Body

A comprehensive study of monkeys given the breast cancer drug letrozole reveals side effects that impact the brain. Published in JNeurosci, the research establishes the common marmoset as an important nonhuman primate model for studying the effects of estrogen-reducing treatments on the nervous system.

Letrozole is used to prevent breast cancer recurrence by interfering with the production of estrogens. Although side effects such as mood disturbances and memory issues have been reported in both humans and animals, little is known about how the drug impacts the brain.

Nicole Gervais and colleagues administered Letrozole to male and female marmosets via pudding for four weeks and observed many of the same behavioral changes, including hot flashes and increased anxiety, experienced by women receiving similar treatment. Letrozole also compromised the function of neurons in the hippocampus and impaired spatial memory. Together these findings emphasize the need for further investigation of breast cancer treatments and their effects on the brain.

Prostate cancer is the second prevent type of cancer that exists. Prostate cancer is usually a slowly progressing disease but it can sometimes manifest as an aggressive cancer. Prostate imaging is the primary way to diagnose the disease and this necessity drives its demand in the clinic.

This review covers traditional and new imaging methods for screening the prostate gland for the occurrence of neoplasms. A special focus is given to Prostate Specific Membrane Antigen (PSMA), Bombesin (BN) and Androgen Receptor (AR) targeted imaging using Positron Emission Tomography (PET) and Single Positron Emission Computed Tomography (SPECT) based on 99mTc and other radiotracers.

The reviewers conclude that androgen receptor based imaging is the future direction for prostate specific imaging and can be a better way to diagnose prostate cancer using non-steroidal antiandrogen agents.

A homeless individual is one who lacks fixed and reliable housing, and approximately 553,000 people fit that description on any given night in the United States. A new retrospective cohort study led by investigators from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital examines patterns, causes and outcomes of acute hospitalizations between 2007 and 2013 for homeless individuals and non-homeless control groups in three populous and diverse U.S. states: Florida, California and Massachusetts. Data suggest a rise in acute hospital use among homeless individuals for mental illness and substance use disorder. The results were published in the journal Medical Care.

"The homeless population is aging, and the rate of hospitalizations for homeless individuals is increasing," said lead author Rishi Wadhera, MD, an investigator in the Smith Center for Outcomes Research in Cardiology at BIDMC. "Although there has been a recent push to establish better policy and public health measures to improve the health of homeless adults, few studies have examined the patterns and causes of hospitalizations in this population. We found that hospitalizations among homeless adults tend to be for a very different set of conditions than non-homeless adults, even after accounting for differences in demographics."

To examine these trends, hospital discharge data was acquired from Massachusetts and Florida between 2001 and 2013 and from California between 2007 and 2011. This information came from the State Inpatient Databases (SID) of the Healthcare Cost and Utilization Project, created by the Agency for Healthcare Research and Quality. This dataset includes information such as homeless status, billing, demographics, and diagnoses. Hospitalization costs were determined by applying American Hospital Association cost-to-charge ratios to the total hospital charges provided in the SID.

Overall, the researchers analyzed more than 185,000 hospitalizations for homeless individuals and 32 million hospitalizations for non-homeless individuals. Between 2007 and 2013 (2011 for Calif.), acute hospitalizations for homeless individuals increased in all three states. Massachusetts experienced an increase from 294 to 420 per 1,000 homeless individuals, Florida increased from 161 to 240/1,000, and California grew from 133 to 164/1,000. Homeless adults were more often white (62 percent), male (76.1 percent), around 46 years old, and either uninsured (41.9 percent) or insured by Medicaid (31.7 percent).

The researchers found that reasons for hospitalization among the two groups differed starkly. More than 50 percent of hospitalizations among homeless individuals were related to mental illness and substance use disorder, while these conditions explained less than 20 percent of hospitalizations among demographically comparable non-homeless individuals. Homeless adults also had a longer mean length of stay (6.5 vs. 5.9 days). However, homeless individuals had lower in-hospital mortality rates (0.9 percent vs. 1.2 percent) and lower mean costs per day ($1,535 vs. $1,834) than the comparable non-homeless control group.

"Some states, such as Massachusetts, have expanded Medicaid eligibility, which has increased rates of insurance among homeless individuals and improved access to care; this could have led to greater use of hospital services," said Wadhera, who is also a cardiology fellow in the Cardiovascular Division at Brigham and Women's Hospital. "The increase in hospitalizations could also reflect more concerning trends. The opioid epidemic has disproportionately impacted homeless population, and a repercussion of this may be an increase in acute hospitalizations. It is also possible that these patterns suggest inadequate outpatient care for homeless individuals, and that we need to do a better job of providing more consistent, reliable outpatient care to this population."

"There is an urgent need to reduce financial and nonfinancial barriers to the use of ambulatory care, for behavioral health services in particular, to improve long-term management of physical and mental illness for homeless individuals," said senior author Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. "We need better longitudinal data and further studies to understand how Medicaid expansion and other policy initiatives affect the health of this highly vulnerable population."

CHICAGO --- Northwestern Medicine scientists have discovered two successful therapies that slowed the progression of pediatric leukemia in mice, according to three studies published over the last two years in the journal Cell, and the final paper published Dec. 20 in Genes & Development.

When a key protein responsible for leukemia, MLL, is stabilized, it slows the progression of the leukemia, the most recent study found. The next step will be to combine the treatments from the past two years of research into a pediatric leukemia "super drug" to test on humans in a clinical trial.

The survival rate is only 30 percent for children diagnosed with MLL-translocation leukemia, a cancer that affects the blood and bone marrow. Patients with leukemia have a very low percentage of red blood cells, making them anemic, and have approximately 80 times more white blood cells than people without cancer.

"These white blood cells infiltrate many of the tissues and organs of the affected individuals and is a major cause of death in leukemia patients," said senior author Ali Shilatifard, the Robert Francis Furchgott Professor of Biochemistry and Molecular Genetics and Pediatrics, the chairman of biochemistry and molecular genetics and the director of Northwestern's Simpson Querrey Center for Epigenetics. "This is a monster cancer that we've been dealing with for many years in children."

There are several types of leukemia. This research focused on the two most common found in infants through teenagers: acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).

For the past 25 years, Shilatifard's laboratory has been studying the molecular function of MLL within its complex known as COMPASS (Complex Proteins Associated with Set1). Most recently, it was demonstrated that COMPASS components are one of the most frequently identified mutations in cancer. The next step of this work will be to bring the drug to a clinical trial setting, which Shilatifard said he hopes will happen in the next three to five years.

"I've been working on this translocation for more than two decades, and we're finally at the point where in five to 10 years, we can get a drug in kids that can be effective," Shilatifard said. "If we can bring that survival rate up to 85 percent, that's a major accomplishment."

Earlier work from Shilatifard's laboratory published in Cell in 2018 identified compounds that could slow cancer growth by interrupting a gene transcription process known as "Super Elongation Complex" (SEC). It was the first compound in its class to do this.

This MLL stabilization process discovered in the most recent paper could potentially work in cancers with solid tumors, such as breast or prostate cancer, said first author Zibo Zhao, a postdoctoral research fellow in Shilatifard's lab.

"This opens up a new therapeutic approach not only for leukemia, which is so important for the many children who are diagnosed with this terrible cancer, but also for other types of cancers that plague the population," Zhao said.

"The publication of these four papers and the possibility of a future human clinical trial could not have happened if it weren't for the cross-disciplinary collaboration at Northwestern," Shilatifard said.

December 21, 2018 - At least for brief periods, overlapping surgery is safe for patients undergoing outpatient or "same-day" orthopaedic surgery procedures, reports a study in the December 19, 2018 issue of The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

The study adds to a growing body of evidence showing no increase in the risk of complications for patients undergoing overlapping orthopaedic surgery - procedures where a single surgeon is the primary surgeon for more than one patient simultaneously in separate operating rooms. "Our data suggest that briefly overlapping surgery is a safe practice in the ambulatory orthopaedic surgery center," comments lead author Charles A. Goldfarb, MD, of Washington University School of Medicine, St. Louis.

New Data on Safety of Overlapping Ambulatory Orthopaedic Surgery

Dr. Goldfarb and colleagues compared the outcomes of overlapping versus nonoverlapping surgery at their university-affiliated orthopaedic ambulatory surgical center (ASC). In overlapping surgery, the attending surgeon is present for "critical" parts of the procedure, leaving another surgeon to perform noncritical portions - typically skin closure. Overlapping surgery is commonly used to maximize operating room efficiency.

Although this practice is not new, it has become controversial in the wake of recent high-profile media reports. Most previous studies of overlapping surgery have focused on inpatient procedures, performed on hospitalized patients.

The analysis included more than 22,000 outpatient orthopaedic procedures performed between 2009 and 2015. The patients underwent a wide range of elective surgeries, including knee, hand, and shoulder procedures. No joint replacement or spine operations were included in the analysis.

Twenty-three percent of the procedures were overlapping surgeries. Median overlap time in these procedures was eight minutes. According to this ASC's policy, another attending surgeon -not a resident or fellow in training - was present during the overlapping portion of the procedure.

The overall complication rate (morbidity) was 0.66 percent in the overlapping surgery group and 0.54 percent in the nonoverlapping surgery group. After the authors adjusted for other factors, the morbidity risk was not significantly different between groups. The same was true for all individual complications considered: surgical site infections, noninfection surgical complications, and transfer to an inpatient hospital.

Anesthesia and overall surgery times were slightly longer in the overlapping surgery group, but these surgical factors did not increase the risk of complications.

Most studies of orthopaedic and other types of overlapping surgery have reported no difference in complications, compared to non-overlapping surgery. A recent study in Journal of Bone and Joint Surgery found no increase in complication rate among inpatients undergoing overlapping orthopaedic surgery, compared to nonoverlapping cases.

The researchers note that although this study includes a large number of outpatient orthopaedic surgery cases, the data represent the experience of only one ASC. Nevertheless, the results suggest that overlapping orthopaedic surgery can be safely carried out in ambulatory surgery settings - at least as practiced at the authors' institution.

Dr. Goldfarb and colleagues conclude, "Practitioners, payers, and patients should be reassured that limited overlapping surgery is appropriate and reasonable in this setting."

Click here to read "Complications Following Overlapping Orthopaedic Procedures at an Ambulatory Surgery Center."

DOI: 10.2106/JBJS.18.00244

PISCATAWAY, NJ - College students who binge drink are frequently posting on social media while intoxicated and show signs of social media "addiction," according to a new study.

Students later may regret their drinking-related posts and experience other negative consequences from combining social media and alcohol use. The research appears in the latest edition of the Journal of Studies on Alcohol and Drugs.

"During these times when young students are feeling disinhibited by alcohol, they may be even more likely than usual to post inappropriate material without considering the future impact," says lead researcher Natalie A. Ceballos, Ph.D., of the Department of Psychology at Texas State University in San Marcos. "In some cases, these sorts of mistakes have even influenced college admission and later job applications."

Further, friends who view their posts of heavy drinking may then be more likely to perceive intoxication as exciting and fun, Ceballos's group notes.

However, social media also may prove to be an avenue for prevention efforts among student drinkers.

"While college students' reliance on social media has been identified as a risk factor for alcohol-related problems," Ceballos says, "it might also present an opportunity for innovative interventions."

Because social media use has exploded in recent years and trends among young people have changed so quickly, the researchers sought to define exactly what platforms college students are using and how they are using them, particularly in relation to alcohol use.

To do this, the research group recruited 425 undergraduate students, ages 18 through 25, asking about students' alcohol use, including the quantity and frequency with which they drank and if they had ever "binged" (in the study, defined as ever having five drinks at one time for men and four or more for women).

The researchers also queried about students' use of social media, including Snapchat, Instagram, Facebook and Twitter, and whether students posted social media messages while drinking and while intoxicated. Students then were asked about their social media "addiction" -- that is, if they experienced negative consequences from their social media use. (Currently, however, there is no official psychiatric diagnosis of addiction to social media.)

Compared with students who had never binged, student binge drinkers were more likely to have posted on any social media platform while drinking and while intoxicated. Binge drinkers also showed greater "intensity" toward social media (more emotional investment that allowed social media to become part of their identities) and a non-statistically significant trend toward being more addicted to social media. They also used more social media platforms than non-binge drinkers.

"These findings suggest that, in terms of common brain reward mechanisms, perhaps when students get a positive response on social media, this might be "rewarding" to them in a way that is similar to other addictive behaviors, and then over time they get 'hooked'," Ceballos notes.

However, social media may turn out to be a good platform for interventions to reduce heavy drinking. Studies of pathological gambling have shown that harm-reduction messages delivered "in the moment" can help disrupt this behavior. The research group suspects that similar interventions, timed while students are socially drinking but before significant impairment occurs, "might be useful in preventing an episode of social drinking from escalating into a binge," according to the study.

"As for what form this intervention might take, we're not really there yet," Ceballos reports. "However, I believe that pairing recent advances in alcohol biosensor technology (to detect a drinking episode when it occurs) and ecological momentary interventions (to reach out to clients via mobile phones 'in the moment') could make this type of intervention a reality in the very near future."

Knowing which social media platforms students are using is important for such interventions. The study showed that Snapchat and Instagram are the most popular sites used by college students, followed by Facebook and Twitter. "Facebook is waning in popularity among younger users," the researchers write, "whereas Snapchat is becoming more popular." Therefore, they note, interventions should be geared toward the more frequently used sites. However, binge drinkers, specifically, used Snapchat and Facebook more frequently.

Research carried out by scientists at the University of Southampton has shown that simple tests in GP surgeries could potentially double the diagnosis rate of liver disease where patients are not displaying any symptoms.

Chronic liver disease is an escalating problem both in the United Kingdom and worldwide. In the UK mortality rates have risen sharply and it is now the third most common cause of early death. The disease progresses silently, with few symptoms appearing before serious liver scarring (known as cirrhosis) develops. The increase is predominantly due to alcohol, however the increasing prevalence of non-alcohol related fatty liver disease both in the UK and elsewhere is also of concern.

The objective of this research, published today in PLOS ONE was to identify previously undiagnosed liver disease within Primary Care using a nurse-led specialist liver clinic. Ten GP practices were allocated to either intervention (where patients were tested by specialist liver nurse) or care as usual. Participants recruited to the intervention practices had a full liver assessment which involved a simple examination; taking blood samples and measuring liver stiffness using a portable FibroScan®402 ultrasound device, a machine that offers a non-invasive liver assessment. All participants had their case notes reviewed by a consultant hepatologist and ascribed as 'no fibrosis', 'liver warning', 'progressive fibrosis' or 'probable cirrhosis'.

Of the 910 participants seen in the nurse led clinic nearly half were found to have some form of liver disease. 44 of these patients (4.8%) had probable cirrhosis, 141 (15.5%) had progressive fibrosis, and 220 (24.2%) had liver warnings. Overall the nurse led clinic diagnosed twice as many cases as the care as usual clinics.

Lead Author Dr Magdy El-Gohary from the School of Medicine at the University of Southampton said:

"Incorporating a liver nurse within Primary Care was simple to arrange and yielded a much higher number of new diagnoses of liver disease compared to usual care. The next step is to roll this service on a larger scale so that we can show whether early diagnosis is able to prevent the liver disease developing to the stage where an emergency admission to hospital is required."

The aim of this programme of work is to reduce the number of avoidable premature deaths from undiagnosed liver disease. Offering a specialist liver clinic within Primary Care means that patients can be assessed and diagnosed quickly and may reduce or halt the progression of liver disease.

Congenital heart disease (CHD) is the most common birth defect. And even with remarkable advances in care, it remains the leading cause of non-infectious death in infants.

CHD is the result of a complicated interplay between genetic and non-genetic, or "environmental," factors acting on the fetus. While the genetic contributors have become increasingly defined as was recently summarized in an American Heart Association Scientific Statement published in Circulation that was co-authored by Vidu Garg, MD, the environmental factors are an important area of investigation. One of those environmental factors is maternal hyperglycemia. In a comprehensive review recently published in Birth Defects Research, Vidu Garg, MD, and Madhumita Basu, PhD, offer a "state of the science" look at the impact of maternal diabetes, and potential gene-environmental influences in that context, on fetal heart development.

"Many epidemiological studies have demonstrated a strong correlation between maternal diabetes and increased risk of CHD in babies born to affected mothers," says Dr. Garg, Director of the Center for Cardiovascular Research in The Research Institute at Nationwide Children's Hospital. "And many factors, including the type of diabetes, other environmental influences, and potentially certain genetic predispositions can influence which CHD subtypes are likely to develop."

For example, type 1 and type 2 diabetes are linked with specific CHD subtypes. Babies born to mothers with type 1 diabetes had a greater association with conotruncal malformations and atrioventricular septal defects. Those born to mothers with type 2 diabetes had the highest risk of heterotaxy and left ventricular outflow tract obstructive malformations. Both types of maternal diabetes also increased the risk of other types of CHD in the infants, including right ventricular outflow tract obstructive malformations and atrial and ventricular septal defects, albeit to lower levels.

The gestational age at which the fetus is exposed to maternal diabetes is also important. Maternal diabetes before conception and during the first trimester is associated with diabetic embryopathy in the fetus, which affects the heart, great vessels and neural tube. When maternal diabetes develops in the latter half of pregnancy, it is associated with fetal macrosomia, cardiomyopathy, increased incidence of perinatal complications and mortality.

Diabetes is a complex disease, with abnormal homeostasis of multiple components in metabolism that ultimately lead to the overall metabolic syndrome. Despite this complexity, hyperglycemia has been determined to be the primary teratogen in all forms of diabetes. How exactly maternal hyperglycemia causes birth defects in infants is still unknown, however-

"The underlying molecular mechanisms by which alterations in maternal glucose levels act to cause the congenital heart defects are actively under investigation in our lab and others," says Dr. Basu, Research Assistant Professor in the Garg lab in the Center for Cardiovascular Research. "We suspect that this gene-environment interaction is related to the dysregulation of specific epigenetic processes in the fetal heart."

According to the review, the current evidence points to the following processes and pathways:

Reactive oxygen species (ROS)-mediated effects on cardiac morphogenesis

Alterations of signaling pathways critical for cardiac development, including Wnt, Notch, Hif1α and Tgfβ at the transcriptional and translational levels in response to maternal hyperglycemia and associated oxidative stress

Potential changes in the cell-type specific epigenetic landscape in the setting of maternal diabetes.

"We think that maternal diabetes can ultimately affect the levels at which genes are expressed during fetal development," says Dr. Garg.

"Teasing out the cellular and molecular changes in the developing heart during hyperglycemic conditions is possible with newer high throughput genomic technologies," he adds. "Doing so will enable us to define these perturbations mechanistically, and even down to a single-cell level."

Unlocking these cellular secrets opens the door to potential interventions to reduce the risk of the fetus developing CHD.

"Ultimately, our hope is to translate these findings by screening mothers with environmental risk factors and their children for genetic variants in cardiac regulatory genes," says Dr. Basu. "We predict that these genetic variants will serve as risk factors for the development of CHD in high-risk populations, such as those with maternal diabetes."

Hundreds of new genes linked to blindness and other vision disorders have been identified in a screen of mouse strains. Many of these genes are likely important in human vision and the results could help identify new causes of hereditary blindness in patients. The work is published Dec. 21 in Nature Communications Biology.

"This is extremely valuable for people with hereditary eye disease," said Ala Moshiri, associate professor of ophthalmology and vision science in the University of California, Davis, School of Medicine and Eye Center. "The whole ophthalmic community is going to start using these data."

The results are the latest to come from the International Mouse Phenotyping Consortium, of which UC Davis' Mouse Biology Program is a founding member. The goal of the consortium is to identify a function for every gene in the mouse genome, by creating lines of "knockout" mice that lack a single specific gene and screening them for their effects. Consortium researchers have previously identified a set of genes essential to life, genes linked to deafness and even those linked to hereditary bad breath.

To date, the consortium has generated more than 7,000 strains of gene-knockout mice, of which 4,364 have been characterized across 11 organ systems.

"The data being generated by the IMPC is accelerating the application of genomics in clinical medicine," said Kent Lloyd, director of the UC Davis Mouse Biology Program and principal investigator of the Knockout Mouse Production and Phenotyping (KOMP2) project at UC Davis.

261 new genes linked to blindness

The team led by Bret Moore, resident at the UC Davis Veterinary Medical Teaching Hospital, Moshiri and colleagues combed the consortium database for genes linked to eye and vision defects. They identified 347 genes, of which 86 were either well-established as involved in eye disease or were associated with vision in some way. Three-quarters of the genes -- 261 -- were not previously known to cause eye disease in any species.

"In 2018, if someone has a form of hereditary blindness, we can identify the cause 50 to 75 percent of the time," Moshiri said. "In the remaining cases, we know the mutation is there but we don't know where to look. Now eye centers that do DNA sequencing can call back patients and screen them for these new genes."

While the mouse and human genomes clearly differ, most human genes have an analogous counterpart in mice. The UC Davis team is collaborating with eye centers at Baylor College of Medicine in Houston and the University of Iowa to check the newly identified mouse genes against their human equivalents, Moshiri said.

The new genetic information could also enable new therapies for hereditary eye disease. In 2017, the FDA approved the first gene therapy for any disease -- treating hereditary blindness caused by a defect in the retinal gene RPE65.

"We expect that more and more of these genetic diseases will be treatable," Moshiri said.

Chapel Hill, N.C. - Chinese gay men who were offered a free screening for gonorrhea and chlamydia and then asked to donate to the testing of another man were 48 percent more likely to get tested than men who were offered the standard of care. Researchers at the University of North Carolina at Chapel Hill's UNC Project-China site said their findings prove this pay-it-forward model could be used to expand other infectious diseases screening, like HIV testing, among gay men in China. Their results were published in The Lancet Infectious Diseases.

"We found that a pay-it-forward model substantially increased test uptake compared to the standard of care," said Joseph Tucker, M.D., Ph.D., the study's co-author and director of UNC Project-China. "The program reached many untested men and identified new positive cases."

Gonorrhea and chlamydia are common sexually transmitted diseases (STDs), which spread rapidly and silently through communities of gay men. The prevalence of gonorrhea and chlamydia among Chinese gay men is as high as 10-20 percent. These two STDs are known to increase the risk of HIV acquisition and transmission, but are often asymptomatic. Previous studies suggest that less than half of gay men have ever received a gonorrhea or chlamydia test.

This study took place at two sites in Guangzhou, China. One was an STD clinic for gay men and the other was a local gay community-based organization. At both of the program sites, gay men who were waiting for HIV and syphilis testing were offered dual gonorrhea/chlamydia testing. In the pay-it-forward group, each man's gonorrhea and chlamydia test fees were covered by a combination of the initial funding pool from the program organizers and the donations from previous participants. Each man was told donating for future men to be screened was optional and a donation of any amount was appreciated. In the standard of care group, men were offered gonorrhea and chlamydia testing at the standard patient price of $24USD.

In total, 408 men were screened for gonorrhea and chlamydia. This was the first gonorrhea or chlamydia test for 86 percent of the men. Of the 203 men in the pay-it-forward group, 54 percent opted to be tested. Eighty-nine percent of the men in the pay-it-forward group donated some amount to the testing of another man. Of the 205 men in the standard of care group, only 6 percent agreed to be screened.

"Our study identified a high percentage of previously untested gay men, highlighting the low test uptake and the need for improved gonorrhea and chlamydia testing for Chinese gay men," Tucker said. "A pay-it-forward testing program may be a promising strategy for creating a sustainable program for integrated HIV/STD testing among key populations."

Three papers from research teams led by a Massachusetts General Hospital (MGH) physician examine the current readiness of U.S. emergency departments (EDs) to care for children and describe an initiative that led to the appointment of a Pediatric Emergency Care Coordinator (PECC) - a step considered the single best intervention to improve pediatric emergency care - in all Massachusetts EDs. The three reports appear in the December issue of Academic Emergency Medicine.

"According to the 2007 Institute of Medicine (IOM) report on pediatric emergency care, not all EDs are prepared to adequately care for children. Many lack essential supplies for managing pediatric emergencies, and treatment patterns can vary widely across providers," says Carlos Camargo, MD, DrPH, of the MGH Department of Emergency Medicine, corresponding author of all three papers. "Our three papers describe the national ED landscape and provide new information about potential approaches to improving pediatric emergency care."

All three papers are based on data from the annual National Emergency Department Inventory (NEDI)-USA survey, sent to the directors of the 5,273 non-federal, non-specialty U.S. EDs open in 2015 and the 5,375 U.S. EDs open in 2016.

Pediatric areas in emergency departments

The 2015 survey asked whether each ED included a separate pediatric area, and only 426 (10 percent) of the 4,407 responding general EDs - those that treat both adults and children - indicated having such an area. Pediatric areas were most commonly reported in larger EDs in the Northeast or the South; and while 66 percent of general EDs with pediatric areas reported having at least one PECC, only 11 percent of general EDs without a pediatric area had at least one PECC.

In 2017, a second survey was sent to 130 of the EDs that indicated having a pediatric area in their response to the 2015 survey, asking specific questions about the structure and staffing of these areas. Of 105 responding EDs, 11 indicated they did not actually have a pediatric area, which the authors note points to the need for better definition of a pediatric ED area. Of those with a pediatric area, 93 percent reported having designated beds for pediatric patients, and 74 percent reported having at least one pediatric emergency physician on staff.

Pediatric emergency telemedicine services

A second study began with questions on the 2016 NEDI-USA survey regarding whether EDs received pediatric telemedicine services. Telemedicine allows clinicians in one ED - often with limited facilities and services - to consult with specialists at another ED or hospital who may assist with diagnosis, recommend treatment or facilitate transfers. Provision of pediatric critical care telemedicine to rural hospital EDs has been associated with higher physician-rated quality of care and a reduced risk of medication errors. The 337 EDs (8 percent of all) that indicated receiving pediatric telemedicine services during 2016 were less likely to be in urban areas, and more than half were in critical access hospitals - small, rural hospitals deemed essential providers for their communities.

Of the EDs that received pediatric telemedicine in 2016, 130 were sent a follow-up survey regarding their use of telemedicine. Challenges to the use of pediatric telemedicine indicated in their responses included concerns about the process - such as interrupting providers' workflow - and the technology. A frequently cited obstacle was the need to remind staff members that telemedicine was an available resource for pediatric care. The authors note that the fact that EDs using pediatric telemedicine tended not to have either a pediatric emergency physician or a pediatrician assigned to the ED suggested that telemedicine was being used to fill a gap in pediatric ED services.

Increasing the appointment of Pediatric Emergency Care Coordinators

Pediatric Emergency Care Coordinators (PECCs) are health professionals - physicians, nurses or others - who manage pediatric care in their EDs and help to educate their colleagues on emergency care for children. Although the 2007 IOM report included appointment of a PECC among its key recommendations, less than 20 percent of EDs responding to the 2015 and 2016 NEDI-USA surveys reported having a PECC. In light of that information and the fact that many EDs have limited resources for pediatric care, Camargo and colleagues from the MGH, Boston Medical Center and Floating Hospital for Children/Tufts Medical Center initiated a grassroots intervention to encourage appointment of at least one PECC in every ED in Massachusetts.

With the endorsement of the Massachusetts College of Emergency Physicians, from 2017 to 2018 the team contacted the directors of all 73 EDs in the state. Initial emails were followed up with phone calls addressing both the IoM report and efforts of the National Pediatric Readiness Project to improve pediatric emergency care. Acknowledging that most general EDs may not have the funds required to support even a part-time PECC, team members advocated identifying at least one staff member who could volunteer two to four hours a month to improving pediatric care in their ED.

As a result of this intervention, the percentage of EDs with an appointed PECC increased from around 30 percent in 2016, to 85 percent in 2017, and 100 percent in 2018 - making Massachusetts the first state with assigned PECCs in all EDs. While most newly-assigned PECCs spend from one to fours hours a month in that role, the paper's authors indicate that many improvements to pediatric emergency care can be made without substantial resources or time. The team also created the MassPediatricToolkit website, which offers educational and other information to support PECCs throughout the state.

"We believe an intervention like this one could have similar results elsewhere, and we have started to replicate the project in a few volunteer states," says Camargo. "Although each state is different, we estimate that around 10 states will have PECCs in at least 80 percent of their EDs by the end of 2019. While the impact of PECCs on actual clinical outcomes requires further study, we are confident that even having a volunteer professional focusing on improving pediatric emergency care is better than not having anyone doing so."

A professor of Emergency Medicine at Harvard Medical School, Camargo adds, "Anyone can quickly find the distance and directions from their current location - or a searched location - to the closest EDs by using the publicly available EMNet findERnow smartphone app, which is available for both iPhone and Android phones. We just updated the app to provide the option of sorting the closest EDs by current driving time - including traffic! With a 99-cent subscription to the pediatric version, app users can also quickly see whether their ED has a pediatric area or a PECC." All three studies were supported by a grant from the R Baby Foundation.

Exercise may be as effective as prescribed drugs to lower high (140 mm Hg) blood pressure, suggests a pooled analysis of the available data, in what is thought to be the first study of its kind, and published online in the British Journal of Sports Medicine.

But there are no direct head to head comparative trials of exercise and blood pressure lowering drugs, and the numbers of participants in some of the included studies were relatively small, caution the researchers.

While promising, the findings shouldn't persuade patients to ditch their blood pressure lowering drugs in favour of an exercise regimen just yet, although patients might want to boost their physical activity levels, advises the lead study author in a linked podcast.

Exercise can lower systolic blood pressure--the amount of pressure in the arteries when the heart is beating and expressed as the top number in any blood pressure reading. But what isn't clear is how exercise compares with blood pressure lowering drugs, of which there are several types, as no direct head to head clinical trials have been carried out.

To get round this, the researchers pooled the data from 194 clinical trials looking at the impact of drugs on lowering systolic blood pressure and 197 trials looking at the impact of structured exercise, and involving a total of 39,742 people.

Structured exercise was categorised as: endurance, to include walking, jogging, running, cycling and swimming, and high intensity interval training; dynamic resistance, to include strength training--for example, with dumbbells or kettle bells; isometric resistance, such as the static push-up (plank); and a combination of endurance and resistance.

Three sets of analyses were done: all types of exercise compared with all classes of blood pressure lowering drugs; different types of exercise compared with different types of drug; and different intensities of exercise compared with different drug doses.

And finally, these analyses were repeated, but in a group of exercise trials that included only participants with high blood pressure, as most of these trials were of young healthy participants with normal blood pressure.

The results showed that blood pressure was lower in people treated with drugs than in those following structured exercise programmes.

But when the analyses were restricted to those with high blood pressure, exercise seemed to be just as effective as most drugs. What's more, the effectiveness of exercise increased the higher the threshold used to define high blood pressure--that is, anything above 140 mm Hg.

The researchers also found "compelling evidence that combining endurance and dynamic resistance training was effective in reducing [systolic blood pressure]."

But structured exercise trials were fewer and smaller than those for drugs, they caution.

The researchers point out that prescriptions for drugs to lower blood pressure have risen sharply in recent years. In England alone the number of adults prescribed them increased by 50 per cent between 2006 and 2016.

This trend is likely to continue, say the researchers, given that major clinical practice guidelines have recently lowered the threshold for high systolic blood pressure to 130 mm Hg.

But substituting exercise for drugs may be challenging as people with high blood pressure often have several long term conditions, and an estimated 40 per cent of adults in the US and many European countries are physically inactive, they say.

"We don't think, on the basis of our study, that patients should stop taking their antihypertensive medications," says lead author Dr Huseyin Naci, Department of Health Policy, London School of Economics and Political Science, in a linked podcast.

"But we hope that our findings will inform evidence based discussions between clinicians and their patients," he adds.

As to whether doctors should be handing out prescriptions for exercise to patients with high blood pressure, there are some issues to consider, he suggests.

"It's one thing to recommend that physicians start prescribing exercise to their patients, but we also need to be cognisant of the resource implications and ensure that the patients that have been referred to exercise interventions can adhere to them and so really derive benefit," he emphasises.

Please contact the BJC press office for the full paper or with any other questions on 0203 469 8300, out of hours, 07050 264 059 or bjcpress@cancer.org.uk. Scientists can be directly contacted regarding media interviews using the contact details provided.

Please reference the British Journal of Cancer in any media activity.

Paper: Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: Joint analysis of three national cohorts
Corresponding author: Dr. Marta Roman
Contact: mroman@parcdesalutmar.cat

Author summary: Most European countries invite women ages 50 to 69 years for a screening mammography every two years with the goal to diagnose asymptomatic breast cancers in an early stage. It is known that one in every five women screened on a regular basis during this age range will be recalled for further assessments due to mammographic abnormalities where malignancy is finally ruled out, the so called false-positive screening result.

In our study, we found that women who experience a false-positive result have a two-fold risk of being diagnosed with a screen-detected cancer or interval breast cancer later in life. And most importantly, they remained at an elevated risk over a decade after the false-positive result. In addition, women who experienced a second false-positive result had a four-fold increase in risk.
Women with mammographic abnormalities leading to a false-positive result have a biological susceptibility to develop future breast cancer. This information should be considered to design personalized screening strategies based on individual risk.
Post embargo link: https://doi.org/10.1038/s41416-018-0358-5
DOI: s41416-018-0358-5

Paper: Whole colon investigation versus flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study
Corresponding author: Dr. Amanda Cross
Contact: Imperial press office - Faculty of Medicine
Ryan O'Hare +44 (0)20 7594 2410, r.ohare@imperial.ac.uk
Kate Wighton (Monday/Wednesday/Friday), +44 (0)20 7594 2409, k.wighton@imperial.ac.uk

Author summary: A study of 7375 patients referred to hospital with suspected bowel cancer has shown that the type of diagnostic investigation may be decided by considering each patient's particular symptoms. Most patients with suspected bowel cancer are referred for colonoscopy, an examination of the inside of the entire bowel, placing enormous pressure on these NHS services. Flexible sigmoidoscopy is a quicker and safer examination of the inside of the lower part of the bowel only. This study revealed that patients with just rectal bleeding or increased stool frequency, but crucially, no anaemia or abdominal mass, had a low risk (0.4%) of having cancer in the upper part of the bowel; therefore, these patients could be examined safely by flexible sigmoidoscopy alone. If these criteria were incorporated into guidelines, the burden of colonoscopy on patients and the NHS would be alleviated and the risk of missing cancers in the upper part of the bowel minimised.
Post embargo link: https://doi.org/10.1038/s41416-018-0335-z
DOI: s41416-018-0335-z

Paper: Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations
Corresponding author: Professor Mitch Dowsett
Contact: Ben Kolbington, ICR media office
Telephone: 020 7153 5380
E-mail: ben.kolbington@icr.ac.uk

Author summary: Breast cancers (BCs) containing oestrogen receptor (ER) are diagnosed in >45,000 women per year in UK. Growth of most is driven by oestrogen such that recurrence and mortality from the disease is reduced by about 50% and 40%, respectively, by aromatase inhibitors (AIs) that stop oestrogen production. Nonetheless about 9,000 women with ER+ disease recur each year. To identify mechanisms of AI-resistance we assessed the genetic make up of BCs recurring in 41 AI-treated patients who had become resistant to an AI. While many genetic changes occurred at recurrence we found that each change was present in only a few patients which means that the genetic make-up of individual tumours needs to be characterised to allow fully personalised therapy. Mutation of the ER itself was the most frequent change; for the first time we showed the way in which this mutated-ER stimulated the tumour in the absence of oestrogen.
Post embargo link: https://doi.org/10.1038/s41416-018-0345-x
DOI: s41416-018-0345-x

Paper: Kidney stones and the risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Study
Corresponding author: Jeroen van de Pol, Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University
Email: jeroen.vandepol@maastrichtuniversity.nl
Telephone: +31 43 3883423

Author summary: Kidney stones linked to developing kidney cancer and cancer of the upper urinary tract. In this study, participants with a history of kidney stones were approximately 1.5 times more likely to develop kidney cancer and cancer of the upper urinary tract, compared to participants without kidney stones. By assessing the relationship between kidney stones and kidney cancer in more detail, the researchers found that participants with kidney stones were three times more likely to develop a less common kidney cancer subtype, called papillary renal cell carcinoma. This study was performed in the Netherlands Cohort Study in which over 120,000 participants with the age of 55-69 years were followed over a period of more than 20 years. In total, 608 participants developed kidney cancer and 152 participants developed cancer of the upper urinary tract. The findings of this research hint that a lifestyle, which may lead to the formation of kidney stones, may also play a crucial role in the development of specific cancer subtypes.
Post embargo link: https://doi.org/10.1038/s41416-018-0356-7
DOI: s41416-018-0356-7

Food allergies are associated with heightened levels of disease activity in patients with multiple sclerosis (MS), shows research published online in the Journal of Neurology Neurosurgery & Psychiatry.

Allergic patients had more relapses and greater odds of further nerve damage visible on MRI scans, the findings indicate.

Both genetic and environmental factors are thought to have a role in the development of MS, and known risk factors include high altitude, female gender, smoking, low vitamin D levels, Epstein Barr virus infection, and teen obesity.

But exactly how these factors might be linked to a heightened risk of developing the condition isn't clear. Allergies to pollen, dust mites, grass, and pets (environmental); drugs; and foods, such as dairy products, shellfish, wheat, and nuts, have been mooted as potential risk factors, but the research to date has been inconclusive.

To try and shed further light on potential triggers, the researchers assessed possible links between environmental, drug, and food allergies and MS flare-ups and evidence of disease activity on MRI (magnetic resonance imaging) scans in 1349 adults with the condition.

All the participants were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) in the US, and each of them provided detailed information on any food, drug, or environmental allergies and associated symptoms between 2011 and 2015.

Some 427 had no known allergy, while 922 had one or more allergies. Of these, 586 had an environmental allergy; 238 had a food allergy; and 574 were allergic to prescribed drugs.

The researchers added up the cumulative number of relapses each participant had had over the course of their illness, which averaged 16 years, and included any MRI scan evidence of disease activity as well as patients' own assessments of their symptom severity on their last clinic visit.

Initial analysis indicated that any allergy was associated with a 22 percent higher rate of cumulative disease bouts, but when potentially influential factors were taken into account, this difference disappeared.

However, when compared with those patients with no known allergy, food allergy was associated with a cumulative rate of disease flare-ups that was 27 percent higher, even after adjusting for potentially influential factors.

And any type of allergy was associated with higher odds of active disease, as detected on an MRI scan at the last clinic visit. But a food allergy was associated with more than twice the likelihood of active disease compared with no allergy.

No associations were observed for symptom severity or disability with any type of allergy.

This is an observational study, and as such, can't establish cause, added to which questionnaire responses were gathered at one point in time and relied on subjective assessment. And further research will be needed to confirm the findings.

But, say the researchers, there are one or two possible explanations for their observations. Food allergies might boost MS inflammatory activity: genetic data suggest that MS and various autoimmune diseases share some key features in common. And food allergies may also alter gut bacteria, which can produce neuroactive chemicals that affect the central nervous system.

"Our findings suggest that MS patients with allergies have more active disease than those without, and that this effect is driven by food allergies," write the researchers.

Respectful, inclusive practices in primary care clinics can significantly improve the health of low-income, marginalized people who may have previously experienced trauma or discrimination, a new study from the University of British Columbia and Western University has found.

"As health-care providers, we need to make everyone feel safe and comfortable when they walk into a clinic, and this is even more critical when the client is struggling with chronic health challenges or has experienced racism or prejudice, which may have stopped them from accessing health care in the past," said the study's lead researcher, Annette Browne, a professor of nursing at UBC.

These practices and policies--which can be as simple as greeting patients warmly and being genuinely concerned about what's important in their life--were the focus of a study on the impact of what the researchers call equity-oriented health care.

"Equity-oriented care means paying particular attention to those at greatest risk of poor health, and that typically means people who have been or remain the most marginalized in our society," said Browne.

"In practical terms, this means care that promotes harm reduction and respects their cultures and any experiences of trauma or violence. It's avoiding using judgmental language or making immediate assumptions about people. It means being interested in what else is going on and telling them they don't need to limit their visit to one problem alone."

For the study, researchers worked with four primary care clinics--two located in B.C. and two in Ontario--that serve large numbers of low-income groups, including Indigenous communities and people with complex health conditions.

They developed information and educational modules on providing equity-oriented care for the clinic staff. Each clinic then tailored the recommended practices and policies to fit their specific clinic and community needs. Afterwards, the team interviewed 395 individuals who had received care at the clinics.

"We found that participants felt comfortable about the care they received, and this in turn gave them more confidence in their ability to prevent and manage health problems," said Marilyn Ford-Gilboe, a professor in Western's Arthur Labatt Family School of Nursing, who co-led the study. "As these things happened, clients started reporting less pain, fewer depression and trauma symptoms, and improved quality of life."

The study, described recently in the Milbank Quarterly, is the first to show that providing equity-oriented health care predicts improvements in client health over time, said study co-author Colleen Varcoe, a professor of nursing at UBC.

"It's important to spread these types of health-care policies and practices more widely," said Varcoe, adding that primary care clinics are often people's first experience of the health-care system, and in many cases their only experience of it. "We should provide care that is mindful of their complex needs and histories of abuse, discrimination or trauma."

Researchers acknowledged that such a culture shift will require serious commitment from everyone involved. These kinds of changes in organizational culture can be disruptive and require extra planning by staff and leaders, but one way to start is by empowering clinic staff, suggested study co-lead Nadine Wathen.

"Clinic staff can be encouraged to take the initiative, even for things as basic as offering water or coffee in the waiting area," said Wathen, a professor in the faculty of information and media studies and the Arthur Labatt Family School of Nursing at Western. "By creating a culture that allows all staff members to advocate for the poorest and most marginalized individuals, we can start building a stronger health care system that ensures better health for all Canadians."