Body

April 17, 2018 - Can medical marijuana help to fight the opioid epidemic? Many believe that it can. But a new study finds that people who use medical marijuana actually have higher rates of medical and non-medical prescription drug use--including pain relievers. The study appears in the Journal of Addiction Medicine, the official journal of the American Society of Addiction Medicine (ASAM), published by Wolters Kluwer.

Rather than being at lower risk, people who use medical marijuana may be at higher risk for non-medical prescription drug use, suggests the study by Theodore L. Caputi, BS of University College Cork's School of Public Health and Keith Humphreys, PhD, of Stanford University. However, an accompanying commentary questions whether medical cannabis is the cause of higher prescription drug use, or whether other factors explain the association.

Does Use of Medical Marijuana Increase or Decrease Prescription Drug Use?

The researchers analyzed more than 57,000 responses to the 2015 National Survey on Drug Use and Health. Participants were asked about medical and non-medical ("inconsistent with doctor's instructions") use of prescription drugs. The survey also asked about marijuana use, including whether it was recommended by a healthcare professional. The survey identified 776 people who used medical marijuana--about 1.4 percent of all responders.

People who used medical marijuana were more likely to say they had used prescription drugs in the past year. They were about 60 percent more likely to report any prescription drug use, relative to those who did not use medical marijuana.

People who used medical marijuana were also more than twice as likely to report non-medical use of prescription drugs, including pain relievers, stimulants, and tranquilizers. "Non-medical use of pain relievers is of particular interest because of pain relievers' role in the opioid overdose epidemic," Mr. Caputi and Dr. Humphreys observe.

Higher levels of non-medical prescription drug use by people who used medical marijuana persisted in an analysis limited to people who used prescription drugs. The researchers write, "This suggests that the elevated risk for prescription drug non-medical use among people who use medical marijuana cannot be ascribed simply to their having a medical concern or greater access to prescription drugs."

Previous studies have reported that states where medical marijuana is legal have lower rates of medical and non-medical prescription drug use and related harms--including opioid overdose. "These reports have led many to believe that use of medical marijuana is a protective factor against non-medical prescription drug use," Mr. Caputi comments. "However, individual-level inferences cannot be made using the ecological studies cited frequently in the debate over medical marijuana."

Mr. Caputi notes the lack of large-scale follow-up data on whether patients are using cannabis together with or in place of prescription drugs. However, he adds, "Physicians and practitioners should know that, from cross-sectional data, medical marijuana use is positively associated with non-medical prescription drug use.

"Our findings don't prove a causal connection between marijuana and opioid use, but they do suggest physicians can use medical marijuana as a marker for high risk of non-medical prescription drug use."

In the accompanying commentary, Marcus A. Bachhuber, MD, MSPH, and colleagues at Montefiore Medical Center/Albert Einstein College of Medicine point out that the findings do not show that medical cannabis causes increased use of prescription drugs. Dr. Bachhuber is author of an ecological study finding a protective effect of medical marijuana regulation on opioid overdose mortality,

"Given that people who take medical cannabis and those who do not are likely to have different underlying medical conditions, it is possible that medical cannabis use reduces prescription drug use yet prescription drug use remains relatively high in that group," Dr. Bachhuber comments, He notes that chronic pain is the most common reason for medical marijuana use.

In other studies, people who take medical marijuana consistently report substituting cannabis for other prescription and illicit drugs. Dr. Bachhuber and coauthors conclude: "To fully understand the effect of medical cannabis on the use of other drugs, prospective longitudinal studies randomizing patients to cannabis versus other treatments are urgently needed."

WASHINGTON -- Hotspots of type 1 diabetes in New York City are found in food swamps, areas with a higher proportion of fast food restaurants, for children and adults with type 1 diabetes, according to a new study published in the Endocrine Society's Journal of the Endocrine Society.

Patients with type 1 and type 2 diabetes share the same problem of high blood sugar levels, but the cause and development of the conditions are quite different. Type 1 diabetes is an autoimmune disease in which the body's immune system attacks the cells in the pancreas that make insulin, and it currently affects over 1.3 million U.S. adults. Type 2 diabetes results from a combination of insulin resistance and deficiency, and is the more common of the two, affecting more than 21 million U.S. adults. Patients with type 1 diabetes need insulin to survive, while those with type 2 diabetes also may use diet, exercise and oral medication to help manage the condition.

"Traditionally, we've associated type 1 diabetes with genetics and type 2 diabetes with obesity," said one of the study's authors, David C. Lee, M.D., M.S., of New York University School of Medicine in New York. "Our research suggests that an adverse food environment has an important influence in type 1 diabetes, and a more thorough investigation of genetics, health behaviors and cultural influences should be considered for type 2 diabetes."

In the retrospective cohort study, researchers from New York University School of Medicine used emergency claims data to locate New York City residents who visited a New York State emergency department at least once between 2009 and 2013 and had a history of type 1 or type 2 diabetes. Geospatial analysis was used to estimate diabetes prevalence among adults and children by census tract.

The researchers leveraged data from the city restaurant inspections and state retail food store inspections to determine which census tracts had a higher proportion of fast food restaurants and small convenience stores, which tend to offer fewer healthy food options than large grocery stores.

The researchers found higher rates of all forms of diabetes in food swamps except for children with type 2 diabetes. Those cases of pediatric type 2 diabetes were concentrated in neighborhoods with a higher proportion of black residents, suggesting there could be a genetic component at work.

"Future studies should seek to further validate these methods of estimating type 1 and type 2 diabetes prevalence among adults and children using alternative data sources," Lee said. "Factors like cultural dietary patterns and ingrained patterns of belief around how one develops diabetes should be explored to determine what causes certain neighborhoods to face a much higher burden of disease."

A new automated text messaging service may curb opioid abuse and reduce the likelihood of relapse while also decreasing treatment costs, according to researchers at Washington University School of Medicine and Epharmix, a St. Louis-based digital health company.

The service provides automated text messages and phone calls to patients being treated for opioid addiction. Such messages ask patients if they're feeling OK or struggling with potential relapse. Patients also can activate a panic button for immediate help.

Time saved from monitoring patients through individual phone calls and in-person appointments may trim medical costs and permit health-care workers to treat more patients without accruing heavier workloads.

Findings of the small study are published April 17, 2018, in NEJM Catalyst, a publication of The New England Journal of Medicine Group.

"There is an urgent need to address the opioid crisis in powerful new ways," said the study's senior author, Avik Som, an MD/PhD student at Washington University. Som, who has completed his doctorate in biomedical engineering and will receive his medical degree in May, helped develop the text-messaging technology as chief medical officer at Epharmix, a digital health company he founded with classmates in 2015. The company creates mobile technologies aimed at managing chronic conditions such as diabetes, depression and hypertension.

"With the opioid epidemic, time is of the essence because of how quickly it's grown and the lives that are lost," Som said.

Nearly 100 people die each day due to opioid overdoses, according to the Centers for Disease Control and Prevention. A highly addictive class of drugs, opioids include prescription painkillers, heroin and fentanyl.

The mobile technology is designed to supplement cognitive behavioral therapy, support services and other treatments aimed at combating opioid addiction. "This is not meant to replace important programs or face-to-face contact between patients and providers," Som said. "Rather, it is an additional tool that is affordable and immediate. It doesn't require costly, time-consuming measures such as opening substance-abuse centers, and training and hiring new staff.

The 21 patients in the study began using the texting service in late 2016 as part of their treatment at Preferred Family Healthcare, a community-based organization in St. Louis that offers treatment for substance abuse.

Data collected via the text messaging service found that at the time of enrollment, nine patients (43 percent) reported substance abuse use in the previous three days, and nine patients (43 percent) reported no use, while the remaining did not respond. After three months, half of the 21 total patients reported no substance use, while the number of patients using dropped to two (10 percent). The researchers can't attribute the positive trend solely to the app but said the data are encouraging.

"Opioid users face strong urges to relapse because of the addictive power of the drug," Som said. "As a result, health-care workers struggle to keep patients engaged."

Patients and caregivers reported that they preferred the ease and familiarity of text message communication. "Texting is convenient, immediate and nonjudgmental," Som said. "It has become an integral part of how we communicate in society. Patients reported feeling more connected to health-care providers."

The service includes a "panic button" for patients facing relapse or other health struggles. Once the button is activated, health-care workers phone patients and provide counseling, scheduling for in-person appointments, or other resources.

Additionally, texts allow caregivers to monitor patients daily with automated questions such as "Have you used in the last day?" and "Have you had urges to use?" Patients who reported struggling received automated follow-up questions that classified their risk for relapse as high, moderate or low. At the same time, health-care workers were alerted to intervene immediately.

"Health-care providers can be proactive," Som said. "It is so much more powerful to curb the temptation and break the cycle in advance of relapse rather than providing treatment only after the event has occurred."

The patients in the study were on Medicaid and individually had accrued more than $20,000 in medical costs related to substance abuse and other health issues. Researchers calculated that per-patient costs for caregiver services specific to addiction-related care would drop 19 percent, from $926 annually to $753.

Reduced costs from staff time savings were attributed to the texting service, enabling more efficient patient follow-up and better targeting to provide treatment to the right patients. "Cost savings could be realized with this tool as opioid addiction continues to rise and caregivers increasingly are being asked to manage additional patients," said the study's first author, Jordan Feltes, an Epharmix researcher and a second-year medical student at Saint Louis University.

Further studies will allow researchers to examine the text-messaging strategy in a larger patient group, and better gauge potential savings in Medicaid funding and related costs.

"In the midst of this national emergency, it is critical that patients and providers have clear, open channels of communication in order to mitigate the devastating impact of the opioid crisis," said Will Ross, MD, associate dean for diversity and a professor of medicine at Washington University. He mentored the researchers as principal investigator for Epharmix.

MAYWOOD, IL - While antibiotics have greatly reduced the dangers of ear infections, serious neurological complications, including hearing loss, facial paralysis, meningitis and brain abscess still occur, according to a report in the journal Current Neurology and Neuroscience Reports.

The article was written by Loyola Medicine otolaryngologists Michael Hutz, MD, Dennis Moore, MD, and Andrew Hotaling, MD.

Otitis media occurs when a cold, allergy or upper respiratory infection leads to the accumulation of pus and mucus behind the eardrum, causing ear ache and swelling. In developed countries, about 90 percent of children have at least one episode before school age, usually between the ages of six months and four years. Today, secondary complications from otitis media occur in approximately 1 out of every 2,000 children in developed countries.

The potential seriousness of otitis media was first reported by the Greek physician Hippocrates in 460 B.C. "Acute pain of the ear with continued high fever is to be dreaded for the patient may become delirious and die," Hippocrates wrote.

The deadliest complication of otitis media is a brain abscess, an accumulation of pus in the brain due to an infection. The most common symptoms are headache, fever, nausea, vomiting, neurologic deficits and altered consciousness. With modern neurosurgical techniques, most brain abscesses can be suctioned or drained, followed by IV antimicrobial treatment for six to eight weeks. During the past 50 years, mortality worldwide from brain abscesses has decreased from 40 percent to 10 percent and the rate of full recovery has increased from 33 percent to 70 percent.

Other complications include:

Bacterial meningitis: Symptoms include severe headache, high fever, neck stiffness, irritability, altered mental status and malaise. As the infection spreads, the patient develops more severe restlessness, delirium and confusion. Treatment is high-dose IV antibiotics for 7 to 21 days.

Acute mastoiditis: This is an infection that affects the mastoid bone located behind the ear. It must be treated to prevent it from progressing to more serious complications. Treatments include IV antibiotics and placement of a drainage tube.

Hearing loss: Permanent hearing loss is rare, occurring in about 2 out of every 10,000 children who have otitis media.

Facial paralysis: Prior to antibiotics, this debilitating complication occurred in about 2 out of 100 cases of otitis media. Since antibiotics, the rate has dropped to 1 in 2,000 cases. It should be treated as an emergency. About 95 percent of otitis media patients who develop facial paralysis recover completely.

"Antibiotic therapy has greatly reduced the frequency of complications of otitis media," Drs. Hutz, Moore and Hotaling wrote. "However, it is of vital importance to remain aware of the possible development of neurologic complication. . . . In order to reduce morbidity, early deployment of a multidisciplinary approach with prompt imaging and laboratory studies is imperative to guide appropriate management."

Dr. Hutz is a resident, Dr. Moore is an assistant professor and Dr. Hotaling is a professor emeritus in Loyola Medicine's department of otolaryngology. Their paper is titled, "Neurological Complications of Acute and Chronic Otitis Media."

Women in the United States who have experienced heart attacks are less likely than men to receive the high-intensity statins recommended to prevent further heart attacks and strokes, new research by The George Institute for Global Health at the University of Oxford has found.

The study, of more than 88,000 adults in the United States who picked up a statin prescription following a heart attack in 2014-15, suggests that the substantial efforts made recently to reduce sex disparities in the use of recommended treatments after a heart attack have not been successful.

'Prior studies have found that women are less likely than men to receive treatment with statins following a heart attack. Our study shows that even when women are prescribed statins, these continue to be in lower intensities than the guidelines recommend,' said Dr Sanne Peters, Research Fellow in Epidemiology at The George Institute, Oxford, who led the study.

'The discrepancies in high-intensity statin use may explain, at least in part, why mortality rates for women with a history of heart disease and stroke are higher than for men. Our research suggests some deaths could be prevented if the guidelines on treatment with high-intensity statins were adhered to.'

US guidelines issued in 2013 recommend that all patients aged 75 and under who have experienced heart disease or stroke should be treated with high-intensity statins, based on clear evidence of their effectiveness and safety. A number of initiatives have attempted to raise awareness of heart disease in women and reduce sex differences in treatment, including the 'Go Red for Women' campaign.

However, the new study from The George Institute, Oxford, conducted in conjunction with investigators from the University of Alabama at Birmingham, found that among people picking up statin prescriptions after being discharged from hospital following a heart attack, 47% of women picked up a high-intensity statin, compared with 56% of men. While these rates were higher than a decade ago, the sex differential has persisted: women remain less likely than men to receive a high-intensity statin, even after accounting for differences in age, affluence, and other health conditions.

'Our research suggests that the lower use of high-intensity statins in women is not related to age, or to them having a higher number of other health conditions. Nevertheless, while the underuse of high-intensity statins was seen across all patient groups, the disparity was largest among the youngest and oldest adults and for those without other known health problems,' said Dr Peters.

The study, which was funded by the biopharmaceutical company Amgen, assessed sex differences in prescription collections for high-intensity statin therapy. The study was not able to assess what medications were actually taken. Neither was there data on what treatments were prescribed. It's therefore not clear whether prescription rates for high-intensity statins were similar for men and women but women were less likely to pick them up, or whether the discrepancies are the result of lower prescription rates in women.

However, the latter may be more likely, potentially as a result of concerns that these treatments carry a greater risk of side effects in women, or to a perception among healthcare providers that women are less likely to experience another heart attack.

'We need further research to understand the barriers to guideline-recommended treatment in women,' said Dr Peters. 'There is clearly more work to be done to raise awareness of the benefits of high-intensity statins for both women and men who have experienced heart attacks, in order to eliminate these disparities.'

Eating several servings of nuts every week may help lower the risk of developing the heart rhythm irregularity, atrial fibrillation, also known as heart flutter, finds research published online in the journal Heart.

This level of consumption may also lessen the risk of developing heart failure, although the findings are less consistent, the research indicates.

Previous studies have suggested that eating nuts regularly is associated with a lower risk of heart disease/stroke and associated death, but it's not clear which particular aspects of cardiovascular disease nut consumption may be linked to.

To explore this in more depth, the researchers drew on the completed Food Frequency Questionnaire responses and lifestyle information from more than 61,000 Swedish 45-83 year olds. Their cardiovascular health was then tracked for 17 years (to the end of 2014) or until death, whichever came first.

People who ate nuts tended to be better educated and to have healthier lifestyles than those who didn't include nuts in their diet. They were less likely to smoke or to have a history of high blood pressure. And they were leaner, more physically active, drank more alcohol and ate more fruit and vegetables.

During the monitoring period, there were 4983 heart attacks, of which 917 were fatal; 3160 cases of heart failure; 7550 cases of atrial fibrillation; 972 cases of aortic valve narrowing; 983 abdominal aortic aneurysms (a bulge or swelling in the aorta, a major artery); and 3782 cases of stroke caused by a blood clot (ischaemic) and 543 caused by a brain bleed (intracerebral haemorrhage).

Nut consumption was associated with a lower risk of heart attack, heart failure, atrial fibrillation and abdominal aortic aneurysm, after taking account of age and sex.

But when several potentially influential known risk factors were accounted for, including lifestyle, general diet, diabetes, and family history, only associations with atrial fibrillation and with heart failure emerged.

The more often nuts were included in the diet, the lower was the associated risk of atrial fibrillation, the findings showed.

Eating a serving of nuts one to three times a month was associated with a lowered risk of just 3 percent, rising to 12 percent when eating them once or twice a week, and to 18 percent when eating them three or more times a week.

The findings for heart failure were less consistent: moderate, but not high, weekly nut consumption was associated with a 20 percent lower risk.

Each additional portion of nuts eaten during the week was associated with a 4 percent lowering in atrial fibrillation risk.

Eating nuts regularly was not associated with a lower risk of the narrowing of the valve serving the heart's largest artery, the aorta, or with the risk of stroke.

This is an observational study, and as such, cannot establish causation. And the researchers emphasise that those who ate nuts had fewer cardiovascular risk factors to start with, which may have affected the findings.

But the strength of the study lies in its large size and the large number of cardiovascular disease cases reported during the monitoring period, they say.

Nuts are a rich source of healthy fats, minerals, and antioxidants, all of which may aid cardiovascular health, they explain.

"Nut consumption or factors associated with this nutritional behaviour may play a role in reducing the risk of atrial fibrillation and possibly heart failure," they write.

And they suggest: "Since only a small proportion of this population had moderate (about 5%) or high (less than 2%) nut consumption, even a small increase in nut consumption may have large potential to lead to a reduction in incidence of atrial fibrillation and heart failure in this population."

EMBARGOED UNTIL 2 P.M. ET, Monday, April 16, Cleveland: A landmark 2016 Cleveland Clinic study of widely used pain-relieving drugs showed that celecoxib (Celebrex) was associated with comparable cardiovascular safety and better gastrointestinal (GI) and kidney safety when compared with either naproxen (Naprosyn) and ibuprofen (Motrin).

A new substudy, published today in the Journal of the American College of Cardiology, analyzed outcomes in PRECISION based on the presence or absence of aspirin use with specific NSAIDs (nonsteroidal anti-inflammatory drugs). The research shows that taking aspirin with celecoxib lessened its cardiovascular safety advantage, although it was still associated with fewer GI problems than either of the other drugs and fewer kidney issues than ibuprofen.

The decade-long PRECISION trial - Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen - studied osteoarthritis or rheumatoid arthritis patients who required daily prescription use of NSAIDs for pain relief. All participants had pre-existing heart disease or increased risk for developing heart disease.

The researchers reviewed occurrences of major adverse cardiovascular events such as heart attack or stroke, noncardiovascular death, clinically significant GI events, anemia of GI origin or serious renal events. GI problems including ulcers or chronic bleeding are known complications of NSAIDs, and NSAIDs are also known to cause kidney complications.

The substudy followed nearly 24,000 patients with osteoarthritis or rheumatoid arthritis who were taking daily prescription doses of either celecoxib, naproxen or ibuprofen for a minimum of 18 months. Of those patients, 11,000 were also taking aspirin. Adding aspirin diminished some of the safety advantage for celecoxib that was observed in the PRECISION trial - as patients taking both had more of a risk for major adverse events compared to those on just celecoxib alone. However, even with aspirin, celecoxib patients still had slightly less overall adverse outcomes than those taking ibuprofen with aspirin (6 percent vs 7.1 percent). There was not a significant overall difference between celecoxib and naproxen with aspirin. In addition, celecoxib patients had fewer GI problems than ibuprofen (0.9 percent vs. 1.4 percent) or naproxen (1.6 percent) and fewer renal issues than ibuprofen (0.6 percent vs. 1.2 percent).

"NSAIDS are some of the most widely used drugs in the world with more than 100 million prescriptions issued annually in the United States. Past studies have reported conflicting results regarding using NSAIDs together with aspirin, but we know that many patients do combine the medications, so it was vital to understand the risks and differences among the drugs," said Steve Nissen, M.D., chairman of Cardiovascular Medicine at Cleveland Clinic, and the study's principle investigator.

"The outcomes of this study could lead to changes in clinical practice. If a patient is not on aspirin, these results suggest that in many cases, celecoxib may be the NSAID of choice," said Grant Reed, M.D., an interventional cardiology fellow at Cleveland Clinic, and the study's first author. "Our findings underscore how important it is that physicians counsel their patients when starting them on an NSAID and consider the potential effects of use together with aspirin."

The PRECISION trial was initiated following the withdrawal of rofecoxib (Vioxx) - a drug in the same class as celecoxib that worked similarly - from the market in 2004. The FDA mandated a clinical trial to determine if celecoxib shared a similar increased risk of heart-related complications. PRECISION, known as a non-inferiority trial, demonstrated celecoxib is not more risky than the other two drugs, which are older and work in a different way. The primary outcomes of heart attack, stroke or death occurred in 2.3 percent of patients taking celecoxib, 2.5 percent of patients taking naproxen, and 2.7 percent of patients taking ibuprofen. PRECISION also assessed a broader measure of cardiovascular safety - the primary outcome plus hospitalization for unstable angina or coronary revascularization (stenting or bypass) - and showed a 15 percent higher risk for ibuprofen than celecoxib, but this difference was borderline in statistical significance.

The PRECISION trial also assessed GI and renal complications. GI problems including ulcers or chronic bleeding are known complications of NSAIDs. Celecoxib and rofecoxib were introduced in 1999 as a new type of NSAID designed to reduce the risk of GI complications. In the PRECISION trial, the rate of ulcers or GI bleeding was 54 percent higher for ibuprofen, and 41 percent higher for naproxen than celecoxib.

NSAIDs are also known to cause kidney complications and the trial showed a statistically significant 64 percent higher risk of worsening kidney function for ibuprofen compared with celecoxib. Numerically more kidney complications occurred with naproxen, but the difference was not statistically significant. Death from any cause was approximately 25 percent higher with naproxen than celecoxib, but this difference was borderline in statistical significance.

Osteoarthritis is the most common form of arthritis affecting more than 16 million Americans. Rheumatoid arthritis is a type of chronic arthritis that is an autoimmune disease affecting joints on both sides of the body. Rheumatoid arthritis is 2.5 times more common in women than men and affects more than 1.3 million people in the United States. Patients with rheumatoid arthritis are at an increased risk for heart disease. In the trial, 90 percent of patients had osteoarthritis and 10 percent had rheumatoid arthritis.

In a study of more than 15,000 girls and their mothers -- all Kaiser Permanente members in Northern California -- maternal overweight and hyperglycemia were linked to the earlier onset of puberty in girls 6 to 11 years old. Early puberty has been linked to multiple adverse health developments as girls grow up.

The study, "Associations between maternal obesity and pregnancy hyperglycemia and timing of pubertal onset in adolescent girls: A population-based study," was published today in American Journal of Epidemiology. The girls in the study were from diverse cultures and ethnicities.

"We know that maternal weight can influence childhood weight. What we are learning is that the in utero environment may also affect the timing of future pubertal development in offspring, which makes sense since human brains are developed in utero and the brain releases hormones affecting puberty," said lead author Ai Kubo, MPH, PhD, research scientist with the Kaiser Permanente Northern California Division of Research.

This research builds on previous Kaiser Permanente research that demonstrated earlier onset of puberty in American girls, as well as the possible role of environmental, perinatal and other risk factors. Early puberty, including the early onset of breast development or menarche (initiation of menstruation), increases the risk of adverse health outcomes including obesity, type 2 diabetes, polycystic ovarian syndrome, and cancer in adolescence and adulthood. For girls, it has been linked to a higher risk of adverse emotional and behavioral outcomes including depression, anxiety, earlier sexual initiation and pregnancy.

In 2010, Kaiser Permanente pediatricians in Northern California began routinely documenting Tanner stages, a standardized measure of pubertal development, in electronic health records during routine pediatric exams. This study is the largest to link the Tanner-stage measurements of girls with the medical records of their mothers in order to assess the role of pregnancy-related factors on pubertal timing.

Researchers found that maternal obesity (body mass index of 30 or more) and overweight (body mass index between 25 and 30) in mothers was associated with 40 percent and 20 percent greater chance of earlier breast development in girls, respectively. The study also found a 7-month difference in onset of breast development in daughters of obese versus underweight mothers.

For pubic hair development, similar associations between maternal obesity and earlier onset were found. However, the data suggest that the associations may differ by race and ethnicity. For instance, Asian girls with obese mothers were 50 percent more likely to experience earlier onset of pubic hair than Asian girls with normal-weight mothers, while there were no associations among African-American girls.

The study also found a significant relationship between hyperglycemia (elevated blood sugar during pregnancy) in mothers and the earlier onset of breast development, but not in mothers with gestational diabetes.

"It's possible that women with the diagnosis of gestational diabetes were more careful about weight and diet, which might have changed the amount of weight gain and offspring development patterns, but other studies need to replicate the finding to be able to conclude that there is an association," Kubo noted.

Senior author Lawrence H. Kushi, ScD, research scientist with the Division of Research, said the study provides new avenues for slowing the trend toward earlier sexual maturation in girls. "Understanding the intergenerational effects of in utero exposures is helping health care systems such as Kaiser Permanente to develop new strategies for assisting women to manage weight and hyperglycemia before and during pregnancy, not only for their own health, but also for that of their children."

Kaiser Permanente, the nation's largest integrated health system, is uniquely positioned to conduct research over the life course because its members stay with the health system for many years. This stable membership -- in conjunction with comprehensive electronic medical records -- enables studies such as this one, in which the long-term effects of exposures during pregnancy can be examined. For example, previous studies have examined the relationships between breastfeeding and the risk of breast cancer recurrence; maternal obesity, gestational diabetes and the early onset of puberty; and the early onset of puberty and obesity in girls.

DALLAS, April 16, 2018 -- African Americans who smoke appear to be at far greater risk of developing heart failure than those who never smoked, or those who quit, according to new research in the American Heart Association's journal Circulation.

"Previous research has focused on smoking and atherosclerosis, or hardening of the arteries, but not enough attention has been given to the other bad effects of smoking on the heart," said Michael E. Hall, M.D., M.S., a cardiologist at the University of Mississippi Medical Center in Jackson and senior study author. "With increasing rates of heart failure, particularly among African Americans, we wanted to look at the link between smoking and heart failure."

Patients with heart failure are unable to pump enough blood and oxygen to their bodies to remain healthy. According to the American Heart Association, 1 of every 5 Americans over the age of 40 is expected to develop heart failure in their lifetime--and that number is growing.

The study included 4,129 participants in the Jackson Heart Study with a median follow up of 8 years. At enrollment, none of the participants (average age 54) had heart failure or hardening of the arteries, which can lead to heart failure. Among participants there were 2,884 people who never smoked, 503 who were current smokers and 742 who were former smokers. During the study period, there were 147 hospitalizations for heart failure.

The study found hospitalizations for heart failure were:

Nearly three times more likely among current smokers;

Three-and-a-half times more likely among current smokers who smoked a pack or more a day; and

Twice as likely among those with a smoking history equivalent to smoking a pack a day for 15 years.

Researchers also found a link between current smoking and a larger left ventricle, the heart's main pumping chamber, which showed early signs that the left ventricle was not working properly. Hall said these changes in the left ventricle's structure and function likely put a person at greater risk of developing heart failure.

Importantly, researchers did not find a link between former smokers and heart failure hospitalization or changes in the left ventricle.

The study took into account high blood pressure, diabetes, body mass and other factors that might have biased results. Researchers said the association between smoking, heart failure hospitalizations and left ventricle changes remained even after also accounting for those participants who developed coronary heart disease during the study period.

Study limitations include the fact that the participants lived in only three counties in the Jackson, Mississippi metropolitan area, so findings may not be generalizable to African Americans living elsewhere.

"Still, the study clearly underscores the harms of smoking and the benefits of quitting," Hall said. As healthcare professionals, we would recommend that all patients quit smoking anyway, but the message should be made even more forcefully to patients at higher risk of heart failure."

A phase I, first-in-human study led by The University of Texas MD Anderson Cancer Center reveals for the first time, an investigational drug that is effective and safe for patients with cancers caused by an alteration in the receptor tyrosine kinase known as RET. The drug appears to be promising as a potential therapy for RET-driven cancers, such as medullary and papillary thyroid, non-small cell lung, colorectal and bile duct cancers, which have been historically difficult to treat.

The oral drug, BLU-667, is being investigated in a multi-center, open label trial. The pre-clinical and early clinical validation are published in April 15 online issue of Cancer Discovery. The results from the trial were presented April 15 at the American Association for Cancer Research Annual Meeting 2018 in Chicago.

"There is a critical un-met need for effective drugs against cancers that have the RET alteration, as there are no highly potent inhibitors currently approved specifically for these RET-driven cancers," said Vivek Subbiah, M.D., Assistant professor of Investigational Cancer Therapeutics. "The current treatments for these cancers are limited to traditional chemotherapy and earlier generations of multiple kinase inhibitors. These options have had limited success with often considerable side effects that significantly impact the patient's quality of life."

Subbiah's study is investigating BLU-667 as a novel precision-targeted drug that, through a proof-of-concept trial, has shown promising activity and disease control as a highly selective RET inhibitor. The drug targets RET-altered cancers with fewer side effects affecting non-cancerous organs.

RET is linked to half of all medullary thyroid cancers, 20 percent of papillary thyroid cancers and 1 to 2 percent of non-small cell lung cancers. Subbiah's team followed 43 patients with advanced tumors not eligible for surgery. The investigation also studied 26 patients with medullary thyroid cancer, 15 with non-small cell lung cancer and two with other RET-driven cancers.

"Tumor reductions and durable responses were observed in most patients, especially those patients whose cancer progressed with chemotherapy and multi-kinase inhibitors," said Subbiah. "Our study reported an overall response rate of 37 percent for RET-driven cancers, with responses of 45 percent for non-small cell lung cancer and 32 percent for medullary thyroid."

BLU-667 was chosen for investigation because it is 100 times more selective for RET than other kinases tested, and has proved effective in stopping genetic mutations known as gatekeepers, which have been tied to resistance to multiple kinase therapy.

"Overall, the data show the precision targeted therapy with next-generation kinase inhibitors can have a powerful impact for patients with RET-driven cancers," said Subbiah. "By offering a highly selective medicine tailored for this oncogenic driver, we hope this new therapy will enable patients to benefit from the recent advances in genomic profiling that have revolutionized treatment options for patients with kinase-driven diseases."

HERCULES, Calif. -- April 14, 2018 -- New research showcasing the importance of Bio-Rad's Droplet Digital PCR (ddPCR) technology in clinical applications will be featured in more than 60 presentations at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, April 14-18.

One growing application area of ddPCR technology is guiding therapeutic decisions. Doctors need to know as quickly as possible whether their prescribed treatment is working or not so they can adjust the regimen. The key in making that determination is identifying and consistently measuring a biomarker that can indicate treatment outcome. Use of ddPCR technology in the clinic is increasing due to the technology's ability to reliably detect and quantify these biomarkers, as well as ddPCR's technical simplicity, speed, and cost-effectiveness.

Researchers continue to find novel ways to explore these biomarkers using ddPCR technology, whether they are epigenetic markers to determine cancer recurrence after surgery or cell-free DNA (cfDNA) derived from a tumor that reveals the effectiveness of immunotherapy. Below, we highlight a few of these studies that will be presented at this year's AACR meeting.

Using ddPCR Technology to Identify a Potential Epigenetic Biomarker of Lung Cancer

For patients with early-stage non-small cell lung cancer (NSCLC), the only recommended treatment option is surgery. Following surgery, approximately a third of these patients relapse after five years. Drs. Ana Robles, Delphine Lissa, Curtis Harris, and collaborators at the National Cancer Institute in Bethesda, Maryland, sought prognostic biomarkers that could predict relapse in patients with stage I lung adenocarcinoma, a major subtype of NSCLC.

With the knowledge that the HOXA9 promoter is methylated in stage I tumors, Robles, Lissa, and team used ddPCR technology to analyze HOXA9 promoter methylation in formalin-fixed, paraffin-embedded tumor specimens. They found an association between higher methylation levels and increased recurrence rates after five years. This indicated that HOXA9 methylation levels, as detected via ddPCR technology, could be used in combination with other biomarkers to identify high-risk stage IA and IB patients and potentially steer these patients for follow-up chemotherapy to prevent recurrence.

This poster (abstract #4208) will be presented on Tuesday, April 17, 1-5 PM in Section 10.

ddPCR Helps Detect Metastatic Cervical Cancer and Monitor Immunotherapy Response

Human papillomavirus (HPV) cfDNA in the blood is a unique tumor marker for metastatic cervical cancers. Dr. Liang Cao and his team at the National Cancer Institute investigated whether this biomarker could be used to identify patients with HPV16- or HPV18-positive metastatic cervical cancer and to assess the patient's response to tumor-infiltrating lymphocyte (TIL) immunotherapy.

Using ddPCR, Dr. Cao's team genotyped and quantified circulating HPV cfDNA in serum samples from patients with HPV-positive metastatic cervical cancer. They found HPV cfDNA in all samples from known cancer patients and none in samples from healthy blood donors. In patients who exhibited a positive response to TIL therapy, the researchers were able to use ddPCR technology to detect a transient peak in HPV cfDNA, a sign of tumor death.

This poster (abstract #1581) will be presented on Monday, April 16, 8 AM -12 PM in Section 26.

Early Prediction of Treatment Response in HPV-associated Oropharyngeal Cancer with ddPCR Technology

HPV is also associated with most oropharyngeal squamous cell carcinomas (OPSCCs), a disease in which distant metastatic disease can occur in up to 10% of patients. Monitoring this condition with imaging can be challenging and slow, so Dr. Glenn Hanna and his colleagues at the Robert and Renée Belfer Center for Applied Cancer Research at the Dana-Farber Cancer Institute investigated the feasibility of using ddPCR technology in identifying signs of OPSCC and monitoring patients' response to treatment.

"While HPV-specific serum and salivary antibody testing has been evaluated, HPV cfDNA has not been well studied as a biomarker to characterize metastatic or advanced oropharyngeal cancer causally related to HPV," said Dr. Hanna. "Some small studies have looked at HPV DNA via qPCR or antibodies in patients with newly diagnosed HPV oropharynx cancers to try and understand viral clearance after chemoradiation, but these efforts have been limited by the sensitivity of the assays."

Using ddPCR, the team detected and quantified five strains of HPV cfDNA in blood samples from a small cohort of patients with recurrent metastatic HPV-positive OPSCC, who were undergoing either conventional treatment or immunotherapy. They found that HPV cfDNA levels strongly correlated with both disease burden and distant sites of metastasis. In three cases, Dr. Hanna and team detected a decline in cfDNA levels up to 14 days prior to imaging evidence that later confirmed treatment response.

"This study shows that ddPCR is a feasible alternative to imaging for measuring disease burden: it offers greater sensitivity for detecting HPV cfDNA with relatively low sample volumes," Dr. Hanna said. "It also uses peripheral blood and therefore could potentially act as a liquid biopsy if it were validated for clinical use."

Financial support for this study was provided by the Expect Miracles Foundation and the Robert A. and Renée E. Belfer Foundation.

This poster (abstract #2581) will be presented on Monday, April 16, 1-5 PM in Section 25.

Bio-Rad will also host an Exhibitor Spotlight Presentation in Theater A, McCormick Place South, entitled: "Droplet Digital PCR and the Power of Partitioning: Advanced Applications for Liquid Biopsy" on Tuesday, April 17, at 12:30 PM. The presentation will feature scientific talks by Dr. Marzia Del Re, PharmD, PhD, from the University Hospital of Pisa, Italy, and Dr. Ed Schuuring, PhD, from The University Medical Center Groningen, the Netherlands.

Bio-Rad's new, fully automated 4-color multiplexed digital PCR system, the QX ONE ddPCR System, will be on display at Bio-Rad's booth (#1031). The booth will also feature the company's award-winning QX200 Droplet Digital PCR System, the Illumina Bio-Rad Single-Cell Sequencing Solution, and several new ddPCR assays available on Bio-Rad's Digital Assay Site.

Please visit bio-rad.com/digitalPCR to learn more about Bio-Rad's Droplet Digital PCR technology at AACR.

Bio-Rad, QX200, QX ONE, Droplet Digital, and ddPCR are trademarks of Bio-Rad Laboratories, Inc. in certain jurisdictions. Illumina is a trademark of Illumina, Inc. in certain jurisdictions.

The QX ONE and QX200 Droplet Digital PCR Systems are for research use only and are not intended for use in diagnostic procedures.

Heat and cold waves affect people with certain health conditions differently, highlighting the need for tailored public service risk communication.

Extreme hot and cold weather increase the number of deaths and emergency room visits but affect specific at-risk populations differently, according to new research from the U.S. and Japan.

The study, published in the journal Risk Analysis, found that extreme cold increased mortality and morbidity risks for people with cardiovascular and respiratory diseases, while extreme heat was risky for people with renal diseases. "We analyzed the data from Twin Cities, Minnesota, in the U.S., and found patterns with universal validity across the globe," says Matteo Convertino, an Associate Professor of Hokkaido University who led the study. The results highlight the potential for tailoring public service messages for people with specific health conditions.

While well known that extreme weather can be dangerous, not enough analysis has been done to compare specific temperatures against deaths and disease to know when public service messaging will be most effective.

Convertino teamed up with the University of Minnesota Twin Cities and the Minnesota Department of Health to determine which critical temperatures should trigger critical public health warnings. The Twin Cities are known for their harsh winters and hot, humid summers. The team gathered extreme temperature data and compared it to deaths in the city between 1998 and 2014 and emergency department visits from 2005 to 2014.

They found that the relative risk for mortality and morbidity increased generally with more extreme temperatures, but that at-risk populations were affected differently depending on their health conditions. Risk for people with cardiovascular disease or respiratory illness increased in the winter, but not significantly in the summer, which was the opposite for people with renal diseases. Diabetics showed no clear response to extreme temperature. They also found that percentile-based temperature thresholds and heat index are more appropriate than absolute temperatures for determining when to initiate emergency risk communications.

"Considering climate variability over space and time, tailored emergency risk communication programs are extremely important for informing the general public about potential health risks, such as severe heat waves or cold snaps, and how individuals can protect themselves. Our model can determine such temperature thresholds to start risk communications, which is important for saving human lives," says Convertino.

13 April 2018, Paris, France: Deep-learning approaches to pattern recognition in liver biopsy samples have moved one step closer to clinical application, with a new study reporting a good correlation between an automated image analysis system and an expert reviewer for the identification of key markers of disease activity in a pre-clinical model of non-alcoholic steatohepatitis (NASH). The study reported today at The International Liver Congress™ 2018 in Paris, France, found that deep-learning algorithms applied using open-source pathology software (QuPath1) could accurately identify cell histology patterns consistent with lobular inflammation and hepatocellular ballooning - markers of disease activity that are essential to establish the diagnosis and severity of NASH.2

Non-alcoholic steatohepatitis is the progressive form of non-alcoholic fatty liver disease (NAFLD), in which excessive fat accumulates in the liver of individuals who do not have a history of alcohol abuse.2,3 NAFLD is regarded as a hepatic manifestation of metabolic syndrome, with the number of individuals with NAFLD/NASH increasing rapidly worldwide, in parallel with the increasing prevalence of obesity.3 Although clinical algorithms based on blood test results are being developed to identify patients with progressive NASH,4-6 liver biopsy remains essential to establish both the diagnosis of NASH and the severity of the disease.2

'The histological evaluation of NASH by microscopy is time consuming and limited by inter- and intra-observer variability', explained Mr John Brozek from the French biotechnology company, GENFIT, which is developing the deep-learning system. 'We have been working to eliminate the subjectivity associated with interpreting histological images and have recently used deep-learning technologies to quantify histological patterns associated with NASH in an animal model'.7,8

In the study presented today by Mr Brozek, animal models (rats or mice fed a choline-deficient, L-amino-acid-defined diet supplemented with cholesterol) were used to evaluate hepatocellular ballooning and lobular inflammation in liver biopsy samples. An expert histopathologist determined the ballooning and inflammation scores for all the animals included in the study, and deep-learning models were constructed to detect and analyze these histological features. An initial training set (n=31) was used to calibrate ballooning and inflammation for subsequent prediction of these histological features in four independent cohorts (n=271).

According to Mr Brozek, the deep-learning system was able to predict cell histological patterns relating to ballooning and inflammation with accuracies of 98% and 91%, respectively. Excellent agreement was observed between the expert and fully automated scores of ballooning at a cellular level for each of the cohorts (k=0.84 and k=0.81). An excellent correlation was also observed with the full tissue samples (k=0.71), and between whole slide imaging-based automatic scoring of inflammation on the training cohort (Rho=0.907).

'Deep-learning-based scoring systems allow an exhaustive and reproducible analysis of all cells in a biopsy sample, and they can analyze specific regions of cells that can be difficult to interpret manually, even if you are an expert', said Mr Brozek. 'Our automated scoring system for ballooning and inflammation showed a high correlation with expert evaluation and it is ready to be used for high-throughput activity scoring in pre-clinical studies or, in the near future, as a companion diagnostic tool for clinical application'.

'There are key challenges in the consistency of liver biopsy interpretation and machine learning offers the promise of a more standardized, objective approach that allows for the analysis of biopsies in clinical trials', said Prof. Phil Newsome from the Queen Elizabeth Hospital and University of Birmingham, UK, and EASL Governing Board Member.

PHILADELPHIA - More than 16 million Americans suffer from dry eye, an often chronic condition that causes burning, itching, or stinging sensations in the eye, as well as impaired vision. For years, patients and their eye doctors have turned to omega-3 fatty acids commonly found in fish-derived supplements as a treatment for the disease. Findings from a new randomized clinical trial, now show omega-3 supplements are no more effective than placebo at alleviating dry eye symptoms. The results are published today in the New England Journal of Medicine and presented at the Annual Meeting of the American Society of Cataract and Refractive Surgery in Washington, D.C.

The three year, 27-center DREAM study was led by researchers from the Perelman School of Medicine at University of Pennsylvania and the Icahn School of Medicine at Mount Sinai with 25 other sites located at universities and private practices throughout the United States. Data from the study revealed that even the highest dose of omega-3 supplements ever tested, did not improve outcomes for participants.

"Our findings provide evidence that, contrary to a long held belief in the ophthalmic community, omega-3 supplements are not significantly better than a placebo at reducing dry eye symptoms," said Maureen Maguire, PhD, a professor of Ophthalmology at Penn Medicine and the principal investigator of the Coordinating Center for the study. "Many patients receiving omega-3 supplements did have substantial improvement in their symptoms, but just as many patients taking placebo had improvements."

The researchers enrolled a total of 535 participants with at least a six-month history of moderate to severe dry eye. Participants were randomly assigned to receive either a daily dose of an omega-3 supplement or an olive oil placebo. Each omega-3 dose contained 2,000 milligrams of EPA and 1,000 milligrams of DHA. Each placebo dose contained 5 grams, or roughly one teaspoon, of olive oil. A total of 349 participants received daily doses of fish-derived omega-3 fatty acids and 186 participants received a daily dose of olive oil. The doses were delivered in identical capsules and neither the patients nor their eye doctors knew which treatment group they were in.

After 12 months, the researchers found that participant's symptoms had improved substantially in both groups, but there was no significant difference in the degree of symptom improvement between the groups. Overall, 61 percent of people in the omega-3 group and 54 percent of those in the control group achieved at least a 10-point improvement in their symptom score, but the difference between the groups was not statistically significant.

"We were surprised that the omega-3 supplements had no beneficial effect," said Vatinee Y. Bunya, MD, an assistant professor of Ophthalmology at Penn Medicine, and co-director of the Penn Dry Eye & Ocular Surface Center, who served as principal investigator for the clinical center at Penn. "The results are significant and may change the way a lot of ophthalmologists and optometrists treat their patients."

Omega-3 fatty acid supplements taken orally proved no better than placebo at relieving symptoms or signs of dry eye, according to the findings of a well-controlled trial funded by the National Eye Institute (NEI), part of the National Institutes of Health. Dry eye disease occurs when the film that coats the eye no longer maintains a healthy ocular surface, which can lead to discomfort and visual impairment. The condition affects an estimated 14 percent of adults in the United States. The paper was published online April 13 in the New England Journal of Medicine.

Annual sales of fish- and animal-derived supplements amount to more than a $1-billion market in the United States, according to the Nutrition Business Journal. Many formulations are sold over-the-counter, while others require a prescription or are available for purchase from a health care provider.

"The trial provides the most reliable and generalizable evidence thus far on omega-3 supplementation for dry eye disease," said Maryann Redford, D.D.S., M.P.H., program officer for clinical research at NEI. Despite insufficient evidence establishing the effectiveness of omega-3s, clinicians and their patients have been inclined to try the supplements for a variety of conditions with inflammatory components, including dry eye. "This well-controlled investigation conducted by the independently-led Dry Eye Assessment and Management (DREAM) Research Group shows that omega-3 supplements are no better than placebo for typical patients who suffer from dry eye."

The 27-center trial enrolled 535 participants with at least a six-month history of moderate to severe dry eye. Among them, 349 people were randomly assigned to receive 3 grams daily of fish-derived omega-3 fatty acids in five capsules. Each daily dose contained 2000 mg eicosapentaenoic acid (EPA) and 1000 mg docosahexaenoic acid (DHA). This dose of omega-3 is the highest ever tested for treating dry eye disease. The 186 people randomly assigned to the placebo group received 5 grams daily of olive oil (about 1 teaspoon) in identical capsules. Study participants and the researchers did not know their group assignment.

Blood tests at 12 months confirmed that 85 percent of people in the omega-3 group were still compliant with the therapy. In the omega-3 group, mean EPA levels quadrupled versus no change in the placebo group. Mean levels of oleic acid, the constituent of olive oil, remained stable in both treatment groups.

Importantly, unlike in most industry-sponsored trials, all participants were free to continue taking their previous medications for dry eye, such as artificial tears and prescription anti-inflammatory eye drops.

"Omega-3s are generally used as an add-on therapy. The study results are in the context of this real-world experience of treating symptomatic dry eye patients who request additional treatment," said study chair for the trial, Penny A. Asbell, M.D., of the Department of Ophthalmology at the Icahn School of Medicine at Mount Sinai in New York City.

Patient-reported symptoms were measured as change from baseline in the Ocular Surface Disease Index, a 100-point scale for assessing dry eye symptoms, with higher values representing greater severity. After 12 months, mean symptoms scores for people in both groups had improved substantially, but there was no significant difference in the degree of symptom improvement between the groups. Symptom scores improved by a mean of 13.9 points in the omega-3 group and 12.5 points in the placebo group. A reduction of at least 10 points on the index is considered significant enough for a person to notice improvement. Overall, 61 percent of people in the omega-3 group and 54 percent of those in the control group achieved at least a 10-point improvement in their symptom score, but the difference between the groups was not statistically significant.

Likewise, there were no significant differences between the groups in terms of improvement in signs of dry eye. Signs of dry eye were evaluated by the clinician using standardized tests that measure the amount and quality of tears and the integrity of the cornea and the conjunctiva, the surface tissue that covers the front of the eye.

"The findings also emphasize the difficulty in judging whether a treatment really helps a particular dry eye patient," said the leader of the coordinating center for the study, Maureen G. Maguire, Ph.D., of the Department of Ophthalmology at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. "More than half the people taking placebo reported substantial symptom improvement during the year-long study."

"The results of the DREAM study do not support use of omega-3 supplements for patients with moderate to severe dry eye disease," Dr. Asbell concluded.