Wednesday, September 19, 2018

Underperforming big ideas in diabetes and breast cancer

Management of type 2 diabetes and screening for breast cancer make up a large portion of most family physicians' practices, including my own. Care and prevention for these patients is based on straightforward underlying theories of disease causation and behavior. Patients with type 2 diabetes have high blood glucose levels; treatment involves normalizing blood glucose through lifestyle modification and medication. Small, nonpalpable breast cancers eventually become large, symptomatic tumors. Smaller tumors are more likely to be curable, so undergoing regular screening mammography is preferable to not doing so.

But what if these underlying theories are wrong?

In a 2016 editorial in JAMA, Drs. Michael Joyner, Nigel Paneth, and John Ioannidis explored how the "big idea" or narrative that investments in genetics and information technology will lead to a revolution in health care has captured a large share of biomedical research funding and journal publications. They then illustrated how this big idea has "underperformed," as central assumptions of precision/personalized medicine have not been borne out in studies and tens of billions of dollars invested into electronic health records since 2009 have not made patient care measurably better or patient data more accessible to researchers.

Is tight glycemic control for patients with type 2 diabetes mellitus an underperforming clinical big idea? In an analysis in Circulation: Cardiovascular Quality and Outcomes, Drs. Rene Rodriguez-Gutierrez and Victor Montori compared clinical policy statements and practice guidelines for patients with type 2 diabetes between 2006 and 2015 with evidence from randomized controlled trials. Despite little or no evidence that tight glycemic control (hemoglobin A1c less than 6.5 or 7.0%) improves microvascular or macrovascular outcomes compared to less strict hemoglobin A1c goals, the majority of guidelines continued to endorse tight control for one or both of those outcomes. (In contrast, American Family Physician editorials and articles have asserted that "Physicians should not let well-intentioned but misguided concern for glucose levels distract them from attending to other interventions that more profoundly affect mortality [in patients with type 2 diabetes]: smoking cessation, blood pressure control, metformin therapy, and lipid reduction.")

And do small breast tumors detected by mammograms become large, lethal ones? Sometimes, but not as often as most patients and physicians think, according to an observational study in the New England Journal of Medicine that concluded: "Women [with tumors detected on mammography] were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large." This study also concluded that most of the reduction in breast cancer mortality over the past 40 years could be attributed to improved systemic therapy rather than earlier tumor detection. In an editorial on counseling women about breast cancer screening, Dr. Mark Ebell and I discussed the benefits and harms of mammography in younger women and noted that for every additional breast cancer death prevented by starting at age 40, two women will be overdiagnosed with (and overtreated for) breast tumors that never would have become clinically apparent.


This post first appeared on Common Sense Family Doctor on October 26, 2016.

Monday, September 3, 2018

Fracture prevention in older adults: what the evidence says

Hip fractures are a significant preventable cause of morbidity and mortality in older adults. Strategies to reduce hip fracture rates include preventing falls, screening for osteoporosis and prescribing bisphosphonate drugs to increase low bone density, and vitamin D supplementation. Recent studies and guidelines have clarified some of the evidence surrounding hip fracture prevention.

In a Putting Prevention Into Practice case study in the August 15 issue of American Family Physician, Drs. Tina Fan and Elizabeth Erickson discussed two updated U.S. Preventive Services Task Force (USPSTF) recommendations on interventions to prevent falls and supplements for primary prevention of fractures. Although the USPSTF continues to recommend exercise interventions to prevent falls in community-dwelling adults 65 years or older at increased risk of falls, it no longer recommends vitamin D supplements to prevent falls, due to evidence of no benefit and potential harms (increased falls and kidney stones). The Task Force found insufficient evidence to assess the balance of benefits and harms of vitamin D and calcium supplements at daily doses greater than 400 IU of vitamin D and 1,000 mg of calcium (lower doses are not effective) in postmenopausal women without a history of osteoporosis, which may come as a surprise, given how many are taking such supplements.

The USPSTF also recently reaffirmed its previous recommendation to screen for osteoporosis with bone measurement testing in women 65 years and older. Earlier this year, The Lancet published the first randomized controlled trial of osteoporosis screening with fracture outcomes. Although screening did not affect the primary outcome of all osteoporosis-related fractures over 5 years (HR 0.94, 95% CI 0.85-1.03), it reduced the incidence of hip fractures (HR 0.72, 95% CI 0.59-0.89). More controversial was the Task Force's recommendation to screen postmenopausal women younger than 65 years at increased risk for osteoporosis. In a JAMA editorial, Dr. Margaret Gourlay argued that the 2-step screening strategy advised by the USPSTF - clinical risk assessment tool followed by bone density testing if indicated - may not produce a net benefit to patients. Although screening women younger than age 65 has potential benefits, it is unclear if these benefits outweigh the opportunity costs:

If complicated risk tools perform no better than age alone to identify screening candidates, women younger than 65 years may be subjected to inefficient screening procedures. … The clinician could spend half of a 15-minute clinical visit accessing a risk tool and asking the patient about unfamiliar risk factors (eg, secondary causes of osteoporosis) to make 1 decision out of the dozen or more compressed into an annual physical examination. … Given the myriad responsibilities of primary care practices caring for patients with high-acuity conditions, implementation of screening programs that are needlessly complex is burdensome and distracts from high-value medical care.

Finally, for patients with osteoporosis who are eligible for treatment, given concerns about long-term adverse effects of bisphosphonates, including rare osteonecrosis of the jaw, for how long should these drugs be prescribed? A FPIN Help Desk Answer found low-quality evidence that for most women, bisphosphonate therapy beyond 5 years does not further reduce clinical vertebral fractures, nonvertebral fractures, or mortality. However, women with persistent femoral neck T-scores lower than -2.5 may benefit from longer treatment durations.


This post first appeared on the AFP Community Blog.