JAMA just announced its most-read articles in 2019 from across the JAMA Network. The topics of the articles ranged from push-ups and vitamin supplements to liquid biopsies and over-the-counter hearing aids. From the variety of novel and boundary-pushing topics, you can see why these articles proved so popular with physician readers.

Push-up capacity and risk of future cardiovascular events among active adult men

In a longitudinal cohort study published in JAMA Network Open in February 2019, researchers evaluated 1,104 career firefighters, and found that those who could do more than 40 push-ups had significantly less risk for incident cardiovascular disease (CVD) events compared with those who could do fewer than 10 push-ups.

“Push-up capacity is a no-cost, fast, and simple measure that may be a useful and objective clinical assessment tool for evaluating functional capacity and cardiovascular disease risk,” the authors wrote. “The use of push-up capacity has the potential to improve the feasibility and implementation of physical fitness assessment in workplace settings.

Based on the current study, CVD risk factor reduction should be recommended, including lifestyle measures for those with low push-up capacity, especially those capable of 10 or fewer push-ups.”

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Anticholinergic drug exposure and the risk of dementia

In this game-changing study published in June 2019 in JAMA Internal Medicine, investigators showed that different types of anticholinergic medications were associated with an increased risk of dementia in people aged 55 years or older.

Evaluating 58,769 patients with a diagnosis of dementia and 225,574 matched controls, researchers found statistically significant dementia risk associated with exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotic drugs, bladder antimuscarinics, and antiepileptic drugs—with an approximately 50% increased dementia risk for people with the highest cumulative anticholinergic exposure.

Rita F. Redberg, MD, editor of JAMA Internal Medicine commented,

"These findings are definitely practice-changing and could lead doctors to dramatically curtail use of anticholinergic drugs."

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Fluoride exposure during pregnancy and IQ scores in offspring

In a controversial study published in August 2019 in JAMA Pediatrics, researchers found that fluoride exposure during pregnancy was associated with lower IQ scores in children aged 3 to 4 years.

Researchers also noted a significant difference in outcomes between girls and boys. A 1-mg/L increase in maternal urinary fluoride was associated with a 4.49-point lower IQ score in boys, but with no statistically significant change in IQ scores in girls.

Dimitri Christakis, MD, editor of JAMA Pediatrics said,

"Most pediatricians, myself included, have been trained to believe that there is no merit to the arguments that [fluoride] is a potential toxin. This article suggests otherwise."

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Antipsychotic polypharmacy vs monotherapy and psychiatric rehospitalization in schizophrenia

Studies to date have shown that administering two or more antipsychotic medications isn’t more effective than monotherapy for people with schizophrenia; plus, it’s associated with increased adverse effects. But a February 2019 study in JAMA Psychiatry offers evidence to revise that practice.

In this study, investigators found that the risk for rehospitalization was slightly lower when a patient with schizophrenia was prescribed more than one antipsychotic compared with a single drug. If validated in further studies, this finding has the potential to overturn the standard of care.

Dost Öngür, MD, PhD, and editor of  JAMA Psychiatry said,

“Although this single paper is not sufficient to modify treatment recommendations, it raises important questions about whether antipsychotic polypharmacy should be avoided in all cases."

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Vitamin D supplementation and cardiovascular disease risks

Taking vitamin D supplements didn’t reduce major adverse cardiovascular events, including heart attack, stroke, CVD mortality, or all-cause mortality, researchers reported in a meta-analysis published in JAMA Cardiology in June 2019. These findings are in stark contrast to observational studies in which researchers have shown that low vitamin D levels are associated with elevated CVD risks. But observational studies cannot prove cause and effect, the authors pointed out.

This article—the first comprehensive meta-analysis on the subject—included 21 randomized clinical trials and involved more than 83,000 patients.

“In summary, the included trials, although different in their inclusion criteria, showed consistent findings of no significant benefit of vitamin D supplementation in reducing CVD events and all-cause mortality,” the authors concluded.

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Statin use and the risk of dementia after a concussion

Concussions are associated with an increased long-term risk of dementia. In this surprising study, published in May 2019 in JAMA Neurology, researchers found that people taking statins had less risk of dementia after a concussion than those not taking statins. Specifically, among 28,815 older adults with concussion, those who were prescribed a statin within 90 days of their injuries had a 13% reduced risk of dementia compared with those who didn’t get statins. Both groups still had an increased risk for dementia, but the risk was higher in the group not taking statins.

S. Andrew Josephson, MD, editor of JAMA Neurology said,

"While there is some biologic plausibility to this relationship, further studies are needed before we can recommend that patients with concussion be prescribed statins to prevent dementia. "

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Genotyping for personalised metastatic non-small cell lung cancer therapy

Liquid biopsy is showing promise as a testing method for several types of cancer—including non-small cell lung cancer (NSCLC). In a prospective cohort study, published in JAMA Oncology in October 2019, researchers investigated whether plasma next-generation sequencing of circulating tumor DNA (ctDNA) could increase the number of patients with metastatic NSCLC who could benefit from personalised cancer therapy.

Indeed, in this single-center cohort study involving 323 patients with NSCLC,

• tissue testing alone detected targetable mutations for 47 patients, but plasma sequencing increased the detection of targetable mutations to 82
• 86% of patients whose treatment was based on their ctDNA mutations from plasma next-generation sequencing achieved a complete or partial response or stable disease

“This clinical study is, to our knowledge, one of the largest to measure the implications of plasma-based genotyping for the delivery of targeted therapy in NSCLC and clearly demonstrates that liquid biopsy can improve delivery of therapy and, consequently, outcomes,” the authors concluded. “Given the ease of obtaining plasma-based genotyping and the success observed with such a noninvasive approach, our results argue for incorporation of plasma-based genotyping into routine clinical management of patients with NSCLC.”

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Vitamin A intake and cutaneous squamous cell carcinoma risk

Can vitamin A help prevent cutaneous squamous cell carcinoma (SCC), a common skin cancer in people with fair skin? According to the authors of a JAMA Dermatology article, published in July 2019, increased intake of dietary vitamin A is associated with decreased risk of incident SCC.

Vitamin A is a term that encompasses a large number of related compounds also known as retinoids (eg, retinol, retinal, and retinoic acid), and some carotenoids. Previous studies of the association between vitamin A or carotenoid intake and SCC risk have been limited and often inconsistent, the authors of this study noted. So, for their investigation, they used a longer follow-up period (more than 26 years) and a larger sample size (about 123,600 US adults).

“[A]lthough high vitamin A intake may be effective in chemoprevention of skin cancer, high intake of vitamin A, especially the preformed vitamin A (from animal foods, fortified foods, and dietary supplements), may have some adverse health effects, such as potentially increased risk of osteoporosis and hip fracture. More research is needed to understand the appropriate level of vitamin A intake for maximum health benefits. Therefore, risks and benefits of high vitamin A intake should be considered individually,” the authors advised.

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Ranibizumab and aflibercept for wet age-related macular degeneration

Neovascular (“wet”) age-related macular degeneration (AMD) is the most common cause of vision loss in people aged 50 years or older in the United States and worldwide. Treatment for AMD typically involves intraocular injections of vascular endothelial growth factor (VEGF) inhibitors. In a JAMA Ophthalmology article, published in January 2019, researchers compared two VEGF inhibitors—aflibercept and ranibizumab—and found that neither one was better than the other for improving visual acuity during a 1-year regimen.

But the interesting part is that the researchers used a “treat-and-extend” protocol. They began with usual monthly injections but, after an initial period, they allowed the injection intervals to increase or decrease depending on disease activity. Over time, this could allow fewer injections and visits, although this wasn’t shown in this 1-year analysis.

Still, the results are applicable to real-world practice, experts noted in a related commentary: “In particular, the approach to increasing or decreasing the interval between injections according to the presence of one or more features of disease activity could be widely adopted, although with optical coherence tomography interpretation conducted by the local physician.”

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Clinical evaluation of personal sound amplifier products vs hearing aids

Although age-related hearing loss is common, less than 20% of US adults with hearing loss use hearing aids. Two of the biggest reasons for this are the high cost (about $6,000 for a pair of hearing aids) and the inconvenience (ie, multiple fitting appointments). A low-cost alternative to hearing aids are direct-to-consumer, over-the-counter devices known as personal sound amplifier products (PSAPs).

In a JAMA Otolaryngology–Head & Neck Surgery study, published in May 2019, researchers compared the performance of PSAPs against basic and premium hearing aids in 56 adults with mild, moderate, or moderately severe hearing loss. The researchers found that people with mild and moderate hearing loss reported no differences between PSAPs and basic or premium hearing aids in terms of hearing outcomes and user preferences. However, the group with moderately severe hearing loss largely preferred the premium hearing aids, which they reported performed better across most tests.

Jay F. Piccirillo, MD, editor of JAMA Otolaryngology–Head & Neck Surgery said,

“As our population ages, more adults will experience age-related hearing loss. Over-the-counter hearing aids have the ability to radically disrupt current hearing aid dispensing and provide greater access to sound amplification.”

This story is contributed by John Murphy and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.