are examples of cutting-edge research. Visit: http://www.cell.com/cell-reports. To receive Cell Press media alerts, contact press@cell.com.

Common cleanser rapidly disrupts gut bacteria

Public Release: 18-May-2016

 

Oregon State University

CORVALLIS, Ore. – A new study suggests that triclosan, an antimicrobial and antifungal agent found in many consumer products ranging from hand soaps to toys and even toothpaste, can rapidly disrupt bacterial communities found in the gut.

The research was published today in PLOS ONE by scientists from Oregon State University. It was based on findings made with zebrafish, which researchers believe are an important animal model to help determine possible human biological and health impacts of this antimicrobial compound.

Triclosan was first used as a hospital scrub in the 1970s and now is one of the most common antimicrobial agents in the world, found in shampoos, deodorants, toothpastes, mouth washes, kitchen utensils, cutting boards, toys, bedding, socks and trash bags. It continues to be used in medical settings, and can be easily absorbed through the skin.

“There has been a legacy of concern about exposure to microbial pathogens, which has led to increased use of these antimicrobial products,” said Thomas Sharpton, an assistant professor of microbiology and statistics in the OSU Colleges of Science and Agricultural Sciences, and corresponding author on the new study.

“However, there’s now a growing awareness of the importance of the bacteria in our gut microbiome for human health, and the overuse of antibiotics that can lead to the rise of ‘superbugs.’ There are consequences to constantly trying to kill the bacteria in the world around us, aspects we’re just beginning to understand.”

In the new study, researchers found that triclosan exposure caused rapid changes in both the diversity and composition of the microbiome in the laboratory animals. It’s not clear what the implication may be for animal or human health, but scientists believe that compromising of the bacteria in the intestinal tract may contribute to the development or severity of disease.

Some bacteria were more susceptible to the impact of triclosan than others, such as the family Enterobacteriaceae; and others were more resilient, such as the genus Pseudomonas.

“Clearly there may be situations where antibacterial agents are needed,” said Christopher Gaulke, lead author on the study and a postdoctoral microbiology researcher in the OSU College of Science.

“However, scientists now have evidence that intestinal bacteria may have metabolic, cardiovascular, autoimmune and neurological impacts, and concerns about overuse of these agents are valid. Cumulative impacts are also possible. We need to do significantly more evaluation of their effects, some of which might be dramatic and long lasting.”

The gut-associated microbiome performs vital functions for human health, prevents colonization with pathogens, stimulates the development of the immune system, and produces micronutrients needed by the host. Dysfunction of this microbiome has been associated with human disease, including diabetes, heart disease, arthritis and malnutrition, the scientists pointed out in their study.

Humans are routinely exposed to an array of chemicals, metals, preservatives, microbes and nutrients, some of which may be beneficial, some innocuous, and others harmful, the researchers said. Part of the strength of the present study is developing improved ways, through rapid screening of zebrafish, to more easily determine which compounds may be acceptable and which are toxic, scientists say.

Triclosan has been a concern in part because it is so widely used, and it’s also readily absorbed through the skin and gastrointestinal tracts, showing up in urine, feces and breast milk. It also has been associated with endocrine disruption in fish and rats, may act as a liver tumor promoter, and can alter inflammatory responses.

This study showed it was quickly associated with shifts in the microbial community structure and can alter the abundance of specific taxa.

Collaborators on this research included scientists from the OSU Environmental Health Sciences Center and OSU College of Agricultural Sciences.

Study: Symptoms of ‘chronic multisymptom illness’ may be common in Iraq, Afghanistan vets

Public Release: 13-May-2016

 

Veterans Affairs Research Communications

In a Veterans Affairs study of more than 300 enlisted Army National Guard and Army Reserve members who had deployed to Iraq or Afghanistan, a majority reported symptoms consistent with a condition known as chronic multisymptom illness (CMI). The data were collected a year after the soldiers returned home.

The results suggest that deployment to these conflicts could trigger symptoms consistent with CMI.

The ailment presents as a combination of medically unexplained chronic symptoms, such as fatigue, headache, joint pain, indigestion, insomnia, dizziness, breathing problems, and memory problems.

The study, by researchers with VA’s War-Related Illness and Injury Study Center (WRIISC) in New Jersey, appeared online Feb. 22, 2016, in the Journal of Rehabilitation Research and Development.

“As a whole, CMI can be challenging to evaluate and manage,” said lead author Dr. Lisa McAndrew. “CMI is distinct from PTSD or depression. It contributes to significant disability.”

McAndrew is also with the University at Albany.

In the veteran community, chronic multisymptom illness has previously been associated mainly with service during the Persian Gulf War in the early 1990s. At least a quarter of those veterans are affected.

Experts aren’t sure, though, if that condition is the same one that has emerged among more recent veterans, as documented in the newest WRIISC study and one or two earlier ones. Last year, for example, researchers with the Millennium Cohort Study reported that about a third of combat veterans who served in Iraq and Afghanistan had CMI symptoms.

“This condition appears to be similar to that experienced by many Gulf War veterans, in terms of the symptoms, but we don’t really know if it’s the same condition,” says McAndrew. “That still requires study.”

McAndrew and her colleagues surveyed 319 soldiers about their overall health before they deployed and one year after they returned. The VA team found there were 150 soldiers who did not report many symptoms before they deployed but who reported symptoms of CMI one year after deployment, suggesting a link between deployment to Iraq or Afghanistan and CMI.

In total, nearly 50 percent of the overall group met the criteria for mild to moderate CMI, and about 11 percent met the criteria for severe CMI, one year after deployment.

The most common symptoms reported were trouble sleeping, moodiness or irritability, joint pain, fatigue, difficulty remembering or concentrating, headaches, and sinus congestion.

Not surprisingly, the researchers found that veterans who screened positive for CMI scored significantly lower on measures of physical and mental health function.

Of the 319 veterans in the study, 166 had chronic pain, lasting more than three months. Almost all of those with chronic pain–90 percent–also met the criteria for CMI. Similarly, 82 percent of those with CMI reported chronic pain.

The finding underscores the strong link between chronic pain and CMI, say the researchers.

The study also found that almost all veterans with PTSD symptoms also showed signs of CMI–about 98 percent. Only seven patients had PTSD and did not meet the criteria for CMI. In contrast, though, about 44 percent of the veterans with CMI did not have PTSD. In other words, the link between PTSD and CMI was not as robust as that between chronic pain and CMI.

The authors caution that the study looked only at pain and PTSD as factors tied in with CMI. It did not document other conditions that could possibly account for the symptoms of CMI, such as depression, traumatic brain injury, and substance abuse. At the same time, they say these other conditions are unlikely to completely account for the frequency of symptoms seen in the study.

By the same token, other conditions not examined in the study, such as arthritis or multiple sclerosis, could cause symptoms similar to those of CMI. More research is needed to tease out those variables.

Another limitation of the study: The research team used a definition of CMI, established by the Centers for Disease Control and Prevention (CDC), that is based on Gulf War Veterans. They say it might not exactly fit the symptoms of veterans of the more recent conflicts.

Also, it’s unclear whether the Guard and Reserve members surveyed in the study are representative of the larger veteran or military cohort who deployed to Iraq and Afghanistan.

All in all, the research team advises that the results be interpreted with caution.

“We’re taking the approach that an abundance of caution is necessary in the clinical implications of the findings,” says McAndrew. “Respondents self-reported symptoms on pen and paper surveys. The symptoms were not confirmed or evaluated by a clinician. While the CDC case definition is fairly clear-cut, in clinical practice there is a lot of gray area around applying the label of CMI. We used the term ‘symptoms consistent with CMI’ to indicate the uncertainty due to the self-reported, clinician-unverified nature of the classification.”

Pending further research on the topic, McAndrew’s group says clinicians in VA or other settings should consider CMI when evaluating Iraq and Afghanistan Veterans, especially those with chronic pain. Once the condition is identified, clinicians in VA and the Department of Defense do have a clinical practice guideline for managing the condition.

“Acknowledging the presence of multiple symptoms and taking a holistic approach to achieving patient goals is critical in managing CMI,” says McAndrew. For example, pain management may need to be tailored to account for other symptoms of CMI.

The WRIISC study notwithstanding, McAndrew says not enough attention has been focused on the issue to date.

“There have been few studies of CMI among Iraq and Afghanistan veterans. Our findings suggest this could be an overlooked problem.”

###

Senior researcher on the WRIISC study was Dr. Karen Quigley, now at the Edith Nourse Rogers Memorial Veterans Hospital and Northeastern University.

Botox affects the ability to read emotions

Public Release: 12-May-2016

Emotions in the age of Botox

Aesthetic treatments based on botulin toxin affect the perception of emotions

International School of Advanced Studies (SISSA)

By now we are all used to seeing its more or less successful results on Italian and international celebrities, but in fact the market of Botox-based procedures (cosmetic treatments that exploit the effects of type A botulin toxin) involves a large number of individuals. Just to give an idea, about 250,ooo procedures were done in Italy in 2014. It is therefore natural to wonder about the possible side effects of this practice. One fairly unpredictable consequence concerns the emotional domain, and in particular the perception of emotional information and facial expressions. “The thankfully temporary paralysis of facial muscles that this toxin causes impairs our ability to capture the meaning of other people’s facial expressions”, explains Jenny Baumeister, research scientist at the International School for Advanced Studies (SISSA) in Trieste and first author of a study just published in the journal Toxicon (and carried out with the collaboration of Cattinara Hospital in Trieste).

Baumeister’s intuition stems from a very well-known scientific theory, called embodiment. The idea is that the processing of emotional information, such as facial expressions, in part involves reproducing the same emotions on our own bodies. In other words, when we observe a smile, our face too tends to smile (often in an imperceptible and automatic fashion) as we try to make sense of that expression. However, if our facial muscles are paralyzed by Botox, then the process of understanding someone else’s emotion expression may turn out to be more difficult.

Jenny Baumeister had a sample of subjects carrying out a series of different tests assessing their understanding of emotions, immediately before and two weeks after they had had a Botox-based aesthetic procedure, and compared the measurement with a similar sample of subjects that had no treatment. Regardless of the types of measurement (judgement or reaction times) the effect of the paralysis was obvious.

“The negative effect is very clear when the expressions observed are subtle. Instead when the smile is wide and overt, the subjects were still able to recognize it, even if they’ve had the treatment”, explains Francesco Foroni, SISSA researcher who coordinated the study. “For very intense stimuli, although there was a definite tendency to perform worse, the difference was not significant. On the other hand, for “equivocal” stimuli that are more difficult to pick up, the effect of the paralysis was very strong”.

The finding confirms the assumption that, to some extent at least, “embodied” processes help us understand emotions. It also suggests that the negative influence of Botox may be manifest precisely in those situations in which this help could prove most useful. For instance, think of a normal conversation between two individuals, where mutual understanding is vital to ensure proper social interaction: failure to pick up on emotional nuances or sudden changes in the other person’s mood can make the difference between successful communication and communication breakdown.

“Our study was devised to investigate embodied cognition. At the same time, we think that awareness of this consequence will be of use to those involved in aesthetic medicine, not least to adequately inform people seeking to undergo these treatments” commented Foroni.