Body

CLEVELAND, Ohio (May 9, 2018)--Sex shouldn't hurt at any age, yet 75% of postmenopausal women report vaginal dryness, and up to 40% report pain with intercourse. A new study reports that vaginal estradiol tablets just might be what's needed to relieve vulvovaginal problems and improve overall quality of life. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Moderate to severe vulvovaginal symptoms in postmenopausal women are associated with significant decreases in sexual functioning and quality of life. Although there are a number of treatment options available, not all of them have been put to the test and have been documented to work. In the article "Effects of vaginal estradiol tablets and moisturizer on menopause-specific qualify of life and mood in healthy postmenopausal women with vaginal symptoms: a randomized clinical trial," results of a double-blind, placebo-controlled study compared the effectiveness of vaginal estradiol tablets and vaginal moisturizers.

With more than 300 postmenopausal women participating in the study, it was shown that low-dose vaginal estradiol tablets greatly improved quality-of-life scores compared with dual placebo. Treatment with vaginal moisturizers, in contrast, did not yield any more improvement than placebo. This is the first known study to associate method effectiveness with an improvement in quality of life and mood.

"Although vaginal lubricants and moisturizers may help vaginal dryness, they may not be effective for women with more severe vaginal changes because of loss of hormones at menopause," says Dr. JoAnn Pinkerton, NAMS executive director. "Vaginal therapies, including low-dose vaginal estrogen and intravaginal dehydroepiandrosterone, relieve both vaginal dryness and painful sex. This study also showed improvements in quality of life and sexual function for vaginal estradiol tablets over a vaginal moisturizer. Women with vaginal dryness and/or painful sex should talk to their healthcare providers about the best option for their particular situation."

Clinical researchers at Nationwide Children's Hospital have published one of the first health care studies to examine how behavior aligned with Safety II concepts impacts patient safety. Safety II is a novel approach to patient safety that focuses on why processes perform correctly in high-performing units, as opposed to its predecessor, Safety I, which focuses on why processes fail.

Published online today in the journal Pediatrics, the study analyzed the Pediatric Intensive Care Unit (PICU) at Nationwide Children's to identify factors in a hospital microsystem and its individuals that led to more reliable performance and increased ability to handle unusual or unexpected situations while delivering patient care.

Currently, most hospitals use Safety I, which focuses on retrospectively evaluating errors after they occur. Through Safety I, identified system problems are fixed to prevent a similar error from reoccurring. This approach does not prevent future errors unrelated to the "fixed" problem, and does not allow for error avoidance under unusual circumstances. Units that operate using Safety II behaviors are characterized by individuals and systems that are proactive in preventing errors. It is believed that this is one of the first studies to outline how Safety II principles can be implemented in a pediatric hospital setting.

"High-complexity, high-risk environments demand flexibility and resilience among their individuals to avoid errors, and our PICU exemplifies that," said Jenna Merandi, Pharm.D., MS, CPPS, medication safety officer at Nationwide Children's and co-author of the study. "We wanted to understand how the PICU used Safety II concepts to achieve its remarkably low adverse drug event (ADE) rate."

Clinical researchers conducted multidisciplinary focus groups with PICU staff, using open-ended questions to determine how they established safety in their unit. Qualitative analysis of the transcripts identified system characteristics and behaviors that contributed to low ADE rates in the PICU, and 19 common themes within four key domains were identified.

The key domains included individual characteristics; relationships and interactions; structural and environmental characteristics; and innovative approaches. The themes identified in the first three domains are typically observed in Safety I and are adaptable for use in Safety II. The themes within the innovative thinking and approaches domain appear to be uniquely applicable to Safety II: relying on teamwork if something novel is considered; team response to challenging circumstances; skepticism; and bringing atypical approaches from other microenvironments (out-of-box thinking).

"Moving forward, we want to use Safety II to understand how to apply resilience engineering into a health care system, and more testing needs to be done by implementing Safety II in other hospital units in order to achieve that understanding and broaden our program," said Thomas Bartman, MD, PhD, associate medical director of quality improvement at Nationwide Children's and co-author of the study. "For example, we plan to trial end-of-shift debriefing sessions to capture how individuals and systems respond to the unexpected and pass that learning to the next shift."

As an institution that prioritizes patient safety and reducing patient errors, Nationwide Children's adoption of Safety II aligns with Zero Hero: the safety program established in 2009 that focuses on the hospital's public goal to achieve zero preventable harm.

"Safety II does not replace Safety I, but it is a new approach in addition to the old 'finding and fixing' model of addressing patient safety concerns," said Richard J. Brilli, MD, FAAP, MCCM, chief medical officer at Nationwide Children's. "Optimistically, it has the potential to take patient safety to a whole new level."

A new study in the Journal of the National Cancer Institute indicates that survivors of uterine cancer are more likely to experience cardiovascular problems years after treatment.

Endometrial (uterine) cancer is the fourth most commonly diagnosed cancer among women in the United States. Incidence rates among women under the age of 50 have been increasing by 1.3% per year since 1988 and by 1.9% among women over the age of 50 since 2005. It was the 6th most common cause of death from cancer among women in the United States in 2017, with an estimated 10,920 deaths. As of 2017, there were an estimated 757,200 endometrial cancer survivors in the United States.

Previous studies of long-term health effects among endometrial cancer survivors have focused largely on quality of life, mental health, obesity, and adverse sexual side effects. But the high overall survival rate among people diagnosed with the cancer, the projected increase in the number of such cancer diagnoses, the introduction of more complex therapies, and the high mortality due to cardiovascular disease among endometrial cancer survivors, suggest that other long-term health effects are important to assess.

Researchers here identified 3,621 endometrial cancer survivors using the Utah Population Database. Diagnosis data was available for women aged 18 and over diagnosed with this cancer between 1997 and 2012 in Utah.

The results of the study indicate that approximately 25.7% of cancer survivors were diagnosed with heart diseases five to ten years after cancer diagnosis. Endometrial cancer survivors were 47% more likely to be diagnosed with a disease of the heart between one of five years after cancer diagnosis and 33% more likely to be diagnosed with a disease of the heart between five to ten years after the initial cancer diagnosis.

Researchers observed elevated risk during the one-to-five-year time period for peripheral and vascular atherosclerosis, hypotension, phlebitis, thrombophlebitis, thromboembolism, other circulatory diseases, and other diseases of the veins and lymphatics. Researchers found associations for hypotension, diseases of veins and lymphatics, and other diseases of veins and lymphatics.

Between one to five years after diagnosis, researchers observed increased cardiovascular risks among endometrial cancer survivors for phlebitis, thrombophlebitis and thromboembolism, lymphatic diseases, pulmonary heart disease, and atrial fibrillation. Some elevated risk persisted for cardiovascular diseases at five to ten years. Compared to patients who had surgery, patients who additionally had radiation therapy and/or chemotherapy were at increased risk for heart and circulatory system disorders between one to five years after cancer diagnosis.

Prior studies have reported similar proportions of endometrial cancer survivors who have hypertension diagnoses, but this study is the first to quantify risk for hypertension after cancer diagnosis among uterine cancer survivors compared to the general population.

This study suggests that increased monitoring for cardiovascular diseases may be important for endometrial cancer patients for 10 years after cancer diagnosis.

Philadelphia, May 8, 2018 - High levels of cytoskeleton-associated protein 4 (CKAP4) have been identified in the blood of patients with lung cancer. In a novel study in The American Journal of Pathology investigators found that CKAP4 levels were significantly higher in patients with lung cancer than in healthy individuals. They further determined that CKAP4 levels are already elevated in the blood of patients with stage I disease, making it a potential noninvasive diagnostic marker that could change current practices in the diagnosis and treatment of some types of lung cancer, including non-small-cell lung cancer and squamous cell carcinoma, and improve patient outcomes.

Lung cancer is the leading cause of cancer deaths in both men and women in the United States and worldwide. The disease is associated with a poor prognosis because most lung cancers are only diagnosed at an advanced stage.

"The identification of patients at an early stage of cancer when it can be treated surgically is extremely important to improve prognosis," explained Yuichi Sato, PhD, Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan, who led the study. "We need better biomarkers for early diagnosis."

Current biomarkers for lung cancer include carcinoma embryonic antigen (CEA), sialyl Lewis X antigen (SLX), squamous cell carcinoma (SCC) antigen, and cytokeratin fragment (CYFRA) 21-1, but these are not sensitive enough to detect tumors early, according to co-investigator Ryo Nagashio, PhD, from the Kitasato University School of Allied Health Sciences. "The results of our study provide evidence that the CKAP4 protein may be a novel early sero-diagnostic marker for lung cancer."

Researchers performed reverse-phase protein array analysis using a monoclonal antibody designated as KU-Lu-1 antibody on the blood of 271 lung cancer patients and 100 healthy individuals. KU-Lu-1 reacted only with tumor cells and tumor stromal fibroblasts in lung cancer tissues and not with normal lung tissues. Using immunoprecipitation and mass spectrometry, they confirmed that the KU-Lu-1 antibody recognized CKAP4 in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. In addition, a validation set consisting of samples from 100 patients with lung cancer and 38 healthy controls was also studied.

CKAP4 was recently identified as a receptor of Dickkopf1 (DKK1). Expressions of DKK1 and CKAP4 were frequently observed in tumor lesions of human pancreatic and lung cancers, and the simultaneous expression of both proteins in tumor tissues was inversely correlated with prognosis and relapse-free survival.

Across disease stages I-IV, the sensitivities of serum CEA, CYFRA, and SCCA are reported with 30 to 52, 17 to 82, and 24 to 39 percent, respectively. In this study, the sensitivity of serum CKAP4 was 81 percent in the training set and 69 percent in the validation set. These rates are higher than those of the current sero-diagnostic markers. Furthermore, the sensitivity of serum CKAP4 was also high even in stage I non-small-cell lung cancer and squamous cell carcinoma.

"The use of CKAP4 as a biomarker could change current practices regarding the treatment of lung cancer patients, and the diagnostic accuracies may be markedly improved by the combination of CKAP4 and conventional markers," concluded Dr. Sato.

MADISON -- In order to spread their destruction, ovarian cancer cells must break free from their tumor home, travel through the fluid in the peritoneal cavity and attach to the outside of the abdominal organs--surfaces that are, by necessity, not sticky.

Despite these challenges, most patients with ovarian cancer are diagnosed after metastasis has begun, resulting in poor patient outcomes. While ovarian cancer is only the 11th-most common form of cancer among women in the United States, it accounts for the fifth-most deaths, according to the Ovarian Cancer Research Fund Alliance.

New research from the lab of Pamela Kreeger, a University of Wisconsin-Madison biomedical engineering professor, has identified one way ovarian cancer cells appear to successfully spread. The work, detailed today in the journal Cancer Research, could lead to new therapies to curb metastasis of these tumors.

"Like most cancers, it's not the primary tumor that's usually the problem. It's the spread of the tumor to nearby organs that leads to serious complications," Kreeger says. "So if you can slow that process down, it's possible the patient will live longer and/or have a better quality of life."

In studying high-grade serous ovarian cancer -- the most common but also most aggressive type -- Kreeger, postdoctoral fellow Molly Carroll and other lab members have teased out how one type of immune cells helps cancer cells attach in the peritoneal cavity, enabling metastasis. Higher levels of these immune cells, called alternatively activated macrophages, are associated with worse outcomes. But the question remained: Do these macrophages encourage metastasis?

To find out, Kreeger's team created a micro-culture device that allowed them to bring together the key players: macrophages, cancer cells and mesothelial cells, which line the peritoneal cavity. Experiments revealed macrophages increase tumor cell attachment to the mesothelial cells by making the mesothelial cells stickier.

"For me that was one of those scientific 'ah ha' moments -- the interactions between the normal cells in our body can influence metastasis. In other words, it's not all about the tumor cell," says Kreeger.

But which of the 25 proteins the team detected in the co-culture device was responsible for this effect? Computational modeling revealed the culprit. The macrophages produce a protein called MIP-1β, which causes the mesothelial cells to produce more of an adhesion protein called P-selectin. P-selectin, in turn, allows the cancer cells to stick.

A preliminary experiment in mice validated those results, while human samples--obtained through collaborators in the UW-Madison School of Medicine and Public Health--showed that patients with ovarian cancer had higher levels of MIP-1β and P-selectin.

The good news: There are already several existing drugs, developed for other diseases, that could prove useful. Maraviroc, which is used to treat HIV, inhibits the receptor for MIP-1β, while two different drugs that target P-selectin are in clinical trials for blood disorders.

"We're interested in pursuing multiple avenues, because it's possible one will work better than another," says Kreeger, whose group has filed a provisional patent on the findings with the Wisconsin Alumni Research Foundation. "It's also possible one will have more tolerable side effects than another."

Kreeger will use a recently awarded grant from the Rivkin Center for Ovarian Cancer to further validate the findings in long-term experiments in mice in order to set the stage for pre-clinical testing of drug treatments.

Carroll, the first author on the paper, says being able to target another aspect of the cancer's spread beyond combatting tumor growth with chemotherapy opens new avenues for treatment.

"Treatment for ovarian cancer really has not changed in the past 20 years," she says. "Hopefully through the development of such maintenance therapies, we can prevent the establishment of new tumor metastases."

New evidence published today in the Cochrane Library shows that human papilloma virus (HPV) vaccines protect against cervical lesions in young women, particularly in those who are vaccinated between the ages of 15 and 26. It also summarizes findings on harms that have been assessed in randomized controlled trials.

Most people who have sexual contact at some point in their life will be exposed to the human papilloma virus (HPV). In the majority of women, HPV infection will be cleared by the immune system. When the immune system does not clear the virus, persistent HPV infection can cause abnormal cervical cells. These lesions are known as cervical 'precancer' because over time they can progress to cervical cancer if left untreated.

There are many different types of HPV. Some are associated with the development of cervical lesions that can become cancerous and are considered as high-risk HPV types. Two of these high-risk types (HPV16 and HPV18) account for about 70% all cases of cervical cancer worldwide. Vaccines have been developed that help the immune system to recognize certain HPV types. Because cervical cancer can take several years to develop, regulatory bodies and international health agencies such as the World Health Organization (WHO) regard cervical lesions as the preferred outcome measure for HPV vaccine trials.

A team of Cochrane researchers has summarized results of 26 studies in 73,428 women conducted across all continents over the last eight years. Most women in the studies were under the age of 26 years old, although three trials recruited women between 25 and 45 years. The studies were well-designed, randomizing the women to either HPV vaccine or a placebo. The review evaluates evidence for two vaccines: the bivalent vaccine targeting HPV16 and 18, and the quadrivalent vaccine targeting HPV16/18 and two low-risk HPV types causing genital warts. The newer vaccine that targets nine HPV types was not included in the review since it has not been compared against a placebo in a randomized controlled trial.

The review looked at two groups of people: women who are free of high-risk HPV at the time of vaccination and all women regardless of HPV status at vaccination. The effects of the vaccine were measured as precancer associated with HPV16/18 and precancer irrespective of HPV type. The review looked at data from ten trials assessing cervical lesion data at between three and a half to eight years after vaccination.

None of the studies have followed up participants for long enough to detect an effect on cervical cancer. The researchers looked at precancer cervical lesions instead. They found that in young women who did not carry HPV, vaccination reduced the risk of developing precancer. About 164 per 10,000 women who got placebo and 2 per 10,000 women who got the vaccine went on to develop cervical precancer.

The researchers also looked at data from all enrolled women regardless whether they were free of high-risk HPV at vaccination or not. Among women aged 15 to 26 years, vaccines reduced the risk of cervical precancer associated with HPV16/18 from 341 to 157 per 10,000. HPV vaccination reduced also the risk for any precancer lesions from 559 to 391 per 10,000.

In older women vaccinated between 25 to 45 years the HPV vaccine does not work as well. This might be because older women are more likely to have been exposed already.

The evidence also shows that the vaccines do not appear to increase the risk of serious side effects which was about 7% in both HPV vaccinated or control groups. The researchers did not find increased risk of miscarriage in women who became pregnant after vaccination. However, they emphasize that more data are required to provide greater certainty about very rare side effects and the effect vaccines have on rates of stillbirth, and babies born with abnormalities in those who became pregnant around the time of vaccination.

Cochrane lead author, Dr. Marc Arbyn, of the unit Cancer Epidemiology, Belgian Cancer Centre, Sciensano, said: "The findings of this review should be viewed within the context of multiple global surveillance studies, which have been conducted by the Global Advisory Committee on Vaccine Safety from the WHO since the vaccinations were licensed. The committee concluded that the risk-benefit profile of prophylactic HPV vaccines remains favourable and expressed its concerns about unjustified claims of harm that lack biological and epidemiological evidence, and which may affect the confidence of the public. At the same time, the Committee encouraged health authorities to continue surveillance and examination for potential adverse events."

Dr. Jo Morrison, Consultant in Gynaecological Oncology at the Musgrove Park Hospital, Somerset, UK, said: "Vaccination aims to prime the immune system to produce antibodies that can block subsequent natural HPV infection. These data show that immunizing against HPV infection protects against cervical precancer, and it is very likely that this will reduce cervical cancer rates in the future. However, it cannot prevent all cervical cancer and it is still important to have regular screening, even if you have been vaccinated."

She added: "Cervical cancer can take many years to develop following HPV infection and development of precancer lesions, therefore long-term follow-up studies are needed to find out the effects of HPV vaccination on cervical cancer rates."

ANN ARBOR, Mich. -- More than one-third of cirrhosis cases are related to alcohol, a seven-year national study of more than 100 million privately insured people has found.

Among that group, 294,215 people had cirrhosis; 105,871 (36 percent) had alcohol-related cirrhosis. The latter group was sicker and admitted or readmitted to a hospital more often, incurring nearly twice the health care costs per person: $44,835 versus $23,329.

"When I look at this data, it tells me that this is a big problem," says Jessica Mellinger, M.D., a Michigan Medicine gastroenterologist and health services reserchers at the University of Michigan Institute for Healthcare Policy and Innovation.

And it could be a particularly big problem for women, who in recent years have been diagnosed with alcohol use disorders at a rate nearly twice that of men.

Mellinger's study, published in the journal Hepatology, found that women showed a 50 percent increase in alcohol-related cirrhosis during that seven-year period; men showed a 30 percent increase.

Although biology doesn't explain why women appear to be consuming more alcohol then they used to, it does shed light on the effects.

"Women process alcohol differently than men and they are more susceptible to damage in the liver than men," says Mellinger. "They can develop cirrhosis with less alcohol and in a shorter time frame. The hypothesis is that certain hormones make women more susceptible, though we don't know exactly why they are so much more susceptible."

A costly, widespread issue

To conduct their study, Mellinger and her team examined privately insured individuals ages 18 to 64 by using the Truven MarketScan Commercial Claims and Encounters database. It is the largest dataset of claims for people with private insurance obtained through their employers.

The study's goal was to determine the prevalence, health-care utilization and costs of alcohol-related cirrhosis among privately insured people in the United States. The research showed:

Patients with alcohol-related cirrhosis aren't uncommon. The figures nearly surpass those of some common cancers.
Health care for these patients is costly, sometimes as much as the cost for cancer patients.
Cirrhosis has already progressed when many patients see a doctor for symptoms, preventing a chance for early diagnosis and treatment.

But it only looked at one segment of the population.

"At the time we did this study, we also considered using data sets from Medicare and Medicaid, but they were restricting reporting of claims related to substance abuse, and we knew we'd be missing information," says Mellinger.

Since that time, the Centers for Medicare and Medicaid Services began reporting substance abuse; that information is now open to researchers. Mellinger expects alcohol-related cirrhosis statistics to increase significantly after that patient data is reviewed.

The reason: "Many people with [alcohol-related cirrhosis] are too sick to remain employed, so more of these patients are insured through government-sponsored insurance such as Medicare and Medicaid," she says, noting that another limitation of the study was a lack of information about race and ethnic groups.

Alcohol-use treatment programs vital

Prior research has shown that there is no ethical justification for deprioritizing patients from receiving a transplant because they have alcohol-related liver disease.

"But first they will need alcohol cessation treatment before they can be transplanted with success," says Mellinger. "Alcohol-use treatment is effective and many patients do stop drinking, obtain transplant and do well afterward."

Although there is stigma to alcohol-related cirrhosis, it is common and it's not a moral failure, she adds. "Many people in the medical community think that alcohol use is not treatable, but it is. There is a lot of collaboration at U-M to provide the right help for patients with alcohol-related liver disease."

Getting that help is crucial: When patients have advanced liver disease, the only action that affects whether they live or die is if they stop drinking.

"Once you have cirrhosis, or scar tissue on the liver, it's permanent," says Mellinger, who works closely with the University of Michigan psychiatry department and the University of Michigan Addiction Treatment Services.

"But even though the damage is still there, your liver function can improve dramatically" if you stop drinking.

Set to embark on further study with all insurance payers, Mellinger hopes her current work will help physicians better understand that alcohol-related cirrhosis is a growing problem that demands attention and resources.

"We're only touching the tip of the iceberg," she says. "By demonstrating that alcohol-related cirrhosis is a high-burden health care problem that could be prevented, we hope that it will increase funding for early detection of alcohol use and for greater utilization of alcohol-use treatment programs."

GALVESTON, Texas -A new collaborative study has identified and studied Ebola antibodies that could be used to design universal therapeutics that are effective against many different Ebola species. The findings were recently published in Nature Microbiology.

The Ebola virus causes a severe illness with high mortality rates in humans. Several strategies have been developed to treat Ebola infection, including ZMapp, which has been shown to be effective in non-human primates and has been used under compassionate-treatment protocols in humans.

"The trouble with ZMapp is that although it is effective against the Ebola species that was largely responsible for the last Ebola outbreak, it does not neutralize other Ebola species, including Ebola Bundibugyo, Reston or Sudan," said virologist Alex Bukreyev, co-senior author and a University of Texas Medical Branch at Galveston professor in the department of pathology. "We identified and studied three naturally-occurring antibodies from human survivors of Ebola Bundibugyo that neutralize and protect against infection with the several different Ebola virus species."

The newly identified antibodies bond at a different site on the Ebola virus than other antibodies currently used to develop Ebola therapies.

Information on the Ebola virus:

According to the Centers for Disease Control, Ebola was first discovered in 1976 near the Ebola River in what is now the Democratic Republic of Congo. Since then, the virus has been infecting people from time to time, leading to outbreaks in several African countries.

Some of the different kinds of Ebola viruses are:

Ebola virus (Zaire ebolavirus)

Sudan virus (Sudan ebolavirus)

Taï Forest virus (Taï Forest ebolavirus, formerly Côte d'Ivoire ebolavirus)

Bundibugyo virus (Bundibugyo ebolavirus)

Reston virus (Reston ebolavirus), known to cause disease in nonhuman primates and pigs, but not in people

Many US Airbnb venues may be falling short on fire safety, indicate the results of a snapshot survey of more than 120,500 rentals in 16 cities, published in the journal Injury Prevention.

While the data suggest that most properties were fitted with smoke alarms, less than half had fire extinguishers or first-aid kits on the premises.

Airbnb is the world's leading peer to peer online hospitality service, with over 4 million venues in 65,000 cities in 191 countries. Some 660,000 listings are in the US.

Most venues are in private homes to which national fire safety requirements don't usually apply. Although some states and municipalities do stipulate specific standards for rental properties, these are far from universal.

And while Airbnb has carried out fire safety campaigns and strongly encourages hosts to instal smoke detectors and carbon monoxide (CO) alarms, it doesn't require them to provide proof.

In 2015 alone, there were more than 1 million fires in the US, which killed 2500 people and caused US$ 14 billion in property damage: most of these fires were in residential buildings.

To find out what sort of fire safety precautions Airbnb venue hosts had taken, the researchers used data from InsideAirbnb.com for 120, 691 listings in 16 cities from Austin, Texas to Washington, DC, between October 2015 and December 2016.

InsideAirbnb.com is an independent website that compiles publicly available information about Airbnb listings posted by Airbnb hosts.

The data were mined to find out if the hosts had reported any or all of: smoke detectors; CO alarms; fire extinguishers; and first-aid kits on their premises.

Across all 16 cities in the sample, most had smoke detectors (80%), ranging from 3 out of 4 in Austin to 9 out of 10 in Nashville.

Around half had a CO alarm (58%), ranging from around 1 in 3 (just under 37%) venues in Austin to nearly 3 out of 4 in Denver (just under 74%).

Fire extinguishers were less common, ranging from around 1 in 4 (29%) in New York City to over 70 percent in Austin. Portland, Oregon was the only city in the sample to have first aid kits in more than half of its Airbnb venues.

It's reassuring that most Airbnb venues had smoke detectors and a goodly proportion CO alarms, say the researchers, but they point out that "this is substantially lower than the universal requirement for hotels," which are legally obliged to comply with national (NFPA) fire safety regulations.

The researchers highlight that their data refer to a wide ranging period and reflect only a snapshot of the available venues in each city. And certain hosts may be in condominiums or apartment buildings that have their own safety features.

Nevertheless, "the low proportions reported from some cities are troubling and suggests the need for further investigation and intervention," they suggest.

"Distributing safety information and products to hosts is an initial step, but the rates reported here suggest that Airbnb and other similar [peer to peer] models should consider requiring safety regulations for hosts," they say.

"Finally, public information efforts to make guests more aware of the importance of these safety amenities could facilitate demand for them, which might also increase the number of hosts who offer them," they write.

WHO: Aaron Kesselheim, MD, MPH, Director, Program On Regulation Therapeutics And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital

WHAT: Kesselheim, the senior author of two separate articles published in the May issue of Health Affairs, members of the PORTAL research group and co-authors, examine the fast approvals of precision medicines in one paper while evaluating the impact of the Orphan Drug Act's seven-year market exclusivity in the other.

"Precision Medicines Have Faster Approvals Based on Fewer and Smaller Trials Than Other Medicines," Lisette Pregelj et al, and Aaron Kesselheim

The outcome of clinical trials evaluating the effectiveness of precision medicines suggests such medicines, which can offer successful individualized treatments benefitting patients, will reach the market more rapidly than traditional drugs.

In this study, researchers examined the development and review of precision medicines by the FDA from 2013-2017. They found the process to be almost two years faster than comparable medicines, in part due to various special accelerated or priority pathways like the "breakthrough therapy" designation for which these drugs qualify.

In addition, however, the authors found that precision medicines were approved based on fewer pivotal trials of these drugs that enrolled fewer patients, and the trials were less likely to be blinded, randomized or controlled by comparing to placebo. The authors note that these trends raise separate questions about the quality and reliability of the data used for FDA approval.

Kesselheim also authored a study published in April in the Journal of Clinical Oncology, that showed how breakthrough-designated cancer drugs were associated with faster review and approval times, but no apparent improvement in safety or effectiveness when compared with traditional drugs.

"Evaluating The Impact Of The Orphan Drug Act's Seven-Year Market Exclusivity Period," Ameet Sarpatwari, PhD, assistant director, PORTAL, BWH et al, and Aaron Kesselheim

Among other incentives, the Orphan Drug Act of 1983 provides seven years of market exclusivity, which many believe acts as a strong incentive for pharmaceutical manufacturers to invest in drugs to treat rare diseases.

This study reviewed a cohort of drugs approved in the period from 1985-2014 that had at least one indication for an orphan-designated disease as of January 1, 2017. The investigators found that patent protection for these rare disease drugs often far outlasts the seven-year period provided under the Orphan Drug Act. The authors concluded that the explosion in new drugs for rare diseases is being incentivized by scientific advances and other features of the market, and not the statute's market exclusivity provision. The authors recommend that policymakers looking to replicate the Orphan Drug Act's success in other fields should leverage these other factors and not replicate the Orphan Drug Act's exclusivity provision.

Prescription drug monitoring programs (PDMPs) are a key component of the President's Prescription Drug Abuse Prevention Plan and considered a critical tool for reducing prescription opioid-related illness and death. The results of a study just conducted at Columbia University's Mailman School of Public Health and University of California, Davis, show there is insufficient evidence to confirm whether implementing these programs actually increases or decreases overdoses. The findings are published online in Annals of Internal Medicine.

"Our aim was to systematically search and review the literature to assess whether these programs are associated with changes in nonfatal or fatal overdoses," said David Fink, MPH, MPhil, doctoral candidate in Epidemiology at the Mailman School of Public Health, and first author. "The evaluations would also help us determine whether specific administrative features of PDMPs correlate with these outcomes and, if so, which elements are most influential."

"We also hoped to learn of any potential unintended consequences associated with PDMPs," said Magdalena Cerdá, DrPH, associate professor, Department of Emergency Medicine
at UC Davis and co-senior author, "What we found was that vast variations in programs and their administrative features make them especially challenging to study."

Using a meta-analysis of publications indexed on MEDLINE, Clarivate Analytics, and ProQuest Dissertations indexed through December 2017, they found that of 2,661 articles, 17 of them met the inclusion criteria, 10 of which linked the implementing of programs to reducing fatal opioid overdoses. Mandatory review by providers of PDMP data, composed of a comprehensive prescribing history for each patient before writing prescriptions was the most studied program feature associated with this outcome.Other elements correlating with a decrease in fatal overdoses were frequent--at least weekly--updates of PDMP data, provider authorization to access PDMP data, and monitoring of nonscheduled drugs.

Three studies showed an increase in heroin overdose deaths after the monitoring programs had been implemented.

"This suggested to us that heroin substitution may have increased after PDMP-inspired restrictions on opioid prescribing," observed Silvia Martins, MD, PhD, associate professor of Epidemiology and co-senior author. "We therefore caution that programs aimed at reducing prescription opioids should also address the supply and demand of illicit opioids."

Opioid prescribing has increased 350 percent between 1999 and 2015. During the same timeframe, the rate of overdose deaths from both prescription opioids and heroin also increased substantially. PDMPs utilize centralized statewide data systems to transmit prescription data, which can flag patients who are potentially abusing opioids or physicians who are overprescribing.

Currently, all 50 states and the District of Columbia have either implemented a PDMP or have passed legislation to begin doing so. "As such, it is crucial to determine if these programs are helping to reduce opioid overdose," noted Fink. "So far, the definitive conclusion we can draw from our evaluation is that the evidence is insufficient and that much more research is needed to identify a set of 'best practices.'"

High intensity interval training reduces tiredness and improves self-esteem for testicular cancer survivors, according to a study published in the British Journal of Cancer today (Tuesday)*.

It found that men who had been treated for testicular cancer and had the lowest fitness levels benefited the most from this strenuous exercise regime.

Researchers invited 63 testicular cancer survivors to take part in a 12-week exercise programme which included repeatedly walking fast uphill on a treadmill set at an incline for two minutes and then at a slower pace on the flat for the same length of time.

The men reported significant improvements in energy levels and self-esteem compared to those who just received their usual follow up care. They also felt less tired and had more vitality three months later.

In the UK around 2,300 men are diagnosed with testicular cancer each year and it is most common in those in their early 30s.** Patients are likely to experience treatment-related fatigue.

Study senior author Professor Kerry S Courneya based at the University of Alberta in Canada, said: "This small study shows the men who had the biggest increase in fitness saw the greatest benefits. This indicates higher intensity exercise, which increases fitness levels, has more impact than more moderate activity.

"What's so exciting is that this programme would be easy to introduce to patients as it's as simple as jogging for two minutes and walking for two minutes. It can also be specifically targeted at men who aren't fit and suffer with tiredness."

Martin Ledwick, Cancer Research UK head information nurse said: "This adds to the increasing evidence that exercise programmes can improve wellbeing and fatigue after cancer treatment.

"Tiredness can be really debilitating for patients so it is great that simple and specific ways to help combat this are being explored."

ANN ARBOR, Mich. -- New immunotherapy treatments offer a remarkable chance for survival for patients with advanced melanoma and hard-to-treat cancers of the bladder, kidney and lung.

But the treatments, designed to unleash the immune system to attack cancer, can also spur an assault on healthy organs, including the eye.

The cases of three recent patients, published by University of Michigan Kellogg Eye Center in JAMA Ophthalmology, highlight the issue. Patients receiving immune checkpoint inhibitors developed uveal effusions and eye inflammation that affected their vision.

Although it is rare, knowledge of this risk is important both for the ophthalmologists who treat it and for the oncologists prescribing the anti-cancer treatment, say Michigan Medicine researchers.

With certain inhibitor drugs, the anti-PD-1 (programmed cell death protein-1) and anti-PD-L1 (programmed cell death ligand-1) monoclonal antibody immune checkpoint inhibitors block the interaction between PD-1 receptors on T cells and their counterpart proteins, PD-L1. This blockage allows the T cells in the immune system to do their job: attack and kill the cancer tumor cells.

"In our three patients who had been receiving these immune checkpoint inhibitors, we noticed large uveal effusions. In addition, there was anterior chamber inflammation in two of our patients," says Hakan Demirci, M.D., the Richard N. and Marilyn K. Witham Professor at the University of Michigan Kellogg Eye Center.

All three patients were receiving an anti-PD-1 or anti-PD-L1 antibody immune checkpoint inhibitor drug: atezolizumab, nivolumab or pembrolizumab.

On development of uveal effusions, Merina Thomas, M.D., a senior vitreoretinal surgery fellow at Kellogg says: "It happened quickly, between one and three months after the patients had received at least two infusions of the immune checkpoint inhibitors. That raised our suspicion."

There's no treatment for the side effects of the immune checkpoint inhibitors other than stopping the medication. "We asked each patient's oncologist if the patient's immune checkpoint inhibitor could be discontinued," says Thomas.

"But not all patients can stop the therapy, because they have widespread, life-threatening cancer," adds Demirci.

In two of the three patients, six weeks to three months after stopping the medication, the uveal effusions had improved and the affected eye looked normal. The third patient with a uveal effusion continued with the immunotherapy for his melanoma, but he died four months later.

Immune response in the eye

In the wall of the normal eye, there are three layers with no fluid among them. But inflammation in the eye can cause the layers to swell and fluid to accumulate between the layers.

Uveal effusions can occur when patients have eye injuries or operations, receive certain drugs, or for unknown causes. When the uveal effusion involves the fovea, where eyesight is the sharpest, it affects the vision.

In a previous review of 576 patients treated with nivolumab, 71 percent had side effects such as fatigue, itching and problems with the gastrointestinal or endocrine systems. Another study noted that uveitis and dry eye were the only ocular toxicities in patients taking PD-1/PD-L1 inhibitors, with the incidence of uveitis ranging from 0.3 to 0.6 percent, and no specifics regarding the pattern or management of the uveitis.

But the Kellogg experts say it's important for oncologists to refer patients with eye problems to an ophthalmologist, and it's equally important for ophthalmologists who see patients with uveitis or uveal effusion to ask them questions about the medications they may be receiving.

More than other organs in the body, the eye is known as an immune-privileged site. The normal immune response to antigens is absent. This means corneal transplants are very successful because the antigens from the grafts seldom produce inflammation in the eye. High levels of PD-L1 in ocular tissues may play a role in the eye's immune privilege. Thus, blockade of the regulatory T cells might have played a role in the toxicity in these patients.

"The immune system is tricky. It can help fight cancer cells but can also start fighting the body itself and cause side effects such as the uveal effusions in these patients," says Thomas.

As the use of immunotherapy becomes more widespread, researchers plan to observe whether more patients are experiencing similar side effects.

TORONTO-(May 5, 2018)-The volume of carbohydrates, proteins, lipids and calories consumed by very vulnerable preemies significantly contributes to increased brain volume and white matter development, however additional research is needed to determine specific nutritional approaches that best support these infants' developing brains, according to research to be presented during the Pediatric Academic Societies 2018 annual meeting.

During the final weeks of pregnancy, the fetal brain undergoes an unprecedented growth spurt, dramatically increasing in volume as well as structural complexity as the fetus approaches full term.

One in 10 infants born in the U.S. in 2016 was born before 37 weeks of gestation, according to the Centers for Disease Control and Prevention. Within this group, very low birthweight preemies are at significant risk for growth failure and neurocognitive impairment. Nutritional support in the neonatal intensive care unit (NICU) helps to encourage optimal brain development among preterm infants. However, their brain growth rates still lag behind those seen in full-term newborns.

"Few studies have investigated the impact of early macronutrient and caloric intake on microstructural brain development in vulnerable pre-term infants," says Katherine Ottolini, lead author of the Children's-led study. "Advanced quantitative magnetic resonance imaging (MRI) techniques may help to fill that data gap in order to better direct targeted interventions to newborns who are most in need."

The research team at Children's National Health System enrolled 69 infants who were born younger than 32 gestational weeks and weighed less than 1,500 grams. The infants' mean birth weight was 970 grams and their mean gestational age at birth was 27.6 weeks.

The newborns underwent MRI at their term-equivalent age, 40 weeks gestation. Parametric maps were generated for fractional anisotropy in regions of the cerebrum and cerebellum for diffusion tensor imaging analyses, which measures brain connectivity and white matter tract integrity. The research team also tracked nutritional data: Grams per kilogram of carbohydrates, proteins, lipids and overall caloric intake.

"We found a significantly negative association between fractional anisotropy and cumulative macronutrient/caloric intake," says Catherine Limperopoulos, Ph.D., director of Children's Developing Brain Research Laboratory and senior author of the research. "Curiously, we also find significantly negative association between macronutrient/caloric intake and regional brain volume in the cortical and deep gray matter, cerebellum and brainstem."

Because the nutritional support does contribute to cerebral volumes and white matter microstructural development in very vulnerable newborns, Limperopoulos says the significant negative associations seen in this study may reflect the longer period of time these infants relied on nutritional support in the NICU.

Pediatric Academic Societies 2018 annual meeting presentations:

Sunday, May 6, 2018

"Impact of early nutrition on microstructural brain development in very low birth weight infants."
4:15 p.m. to 4:30 p.m. (ET)
Katherine Ottolini; Nickie Andescavage, M.D., Attending, Children's Neonatal-Perinatal Medicine; Kushal Kapse; Catherine Limperopoulos, Ph.D., director, Children's Developing Brain Research Laboratory

Antibody Drug Conjugates (ADCs) are relatively new anti-cancer drugs. They consist of an antibody to which a cell-killing molecule (chemotherapy) is attached. Antibodies can recognize and bind to certain receptors (the 'hands' on the outside of a cell) in a very targeted way. The antibody in an ADC is designed to adhere exclusively to receptors that are characteristic of a tumor cell. The chemotherapy drug is not released until the receptor has brought the entire structure into the cell, and then the chemotherapy drug can do its job.

ADCs are currently already used for the treatment of lymphoma and metastatic breast cancer. "These ADCs work very well," says Marc Robillard of Tagworks Pharmaceuticals, a company based at Radboud university medical center. "But for many other tumors, including colon cancer and ovarian cancer, this method is not yet applicable. The problem is that there are not many suitable cancer-specific receptors that automatically drag such an ADC into the cell, and if the ADC gets stuck on the outside, the chemotherapy drug will not be released and therefore can't do its job."

Chemotherapy drug released

It is vital to ensure that the chemotherapy drug is also released if the ADC remains on the outside of the tumor cells. To achieve this objective, Tagworks has designed a smart variant of the ADCs. The ADC is injected and then binds to the receptors on the tumor cells. After a day or two, the tumor is filled with these ADCs. So far, this is nothing new. Robillard: "Our innovation is that we inject a second component that 'click-releases' the chemotherapy drug from the ADC. As a result, a large quantity of chemotherapy is released very quickly, attacking the tumor. This method will hopefully enable us to treat many more types of cancer."

Effective in mice

The first results of this new 'click-to-release' method in mice have now been published in Nature Communications. Robillard: "We studied ovarian cancer and an aggressive form of colon cancer. In both cases we observed a pronounced anticancer effect. For control purposes, we also applied a 'traditional' ADC, i.e., without the second component that causes the chemotherapy drug to release, but this approach had no therapeutic effect in these forms of cancer."

Cooperation

In Nijmegen, Tagworks collaborates with a variety of research groups, Technology Centers and Research Facilities, which have been specifically set up for cooperation with the business community, including the Radboudumc Technology Center for Mass Spectrometry. In addition, Tagworks cooperates with specialized small and medium-sized enterprises that are also co-authors of the publication. According to Robillard, this illustrates the importance of cooperation. "Developing new drugs for cancer is very complex and requires the expertise of specialists. No party can do this by itself. I believe this result is a fine example of how you can maximize the innovative power of small and medium-sized businesses by joining forces and connecting with the advanced facilities and high-quality knowledge of institutions such as Radboud university medical center and Radboud University."