Body

LGBT+ women face barriers when accessing healthcare, according to a review published in the International Journal of Environmental Research and Public Health.

The research, led by Professor Catherine Meads of Anglia Ruskin University (ARU), examined the experiences of LGBT+ women in the UK between 2010 and 2018 by analysing numerous studies in different health areas.

It showed similar problems faced by sexual minority women, who frequently experienced ignorance and prejudice from healthcare professionals, as well as barriers when raising concerns and complaints.

One woman cited in the review said: "If you were feeling bad about yourself, you've got low self-esteem or had the experience of homophobic abuse, and then you went somewhere and couldn't find the information you wanted, it reinforces the difference."

Women also complained of negative responses to coming out and frequent assumptions of heterosexuality. One woman, who accompanied her partner who was receiving treatment, said: "The locum first ignored my introduction as 'partner' and continued to call me 'friend' for the rest of the session."

Another contributor said: "(The receptionist) refused to put down my partner's name and partner/next of kin, kept saying 'I'll just put friend', I said, no, I want you to put partner and she looked at me all lips pursed and said, 'I'll just put friend'."

The study also highlighted a surprising level of ignorance amongst healthcare staff. Another person quoted in the study said: "I was scheduled for a small bit of surgery and was asked to give a pregnancy test. I pointed out that I was not only a gay woman but also post-op male-to-female trans. The reply was 'Well, best to be sure'".

Lead author Catherine Meads, Professor of Health at Anglia Ruskin University (ARU), said: "Many healthcare staff do not feel they need to know about their patients' sexuality. However, our research uncovered a worrying lack of knowledge of the issues, unfairness, negativity, and blatant discrimination.

"These studies found significant barriers to sexual minority women, highlighting the need for explicit and consistent education for healthcare professionals on the issues facing these women.

"This is the first review of its kind focusing purely on the experiences of sexual minority women and healthcare in the UK, drawing on 26 different studies."

PHILADELPHIA (September 19, 2019) - Disparities in rates of sexually transmitted infections (STIs) and HIV between Black/African American and Hispanic/Latino adolescents and their white counterparts are well documented. Culturally and developmentally appropriate efforts targeted to help these youth establish healthy practices to lower their risk of sexually transmitted infections are warranted. However, such interventions present unique challenges in recruiting and retaining research participants.

A new paper published in the Journal of Racial and Ethnic Health Disparities outlines successful practices in facilitating recruitment, achieving study aims for adolescent engagement, and ensuring more efficient use of human and material resources in racial/ ethnic minority adolescent STI/HIV prevention research.

"Taking the time to conduct thoughtful, considerate research that directly engages adolescents and young adults is a vital part of developing effective interventions to decrease the heavy STI/HIV burden within this age group and, over time, decrease STI/HIV disparities," said Penn Nursing's Bridgette M. Brawner, PhD, APRN, Associate Professor. Brawner is one of the authors of the paper "Successfully Recruiting Black and Hispanic/Latino Adolescents for Sexually Transmitted Infection and HIV Prevention Research."

Using their experience in successfully conducting research with Black and Hispanic/Latino adolescents, the authors provide insight about how to plan for successful recruitment and retention of adolescents, including the effective engagement strategies like using youth community advisory boards, social media and public venues for outreach. They share experiences about how to select and train recruitment and retention staff, monitor and pilot testing strategies, obtain parental consent, and insight about legal issues.

Co-authors of the article include Erin L.P. Bradley and Madeline Sutton, both of the Centers for Disease Control and Prevention; Yzette Lanier of New York University, Rory Meyers College of Nursing; and Afekwo Ukuku Miller, Kennesaw State University, Department of Health Promotion and Physical Education.

Non-alcoholic fatty liver disease (NAFLD) is the build-up of fat in the liver due to factors other than alcohol. It affects about a quarter of the adult population globally, but its cause remains unknown. Now, researchers have linked NAFLD to gut bacteria that produce a large amount of alcohol in the body, finding these bacteria in over 60% of non-alcoholic fatty liver patients. Their findings, publishing September 19 in the journal Cell Metabolism, could help develop a screening method for early diagnosis and treatment of non-alcoholic fatty liver.

"We were surprised that bacteria can produce so much alcohol," says lead author Jing Yuan at Capital Institute of Pediatrics. "When the body is overloaded and can't break down the alcohol produced by these bacteria, you can develop fatty liver disease even if you don't drink."

Yuan and her team discovered the link between gut bacteria and NAFLD when they encountered a patient with severe liver damage and a rare condition called auto-brewery syndrome (ABS). Patients with ABS would become drunk after eating alcohol-free and high-sugar food. The condition has been associated with yeast infection, which can produce alcohol in the gut and lead to intoxication.

"We initially thought it was because of the yeast, but the test result for this patient was negative," Yuan says. "Anti-yeast medicine also didn't work, so we suspected [his disease] might be caused by something else."

By analyzing the patient's feces, the team found he had several strains of the bacteria Klebsiella pneumonia in his gut that produced high levels of alcohol. K. pneumonia is a common type of commensal gut bacteria. Yet, the strains isolated from the patient's gut can generate about four to six times more alcohol than strains found in healthy people.

Moreover, the team sampled the gut microbiota from 43 NAFLD patients and 48 healthy people. They found about 60% of NAFLD patients had high- and medium-alcohol-producing K. pneumonia in their gut, while only 6% of healthy controls carry these strains.

To investigate if K. pneumonia would cause fatty liver, researchers fed germ-free mice with high-alcohol-producing K. pneumonia isolated from the ABS patient for 3 months. These mice started to develop fatty liver after the first month. By 2 months, their livers showed signs of scarring, which means long-term liver damage had been made. The progression of liver disease in these mice was comparable to that of mice fed with alcohol. When the team gave bacteria-fed mice with an antibiotic that killed K. pneumonia, their condition was reversed.

"NAFLD is a heterogenous disease and may have many causes," Yuan says. "Our study shows K. pneumonia is very likely to be one of them. These bacteria damage your liver just like alcohol, except you don't have a choice."

However, it remains unknown why some people have high-alcohol-producing K. pneumonia strain in their gut while others don't.

"It's likely that these particular bacteria enter people's body via some carriers from the environment, like food," says co-author Di Liu at the Chinese Academy of Sciences. "But I don't think the carriers are prevalent--otherwise we would expect much higher rate of NAFLD. Also, some people may have a gut environment that's more suitable for the growth and colonization of K. pneumonia than others because of their genetics. We don't understand what factors would make someone more susceptible to these particular K. pneumonia, and that's what we want to find out next."

This finding could also help diagnose and treat bacteria-related NAFLD, Yuan says. Because K. pneumonia produce alcohol using sugar, patients who carry these bacteria would have a detectable amount of alcohol in their blood after drinking a simple glucose solution. "In the early stages, fatty liver disease is reversible. If we can identify the cause sooner, we could treat and even prevent liver damage."

"Having these bacteria in your gut means your body is exposed to alcohol constantly," Liu says. "So does being a carrier mean you would have higher alcohol tolerance? I'm genuinely curious!"

(PHILADELPHIA) - From 2000 to 2014, rates of filled opioid prescriptions after eye surgery rose considerably, despite reduced invasiveness of these procedures, according to a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania. The results are published today in JAMA Ophthalmology.

"This really is surprising, given that there have been tremendous strides in the past decade to reduce the invasiveness and recovery time for these procedures. We would have expected rates to go down, not up," said the study's senior author Brian VanderBeek, MD, MPH, MSCE an assistant professor of Ophthalmology.

The overall rate of filled opioid prescriptions after these procedures more than doubled, from 1.2 percent in 2000-01 to 2.5 percent in 2014, across six different ocular subspecialties. Rates dropped for the first time during this time period to 2.2 percent in 2015 and then to 2.1 percent in 2016. However, the researchers found that after controlling for differences among the types of surgeries, the odds of having an opioid medication filled after any incisional ocular surgery was over three times higher in 2014-16 compared to 2000-04.

While opioid prescription rates for eye surgery patients were small compared to other types procedures -- a recent study found, for instance, that nearly half of new mothers in the U.S. were prescribed opioids before or after delivery over the last decade -- the considerable uptick across all ocular subspecialties is concerning to the researchers. For cataract surgery, for instance, VanderBeek could not explain the jump in opioid prescriptions from 0.4 percent in year 2000-1 to 1.4 percent in 2014, as he noted that this specific procedure is not typically painful for patients.

"Each subspecialty is completely unrelated to the other, and yet we saw opioid rates rise almost identically through the years in every single category," VanderBeek said.

Opioid overdoses accounted for over 47,000 deaths in 2017, more than any previous year on record, according the U.S. Department of Health and Human Services (HHS). Many experts have attributed the current opioid epidemic to a rise in prescription opioid medications in the '90s and early 2000s, which led to their widespread misuse. In response to the opioid crisis, the HHS released a report in 2019 on acute and chronic pain management, and governing bodies of some medical specialties have created specific guidelines for opioid prescribing. However, given the few number of studies that characterize how opioids are used in ophthalmic settings, there are no specific guidelines for their use in eye surgery.

VanderBeek and his team set out to better understand the relationship between opioids and incisional eye surgeries, as well as whether there is a connection to demographic factors, including race and geographic location. For their study, the researchers used data from a large national U.S. insurer's medical claims database to evaluate filled prescriptions between year 2000 and 2016. (The years 2000 and 2001 were combined due to low number of surgeries meeting inclusion criteria in 2000.) In total, 2,407,962 incisional ocular surgeries were included in the study, and patients from all 50 states were represented. While only 45,776, or about 2 percent of all surgeries, were associated with an opioid prescription, the researchers found a steady rise from 2000 to 2014. Grouping the years into four to five-year cohorts also showed a similar trend.

When comparing opioid fills with demographic data, the researchers found that geographic location was highly associated with odds of filling an opioid prescription after eye surgery, with the lowest odds in the Northeast and the highest in the Mountain states. Decreased opioid prescription rates in the Northeast have been found in other studies, the authors write, and may be due to state-specific regulations. Odds of filling a prescription were also higher for blacks, males, and for those without a bachelor's degree.

The study authors note that the increase in opioid rates over time is inconsistent with recent trends in ophthalmic surgery, which have included smaller incisions, as well as a shift toward topical anesthesia, which is intended to result in shorter recovery periods and high patient satisfaction. While the reasons for the steady increase remains unclear, it is likely multifactorial, VanderBeek said. Potential reasons may include insufficient physician education regarding opioid prescribing, increased focus on pain management following the induction of pain scales in the early 2000s, and a lack of standard state and national opioid prescription regulations.

"It is our hope that these findings shed light on the trends in opioid medication filling patterns after incisional surgery and will motivate clinicians to evaluate their opioid medication prescribing practices," said the study's first author Anton M. Kolomeyer, MD, PhD, who was a fellow at Penn Medicine when he conducted the study. As a caveat, the study authors noted that they analyzed data for "prescriptions filled" rather than "prescriptions written," and that they were unable to look at numbers past 2016, when the HHS declared opioid use a public health emergency.

VanderBeek, who performs retina surgeries, said his standard clinical strategy is to recommend over-the-counter pain medications post-operatively and provide patients with a pain "block" during the surgery which lasts for several hours after the surgery.

"Whenever you have an epidemic, I think it's reasonable to ask what you can do to curb it. Even if eye surgeries are a minor source of the problem, if we can limit some of the exposure to opioids, in light of the national emergency, we are obligated to do what we can," VanderBeek said. "We don't want people to be in pain, but we also don't want to continue to fuel the problem if we can avoid it."

Early palliative care is associated with better survival in patients with advanced lung cancer, according to a study by VA Portland Health Care System and Oregon Health and Science University researchers.

Lead author Dr. Donald Sullivan, with the VA Portland Health Care System Center to Improve Veteran Involvement in Care (CIVIC) and the Oregon Health and Science University Division of Pulmonary and Critical Care Medicine, explains that this research is the first time in a real-world clinical setting that palliative care has been linked to increased survival in lung cancer patients.

"This therapy that is already known to offer improved symptom burden, quality of life, and support also works like other cancer therapies to improve survival," he says.

The results will appear Sept. 19, 2019, in JAMA Oncology.

The goal of palliative care is to improve the quality of life and mood of a patient with a life-limiting illness. It focuses on providing a patient with relief from physical symptoms of a disease--such as pain and stress--rather than trying to cure or modify the disease. Treatment includes a variety of practices, such as using medication to reduce pain, treating nausea caused by chemotherapy, and counseling to deal with psychological distress and depression that often accompany a serious illness.

While palliative care can provide relief and comfort to patients with diseases such as advanced lung cancer, it is often underutilized or provided too late to offer any meaningful benefit.

According to the researchers, both patients and clinicians often associate palliative care only with poor prognosis at the very end of life. It is often confused with hospice. Palliative care can be appropriate for anyone with a complex illness. Hospice care provides a variety of end-of-life care that includes handling legal and ethical matters concerning death in addition to symptom relief. Many people think of palliative care as "giving up" because it is seen as something done only when nothing else works, or when life-prolonging therapies are no longer advised.

Many even believe that palliative care can have negative effects. Some oncologists have expressed concern that palliative care destroys patients' hope. Results of past research on the effects of palliative care on survival have been mixed. However, the Portland researchers write that their new results "help dispel the belief that early palliative care among patients with lung cancer is associated with shortened survival."

The study shows that palliative care may actually increase survival when provided shortly after a lung cancer diagnosis. It is most effective when included in the initial disease treatment rather than as part of the dying process, say the researchers. They conclude that palliative care should be considered a complementary approach in patients with advanced lung cancer, given alongside treatment to fight the cancer.

Sullivan explains that, while more research is needed to define the most beneficial elements of palliative care for survival, the result could lead to changes in how Veterans with lung cancer are treated in VA.

"I think research like this gets more clinicians and patients thinking about the importance of palliative care," he says, "and I believe more Veterans with advanced cancer will receive this care along with other cancer therapies."

To learn how palliative care affects survival, the researchers looked at data on 23,154 patients with advanced lung cancer who received care through the Veterans Health Administration. Of those, 57% received palliative care. The team found that patients who received palliative care between 31 and 365 days after their diagnosis lived longer than patients who did not receive palliative care at all.

According to Sullivan, outpatient palliative care seemed to be a significant driver of the finding, meaning that "palliative care offered in outpatient settings rather than the intensive care unit is going to be an important component of this type of care."

Patients receiving palliative care more than a year after lung cancer diagnosis had no difference in survival compared with those not receiving such care. Patients who received palliative care between 0 and 30 days after diagnosis had decreased survival rates.

The researchers suggest that patients who receive palliative care very soon after diagnosis are likely more seriously ill, perhaps beyond the point at which any treatment would prolong life. Palliative care is intended, in those circumstances, to ease the dying process rather than improve survival. The results show that many of these patients died shortly after their diagnosis, meaning patients had little time to experience palliative care.

The results suggest that the timing of palliative care is important. The researchers recommend moving palliative care earlier in the lung cancer treatment process to take advantage of its benefits. Sullivan explains that currently, palliative care is typically offered when all other treatments fail at the very end of life rather than integrated intro treatment earlier on. However, professional societies are beginning to offer guidelines that focus on early integration. Recent American Society of Clinical Oncology guidelines suggest palliative care be delivered within eight weeks of diagnosis.

Changing the current culture will take time, says Sullivan. More emphasis also may need to be placed on primary care providers such as oncologists and pulmonologists, he explains, because of a shortage in palliative care specialists.

The researchers offer several explanations as to why early palliative care may prolong life. Patients who receive early palliative care are more likely to benefit from its multidisciplinary, patient-centered approach, which may help increase survival. By enhancing patients' understanding of their illness and promoting shared decision-making, palliative care may also decrease overly aggressive end-of-life care, which can often do more harm than good.

Furthermore, negative symptoms, mood, and quality of life have been linked to decreased survival among patients with cancer in other studies. By relieving these burdens, palliative care may improve patients' outlook and therefore their survival odds.

The study found an additional benefit of early palliative care beyond increased survival. Early palliative care was linked to reduced odds of death in an acute health care setting (meaning a hospital ward or intensive care unit). Surveys have shown that terminally ill patients would prefer to die at home rather than in the hospital. So while palliative care will not increase survival for all patients, it can still improve their quality of life and help them die on their own terms.

Sullivan and his colleagues are already at work building on the research. The finding are being disseminated to other clinicians in VA. The research team has several other studies underway examining the impact of palliative care within VA and ways to improve value and quality in lung cancer care. While the work is focused on lung cancer, Sullivan says that "I have no reason to believe these findings could not be generalizable to patients with other serious conditions."

New Orleans, LA - Research conducted by Suresh Alahari, PhD, Professor of Biochemistry and Genetics at LSU Health New Orleans School of Medicine, has found that metformin, a commonly prescribed drug for Type 2 Diabetes, may be effective in treating cancers that lack a protein called Nischarin. The findings are published online in the International Journal of Cancer available here.

Dr. Alahari discovered Nischarin, a protein involved in many biological processes that also acts as a tumor suppressor. Much of his research on this novel protein has been in breast cancer. In the current study, his lab showed that disruption of the Nischarin gene delays mammary gland development, enhances tumor growth and metastasis, and also decreases activation of an enzyme called AMPK. AMPK plays a major role in metabolism and is considered to be a therapeutic target for metabolic diseases and even some cancers. Metformin's precise mechanism of action remains unclear, but it appears to work at least partly through the activation of AMPK.

"The clinical documentation that diabetic patients on a metformin regimen display reduced risks of developing cancer poses the tantalizing possibility that this approach to treating cancer might prove to be an effective and unrealized therapeutic opportunity," says Alahari.

In this study, the researchers showed that metformin activates AMPK and has a strong inhibitory effect of growth on tumors that do not express functional Nischarin, suggesting metformin has a great therapeutic value in Nischarin-lacking tumors.

"We found that Nischarin-deleted tumor cells had lower AMPK activity than Nischarin-positive cells," notes Alahari, "and that metformin treatment activated AMPK more efficiently in Nischarin-deleted mice, and metformin suppressed tumor growth of Nischarin-deleted mice. Collectively, our data suggest that Nischarin disruption promotes breast tumor development, AMPK signaling is important for Nischarin-mediated suppression of breast tumors, and activation of AMPK by metformin suppresses breast tumor growth in Nischarin-lacking mice."

These findings have added clinical significance because Nischarin expression is frequently reduced in human breast cancer, especially triple negative breast cancers, and is associated with reduced long-term survival.

"The discovery that the effectiveness of certain drugs, such as metformin, are influenced by the level of Nischarin expression could help identify specific patients in whom it is most likely to prove beneficial," Alahari adds. "In this way, Nischarin expression could serve as a biomarker to help inform decisions in management by identifying a subset of patients most likely to benefit from AMPK activator therapies."

AURORA, Colo. (Sept. 18, 2019) - Researchers from the University of Colorado School of Medicine have released a study that shows that a new imaging method "fast MRI" is effective in identifying traumatic brain injuries in children, and can avoid exposure to ionizing radiation and anesthesia.

The results of the study, which are published in the journal Pediatrics, establish a new, low-risk way to test for brain injuries. The study was designed to determine the feasibility and accuracy of "fast MRI," or magnetic resonance imaging, when compared to computed tomography (CT) scanning.

"We found that fast MRI is a reasonable alternative to CT," said Daniel Lindberg, MD, associate professor of emergency medicine at the CU School of Medicine and lead author of the article. "Nearly all - 99 percent - of fast MRIs were completed successfully, with accuracy that was similar to CT, while avoiding the harms of radiation exposure."

Each year as many as 1.6 million children visit U.S. emergency departments with a concern for traumatic brain injury. As many as 70 percent undergo CT scanning, which exposes the children to ionizing radiation and increased risk of cancer.

Conventional MRI can identify injuries without radiation exposure, but requires the child to remain motionless for several minutes. Conventional MRI requires anesthesia, which is not practical in many injured children and may expose them to mild cognitive injury. Fast MRI avoids the need for sedation by using faster, and more motion-tolerant imaging techniques.

Between June 2015 and June 2018, the CU researchers recruited participants to their study. Children less than six years old who had already undergone CT scans during their emergency care were eligible to participate and those enrolled received fast MRI as soon as possible, usually within 24 hours of the CT scan.

Of the 225 children enrolled, fast MRI was completed in 223. The median imaging time in fast MRI was 6 minutes, 5 seconds. Fast MRI results matched those of CT in greater than 90 percent of cases. CT showed better accuracy for identifying fractures or breaks to the skull, while fast MRI did a better job of imaging the brain and the space between the brain and skull.

One limitation of the study is that it may not apply to other settings without access to cutting-edge MRI scanners or experienced pediatric radiologists. "We were fortunate to be using newer scanning equipment and highly experienced technicians and pediatric radiologists," Lindberg said. "While we believe our findings reveal a feasible alternative to CTs in pediatric specialty centers, further study is necessary to test the results in other settings."

Philadelphia, September 18, 2019 - Even though nonverbal or minimally verbal people who have autism spectrum disorder (ASD) make up between 25 and 30 percent of the total autistic population, almost no studies have been done focusing on this group and their particular needs.

To address this gap in knowledge of the true spectrum of autism, researchers at Children's Hospital of Philadelphia (CHOP)'s Intellectual and Developmental Disabilities Research Center used state-of-the-art brain imaging techniques to determine how this specific group of children who have autism processes auditory stimuli, which could have important diagnostic and prognostic implications across the autism spectrum. The findings were published in the journal Molecular Autism.

Previous brain imaging studies have found that children on the autism spectrum have prolonged or delayed auditory processing responses compared with their neurotypical peers. However, most imaging studies have focused on verbal children with autism. Children with limited or no speech have previously been excluded because they are more likely to have difficulty understanding the demands and requirements of the imaging process and are less likely to tolerate loud noises or other sensory experiences related to imaging techniques such as magnetic resonance imaging (MRI).

In order to bridge this gap in understanding and to help answer questions about nonverbal or minimally verbal children with autism, CHOP scientists utilized a magnetoencephalography (MEG) technology, which allowed them to measure magnetic fields produced by electrical activity in the brain. This technology has previously been used to study brain signatures associated with autism.

With the support and input from parents and providers from the community, the study team developed the MEG Protocol for Low Language/Cognitive Ability (MEG-PLAN) specifically designed for this group of patients and for use with MEG technology. The interdisciplinary research team partners with families to implement MEG-PLAN.

"By using this plan, we're able to provide families with materials that help familiarize them with the entire research visit process," said Emily Kuschner, PhD, a licensed clinical psychologist and scientist at in the Lurie Family Foundations Magnetoencephalography (MEG) Center and the Center for Autism Research at CHOP. "For example, if a child has sensory sensitivities, they might be given scrubs to take home so they can get used to how they feel, or we might provide them with the adhesives used to attach the sensors to the face to desensitize a child to the experience."

"Since MEG is less invasive and does not expose the child to radiation, it can be less demanding than other imaging methods. We felt like we were in a better position to use this technology to study this population of children," said Timothy Roberts, PhD, Vice-chair of Research for the Department of Radiology and the Oberkircher Family Endowed Chair in Pediatric Radiology, director of the Lurie Family Foundations MEG Imaging Center at CHOP and first author of the study.

A total of 105 patients were enrolled in the study (16 minimally verbal or nonverbal with autism, 55 verbal with autism, and 34 neurotypical patients to serve as a control). The researchers found that minimally verbal or nonverbal participants had delayed responses to simple auditory tones, and longer times to response were associated with poorer communication skills as measured by a standardized questionnaire completed by parents.

Based on these findings, the authors said this study indicated that longer latency delays were associated with poorer language ability. Additionally, the findings suggest that measuring brain activity in the auditory cortex could serve as important objective markers for how these patients respond to sound.

"Given their association with language activity, we believe these measurements of response time have both prognostic and treatment ramifications," Kuschner said. "It would be exciting if down the road we could use these MEG markers to understand the course of language development or personalize which treatment approach might be best for a particular child."

New research presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September) shows that a child's intake of gluten at age 18 months is associated with a 46% increased risk of developing type 1 diabetes for each extra 10g of gluten consumed. There was no association found between the mother's intake of gluten during pregnancy and type 1 diabetes in her child, conclude the authors who include Dr Nicolai Lund-Blix, Oslo University Hospital, and the Norwegian Institute of Public Health, Oslo, Norway.

A previous study from Denmark suggested that a high maternal gluten intake during pregnancy increased the risk of type 1 diabetes in the child. No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood. This new study examined the association between the maternal gluten intake during pregnancy, child's gluten intake at age 18 months, and the risk of type 1 diabetes in the child in a Norwegian population-based nationwide study.

The study included 86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 to 2009, followed up until April 2018. The outcome was clinical type 1 diabetes, ascertained in a nationwide childhood diabetes registry. Increased risk was calculated using statistical modelling for maternal gluten intake during pregnancy and child's gluten intake at 18 months. The authors estimated the amount (g/day) of gluten intake from a semi-quantitative food frequency questionnaire at week 22 of pregnancy and from a questionnaire completed by the guardian when the child was 18 months old.

During a mean follow-up of 12.3 years, 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child. However, the child's gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes, with risk increasing by 46% for each 10g per day increase in gluten intake.

The authors conclude: "This study suggests that the child's gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child. Our observations may motivate future interventional studies with reduced gluten intake to establish whether there is a true causal association between amount of gluten intake in the child's early diet and type 1 diabetes in susceptible individuals."

The authors discuss some possible reasons for the findings, saying: "There is some evidence that gluten intake may influence the gut microbiota and induce inflammation in so-called 'leaky gut' (increased absorption of dietary antigens and/or gut infections). These are plausible mechanisms, but the exact mechanism explaining our findings is not known. If anything, we believe that gluten works in combination with another environmental factors such as virus infections in predisposed children."

In this Norwegian study, the main sources of gluten in the diet are cereal and bread. However, at this stage the authors say their study, together with existing evidence, is not enough to encourage people to avoid or reduce gluten intake.

They say: "We need confirmation from further studies, and ideally a randomised controlled trial (RCT) to determine any relationship between gluten intake and type 1 diabetes with certainty. Since our findings show the highest risk of developing T1D is in the group with the highest gluten consumption, it could be that simply reducing gluten intake would be enough to reduce risk and this is easier to achieve than complete avoidance. Based on experiences from patients with celiac disease, complete avoidance of gluten is hard but manageable, but this would probably not be necessary.".

When does childhood end? That's the question international researchers are asking as they chart age cut-offs for paediatric services around the world.

Adolescent Health Professor at the Murdoch Children's Research Institute and the University of Melbourne Susan Sawyer says previous research has found that global health systems do not meet adolescents' needs.

"Yet pediatricians are well placed to provide age-appropriate care to adolescents - especially if they are trained in adolescent medicine," she says.

"The World Health Organization defines adolescents as aged being 10 to 19 years, however there's been little research into the age of patients that pediatricians actually treat and how this varies across the world."

The researchers developed an online survey to explore these questions and obtained responses from 1,372 pediatricians in 115 countries. They report the results in a policy paper, 'The Age of Paediatrics'*, published in The Lancet Child and Adolescent Health.

"There was a striking difference in the upper age by country and disappointingly only a handful of countries had a mean upper age of 19 years," Prof Sawyer says.

"South Africa had the lowest upper age at 11.5 years, it seems pediatrics is yet to embrace adolescence. The US had the highest upper age, with 19.5 years."

Despite similar health care systems, Australia's mean upper age of pediatric care was 17.8 years while New Zealand's was 15.6 years.

"The world mean is 17.4 years," says Prof Sawyer. "This average has increased over the past 20 years, rapidly in some countries."

"The discipline of pediatrics has historically focused on very young children, largely neglecting adolescents, but the pattern of disease across childhood and adolescence is changing. Public health interventions and medical advances have seen the mortality rate of young children fall dramatically.

"This is not mirrored in adolescents, whose more complex disease burden remains relatively unchanged. The World Health Organization estimates that more than one million adolescents die every year.

"Young people face childhood and adult health burdens, including chronic physical conditions like diabetes and asthma, mental health disorders, anaemia, rising levels of obesity, interpersonal violence, diarrheal and bronchial illnesses, drug and alcohol abuse, sexually transmitted disease and road trauma."

Co-author Professor Jonathan Klein from the University of Illinois and Coordinator of the International Pediatric Association Executive Committee said few nations paid sufficient attention to including adolescent heath within pediatric training.

"To meet the health needs of young people, a diverse workforce is required including pediatricians, family physicians, nurses, and community and school health workers, all schooled in adolescent health.

"The evidence is clear. Our health care systems need to be more attuned to the needs of adolescents and young adults," he said. "Improving adolescent care is a critical step if we hope to reach the United Nations' Every Woman, Every Child, Every Adolescent promises (#EWECisMe), and achieve the 2030 Sustainable Developmental Goals (#SDGs; #Globalgoals)

Prof Sawyer says investment in adolescent health training is most needed in countries with a low upper age, a large number of adolescents, or an upper age that has only recently risen.

"Yet, a poor report card on the quality of adolescent health training across the world suggests that investments to improve adolescent health care are universally required."

Combining a new class of drug with two other compounds can significantly shrink lung tumours in mice and human cancer cells, finds a new study led by the Francis Crick Institute and The Institute of Cancer Research, London.

The study, published in Science Translational Medicine, looked at G12C KRAS inhibitors. This new type of drug targets a specific mutation in the KRAS gene that can cause cells to multiply uncontrollably and lead to fast-growing cancers.

These mutations are found in 14% of lung adenocarcinomas, the most common form of lung cancer. There are still no effective treatments for most patients, and more than eight in ten will die within five years of diagnosis. Every year, around 2,800 people in the UK will develop lung cancers with the deadly G12C KRAS mutation.

Drugs targeting G12C KRAS mutations are showing promising anti-tumour activity and few adverse effects in US clinical trials, but it is unclear how long any response will last before the cancer becomes resistant.

"It's likely that tumours will develop resistance to the new drugs, so we need to stay one step ahead," explains senior author Professor Julian Downward, who led the research at the Crick and ICR. "We found a three-drug combination that significantly shrank lung tumours in mice and human cancer cells. Tumours treated with the combination shrank and stayed small, whereas those treated with the G12C KRAS inhibitor alone tended to shrink at first but then start growing again after a couple of weeks. Our results suggest that it would be worth trying this combination in human trials in the coming years, to prevent or at least delay drug resistance."

The other compounds in the combination block the mTOR and IGF1R pathways, both of which have been previously tested in cancer patients. There are already licensed mTOR inhibitors on the market, while IGF1R inhibitors are still at the trial stage.

To develop this combination, the team used tumour cells derived from patients with the G12C KRAS mutation. They edited these cells to block the activity of 16,019 different genes and treated them with compounds that KRAS mutant cancers are known to be susceptible to.

"We found that cell lines without the MTOR gene were significantly more vulnerable to both KRAS and IGF1R inhibitors," explains first author Dr Miriam Molina-Arcas, Senior Laboratory Research Scientist at the Crick. "When we blocked all three pathways, the mutant cancer cells were simply unable to survive. This makes it a promising avenue for human trials in the coming years, although this is still early research. Promising results in mice and cells can tell us what's worth trying, but it's impossible to predict how patients will respond until we actually try."

What The Study Did: Data on 500,000 children born in Sweden were used to examine the association between mothers with anemia during pregnancy and the risk of children being diagnosed with autism spectrum disorder, attention-deficit/hyperactivity disorder and intellectual disability.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Renee M. Gardner, Ph.D., of the Karolinska lnstitutet in Stockholm, Sweden, is the corresponding author.

(doi:10.1001/jamapsychiatry.2019.2309)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

ROCHESTER, Minn. -- Pancreatic adenocarcinoma (PDAC) is a lethal malignancy that most often is resistant to chemotherapy. Researchers have been searching for ways to increase the sensitivity of the tumors to cancer-fighting drugs.

A Mayo Clinic-led study published today opens a promising new front in that battle.

Using patient cell lines and tumor-bearing models, researchers found that inhibition of GSK-3, an enzyme involved in many cancer-promoting processes, sensitizes PDAC cell lines to gemcitabine, the most commonly used chemotherapy. They found that GSK-3 inhibitor treatment prevented cancer cells' ability to repair single-strand DNA damage induced by gemcitabine.

The findings, published in Clinical Cancer Research, the journal of the American Association for Cancer Research, suggest that GSK-3 inhibitors may overcome resistance to gemcitabine as well as to other chemotherapies, says Daniel D. Billadeau, Ph.D., a Mayo Clinic researcher whose work focuses on pancreatic cancer.

"Our study identified a previously unknown role for GSK-3 in the regulation of the cell's ability to respond to and repair its DNA following chemotherapy," says Dr. Billadeau, professor of immunology, biochemistry and molecular biology at Mayo Clinic College of Medicine and Science. "The findings suggest that by inhibiting GSK-3, we can impede the cells' DNA damage response, leading to synergistic tumor cell death even in cells that are naturally resistant to chemotherapy."

PDAC constitutes 93% of pancreatic cancers and is predicted to be the second leading cause of cancer-related deaths in the United States by 2030. The 5-year relative survival rate of PDAC patients is less than 10%.

In this study, pancreatic cancer cell lines and patient-derived tumor samples were treated with a new GSK-3 inhibitor, called 9-ING-41, alone or in combination with chemotherapy. Researchers found that the GSK-3 inhibitor significantly increased pancreatic tumor cancer cell death and prolonged survival in tumor-bearing models when combined with chemotherapy.

"Many pancreatic cancer tumors are resistant to the two most commonly used chemotherapies," says Li Ding, Ph.D., a Mayo Clinic senior research fellow and the study's lead author. "Thus, identifying ways in which to make resistant tumors sensitive, or to increase the effectiveness of chemotherapy, is vital."

The GSK-3 inhibitor used in this study is in a Phase 1a/1b clinical study at Mayo Clinic, and the results from this study are highly relevant to that work, Dr. Ding says.

Lesbian, gay, and bisexual (LGB) individuals who report being discriminated against but who feel close to their fathers have lower levels of C-reactive protein (CRP)--a measure of inflammation and cardiovascular risk--than those without support from their fathers, finds a new study from researchers at NYU College of Global Public Health.

The findings, published in the journal Psychoneuroendocrinology, suggest that fathers can play a role protecting against the negative effects of discrimination and, surprisingly, mothers may not play the same role. More generally, the study illustrates how prolonged exposure to stress can hurt sexual minorities.

LGB people experience stress and discrimination related to their sexual orientation, including dealing with stigma, microaggressions, and the process of coming out. Research shows that prolonged or repeated exposure to stress, including discrimination, leads to the production of inflammatory proteins such as CRP and raises one's risk for heart disease.

"I'm interested in understanding how discrimination gets under the skin and is linked to poor health outcomes," said Stephanie Cook, assistant professor of biostatistics and social and behavioral sciences at NYU College of Global Public Health and the study's senior author. "What factors make people more resilient and can protect them from these health effects? We know that social support can act as a buffer, but wanted to better understand the role parents play in how their children experience discrimination and its health effects."

In this study, the researchers analyzed data from the National Longitudinal Study of Adolescent to Adult Health. Adults 24 to 33 years old were surveyed about their sexual orientation, how close they felt with their mothers or mother-figures and fathers or father-figures, and whether they felt discriminated against or treated with less respect than others in their day-to-day lives. The researchers focused on 3,167 adults describing their relationships with their fathers and 3,575 describing their relationships with their mothers. Blood samples were used to measure CRP levels.

The researchers found that when LGB people felt discriminated against in their day-to-day lives but described being close to their fathers, they had lower CRP levels than other sexual minorities who were discriminated against but did not have close relationships with their fathers.

Relationships between LGB people and their fathers can act as either a buffer or an additional source of stress. On one hand, positive social support from a father appears to protect sexual minorities from harmful experiences related to discrimination. On the other, poor social support from one's father--for instance, fathers who do not accept their children's sexual orientation after they come out--may lead to exacerbated stress and less ability to shield against harmful experiences related to discrimination.

Interestingly, the researchers found that closeness with mothers did not act as a buffer for LGB or heterosexual individuals who experienced discrimination.

"We often talk about the importance of support from mothers and how mothers can help buffer the negative effects of discrimination on health broadly. But this study suggests that we've been neglecting the role of fathers, and their role is really important when it comes to their LGB children," said Cook, who leads the Attachment and Health Disparities Research Lab at NYU College of Global Public Health.

"If we're trying to understand the effects of discrimination on sexual minorities and figure out what we can do to intervene or prevent these outcomes, we should look beyond support from just peers and mothers to include fathers in our efforts," said Erica Wood, a research scientist in the Attachment and Health Disparities Research Lab at NYU College of Global Public Health and the study's first author. "For instance, professionals can work with fathers who reject their children because of their sexual identity to show them the importance of the father-child relationship in reducing the negative effects of stress."

A minority of people who use illicit opioids indicated a preference for fentanyl, the super-potent synthetic opioid that accounts for much of the recent rise in U.S. overdose deaths, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

The study, based on surveys of 308 people who use opioids in Baltimore, Maryland; Boston, Massachusetts and Providence, Rhode Island, found that 27 percent indicated a preference for opioids containing fentanyl, and that people who prefer fentanyl are more likely to be younger, white, and daily users. The median age of those who prefer fentanyl was 38 years compared to 45 years for those who don't prefer fentanyl. Fifty-nine percent of fentanyl preferers identified as non-Hispanic white, compared to only 29 percent among the non-preferers.

The study, published online in the journal Drug and Alcohol Independence, is thought to be the first to characterize fentanyl-preferring opioid users.

"These findings will help us think about how best to target interventions to prevent opioid overdoses," says study senior author Susan Sherman, PhD, professor in the Department of Health, Behavior and Society at the Bloomberg School. "Preference for fentanyl for a minority of participants likely reflects the fact that in their street opioid markets, fentanyl-containing products are all they've known and used."

The opioid crisis in the U.S. includes an epidemic of overdose deaths, which reached about 70,000 in 2017, compared to fewer than 17,000 overdose deaths in 1999. Synthetic opioids, which mostly include fentanyl and related compounds, have been a leading factor in these fatal overdoses; deaths in this category jumped from 3,105 in 2013 to 20,145 in 2016.

The crisis has prompted public health researchers to consider how best to reduce these fatal overdoses. As part of that broad effort, Sherman and collaborating researchers in 2017 initiated a study called FORECAST (Fentanyl Overdose Reduction Checking Analysis Study). A key goal of the study was understanding participants' experiences with overdose, including their interest in drug checking, a harm reduction service that screens street drugs. Another study goal was to illuminate the characteristics associated with fentanyl preference as fentanyl use is strongly associated with a risk of fatal overdose.

The new study, fielded in the summer of 2017, was based on the responses of 308 street users who said that they had used illicit opioids in the previous six months. Of these users, 27 percent indicated that they "somewhat agreed" or "strongly agreed" with the statement "I prefer drugs with fentanyl in them."

Those preferring fentanyl also reported using opioids more frequently. About 92 percent of the fentanyl-preferring users reported daily drug use, compared to 76 percent of the fentanyl-non-preferring users. Among daily users, rates of fentanyl use did not change between people who prefer it and those who do not, implying that fentanyl is already present in the drug supply rather than being generally sought out. Moreover, fentanyl-preferring users more often (31.3 percent) than non-preferring users (17.3 percent) reported having overdosed more than a year prior to the survey. "The difference in recent overdose could reflect the fact that a higher percentage of those who overdosed in the past year experienced a fatal one," Sherman says.

She and her colleagues suggest that the younger, whiter profile of users who prefer fentanyl points to the dominance of fentanyl in the northeastern regional markets where these users have been buying opioids, particularly in recent years. The researchers also suspect that people who are more likely to have used opioid medications may find a similar effect with fentanyl-adulterated heroin.

"In Baltimore we have found that longer-term, African American heroin users are less likely to prefer fentanyl," Sherman says. The study identified more African Americans as fentanyl non-preferring users (45.3 percent) compared to fentanyl-preferring users (24.1 percent), and they were less likely to have ever been prescribed an opioid.

Sherman and colleagues recommend that harm-reduction strategies to prevent overdoses should target users who fit the profile suggested by the study results. One intervention: portable "drug checking" technologies that allow individuals to test street drugs for fentanyl content before users consume them.

"Drug checking was of interest to a majority of participants, regardless of fentanyl preference," says Sherman. "Given this widespread interest in drug checking, it seems unlikely that drug checking would 'enable' preferers to pursue fentanyl and may in fact help non-preferers avoid fentanyl."