Body

Any time a pregnant woman presents in heart failure there are risks to both mother and baby. What does it take to protect the mother and her growing baby for the best possible outcome?

According to clinicians at Intermountain Healthcare in Salt Lake City, the key to survival is a multidisciplinary team-based approach, involving cardiac and maternal/fetal/newborn specialists -- who normally don't work together -- to team up to successfully save mom and baby.

In a case study presented at the American College of Cardiology Scientific Sessions in New Orleans on March 16, clinicians from the Intermountain Healthcare Heart Institute demonstrated how multiple medical teams across several different disciplines saved the life of both the mother and child after she was transferred from a smaller, local hospital.

"This case represents an enormous team effort and shows what it takes to see a critically-ill patient through the course of a unique and very challenging illness," said Kismet Rasmusson, DNP, FNP, of the Intermountain Healthcare Heart Institute.

The 36-year-old patient was 22 weeks pregnant when she came to an Intermountain hospital with shortness of breath, but no prior history of heart disease.

When doctors realized her heart was failing -- either from idiopathic cardiomyopathy with an unknown cause, or pregnancy associated cardiomyopathy -- she was transferred to the Intermountain Medical Center Heart Institute.

Cardiomyopathy leads to heart failure - a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body. About 6.2 million Americans have some type of heart failure, including women and men. According to a recent study in JAMA, maternal deaths in the US are high, with 10% of them related to cardiomyopathy, yet 60% of these are preventable with optimal treatments and coordinating care. That's exactly what this team had to offer this patient.

For seven weeks, the mother's care was managed by multiple teams, including heart failure cardiologists with the OB team. To develop a full plan of care, the rest of the team was assembled that included critical care physicians, interventional cardiologists, cardiothoracic surgeons, specialized nurses, cath lab and surgical staff, the staffs of Intermountain Medical Center's Thoracic ICU and Newborn ICU, pharmacists, advanced practice clinicians, and cardiovascular nurses. Social workers also supported both the patient and her spouse.

"We had two goals -- first to let the baby mature enough so the baby would have a better outcome, and second to keep the mom as stable as we could with her terribly weak heart muscle," said Rasmusson.

The baby was delivered at 29 weeks - about 11 weeks early. The team knew the delivery was risky and required advanced planning ahead of time. They held two meetings before the delivery date to discuss the sequence of events and roles of all team members, which included mechanically-supporting the mother's heart during a cesarean-section surgery in the cardiac catheterization lab.

The sequence of the complicated delivery included intubation, pulmonary artery catheter insertion, temporary mechanical support insertion, cesarean-section delivery, sending the baby to the newborn intensive care unit with her father, and post-delivery intensive care monitoring.

After delivery, the mother's heart remained very weak, so she had a left ventricle assist device (LVAD) implanted, which provided more durable mechanical support for her heart and served as a bridge to a heart transplant, which she received eight months after delivery.

The baby is now nearly five years old, and both the baby and mother are doing well, Rasmusson said.

"The patient in this unique case had the best possible outcome we all hoped for," she added. "Only through the experts within our different teams, having the depth of their skill and experience, and our commitment to delivering the best care could this be possible for women as in this case and for others like her."

People with diabetes who undergo joint replacement surgery are at sharply higher risk of experiencing elevated blood sugar after the operation, increasing their chances of developing infections and other complications, according to a new study by researchers at Hospital for Special Surgery (HSS) in New York City and The Ochsner Health System in New Orleans.

Previous studies have shown that high blood sugar, or hyperglycemia, during the perioperative period of orthopedic joint replacement surgery is a risk factor for infection. The new study, by Bradford Waddell, MD, a hip and knee surgeon at HSS, took a narrower look at the question. It included patients with a diagnosis of diabetes whose blood sugar was being controlled using the hormone insulin and compared them to diabetics who did not require insulin. Patients requiring insulin can be considered to have more severe diabetes and have a greater chance of experiencing elevated blood glucose in the perioperative period, Dr. Waddell said.

For the new study, Dr. Waddell and his colleagues reviewed the medical charts of 773 men and women who had undergone total hip or knee replacement between 2011 and 2016. Of those, 437 had been diagnosed with insulin-dependent diabetes, while 336 had not been diagnosed with the condition.

Patients with insulin-dependent diabetes were more than five times as likely as those without the condition to develop hyperglycemia, or high blood sugar, after surgery (odds ratio, 5.2; P

Despite the increased risk for elevations in blood sugar after surgery, however, the incidence of post-operative joint infections did not differ between the two groups of patients. However, Dr. Waddell noted that a limitation of the study was that it was underpowered to detect the risk of infection.

The bottom line for clinicians, Dr. Waddell said, is "if your patient comes in with diabetes and is dependent on insulin, you need to be more cognizant of controlling their blood sugar in the perioperative period because they're at higher risk."

Scientists have found that men with high neuroticism - between a quarter and a fifth of men in developed countries - are significantly more likely to suffer from adverse events such as erectile dysfunction and incontinence, which may put their recovery from prostate cancer surgery at risk. The researchers say that this means cancer teams may need to consider testing for personality types to try to ensure that patients being treated for prostate cancer receive the best care. This work is presented at the European Association of Urology Congress in Barcelona.

The researchers surveyed 982 men who had undergone prostate surgery (radical prostatectomy) at the University Hospital in Oslo, Norway. 761 of the respondents reported on their recovery from the surgery while also self-reporting on neuroticism with a standard questionnaire.

22% of the men scored high for neuroticism, which is in line with the prevalence of high-neurotic personality in national surveys in Norway (22 %,) and other countries such as the Netherlands (25%). These men showed significantly worse scores when surveyed on their recovery from radical prostatectomy (*See below for notes on questionnaires).

Lead researcher, Dr Karol Axcrona (from Akershus University Hospital, Norway) said:

"Around a fifth of the men scored highly for neuroticism, which is pretty much what would be expected. These men showed significantly more adverse effects after prostate cancer surgery. We use a standard questionnaire to measure the Quality-of-Life in men after prostate cancer surgery, and on average the highly neurotic patients scored around 20% worse than the non-neurotic patients on a variety of side effects, including erectile dysfunction, urinary leakage, and bowel problems. This mirrors work which has shown the effect of personality on disease recovery in general, but we still need to see this work replicated in other studies".

Until now differences in outcomes from prostate cancer surgery had been thought to be largely due to differences in surgical technique and the circumstances of the prostate cancer. This work shows that personality may also be a contributory factor to surgical outcomes.

Dr Axcrona continued:

"Neuroticism is not an illness, but a basic personality trait, like extraversion or openness; we all have some degree of neuroticism. What we found was that those patients who show a greater tendency towards neuroticism have worse outcomes 3 years after prostate cancer surgery. This is a real effect, and doctors need to take account of this, in the same way that we would take physical factors into account before and after cancer treatment. This means we may need better advance personality testing for identification and counselling, and perhaps a more specialised follow-up of those men who might be at risk of poorer outcomes. We believe the increased risk of adverse events is likely to impede the overall patient recovery, although the study was not designed to measure that"

Commenting, Director of the European Association of Urology Scientific Office, Professor Arnulf Stenzl (Tuebingen, Germany) said:

"This is interesting and novel work. It would be very valuable for those affected, but it may be difficult to test all patients; so in practical terms we may need to pre-select those who are at most at risk. We know that roughly one out of five will tend to neuroticism, but we need to be more sure how this translates into postoperative clinical or psychological effects, so more we need more data".

Tiny organisms in a child's nose could offer clues to improving the diagnosis and treatment of severe lung infections, research shows.

Experts found that the composition of the microbiome - the population of bacteria and viruses found in vast numbers in the body - was altered in the noses of children with respiratory infections, compared with healthy peers.

This difference predicted how long children had to spend in hospital and helped spot those likely to recover naturally, potentially reducing the need for antibiotics.

Researchers say the results also help explain why some children are more prone to developing infections than others and could be key to preventing serious lung infections.

Lower respiratory tract infections (LRTIs), including pneumonia and bronchiolitis, are a leading cause of death in under-fives worldwide. Symptoms include shortness of breath, weakness and fever.

Doctors from the University of Edinburgh worked with teams in The Netherlands to take samples from more than 150 children under the age of six hospitalised with LRTI. They compared these with samples from 300 healthy children.

They found that the microbiome in the back of the nose and throat was related to that seen in the lungs, making it easier to understand and diagnose infections.

Children with LRTI had a different microbiome profile - including the types and amounts of individual viral and bacterial organisms - compared with the healthy children, experts found.

These profiles could identify 92 per cent of children as being healthy or ill when combined with factors such as the child's age. This was true no matter what symptoms the child had.

Experts say this breaks with traditional thinking that symptoms predict whether either a virus or bacteria is causing the illness and could impact on a decision of whether or not to use antibiotics.

The microbiome profile also helped the scientists predict the length of the child's hospital stay, a marker of infection severity.

Research performed over the last several decades has led to an increased understanding of the genetics of cancer. The clinical application of this knowledge for pediatric cancer has lagged behind studies performed for adults. In a perspectives article published in the prestigious journal Science, Dr. Jaclyn Biegel, from Children's Hospital Los Angeles, and Dr. Alejandro Sweet-Cordero, of the University of California, San Francisco, survey the landscape of this young field and present opportunities for using genomic information to advance a new era of care for children with cancer.

Cancer arises from genetic changes, including DNA mutations, that are either present at birth, or are acquired over time. Many adult cancers are initiated by mutations acquired through exposure to substances like smoking and radiation or simply from aging. The tumors may contain hundreds of sequence alterations, and identifying which changes drive the growth of the tumors, and impact treatment response can be challenging. In contrast, pediatric malignancies often develop from a very small number of mutations, only some of which overlap with the types of mutations seen in adult cancers. Furthermore, an estimated 20% of pediatric cancers arise in children who have a genetic predisposition to malignancy. For this reason, the clinical genetic assays developed to inform prognosis and treatment decisions for adult cancers have not been as useful in pediatrics.

OncoKids® was one of the first next-generation sequencing panels to detect DNA and RNA changes that characterize pediatric cancers. The panel was developed at Children's Hospital Los Angeles under the guidance of author Jaclyn Biegel, PhD, FACMG, Director of CHLA's Center for Personalized Medicine. The OncoKids® panel provides a molecular diagnosis, informs prognosis, and highlights novel therapeutic targets across the broad spectrum of cancers in children, including leukemias, brain tumors and other solid tumors.

"To truly achieve personalized medicine in pediatric oncology, we need to be able to determine if a child is genetically predisposed to develop cancer," said Dr. Biegel. In addition to tumor testing, germline testing that uses a sample of a patient's blood, is critical for identifying those children who have a genetic risk for developing cancer in the future. Besides benefiting the patient, this information has implications for the entire family, since an abnormality that is passed down from parent to child can also raise the risk of developing cancer in siblings.

Although tremendous progress has been made in pediatric cancer care, treatment resistant disease and relapse continue to negatively impact patient outcomes. Genetic profiling of pediatric cancers is typically done at the time of diagnosis or at the time of relapse to help determine treatment planning. According to Dr. Biegel, future studies that may be performed over the course of treatment and at remission have the potential to provide critical information about the mechanisms of tumor progression, treatment resistance and metastasis.

Tremendous opportunity exists for changing outcomes in children with cancer by using an integrated approach to evaluating children and their families that includes genomic medicine as a central component in their care.

First evidence that repeated mass administration of ivermectin can reduce malaria incidence in children aged five or younger without an increase in adverse events for the wider population given the drug.

Childhood malaria episodes could be reduced by 20% -- from 2.49 to 2 cases per child -- during malaria transmission season if the whole population were given a drug called ivermectin every three weeks, according to the first randomised trial of its kind including 2,700 people including 590 children from eight villages in Burkina Faso, published in The Lancet.

In addition, repeated mass administration of ivermectin showed no obvious drug-related harms among fellow villagers taking the drug.

Since 2000, deaths from malaria have dropped by 48% around the world and there are fewer endemic regions, but progress is stalling due to growing resistance to artemisinin; the drug that has been integral to that success.

Ivermectin is used to treat parasite infections from river blindness and scabies to head lice. It is regularly distributed in mass drug administrations for the control of neglected tropical diseases. Previous studies have shown it kills mosquitoes when they ingest ivermectin-treated human or animal blood, but none have looked at its effect on clinical malaria incidence.

Study author, Dr Brian D Foy of Colorado State University, USA, says: "Ivermectin reduces new cases of malaria by making a person's blood lethal to the mosquitoes who bite them, killing mosquitoes and therefore reducing the likelihood of infection of others. Because ivermectin has a unique mode of action compared to other malaria control insecticides and antimalarial drugs, it could be used alongside drugs that treat malaria to combat residual transmission of the disease." [1]

The study authors set out to test the safety and efficacy of repeated mass ivermectin administration to control malaria during an 18-week trial during the 2015 rainy season. The research looked at children as they have the highest disease burden in hyperendemic communities because of their underdeveloped immunity. They invited eight villages to participate and four were assigned to each group. The intervention group had 1,447 participants including 327 children, and the control group 1,265 including 263 children.

All eligible residents -- 1,080 in the intervention group and 999 in the control -- received a single 150-200μg/kg dose of ivermectin plus 400mg of albendazole - an anti-worm medication. The intervention group received five further three-weekly doses of ivermectin alone, reaching 70-75% mass drug administration coverage. [2]

In the villages, children aged five or younger were tested for malaria every two weeks, and treated if needed. In the intervention group 648 malaria episodes occurred in 327 children, and the control group saw 647 among 263 children. Malaria episodes per child in the study villages were reduced by 20% in the intervention group compared to the control -- from 2.49 to 2 cases per child -- without any obvious drug-related harms to the population.

More than double the amount of children in the intervention group had no malaria episodes, compared with children in the control group: 20% [64/327 children] vs 9% [23/264 children].

Adverse reactions such as vomiting, pruritus, oedema in the limbs were recorded in 3% (45 out of 1,447) of the intervention group and 2% (24 out of 1,265) of the control group. There were similar levels of adverse reactions in the children (6% [18 of 327 children] in the intervention group and 5% [14 of 263 children] in the control group.

"Because of mosquitoes' ability to adapt to control tools, new methods of preventing the transmission of malaria are needed, in particular those that target residual transmission. Ivermectin is well tolerated and widely used so it could be a useful tool in disease reduction if further trials show similar results." Continues Dr Foy. [1]

The authors note that the villages selected had been studied previously and regularly treated with ivermectin and albendazole in the years before this study. In addition, their sample size is relatively small, and it was not possible to administer a placebo meaning participants and study teams knew who was and was not receiving treatment. The researchers aimed to mitigate this by assigning each nurse to work in one intervention group village and one control group village to control for nurse effects, and the field physician constantly monitored their work.

The researchers suggest there could be bias in the self-reporting of adverse events because villagers knew which group they were in. They note that there were more events reported in the intervention group, but none were drug related and very few were classified as serious adverse events.

These results are the first proof of principal of antimalarial effects of ivermectin and further work is required to test dosing and distribution approaches. The team call for further trials, in particular double-blinded trials from other endemic areas to test the drug against different malaria ecologies. Studies are also needed to examine the suspected direct antimalarial effects of repeated ivermectin treatment in infected humans. The authors also call for more safety studies in large populations.

Writing in a linked Comment, Dr N Regina Rabinovich of the Harvard T Chan School of Public Health, USA, says: "Foy and colleagues' work is an important step for a promising, preventive intervention for malaria. The development of this new tool will require clear epidemiological (ie, human disease) impact and coordination with the neglected tropical diseases community, but the ultimate results could help us to get back on track to meet the global malaria goals."

CHAMPAIGN, Ill. -- Scientists at the University of Illinois have found that free fatty acids in the blood appear to boost proliferation and growth of breast cancer cells. The finding could help explain obese women's elevated risk of developing breast cancer after menopause.

"When taken up by estrogen-receptor positive breast cancer cells, these fatty acids activated pathways that increased tumor cell growth, survival and proliferation," said food science and human nutrition professor Zeynep Madak-Erdogan, who led the study.

"Our clinical data provide a more complete understanding of the mechanisms that connect obesity with breast cancer, and provide an opportunity to assess the ability of pathway-preferential estrogens to decrease breast cancer risk in obese postmenopausal women," said Madak-Erdogan, also the director of the Women's Health, Hormones and Nutrition Lab.

The findings were published today by the journal Cancer Research.

Scientists have long known that excess body weight increases women's risks of ER-positive breast cancer after menopause, but the specific metabolic pathways and genetic processes that trigger the disease have been less clear. Pathway-preferential estrogens are chemically modified to reduce their potential adverse effects on reproductive and breast tissues.

To explore associations of body mass index with breast cancer risk, Madak-Erdogan's group obtained blood samples from the Susan G. Komen Tissue Bank and compared those of healthy women with the samples of women who were healthy at the Baltimore study's outset but later developed breast cancer, looking for the presence of various metabolites, biomarkers of inflammation and cancer-related proteins.

Women who developed breast cancer - and women who were overweight or obese - had significantly higher blood concentrations of five free fatty acids and glycerol, which are released as byproducts when fat tissue breaks down triglycerides.

Madak-Erdogan's research group analyzed additional blood samples from 37 nonobese and 63 obese postmenopausal women, as well as samples from 21 postmenopausal women who previously were obese but lost weight. All of the women were participants in the Midlife Women's Health Study, a long-term study of women ages 45-64 in the Baltimore area.

They found that obese women's levels of free fatty acids were significantly higher; however, blood levels of all the fatty acids fell significantly in women who were obese at the outset of the Baltimore study but later lost a significant amount of weight.

To explore the impact that obesity has on ER-positive cancer cells, the researchers treated several lines of primary tumor and metastatic cancer cells with the blood of obese women. They found that the cancer cells became more viable and multiplied - effects that increased as the fatty acid levels in the women's blood samples increased.

Exposure to the fatty acids in the women's blood also appeared to make the disease more aggressive. One line of primary tumor cells became more motile and an enzyme pathway that regulates cell growth, proliferation and survival in a metastatic cell line was activated, according to the study.

The greater the cells' level of exposure to the fatty acids, the more pronounced was the effect on this enzyme pathway, known as the mammalian target of rapamycin, or mTOR pathway.

In previous studies, Madak-Erdogan's team found that modifying the mTOR pathway's interaction with ER-positive cells through a pathway-preferential estrogen compound elicited favorable responses in certain genes, such as preventing fat accumulation in mouse livers, without adversely affecting reproductive tissues.

To examine how this estrogen would affect gene expression in the current study, they treated one group of breast cancer cells with oleic acid - a fatty acid - and another group of cells with a combination of oleic acid and the estrogen.

Among other effects, oleic acid increased the expression of genes involved in cell proliferation and downregulated about 500 genes, including those involved in fatty acid metabolism and adhesion with other cells.

However, these effects were greatly reduced in cells that were treated with the estrogen and oleic acid combination, the research team found.

Women who find their jobs mentally tiring are more likely to develop type 2 diabetes, according to a study published in the European Journal of Endocrinology. The study findings suggest that mentally draining work, such as teaching, may increase the risk of diabetes in women. This suggests that employers and women should be more aware of the potential health risks associated with mentally tiring work.

Type 2 diabetes is an increasingly prevalent disease that places a huge burden on patients and society, and can lead to significant health problems including heart attacks, strokes, blindness and kidney failure. Numerous factors can increase the risk of developing type 2 diabetes including, obesity, diet, exercise, smoking or a family history of the disease. A recent review suggested that work-related stress might be associated with an increased risk of type 2 diabetes in women, but more investigation is needed.

In a French study, Dr Guy Fagherazzi and colleagues from the Centre for Research in Epidemiology and Population Health at Inserm, examined the effect of mentally tiring work on diabetes incidence in over 70,000 women, during a 22-year period. Approximately 75% of the women were in the teaching profession and 24% reported finding their work very mentally tiring at the beginning of the study. The study found that women were 21% more likely to develop type-2 diabetes if they found their jobs mentally tiring at the start of the study. This was independent of typical risk factors including age, physical activity level, dietary habits, smoking status, blood pressure, family history of diabetes and BMI.

Dr Guy Fagherazzi comments, "Although we cannot directly determine what increased diabetes risk in these women, our results indicate it is not due to typical type 2 diabetes risk factors. This finding underscores the importance of considering mental tiredness as a risk factor for diabetes among women."

Dr Guy Fagherazzi states, "Both mentally tiring work and type 2 diabetes are increasingly prevalent phenomena. What we do know is that support in the workplace has a stronger impact on work-related stress in women than men. Therefore, greater support for women in stressful work environments could help to prevent chronic conditions such as type 2 diabetes."

The team now plans to study how mentally tiring work affects patients with diabetes, including how they manage their treatment, their quality of life and the risks of diabetes-related complications. This research may help to identify new approaches that could help improve the lives of patients living with diabetes.

A national call for restraint in opioid prescribing has yielded dramatic progress in clinician prescribing patterns, with some notable room for improvement.

These are the findings of a new study from Harvard Medical School showing a drop of more than 50 percent in monthly opioid prescribing for new patients.

Despite this marked decrease, the research showed, a subset of physicians have persisted in doling out scripts for these potent drugs at concerning dosages and lengths. At the same time, others have ceased any new prescriptions for opioid pain relief, raising the question of whether some patients might be getting less-than-adequate treatment for their pain.

The study findings, based on an analysis of more than 86 million privately insured patients across the United States between 2012 and 2017, appear March 14 in The New England Journal of Medicine. (DOI: 10.1056/NEJMsa1807069)

The findings show a dramatic drop--54 percent--in the rate of monthly opioid prescriptions to patients who have never used these drugs or had been off them for at least six months, a group commonly referred to as the "opioid naive." First-time prescriptions are deemed an important gateway to long-term opioid use and misuse and have become a target for risk reduction, the researchers said.

Yet, at the same time, the analysis reveals that a subset of clinicians persistently prescribed such drugs to the opioid naive at concerning dosages and durations.

The researchers say the results are reassuring because of the significant drop in prescriptions and alarming because of the persistence of potentially inappropriate prescribing in some cases and the possibility of undertreatment of pain in other cases.

"The challenge we have in front of us is nothing short of intricate: Curbing the opioid epidemic while ensuring that we appropriately treat pain," said Nicole Maestas, senior investigator on the study and associate professor of health care policy in the Blavatnik Institute at Harvard Medical School. "It's a question of balancing the justified use of potent pain medications against the risk for opioid misuse and abuse."

The researchers caution that, because the insurance claims they examined lacked details about key specifics of the clinical encounter, their analysis was not designed to determine the appropriateness of physicians' decisions to prescribe or withhold opioids.

Still, the team warns, the patterns of prescribing raise some concerns.

Between 2012 and 2017, the monthly incidence of initial opioid prescriptions declined by more than half, from 1.63 percent to 0.75 percent, with fewer clinicians initiating opioids for any opioid-naive patient. The number of providers who prescribed opioids for any opioid-naive patient decreased by nearly 30 percent, from 114,043 to 80,462.

Among the shrinking number of physicians who did initiate opioid prescriptions, risky prescribing--defined as either a morphine-equivalent dose of 50 milligrams per day or more, or any dose prescribed for longer than three days--persisted at an average rate of more than 115,000 high-risk prescriptions per month out of 15.9 million opioid-naive individuals. A small portion of these high-risk prescriptions were particularly alarming: More than 7,700 exceeded 90 morphine milligram equivalents per day, a dose that places patients at a substantially higher risk of both nonfatal and fatal overdose.

With the United States in the midst of a crippling opioid epidemic, spurred in large part by overuse of prescription opioids, the researchers set out to analyze trends in the rate at which opioid therapy was initiated among commercially insured patients. During the years covered by the study, physicians and policymakers were paying more attention to the dangers of opioids. One major turning point during this time was the prominent release of prescribing guidelines in 2016 by the U.S. Centers for Disease Control and Prevention, which were meant to cut back on prescriptions of high-dosage and long-duration courses of opioids, the researchers said.

For their analysis, the investigators used de-identified insurance data claims from BCBS Axis®, the largest collection of commercial insurance claims, medical-professional and cost-of-care information. They estimated the percentage of opioid-naive individuals receiving a new opioid prescription, the percentage receiving a long-duration or high-dose opioid prescription and the number of clinicians who started any opioid-naive patient on opioid therapy. The sample consisted of 15,897,673 opioid-naive patients each month, representing a total of 63,817,512 opioid-naive individuals over the five-year study period.

Above all, the findings underscore the need for further analysis into how clinical decisions are made about whether to use opioids and, if so, at what dose and for how long.

"The ultimate goal should be creating interventions that promote safer prescribing by balancing the importance of pain relief with the risks of opioid treatment, rather than an all-or-nothing approach," Maestas said.

According to the American Cancer Society, prostate cancer is the second most common cause of cancer-related death among men in the United States in 2018. Currently, the standard of care treatment for high-risk, localized prostate cancer is a combination of radiotherapy (RT) and long-term (24-36 month) androgen suppression (AS). Researchers theorized that adding adjuvant docetaxel, a cytotoxic chemotherapy drug, to the standard of care RT and long-term AS treatment could potentially improve overall survival and clinical outcomes for men with localized, high-risk prostate cancer.

Docetaxel-based chemotherapy has improved overall survival among men with castration-resistant and castration-sensitive prostate cancers, is typically well-tolerated by patients, and may be able to target hormonally resistant cells, thus complimenting the abilities of AS to target hormonally sensitive cells. Therefore, the NRG Oncology clinical trial NRG-RTOG 0521 was designed to compare the standard of care with and without docetaxel-based chemotherapy and to determine if the addition of docetaxel improved OS, disease-free survival (DFS) and rates of distant metastasis (DM) for men with high-risk non-metastatic prostate cancer. The results of this study were recently published in the Journal of Clinical Oncology.

The multicenter, Phase III trial NRG-RTOG 0521 randomly assigned men to one of two possible treatment arms. Both treatment arms received eight weeks of AS followed by RT with concurrent AS and then adjuvant AS treatment for 24 months. The standard of care plus chemotherapy arm received an additional six cycles of docetaxel and prednisone given concurrently with AS beginning 28 days after their completion of RT.

"The addition of cytotoxic chemotherapy to androgen suppression and radiotherapy improved overall survival from 89% to 93% at 4 years following randomization. There was also improvement in disease-free survival and reduced rates of distant metastases," stated Seth A. Rosenthal, MD, FACR, FASTRO, of Sutter Medical Group and Sutter Cancer Centers, Sacramento, California, and corresponding author for NRG-RTOG 0521. "These are promising results. The trial results suggest that the addition of docetaxel chemotherapy to standard treatment with long-term androgen suppression therapy and RT, is a viable treatment option for men with high-risk non-metastatic prostate cancer. Physicians should be considering the discussion of this option with selected patients who are fit for chemotherapy"

Of the 563 evaluable patients on NRG-RTOG 0521, there were no unexpected toxicity signals during the conduct of the trial and treatment was well-tolerated on both arms. 4-year OS rates were 89% [95% CI: 84-92%] for AS and RT treatment arm and 93% [95% CI: 90-96%] for AS and RT plus chemotherapy treatment arm (one-sided p= 0.034, HR=0.69 [90% CI: 0.49, 0.97]). 6-year rate of DM were 14% for AS and RT treatment arm and 9.1% for AS and RT plus chemotherapy treatment arm (two-sided p=0.044, HR=0.60 [95% CI: 0.37, 0.99]) and 6-year disease-free survival (DFS) rates were 55% for AS and RT treatment arm and 65% for AS and RT plus chemotherapy treatment arm, (two-sided p=0.043, HR=0.76 [95% CI: 0.58, 0.99]).

A study of over 64,000 women of childbearing age in the USA has found that infertility is associated with a higher risk of developing cancer compared to a group of over three million women without fertility problems, although the absolute risk is very low at just 2%.

As cancer is unusual in pre-menopausal women, the researchers used a US database of health insurance claims in order to obtain large enough numbers to provide meaningful results. Many insurance companies in the US offer coverage for infertility testing and treatment. The research is published today (Wednesday) in Human Reproduction [1], one of the world's leading reproductive medicine journals.

Dr Gayathree Murugappan, a fellow in reproductive endocrinology and infertility at Stanford University School of Medicine (California, USA), who led the study, said: "We do not know the causes of the increase in cancer that we found in this study, whether it might be the infertility itself, the causes of the infertility, or the infertility treatment. We can only show there is an association between them. In the future, we hope that we will be able to understand why infertile women are at higher risk of cancer; for example, by identifying a common, underlying mechanism that can cause cancer and infertility."

Dr Murugappan and her colleagues analysed data from 64,345 women who had been identified as being infertile by diagnosis, testing or treatment in the Clinformatics® Data Mart database between 2003 and 2016. The database contained a geographically diverse group of patients, across 50 US states, although the majority of them were Caucasian. They compared them with 3,128,345 women who were not infertile and who were seeking routine gynaecological care. The women were in their 30s and the researchers followed their progress for an average of nearly four years.

During the follow-up period there were 1,310 cancers diagnosed among the infertile women and 53,116 among the control group of women who were not infertile. Breast cancer was the most common cancer in both groups. After taking into account factors that could affect the results such as smoking, obesity, age, education and reproductive age, they found that infertile women had an overall 18% higher risk of developing cancer compared to the control group, with absolute risks of 2% compared to 1.7%.

Senior author of the paper, Associate Professor Michael Eisenberg from Stanford University School of Medicine, said: "The low overall incidence of cancer among these women means that one in 49 infertile women would develop cancer during the follow-up period compared to one in 59 women in the women who were not infertile."

The researchers found that giving birth conferred some protection on women in both groups. Among the infertile women, 22,024 (34%) had at least one baby during the period studied, and 626,532 (20%) of women in the control group gave birth. The absolute risk of cancer was one in 56 infertile women and one in 86 women in the control group.

When the researchers excluded women who had polycystic ovary syndrome (PCOS) or endometriosis, which have been linked to an increased risk of uterine and ovarian cancers respectively, the absolute risk of cancer was one in 55 among the infertile women and one in 88 among the control group.

Looking at the risk of particular cancers, they found a slightly higher risk of hormone-driven cancers of the ovary and uterus among the infertile women, although the risk of breast cancer was similar between the two groups. They also found a slightly higher risk of cancers that were not driven by hormones among the infertile women, including lung, thyroid, liver and gallbladder cancers and leukaemia. "While several of these associations were significant, it is important to note that the absolute increases in risk were modest," said Dr Murugappan.

As the majority of cancers are diagnosed in older people, one of the limitations of the study is the age of the women, and also the short follow-up period. Other limitations include that women may have sought fertility treatment outside the US insurance system; some women might be infertile without knowing because they might have been using contraception, for instance; and the cause of infertility and the treatment given was not available from the insurance claims data.

Prof Eisenberg concluded: "Although the absolute increase in cancer risk among infertile women was small, this increase was seen in only a short period of four years of follow-up. We need to carry out further research with longer follow-up to determine what factors may be influencing the long-term risk of cancer for infertile women."

ATLANTA--Youth living in the slums of Uganda who are infected with both HIV and sexually transmitted infections are more likely to engage in problem drinking, according to a study led by Georgia State University.

HIV prevalence among individuals living in Uganda is high (6.5 percent), and Uganda is one of the few countries where HIV rates are increasing rather than decreasing. However, HIV prevalence is even higher among youth living in the slums of Kampala. They are vulnerable because of food scarcity, lack of parental oversight and limited infrastructure.

Having both HIV and a sexually transmitted infection, known as co-infection, may result in severe complications, including increased mortality, challenges with treating HIV and increased transmission of HIV. This public health matter warrants urgent attention, and it's important to identify risk factors associated with co-infection of HIV and sexually transmitted infections in Ugandan youth to reverse this trend.

Overall, 13.8 percent of youth (ages 12 to 18) living in the slums of Kampala, Uganda reported having HIV and 42.8 percent reported having a sexually transmitted infection. Among those living with HIV, 72 percent reported having another sexually transmitted infection, such as herpes or syphilis. This is nearly seven times higher than co-infection percentages among people living with HIV in other areas of sub-Saharan Africa.

When identifying risk factors for reporting both HIV and sexually transmitted infections, the researchers found that 32.8 percent of co-infected youth reported problem drinking and 29 percent reported participating in commercial sex work. The findings are reported in the journal AIDS and Behavior.

"Our results demonstrate there is a high prevalence of co-infection with HIV and sexually transmitted infections among young, sexually active youth living in the slums of Kampala, Uganda," said Rachel Culbreth, lead author of the study and a Ph.D. candidate in the School of Public Health at Georgia State. "The findings reinforce the need for comprehensive alcohol reduction and prevention strategies. The legal drinking age in Uganda is 18, and stronger alcohol policies may prevent youth from getting HIV and sexually transmitted infections and other negative alcohol-related outcomes. Ugandan policies also don't address particularly vulnerable groups, such as youth engaging in sex work.

"The results also emphasize the need for preventive strategies targeted at increasing the number of testing centers, teaching youth about how HIV is transmitted and informing youth of the health complications that result from being infected with another sexually transmitted infection."

The researchers surveyed 1,134 youth (ages 12 to 18) who live on the streets or in the slums of Kampala, Uganda. The youth were asked to self-report if they've ever had sexual intercourse and if they've ever been told by a doctor, nurse or HIV counselor they have HIV or a sexually transmitted infection such as syphilis, herpes, bola bola or gonorrhea.

The study was conducted in partnership with the Uganda Youth Development Link, which offers services and vocational training for vulnerable youth in the slums.

"We are very grateful for our long-standing collaboration with the Uganda Youth Development Link and their executive director, Mr. Rogers Kasirye, and his great staff," said Dr. Monica Swahn, Distinguished Professor in the School of Public Health at Georgia State and principal investigator for this National Institutes of Health-funded study.

"Because these results were self-reported, the youth potentially underreported HIV and sexually transmitted infection due to social desirability," Culbreth said. "So it's possible the prevalence of these infections is much higher. Despite the study's limitations, we believe the results are significant because the study is among the first to report the prevalence of co-infection with HIV and sexually transmitted infections and associated risk factors among these youth."

The results also point to modifiable risk factors and possible prevention interventions that could help avoid acquisition of HIV among youth living with a sexually transmitted infection. For instance, youth who reported sexually transmitted infections were more likely to be female, reported multiple sexual partners and reported problem drinking and drinking alcohol in general.

In the future, the researchers would like to use laboratory testing to confirm infection with HIV and sexually transmitted infections.

An imaging technique used to detect some forms of cancer can also help detect preeclampsia in pregnancy before it becomes a life-threatening condition, a new Tulane study says.

Preelcampsia is a hypertensive disorder that accounts for 14 percent of global maternal deaths annually and affects 5 to 8 percent of all pregnancies. Symptoms may include high blood pressure and protein in the urine and typically occurs after the 20th week of pregnancy.

The study, published in the open-access journal Scientific Reports was led by Carolyn Bayer, an assistant professor of biomedical engineering, along with a team of graduate students and researchers with the Tulane School of Medicine and Tulane School of Public Health and Tropical Medicine.

The study was conducted on pregnant rats using spectral photoacoustic imaging, a noninvasive procedure that can detect placental ischemia - a sign of possible preeclampsia - prior to the onset of symptoms, such as high blood pressure, severe headaches and dizziness.

Photoacoustic images were acquired of the placenta of normal pregnant rats and rats with preeclampsia on various days of gestation. Two days after inducing preeclampsia, the average placental oxygenation decreased 12 percent in comparison to normal pregnant rats.

"Spectral photoacoustic imaging is a powerful preclinical tool that has many promising applications in the understanding and treatment of pregnancy-related diseases," Bayer said.

"It provides new imaging techniques to look at the progression of the disease through gestation, which might be a better way to understand which patients need interventions to treat the preeclampsia."

Because it is a noninvasive procedure, it poses little to no risk to the fetus, compared to cordocentesis, a fetal blood sampling that is much more dangerous.

Photoacoustic imaging may be used to detect breast, ovarian and other types of cancers.

DURHAM, N.H. - Researchers at the University of New Hampshire are one step closer to helping answer the question of why autism is four times more common in boys than in girls after identifying and characterizing the connection of certain proteins in the brain to autism spectrum disorders (ASD).

"Our study is the first to look at the gender-biased regulation of proteins in the brain and how they may play a role in affecting abnormal changes in the body that results in autism," said Xuanmao (Mao) Chen, assistant professor of neurobiology. "Our findings point to a new direction for autism research and suggest promising possibilities for creating novel treatment strategies."

In the study, recently published in the journal Frontiers in Cellular Neuroscience, the researchers looked at an enzyme called AC3 which is genetically connected to major depressive disorder (MDD), obesity, and autism spectrum disorders (ASD). However, not much is known about how AC3 functions in the brain. What is known is that many neurodevelopmental disorders or psychiatric diseases, such as depression and autism, exhibit profound differences between males and females, known as sexual dimorphism. For example, females have a higher risk of depression, whereas autism affects more males, with a boy to girl ratio of four to one. The problem is that it is unclear what causes the differences.

The researchers took a closer look at the phosphorylation in the brain, a process when groups of chemicals called phosphates attach to proteins to regulate them, to see which were influenced based on gender. They identified 204 proteins that were more highly regulated in females than in males. Of those, a large percentage (31%) were associated with autism.

"Our results suggest that proteins in the female brain, particularly autism-related proteins, are more tightly regulated than those in the male brain possibly helping to prevent the development of autism in females," said Chen.

The researchers point to evolution for possibly playing a part in how these proteins behave based on the key roles or functions of each sex. The female role has traditionally been multi-tasking several activities like childrearing, caring for the family, the home, and preparing meals whereas male tasks were more specifically focused on functions like hunting and gathering. You can see this highly focused trait in autistic males who are very smart but tend to be fixated on one thing and not interested in, or cannot handle, other social interactions.

Chen says that this research is still in the early phase with mouse models and more studies are needed, but he is hopeful that it may open up a new research direction and one day could possibly lead to a new pharmacological treatment.

Standard tests used to identify dehydration are not working for older people living in care homes - according to new research from the University of East Anglia.

Carers often use simple tests to see if an older person is dehydrated. These include looking at their eyes, skin, or asking if someone feels thirsty, tired or has a headache.

But new research published today finds that these tests do not accurately identify dehydration in older people, when compared against 'gold standard' blood tests.

Lead researcher Dr Lee Hooper, from UEA's Norwich Medical School, said: "Low-intake dehydration happens when people don't drink enough fluids to stay healthy, and is very common in older people, including those living in care homes.

"It happens for all sorts of reasons, such as weakened thirst sensation - which happens as we age, not remembering to drink or difficulties fetching, carrying and reaching drinks.

"Standard tests for dehydration include looking at the eyes, skin, inside the mouth or feeling under the arm to check for dryness, measuring for a drop in blood pressure, or asking if someone feels thirsty, headachy or tired.

"These tests have long been described as standard clinical indicators of dehydration and their use is advocated in nursing and medical text books, care guidelines and many health-related websites.

"But we wanted to know if these tests work in older people living in care homes, how accurate they are, and whether they really tell us if someone is dehydrated. This is important to know because using a test which doesn't work is telling us the wrong thing and health professionals might provide the wrong care as a result."

The research team studied 188 men and women living in care homes in Norfolk and Suffolk. Participants underwent a number of standard dehydration tests such as looking in their mouth and feeling under their arm, having blood pressure, pulse and temperature measured, and answering questions about how they were feeling, including whether they felt thirsty or not.

They were also given a blood test to test for serum osmolality - the most accurate test available for measuring low-intake dehydration. The results of all the other tests were compared to this 'gold standard'.

Lead author, Dr Diane Bunn, from UEA's School of Health Sciences, said: "When we analysed the results of all the simple tests, we found that none of them were able to accurately identify people with dehydration, and we recommend that they are withdrawn from practice.

"Whilst blood tests are the most accurate way of telling if someone is dehydrated, this is expensive and not easily done in care homes unless a doctor orders the test. We really need an inexpensive easy-to-do test for dehydration in older people, and one which works."