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Background: Stroke rates in patients with nonvalvular atrial fibrillation (AF) who are not receiving anticoagulant therapy vary widely across published studies; the resulting effect on the net clinical benefit of anticoagulation in AF is unknown. Objective: To determine the effect of variation in published AF stroke rates on the net clinical benefit of anticoagulation. Design: Markov model decision analysis. Warfarin was the base case, and non–vitamin K antagonist oral anticoagulants (NOACs) were modeled in a secondary analysis. Setting: Community-dwelling adults. Patients: 33 434 adults with incident AF. Measurements: Quality-adjusted life-years (QALYs). Results: Of the 33 434 patients, 27 179 had a CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) score of 2 or more. The population benefit of warfarin anticoagulation for these patients was least using stroke rates from the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study and greatest using those from the Danish National Patient Registry (6290 QALYs [95% CI, ±2.3%] vs. 24 110 QALYs [CI, ±1.9%]; P < 0.001). The optimal CHA2DS2-VASc score threshold for anticoagulation was 3 or more using stroke rates from ATRIA, 2 or more using those from the Swedish AF cohort study, 1 or more using those from the SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) study, and 0 or more using those from the Danish National Patient Registry. Accounting for lower rates of NOAC-associated intracranial hemorrhage decreased optimal CHA2DS2-VASc score thresholds, but these thresholds still varied widely. Limitation: Measured benefit may not generalize to other populations. Conclusion: Variation in published AF stroke rates for patients not receiving anticoagulant therapy results in multifold variation in the net clinical benefit of anticoagulation. Guidelines should better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation. Primary Funding Source: None.

Pharmacy Benefit Managers, Brand-Name Drug Prices, and Patient Cost Sharing

Lost in Translation: Linking Biomedical Research and Clinical Practice at the National Institutes of Health, 1977 to 2013

This article examines the history and effect of the Consensus Development Program (CDP) at the National Institutes of Health (NIH). Introduced at a time when the relationship between the U.S. public and the medical profession was at a nadir, the CDP frequently placed the NIH in the middle of broader debates in medical practice and health policy during the last quarter of the 20th century. Drawing on published and archival sources, this paper sheds light on the challenges associated with collecting, assessing, and communicating evidence to medical professionals and convincing them to act on it in the name of improved health care. Administrators at the NIH sought a middle ground between changing medical practice and respecting professional autonomy, with varying degrees of success. This debate has continued implications today as tensions persist between scientific guidelines and the clinical medicine practiced by physicians and expected by patients.

Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case–Control Study: Annals of Internal Medicine: Vol 168, No 6

Background: Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown. Objective: To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD). Design: Nested case–control study. Setting: Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014). Patients: 1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence. Measurements: Opioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately. Results: Persons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately. Limitations: Unmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured. Conclusion: Opioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases. Primary Funding Source: National Institutes of Health.

Medicare Formulary Coverage Restrictions for Prescription Opioids, 2006 to 2015

Population Health Science and the Challenges of Prediction

Preventability of Early Versus Late Hospital Readmissions in a National Cohort of General Medicine Patients

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Many experts believe that hospitals with more frequent readmissions provide lower-quality care, but little is known about how the preventability of readmissions might change over the postdischarge time frame. Objective: To determine whether readmissions within 7 days of discharge differ from those between 8 and 30 days after discharge with respect to preventability. Design: Prospective cohort study. Setting: 10 academic medical centers in the United States. Patients: 822 adults readmitted to a general medicine service. Measurements: For each readmission, 2 site-specific physician adjudicators used a structured survey instrument to determine whether it was preventable and measured other characteristics. Results: Overall, 36.2% of early readmissions versus 23.0% of late readmissions were preventable (median risk difference, 13.0 percentage points [interquartile range, 5.5 to 26.4 percentage points]). Hospitals were identified as better locations for preventing early readmissions (47.2% vs. 25.5%; median risk difference, 22.8 percentage points [interquartile range, 17.9 to 31.8 percentage points]), whereas outpatient clinics (15.2% vs. 6.6%; median risk difference, 10.0 percentage points [interquartile range, 4.6 to 12.2 percentage points]) and home (19.4% vs. 14.0%; median risk difference, 5.6 percentage points [interquartile range, −6.1 to 17.1 percentage points]) were better for preventing late readmissions. Limitation: Physician adjudicators were not blinded to readmission timing, community hospitals were not included in the study, and readmissions to nonstudy hospitals were not included in the results. Conclusion: Early readmissions were more likely to be preventable and amenable to hospital-based interventions. Late readmissions were less likely to be preventable and were more amenable to ambulatory and home-based interventions. Primary Funding Source: Association of American Medical Colleges.

Annals for Hospitalists Inpatient Notes - The Opioid Epidemic—What's a Hospitalist to Do?

Reimagining Halfway Technologies With Behavioral Science

Mid- and Long-Term Outcome Comparisons of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 167, No 9

Background: Percutaneous coronary interventions to implant bioresorbable vascular scaffolds (BVSs) were designed to reduce the late thrombotic events that occur with metallic stents. Purpose: To estimate the incidence of scaffold thrombosis after BVS implantation and compare everolimus-eluting BVSs with everolimus-eluting metallic stents (EESs) in terms of safety and efficacy at mid- and long-term follow-up in adults who had a percutaneous coronary intervention. Data Sources: PubMed, EMBASE, the Cochrane Library, conference proceedings, and relevant Web sites from inception until 20 May 2017, without language restriction. Study Selection: 7 randomized trials and 38 observational studies (each with a minimum of 6 months and 100 patient-years of follow-up) in adults with coronary artery disease who had a BVS or an EES and reported scaffold or stent thrombosis (main outcome) or other secondary outcomes (such as death, myocardial infarction, or revascularization). Data Extraction: 2 reviewers independently extracted study data, rated study quality, and assessed strength of evidence. Data Synthesis: The pooled incidence of definite or probable scaffold thrombosis after BVS implantation was 1.8% (95% CI, 1.5% to 2.2%) at a median follow-up of 1 year (41 studies, 21 884 patients) and 0.8% (CI, 0.5% to 1.3%) beyond 1 year (14 studies, 4688 patients). Seven trials involving 5578 patients that directly compared BVSs with EESs showed an increased risk for definite or probable scaffold thrombosis (odds ratio [OR], 3.40 [CI, 2.01 to 5.76]) with BVSs at a median follow-up of 25 months. Increased risks were present at early (prominently subacute), late, and very late stages, and odds beyond 1 year were almost double those seen within 1 year. Bioresorbably vascular scaffolds increased risks for myocardial infarction (OR, 1.63 [CI, 1.26 to 2.10]), target lesion revascularization (OR, 1.31 [CI, 1.03 to 1.67]), and target lesion failure (OR, 1.37 [CI, 1.12 to 1.66]); the odds for these 3 end points also increased over time. The incidences of all-cause, cardiac, and noncardiac death and of target vessel and any revascularization did not differ. Limitation: Quality of observational studies was unclear, and some data were unpublished. Conclusion: Compared with EESs, BVSs increased the risks for scaffold thrombosis and other thrombotic events at mid- and long-term follow-up, and risks increased over time. Primary Funding Source: National Natural Science Foundation of China.

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