Benefits and Harms of Osteoporosis Medications in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 166, No 9

Background: Complications of chronic kidney disease (CKD) include weak bones and increased fracture risk. Purpose: To review the benefits and harms of osteoporosis medications (bisphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active control in terms of bone mineral density (BMD), fractures, and safety in patients with CKD. Data Sources: PubMed and the Cochrane Central Register of Controlled Trials from December 2006 through December 2016. Study Selection: Paired reviewers independently screened abstracts and full-text articles for English-language, randomized, controlled trials that had at least 6 months of follow-up; evaluated osteoporosis medications among patients with CKD; and reported on BMD, fractures, or safety (mortality and adverse events). Data Extraction: Two reviewers serially abstracted data and independently assessed risk of bias and graded the strength of evidence (SOE). Data Synthesis: There were 13 trials (n = 9850) that included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials). Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients (moderate SOE), but their effects on fractures and safety in transplant recipients and others with CKD are unclear. Raloxifene may prevent vertebral fractures but may not improve BMD (low SOE). Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE), and these medications may increase risk for some safety outcomes. Limitation: Unclear rigor of evidence, possible reporting biases, and scant evidence among patients with stage 3 to 5 CKD. Conclusion: Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established. Primary Funding Source: Kidney Disease: Improving Global Outcomes.

Increasing Incidence of Multiply Recurrent Clostridium difficile Infection in the United States: A Cohort Study: Annals of Internal Medicine: Vol 167, No 3

Background: Clostridium difficile infection (CDI), the most common health care–associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI). Objective: To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI. Design: Retrospective cohort study. Setting: United States. Participants: 38 911 718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45 341 developed CDI. Measurements: Age- and sex-standardized incidence rates for CDI and mrCDI. Results: From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI. Limitation: The primary analyses included only commercially insured patients in the United States. Conclusion: Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases.

Metformin Use in Patients With Historical Contraindications

Safety-Net Hospitals, Neighborhood Disadvantage, and Readmissions Under Maryland's All-Payer Program: An Observational Study: Annals of Internal Medicine: Vol 171, No 2

Background: Safety-net hospitals have higher-than-expected readmission rates. The relative roles of the mean disadvantage of neighborhoods the hospitals serve and the disadvantage of individual patients in predicting a patient's readmission are unclear. Objective: To examine the independent contributions of the patient's neighborhood and the hospital's service area to risk for 30-day readmission. Design: Retrospective observational study. Setting: Maryland. Participants: All Maryland residents discharged from a Maryland hospital in 2015. Measurements: Predictors included the disadvantage of neighborhoods for each Maryland resident (area disadvantage index) and the mean disadvantage of each hospital's discharged patients (safety-net index). The primary outcome was unplanned 30-day hospital readmission. Generalized estimating equations and marginal modeling were used to estimate readmission rates. Results were adjusted for clinical readmission risk. Results: 13.4% of discharged patients were readmitted within 30 days. Patients living in neighborhoods at the 90th percentile of disadvantage had a readmission rate of 14.1% (95% CI, 13.6% to 14.5%) compared with 12.5% (CI, 11.8% to 13.2%) for similar patients living in neighborhoods at the 10th percentile. Patients discharged from hospitals at the 90th percentile of safety-net status had a readmission rate of 14.8% (CI, 13.4% to 16.1%) compared with 11.6% (CI, 10.5% to 12.7%) for similar patients discharged from hospitals at the 10th percentile of safety-net status. The association of readmission risk with the hospital's safety-net index was approximately twice the observed association with the patient's neighborhood disadvantage status. Limitations: Generalizability outside Maryland is unknown. Confounding may be present. Conclusion: In Maryland, residing in a disadvantaged neighborhood and being discharged from a hospital serving a large proportion of disadvantaged neighborhoods are independently associated with increased risk for readmission. Primary Funding Source: National Institute on Minority Health and Health Disparities and Maryland Health Services Cost Review Commission.

Can Primary Care Practices Help Address the Health Crisis Fueled by Prescription Opioids?

Developing Recommendations for Evidence-Based Clinical Preventive Services for Diverse Populations: Methods of the U.S. Preventive Services Task Force

The U.S. Preventive Services Task Force (USPSTF) summarizes the principles and considerations that guide development of its recommendations for diverse U.S. populations. It uses these principles through each step in the evidence-based guideline process: developing the research plan, conducting the evidence review, developing the recommendation, and communicating to guideline users. Three recent recommendations provide examples of how the USPSTF has used these principles: the 2015 recommendation on screening for abnormal blood glucose and type 2 diabetes; the 2016 recommendation on screening for breast cancer; and the recommendation on screening for prostate cancer, which is currently in progress. A more comprehensive list of recommendations that includes considerations for specific populations is also provided.

Associations Between American Board of Internal Medicine Maintenance of Certification Status and Performance on a Set of Healthcare Effectiveness Data and Information Set (HEDIS) Process Measures

Background: The value of the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program has been questioned as a marker of physician quality. Objective: To assess whether physician MOC status is associated with performance on selected Healthcare Effectiveness Data and Information Set (HEDIS) process measures. Design: Annual comparisons of HEDIS process measures among physicians who did or did not maintain certification 20 years after initial certification. Setting: Fee-for-service Medicare. Participants: 1260 general internists who were initially certified in 1991 and provided care for 85 931 Medicare patients between 2009 and 2012. Measurements: Annual percentage of a physician's Medicare patients meeting each of 5 HEDIS annual or biennial standards and a composite indicating meeting all 3 HEDIS diabetes standards. Results: Among the 1260 physicians, 786 maintained their certification from 1991 to 2012 and 474 did not. The mean annual percentage of HEDIS-eligible diabetic patients who completed semiannual hemoglobin A1c testing was 58.4% among physicians who maintained certification and 54.4% among those who did not (regression-adjusted difference, 4.2 percentage points [95% CI, 2.0 to 6.5 percentage points]; P < 0.001). Diabetic patients of physicians who maintained certification more frequently met the annual standard for low-density lipoprotein (LDL) cholesterol measurement (83.1% vs. 80.5%; regression-adjusted difference, 2.3 percentage points [CI, 0.6 to 4.1 percentage points]; P = 0.008) and all 3 diabetic standards (46.0% vs. 41.6%; regression-adjusted difference, 3.1 percentage points [CI, 0.5 to 5.7 percentage points]; P = 0.019). The regression-adjusted difference in biennial eye examinations was statistically insignificant (P = 0.112). Measures for LDL cholesterol testing in patients with coronary heart disease and biennial mammography were also met more frequently among physicians who maintained certification (79.4% vs. 77.4% and 72.0% vs. 67.8%, respectively), with regression-adjusted differences of 1.7 percentage points (CI, 0.2 to 3.3 percentage points; P = 0.032) and 4.6 percentage points (CI, 2.9 to 6.3 percentage points; P < 0.001), respectively. Limitation: Potential confounding by unobserved patient, physician, and practice characteristics; inability to determine clinical significance of observed differences. Conclusion: Maintaining certification was positively associated with physician performance scores on a set of HEDIS process measures. Primary Funding Source: American Board of Internal Medicine.

Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 167, No 5

Background: Bone health is a significant concern in men with prostate cancer. Purpose: To evaluate the effectiveness of drug, supplement, and lifestyle interventions aimed at preventing fracture, improving bone mineral density (BMD), or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer. Data Sources: Ovid MEDLINE (1946 to 19 January 2017), EMBASE (1980 to 18 January 2017), and the Cochrane Database of Systematic Reviews (19 January 2017). Study Selection: Randomized trials and systematic reviews of trials that were published in English; involved men with nonmetastatic prostate cancer; and compared bone-targeted therapies with placebo, usual care, or other active treatments. Data Extraction: Two reviewers independently extracted study characteristics and assessed study risk of bias for each outcome. Data Synthesis: Two systematic reviews and 28 reports of 27 trials met inclusion criteria. All trials focused on men with nonmetastatic prostate cancer who were initiating or continuing androgen deprivation therapy (ADT). Bisphosphonates were effective in increasing BMD, but no trial was sufficiently powered to detect reduction in fractures. Denosumab improved BMD and reduced the incidence of new radiographic vertebral fractures in 1 high-quality trial. No trials compared calcium or vitamin D versus placebo. Three lifestyle intervention trials did not show a statistically significant difference in change in BMD between exercise and usual care. Limitations: Most trials were of moderate quality. Only 2 randomized controlled trials were designed to examine fracture outcomes. Potential harms of treatments were not evaluated. Conclusion: Both bisphosphonates and denosumab improve BMD in men with nonmetastatic prostate cancer who are receiving ADT. Denosumab also reduces risk for radiographic vertebral fractures, based on 1 trial. More trials studying fracture outcomes are needed in this population. Primary Funding Source: Program in Evidence-Based Care.

Accuracy of Cardiovascular Risk Prediction Varies by Neighborhood Socioeconomic Position: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 167, No 7

Background: Inequality in health outcomes in relation to Americans' socioeconomic position is rising. Objective: First, to evaluate the spatial relationship between neighborhood disadvantage and major atherosclerotic cardiovascular disease (ASCVD)–related events; second, to evaluate the relative extent to which neighborhood disadvantage and physiologic risk account for neighborhood-level variation in ASCVD event rates. Design: Observational cohort analysis of geocoded longitudinal electronic health records. Setting: A single academic health center and surrounding neighborhoods in northeastern Ohio. Patients: 109 793 patients from the Cleveland Clinic Health System (CCHS) who had an outpatient lipid panel drawn between 2007 and 2010. The date of the first qualifying lipid panel served as the study baseline. Measurements: Time from baseline to the first occurrence of a major ASCVD event (myocardial infarction, stroke, or cardiovascular death) within 5 years, modeled as a function of a locally derived neighborhood disadvantage index (NDI) and the predicted 5-year ASCVD event rate from the Pooled Cohort Equations Risk Model (PCERM) of the American College of Cardiology and American Heart Association. Outcome data were censored if no CCHS encounters occurred for 2 consecutive years or when state death data were no longer available (that is, from 2014 onward). Results: The PCERM systematically underpredicted ASCVD event risk among patients from disadvantaged communities. Model discrimination was poorer among these patients (concordance index [C], 0.70 [95% CI, 0.67 to 0.74]) than those from the most affluent communities (C, 0.80 [CI, 0.78 to 0.81]). The NDI alone accounted for 32.0% of census tract–level variation in ASCVD event rates, compared with 10.0% accounted for by the PCERM. Limitations: Patients from affluent communities were overrepresented. Outcomes of patients who received treatment for cardiovascular disease at Cleveland Clinic were assumed to be independent of whether the patients came from a disadvantaged or an affluent neighborhood. Conclusion: Neighborhood disadvantage may be a powerful regulator of ASCVD event risk. In addition to supplemental risk models and clinical screening criteria, population-based solutions are needed to ameliorate the deleterious effects of neighborhood disadvantage on health outcomes. Primary Funding Source: The Clinical and Translational Science Collaborative of Cleveland and National Institutes of Health.

Having Cancer and Seeking the Point