Body

In Sub-Saharan Africa, the leading causes of death are changing. Fewer people are dying of infectious diseases like malaria or tuberculosis, but non-communicable diseases, including heart disease and diabetes, are on the rise. The situation is particularly grim in South Africa, where citizens are just as likely to die from a non-communicable disease as from anything else.

A healthy diet and regular exercise can greatly reduce the risk of developing most non-communicable diseases. But many South Africans, like many Americans, are overweight or obese due to poor nutrition and lack of physical activity. Researchers interested in public health have sought to address these issues with little success.

However, a new study from the Annenberg School for Communication at the University of Pennsylvania published this week in the Journal of Adolescent Health found that a specially designed health intervention given to South African youth improved healthy eating and exercise, with effects lasting at least 4.5 years.

Administered to sixth grade students, the intervention consisted of 12 one-hour educational modules, implemented over six sessions and given on consecutive school days. Students participated during their extracurricular time at school, in lieu of some other leisure activity.

Aimed at teaching students the importance of eating fruits and vegetables and exercising regularly, the modules were taught by trained facilitators, not the students' regular teachers, and consisted of interactive lessons and games, including "Health Jeopardy." The researchers also developed a series of comic books addressing health issues that were used in the modules.

"We spent years developing the intervention before launching the study," says Annenberg professor John B. Jemmott III, lead author on the paper. "We conducted a series of focus groups with local South Africans to ensure we created something culturally relevant. It was also important to us that the intervention be conducted in isiXhosa, the local language."

More than 1,000 students from 18 schools participated in the study voluntarily and with parental permission. The study was extremely popular among students, so much so that at some schools the demand could not be met due to space constraints. In addition, the study had more than 90% participation for the duration of the data collection period, even at the final follow up, which occurred 4.5 years after the initial intervention.

"We had extremely high attendance rates at the intervention sessions and at all the follow-up visits," Jemmott says. "I've never had attendance rates and return rates for data collection as high as this study."

Immediately before and after the intervention, students completed questionnaires, self-reporting on their eating and exercise habits. Researchers later returned to collect self-reported data at 3, 6, 12, 42, and 54 months.

Participants in the intervention had greater odds of meeting guidelines for healthy eating and physical activity than the control group. They also reported consuming more servings of fruits and vegetables and fewer servings of fried food, and engaging in more days of aerobic exercise and muscle-strengthening activity, than those in the control group.

"The results of the study are impressive," Jemmott says. "One six day intervention creating behavior change that lasts for 4.5 years is quite promising, and I'd like to see additional research to better understand how we can encourage healthy behavior."

Lung cancer in people who have never smoked is more common than most people think, and on the rise

Historically strong, and correct, messaging on smoking and lung cancer has inadvertently contributed to lung cancer receiving much less attention than breast, prostate and ovarian cancers

Increasing awareness could help lead to earlier diagnosis, reduce the blame culture around lung cancer and re-balance research funding

A group of respiratory medicine and public health experts are calling for lung cancer in never-smokers to be given greater recognition. Writing in the Journal of the Royal Society of Medicine, they say that lung cancer in people who have never smoked is under recognised and presents a diagnostic challenge, particularly for GPs seeking to balance over-investigation with early diagnosis and high quality care.

It is estimated that around 6,000 people in the UK who have never smoked die of lung cancer every year, greater than the numbers of people who die of cervical cancer (900), lymphoma (5,200), leukaemia (4,500) and ovarian cancer (4,200).

Major contributors to lung cancers in never-smokers include second-hand smoke, occupational carcinogen exposure and outdoor pollution. Globally, the use of solid fuels for indoor cooking and second-hand smoke exposure are important contributions to lung cancer in never-smokers and disproportionately affect women.

Lead author, Professor Paul Cosford, Director for Health Protection & Medical Director, Public Health England, said: "This paper demonstrates an estimated 6,000 people who have never smoked die each year from lung cancer in the UK. This makes it, by itself, the eighth most common cause of cancer related death in the UK.

"For too long having lung cancer has only been thought of as a smoking related disease. This remains an important association but, as this this work shows, the scale of the challenge means there is a need to raise awareness with clinicians and policy makers of the other risk factors including indoor and outdoor air pollution.

"This is one reason why PHE published its review of the evidence and recommended specific actions local authorities can take to improve their air quality. By delivering on the promise of a clean air generation we can reduce the number of lung cancers among those who have never smoked."

Co-author Professor Mick Peake, clinical director of the Centre for Cancer Outcomes, University College London Hospitals Cancer Collaborative, said: "Despite advances in our understanding, most people who have never smoked do not believe they are at risk and often experience long delays in diagnosis, reducing their chances of receiving curative treatment."

Prof Peake added: "The stigma of smoking has been the major factor behind the lack of interest in, knowledge of and research into lung cancer. Therefore, in many ways, never-smokers who develop lung cancer are, as a result, disadvantaged.

"Drawing attention to the contribution of underlying risk factors to lung cancer in never-smokers presents opportunities to reinforce efforts to tackle other major public health challenges. For example, the impact of passive smoking and air pollution on lung cancers adds weight to the government's ambitions to improve air quality and the public, clinicians and policy makers must all be aware of this relationship."

New study reveals wide variation in spending across the 106 countries, based on whether countries are seeking to control the disease or eliminate it

Development assistance for malaria has plateaued, with 2018 levels virtually unchanged since 2010

Flat-lined funding threatens to stall progress in some low-income countries

SEATTLE - A first-of-its-kind study reveals malaria spending in 2016 totaled $4.3 billion globally, far short of the annual funding target of $6.6 billion set by the World Health Organization.

"A persistent challenge remains as funds are stagnating," said Dr. Joseph Dieleman, a senior author on the study, health economist, and assistant professor at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine. "More resources are needed. This is particularly evident in the poorest countries, especially as they seek to control, or even eliminate, the disease."

An increase of more than 50% in resources is needed annually to bridge the considerable $2.3 billion gap and meet the WHO target.

Dieleman emphasized that the first-of-its-kind study fills a major gap in understanding spending on malaria globally. Published today in the international medical journal The Lancet Infectious Diseases, the analysis provides comprehensive and comparable estimates of total spending on the disease, and also tracks government, out-of-pocket, and donor spending.

"These estimates empower donors, including government agencies, corporations, foundations, and philanthropists, as well as each country's national malaria control program, to evaluate how best to fill crucial gaps between current financing and fast-approaching global targets," he said.

The study spans from 2000 to 2016 and covers 106 countries organized into three groups: malaria control countries, malaria elimination countries, and countries that eliminated the disease after 2000. Malaria control countries are those seeking to aggressively control the disease in high-burden areas, whereas malaria elimination countries have formally declared, or are strongly considering, an evidence-based goal to halt malaria transmission nationally.

Researchers found malaria funding sources shifted substantially over the 17-year study period. Government expenditures accounted for more than half (55.3%, or $643 million) of global malaria spending in 2000, but constituted a much smaller share in 2016 at 28.2% ($1.2 billion). By comparison, government spending accounted for 60.1% of global spending for HIV/AIDS the same year in the 106 countries in the study.

Conversely, development assistance for malaria was a major driver of overall growth in malaria spending between 2000 and 2016, increasing 18.0% per year. At $2.4 billion in 2016, development assistance represented more than half (56.5%) of total malaria spending that year, up from 14.7% ($171 million) in 2000.

While development assistance for malaria accounted for more than $10 billion in total spending between 2000 and 2010, it plateaued in recent years, with 2018 levels virtually unchanged since 2010. To sustain progress, study authors noted funding above current levels of development assistance for malaria is needed.

"We are 11 years away from the date set by the United Nations for 'ending the epidemic' of malaria," lead author Annie Haakenstad said. "The world is watching, and unless more financial resources emerge, that goal will represent a great lost opportunity."

Additionally, the study exposes wide variations in malaria spending across the 106 countries, depending on whether countries were seeking to control the spread of the disease or eliminate it. Between 2000 and 2016, nearly $30 billion was spent on malaria in the 47 control countries, representing the bulk (72.8%) of total spending globally on the disease. $2.6 billion was spent in these countries in 2016 alone.

Findings demonstrate that as malaria incidence declines toward zero, government financing becomes by far the largest source of financing. In 2016, governments in elimination countries contributed a larger share (47.9%) of malaria spending than those in control countries (28.3%).

Additional findings include:

The United States government has been the largest source of malaria funding since 2008, with a contribution of $876 million in 2018 alone.

In terms of disbursements, the largest shares of development assistance for malaria in 2018 were distributed through the Global Fund ($1.0 billion, or 42.6% of the total) and US bilateral aid agencies including the President's Malaria Initiative ($374 million, or 15.5% of the total).

The share of malaria spending sourced out-of-pocket declined from 26.4% ($307 million) in 2000 to 13.0% ($556 million) in 2016, and is highest in countries with the largest malaria burden.

Between 2000 and 2016, a quarter ($10.1 billion) of total malaria spending occurred in the 41 eliminating countries, with $854 million expended in 2016 alone.

In 2016, malaria spending in control countries was $14 per incident case on average; this amount was twice as high, $28, in elimination countries, due in part to lower incidence.

With four of every five malaria cases globally occurring in sub-Saharan Africa, the share of malaria spending in the region in 2016 amounted to $2.7 billion, or 62.8% of global malaria spending.

Highest total spending on malaria ($USD), 2016

Nigeria: $424.4 million

Democratic Republic of the Congo: $189.2 million

Tanzania: $183.6 million

Uganda: $173.9 million

Ghana: $172.0 million

Mozambique: $131.4 million

Angola: $119.9 million

Zambia: $119.5 million

India: $118.6 million

Countries with largest fraction of malaria spending that is out-of-pocket (%), 2016

Niger: 58.4%

Cameroon: 51.6%

Somalia: 47.6%

Nigeria: 37.8%

Equatorial Guinea: 35.0%

Sierra Leone: $32.6%

India: 28.4%

Republic of the Congo: 27.5%

Yemen: 27.5%

Ghana: 24.8%

Countries with largest fraction of malaria spending that is development assistance (%), 2016

Madagascar: 91.8%

Haiti: 86.8%

Afghanistan: 85.1%

Comoros: 85.1%

Laos: 84.9%

Guinea-Bissau: 83.6%

Senegal: 82.5%

Rwanda: 82.4%

The Gambia: 81.4%

Chad: 81.3%

The study is entitled "Tracking spending on malaria by source in 106 countries, 2000-2016: an economic modelling study."

Kaiser Permanente researchers find long-term benefits for patients and health organizations that employ screenings, interventions, and referrals.

Screenings, interventions, and referrals can help adolescent teens overcome substance abuse in the short-term. Less is known about the long-term effects of those efforts. A new study from Kaiser Permanente, published in the journal Pediatrics, suggests that the benefits can last for many years and can include sustained reductions in mental health conditions.

In a new study titled "Health Care Utilization Over 3 Years After Adolescent SBIRT," researchers led by Stacy Sterling, DrPH, MSW, of Kaiser Permanente's Division of Research in Northern California, found that adolescents with access to SBIRT -- short for "screening, brief intervention, and referral to treatment" -- were less likely to have mental health or chronic medical conditions after 1 year.

Substance abuse is "closely associated with the top three causes of mortality and morbidity among adolescents -- injuries, suicide and homicide," write the authors. And, they note, adolescent substance use often goes hand-in-hand with other medical and mental health conditions and can lead to higher use of health care services.

In this new study, they found that those with access to SBIRT services had fewer psychiatry visits over 1 and 3 years, and fewer total outpatient visits at 3 years, leading to lower costs and utilization of health care.

"The fact that we saw a difference in substance use problems even 3 years out was surprising," said Sterling, the study's lead author. "It suggests that providing access to SBIRT may plant a seed for patients and their care teams, creating awareness about substance use that may help kids avoid future problems."

The study used data from electronic health records to examine how much health care was used among adolescents with access to SBIRT services, from a randomized clinical trial that compared usual care to 2 other methods of delivering SBIRT in pediatric primary care -- delivered by a pediatrician or by an embedded behavioral clinician.

The study was conducted at Kaiser Permanente in Northern California, an integrated health care delivery organization. The sample was taken from the pediatrics department in Oakland, California, and consisted of 1,871 adolescents ages 12 to 18.

"We found that adolescents with access to SBIRT services, regardless of whether it was through their pediatrician or an embedded behavioral health clinician, were less likely to have mental health or chronic medical conditions after 1 year," Sterling said. "We also found that SBIRT likely leads to lower health care utilization."

The authors suggest that pediatric primary care and adolescent medicine clinics should consider implementing SBIRT, whether through training pediatricians or embedding SBIRT-trained behavioral health clinicians (or both) into the care team. Increased attention, training, and capacity to address substance use and other behavioral health problems can have a significant impact on future health problems and health care use.

"We need to increase resources and focus on the role of behavioral health on the overall health and well-being of children and teenagers in our care," added Sterling. "I think more research is needed on SBIRT and these important, long-term health impacts."

An open-label, multi-cohort Phase II trial, led by investigators at The University of Texas MD Anderson Cancer Center, reports that treatment with the drug tagraxofusp resulted in high response rates in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare but highly aggressive - and often fatal bone marrow and blood disorder - for which there are no existing approved therapies.

Study findings were published in this week's online issue of the New England Journal of Medicine. The trial was the largest prospectively designed multi-center, multi-cycle clinical study specifically dedicated to patients with BPDCN and was led by Naveen Pemmaraju, M.D., associate professor, Hagop Kantarjian, M.D., chair, and Marina Konopleva, M.D., Ph.D., professor, all in in the Department of Leukemia.

"In adults with BPDCN, tagraxofusp led to clinical responses regardless of whether patients had received previous therapy," said Pemmaraju. "We observed high response rates including an overall response rate of 90 percent among frontline-treated patients. These findings offer hope for patients who have had no treatments specific to this disorder."

The primary outcome occurred in 72 percent of patients with an overall response rate of 90 percent. Of these patients, 45 percent went on to undergo stem cell transplantation. Survival rates at 18 and 24 months were 59 percent and 52 percent respectively. Among the previously untreated patients, the response rate was 67 percent and median overall survival was 8.5 months.

BPDCN can affect multiple organs, including the lymph nodes and the skin, and often presents as leukemia or evolves into acute leukemia. Patients historically have experienced poor outcomes and low response rates after chemotherapy treatment following diagnosis. Treatment typically included chemotherapy approved for other blood cancers, and/or stem cell transplants. However, the majority of patients are older with a median age of 68 to 72 years, an age at which many patients are unable to undergo intensive chemotherapy and cannot undergo stem-cell transplantation which requires chemotherapy as a first treatment.

Forty-seven patients with a median age of 70 years were enrolled in the seven-site study which provided tagraxofusp as a first-line or relapsed/refractory treatment. Of those patients, 32 were given tagraxofusp as first-line treatment, and 15 had previous standard-of-care therapy. Median follow-up was
13.8 months and treatment was continued until disease progression or unacceptable side effects. The primary outcome was the combine rate of complete response and clinical complete response among patients who had not previously received any treatment. A secondary outcome was duration of response.

Tagraxofusp is a novel targeted therapy that targets CD-123, a cell surface receptor, expressed in BPDCN and other hematologic malignancies. The drug is also being investigated in other clinical trials, including for patients with chronic myelomonocytic leukemia (CMML) and myelofibrosis. Tagraxofusp was approved by the U.S. Food and Drug Administration in December for BPDCN treatment in adults, and in pediatric patients over age 2.

Drug side effects include low albumin and increased liver enzyme levels, and a potentially serious condition called capillary leak syndrome. Safety measures were instituted to identify symptoms early and reduce adverse outcomes.

Women who take antibiotics over a long period of time are at increased risk of heart attack or stroke, according to research carried out in nearly 36,500 women.

The study, published in the European Heart Journal [1] today (Thursday), found that women aged 60 or older who took antibiotics for two months or more had the greatest risk of cardiovascular disease, but long duration of antibiotic use was also associated with an increased risk if taken during middle age (aged 40-59). The researchers could find no increased risk from antibiotic use by younger adults aged between 20-39.

Professor Lu Qi, director of the Tulane University Obesity Research Centre, Tulane University, New Orleans, and adjunct professor of nutrition at Harvard T.C. Chan School of Public Health, Boston, USA, who led the research, says that a possible reason why antibiotic use is linked to an increased risk of cardiovascular disease is because antibiotics alter the balance of the micro-environment in the gut, destroying "good" probiotic bacteria and increasing the prevalence of viruses, bacteria or other micro-organisms that can cause disease.

"Antibiotic use is the most critical factor in altering the balance of microorganisms in the gut. Previous studies have shown a link between alterations in the microbiotic environment of the gut and inflammation and narrowing of the blood vessels, stroke and heart disease," he said.

The researchers studied 36,429 women who took part in the Nurses' Health Study, which has been running in the USA since 1976. The current study looked at data from 2004 to June 2012. In 2004 the women were aged 60 or older, and they were asked about their use of antibiotics when they were young (20-39), middle-aged (40-59) or older (60 and older). The researchers categorised them into four groups: those who had never taken antibiotics, those who had taken them for time periods of less than 15 days, 15 days to two months, or for two months or longer.

During an average follow-up period of nearly eight years, during which time the women continued to complete questionnaires every two years, 1056 participants developed cardiovascular disease.

After adjustments to take account of factors that could affect their results, such as age, race, sex, diet and lifestyle, reasons for antibiotic use, overweight or obesity, other diseases and medication use, the researchers found that women who used antibiotics for periods of two months or longer in late adulthood were 32% more likely to develop cardiovascular disease than women who did not use antibiotics. Women who took antibiotics for longer than two months in middle age had a 28% increased risk compared to women who did not.

These findings mean that among women who take antibiotics for two months or more in late adulthood, six women per 1,000 would develop a cardiovascular disease, compared to three per 1,000 among women who had not taken antibiotics.

The first author of the study is Dr Yoriko Heianza. a research fellow at Tulane University. She said: "By investigating the duration of antibiotic use in various stages of adulthood we have found an association between long-term use in middle age and later life and an increased risk of stroke and heart disease during the following eight years. As these women grew older they were more likely to need more antibiotics, and sometimes for longer periods of time, which suggests a cumulative effect may be the reason for the stronger link in older age between antibiotic use and cardiovascular disease."

The most common reasons for antibiotic use were respiratory infections, urinary tract infections and dental problems.

The study is the largest prospective study to investigate the link between antibiotic use and risk of heart disease and stroke, and this is one of the strengths of the study, as well as the long follow-up and comprehensive information on factors that could affect the results such as life style, diet, age, other diseases and medication use.

Limitations include the fact that the participants reported their use of antibiotics and so this could be mis-remembered. However, as they were all health professionals, they were able to provide more accurate information on medication use than the general population. The researchers did not have information on the different classes of antibiotics used, but believe that the most common type of prescription tends to depend on the infections it is treating, and information on these was included in their analysis. As the study only looked at middle-aged and elderly women, the results cannot necessarily be extrapolated to younger ages and to men.

Prof Qi concluded: "This is an observational study and so it cannot show that antibiotics cause heart disease and stroke, only that there is a link between them. It's possible that women who reported more antibiotic use might be sicker in other ways that we were unable to measure, or there may be other factors that could affect the results that we have not been able take account of.

"Our study suggests that antibiotics should be used only when they are absolutely needed. Considering the potentially cumulative adverse effects, the shorter time of antibiotic use the better."

A multi-institutional clinical trial has given good results for a targeted therapy to treat a rare, aggressive blood cancer known as blastic plasmacytoid dendritic-cell neoplasm (BPDCN). Details on the trial, which supported Food and Drug Administration approval of the tagraxofusp therapy in December 2018, have been published in the New England Journal of Medicine.

Diagnosed in several hundred people in the United States each year, BPDCN is a cancer of dendritic cells--a type of immune cell. BPDCN has some of the features of leukemia and lymphoma, and typically produces skin tumors as well. The standard treatment is chemotherapy, with the goal of proceeding to allogeneic stem cell transplants. However, the median age of diagnosis is about 65, and many patients are not robust enough for the intensive chemotherapy usually required to prepare for stem cell transplant.

"The response rate to this drug was quite high, particularly in patients who had not previously been treated," said Andrew Lane, MD, PhD, co-first author of the paper and director of Dana-Farber's BPDCN Center.

Notably, among 29 previously untreated patients with BPDCN who were given a recommended dose of tagraxofusp therapy, 45% did well enough to proceed to stem cell transplants--until recently, the best known hope for treating the cancer in the long-term. At the time the paper's analysis was completed, the overall survival rate for this population was 59% at two years, which compares favorably with typical survival rates.

Tagraxofusp is a biological therapy that targets a protein known as CD123 that is over-expressed by BPDCN tumor cells but not on other immune cells. The therapy includes a diphtheria toxin to kill the tumor cells.

Phase 1 of the trial recruited participants with either BPDCN or acute myeloid leukemia. They were infused with 7 or 12 micrograms per kilogram of body weight of tagraxofusp, daily for five days of a 21-day cycle. Among 47 patients overall treated for BPDCN in both phases of the trial, 32 had not been previously treated and 15 had been treated. The trial's primary outcome for BPDCN was a combination of complete response and "clinical complete response" among previously untreated patients. (To achieve clinical complete response, signs of the disease had to disappear in every site except the skin, where it was no longer active.)

In the 29 first-line patients given the 12 microgram dose, the overall response rate was 90%. Among previously treated patients, the response rate was 67% and median overall survival was 8.5 months.

"We treated patients up to the age of mid-80s, and there was no obvious difference in toxicity by age, which is not the case in standard chemotherapy," said Lane. "Unlike standard chemotherapy, there doesn't seem to be a cumulative toxicity with this drug. In fact, its side effects are most prominent in the first treatment cycle." Patients who didn't become eligible for a stem cell transplant often stayed on tagraxofusp for many cycles, with two patients remaining on the drug for over a year.

The drug's most significant side effect was a potentially dangerous condition known as capillary leak syndrome. During the trial, the investigators tightened the inclusion criteria to ensure that participants displayed normal cardiac function. Additionally, the researchers established procedures to detect and treat the syndrome during treatment.

Nine cancer centers participated in the study, gathering patients from all over the world. Co-first author on the paper is Naveen Pemmaraju, MD, and senior author is Marina Konopleva, MD, PhD, both of The University of Texas MD Anderson Cancer Center.

"We can celebrate this new drug; it's great to have approval," said Lane. "Still, we continue to work on improving outcomes for patients." Among his ongoing research, he's leading two other clinical studies of targeted therapies for BPDCN.

One trial is testing venetoclax, an inhibitor of a protein called BCL2 that helps to regulate cell death. Preclinical work showed that BPDCN might be vulnerable to BCL2 inhibition, and an off-label study of venetoclax (which is approved for chronic lymphocytic leukemia) showed promise in two BPDCN patients.

The second trial is for a therapy that binds to the CD123 protein and delivers chemotherapy directly to the BPDCN cells.

The Lane Laboratory is currently studying ways to effectively combine tagraxofusp with other drugs. Preclinical experiments showed that a class of drugs known as "hypomethylating agents" may be particularly promising. Lane is now heading a trial that pairs up tagraxofusp with one such agent to treat two other blood cancers, and this combination may eventually be tested with BPDCN patients.

Given BPDCN's rarity and sometimes puzzling presentation, the disease was only officially defined by the World Health Organization in 2008. "Going from naming the disease to having a drug approved by the FDA in ten years is very encouraging," said Lane.

Philadelphia, April 23, 2019 - Boys are four times more likely than girls to be diagnosed with autism spectrum disorder (ASD), yet a growing body of research shows that the condition is more common in girls than previously thought, strongly suggesting that new methods are required to diagnose the disorder at younger ages.

A new study from Children's Hospital of Philadelphia (CHOP) examined differences in the way girls and boys on the autism spectrum used certain types of words during storytelling. This study found that autistic girls used significantly more "cognitive process" words such as "think" and "know" than autistic boys, despite comparable autism symptom severity. The results were recently published in the journal Molecular Autism.

The authors suggest that identifying differences like these opens the door to making sure girls with ASD receive the diagnosis and support they need to achieve the best possible quality of life.

"In order to place these findings in context, it's important to understand that because girls tend to exhibit different traits than autistic boys do, they are often incorrectly diagnosed or missed entirely by standard diagnostic tools. That discrepancy also skews the research literature," explained lead author Julia Parish-Morris, PhD, a scientist in the Center for Autism Research and faculty member in the Departments of Child Psychiatry and Biomedical & Health Informatics at CHOP. "Autism studies have historically included three to six times as many males as females. This means that we don't yet know enough about gender differences in autism, and so we miss girls whose traits differ from those of boys."

A misdiagnosis means many girls do not receive early intervention and that standard interventions may not be appropriate for meeting girls' unique needs. Many autistic women are not diagnosed until they are adults and report significant social challenges and a profound sense of being different from their typically developing peers.

"Autism is a social condition diagnosed using observable behavior, so we wanted to study an observable skill that relates to social ability," Parish-Morris said. "We chose storytelling because it involves much more than grammar and vocabulary; it relies on a sense of social appropriateness and sheds light on what speakers decide is important to convey."

The researchers focused on how participants used nouns (object words) compared with cognitive process words, because prior studies found that reduced use of cognitive process words predicted social challenges in ASD. Although past studies used primarily male samples, the results were assumed to generalize to girls, and prior ASD studies never included enough girls to test whether sex differences that exist among typically developing individuals persist in those with ASD.

Parish-Morris and her co-authors studied 102 verbally fluent school-aged children who either had a diagnosis of ASD (21 girls and 41 boys) or were typically developing (19 girls and 21 boys), and were matched on age, IQ and maternal education. The children viewed a sequence of pictures involving a fisherman, a cat and a bird, and told a story based on what they saw.

Results revealed that autistic girls used significantly more cognitive process words than autistic boys did, even when they had similar levels of autism severity. Girls with ASD and typical girls used comparable numbers of cognitive process words. Interestingly, autistic boys and girls both used more nouns than typically developing children, demonstrating object-focused storytelling. Thus, autistic girls showed a unique narrative profile that overlapped with typical girls and boys as well as with autistic boys.

"Through storytelling, we were able to identify key similarities and differences in the language patterns of autistic girls and boys," Parish-Morris said. "These findings suggest that sex-informed screening and diagnostic methods may help us identify autism in verbal girls at an earlier age, which should spur efforts to develop appropriate, personalized early interventions resulting in improved support for girls and women with ASD."

Far Eastern Federal University (FEFU) scientists teamed up with colleagues from the UK and Mauritius and experimentally demonstrated that extracts of the endemic (i.e. growing only on this island) medicinal herb leaves Acalypha integrifolia, Eugenia tinifolia, and Labourdonnaisia glauca stop the proliferation of oesophageal squamous carcinoma cells, ones of the most deadly cancer type worldwide. A related article is published in the "Acta Naturae" journal.

Researchers found out that the extracts contain natural chemical compounds to inhibit the propagation of cancer cells. Namely, they restrain the G2/M stages transition in malignant tumor cells by activating AMPK signaling pathway. Currently, the search for AMPK activators is an urgent problem in molecular oncology. Having studied the medical herbs of Mauritius, scientists may have accomplished an important step, if not a breakthrough in this direction.

"Mauritius Island is a treasure island of the global biodiversity, and the story of continuing tragedy of human greed, barbarian appetite (remember the Dodo bird from the Alice story, RIP) and neglection of true wonders of the planet designed to save human lives. About one-third of the local plants are used in traditional medicine, but there is still a lack of scientific evidence of their therapeutic potential, while genocide of nature is most evident on such small pieces of lost paradise. To date, only 15 percent of the island's plant species have been examined for their medicinal properties, which is still better than in many countries. Ethnobotany combined with modern organic chemistry and cell biology is an extremely fruitful interdisciplinary field for scientific research. We hope to proceed working in this direction, thanks to the growing globally Bio2bio* movement supported by the Global Young Academy**. In particular, further study of the active compounds from the leaves extracts of A. integrifolia, E. tinifolia and L. Glauca promises to reveal prototypes of the future drugs to treat oesophageal cancer, and other deadly diseases" - said Alexander Kagansky, the Head of the Center for Genomic and Regenerative Medicine of the School of Biomedicine FEFU, an expert in the field of cancer epigenetics and chromosome biology.

The lead scientist noted that oesophageal cancer is a growing global concern due to the diets and other detrimental side effects of modern lifestyles, technologies, and culture. At the present time, there is not enough effective means of its treatment, while the existing radiotherapy, chemotherapy resection may prolong lives by few months, usually spent in tremendous suffering. The aggressive disease prevents eating, digestion, and come along with a very negative prognosis. Oesophageal squamous carcinoma together with adenocarcinoma represent the sixth main death cause in the global oncological practice. Less than 15 percent of patients survive for five years from the time of diagnosis. On average, people with such diagnoses live less than a year. These types of cancer are treated with broad-spectrum chemo. The drugs are extremely toxic and evoke a number of side effects worsening the patients' quality of life. At the same time, the efficacy of current chemotherapy for this disease is not very assuring, to say the least.

More than half of all anti-cancer drugs employing today were developed from natural sources. At the same time, most of the world's population treats cancer by means of thousands of herb species that have been known to traditional medicine for centuries, each of those coming with many different naturally chemistries, evolved for use in nature for millions of years. Taking into the account centuries-old human understanding of nature, modern biomedicine needs to develop new anti-cancer compounds from a wide range of natural sources, such as plants, fungi, bacteria, insects, and marine organisms.

During the study, FEFU scientists in cooperation with foreign colleagues studied in the laboratory carefully isolated and fractionated extracts of five species of Mauritian endemic medicinal plants: Acalypha integrifolia Willd (Euphorbiaceae), Labourdonnaisia glauca Bojer (family Sapotaceae), Dombeya acutangula Cav. subsp. rosea Friedmann (Malvaceae), Gaertnera psychotrioides (DC.) Baker (Rubiaceae), Eugenia tinifolia Lam (Murtaceae). They were tested on the cell lines from two different types of patients' malignant tumors. Three of the five biologically active substances of these species have shown to contain effective inhibitors of oesophageal cancer cells, stopping their growth and contributing to their death.

Alexander Kagansky emphasized that the future of global medicine depends on the saving of the planet's biodiversity. He reminded that currently the total number of living species is steadily declining. Bringing on the example of medicinal plants of Mauritius, which he and colleagues took an effort to study, the scientist pointed out that they are devastated at an incredible rate at which species are being erased from existence as a result of human 'progressive' activities, such as lumber, energy, and food generation. At the meanwhile, so far these unique species do not grow anywhere else on the planet, a few additional 5-star hotels, bank building, or a golf-course could end up their existence once and for all. Given this, Kagansky became a co-organizer of the Bio2Bio* international consortium thanks to the support of the Global Young Academy and the Interacademy Partnership***. The task of Bio2bio is to protect biodiversity and nature which are sources of valuable biological compounds, as well as to create a database of natural molecules that will provide a basis for drug components elucidation, and for linking traditional medicine systems with each other and modern medicine via integration of other areas such as pharmacognosy, ethnobotany, synthetic and analytic chemistry, immunology, pharmacology, molecular and cell biology, metabolomics, etc.

"Our research should serve the benefit of humanity and show by evidence that on the mechanistic level people depend on natural chemistries, which will reward us by reducing deaths and suffering of ourselves, our parents, and children", the scientist said.

April 22, 2019 - Even with a good diet and workout routine, some men and women have trouble getting the toned abdominal appearance they want. For these patients, a technique called abdominal etching can help in creating the classic "six-pack abs" physique in men or three-vertical-line abdomen in women, reports a study in the April issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

The procedure uses precisely targeted liposuction to achieve greater definition of the abdominal muscles, according to the paper by Tarik M. Husain, MD, FACS, of University of Miami Leonard M. Miller School of Medicine and colleagues. "Abdominal etching using power-assisted liposuction is a novel method of sculpting an ideal abdomen," Dr. Husain comments. "Our study shows that this is a safe and effective method to create a defined anterior abdominal wall in both male and female patients."

Emerging Liposuction Technique Produces Abdominal 'Six-Pack'

The researchers review their experience with liposuction to improve the appearance of the abdomen in 50 patients: 26 men and 24 women, average age 36 years. Patients seeking abdominal etching were in good shape, with a healthy diet and regular exercise routine, but had "certain resistant areas of fat" that made it difficult to achieve the abdominal muscle definition they desired.

Dr. Husain and coauthors outline the procedure in detail, starting with patient selection and preoperative markup. Following meticulous liposuction technique, the plastic surgeon sculpts the abdominal fat in both the superficial and deeper layers, accentuating the patient's natural "six-pack" lines in males and 3 vertical lines in females. Hip lines are usually desired by both sexes. The technique can be altered to provide a softer, shallower or a harder, more-defined degree of abdominal etching, depending on the patient's preference. The online version of the article on the Plastic and Reconstructive Surgery website includes a video illustrating key aspects of the procedure for plastic surgeons.

The authors spell out critical steps for postoperative care. Foam dressings are cut to size to compress the newly etched lines for at least three days. This is followed by full-time compression for two weeks postoperatively and two weeks part-time after that.

It is critical to have regular follow up early on to assess for any fluid collections, or seromas. To ensure good results, these seromas - typically regarded as a minor complication - need to be treated aggressively if they occur.

Patients can resume light exercise not engaging the core after two weeks, and more rigorous exercise after four weeks. The researchers stress the importance of maintaining good long-term results, with the assistance of a sports nutritionist and/or integrated medicine physician to optimize nutrition, exercise plan, and hormone imbalances. Patients have maintained good results of abdominal etching at follow-up times up to six years.

None of the 50 patients undergoing abdominal etching had major complications requiring hospitalization or return to the operating room. Minor complications occurred in 22 percent of patients, such as contour irregularities (usually "over-etching") that typically soften up and improve over time. Seromas developed in 10 percent of patients, and were promptly managed by a simple office procedure.

"The patients exemplify that the procedure can be performed with optimal aesthetic results, and minimal postoperative complications," Dr. Husain and coauthors conclude. They hope their technique and experience of abdominal etching will serve as a useful guide to other plastic surgeons who are interested in offering this relatively new procedure. The authors add, "We also highlight our extensive post-operative management, with the addition of a multidisciplinary nutrition and personal training team with the goal to maintain [patients'] long-term results and retain their newly etched abdominals."

April 22, 2019 - "Tummy tuck" surgery (abdominoplasty) can be safely performed in obese patients, with no increase in complications compared to non-obese patients, reports a study in the April issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

"Abdominoplasty, with or without concurrent liposuction, in obese patients is a safe and effective procedure with similar perioperative complication rates as the non-obese patient population," write ASPS Member Surgeon Laurence Glickman, MD, MSc, FACS, and colleagues of Long Island Plastic Surgical Group, Garden City, NY. The findings help to alleviate concerns that obese patients are at higher risk of complications after tummy tuck.

Good Outcomes and Safety of Abdominoplasty in Patients with Obesity

The study included 82 patients who underwent abdominoplasty - a popular cosmetic surgery procedure to improve the appearance of the abdomen - over a seven-year period. Twenty-one patients were classified as obese, based on an average body mass index (BMI) of 35 kilograms per square meter (kg/m2). The remaining 62 patients were classified as non-obese, average BMI 25 kg/m2.

Complication rates were compared between groups, with an average follow-up time of close to one year. Obese patients were more likely to have high blood pressure; otherwise, risk factors were similar between groups. All procedures were performed by Dr. Glickman, following the same technique. For most patients in both groups, tummy tuck surgery was combined with liposuction.

As in previous studies of abdominoplasty, there was a significant risk of complications. However, all complication rates were similar between groups. Obese patients had a higher rate of fluid collections under the skin (seromas) requiring drainage: 22.5 versus 14.2 percent. However, the difference between groups was not statistically significant.

Rates of other complications were also similar between groups, including infections, wound-healing problems (dehiscence), and blood collections under the skin (hematomas). No patient in either group developed problems with blood clots (venous thromboembolism), a more serious type of complication.

Abdominoplasty is the fifth most common cosmetic procedures in the United States, with nearly 130,000 procedures performed in 2017, according to ASPS statistics. Although widely performed, abdominoplasty carries the highest complication rate of all cosmetic procedures.

"Many surgeons elect not to perform abdominoplasty on patients with a high BMI, fearing an increased risk of perioperative complications," Dr. Glickman and coauthors write. Most previous studies of abdominoplasty in high-BMI patients have focused on those who have undergone bariatric surgery (such as gastric bypass), who are at increased risk of complications.

The findings help to clarify the "risks and rewards" of abdominoplasty in non-bariatric surgery patients with a BMI in the obese range. "Our study results suggest that patients with a BMI greater than 30 in and of itself should not be viewed as a strict contraindication to abdominoplasty," Dr. Glickman and coauthors conclude. They cite a previous study suggesting that decisions about tummy-tuck surgery should consider the individual patient's risk factors, and not be based on BMI alone.

"Plastic surgeons should evaluate patients on a case-by-case basis and patients should be counseled as to the potential perioperative risks of this procedure," the researchers add. They also emphasize the importance of discussing realistic postoperative goals with patients considering abdominoplasty.

In 2015, about half of the world's 28 million human deaths were the result of medical emergencies, with the bulk of the burden borne by poorer nations, according to a statistical analysis of information from nearly 200 countries by a Johns Hopkins Medicine researcher. The analysis, described in April in the journal BMJ Global Health, offered what is believed to be a first-of-its-kind look at the lethal impact of medical emergencies worldwide.

"In terms of global health, most of the research has traditionally focused on primary care and disease prevention, and emergency care has not been a priority," says Junaid Razzak, M.B.B.S, Ph.D., professor of emergency medicine at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Center for Global Emergency Medicine. "We believe our study is among the first to identify the scope of the burden emergency medical conditions -- combining injuries, strokes, heart attacks and lung infections -- impose overall and in specific countries." The results, he added, could lead to future public health strategies that save lives and redirect resources.

In their study, Razzak and fellow researchers started with morbidity and mortality data involving more than 30 emergency medical conditions in 195 countries. The data were drawn from the 1990 and 2015 Global Burden of Disease (GBD) studies, an internationally collaborative database of hundreds of medical condition statistics housed at the Institute for Health Metrics and Evaluation at the University of Washington and commonly used by researchers around the globe. In general, an emergency condition was defined as those requiring interventions within minutes to hours to reduce the chance of disability and death and improve health outcomes.

Razzak and his team's results show a 6 percent increase in deaths of adults and children due to emergency conditions between 1990 and 2015. Over the 25-year period, the most significant decrease was found in upper-middle-income countries, and the lowest level of decrease -- between 11 and 15 percent -- in poorer nations. Overall, the mortality burden of medical emergencies was found to be more than four times to five times higher in low-income countries around the world compared to high-income countries.

Globally, injuries from accidents, falls and burns (22 percent), heart attacks (17 percent), lung infections (11 percent) and strokes (7 percent) made up the top emergency conditions and diseases in 2015. Other conditions such as diarrheal diseases and malaria had a lower overall global burden, but were more prevalent in low-income countries. The analysis also showed that emergency diseases affect men much more than women, and half of all the emergency disease burden was among people younger than 45 years old.

Countries with the lowest mortality and morbidity burden of medical emergencies included Bahrain, Israel and Kuwait, while Chad, Niger and Mali had the highest burdens. China, India and the United States, the three most populous countries studied, were ranked globally at 64th, 144th and 47th out of 195, respectively, in terms of the lowest burden of emergency diseases. "The level of disparity between richer and poorer nations is significant, and should not be acceptable to the global community," Razzak says.

To determine the statistics, the researchers developed two novel "indicators" -- the Emergency Disease Mortality Rate (EDMR) and the Emergency Disease Burden (EDB) -- designed to standardize, measure and rank the scope and scale of emergency care and deaths at national, regional and global levels. The EDMR is based on deaths caused by about 30 selected emergency conditions, and was calculated using a computer algorithm, or formula. The EDB is a separate computer algorithm using disability adjusted life years (DALYs), the total number of years lost due to death or disability based on the life expectancy of a healthier population, or the years of lost life (YLL), which estimates the average years a person would have lived if not for premature death.

Razzak cautions there are limitations in interpreting the statistics because some emergency conditions have chronic precedents and components. He says hypertension, for example, can become an "emergency" stroke even after years of "silent" impact if it's untreated or undertreated. Still, he hopes the research appeals to policymakers and enhances investments in emergency care, whether in ambulance systems or in the emergency departments themselves. "As policymakers start to focus and improve emergency care, we hope fewer lives will be lost," he says.

ATLANTA --In a commentary published in the American Journal of Kidney Diseases, public health researchers suggest adjustments to recently proposed rule changes on how Medicare pays for dialysis services.

Medicare spends approximately $35 billion annually on care for beneficiaries with end-stage renal disease (kidney failure), more than 7 percent of Medicare's total paid claims. Over half a million people receive regular dialysis treatments to manage this condition, with treatment costs averaging about $85,000 a year, according to the study.

"A year ago, rule changes were proposed that would limit how many dialysis treatments per week Medicare would pay for," says first author Adam S. Wilk, PhD. "Nephrologists, patients and other interest groups expressed concern that this would have the effect of limiting dialysis patients' access to innovations in treatment, like 'frequent hemodialysis,' that have the potential to improve outcomes and quality of life in this population." Wilk is assistant professor of health policy and management at the Emory Rollins School of Public Health.

Under the current system, Medicare covers three hemodialysis treatments weekly per patient, but it will often pay for additional treatments when the treating nephrologist provides sufficient medical justification. The recently proposed rule changes would limit such additional payments to exceptional circumstances (for example, patients with temporary, acute kidney treatment needs). Although nephrologists would not be prevented from providing any "extra" treatments they believe are needed, they would typically bear the costs of doing so.

In their article, Wilk and colleagues discussed the limitations of the current evidence on frequent dialysis treatment, which to date has yielded mixed conclusions. The researchers' suggested changes to Medicare's dialysis payment system were designed to account for these limitations and give Medicare the flexibility to further modify the system in the future as new evidence comes to light. Under the most provocative of their proposals, Medicare would establish a new, separate prospective payment system for frequent hemodialysis treatment.

"If Medicare were to adopt the policy options we describe, nephrologists would have greater clarity about how they would be paid for their dialysis care, giving them greater freedom to identify better ways to treat their dialysis patients. Given the poor prognoses most patients undergoing dialysis have, such innovations are greatly needed to improve this population's longevity and quality of life," says Wilk.

There is an important association between maternal cigarette smoking cessation during pregnancy and risk of preterm birth, according to a new Dartmouth-led study published in JAMA Network Open.

The negative health impacts of cigarette smoking during pregnancy--which include low birth weight, delayed intrauterine development, preterm birth, infant mortality, and long-term developmental delays--are well known. In good news, the proportion of women who start their pregnancy as smokers has been declining in recent years.

"Of concern, though, given the substantial benefits of smoking cessation during pregnancy, is the proportion of pre-pregnancy smokers who quit smoking during pregnancy has remained essentially stagnant since 2011," explains lead author Samir Soneji, PhD, an associate professor at The Dartmouth Institute for Health Policy and Clinical Practice, who collaborated with Hiram Beltrán-Sánchez, PhD, an associate professor at the University of California, Los Angeles, on the study.

The investigators sought to assess the probability of preterm birth among expectant mothers who smoked before pregnancy and quit at the start or during pregnancy. Using data from the U.S. National Center for Health Statistics, they conducted a cross-sectional study of more than 25 million pregnant women (modal age 25-29) who gave birth to live neonates during a six-year period (2011-2017)--measuring their smoking frequency three months prior to pregnancy and for each trimester during pregnancy.

Notably, their analysis not only showed that quitting smoking was associated with reduced risk of preterm birth, it showed that the probability of preterm birth decreased more the earlier smoking cessation occurred in pregnancy--up to a 20 percent relative decrease if cessation occurred at the beginning of pregnancy.

However, the study also found that only about 25 percent of women who smoked prior to pregnancy were able to quit throughout their pregnancy, and approximately 50 percent of women who smoked during their pregnancy did so with high frequency (more than 10 cigarettes per day).

"Pregnancy can be a stressful time in a woman's life," says Soneji. "And women who smoked prior to pregnancy may turn to smoking or continue to smoke as a way to mitigate this stress.

"Thus, it is incumbent upon healthcare providers who care for pregnant women to have a renewed focus on smoking cessation," he says. "Pregnancy is often a time when women have more frequent contact with the healthcare system, and this increased contact provides expectant mothers an opportunity to discuss their concerns about smoking, including their attempts to stop, and receive the support and resources they need to safely and successfully quit."

Another positive takeaway from the study is that the benefits gained from cessation extend to heavy smokers. "Even among women who smoke a pack a day or more, there can be a substantial reduction in the risk of premature births if these heavy smokers quit early in pregnancy," Soneji says.

Next, Soneji plans to look at quit rates and smoking intensity and their impact on the risk of infant mortality. "Thankfully most premature babies end up doing well," he says. "But premature birth is strongly linked to infant mortality. If we determine quitting, and quitting early, reduces the risk of infant mortality, then that may speak to mothers even more saliently about the importance of smoking cessation."

Patients prescribed opioid pain medications whose doses varied over time were 3 times more likely to experience an overdose than patients prescribed stable opioid doses, according to an observational study from Kaiser Permanente published today in JAMA Network Open. The study also showed that patients who discontinued long-term opioid therapy for 3 or more months had half the risk of opioid overdose.

"Our study suggests that safely managing long-term opioid therapy is complex," said Ingrid Binswanger, MD, senior investigator at Kaiser Permanente Institute for Health Research in Colorado and co-author of the study.

"This study suggests going up and down on opioid doses -- also called dose variability -- could present an increased risk of overdose," Dr. Binswanger said. "Through this study, we also found eventually discontinuing opioid therapy may prevent overdoses. With continued studies, we hope to find out how care providers can help patients with their pain without putting them at unnecessary risk due to rapid changes in their dose."

The 12-year study included more than 14,000 Kaiser Permanente members in Colorado who were prescribed long-term opioids. Researchers used electronic health records to track the history of patients to see if they had dose changes and overdoses from opioid pain medications and other opioid drugs.

The research team obtained a follow-up $2 million, 4-year grant from the National Institutes for Health. The study will look at how patients and doctors manage changes in opioid doses, including any long-term risks and benefits of discontinuing opioid pain medications.

"Kaiser Permanente, like many health care organizations across the country, has made significant changes to safely reduce opioid prescriptions for our members," said Jason Glanz, PhD, senior investigator at the Institute for Health Research and co-author on the study.

"This study represents the first of many investigations that we plan to do on the topic," Dr. Glanz said. "Our goal is to help identify the most safe and effective approaches for managing long-term opioid therapy. We want to be able to minimize patients' pain and reduce their risk for overdose."