Continuation of Annual Screening Mammography and Breast Cancer Mortality in Women Older Than 70 Years

Background: Randomized trials have shown that initiating breast cancer screening between ages 50 and 69 years and continuing it for 10 years decreases breast cancer mortality. However, no trials have studied whether or when women can safely stop screening mammography. An estimated 52% of women aged 75 years or older undergo screening mammography in the United States. Objective: To estimate the effect of breast cancer screening on breast cancer mortality in Medicare beneficiaries aged 70 to 84 years. Design: Large-scale, population-based, observational study of 2 screening strategies: continuing annual mammography, and stopping screening. Setting: U.S. Medicare program, 2000 to 2008. Participants: 1 058 013 beneficiaries aged 70 to 84 years who had a life expectancy of at least 10 years, had no previous breast cancer diagnosis, and underwent screening mammography. Measurements: Eight-year breast cancer mortality, incidence, and treatments, plus the positive predictive value of screening mammography by age group. Results: In women aged 70 to 74 years, the estimated difference in 8-year risk for breast cancer death between continuing and stopping screening was −1.0 (95% CI, −2.3 to 0.1) death per 1000 women (hazard ratio, 0.78 [CI, 0.63 to 0.95]) (a negative risk difference favors continuing). In those aged 75 to 84 years, the corresponding risk difference was 0.07 (CI, −0.93 to 1.3) death per 1000 women (hazard ratio, 1.00 [CI, 0.83 to 1.19]). Limitations: The available Medicare data permit only 8 years of follow-up after screening. As with any study using observational data, the estimates could be affected by residual confounding. Conclusion: Continuing annual breast cancer screening past age 75 years did not result in substantial reductions in 8-year breast cancer mortality compared with stopping screening. Primary Funding Source: National Institutes of Health.

Reassessment of Risk for Stroke During Follow-up of Patients With Atrial Fibrillation

Relationship of Interleukin-1β Blockade With Incident Gout and Serum Uric Acid Levels: Exploratory Analysis of a Randomized Controlled Trial: Annals of Internal Medicine: Vol 169, No 8

Background: Although studies have shown that interleukin-1β (IL-1β) inhibitors can shorten gout attacks, whether they can prevent gout attacks is unclear. Objective: To examine the relationship among canakinumab, a monoclonal antibody targeting IL-1β; serum uric acid levels; and the incidence of gout attacks. Design: Secondary exploratory analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01327846) Setting: Many clinical sites in 39 countries. Participants: 10 059 patients with a prior myocardial infarction and a high-sensitivity C-reactive protein (hsCRP) level of at least 19.1 nmol/L. Intervention: Random allocation to canakinumab (50 mg, 150 mg, or 300 mg) versus placebo, administered subcutaneously every 3 months. Measurements: Rates of gout attacks were compared across patients with different baseline concentrations of serum uric acid (≤404.5 µmol/L, 404.6 to 535.3 µmol/L, and ≥535.4 µmol/L) and in different intervention groups in Cox proportional hazards regression models. Results: The median baseline concentration of serum uric acid was 362.9 µmol/L (interquartile range, 309.3 to 428.3 µmol/L), and median follow-up was 3.7 years. Among participants receiving placebo, incidence rates of gout attacks for serum uric acid concentrations of 404.5 µmol/L or lower, 404.6 to 535.3 µmol/L, and 535.4 µmol/L or higher were 0.28, 1.36, and 5.94, respectively, per 100 person-years. Canakinumab did not affect serum uric acid levels over time yet significantly reduced rates of gout attacks at all baseline concentrations of serum uric acid: Hazard ratios were 0.40 (95% CI, 0.22 to 0.73) for concentrations of 404.5 µmol/L or lower, 0.48 (CI, 0.31 to 0.74) for those between 404.6 and 535.3 µmol/L, and 0.45 (CI, 0.28 to 0.72) for those of 535.4 µmol/L or higher. Limitation: No adjudication of gout attacks. Conclusion: Quarterly canakinumab administration was associated with significantly reduced risk for gout attacks without any change in serum uric acid levels. These data have relevance for the development of agents for gout that target the IL-1β pathway of innate immunity. Primary Funding Source: Novartis.

Clinical Outcomes Associated With Sickle Cell Trait: A Systematic Review: Annals of Internal Medicine: Vol 169, No 9

Background: Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose: To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources: English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection: Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction: A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis: Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Limitation: Publication bias was possible, and high-quality evidence was scant. Conclusion: Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT. Primary Funding Source: National Human Genome Research Institute.

Variation in Prescription Drug Prices by Retail Pharmacy Type: A National Cross-sectional Study: Annals of Internal Medicine: Vol 171, No 9

Background: Cash prices for prescription drugs vary widely in the United States. Objective: To describe cash price variation by retail pharmacy type for 10 generic and 6 brand-name drugs throughout the United States and stratified by ZIP code. Design: Cross-sectional study. Setting: Drug pricing data from GoodRx, an online tool for comparing drug prices, representing more than 60 000 U.S. pharmacies (fall 2015). Measurements: Cash prices for a 1-month supply of generic and brand-name drugs were ascertained. Stratified by ZIP code, relative cash prices for groups of generic and brand-name drugs were estimated for big box, grocery-based, small chain, and independent pharmacies compared with a reference group of large chain pharmacies. Results: Across 16 325 ZIP codes, 68 353 unique pharmacy stores contributed cash prices. When stratified by 5-digit ZIP code, the relative cash prices for generic drugs at big box, grocery-based, small chain, and independent pharmacies compared with those at large chain pharmacies were 0.52 (95% CI, 0.51 to 0.53), 0.82 (CI, 0.81 to 0.83), 1.51 (CI, 1.45 to 1.56), and 1.61 (CI, 1.58 to 1.64), respectively. The relative cash prices for brand-name drugs were 0.97 (CI, 0.96 to 0.97), 1.00 (CI, 0.99 to 1.00), 1.06 (CI, 1.05 to 1.08), and 1.03 (CI, 1.02 to 1.04), respectively. Limitation: Results may not reflect current drug prices and do not account for point-of-sale discounts or price matching that may be offered by smaller pharmacies. Conclusion: Compared with large chains, independent pharmacies and small chains had the highest cash prices for generic drugs and big box pharmacies the lowest. Relative differences in cash prices for brand-name drugs were modest across types of retail pharmacies. Primary Funding Source: Arnold Ventures.

Clinical–Community Partnerships to Reduce Food Insecurity Among High-Need, High-Cost Medicaid Patients

Deriving Real-World Insights From Real-World Data: Biostatistics to the Rescue

Medicare Beneficiary Out-of-Pocket Costs for Generic Cardiovascular Medications Available Through $4 Generic Drug Discount Programs

How Would You Manage This Patient With Osteoporosis?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 168, No 11

Osteoporosis is a skeletal disorder characterized by reduced bone strength that increases the risk for fracture. Approximately 10 million men and women in the United States have osteoporosis, and more than 2 million osteoporosis-related fractures occur annually. In 2016, the American Association of Clinical Endocrinologists issued the “Clinical Practice Guideline for the Diagnosis and Treatment of Postmenopausal Osteoporosis,” and in 2017, the American College of Physicians issued the guideline “Treatment of Low Bone Density or Osteoporosis to Prevent Fracture in Men and Women.” Both guidelines agree that patients diagnosed with osteoporosis should be treated with an antiresorptive agent, such as alendronate, that has been shown to reduce hip and vertebral fractures. However, there is no consensus on how long patients with osteoporosis should be treated and whether bone density should be monitored during and after the treatment period. In this Beyond the Guidelines, 2 experts discuss management of osteoporosis in general and for a specific patient, the role of bone density monitoring during and after a 5-year course of alendronate, and treatment recommendations for a patient whose bone density decreases during or after a 5-year course of alendronate.

Guidelines Versus Guidelines: What's Best for the Patient?