Body

Bioanalysis explores novel LC-MS assays impacting CYP and transporter DDI evaluations

Bioanalysis, a leading MEDLINE indexed journal for bioanalytical scientists, has published a Special Focus Issue on LC-MS assays impacting CYP and transporter DDI evaluations. The journal is published by Future Science Group.

The Special Focus Issue, guest Edited by Ragu Ramanathan (Pfizer), explores novel LC-MS assays impacting CYP and transporter DDI evaluations, through original research articles, as well as expert perspectives in the form of commentary-style articles.

The issue discusses new technologies in MS as well as looking into multiplexing, and getting more information using HRMS, as well as sample pooling approaches. Proposals of several endogenous biomarkers for evaluating DDI at early stages in clinical trials, so DDI studies do not need to be continued into the latter stages, are also explored.

"There is a growing interest in exploring novel LC-MS/MS, LC-high resolution accurate MS (LC-HRMS), or LC-MS/HRMS assays early in drug development to ensure DDI related liabilities to establish safety and efficacy of a NCE. This special issue brings together some the novel LC-MS applications and outlook from leaders in the field" said Ragu Ramanathan (Pfizer).

"I am delighted to have worked with experts in the field to produce this Special Focus Issue, which appears to demonstrate the expansion of interest in using sensitive and selective LC-MS assays for evaluations of DDI potentials early in development of new chemical entities to assure safety and efficacy." commented Sankeetha Nadarajah (Managing Commissioning Editor, Bioanalysis).

To read the full issue, please visit https://www.future-science.com/toc/bio/10/9

The guest editors' free-access foreword article is available online here: https://www.future-science.com/doi/10.4155/bio-2018-0086

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Future Science Group

Campylobacter -- the germ on chicken eggs

Eggs are a popular food. In fact, Germans consumed almost 20 billion of them in 2016, which equates to a per capita consumption of 235 eggs. It is therefore easy to understand why the detection of chemicals in eggs, such as the insecticide fipronil recently, caused quite a stir, not to say an outrage. What is largely unknown, though, is that the most common bacterial pathogen for food infections is also to be found on chicken eggs.

We are talking about Campylobacter bacteria, which cause intestinal inflammation (enteritis) accompanied by stomach ache, fever and - sometimes even bloody - diarrhoea. The German Federal Institute for Risk Assessment (BfR) has now determined the level of knowledge about the occurrence of Campylobacter on chicken eggs and is giving advice on how infections can be prevented.

Link to opinion:
Hygiene for chicken eggs - protection from Campylobacter

Roughly 70,000 cases of Campylobacter enteritis are reported to the Robert Koch-Institute every year, with a slight increase expected. Furthermore, there is a large number of unreported cases. The disease- induced by bacteria usually originates from chicken intestines in which they live but cannot cause harm. These bacteria are often transferred to humans via insufficiently cooked chicken meat. Although the infection risk through chicken eggs is estimated to be much lower, infection can be spread through bacteria-containing excrement which sticks to the eggshell. Food companies should therefore reduce the contamination of chicken eggs with chicken excrement through hygiene measures during production and packaging.

"The risk of infection can be reduced even further by maintaining good kitchen hygiene," explains BfR President, Professor Dr. Dr. Andreas Hensel. "Kitchen utensils and hands should be washed thoroughly after contact with raw eggs. And if dishes that have been prepared with eggs are heated sufficiently, Campylobacter and other disease pathogens are killed reliably."

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BfR Federal Institute for Risk Assessment

Soy lecithin NSAID combo drug protects against cancer with fewer side effects, UTHealth reports

image: Fighting colorectal cancer at UTHealth are Lenard Lichtenberger, Ph.D., (right) and Dexing Fang, Ph.D.

Image: 
PHOTO CREDIT Rob Cahill, UTHealth

When scientists at The University of Texas Health Science Center at Houston (UTHealth) applied a chemical found in soybeans to a non-steroidal anti-inflammatory drug (NSAID), they increased its anticancer properties and reduced its side effects. Findings of the preclinical study of phosphatidylcholine, also called lecithin, appear in the journal Oncology Letters.

"The results support the potential use of NSAIDs associated with phosphatidylcholine for the prevention and treatment of colorectal cancer," said Lenard Lichtenberger, Ph.D., the study's lead investigator and a professor of integrative biology and pharmacology at McGovern Medical School at UTHealth.

The NSAID indomethacin associated with phosphatidylcholine was studied in a head-to-head comparison with three other NSAIDs (one of them aspirin). According to the results, the combination provided superior colorectal cancer protection with less gastrointestinal bleeding. The study was conducted in a mouse model and in laboratory experiments.

Colorectal cancer is the third leading cause of cancer-related death in the United States and is expected to claim 50,630 lives this year.

NSAIDs work by decreasing the production of substances that promote inflammation, pain and fever. They are used to prevent heart disease and reduce arthritis pain. NSAIDs, notably aspirin, also guard against colorectal cancer.

"Many cancers are inflammation based," he said. "The anti-inflammatory drugs also have the potential use for cancer therapy."

However, when taken on a daily basis for months to years, NSAIDs can cause problems, Lichtenberger said. "The intestinal injury is worse than the stomach ulcers, for non-aspirin NSAIDs like indomethacin," he said.

"This is our latest preclinical study on the use of phosphatidylcholine to mitigate the side effects of using NSAIDs and protect against a number of cancers," he said.

Credit: 
University of Texas Health Science Center at Houston

Smoking, lack of exercise linked to early death after divorce

A growing body of research links divorce to a wide range of poor health outcomes, including greater risk for early death. However, the reason for the connection is not well understood.

A new study by the University of Arizona points to two possible culprits: a greater likelihood of smoking after divorce and lower levels of physical activity.

"We were trying to fill in the gap of evidence linking marital status and early mortality," said UA psychology doctoral student Kyle Bourassa, lead author of the study, which is published in Annals of Behavioral Medicine. "We know marital status is associated with both psychological and physical health, and one route from divorce to health risk is through health behaviors, like smoking and exercise. We also know that health behaviors are often linked to psychological variables, like life satisfaction."

Bourassa and his UA colleagues David Sbarra and John Ruiz based their findings on data from the English Longitudinal Study of Aging, a long-term health study of adults over age 50 living in Great Britain. The study includes seven waves of data, collected from participants every two years beginning in 2002.

The researchers analyzed data from 5,786 study participants, 926 of whom were divorced or separated and had not remarried, and the rest of whom were married. They looked at participants' self-reported life satisfaction, exercise frequency and smoking status, as well as measurements of participants' lung function and levels of inflammation.

They also kept track of who passed away during the study period, finding that participants who were divorced or separated had a 46 percent greater risk of dying during the study than their still-married counterparts.

As to why that might be, Bourassa and his co-authors found that divorced or separated participants, especially women, reported lower life satisfaction than married participants. Lower life satisfaction, in turn, predicted lower levels of physical activity, which is linked to greater risk for early death.

Divorced participants also were more likely than married participants to smoke and, as a result, had poorer lung function, which predicted early mortality.

The researchers controlled for variables like gender, self-reported health, age and socioeconomic status.

While the study didn't explicitly examine why divorce seems to be associated with greater likelihood of smoking and lower levels of exercise, one possible explanation, supported by existing research, is that divorced individuals no longer have spouses holding them accountable for their health behaviors, Bourassa said.

"Partner control of health might play a role," he said. "If you imagine a husband or wife who doesn't smoke and their partner does, one might try to influence the other's behavior. In many ways, when relationships end, we lose that important social control of our health behaviors."

Future research should consider the roles of other health behaviors, like diet and alcohol consumption, as well as other marital statuses, such as widowed or remarried adults, Bourassa said. In addition, studies might look at the effects of changes in behavior -- for example, quitting smoking or starting smoking for the first time -- which is something the current study did not consider, he said. More work also is needed to know if the findings regarding smoking and exercise for aging adults after divorce are generalizable to younger divorced populations, too.

It's important to note that divorce doesn't always lead to negative health outcomes. Quality of life, for example, can significantly improve for individuals who have ended unhealthy relationships.

Still, since divorce overall continues to be linked to poorer health, knowing that smoking and exercise may be part of the explanation could help inform interventions for those who've gone through a separation, Bourassa said.

"This is a subgroup of people that are at greater risk for these poorer health behaviors, so the goal might be to target them for interventions to hopefully improve their long-term health," he said.

"We have interventions for people who smoke, and we have interventions for people who don't get enough exercise, so if we know someone who is divorced, maybe we should ask, 'Are you smoking? Are you getting enough physical activity?'" he said. "Finding that life satisfaction seems to link divorce to physical activity levels also suggests that interventions to improve people's life satisfaction and psychological wellbeing could translate downstream to physical health improvements."

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University of Arizona

High protein diet associated with small increased heart failure risk in middle-aged men

DALLAS, May 29, 2018 - For middle-aged men, eating higher amounts of protein was associated with a slightly elevated risk for heart failure than those who ate less protein, according to new research in Circulation: Heart Failure, an American Heart Association journal.

Despite the popularity of high protein diets, there is little research about how diets high in protein might impact men's heart failure risk.

"As many people seem to take the health benefits of high-protein diets for granted, it is important to make clear the possible risks and benefits of these diets," said Jyrki Virtanen, Ph.D., study author and an adjunct professor of nutritional epidemiology at the University of Eastern Finland in Kuopio. "Earlier studies had linked diets high in protein - especially from animal sources -- with increased risks of Type 2 diabetes and even death."

The American Heart Association estimates that one in five Americans 40 and older will develop heart failure - the body is unable to pump enough blood and oxygen to remain healthy. Heart failure can shorten life expectancy. And with no cure, preventing heart failure through diet, lifestyle and more is vital.

Researchers studied 2,441 men, age 42 to 60, at the study's start and followed them for an average 22 years. Overall, researchers found 334 cases of heart failure were diagnosed during the study and 70 percent of the protein consumed was from animal sources and 27.7 percent from plant sources. Higher intake of protein from most dietary sources, was associated with slightly higher risk. Only proteins from fish and eggs were not associated with heart failure risk in this study, researchers said.

For this study, researchers divided the men into four groups based on their daily protein consumption. When they compared men who ate the most protein to those who ate the least, they found their risk of heart failure was:

33 percent higher for all sources of protein;

43 percent higher for animal protein;

49 percent higher for dairy protein.

17 percent higher for plant protein.

"As this is one of the first studies reporting on the association between dietary protein and heart failure risk, more research is needed before we know whether moderating protein intake may be beneficial in the prevention of heart failure," said Heli E.K. Virtanen, M.Sc., first author of study, Ph.D. student and early career researcher at the University of Eastern Finland in Kuopio. "Long-term interventions comparing diets with differential protein compositions and emphasizing differential protein sources would be important to reveal possible effects of protein intake on risk factors of heart failure. More research is also needed in other study populations."

The American Heart Association recommends a dietary pattern that includes a variety of fruits and vegetables, whole grains, low-fat dairy products, poultry, fish, beans, non-tropical vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages and red meats.

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American Heart Association

Genomic medicine may one day revolutionize cardiovascular care

DALLAS, May 29, 2018 -- A new scientific statement from the American Heart Association summarizes the state-of-the-science of genomic medicine -- the study of the health effects of the molecular interactions of a person's unique genes -- for studying cardiovascular traits and disorders and for therapeutic screening.

"The promise of genomic medicine is to be able to use a patient's specific genetic material to make a personalized forecast of their risk for heart disease, and if they develop disease, predict its course and determine the particular medications that are more likely to help with their disease," said Kiran Musunuru, M.D., Ph.D., M.P.H., chair of the writing committee for the statement and an associate professor of cardiovascular medicine and genetics at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

"Over the next decade, as we learn about cardiovascular disease at the molecular level, the hope is that we can develop therapies that will take advantage of this knowledge and be able to either treat or potentially cure disease," Musunuru said.

DNA and RNA are two types of molecules found in most living organisms. DNA contains genetic information that is "translated" by means of RNA into proteins and metabolites, the tiny components that form cells and which play many other critical roles in the body. While genes, which are made up of DNA, carry traits inherited from your ancestors and are relatively stable during your lifetime, their "translation" can be altered by environmental factors, such as tobacco smoke, diet and exercise, for example.

Genomic medicine looks at all the types of molecular variation, from the DNA and RNA to the microorganisms in the human gut that seem to play an increasingly important role in maintaining health, and it seeks to find associations between patterns in these data and health outcomes.

An example of genomic medicine that is currently available to doctors is a noninvasive blood test for heart transplant patients, which measures the levels of 11 different RNA molecules to determine whether the patient's immune system is rejecting the transplant. Traditionally, physicians biopsy cells from the patient's heart on a weekly or biweekly basis by inserting a catheter into the heart to extract cells to monitor the transplanted organ for signs of rejection. While biopsies are considered relatively safe, there are risks, costs and discomfort for the patient.

"The hope is that with genomic medicine, there will be hundreds of examples of noninvasive tests like this that doctors can do to better forecast and better manage disease," Musunuru said.

Researchers similarly hope that induced pluripotent stem cells (iPSCs) -- stem cells that are grown from mature cells in the body, such as skin or blood, and can be converted into any type of cell -- can provide clinicians with a noninvasive method to learn more about a person's risk of cardiovascular disease and test potential treatments before they are given to a patient.

For example, doctors could use iPSCs to grow millions of a patient's heart cells in the laboratory and use these cells to identify the best course of treatment to benefit the patient.

The use of iPSCs is still in early testing and not yet available to patients, but the preliminary results are promising, Musunuru said.

"With induced pluripotent stem cells, we will be able to determine upfront which medications are going to work better and get a sense of a medication's potential side effects," Musunuru said. "I am confident we will reach the point where we can start incorporating these kinds of cells into actual patient care."

The statement is published in the American Heart Association journal Circulation: Genomic and Precision Medicine, where Musunuru serves as editor-in-chief.

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American Heart Association

Sex hormone levels may affect heart disease risk in post-menopausal women

In post-menopausal women, having a higher blood level of a male hormone (testosterone) and a higher ratio of the male-type to-female type (estrogen) of hormones is associated with a higher risk of heart disease later in life, according to research published today in the Journal of the American College of Cardiology.

The risk for cardiovascular disease is much lower in women than men until women reach the age of 50 years of age, then risk rises dramatically after menopause. Previous studies have demonstrated that higher androgen and lower estrogen levels are associated with risk factors for heart disease in post-menopausal women; however, other studies show conflicting results, so the relationship between sex hormones and cardiovascular events in post-menopausal women remains unclear.

In this study, which is one of the largest and among the longest follow up of studies of this kind, researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to evaluate the association of sex hormone levels with incident cardiovascular disease, coronary heart disease and heart failure over a 12-year follow-up in 2,834 post-menopausal women free of cardiovascular disease at baseline.

Sex hormone concentrations were measured using fasting serum samples. Every nine-12 months, participants or their next of kin were interviewed over the telephone regarding hospital admissions, outpatient cardiovascular diagnoses and procedures, and death. Hospital records were obtained for 98 percent of reported hospitalized cardiovascular disease events and some medical record-based information was obtained for 95 percent of outpatient encounters.

A higher testosterone to estradiol ratio was associated with an elevated risk for incident cardiovascular disease, coronary heart disease and heart failure. Higher total testosterone was associated with an increased risk for coronary heart disease and total cardiovascular disease (defined as coronary disease plus stroke events), while higher estradiol levels were associated with a lower risk of coronary heart disease. Additionally, the risk for cardiovascular disease and coronary heart disease were approximately linear across the range of total testosterone, testosterone to estradiol ratio and estradiol levels, but there was a U-shaped associated between testosterone to estradiol ratio and heart failure with the extreme ends at a higher risk for heart failure.

"Although sex hormone levels may be linked to future cardiovascular events, it is unclear what the best intervention is to modify sex hormone levels for risk reduction," said Erin D. Michos, MD, MHS, associate professor of medicine at the Johns Hopkins University School of Medicine and senior author on the study. "However, a sex hormone profile higher in male hormones may identify a woman at higher risk for cardiovascular disease who may benefit from other risk reduction strategies."

In an accompanying editorial comment, Virginia M. Miller, PhD professor of physiology and surgery and director of the Mayo Clinic Women's Health Research Center writes that while this study provides new insight into relationships and endogenous hormones and cardiovascular events, more research is needs to better understand the "complex hormonal environment affecting cellular and organ functions involved in the development and progression of cardiovascular disease in women as they age."

Miller said, "Defining cardiovascular risk for women should account for individualized profiles of genetic variants in enzymes associated with steroid metabolism, uptake and receptors in conjunction with risk for specific cardiovascular pathologies. This approach is precision medicine."

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American College of Cardiology

Man against machine: AI is better than dermatologists at diagnosing skin cancer

Researchers have shown for the first time that a form of artificial intelligence or machine learning known as a deep learning convolutional neural network (CNN) is better than experienced dermatologists at detecting skin cancer.

In a study published in the leading cancer journal Annals of Oncology [1] today (Tuesday), researchers in Germany, the USA and France trained a CNN to identify skin cancer by showing it more than 100,000 images of malignant melanomas (the most lethal form of skin cancer), as well as benign moles (or nevi). They compared its performance with that of 58 international dermatologists and found that the CNN missed fewer melanomas and misdiagnosed benign moles less often as malignant than the group of dermatologists.

A CNN is an artificial neural network inspired by the biological processes at work when nerve cells (neurons) in the brain are connected to each other and respond to what the eye sees. The CNN is capable of learning fast from images that it "sees" and teaching itself from what it has learned to improve its performance (a process known as machine learning).

The first author of the study, Professor Holger Haenssle, senior managing physician at the Department of Dermatology, University of Heidelberg, Germany, explained: "The CNN works like the brain of a child. To train it, we showed the CNN more than 100,000 images of malignant and benign skin cancers and moles and indicated the diagnosis for each image. Only dermoscopic images were used, that is lesions that were imaged at a 10-fold magnification. With each training image, the CNN improved its ability to differentiate between benign and malignant lesions.

"After finishing the training, we created two test sets of images from the Heidelberg library that had never been used for training and therefore were unknown to the CNN. One set of 300 images was built to solely test the performance of the CNN. Before doing so, 100 of the most difficult lesions were selected to test real dermatologists in comparison to the results of the CNN."

Dermatologists from around the world were invited to take part, and 58 from 17 countries around the world agreed [2]. Of these, 17 (29%) indicated they had less than two years' experience in dermoscopy, 11 (19%) said they were skilled with between two to five years' experience, and 30 (52%) were expert with more than five years' experience.

The dermatologists were asked to first make a diagnosis of malignant melanoma or benign mole just from the dermoscopic images (level I) and make a decision about how to manage the condition (surgery, short-term follow-up, or no action needed). Then, four weeks later they were given clinical information about the patient (including age, sex and position of the lesion) and close-up images of the same 100 cases (level II) and asked for diagnoses and management decisions again.

In level I, the dermatologists accurately detected an average of 86.6% of melanomas, and correctly identified an average of 71.3% of lesions that were not malignant. However, when the CNN was tuned to the same level as the physicians to correctly identify benign moles (71.3%), the CNN detected 95% of melanomas. At level II, the dermatologists improved their performance, accurately diagnosing 88.9% of malignant melanomas and 75.7% that were not cancer.

"The CNN missed fewer melanomas, meaning it had a higher sensitivity than the dermatologists, and it misdiagnosed fewer benign moles as malignant melanoma, which means it had a higher specificity; this would result in less unnecessary surgery," said Professor Haenssle.

"When dermatologists received more clinical information and images at level II, their diagnostic performance improved. However, the CNN, which was still working solely from the dermoscopic images with no additional clinical information, continued to out-perform the physicians' diagnostic abilities."

The expert dermatologists performed better at level I than the less experienced dermatologists and were better at detecting malignant melanomas. However, their average ability to make the correct diagnosis was still worse than the CNN at both levels.

"These findings show that deep learning convolutional neural networks are capable of out-performing dermatologists, including extensively trained experts, in the task of detecting melanomas," he said.

The incidence of malignant melanoma is increasing, with an estimated 232,000 new cases worldwide and around 55,500 deaths from the disease each year [3]. It can be cured if detected early, but many cases are only diagnosed when the cancer is more advanced and harder to treat.

Professor Haenssle said: "I have been involved in research projects that aim at improving the early detection of melanoma in its curable stages for almost 20 years. My group and I are focusing on non-invasive technologies that may help physicians not to miss melanomas, for instance, while performing skin cancer screenings. When I came across recent reports on deep-learning algorithms that outperform human experts in specific tasks, I immediately knew that we had to explore these artificial intelligence algorithms for diagnosing melanoma."

The researchers do not envisage that the CNN would take over from dermatologists in diagnosing skin cancers, but that it could be used as an additional aid.

"This CNN may serve physicians involved in skin cancer screening as an aid in their decision whether to biopsy a lesion or not. Most dermatologists already use digital dermoscopy systems to image and store lesions for documentation and follow-up. The CNN can then easily and rapidly evaluate the stored image for an 'expert opinion' on the probability of melanoma. We are currently planning prospective studies to assess the real-life impact of the CNN for physicians and patients."

The study has some limitations, which include the fact that the dermatologists were in an artificial setting where they knew they were not making "life or death" decisions; the test sets did not include the full range of skin lesions; there were fewer validated images from non-Caucasian skin types and genetic backgrounds; and the fact that doctors may not always follow the recommendation of a CNN they don't trust.

In an accompanying editorial [4] Dr Victoria Mar (Monash University, Melbourne, Australia) and Professor H. Peter Soyer (The University of Queensland, Brisbane, Australia) write: "Currently, diagnostic accuracy for melanoma is dependent on the experience and training of the treating doctor. ..... Haenssle et al...have shown that a computer algorithm using convolutional neural networks outperformed the majority of 58 dermatologists tested .....This shows that artificial intelligence (AI) promises a more standardised level of diagnostic accuracy, such that all people, regardless of where they live or which doctor they see, will be able to access reliable diagnostic assessment."

They highlight a number of issues that would need to be addressed before AI could become standard in clinics, including the difficulty of imaging some melanomas on sites such as the fingers, toes and scalp, and how to train AI sufficiently to recognise atypical melanomas and ones that patients are unaware of.

They conclude: "Currently, there is no substitute for a thorough clinical examination. However, 2D and 3D total body photography is able to capture about 90 to 95% of the skin surface and given exponential development of imaging technology we envisage that sooner than later, automated diagnosis will change the diagnostic paradigm in dermatology. Still, there is much more work to be done to implement this exciting technology safely into routine clinical care."

Credit: 
European Society for Medical Oncology

No link between HPV vaccination and risk of autoimmune disorders: Study in CMAJ

A new study in CMAJ (Canadian Medical Association Journal) found no increased risk of autoimmune disorders in girls who received quadrivalent human papillomavirus (HPV4) vaccination, adding to the body of evidence for the safety of the vaccine.

Human papillomavirus is the most common sexually transmitted disease worldwide, affecting 50%-75% of sexually active people. The HPV4 vaccine is effective at protecting against 90% of the strains that cause cervical and anal cancer. Despite studies showing safety of the vaccine, there have been concerns about a possible link to autoimmune disorders.

"Despite demonstrated effectiveness in real-world settings, concerns continue to persist regarding the safety of the HPV4 vaccine. In light of these concerns, we wanted to study the HPV4 vaccination since it was being offered free to all grade 8 girls in Ontario through school-based clinics," says Dr. Jeffrey Kwong, a study author and a senior scientist at the Institute for Clinical Evaluative Sciences (ICES) and at Public Health Ontario.

To determine whether the HPV4 vaccination triggered autoimmune conditions such lupus, rheumatoid arthritis, type 1 diabetes and multiple sclerosis, researchers looked at data on 290 939 girls aged 12 to 17 years in Ontario who were eligible for vaccination between 2007 and 2013. Of the total 180 819 girls who received the HPV4 (Gardasil and Merck) vaccination in school-based clinics, there were 681 diagnosed cases of autoimmune disorders between one week and two months after vaccination. This rate is consistent with the general rate of diagnosed cases in this age group.

"These findings add to the body of evidence on the safety of the HPV4 vaccine and should reassure parents and health care providers," says Dr. Linda Lévesque, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario.

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Canadian Medical Association Journal

By 2035 over 4 million adults will be morbidly obese across England, Wales, and Scotland

Across England, Wales, and Scotland, morbid obesity (BMI of 40kg/m² or over) rates in adults are expected to soar over the next 17 years, with the number of morbidly obese adults likely to exceed 4 million by 2035--more than double the 1.9 million in 2015, according to new research being presented at this year's European Congress on Obesity (ECO) in Vienna, Austria (23-26 May).

The highest prevalence rates will be seen in Wales, with around 13% of Welsh men and 9% of Welsh women likely to be morbidly obese by 2035 if current trends continue. The prevalence of morbid obesity is expected to vary widely between the three countries and in different age groups. By 2035, 16% of English men aged 55-64 are likely to be morbidly obese. That compares to 0% of Scottish men aged 15-24 (see table).

The authors warn that the study presents a disturbing picture of substantial rises in morbid obesity rates that will have huge health and financial implications for health services and society. They call for concerted action by individuals and governments to reverse this trend.

The prevalence of morbid obesity is increasing worldwide, with numbers doubling in the past 20 years. A recent global study reported morbid obesity levels ranging from less than 0·1% in Chinese women to 23·1% in American women.

Morbid obesity entails far more serious health consequences than moderate obesity and is associated with a higher risk of chronic diseases such as type 2 diabetes, heart disease, stroke, mental illness, and some cancers.

Morbid obesity is already a huge burden on the economy and health services, accounting for around a third of all obesity-related costs.

While overweight and obesity trends for England, Wales, and Scotland have been projected to 2035, until now, no trend estimates existed for morbid obesity.

In this study, Laura Keaver from the CRISP research group at the Institute of Technology, Sligo, Ireland and Dr Laura Webber from the UK Health Forum, London used height and weight data from the Health Survey for England, Welsh Health Survey, and the Scottish Health Survey (2004-14) for adults aged 15 and older (in 5 year age groups) to create a model predicting BMI trends (healthy weight, overweight, obesity, and morbid obesity) over the next 17 years.

The new estimates indicate that rates of morbid obesity in adults will reach 5% in Scotland (compared to 4% in 2015), 8% in England (2.9% in 2016), and 11% in Wales (3% in 2015) by 2035 (see table 1).

According to the authors: "Our study reveals a worrying picture of rising morbid obesity across England, Wales, and Scotland that is likely to weigh heavily on healthcare systems and economies. Strong measures to reverse this future trend must be an important public health priority."

In further analyses, the research team predicted future trends in social inequalities in obesity (BMI of 30kg/m² or over) by modelling BMI data from the health surveys to project trends in adult obesity prevalence (aged 16 or older) according to their sex and social group (occupation and education).

Previous studies have found that lower socioeconomic position is linked with higher adult BMI, and socioeconomic inequalities in obesity are increasing in many European countries. But whether these associations will change over the coming decades is unclear.

By 2035, obesity rates will be highest, and see the greatest rise, in adults working in routine and manual positions. As a result, the difference in obesity levels between those in managerial roles (29% males, 31% females) and those in routine and manual roles (39% males, 40% females) is expected to widen in England and Wales (with the exception of English females where it is expected to reduce; table 2).

In contrast, the gap in obesity levels between those with less than tertiary education (i.e., university or trade school/college) and those with tertiary education is projected to close in all countries with the exception of Welsh females where it is projected to increase (table 3).

The authors conclude: "Our findings highlight that future interventions to tackle obesity must be accessible to everyone and should be designed to impact all sectors of society to further reduce these inequalities."

The authors point out the limitations that apply to the quality, precision, and availability of the data demand cautious interpretation (e.g., weight and height was self-reported in Wales and measured in England and Scotland). They also note that uncertainties always exist when making predictions as past trends do not always predict future trends. In addition, the study cannot predict the effect that future interventions or policies will have on social inequalities in obesity.

Credit: 
European Association for the Study of Obesity

Study reveals gaps in follow-up care after concussion

Being discharged from a hospital trauma center after receiving treatment for a traumatic brain injury (TBI) does not necessarily mean that a patient has fully recovered. TBI can lead to long-lasting physical and cognitive symptoms, but a new study in JAMA Network Open suggests that many patients may not be receiving follow-up care.

Patients in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) initiative, a large, long-term, NIH-funded study of patients who are treated at the emergency room for mild TBI or concussion, were surveyed about their care after hospital discharge. Follow-up care in this study referred to receiving TBI-related educational materials at discharge, a call from the hospital within two weeks after release, seeing a healthcare provider within two weeks, or seeing a healthcare provider within three months.

According to the findings, 44 percent of the 831 patients who completed questionnaires 2 weeks and 3 months after sustaining TBI reported seeing a doctor or other provider within three months. Of those patients, 15 percent visited a clinic that specialized in head injury. Approximately half of the patients saw a general practitioner and close to a third reported seeing more than one type of doctor.

Additionally, among the 279 patients with three or more moderate-to-severe post-concussive symptoms, 41 percent had not had a follow-up visit at three months after discharge. Approximately half of the patients were discharged without TBI educational materials.

Rates and components of follow-up care after TBI varied widely from institution to institution, even among patients with the same initial degree of injury.

Credit: 
NIH/National Institute of Neurological Disorders and Stroke

Regulatory mutations missed in standard genetic screening lead to congenital diseases

Researchers have identified a type of genetic aberration to be the cause of certain neurodevelopmental disorders and congenital diseases, such as autism and congenital heart disease, which are undetectable by conventional genetic testing.

The discovery that genetic mutations called epivariations are involved in these diseases could lead to more advanced diagnostic tools for many congenital and neurodevelopmental disorders, say researchers from the Department of Genetics and Genomics Sciences at the Icahn School of Medicine at Mount Sinai and collaborators from Radboud University Medical Center (The Netherlands), University of Minho (Portugal), and Porto Hospital Center (Portugal). The research team's results were published in May 2018 in Nature Communications.

Epivariations are variations in the DNA molecule that do not affect the basic composition of the DNA molecule, called the DNA sequence, but result in a change in gene function. Because conventional genetic testing analyzes the DNA sequence, diseases that are caused by these epivariations need to be tested for using different mechanisms. The specific epivariation found in this study was caused by excess DNA methylation--when a methyl group, composed of hydrogen and carbon atoms, is attached to a DNA molecule.

"Our study suggests that these epigenetic mutations are a significant contributor to human disease," said Andrew Sharp, PhD, Associate Professor in the Department of Genetic and Genomic Sciences at the Icahn School of Medicine and lead investigator of the study.

The research team studied the genetic profiles of 489 patients with known neurodevelopmental or congenital disorders, who had all previously undergone genetic testing that identified no DNA mutations. These disorders had long been thought to have genetic origins, so the scientists suspected that even though conventional testing hadn't discovered a genetic cause for them, epivariations in their DNA could be present, resulting in gene dysfunction leading to disease. To assess for epivariations, Sharp's team conducted methylation profiling--determining the DNA methylation within each patient's genome--finding epigenetic mutations that could be the cause of disease in approximately 20 percent of the studied cohort. Furthermore, in analyzing more than 5,000 genome profiles of individuals with no known diagnosis of congenital disease or neurodevelopmental disorder, the team discovered epigenetic mutations to be relatively common, and that they could typically be identified via a blood test.

Standard genetic screening methods, such as whole-genome sequencing, are applied to thousands of human genomes around the world. What's missing, says Dr. Sharp, is epigenomic profiling. "These findings can open up a whole new world in what we know about disease and genetic profiling," Dr. Sharp continued. "Investigating DNA methylation when profiling genomes for disease mutations could help us uncover causative defects in congenital and neurodevelopmental diseases that have eluded us for years."

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

UMD food scientist guides students towards revelatory findings in women's health

College Park, MD -- In an effort to sustain and educate the next generation of food safety experts in the United States, Dr. Bob Buchanan of the University of Maryland has served as a scientific mentor to a pair of academically accelerated high school students who are challenging the current food avoidance recommendations for pregnant women as established by the CDC and ACOG. Led by 14-year-olds Valentina Simon and Rachel Rosenzweig, along with professional midwives Katya Simon, Mickey Gillmor and Rebeca Barroso, results of an eleven-page study propose updated recommendations for safe food-handling practices to avoid listeriosis during pregnancy. Their paper was recently accepted by the pre-eminent publication in the women's health field, the Journal of Midwifery and Women's Health, an unprecedented distinction for authors of this age without formal training or advanced degrees.

Simon and Rosenzweig's report represents a critical evaluation of listeriosis prevention guidelines in the United States. Following an in-depth examination of over 850 cases of foodborne illness outbreaks in the Centers for Disease Control and Prevention (CDC) database, as well as numerous product recalls reported in the Food and Drug Administration (FDA), and United States Department of Agriculture (USDA) food recall databases, the students found that the official guidelines were in dire need of revision.

"Rachel and I looked at six categories of foods included within the 800 cases highlighted in the government databases. Six categories were the recommended foods to avoid, and we added a seventh "other" category. We quickly noticed that the current avoidance guidelines only prevented listeriosis cases prior to the year 2000, which is very alarming," said Simon. "We then looked at the years 2015-2016 and found that only 5% of confirmed Listeria related infections stemmed from the six official food groups outlined in the guidelines."

From there, Simon and Rosenzweig explored further and noticed a gradual shift in detection of contamination from hot dogs, smoked seafood and pates, cold cuts, raw milk, unpasteurized soft cheeses, and unwashed raw produce, to new items such as ready-to-eat meals, frozen foods, ready-to-eat salads, and pasteurized dairy products. Essentially, these are foods that have a long refrigerated shelf life. This trend sent up a red flag for Simon and Rosenzweig, and they knew it was time to consult an academic in the field to help them understand the scientific basis of their findings.

"This is a major finding for Valentina and Rachel. I was thrilled when they reached out to me for help interpreting the data. From the start, I encouraged them to research and publish the total number of listeriosis cases as opposed to only identified cases. The CDC will only report identified cases, so going a layer deeper and discovering how many total people have been infected with Listera and the causation of each has really strengthened their paper," said Buchanan. "Within their paper, Valentina and Rachel have published a very eye-opening table that demonstrates the rise in total cases from 2007-2014 from non-traditional foods. This is clear evidence that additional foods may need to be reflected within the CDC guidelines."

Upon review of the paper, Dr. Buchanan wrote close to 60 comments to clarify Simon and Rosenzweig's initial misunderstandings concerning food science and agency protocol. He took a great number of emails, phone-calls, and in-person meetings over the past few months. The collective goal is to push the boundaries of this conversation and convene the major players within food safety to develop modernized guidelines.

Credit: 
University of Maryland

Obese and overweight patients hospitalized with pneumonia are 20 percent to 30 percent less likely to die than normal-weight patients

New research from over 1000 US hospitals* presented at this year's European Congress on Obesity in Vienna, Austria, shows that obese and overweight patients hospitalised for pneumonia are 20-30% less likely to die than patients of a normal weight. The study is by Professor Shy-Shin Chang and Dr Yu-Jiun Lin, Taipei Medical University Hospital, Taipei City, Taiwan, and Dr Jon Wolfshohl, Department of Emergency Medicine, John Peter Smith Hospital, Fort Worth, TX, USA, and colleagues.

Obesity prevalence is increasing steadily throughout the world's population in most countries and pneumonia is one of the most common infectious diseases; however, there is uncertainty about an in¬verse relationship between obesity and pneumonia mortality. A previous me¬ta-analysis** has shown that an 'obesity survival paradox' exists for pneumo¬nia (where obese people had better survival), but high variability existed among these studies. This study aimed to determine the impact of being overweight and obese on pneu¬monia patients, by using data from almost 1.7 million patient episodes of pneumonia across 1000 hospitals in the USA.

Using the Nationwide Readmission database of the US from 2013 to 2014, the authors identified patients hospitalised with pneumonia. A pneumonia-associated hospitalisation was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis. Use of mechanical ventilation was used to stratify pneumonia of different severity. Hospitalized pneumonia patients were categorized into normal (body mass index [BMI] under 25), overweight BMI between 25 and 30), and obese (BMI over 30).

To mini¬mise baseline differences between patients with different body weight, the authors carried out a technique call propensity score (PS)-matched analysis. PS contains 41 variables including demographics, social economic status, chronic comorbidities, and severity of pneumonia. Patients were matched 1:1:1 using this technique across the three groups of normal weight, overweight and obese. The authors then used computer modelling on the PS-matched pairs to assess the association between body weight and 30-day in-hospital mortality.

A total of 1,690,760 pneumonia hospitalisation episode fulfilled the inclusion criteria, of which 17,992 were overweight, 195,889 were obese, and 1,476,879 were normal weight. Compared with normal weight patients without use of ventilator, overweight patients were 23% more likely to survive and obese patients 29% more likely to survive. Similar results were obtained in the cohort of more serious pneumonia requiring the use of ventila¬tor -- overweight and obese patients were 21% and 30% respectively more likely to survive than normal weight patients (see table 1 full abstract).

To investigate whether there was a differential risk of 30- day mortality among different obese populations, the authors stratified patients into different subgroups and adjust the risk for mortality using PS score (see Figure 1 full abstract). Although the survival benefit of obesity is consistent in all subgroups, patients with lower comorbidity burden/severity had substantially better survival. For example, being in the lowest co¬morbidity quartile compared with the highest is associated with 53% improvement in survival, and being in the group with the lowest severity of pneumonia was associated with 67% improvement in survival compared with the highest severity.

The authors conclude: "Using a large and nationally representative sample of over 1,000 hospitals in the US, we found that increase in body mass index was significantly associated with improved survival in patients hospitalised with pneumonia. We also found that severity and comorbidity burden had a modifying effect on survival."

Credit: 
European Association for the Study of Obesity

What your choice of clothing says about your weight

It's commonly said that you can tell a great deal about a person by the clothes they wear. Now new research suggests that choice of garment colour is a predictor of body mass index (BMI).

The findings being presented at this year's European Congress on Obesity (ECO) in Vienna, Austria (23-26 May) reveal that darker and multicolour clothes are preferred by women with higher BMIs, while men with larger BMIs are more likely to choose black or white garments.

Colour plays an important role in influencing moods and emotions, and previous research suggests that the colour of the clothes you wear says a lot about your personality, mood, and even how other people perceive you. The size and colour of the clothing you choose depends on a variety of personal factors, and these may include perceived or actual overweight or obesity.

To investigate this further, Dr Charoula Nikolaou and Professor Stuart Gilmour from St Luke's International University in Tokyo, and Professor Mike Lean from the University of Glasgow's School of Medicine, examined the relationship between BMI and the size and colours of clothes purchased from a global online retail service. Between October and December 2017, data on body weight and height, clothing size, and colour were collected from over 34,000 customers who completed feedback forms. The data, publicly available online, was taken from the AliExpress website, part of the Alibaba group, the China-based multinational e-commerce site. Countries from which the orders were made were grouped by income: low-income, lower-middle income, upper-middle income, and high-income. Clothing colours were also grouped by dark, light, metal, pastel or print colours.

Over a two-month period (covering different seasons in different countries), 27,083 women (8,119 skirts and 18,964 dresses) and 7,295 men (7,295 trousers) from 119 countries purchased items of clothing from 26 clothing brands. Most were purchased by people living in high- and upper-middle income countries. Online sales were mostly to young and middle-aged customers. Over half of trousers sold, almost a quarter of dresses, and 15% of skirts were purchased by someone overweight or obese (BMI>25kg/m2).

The association between customers' BMI and size and colour garments was estimated using linear regression, a form of statistical modelling which adjusts for potential factors that could influence the relationship such as gender, country of origin, income of country of origin.

Results showed that clothing size was closely related to both BMI and waist circumference. Women with a higher BMI were more likely to buy black/blue/dark colour and floral dresses, and multicolour and dot-patterned skirts. Whilst men with a higher BMI tended to stick to black or white trousers.

The authors acknowledge that their findings show observational differences which are not necessarily evidence of cause and effect. They conclude: "Our study suggests that the size and colour of garments purchased can be indicators of weight problems. Online clothing purchase choices could be used to target non-judgemental messages about weight-management and preventing unwanted weight gain."

The authors say that two practical actions to help people with weight-management or preventing weight-gain could result from this study:

Clothing size is a reliable indicator of BMI so non-judgemental messages about weight-management could be provided with purchases of large size-garments

Advice for people who have successfully lost weight could include changing the wardrobe to smaller size garments and switching to colours and patterns favoured by thinner people and which more overweight people tend to avoid.

Credit: 
European Association for the Study of Obesity