Body

Researchers compared 258 certified medical home primary care practices in Minnesota to 136 non-certified practices, to see if certification had any bearing on performance measures related to the quality of diabetes care. Certified practices were found to have slightly more medical home practice systems than uncertified practices. Additionally, certified practices had somewhat better performance outcomes on quality measures related to diabetes care. Uncertified practices, comprising 39 percent of the surveyed practices, were noted to be more rural but had similar patient populations. Practices certified as medical homes have more systems and improved performance for diabetes care, but the differences are modest.

People in Ontario living with HIV had a 34 per cent higher incidence rate of chronic obstructive pulmonary disease (COPD) and were diagnosed with the disease about 12 years younger than HIV-negative individuals, according to a study led by researchers at St. Michael's Hospital of Unity Health Toronto and ICES.

Researchers analyzed incidences of COPD among adults 35 years and older who were living with and without HIV between 1996 and 2015 in Ontario - where over 40 per cent of Canadians living with HIV reside.

People with HIV were diagnosed with COPD at a mean age of 50 years old compared with 62 for HIV-negative individuals.

The study, publishing on Feb. 18, 2020 in CMAJ Open, is the first of its kind to examine the rates of COPD among women living with HIV -- researchers found the rate of COPD among women living with HIV was 54 per cent higher than that of HIV-negative women.

"As people with HIV live longer, it is important to understand how common other illnesses are to ensure that prevention, screening and treatment strategies can be developed," said Dr. Tony Antoniou, a scientist at the Li Ka Shing Knowledge Institute of St. Michael's.

"We wanted to understand how common COPD is in Ontario residents with HIV because COPD is a disease that generally worsens with time, can worsen a person's quality of life and is strongly linked to smoking," added Dr. Antoniou, who is also an adjunct scientist at ICES, the not-for-profit research institute where the Ontario data were analyzed.

COPD affects over 380 million people worldwide and is projected to become the fourth leading global cause of death by 2030. It is potentially preventable and is strongly associated with smoking. In a sensitivity analysis, the higher prevalence of smoking in people with HIV appeared to explain the higher risk of COPD in these patients.

"While other factors may contribute to the development of COPD in people with HIV, our work highlights the importance of trying to help our patients with HIV quit smoking to prevent COPD in the first place and prevent further lung damage in people who are already diagnosed with COPD," said Dr. Antoniou.

Dr. Antoniou would next like to explore the quality of COPD care that people living with HIV are receiving. He also hopes the medical community will begin routinely considering COPD when managing people living with HIV.

Genetic tests to predict a person's risk of heart disease and heart attack have limited benefit over conventional testing.

This is the finding from scientists at Imperial College London, who devised a highly sophisticated test analysing thousands of so-called genetic variants linked to heart health.

The results of the test, published in the Journal of the American Medical Association, revealed only modest improvement over the standard method doctors currently use to measure heart disease and heart attack risk - using factors such as cholesterol, blood pressure, smoking habits and presence of diabetes.

The scientists stressed the study doesn't contradict previous findings that heart disease runs in families, or that a person's genes may place them at higher risk of the condition. Rather, the findings suggest that, at present, genetic data adds only modestly to the information we currently gain using conventional testing. This may change in the future as our knowledge of genes affecting heart disease risk improves.

Dr Ioanna Tzoulaki, lead author of the study from Imperial's School of Public Health, said: "Genetic tests to predict a person's risk of developing a condition are becoming cheaper and cheaper, and will soon become part of routine patient care.

Therefore we needed to evaluate whether these tests can add information to our existing tools of predicting who is at high risk of developing heart disease. Our research suggests that for heart disease these tests do not add much to the information we can gather from assessing factors such as cholesterol levels and blood pressure."

Heart disease is a leading cause of death worldwide and is responsible for around 64,000 deaths in the UK each year. The condition is caused by narrowing of the blood vessels supplying the heart due to the build-up of fatty substances, which then leads to heart attacks.

At the moment, in the UK when doctors want to assess a person's risk of heart disease, they calculate a score called QRISK. This involves analysing factors such as age, sex, cholesterol levels, blood pressure, diabetes and whether a person smokes, to calculate risk of developing heart disease within the next 10 years. If the risk is calculated as above 10 per cent, a patient is recommended treatment such as statins to lower cholesterol.

The researchers behind the current study wanted to see if analysing a person's genetic information could enhance the predictive power of the QRISK score, and a similar score used in the USA.

The team analysed clinical and genetic information from over 350,000 people included in the UK Biobank study. The individuals had no history of cardiovascular disease, and an average age of 55 years old.

The group were tracked for eight years, during which time any heart disease diagnoses or heart attacks were recorded (6,272 of these events occurred in this time frame).

The team then sifted through the genetic data for small DNA changes called single nucleotide polymorphisms (SNPs). These occur when a single nucleotide (building block of DNA) is replaced with another. These changes may cause disease, and the study team used all known SNPs associated with heart disease risk - over one million in total.

The team found that when the genetic results were combined with a patient's QRISK score, approximately 4% of individuals had a more accurate risk assessment compared to QRISK alone, although for some people the prediction was less accurate.

The researchers explained the genetic information was mainly from individuals with European ancestry aged 40-69, and further analyses are required to confirm the findings among people of different ages and ethnicities.

Dr Joshua Elliott, first author of the research explained: "Our study suggests that easy-to-collect information such as age, sex, blood pressure and cholesterol levels are still the most powerful tools we have for peering into the future and predicting your risk of heart disease and heart attack."

A genetic study has found evidence to suggest that women who take statins in the long term could be less likely to develop ovarian cancer, according to new research funded by Cancer Research UK published today (Tuesday 18 February)*.

The same result was also found in women who carry the BRCA1/2 gene fault. Having the BRCA1/2 fault puts women at a higher risk of ovarian cancer than the general population**.

The research published in JAMA studied genes and the extent to which they inhibit the enzyme HMG-CoA reductase - which is responsible for regulating cholesterol in the body - and is the exact enzyme targeted by statin drugs to reduce cholesterol.

While the study suggests that statins could lower ovarian cancer risk, more research needs to be done specifically looking at their use and impact on women's risk of developing the disease.

The researchers based at the University of Bristol looked at 63,347 women between the ages of 20 and 100 years old, of whom 22,406 had ovarian cancer. They also looked at an additional 31,448 women who carried the BRCA1/2 fault, of whom 3,887 had ovarian cancer. The study used an approach called Mendelian randomization***, which involves analysing the genetic data from thousands of people.

Statins may protect against the development of ovarian cancer because they've been shown to induce apoptosis - one of the body's ways of getting rid of old, faulty or infected cells - and to stop tumours from growing in laboratory studies. Another line of thought is that statins lower circulating cholesterol, which helps regulate cell growth, though this research suggests that lower circulating cholesterol was not the method by which statins may reduce ovarian cancer risk.

The findings suggest that long-term statin use could be associated with an estimated 40% reduction in ovarian cancer risk in the general population, although the estimate comes from looking at gene variation rather than statins themselves, and the exact mechanism by which these genes are associated with lower ovarian cancer risk is unclear.

Ovarian cancer is the 6th most common cancer in women in the UK. There are around 7,400 cases each year****, and out of those with a known stage at diagnosis, almost 6 in 10 are diagnosed at a late stage*****. Around 4,100 women die from the disease every year in the UK.

There is no test that reliably picks up ovarian cancer at an early stage, so chemoprevention could be an important approach to saving lives.

Professor Richard Martin, from the University of Bristol, said: "Our findings open up the possibility of repurposing a cheap drug to help prevent ovarian cancer - especially in women who are at a higher risk. It's incredibly interesting that women whose bodies naturally inhibit the enzyme targeted by statins have a lower risk of ovarian cancer, but we don't recommend anyone rushes to take statins specifically to reduce ovarian cancer risk because of this study.

"It's a promising result and I hope it sparks more research and trials into statins to demonstrate conclusively whether or not there's a benefit."

Dr Rachel Orritt, Cancer Research UK's health information manager, said: "This study is a great first step to finding out if statins could play a role in lowering ovarian cancer risk, and justifies future research into this area.

"But there's not yet enough evidence to know if statins themselves could reduce the risk of developing ovarian cancer safely. And it's important to remember that the risk of developing ovarian cancer depends on many things including age, genetics and environmental factors. Speak to your doctor first if you have any concerns about your risk."

About 10% of patients who come to complex care hospitals may have low levels of folate and other indicators of malnutrition, investigators say.

To ensure those patients are identified and helped, those who present with gastrointestinal problems, chronic kidney disease or sepsis -- all associated with malnutrition -- need to have their folate levels tested on admission, they report in the journal Laboratory Medicine.

"We looked at people who had low levels and relatively normal folate levels," says Dr. Gurmukh Singh, vice chair of pathology at the Medical College of Georgia at Augusta University. "The people with low levels had a higher incidence of gastrointestinal disorders like chronic diarrhea as well as sepsis and kidney disease. The other piece was that people who had low levels also had other markers of malnutrition."

Singh and his colleagues were trying to come up with a recommendation for whose folate levels should be tested because of testing inconsistencies he was finding at AU Medical Center, the Augusta-based adult teaching hospital for MCG, including what happened when a low folate level was found.

The investigators compared 1,019 patients with a serum folate level of less than seven nanograms per milliliter, which they considered low, to a group of 300 patients with an intermediate level of at least 15 nanograms per milliliter. A nanogram is one billionth of a gram, and a milliliter is one thousandth of a liter.

Evidence of malnutrition they found in those with low folate levels included 25% with a lower serum albumin, the main protein of the liquid portion of blood that's made by the liver; 55% with low levels of prealbumin, a short-lived protein made by the liver which decreases in supply when the liver isn't getting adequate nutrition; and 11% with a deficiency in vitamin B12, which often works synergistically with folate, which is also a B vitamin. More than 62% of those with low serum folate were deficient in one or more of these malnutrition markers, the investigators say.

Their findings led them to suggest that patients with a folate level of less than seven nanograms per milliliter be evaluated for malnutrition. A state of overweight or obesity should not preclude malnutrition evaluation, they say.

The low folate group also had a significantly higher prevalence of gastrointestinal disorders, sepsis and abnormal serum creatinine. Creatinine is a breakdown product of muscle and protein that is typically eliminated by the kidneys, and high blood levels indicate kidney problems.

The investigators found no significant differences in the high and low folate groups in related factors like diabetes, drug and alcohol abuse or an existing diagnosis of malnutrition.

A complicating factor was that as many as 60% of the patients they reviewed had received a folic acid supplement before they were tested, which meant that low folate levels could be even more prevalent. That finding and other indicators of nutritional deficiency prompted the AU Health System to urge medical staff to do folic acid testing before any supplements or blood products were given, even before patients eat a hospital meal. The health system's Medical Executive Board also approved automatic testing for prealbumin and B12 in those found to have a folate level of less than seven nanograms per milliliter.

The investigators note that B12 levels also need to be tested before a folate supplement is given. Folate and B12 have some overlap in function but both are needed, Singh says. "One cannot make up for the other and they often work together to make blood and keep the nervous system in working order," he says.

Folate, or folic acid, is an essential nutrient, which means our bodies don't make it, we have to consume it.

The availability of folate in so many foods means many of us likely don't need testing or a supplement, he says. "The addition of folate to common foods like cereal has helped us compensate to some extent for even an unhealthy diet," Singh says.

Since 1998, folic acid has been added to bread flour, cornmeal, pasta, rice, breakfast cereal and corn masa flour used to make corn tortillas and tamales, according to the National Institutes of Health Office of Dietary Supplements. Foods like eggs, legumes, asparagus, Brussels sprouts and citrus fruits are some of the healthiest foods that are naturally high in folic acid.

Low folate levels may indicate problems with absorption not just with diet, Singh says. Too little folate can result in the blood disorder megaloblastic anemia, which is characterized by weakness, trouble concentrating and even heart palpitations. Folate can help prevent birth defects like spina bifida and brain defects in developing babies.

Singh reported similar inconsistencies in testing and follow up action in a similar study in Georgia and Missouri published five years ago. He suggested then that serum folate levels be tested on admission as an indicator of nutritional status.

TUCSON, Ariz. - As she jumped to head a soccer ball during her junior year of college, Kelly Farrell collided skulls with a teammate. She later was diagnosed with a concussion, which proved to be severely debilitating.

"I had a lot of trouble concentrating in school and class," said Farrell, a physical therapist and Tucson native, who experienced a constant headache for two days after her concussion. Even after the initial pain subsided, her headache was reactivated by noise, bright light and studying on her computer.

Each year, traumatic brain injuries such as concussions cause nearly 2.5 million visits to an emergency room. The most common problem associated with concussions is headache. In an effort to develop a treatment, researchers at the University of Arizona College of Medicine - Tucson collaborated in a preclinical study with scientists at Teva Biologics and the Mayo Clinic to identify the cause of post-concussion headaches and a possible therapy for the millions of patients who experience this pain each year.

With Edita Navratilova, PhD, assistant professor in the Department of Pharmacology, as lead author and Frank Porreca, PhD, associate head of the department, as a co-author, the group published its findings in Cephalalgia in September 2019.

The scientists investigated whether a drug that blocks a substance elevated in migraine patients, calcitonin gene-related peptide (CGRP), would alleviate the headache pain by modeling human concussion in mice and assessing post-injury pain sensitivity. Researchers administered the anti-CGRP treatment twice - two hours and then seven days after the injury - and found the two doses significantly reduced pain responses.

In addition to immediate or acute headaches, long-lasting or persistent post-traumatic headaches affect injured patients, Dr. Porreca said.

Researchers assessed persistent post-traumatic headaches in their mouse model. Bright light reactivated headaches in injured mice 14 days after injury but caused no headaches in healthy mice.

To prevent stress-induced headaches, scientists administered an additional drug dose before the bright-light stress. When administered before the stress, in addition to after the injury, the drug not only prevented the immediate headache but also prevented bright light from reactivating the headache.

Researchers concluded that CGRP may be the link between traumatic brain injuries and post-injury headaches.

"The sustained prevention of the actions of CGRP with an antibody treatment administered early after a mild traumatic brain injury prevents post-traumatic headache in our preclinical model, as well as the vulnerability for development of persistent post-traumatic headache," Dr. Porreca said.

"The encouraging aspect is that we do have a mechanism which seems to be driving some aspect of the pain, and if treated at the right time in this preclinical model, it seems to be effective," Dr. Porreca said. Although the timing and dosage of the drug would need to be adapted to humans in future clinical trials, he added, it appears immediate treatment is critical to the therapy's success.

In a new study published in Cancer Epidemiology, Associate Professor Dr. Cara Frankenfeld of the George Mason College of Health and Human Services found racial disparities in how the presence of cancer-related diagnostic and treatment technology is related to colorectal cancer (CRC) patient outcomes in Georgia. The findings suggest that the hospital capacity and availability of advanced technologies may benefit white patients, but not black patients, in terms of time-to-treatment and overall survival.

The study, "Racial Disparities in Colorectal Cancer Time-to-Treatment and Survival Time in Relation to Diagnosing Hospital Cancer-Related Diagnostic and Treatment Capabilities," evaluated the time-to-treatment and survival rates of patients in relation to cancer-related technologies of the diagnosing hospital using colorectal tumor-level data from the Georgia Cancer Registry merged with hospital-level data from the American Hospital Association from 2010-2015. There were 11,453 colon tumors and 4,591 rectosigmoid/rectal tumors included in the analyses.

The study found that factors such as hospital capacity or size indicators (e.g., total surgical operations, licensed beds, and emergency room visits) were associated with earlier treatment in white patients, but not black patients. Higher counts of treatment related technologies were also associated with better survival for whites but not blacks. Despite disparities in other factors, availability of virtual colonoscopy technologies emerged as a technology related to survival favorability in both blacks and whites.

Researchers sought to better understand how structural issues at the hospital level influence differences in cancer outcomes across racial groups. Based on the data from the Georgia Cancer Registry, blacks experienced longer time-to-treatment and were less likely--at any point in time--to have received any treatment. Black patients also experienced longer time-to-surgery and longer time-to-treatment, respectively. However, the median time-to-treatment was similar across white and black patients.

These results suggest that characteristics of diagnosing hospitals influence overall treatment and survival but more work is needed to better characterize these influences and differences observed for white and black racial groups before specific recommendations to improve patient outcomes can be made. The study also provides an important foundation for future research in additional geographic locations.

"Structural influences on disease progression need further study, and this work contributes a piece to that complex puzzle," says Frankenfeld. "Understanding the long-term influences or consequences of where people get diagnosed with colorectal cancer and attempting to identify modifiable factors that benefit patients could be helpful to patients, as they think about CRC prevention and detection. Hospitals also benefit as they consider resource acquisition and utilization."

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. Low-dose methotrexate associated with small increase in some adverse events

Abstract: http://annals.org/aim/article/doi/10.7326/M19-3369
Editorial: http://annals.org/aim/article/doi/10.7326/M20-0435
URL goes live when the embargo lifts

A pre-specified secondary analysis of a double-blind placebo-controlled randomized trial found that low-dose methotrexate (LD-MTX) was associated with a small to modest increase in the risk for some adverse events, including skin cancer and gastrointestinal, infectious, pulmonary, and hematologic effects in patients at risk for heart disease. The risk for kidney-related side-effects was decreased. The findings are published in Annals of Internal Medicine.

LD-MTX is the most commonly used drug for systemic rheumatic diseases worldwide and the recommended first-line agent for rheumatoid arthritis. Despite decades of clinical use, few randomized controlled trials have studied adverse events associated with LD-MTX use.

Researchers from Brigham and Women's Hospital randomly assigned 4,786 patients at risk for heart disease to receive LD-MTX or placebo over a median follow-up of 23 months to objectively assess adverse event rates, risk, and risk differences in those receiving LD-MTX. All participants also received folic acid 1mg per day for six days a week. The researchers found that there was a small absolute increase in adverse events with LD-MTX compared to placebo. With the exception of an increased risk of skin cancers, there was no difference between treatment arms for the risk of other malignancies and risk for adverse events such as cirrhosis and pneumonitis in the LD-MTX group was similar to that seen in previous reports. According to the authors, this data provides new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX, which is considered an efficacious and generally well-tolerated treatment for rheumatoid arthritis and other diseases.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Daniel H. Solomon, MD, please contact Haley Bridger at hbridger@bwh.harvard.edu.

2. New guidelines address chronic insomnia disorders and obstructive sleep apnea in military personnel and Veterans

Abstract: http://annals.org/aim/article/doi/10.7326/M19-3575
URLs go live when the embargo lifts

The U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) recently approved a joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). Positive airway pressure therapy, or CPAP, is recommended as a first-line treatment for OSA and cognitive behavior therapy (CBT) is a key recommendation for treating insomnia. A synopsis of the key recommendations is published in Annals of Internal Medicine.

Military service is an established risk factor for sleep disorders. Accordingly, military personnel and Veterans have a higher prevalence of sleep disorders than the general population. Also, these populations have high rates of posttraumatic stress disorder (PTSD), traumatic brain injury (TBI) and other mental health disorder. When patients have insomnia and/or OSA along with PTSD, TBI or other mental health disorders, the treatment of both their sleep and other disorder is challenging. Physicians are beginning to recognize sleep disorders as an important issue to be addressed.

The guidelines recommend CPAP be used for the entirety of a patient's sleep period. For patients who do not use PAP for at least 4 hours per night, this therapy should be continued along with addressing barriers to better PAP adherence. CBT for insomnia (CBT-I) is the recommended treatment; however, brief behavioral therapy for insomnia (BBT-I) is also acceptable. Sleep hygiene is not recommended as standalone therapy for chronic insomnia disorder. Pharmacotherapy with doxepin, nonbenzodiazepine benzodiazepine receptor agonists is second-line treatment for chronic insomnia disorder and should be used for a short course of treatment. Over the counter agents to include diphenhydramine and melatonin are not indicated for the treatment of insomnia.

According to the authors, the guideline is a major step for the VA and DoD in recognizing the importance of appropriately diagnosing and treating sleep disorders in these unique populations. The guidelines highlights commitment of both organizations to adhering to evidence-based practice. The guideline was written by a joint, multi-disciplinary VA/DoD work group that utilized a standardized process to develop 41 evidence-based recommendations. The guideline is relevant to all providers who treat patients with sleep disorders. The full guideline is available at: https://www.healthquality.va.gov/guidelines/CD/insomnia/index.asp.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, James Sall, PhD, FNP-BC, please contact him directly at James.Sall@va.gov.

3. Statins might be effective in treating xanthelasmas in patients with normal lipid levels

Abstract: http://annals.org/aim/article/doi/10.7326/L19-0797
URLs go live when the embargo lifts

Researchers from the Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, observed the regression of xanthelasmas in a patient with normal lipid levels after treatment with a statin. Typical treatments for patients with xanthelasmas with normal lipid levels carry risks and high recurrence rates. The Case Report is published in Annals of Internal Medicine.

Xanthelasmas are benign, yellowish growths made up of cholesterol under the skin that appear on or around the eyelids. In about half of cases, they are associated with familial high cholesterol. In these patients, regression of xanthelasmas can occur with lipid-lowering drugs, such as statins. Many patients with xanthelasmas, however, have normal lipid levels. In these patients, xanthelasmas can be removed with liquid nitrogen, topical trichloroacetic acid, laser ablation, or surgical excision, but these therapies all carry risk for scarring or residual pigmentation and high recurrence rates (up to 40 percent).

To report the effect of statin therapy for a person with xanthelasmas with normal lipid levels, researchers prescribed 10 mg of rosuvastatin, a statin to help lower "bad" cholesterol (mainly LDL) and raise "good" cholesterol, to a 52-year-old woman with normal lipid levels who wanted her xanthelasmas removed for cosmetic reasons. Within three months of treatment, the patient's LDL cholesterol level had decreased by 50 percent, remaining steadily in that range for the next four years. Within 12 months, she reported some regression of her xanthelasmas, and after four years of rosuvastatin, they had almost completely regressed.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Robert A. Hegele, MD, please contact him directly at hegele@robarts.ca.

Also new in this issue:

Getting Incentives Right in Payment Reform: Thinking Beyond Financial Risk
Vinay K. Rathi, MD; J. Michael McWilliams, MD, PhD; Eric T. Roberts, PhD
Ideas and Opinions
Abstract: http://annals.org/aim/article/doi/10.7326/M19-3178

Inpatient Notes: Optimizing Inpatient Nutrition--Why Hospitalists
Should Get Involved
Philipp Schuetz, MD, MPH, and Jeffrey L. Greenwald, MD
Hospitalist Commentary
Abstract: http://annals.org/aim/article/doi/10.7326/M20-0120

Methotrexate is a common drug with a long history; for the past 40 years, it's been used to treat a range of diseases. Today it is the most commonly used drug for systemic rheumatic diseases worldwide and is the first drug a physician will prescribe for a patient with rheumatoid arthritis. But despite its use by millions of people, there is not robust data on the rates of the side effects of the drug. Observational studies have suggested that methotrexate may elevate a person's risk of a variety of adverse events, including liver toxicity, anemia and difficulty in breathing, but the magnitude of risk was unknown. Taking advantage of data from the Cardiovascular Inflammation Reduction Trial (CIRT), a randomized double-blind, placebo-controlled trial, investigators from Brigham and Women's Hospital have been able to far more accurately determine rates of adverse events for people taking methotrexate, finding small-to-moderate elevations in risks for skin cancer, gastrointestinal, infectious, lung, and blood adverse events. Results are published in Annals of Internal Medicine.

"Methotrexate is a cornerstone drug for a variety of inflammatory diseases, especially for rheumatoid arthritis," said Daniel Solomon, MD, MPH, a rheumatologist in the Division of Rheumatology, Inflammation and Immunology at the Brigham. "Over the decades, we've learned about the side effects but only from small studies. Questions for both physicians and patients have lingered about the drug's safety. Our study offers a detailed side-effect profile that I think will help us prescribe methotrexate in an informed way."

Solomon and his colleagues looked at data on 4,786 participants from CIRT who were randomized to receive low-dose methotrexate with folate or a placebo. Of 2,391 subjects who received methotrexate, 87 percent experienced an adverse event of interest compared to 81.5 percent of those who were randomized to placebo.

According to Solomon, the team's most surprising finding was a doubling of risk of skin cancer for participants taking methotrexate (53 incidents of skin cancer versus 26 for placebo). This result may be particularly important because patients with psoriatic arthritis -- a form of arthritis that affects people with psoriasis -- are already at increased risk of skin cancer.

Gastrointestinal, infectious, pulmonary and hematologic adverse events were also elevated, but the increased risk was mild to moderate. As anticipated, the team also saw an increase in liver test abnormalities and five cases of cirrhosis in the methotrexate arm versus zero in the placebo arm. The authors note that CIRT participants did not have rheumatoid arthritis or other rheumatic diseases and it is possible, although unlikely, that adverse event rates may vary outside of the CIRT population.

"We now have real numbers we can share with patients when talking about side effects," said Solomon. "We definitely wouldn't suggest this drug is too dangerous to give. But having a clear side-effect profile allows us to give it with eyes wide open and better balances the risks and benefits of an age-old drug."

(SAN ANTONIO) - Recognizing and addressing the widespread problem of sleep disorders in military personnel and veterans, the U.S. Departments of Veterans Affairs and Defense (VA/DoD) jointly have issued new guidelines for assessment and treatment of insomnia and obstructive sleep apnea.

"This is a major step for these two organizations in recognizing the importance of appropriately diagnosing and treating sleep disorders in these unique populations," said Vincent Mysliwiec, M.D., a sleep medicine physician, researcher and retired U.S. Army colonel who helped author the guidelines.

Dr. Mysliwiec, a professor of research in the Department of Psychiatry and Behavioral Sciences at The University of Texas Health Science Center at San Antonio, is also lead author of a synopsis of the guidelines written for the March 2020 issue of Annals of Internal Medicine, a leading medical journal.

Military service is an established risk factor for sleep disorders, which are considerably more prevalent in military personnel and veterans than in the general U.S. population. These populations also have high rates of traumatic brain injury, posttraumatic stress disorder (PTSD), and other mental health disorders, which combined with insomnia and/or sleep apnea complicate treatment of affected military personnel and veterans.

Nearly half of U.S. military personnel have reported poor sleep quality, including insomnia symptoms. Insomnia is one of the most common sleep disorders and affects up to 41 percent of active-duty military personnel deployed to combat zones, 25 percent of noncombatants and 20 percent of those preparing for deployment.

One study found a six-fold increase in sleep disorders among veterans between 2003 and 2010, when millions were deployed to Iraq and Afghanistan. In that study, 4.5 percent of veterans were diagnosed with sleep-disordered breathing, including sleep apnea, a condition in which blockage of the airway interferes with breathing at night. Importantly, sleep apnea increases the risk of cardiovascular disease and motor vehicle crashes. The study also found that 2.5 percent of veterans were diagnosed with insomnia.

Dr. Mysliwiec's group concluded in the journal article that the actual prevalence of chronic insomnia among veterans likely is considerably higher, because it often is not documented in the medical record. Insomnia can cause daytime sleepiness and cognitive impairment and can adversely affect mental and physical health.

In other research, veterans have reported insomnia rates as high as 50 percent.

The "VA/DoD Clinical Practice Guideline for the Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea" is based on evidence-based and effective therapies for military personnel and veterans with chronic insomnia disorder and sleep apnea, while including evidence from civilian studies. The VA/DoD work group's 41 recommendations in the clinical practice guideline (CPG) are relevant to all military, VA, and civilian providers who treat patients with sleep disorders.

For treatment of sleep apnea, notable recommendations in the CPG include:

Use of positive airway pressure therapy (commonly known as CPAP) for the entirety of a patient's sleep period.

Continued use of CPAP even with patients who do not use it for at least the common insurance provider standard of four hours per night, while addressing barriers to CPAP adherence.

Interventions to improve CPAP adherence in patients with sleep apnea and co-occurring PTSD, anxiety, and/or insomnia upon initial diagnosis because these patients have higher rates of non-adherence.

For chronic insomnia, notable recommendations include:

Cognitive behavioral therapy for insomnia is the recommended treatment, but a shortened version called brief behavioral therapy for insomnia is also acceptable for some patients.

Sleep hygiene - habits that promote nighttime sleep quality, such as limiting length of daytime naps and avoiding stimulants close to bedtime - while important, should not be used as a stand-alone therapy for chronic insomnia disorder.

Some medications may be used as a second-line treatment for chronic insomnia, but anti-psychotic drugs and over-the-counter agents such as antihistamine and melatonin are not helpful for treating chronic insomnia.

"We expect the guidelines to be far-reaching and lead to necessary changes in clinical practice while helping to determine what clinical and research questions will need to be addressed in military personnel and veterans," Dr. Mysliwiec said. "Whereas in the past, problems with sleep disorders have been discounted, there is growing recognition of the importance of sleep health and treating sleep disorders."

Chlorthalidone, the guideline-recommended diuretic for lowering blood pressure, causes more serious side effects than hydrochlorothiazide, a similarly effective diuretic, according to a new study led by researchers at Columbia University Irving Medical Center. The findings, published in JAMA Internal Medicine, contrast with current treatment guidelines recommending chlorthalidone over hydrochlorothiazide.

The researchers found that patients taking chlorthalidone had nearly three times the risk of developing dangerously low levels of potassium and a greater risk of other electrolyte imbalances and kidney problems compared with those taking hydrochlorothiazide. Information from the largest individual database studied by the team revealed that 6.3% of patients treated with chlorthalidone experienced hypokalemia (low blood potassium), compared with 1.9% of patients who were treated with hydrochlorothiazide.

Hypokalemia rates remained higher for patients taking chlorthalidone even when given at a lower dose than hydrochlorothiazide.

"Doctors prescribing chlorthalidone should monitor for certain side effects in their patients," says George Hripcsak, MD, MS, chair and Vivian Beaumont Allen Professor of Biomedical Informatics at Columbia University Vagelos College of Physicians and Surgeons and lead author of the study.

The study, which looked at 17 years of data on more than 730,000 individuals treated for hypertension, is the largest multisite analysis directly comparing the two antihypertensive drugs in the general patient population.

The results were generated by the Large-Scale Evidence Generation and Evaluation in a Network of Databases (LEGEND) Hypertension study, a method for analyzing data in millions of electronic health records around the world developed by the Observational Health Data Sciences and Informatics (OHDSI) network, which has a central coordinating center at Columbia University.

An earlier LEGEND Hypertension study, published in The Lancet, found that thiazide diuretics were more effective and caused fewer side effects than ACE inhibitors when used as first-line antihypertensive drugs.

In the current paper, the researchers found that chlorthalidone and hydrochlorothiazide were similarly effective in preventing heart attack, hospitalization for heart failure, and stroke. However, patients treated with chlorthalidone had a significantly higher risk of side effects, including hypokalemia, which can lead to abnormal heart rhythms; hyponatremia (low sodium), which can cause confusion; kidney failure; and type 2 diabetes.

"The difference in the occurrence of side effects was striking," says Hripcsak. "Hypokalemia, hyponatremia, chronic and acute kidney problems, along with other electrolyte imbalances, are all potentially dangerous side effects."

The new study is not the first to find side effects associated with chlorthalidone. A previous observational study found that the drug was associated with more electrolyte imbalances than hydrochlorothiazide.

Nearly 95% of patients in the study were first treated with hydrochlorothiazide, which was the preferred diuretic for treating hypertension throughout most of the study period (2001-2018). However, in 2017, the American College of Cardiology and American Heart Association issued new guidelines favoring chorothalidone, based on the drug's longer half-life and indirect evidence that it may be more effective in reducing cardiovascular risk.

"Until we have more studies directly comparing the two diuretics, we don't really know whether the risk of the side effects seen in observational studies outweighs the potential cardiovascular benefits," says Hripcsak, who notes that the VA Office of Research and Development is now conducting a randomized clinical trial to help settle the debate.

The research team performed several sensitivity analyses (time at risk, blood pressure, dose), as well as other best practices developed within the OHDSI network (including propensity scoring and the use of negative controls) to ensure a lack of bias in the results. These best practices are used throughout the LEGEND project, which OHDSI collaborators believe will continue to impact critical decisions in health care. These analyses ensure that the compared groups are similar in severity of illness, comorbidities, baseline blood pressures, age, sex, and all other measurable variables.

"LEGEND is a novel approach that could transform the way we use real-world evidence in healthcare," says co-author Patrick Ryan, PhD, adjunct assistant professor of biomedical informatics at Columbia. "Rather than inefficiently conducting bespoke analyses one-question-one-method-one-database-at-a-time, leaving us vulnerable to various threats to scientific validity, LEGEND provides a systematic framework that can reproducibly generate evidence by applying advanced analytics across a network of disparate databases for a wide array of exposures and outcomes."

"Not only does LEGEND offer a path to scale to the real needs of the health care community," Ryan added, "it also provides the complementary diagnostics to help us understand how much we can trust the evidence we've produced."

Increased risk of mortality from any cause is 44% for women who have experienced domestic abuse, according to study jointly led by the Universities of Warwick and Birmingham

Study highlights the increased risk of developing cardiometabolic diseases such as cardiovascular disease (31%) and type 2 diabetes (51%)

More research is required to determine what factors specifically lead to an increase in mortality, some of it may be linked to the increased risk of cardiometabolic disease

Researchers emphasise need for healthcare professionals to be aware of health impacts of domestic abuse

Women who have experienced domestic abuse appear to be more than 40 per cent more likely to die from any cause compared to the general population, a study led by the Universities of Warwick and Birmingham suggests.

The researchers have also identified an increased risk of developing cardiometabolic diseases such as cardiovascular disease and type 2 diabetes in those who have experienced domestic abuse, although more research is required to determine what other factors specifically lead to an increase in their mortality.

Domestic abuse, consisting of physical, psychological, sexual, financial and emotional abuse, is thought to be an extremely common phenomenon, with an estimated 1 in 3 women globally and about 1 in 4 women in the UK having experienced it at some point in their life.

The research, which is part of a wider research agenda into the health impacts of domestic abuse, is published today (17 February) in the Journal of the American Heart Association and explores the association between exposure to domestic abuse in a female population and the subsequent development of cardiometabolic disease (cardiovascular disease, hypertension and type 2 diabetes) and all-cause mortality.

Using medical records from UK GP surgeries between 1995 and 2017, the team were able to identify 18,547 women with a recorded code relating to exposure to domestic abuse. These were matched to 72,231 like for like women (similar in terms of age, body mass index, deprivation level and smoking status) who did not have such an experience recorded.

The researchers then followed both groups whilst they were contributing to the dataset and calculated the risk of developing cardiometabolic illness and all-cause mortality. They found that the risk of developing cardiovascular disease was increased by 31% and type 2 diabetes by 51% in the exposed group. There was no association found with hypertension. They also found that all-cause mortality (i.e. due to any cause throughout the study period) among women exposed to domestic abuse was 44% higher. Although the team were not able to confirm the reason for the increased mortality, it may be partly explained by the increased cardiovascular risk. It is important to note that during the study period, the number of patients who died was relatively few (948 out of a total cohort of 91,778) likely due to the age at cohort entry being young (37 years old). The adjusted relative risk increase was 44%, with the absolute risk of death being 6 per 1,000 women per year in the exposed cohort (recorded exposure to domestic abuse) compared to 3.1 per 1,000 women per year in those without such a record in their medical notes.

However, the research published using GP records has identified a discrepancy found between the abuse reported in GP practices and the national survey data, with an estimated prevalence of 1 in 4 women in survey data who have experienced domestic abuse compared to about 0.5% coded as such in GP data. This means that many of those not coded as exposed to domestic abuse may have actually experienced some abuse. If this is the case, then it would suggest that the displayed results may be an underestimation.

Better linkage and data sharing between public services, such as the NHS and police, could help inform GPs to further support the mental and physical health needs of their patients who have experienced domestic abuse.

Lead author Dr Joht Singh Chandan, from Warwick Medical School and the University of Birmingham's Institute of Applied Health Research, said: "As further in-depth detail of the traumatic experiences is not available in these records it was not possible to assess whether the severity of domestic abuse was associated with a different risk impact. It is important to note that not all cases of domestic abuse go onto develop adverse health outcomes, but from this study we can see that within this dataset, the cohort of women recorded to have experienced domestic abuse are at a greater risk than those without such records present.

"Considering the prevalence of domestic abuse, there is a public health burden of cardiometabolic disease likely due to domestic abuse. Although our study was not able to answer exactly why this relationship exists, we believe that it is likely due to the effects of acute and chronic stress. Additionally, we know that exposure to domestic abuse may be associated with other lifestyle factors (such as poor diet, alcohol and smoking as seen in our study). Although we made attempts to account for the impact of this on our results, these lifestyle factors still contribute risk for the development of cardiometabolic disease, therefore need public health approaches to manage this in women who have experienced domestic abuse.

"Not every woman experiencing domestic abuse will go onto to develop a long-term illness. Our understanding of the physical and mental health effects of domestic abuse is arguably still in its infancy.

"The introduction of the recently formed violence reduction units could play a role in supporting survivors of domestic abuse, as would the Domestic Abuse Bill which would give survivors the rights and support they clearly need."

Senior co-author Dr Krish Nirantharakumar of the University of Birmingham's Institute of Applied Health Research, said: "It is important for us to highlight to the government and public sector bodies to not only continue funding and supporting initiatives that prevent domestic abuse, but also invest in those services which can provide the support and care for survivors who have experienced such trauma, to prevent the development of these negative consequences which can be debilitating and disabling for life. Therefore, this research clearly supports the promotion of a public health approach to abuse and violence."

This work adds to the growing research published by the team at the two Universities exploring the physical and psychological effects of domestic abuse. In 2019, the team published research that showed that women who have experienced domestic abuse are almost twice as likely to develop fibromyalgia and chronic fatigue syndrome, while a previous study published in June 2019 showed that UK survivors of domestic abuse are three times more likely to develop severe mental illnesses.

DALLAS, Feb. 17, 2020 -- Longer sitting times were associated with higher levels of heart disease risk among overweight and obese post-menopausal women overall, according to new research published today in the Journal of the American Heart Association, the open access journal of the American Heart Association.

In this observational study, researchers measured the sitting habits of older women (after menopause; age ?55 years) and who were overweight or obese. Data from study participants was analyzed as a single group and by two ethnic groups - Hispanic women or non-Hispanic women - in order to determine if total sitting time and/or average uninterrupted sitting periods may have an impact on heart disease risk factors and whether these relationships varied by ethnicity.

From this data, the average total sitting time per day and the average time that participants spent in periods of uninterrupted sitting were calculated. Post-menopausal Hispanic women sat, on average, almost one hour less per day than non-Hispanic women of the same age group. They also spent significantly less time in uninterrupted sitting. However, each additional 15-minute increase in uninterrupted sitting was linked with about a 5% higher fasting blood sugar in Hispanic women, compared to a less than 1% increase in non-Hispanic women.

The study included a total of 518 women with an average age of 63 years and an average body mass index (BMI) of 31 kg/m2 (the clinical definition of obesity is a BMI ?30). Study participants wore accelerometers on their right hip for up to 14 days, removing the devices only to sleep, shower or swim. The accelerometers were used to track and record sitting and physical activity of the study participants throughout the day. A single blood test, concurrent with accelerometer wear, measured blood sugar and insulin resistance.

"We were surprised to observe such a strong negative link between the amount of time spent sitting and insulin resistance, and that this association was still strong after we accounted for exercise and obesity," said lead study author Dorothy D. Sears, Ph.D., professor of nutrition at the Arizona State University College of Health Solutions in Phoenix. Insulin resistance is a strong risk factor for both cardiovascular disease and type 2 diabetes.

Analysis of the data revealed the following:

Post-menopausal Hispanic women sat an average of about 8-1/2 hours per day, compared to more than 9 hours per day among non-Hispanic women;

Each additional hour of sitting time per day was linked with a more than 6% higher fasting insulin and a more than 7% increase in insulin resistance; and

Each additional 15 minutes in average sitting period was associated with a greater than 7% higher fasting insulin and an almost 9% increase in insulin resistance.

The analyses were adjusted for age, education, marital status, physical functioning and ethnicity.

Sears added, "The findings of this study build upon earlier research including our own, which showed, among older women, that too much time in sedentary behaviors was associated with higher risk for diabetes and heart disease. Reducing sitting time improves glucose control and blood flow, and engaging in physical activities, even light-intensity daily life activities like cooking and shopping, show favorable associations with reduced mortality risk and prevention of heart disease and stroke."

"In addition, Hispanics are a population that is understudied with respect to health risks," said Sears. "Hispanic women may have genetic differences that may increase the negative effects that sitting has on blood sugar. Health care providers should encourage patients, including older adults, to reduce their sitting time, take breaks in their sitting time and replace sitting with brief periods of standing or light physical activity."

The most recent guidelines for primary prevention recommend aspirin use for individuals ages 40 to 70 years who are at higher risk of a first cardiovascular event, but not for those over 70. Yet, people over 70 are at increasingly higher risks of cardiovascular events than those under 70. There has been considerable confusion from recently reported results of three large-scale randomized trials of aspirin in high risk primary prevention subjects, one of which showed a significant result, but the other two, based possibly on poor adherence and follow up, did not. As a result, health care providers are understandably confused about whether or not to prescribe aspirin for primary prevention of heart attacks or strokes, and if so, to whom.

In a commentary published online ahead of print in the American Journal of Medicine, researchers from Florida Atlantic University's Schmidt College of Medicine and collaborators from the University of Wisconsin School of Medicine and Public Health, and the Harvard Medical School and Brigham and Women's Hospital, provide guidance to health care providers and their patients. They urge that to do the most good for the most patients in primary care, health care providers should make individual clinical judgements about prescribing aspirin on a case-by-case basis.

"All patients suffering from an acute heart attack should receive 325 mg of regular aspirin promptly, and daily thereafter, to reduce their death rate as well as subsequent risks of heart attacks and strokes," said Charles H. Hennekens, M.D., Dr.P.H., senior author, the first Sir Richard Doll Professor, and senior academic advisor in FAU's Schmidt College of Medicine. "In addition, among long-term survivors of prior heart attacks or occlusive strokes, aspirin should be prescribed long-term unless there is a specific contraindication. In primary prevention, however, the balance of absolute benefits, which are lower than in secondary prevention patients, and risks of aspirin, which are the same as in secondary prevention, is far less clear."

The researchers emphasize that, based on the current totality of evidence, any judgments about prescribing long-term aspirin therapy for apparently healthy individuals should be based on individual clinical judgments between the health care provider and each of his or her patients that weighs the absolute benefit on clotting against the absolute risk of bleeding.

The increasing burden of cardiovascular disease in developed and developing countries underscores the need for more widespread therapeutic lifestyle changes as well as the adjunctive use of drug therapies of proven net benefit in the primary prevention of heart attacks and strokes. The therapeutic lifestyle changes should include avoidance or cessation of smoking, weight loss and increased daily physical activity, and the drugs should include statins for lipid modification, and multiple classes of drugs likely to be necessary to achieve control of high blood pressure.

"When the magnitudes of the absolute benefits and risks are similar, patient preference assumes increasing importance," said Hennekens. "This may include consideration of whether the prevention of a first heart attack or stroke is a more important consideration to a patient than their risk of a gastrointestinal bleed."

Individual clinical judgements by health care providers about prescribing aspirin in primary prevention may affect a relatively large proportion of their patients. For example, primary prevention patients with metabolic syndrome, a constellation of overweight and obesity, hypertension, high cholesterol, and insulin resistance, a precursor to diabetes mellitus, affects about 40 percent of Americans over age 40. Their high risks of a first heart attack and stroke may approach those in survivors of a prior event.

"General guidelines for aspirin in primary prevention do not seem to be justified," said Hennekens. "As is generally the case, the primary care provider has the most complete information about the benefits and risks for each of his or her patients."

According to the United States Centers for Disease Control and Prevention, more than 859,000 Americans die of heart attacks or stroke every year, which account for more than 1 in 3 of all U.S. deaths. These common and serious diseases take a very large economic toll, costing $213.8 billion a year to the health care system and $137.4 billion in lost productivity from premature death alone.

People who rely on social media for information were more likely to be misinformed about vaccines than those who rely on traditional media, according to a study of vaccine knowledge and media use by researchers at the Annenberg Public Policy Center of the University of Pennsylvania.

The study, based on nationally representative surveys of nearly 2,500 U.S. adults, found that up to 20% of respondents were at least somewhat misinformed about vaccines. Such a high level of misinformation is "worrying" because misinformation undermines vaccination rates, and high vaccination rates are required to maintain community immunity, the researchers said.

The study, published in the Harvard Kennedy School Misinformation Review, was conducted in the spring and fall of 2019, when the United States experienced its largest measles outbreak in a quarter century. Between the two survey periods, 19% of the respondents' levels of vaccine misinformation changed in a substantive way - and within that group, almost two-thirds (64%) were more misinformed in the fall than in the spring.

Media consumption patterns helped to explain the change in misinformation levels, the researchers found. Those respondents who reported increased exposure to information about measles and the MMR (measles, mumps, and rubella) vaccine on social media were more likely to grow more misinformed about vaccines. By contrast, those people who reported an increased exposure to news accounts about those topics in traditional media were more likely to grow less misinformed about vaccines.

"People who received their information from traditional media were less likely to endorse common anti-vaccination claims," said lead author Dominik Stecula, a postdoctoral fellow in the science of science communication program at the Annenberg Public Policy Center (APPC). He co-authored the study with Ozan Kuru, another APPC postdoctoral fellow, and APPC Director Kathleen Hall Jamieson.

The result is consistent with research suggesting that social media contain a fair amount of misinformation about vaccination while traditional media are more likely to reflect the scientific consensus on its benefits and safety, according to the Annenberg researchers.

'Worrying' levels of vaccine misinformation

The researchers found that:

18% of respondents mistakenly say that it is very or somewhat accurate to state that vaccines cause autism;

15% mistakenly agree that it is very or somewhat accurate to state that vaccines are full of toxins;

20% wrongly report that it is very or somewhat accurate to state that it makes no difference whether parents choose to delay or spread out vaccines instead of relying on the official vaccine schedule from the Centers for Disease Control and Prevention (CDC);

and 19% incorrectly say it is very or somewhat accurate to state that it is better to develop immunity by getting the disease than by vaccination.

Medical experts and media consumption

The researchers also found that an individual's level of trust in medical experts affects the likelihood that a person's beliefs about vaccination will change. Low levels of trust in medical experts coincide with believing vaccine misinformation, the researchers said.

In addition, the research found that vaccine misinformation proved resilient over time. Most of those in the sample (81%) were just as informed or misinformed in the spring (February/March) as they were months later, in the fall (September/October), despite the extensive news coverage of the measles outbreak and attempts by the CDC to educate the public. Among the 19% whose level of knowledge changed substantially, 64% were more misinformed and 36% were better informed.

The researchers point out that although the findings only show correlations between media coverage and individual attitudes - not causation - these findings still hold implications for the effectiveness of national pro-vaccination campaigns, the role of health professionals in addressing misinformation, and the impact of social media misinformation.

The findings, Kuru noted, come as a number of states have been debating whether to tighten their laws surrounding vaccination exemptions and social media companies have been wrestling with how to respond to different forms of misinformation.

The researchers said this study suggests that "increasing the sheer amount of pro-vaccination content in media of all types may be of value over the longer term." They said the findings also underscore the importance of decisions by Facebook, Twitter, YouTube and Pinterest to reduce or block access to anti-vaccine misinformation.