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Hospitals today spend a lot of time and effort to protect their patients from developing new infections while they're hospitalized - especially the most dangerous types that can threaten their health even more than the problem that sent them to the hospital in the first place. They also carefully track these hospital-acquired infections (HAIs), and even get paid more by the Medicare system if they achieve lower rates.

But this massive effort has been missing a key element, according to University of Michigan and RAND researchers. None of the tracking measures take into account how full a hospital was during the hospitalization that the patient acquired the infection - that is, what percentage of its available beds had patients in them, and therefore how thinly stretched the staff were.

Now, the team has developed an approach that they hope will lead to more uniform tracking of this important factor in patient safety.

In a new paper in the Journal of Hospital Medicine, they share the first results from using the approach on real-world data, related to the digestive tract infection known as "C. diff" or Clostridium difficile.

While it might seem obvious that a fuller hospital would mean higher risk of C. diff among its patients, the study finds the opposite to be true.

A patient's C. diff infection risk was highest when the hospital was in the middle range of occupancy on the day the patient was admitted. And when the researchers looked at the average occupancy over the patient's stay, the risk of C. diff infection was more than three times higher when the hospital was between 25 percent and 75 percent full, compared with less than 25 percent or more than 75 percent occupancy.

The study used data from 558,829 patient discharges at 327 hospitals across California, between 2008 and 2012. It focused on patients who had come to the hospitals' emergency rooms for care for a heart attack, heart failure or pneumonia.

In all, 2,045 patients developed a C. diff infection after they reached the hospital. The researchers adjusted for many factors that differed among all the patients, including age, gender, income, education and more.

The data for the study came from California's Office of Statewide Health Planning and Development Patient Discharge Data set, which tracks hospital discharge records for all licensed general acute care hospitals in California.

The study was done after the state instituted minimum nurse-to-patient ratios in 2006, to ensure nurse staffing was adequate.

Lead author Mahshid Abir, M.D., M.Sc., of U-M and RAND notes that the new approach to measuring hospital occupancy takes into account how many beds the hospital actually has open and staffed, rather than how many they're licensed to operate.

This more precise approach, calculated by looking at census data for each hospital, could be used to track many kinds of patient outcomes in relation to occupancy. The researchers approximated the hospital's actual bed capacity by looking at the maximum daily census in a four-month period around each day that they examined. This allowed them to factor in changes in bed availability, for instance when hospitals close units or have lighter staffing due to seasonal variation.

The team broke occupancy into four levels: low (0 to 25 percent), two classes of moderate (25 percent to 50 percent and 51 percent to 75 percent), and high (76 percent to completely full).

Abir and her colleagues note that other studies in Europe and beyond have shown a higher rate of HAIs when hospitals are very full - but those studies used licensed bed counts and did not factor out infections that the patient already had when they got to the hospital.

"Our initial results indicate a complex relationship between hospital occupancy and outcomes, and merit further evaluation," including analysis of hospital protocols that might be triggered or modified when a hospital is in high or low occupancy, says Abir.

She and her co-authors call for collection of hospital occupancy data by infection control officers, so that more precise measurements of occupancy can be used when examining hospital acquired infections and other preventable threats to patient health and safety.

"The theory that infection rates will go up with occupancy, because of staff cutting corners with steps like handwashing, may seem logical but this model shows it's not as simple as that," says Abir, who leads the U-M Acute Care Research Unit and is a member of the U-M Institute for Healthcare Policy and Innovation. "The impacts of emergency department crowding on patient outcomes have been studied extensively, but the effects of occupancy levels on inpatients has been neglected - despite the fact that a crowded ED is often a function of high inpatient occupancy. Some hospitals may be implementing operational factors during high occupancy that improve HAIs; we need to study what those are."

The team is also looking at the connection between hospital occupancy and patient mortality, and other outcomes, as well as the impact of the California nurse staffing ratio requirements.

A simple $20 blood test could help diagnose thousands of patients with hepatitis B in need of treatment in some of Africa's poorest regions.

Researchers have developed an accurate diagnostic score that consists of inexpensive blood tests to identify patients who require immediate treatment against the deadly hepatitis B virus - which can lead to liver damage or cancer (1).

The score consists of two simple blood tests: one measuring presence of antigens, proteins produced by the virus, and another for enzymes produced by the liver in response, to accurately assess patients for treatment.

The score was found to be as accurate as existing methods for identifying the patients in need of immediate treatment but at a fraction of the cost, $20 compared to $100-500 for current tests.

It is also far more accessible than existing methods - such as liver biopsy or HBV DNA, a much more complicated blood sample analysis - which requires resources and laboratories that are not always accessible in sub-Saharan Africa.

Researchers from Imperial College London and Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, collaborating with the Pasteur Institute in Paris and other African and European institutions, used data from hundreds of hepatitis B patients in The Gambia who were part of the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) study (2).

Clinical data from more than 800 hepatitis B patients, who had been tested through the PROLIFICA programme, were used to develop this new score.

The tests were then validated with data from African patients in Senegal, Burkina Faso, Germany, France and the UK. The results are published in the Journal of Hepatology.

The new diagnostic test, called TREAT-B, was found to accurately identify HBV positive patients who require treatment in 85% of cases (called sensitivity), and could accurately identify those who do not need treatment in 77% of cases (called the specificity).

The scientists say that further research is needed but if the test is successful in larger studies it could be used widely to identify patients in need of hepatitis B treatment and refer thousands of people for life-saving treatment. The test could also be developed further to be implemented as a finger-prick test, similar to those used to detect HIV, to get quicker results.

The researchers also discovered that the diagnosis method worked at all stages of the disease - meaning that people in the early stages of liver disease without symptoms could also be screened and identified.

Imperial's Dr Maud Lemoine, co-author of the study, said: "These results show that this simple and inexpensive test could be an accurate way to diagnoses patients in need of hepatitis B treatment in countries with limited resources.

"This could potentially help diagnose and subsequently treat thousands of people across Africa."

Co-author, Yusuke Shimakawa from the Pasteur Institute said: "Once these results are validated by further studies, they could be potentially integrated into the WHO guidelines and local guidelines - and implemented in daily practice.

"There is great potential to diagnose more people and improve access to treatment.

Viral hepatitis is a major global health problem and in 2013 an estimated 1.45 million people died from the virus. It is the seventh leading cause of death worldwide and about half of deaths are attributable to the hepatitis B virus infection.

The hepatitis B virus infects around 250 million people worldwide, and is transmitted through blood and bodily fluids. In Africa, it is commonly transferred from mother to baby during birth or between children. However the virus causes no immediate symptoms, and can remain undetected in the body for decades until triggering severe complications such as liver damage (cirrhosis) and cancer.

The region most affected by hepatitis B is Sub-Saharan Africa, where around 80 million people are infected.

Tokyo, Japan - Researchers from Tokyo Metropolitan University have observed the formation of holes that move by themselves in droplets of ionic liquids (IL) sitting inside water-ethanol mixtures. This curious, complex phenomenon is driven by an interplay between how ionic liquids dissolve, and how the boundary around the droplet fluctuates. Self-driven motion is a key feature of active matter, materials that use ambient energy to self-propel, with potential applications to drug delivery and nano-machine propulsion.

Most people are familiar with how things mix or dissolve. For example, we know that water and ethanol mix very well at room temperature; take alcoholic beverages. How well they mix depends on the environment the mixture is in, like temperature and pressure.

However, dissolution takes a complex turn when we add another component. A team led by Associate Professor Rei Kurita, Department of Physics, Tokyo Metropolitan University, were studying how an ionic liquid (IL) dissolved in a mixture of water and ethanol. Ionic liquids are liquids composed entirely of ions in ambient conditions; properties like their resistance to drying and ability to dissolve otherwise difficult materials have led to their being referred to as a "solvent of the future" [1], with a focus on how they might play a role in industrial processes e.g. battery production, pharmaceuticals, and recycling.

The team placed a small droplet of IL at the bottom of a mixture of ethanol and water. With the temperature and particular ratio of ethanol to water they used, they expected a boundary or interface to form between the IL and the water-ethanol above it, and for the two to mix gradually. Yet, what they saw was startling: over time, holes emerged inside the IL droplet, and the holes could propel themselves inside the droplet.

They found that this curious phenomenon was the result of how the composition of the water-ethanol mixture naturally fluctuated around the interface. The conditions were such that the mixture is close to a critical point, where small variations in composition can have major consequences. In this case, they were enough to locally promote mixing of the IL into the water-ethanol mixture; the unique way in which ILs interact with water led to even further local changes in composition, leading to a positive feedback loop, or instability. The effect was so drastic that they led to variations in the surface tension, driving the surface to become spontaneously bumpy, form holes, and generate the large flows required to move them around. These holes have been dubbed active holes.

Their discovery paves the way for a broad new class of synthetic active matter, materials that can spontaneously take energy from its surroundings and convert it into motion. With possible applications to drug delivery and propulsion at the nanometer scale, this new phenomenon might inspire investigations into novel industrial uses as well as further accelerate academic interest in active phenomena.

The first major paper looking at the causes and consequences of meningitis in the UK has found that viruses are now the most common cause of meningitis in adults and a cause of substantial long-term ill health. The paper also found that the management of many patients with meningitis is sub-optimal.

The study by researchers at the University of Liverpool's Institute of Infection and Global Health, published in The Lancet Infectious Diseases, funded by Meningitis Research Foundation (MRF) and the National Institute for Health Research, studied the diagnosis and treatment of more than 1000 patients with suspected meningitis.

It was found that diagnosis of meningitis is often delayed due to unnecessary brain scans being performed before lumbar puncture - which is the essential investigation to determine the cause of the illness. The majority of patients (81%) had a brain scan and 70% of those took place before lumbar puncture, otherwise known as a spinal tap.

Recommendations in national guidelines* urge doctors to perform a lumbar puncture within the first hour in patients with suspected meningitis unless the patient has particular symptoms which make it unsafe to. Only 12% of patients studied should have had a brain scan prior to lumbar puncture if the guidelines had been followed.

Cases of bacterial meningitis - the life threatening form of the disease - have significantly reduced over the last few decades following the introduction of vaccines against some of the most common types, and the study found that viral meningitis now accounts for the majority of cases. Being able to quickly determine which bacteria or virus is causing the illness is essential for the appropriate treatment of patients. Antibiotics should be given urgently to those with bacterial meningitis, but not viral meningitis, as viruses don't respond to antibiotics.

Delays in diagnosis mean that antibiotics are often inappropriately used in patients with viral meningitis, resulting in a longer than necessary stay in hospital, which poses a considerable burden on patients and the NHS and potentially also contributes to the problem of antimicrobial resistance.

Patients in the new study who were investigated promptly with lumbar puncture were also more likely to have a specific cause of the meningitis identified, and to spend less time in hospital. Overall, the specific virus or bacteria causing the illness was not identified for 43% of patients.

Dr Fiona McGill from the Institute of Infection and Global Health. University of Liverpool, said, "This study provides the first estimate of the incidence of viral meningitis in UK adults. It shows that viral meningitis is now a major cause of meningitis, but often the management is not quite right. It's a concerning finding that so many unnecessary brain scans are taking place and that these appear to be delaying the correct diagnosis."

Dr Mike Griffiths, senior investigator on the study, added, "Diagnosing a specific cause of meningitis quickly is key to getting patients on the right antibiotics, if needed, or avoiding unnecessary antibiotics in those with viral meningitis. Once viral meningitis has been diagnosed, efforts should focus on treatment of the symptoms and expediting discharge from hospital which would be less distressing for patients and ease pressures on the NHS."

Vinny Smith, Chief Executive at MRF said, "Meningitis can strike without warning and the bacterial form of the disease can kill in hours. Many survivors have long-term, disabling after effects as serious as brain damage and deafness. It is impossible to tell the difference between bacterial meningitis and a milder viral infection, even for a doctor. This is why it's crucial not to delay performing the lumbar puncture.

"The findings in this study are really significant. It's clear that the time it takes to get a correct diagnosis is having serious consequences and the national guideline is not being followed. Around the world, there is a pressing need for improved rapid diagnostic tests for meningitis. We are supporting research to that aim."

Deep brain stimulation (DBS) may slow the progression of tremor for early-stage Parkinson's disease patients, according to a Vanderbilt University Medical Center study released in the June 29 online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study is the first evidence of a treatment that slows the progression of one of the cardinal features of Parkinson's, but a larger-scale clinical trial across multiple investigational centers is needed to confirm the finding.

"The finding concerning tremor progression is truly exceptional," said senior author David Charles, MD, professor and vice-chairman of Neurology. "It suggests that DBS applied in early-stage Parkinson's disease may slow the progression of tremor, which is remarkable because there are no treatments for Parkinson's that have been proven to slow the progression of any element of the disease."

Patients in the Vanderbilt study were randomized to receive DBS plus drug therapy or drug therapy alone; the drug therapy alone group was seven times more likely to develop new rest tremor after two years in comparison to the DBS plus drug therapy group.

The trial, which began in 2006, was controversial because it recruited patients with early-stage Parkinson's disease for DBS brain surgery. At that time, DBS was approved for only advanced-stage Parkinson's disease when symptoms were no longer adequately controlled by medication.

"Since this was the first early DBS trial, it was unknown whether there were individual motor symptoms very early in Parkinson's disease that may be more potently improved by DBS," said lead author Mallory Hacker, PhD, research assistant professor of Neurology.

The post hoc analysis showed that 86 percent of the drug therapy patients developed rest tremor in previously unaffected limbs over the course of the two-year period, while that occurred in only 46 percent of patients who had received DBS therapy in addition to drug therapy. Four of the DBS patients had rest tremor improvement and rest tremor completely disappeared from all affected limbs for one DBS patient.

The FDA has approved Vanderbilt to lead a large-scale, Phase III multicenter study that will enroll 280 people with very early-stage Parkinson's disease, beginning in 2019, and 17 other U.S. medical centers have joined the DBS in Early Stage Parkinson's Disease Study Group to participate.

"The field of DBS therapy for Parkinson's disease is moving toward earlier stages of treatment, therefore, we must conduct the pivotal trial to ensure patient safety and provide the Parkinson's community with the best possible medical evidence to guide treatment," Charles said.

June 29, 2018 - Cryolipolysis is a noninvasive cosmetic procedure that eliminates excess fat by freezing it. But a complication called paradoxical adipose hyperplasia (PAH) -a hardened area of localized fat developing after cryolipolysis - may be more common than previously thought, suggests a paper in the July issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

While PAH can be treated successfully with liposuction, patients must wait a few months before treatment, according to the study, led by ASPS Member Surgeons Michael E. Kelly, MD, and Jose Rodríguez-Feliz, MD, of Miami Plastic Surgery. "Surgeons must be extremely sensitive when dealing with patients who have PAH, both when explaining the problem and when offering them a potential surgical solution," the researchers write.

PAH after Cryolipolysis May Not Be a 'Rare' Complication

Drs. Kelly and Rodríguez-Feliz and colleagues share their experience in managing patients with PAH after cryolipolysis: an FDA-approved procedure that works by destroying cold-sensitive subcutaneous fat cells. It has become a popular technique for treating problem fat areas such as belly fat and "love handles."

Paradoxical adipose hyperplasia has been reported as a rare adverse event after cryolipolysis. In this condition, the treated area becomes larger rather than smaller in the weeks after the procedure, leaving a "painless, visibly enlarged, firm, well-demarcated mass" under the skin. Based on data from the manufacturer of the cryolipolysis equipment, PAH has been estimated to occur in 1 out of every 4,000 treatment cycles, for an incidence of 0.025 percent.

The authors describe their experience with 11 patients with PAH. Six patients underwent cryolipolysis at the authors' clinic and five were referred from other practices. The authors note that their experience of 15 PAH events in six patients represents a much higher incidence: 0.72 percent, or about 1 out of every 138 cryolipolysis treatments.

The good news is that PAH was successfully treated in all cases. Most patients needed liposuction only; one patient had liposuction combined with an abdominoplasty ("tummy tuck") procedure. Dr. Rodríguez-Feliz recommend the use of a power-assisted liposuction technique. All patients achieved good cosmetic results and were very satisfied with their final appearance.

However, the patients had to wait several months for treatment. That time is needed for the fat in the area of PAH to soften; otherwise, there is a risk that PAH could recur. In some cases, more than one liposuction treatment was needed.

Drs. Kelly and Rodríguez-Feliz and colleagues acknowledge that it's "very upsetting" for patients who initially sought a noninvasive fat reduction procedure to be faced with the need for an invasive procedure (liposuction) to correct the problem. Two patients with PAH refused further treatment, even though the treatment costs were covered by the manufacturer of the cryolipolysis equipment.

Patients are "initially aggravated by the delay and require continuing reassurance that the problem will ultimately be resolved," the authors note. "Counseling is extremely important during this waiting period." The online version of the article on the Plastic and Reconstructive Surgery website includes a video illustrating the clinical examination findings in a patient with PAH.

"Despite these hurdles, patient satisfaction with the final surgical cosmetic result has been high," Drs. Kelly and Rodríguez-Feliz and coauthors conclude. They emphasize the need for further study to clarify the incidence of PAH after cryolipolysis, to identify possible risk factors, and to evaluate the long-term outcomes of liposuction to correct the problem.

Plastic and Reconstructive Surgery® is published in the Lippincott portfolio by Wolters Kluwer.

-- Introduction of vaccines has successfully reduced prevalence of bacterial meningitis and most cases in the UK today are caused by viruses.

Viruses are the most common cause of meningitis in adults aged 16 and older in the UK, according to new research published in The Lancet Infectious Diseases journal. Although generally seen as a benign condition, this new observational study shows that recovery from viral meningitis can be a long haul for patients, with many still experiencing memory and mental health problems months after they are released from hospital.

Importantly, the findings also reveal substantial delays in diagnostic testing and unnecessary treatment in hospitals across England, which are associated with longer hospital stays. The median time from admission to a lumbar puncture to distinguish between bacterial and viral meningitis was 17 hours - in a quarter of patients it took more than 29 hours.

"Ideally, this crucial diagnostic test should be completed within a few hours," says Dr Fiona McGill, the Institute of Infection and Global Health at the University of Liverpool, UK, who led the research. "It's possible that the 4-hour accident and emergency treatment target is creating unintended pressure, leading to key investigations like lumbar puncture being postponed until patients have been admitted to a ward. Additional delays of several days can also occur if samples are sent to offsite laboratories for analysis." [1]

The study is the first of its kind to examine the incidence, causes, and impact of viral meningitis in UK adults.

Meningitis occurs when there is inflammation of the membranes that protect the brain and spinal cord caused by infection with viruses, bacteria, other microorganisms, and less commonly, drugs. Although symptoms can be similar, individuals with viral meningitis usually get better in a few weeks, while bacterial meningitis can kill within hours and requires urgent treatment with antibiotics.

International guidelines stress the urgency of lumbar puncture in order to rule out bacterial meningitis and reduce unnecessary antibiotic treatment, shorten hospital stays, and lessen healthcare costs. However, this testing is often delayed, leading to difficulties in making a diagnosis.

Since the 1990s, widespread introduction of conjugate vaccines have seen the incidence of bacterial meningitis decline across England. Whilst meningitis cases caused by viruses seem to be on the rise, until now the true burden of viral meningitis was unknown.

The study included over 1100 patients with suspected meningitis presenting to 42 hospitals (including all 24 acute hospitals in the northwestern region) across England between September 2011 and September 2014. All participants either had a lumbar puncture or a bacterial or viral pathogen identified in their blood test or culture. The researchers examined the association between time to lumbar puncture and receiving a microbiologically proven diagnosis. Participants were sent questionnaires to assess their quality of life and cognitive function a year after admission.

Of 1113 patients included in the final analysis, over half (638) were diagnosed with meningitis. Of these, more than a third of cases (231) were caused by a virus; 99 cases (16%) were bacterial; 267 (42%) had an unknown cause; and 41 cases (6%) had other causes identified.

Enteroviruses were the most common viruses identified, accounting for 55% of viral meningitis cases, and 20% of all meningitis cases. Streptococcus pneumoniae was the most common bacterial cause, responsible for 54% of bacteria cases, but just 8% of overall meningitis cases (table 2).

Results showed that unnecessary treatment with antivirals was associated with longer hospital stays - with patients infected with viral meningitis who did not have treatment staying for an average of 3 days compared with 9 days in those treated with antivirals (because most had intravenous treatment requiring inpatient care).

And there was evidence that earlier lumbar puncture resulted in more patients having a specific cause identified than those in whom testing was delayed - with the chances of having a pathogen detected in viral meningitis reduced by 1% for every hour delay in lumbar puncture following admission (figure 2).

"Improved rapid diagnostic testing so that more patients can have a specific cause determined quickly could reduce unnecessary use of antimicrobials (ie, both antibiotics and antivirals) and therefore reduce hospital stays and other investigations." say the authors.

All individuals with viral meningitis reported substantially poorer quality of life in the year following illness compared with the age-matched UK population, with an excess of pain, anxiety, depression, and reduced activity levels up to 48 weeks after admission.

Using data on the incidence of viral meningitis in the northwest region, the researchers estimate that the annual incidence of viral meningitis in UK adults is 2.73 per 100,000 compared with 1.24 per 100,000 for bacterial meningitis.

According to Dr McGill: "It's becoming increasingly clear that individuals with viral meningitis experience many lasting effects on their mental health and quality of life. We must better support them during and after hospitalisation with more rapid diagnostics and better treatments and rehabilitation to ensure quicker recovery and to help improve outcomes." [1]

The authors note some limitations, including that the prospective nature of the study means that some eligible patients may not have been recruited. They also point out that they extrapolated the incidence of viral meningitis from the northwest to the whole country, which assumes that there is minimal variation in incidence across the UK. Finally, they note that they only looked for the most common viruses, and cannot exclude the possibility that other rare or emerging viruses may have been responsible for some cases.

Writing in a linked Comment, Matthijis Brouwer and Diederik van de Beek, the Academic Medical Centre, Amsterdam, the Netherlands, say: "We need to speed up care for patients with CNS infections. There is a clear need to improve diagnostic tests for patients with suspected CNS infections because a substantial proportion of patients do not have a cause-specific diagnosis, which impedes early directed treatment and hinders trials of new treatments. New methods, such as pathogen discovery sequencing, use of RNA biosignatures, and point-of-care PCR tests might improve the yield of CSF examination, and should be tested in large prospective studies, including cost-effectiveness analyses. Implementation of fast diagnostic tests and early identification of pathogens in CSF will, however, be of little use if lumbar puncture is delayed considerably. The current study should be a wake-up call for policy makers to improve care for patients with CNS infections."

June 29, 2018 - Routine assessment by an endocrinologist and laboratory tests to measure hormone levels aren't necessary in most adolescent boys with gynecomastia (male breast enlargement), concludes a study in the July issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

The cause of adolescent gynecomastia can usually be identified without endocrine testing, according to the study by Jugpal S. Arneja, MD, MBA, and colleagues of University of British Columbia, Vancouver, Canada. They propose an "evidence-based rationale for evaluation and workup" for the distressing problem of breast enlargement in adolescent males - including referral for male breast reduction surgery if the problem persists beyond age 16.

Lab Tests Contribute Little to Gynecomastia Diagnosis and Treatment in Teens
The researchers analyzed 197 adolescents with gynecomastia seen at British Columbia Children's Hospital from 1990 through 2015. Although adolescent gynecomastia is a common issue that usually resolves with time, it has been standard practice to send these teens for evaluation by an endocrinologist: a specialist in diseases of the glands and hormones.

Median age was 11.5 years when the patients developed gynecomastia and 14.2 years at their first endocrinology visit. About 70 percent of patients had psychological distress due to their breast enlargement. The study focused on the "utility and diagnostic yield" of routine endocrinology assessment and hormone laboratory testing.

Most patients had known risk factors for adolescent gynecomastia - especially obesity/overweight, present in about 50 percent of patients. Another 15 percent had a family history suggesting an increased risk of gynecomastia, such as the father having breast enlargement as an adolescent.

In only eight percent of patients, some "secondary" cause of gynecomastia was diagnosed. Most of these involved drugs linked to male breast enlargement, including marijuana, the antidepressant drug fluoxetine, or anti-seizure drugs used to treat epilepsy. Some patients had medical causes of breast enlargement - most commonly (three patients) the inherited chromosomal disorder Klinefelter syndrome.

Most patients underwent laboratory testing to measure levels of hormones, such as testosterone and estradiol (a form of estrogen). Importantly, these tests had abnormal results in just three patients: a rate of 1.7 percent. Dr. Arneja and colleagues write, "Endocrinological investigations did not yield new clinical information in 99.4 percent of cases."

Despite their low diagnostic value, these evaluations carried considerable costs. Based on ASPS data on breast reduction surgery for adolescent gynecomastia, a rough estimate of these costs was nearly $5 million for in 2016 alone. The authors note that unnecessary endocrinology referrals may carry an additional opportunity cost in Canada, where patients may face long waiting lists for specialist visits.

Overall, 51 percent of patients received no medical treatment, other than "watchful waiting" or diet and exercise to lose weight. In this group, gynecomastia resolved over time (median age 14.6 years). Five percent of patients were treated with medications. The remaining patients, about 44 percent, underwent plastic surgery to treat their gynecomastia. Median age at surgery was 16.5 years.

Since breast enlargement often resolves with time, "reassurance and monitoring is the mainstay of early management," Dr. Arneja and coauthors write. They suggest that surgery be considered if gynecomastia has persisted for two years or beyond the age of 16, or for patients who are severely distressed.

Dr. Arneja and colleagues discuss the implications for evaluation and management of adolescents with gynecomastia. They highlight the importance of obtaining a thorough medical history - especially since most cases of secondary gynecomastia are medication-related. They conclude, "We do not suggest routine endocrinology workup, as it adds little value."

Plastic and Reconstructive Surgery® is published in the Lippincott portfolio by Wolters Kluwer.

Click here to read "Do Adolescents with Gynecomastia Require Routine Evaluation by Endocrinology?"

DOI: 10.1097/PRS.0000000000004465

June 29, 2018--Higher daily doses of rifampin, a cornerstone of tuberculosis treatment, killed more TB bacteria in sputum cultures, and the higher doses did so without increasing the adverse effects of treatment, according to a randomized controlled trial published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis: A Randomized Controlled Trial," Gustavo E. Velásquez, MD, MPH, associate physician in the Division of Infectious Diseases at Brigham and Women's Hospital in Boston, and co-authors report on a phase 2 trial conducted in Lima, Peru, with 180 adults with new, drug-susceptible TB.
Previous studies looking at whether intermittent delivery of higher doses of rifampin were effective in killing the TB bacterium found intermittent higher doses were more toxic than lower doses.

The authors of the current trial said that the findings were particularly encouraging because they suggest that at a high enough dose of daily rifampin, a treatment period of less than the standard six months may be possible.

"Six months of treatment with four drugs--often delivered with support and supervision--represents a substantial burden on the health care system, as well as on the patient," Dr. Velásquez said. "Patients who cannot complete the full regimen may not be cured, which permits ongoing transmission and the development of drug-resistant TB."

The authors wrote that optimization of rifampin dosing is a priority because it has the most potent sterilizing effect of the four first-line agents, is available throughout the world, and costs only pennies per capsule.

Trial participants were randomized equally to receive a standard dose of 10 mg/kg/day of rifampin or higher doses of 15 and 20 mg/kg/day, along with standard doses of the other first-line anti-TB drugs (isoniazid, pyrazinamide, ethambutol), during the first eight weeks of intensive therapy. After that, participants in all three trial arms received standard doses of rifampin and isoniazid during four months of continuation therapy.

The trial found that each five mg/kg/day increase in rifampin increased the elimination rate of TB bacteria from sputum. The trial also looked at rifampin concentrations in plasma and found that elimination rates of TB bacteria were significantly related to higher rifampin concentrations.
All findings were true even after adjusting for age, sex and extent of disease.

Importantly, the increased efficacy of higher doses did not appear to result in more grade two or higher rifampin-related adverse events. Two commonly reported adverse events of rifampin are liver toxicity and flu-like syndrome. Flu-like syndrome was not observed in this trial.

The trial did not find that rates of culture conversion, a milestone in TB therapy indicating that bacteria are no longer detectable in culture, differed among the three trial arms after the eight-week intensive treatment phase. The authors said the trial was not powered to make that determination.

"The difference was too modest at the tested doses for successful treatment shortening," Dr. Velásquez said. "However, these results, taken together with other recently published reports, support efforts to increase doses of rifampin to 35 mg/kg/day and possibly higher until the maximum tolerable dose is identified."

JAKARTA - Indonesia has made advances in health since 1990, increasing life expectancy by eight years and decreasing rates of health burden from communicable diseases like diarrheal disease and tuberculosis. But the country is facing a growing and expensive wave of health threats from heart disease, diabetes, and other non-communicable diseases, according to a new study.

"Indonesia is wrestling with a 'double burden.' We must remain vigilant in driving down rates of communicable diseases and ailments that affect mothers and infants. At the same time, we need to prevent and treat non-communicable diseases, which is an expensive endeavor," said Dr. Nafsiah Mboi, former Indonesian health minister and lead author of the study. "This gets even more complicated as Indonesians live longer and wrestle with more complex combinations of diseases."

The study, published today in The Lancet, covers 1990 to 2016; it is part of the Global Burden of Disease (GBD) study, a comprehensive effort to quantify health internationally. For this study, Mboi and IHME researchers worked with a diverse team of Indonesians including officials of the Ministry of Health, the National Institute of Health Research and Development, the National Planning Board, the Central Bureau of Statistics, the Eijkman Oxford Institute, University of Indonesia, and the National Social Health Insurance Scheme. Researchers reviewed 333 causes of death and disability in Indonesia and seven comparison countries. It is the largest systemic effort ever to examine Indonesian health trends and their causes.

Indonesians today live longer than ever before: 71.7 years in 2016 compared to 63.6 years in 1990. Women live slightly longer than men. This increase in life expectancy is largely the result of Indonesia's successful efforts against communicable, maternal, neonatal, and nutritional diseases. In 1990, diarrheal diseases, lower respiratory infections (LRI), and tuberculosis (TB) were the top three causes of death and disease. More than 25 years later, TB was the #4 cause of health loss, diarrheal diseases were #10, and LRI dropped from the top 10.

Despite substantial gains, these diseases are still major health challenges, Mboi said.

At the same time, the health loss from non-communicable diseases has dramatically increased. Rates of cardiovascular diseases and diabetes have ballooned in the past 25-plus years. These increases have been fueled by poor diet, high blood pressure, high blood sugar, and tobacco use - now the top risk factors in Indonesia. Diabetes has shown a particularly marked rise. Death and disability from diabetes increased 38.5% since 2006, promising to strain the country's health system for years to come.

Injuries from traffic accidents and non-deadly ailments such as low back and neck pain, along with vision and hearing loss, are also taking an increasing toll on Indonesians' health.

The study comes at a critical time for Indonesia. More than 180 million people - nearly 70% of the population - are enrolled in Jaminan Kesehatan Nasional, the country's national insurance program. This program was launched in 2014 and aims to provide health coverage for all Indonesians, with the government paying premiums of people living in poverty. The government has set the ambitious goal of enrolling 95% of the population by 2019, effectively achieving universal health coverage.

This rapid expansion of health care will require intensified and strategic investments, according to Mboi.

"This study will help the government make more informed health investments and policies in the coming years. We need continued research efforts to increase our understanding of health trends, especially in different provinces of our very large and diverse country," she said.

"The Global Burden of Disease study allows policymakers in Indonesia and beyond to better understand the diseases, injuries, and risk factors that impact health - and how these are changing over time. This information empowers people to make more effective health decisions," said Dr. Christopher Murray, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, whose organization coordinated the study.

In a summer outbreak that posed significant risks to pregnant women and their fetuses, 29 people in Miami-Dade County were infected with the Zika virus between late June and early August of 2016, according to the Centers for Disease Control and Prevention.

To understand people's perceptions, behaviors, and knowledge about the outbreak, and whether county media campaigns had an effect in helping educate the public about the virus, a research team led by University of Miami Assistant Professor of Geography and Regional Studies Imelda Moise surveyed 149 women and 113 men in approximately 262 county households.

According to their findings, women with a bachelor's degree and men who knew someone at high risk for the virus were more likely to have knowledge or concerns about it.

Using the Health Belief Model, the survey included such straightforward questions as: Have you ever heard of the Zika virus? Approximately how many cases of Zika are in Miami-Dade? If a pregnant woman has Zika, what are the risks for her fetus/baby? How confident are you that you can protect yourself and your household members from getting Zika virus?

"Men did care about Zika prevention, especially if they knew a female family member or acquaintance who was pregnant," said Moise, who added that messages that cater to the different needs, attitudes, knowledge, and perceptions of the target audience are most effective. "Targeted prevention and treatment interventions by gender, as well as education level, should definitely be considered by local governments, especially if there is another outbreak."

The study also found that a higher percentage of women (53.7 percent) than men (42.5 percent) viewed Zika as a severe disease and more women than men were afraid of contracting the virus. In addition, the survey indicated that more women than men felt confident they could protect the people in their households from contracting Zika by taking protective measures, such as checking for and draining standing water, and using repellents and window/door screens.

When it came to mosquito control efforts, Moise said, there was a tendency to think that one size fits all. "For example," she said, "there's a perception that the risk is the same everywhere, particularly when mosquito control officials release aerial insecticide over large areas. The risk varies by neighborhood and even the characteristics of the people who live in those neighborhoods are factors. Our study implies that there must be more accurate evidence regarding the connection between individual and neighborhood level socio-demographics and practices executed by local governments to prevent another Zika outbreak."

Washing your hands and cleaning your house frequently may help to lower your contact with common flame-retardant chemicals, according to a new study by researchers at the Columbia Center for Children's Environmental Health (CCCEH) at Columbia University's Mailman School of Public Health. The study is the first to assess whether house cleaning and handwashing can effectively lower exposure to flame retardants. Results appear in the Journal of Exposure Science and Environmental Epidemiology.

Flame retardant chemicals have been added to furniture and electronics since the 1970s to comply with fire safety standards. Manufacturers use of new organophosphate flame retardants (OPFRS) to consumer products has increased since 2005. OPFRs have been linked to endocrine disruption, decreased fertility, and thyroid dysfunction in humans. In this study, researchers examined exposure to a commonly used OPFR, Tris (1,3-dichlorisopropyl) phosphate, known as Tris, and six other flame retardants.

The Environmental Protection Agency (EPA) recommends practical steps like handwashing and housecleaning--dusting with a moist cloth, wet mopping, and vacuuming--to lower exposure to flame retardants. To assess whether handwashing and house cleaning effectively reduced exposure, senior investigator Julie Herbstman, PhD, associate professor of Environmental Health Sciences, designed a twofold behavioral intervention and enrolled 32 women from CCCEH's Sibling-Hermanos birth cohort. Participants were randomly assigned to one of two interventions, house cleaning or handwashing, for the first week of the study. The house cleaning intervention group was given microfiber mops, vacuums, and microfiber cloths and asked to increase the amount they cleaned their home that week. The handwashing group was given hand soaps and asked to focus on washing their hands more than they typically do, especially before meals. During the second week of the study, all participants were asked to do both extra handwashing and housecleaning. Urine samples were collected from participants before the study began and following the first and second weeks of the intervention.

Tris was detected in 97 percent of urine samples. Following the first week of the intervention, the housecleaning group and handwashing group experienced a 47 percent decrease and 31 percent decrease in Tris levels measured in urine, respectively. Women with higher than average exposure to Tris before the intervention began, experienced a 74 percent decrease in their levels following a week of housecleaning. After the second week of the study, when participants were asked to do both housecleaning and handwashing, levels of Tris measured in urine fell 43 percent compared to baseline levels. Women with higher than average levels of exposure at baseline experienced the greatest decrease, with their levels of Tris falling 62 percent. Similar trends in exposure levels were seen for other OPFRs measured in this study.

"The results imply that both handwashing and house cleaning can be effective ways to reduce exposure to flame retardants and this evidence supports the EPA's recommendations," says Elizabeth A. Gibson, the study's first author and a PhD student in the Department of Environmental Health Sciences at Columbia's Mailman School. "However, none of the reported flame retardants were reduced below the limit of detection, indicating that individual behavior cannot entirely reduce exposure."

"As people replace their old furniture, we've seen a reduction in exposures to the earlier generation of flame retardants, polybrominated diphenyl ethers, or PBDEs," says Herbstman. "Going forward, it's important that we continue to study new organophosphate flame retardants to understand what they do to our health and how to protect ourselves, both on an individual and population level."

The Bloomberg School scientists, in a commentary that appears in the July issue of Cancer Causes & Control, point to evidence that social factors help determine people's vulnerability to cancer, and argue that these factors should be considered routinely in studies and risk assessments that bear on clinical care.

"We've been missing opportunities to understand and reduce disparities in breast cancer risk and outcomes," says lead author Lorraine T. Dean, ScD, an assistant professor in the Department of Epidemiology at the Bloomberg School. "Simply put, not enough is being done to understand how race, income level and other social factors tie in to cancer susceptibility."

A 2014 review of over 20 years of National Cancer Institute clinical trials, for example, found that only about 20 percent of the randomized controlled studies reported results stratified by race/ethnicity. In a follow-up analysis of 57 breast cancer observational and randomized controlled trials that were published in 2016, the researchers found that, after excluding those in which the primary focus was disparities, fewer than five percent of studies reported findings stratified by race or other socioeconomic factors.

As Dean and colleagues note in their commentary, it should be obvious that in general, neglecting race/ethnicity and other social factors in medical research can mask important drivers of bad outcomes. For example, a recent high-profile study sorting mortality rates by race and socioeconomic status revealed that midlife mortality is increasing among blue collar whites in the U.S. even though it is declining for the population overall. Those findings drew attention to ongoing increases in suicides and substance-abuse-related deaths for blue collar whites, and led researchers to zero in on economic despair and social decay as the likely causes.

"A lot of scientists don't want to deal with race or socioeconomic position in their studies because they think those characteristics aren't modifiable," Dean says. "But they can actually help identify factors that are modifiable. You can't change your genes, for example, but we still do genetic studies because they illuminate pathways we can change with medicines or other interventions."

Breast cancers are the principal research focus for Dean and colleagues. They see the potential--and many missed opportunities to date--for research to uncover or at least address social-related risk factors for this set of diseases.

They point out, for example, that standard breast cancer risk assessment tools haven't always taken race into account--even though there are significant racial disparities in the risks for certain types of breast cancer as well as breast cancer mortality rates. For many years, a commonly used questionnaire tool for assessing breast cancer risk (now known simply as the Breast Cancer Risk Assessment Tool) was validated only for white women. It tended to underestimate significantly the risks of breast cancers for black women, who have lower rates of mammogram screening and higher rates of breast cancer at younger ages. That error may have kept many black women from participating in cancer-prevention trials of drugs such as tamoxifen.

"The model was revised in 2015 to take race into account, and now estimates black female eligibility for chemoprevention at nearly three times the rate of the original model," says Dean.

Clinical trials and population studies should be powerful tools for uncovering links between social factors and cancer vulnerability, which in turn should lead to better risk reduction and/or treatment strategies. But here too, the necessary information isn't routinely gathered.

To address the issue, Dean and her colleagues recommend increasing education and awareness about the importance of inclusion of social factors in clinical research; adding requirements for data on social factors to journal guidelines for reporting study results; and refining cancer risk assessment tools by including social factors.

"If adopted, these measures would enable more effective design and implementation of interventions," Dean says, "and would help eliminate breast cancer racial and socioeconomic disparities by accounting for the social and environmental contexts in which cancer patients live and are treated."

"Social factors matter in cancer risk and survivorship" was written by Lorraine T. Dean, Sarah Gehlert, Marian L. Neuhouser, April Oh, Krista Zanetti, Melody Goodman, Beti Thompson, Kala Visvanathan, and Kathryn H. Schmitz.

Funding was provided by the National Institutes of Health (K01-CA184288, U54-CA155850, U01-CA116850, U54-CA155496, and P30-CA006973).

Risk largely due to use of 'broad spectrum' antibiotics as alternative to penicillin

Patients who have a penicillin allergy recorded in their medical records are at an increased risk of developing the drug resistant 'superbug' infection MRSA and healthcare-associated infection C difficile, finds a study published by The BMJ today.

The risk is largely due to the use of more 'broad spectrum' antibiotics as alternatives to penicillin, which may be fuelling the development of drug resistant bacteria.

The researchers argue that addressing penicillin allergies "may be an important public health strategy to reduce the incidence of MRSA and C difficile among patients with a penicillin allergy label."

Penicillin allergy is the most commonly documented drug allergy, reported by about 10% of patients. However, previous studies have shown that more than 90% of patients with listed penicillin allergies can be safely treated with penicillins.

To evaluate the public health consequences of a penicillin allergy label, researchers at Massachusetts General Hospital in Boston examined the relation between penicillin allergy and development of MRSA and C difficile.

Using data from the Health Improvement Network (THIN), an electronic medical record database of 11 million UK patients, they identified 64,141 adults with a documented penicillin allergy and 237,258 matched adults of similar age and sex, with recent penicillin exposure but without a penicillin allergy.

None of the participants had any history of MRSA and C difficile infection, and were followed up for an average of six years, during which time use of antibiotics and cases of doctor diagnosed MRSA and C difficile were recorded.

A total of 1,345 participants developed MRSA and 1,688 developed C. difficile over

the follow-up period.

After adjusting for several known risk factors, the researchers found that a penicillin allergy label was associated with a 69% increased risk of MRSA and a 26% increased risk of C difficile.

Once documented, a penicillin allergy was associated with increased use of alternative 'broad spectrum' antibiotics, which act against a wider range of bacteria.

The results show that increased use of broad spectrum antibiotics accounted for more than half (55%) of the increased MRSA risk and more than one third (35%) of the increased C difficile risk among patients with a listed penicillin allergy.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers cannot rule out the possibility that other, unmeasured factors may have affected their results. However, they point out that this was a large, representative sample and the findings remained consistent after further analyses to test the strength of the results.

As such, they conclude that patients with a documented penicillin allergy "have an increased risk of new MRSA and C difficile that may be modifiable, to some degree, through changes in antibiotic prescribing."

As infections with resistant organisms increase, "systematic efforts to confirm or rule out the presence of true penicillin allergy may be an important public health strategy to reduce the incidence of MRSA and C. difficile," they add.

Study targets men whose cancers stopped responding to hormone therapy   

Men taking the drug enzalutamide had delayed cancer re-appearance of almost two years  

Men taking enzalutamide had a 71 percent lower risk of metastasis or death than placebo

Drug already FDA-approved for advanced prostate cancer
 

CHICAGO --- Men with non-metastatic castrate-resistant prostate cancer and a quickly rising PSA level present a medical dilemma. The rising PSA (prostate-specific antigen) means there is cancer activity, but no visible metastasis in a scan.
 

These men are receiving hormone treatments to reduce the testosterone on which their cancer feeds, but their cancers have become resistant to that treatment. Until recently, there has not been an effective treatment to improve their outcome. 
 

Now there might be one, reports a new study by a Northwestern Medicine clinical researcher. The double-blind, randomized phase III trial shows a drug currently used to treat men with metastatic, advanced prostate cancer significantly lowered the risk of metastasis or death when used in men with non-metastatic castrate-resistant prostate cancer and a rising PSA level.
 

Men who took the drug, enzalutamide, had a 71 percent lower risk of metastasis or death than those who took the placebo over the three-year duration of the trial. They also had delayed cancer re-appearance of almost two years compared to those taking a placebo. 

The study will be published June 28 in the New England Journal of Medicine.
 

"I'm delighted with these results," said lead study author Dr. Maha Hussain, the Genevieve Teuton Professor of Medicine at Northwestern University Feinberg School of Medicine and deputy director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "Not only did the drug reduce cancer spread, but many other disease-related effects were impacted."

These include a greater decline in PSA and less need for additional anticancer treatments without a negative impact on quality of life.

Hussain, who is a Northwestern Medicine oncologist, conducted the study when she was at the University of Michigan.
 

"Our goal was to see if we could delay the re-appearance of cancer with the hope it will lead to prolonged life," Hussain said. "We have to do more follow-up over time to see if long-term survival is impacted, but there are early positive trends."  
 

The U. S. Food and Drug Administration is currently reviewing approval of enzalutamide for men with non-metastatic castrate-resistant prostate cancer, Hussain said.

Drug shuts down the runway for male hormones to enter cancer cell
 

Prostate cancer feeds on testosterone. The drug, enzalutamide, targets the androgen receptor on the cancer cell that is like a tiny landing pad for male hormones. It closes down the runway and starves the cell of testosterone and other male hormone-like substances. Some cancer cells may die; some may go dormant.
 

"By treating men earlier when they have less cancer, the drug can be more effective," Hussain said. "It's like weeds in the garden. It's easier to control one weed than a garden full of them." 
 

The international trial included about 1,400 men with PSA levels that had doubled in 10 months or less and were continuing androgen-deprivation therapy. These are patients with the most aggressive form of the disease in this setting. For every three patients in the trial, two got the drug and one got the placebo.
 

The median duration of the trial regimen was 18.4 months in the enzalutamide group and 11.1 months in the placebo group. The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group. When the trial was over, the men on the placebo received the real drug.
 

Historically, men with prostate cancer were treated with surgery to remove their testes, but as technology and drug development improved, they received hormone therapy injections to reduce testosterone production. Either way, the therapy doesn't control other sources of testosterone in the body and "even a whiff of male hormone stimulates the cancer," Hussain said.