Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies

Background: The relationship between body mass index (BMI) and mortality is controversial. Objective: To investigate the relationship between maximum BMI over 16 years and subsequent mortality. Design: 3 prospective cohort studies. Setting: Nurses' Health Study I and II and Health Professionals Follow-Up Study. Participants: 225 072 men and women with 32 571 deaths observed over a mean of 12.3 years of follow-up. Measurements: Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality. Results: Maximum BMIs in the overweight (25.0 to 29.9 kg/m2) (multivariate hazard ratio [HR], 1.06 [95% CI, 1.03 to 1.08]), obese I (30.0 to 34.9 kg/m2) (HR, 1.24 [CI, 1.20 to 1.29]), and obese II (≥35.0 kg/m2) (HR, 1.73 [CI, 1.66 to 1.80]) categories were associated with increases in risk for all-cause death. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those younger than 70 years and never-smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96 [CI, 0.94 to 0.99]) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including death from cardiovascular disease and coronary heart disease. Limitation: Residual confounding and misclassification. Conclusion: The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment. Primary Funding Source: National Institutes of Health.

Copay Assistance for Expensive Drugs: A Helping Hand That Raises Costs

Patient, Provider, and Combined Interventions for Managing Osteoarthritis in Primary Care: A Cluster Randomized Trial: Annals of Internal Medicine: Vol 166, No 6

Background: A single-site study showed that a combined patient and provider intervention improved outcomes for patients with knee osteoarthritis, but it did not assess separate effects of the interventions. Objective: To examine whether patient-based, provider-based, and patient–provider interventions improve osteoarthritis outcomes. Design: Cluster randomized trial with assignment to patient, provider, and patient–provider interventions or usual care. (ClinicalTrials.gov: NCT01435109) Setting: 10 Duke University Health System community-based primary care clinics. Participants: 537 outpatients with symptomatic hip or knee osteoarthritis. Intervention: The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved electronic delivery of patient-specific osteoarthritis treatment recommendations to providers. Measurements: The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months. Secondary outcomes were objective physical function (Short Physical Performance Battery) and depressive symptoms (Patient Health Questionnaire). Linear mixed models assessed the difference in improvement among groups. Results: No difference was observed in WOMAC score changes from baseline to 12 months in the patient (−1.5 [95% CI, −5.1 to 2.0]; P = 0.40), provider (2.5 [CI, −0.9 to 5.9]; P = 0.152), or patient–provider (−0.7 [CI, −4.2 to 2.8]; P = 0.69) intervention groups compared with usual care. All groups had improvements in WOMAC scores at 12 months (range, −3.7 to −7.7). In addition, no differences were seen in objective physical function or depressive symptoms at 12 months in any of the intervention groups compared with usual care. Limitations: The study involved 1 health care network. Data on provider referrals were not collected. Conclusion: Contrary to a previous study of a combined patient and provider intervention for osteoarthritis in a Department of Veterans Affairs medical center, this study found no statistically significant improvements in the osteoarthritis intervention groups compared with usual care. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 167, No 12

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited. Objective: To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice. Design: Retrospective cohort. Setting: National U.S. Food and Drug Administration Sentinel network. Patients: Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014. Measurements: Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score–matched patients starting treatment with dabigatran or warfarin. Results: Among 25 289 patients starting dabigatran therapy and 25 289 propensity score–matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran. Limitation: Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values). Conclusion: In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation. Primary Funding Source: U.S. Food and Drug Administration.

Cardiovascular Risk Assessment: A Systematic Review of Guidelines: Annals of Internal Medicine: Vol 165, No 10

Background: Many guidelines exist for screening and risk assessment for the primary prevention of cardiovascular disease in apparently healthy persons. Purpose: To systematically review current primary prevention guidelines on adult cardiovascular risk assessment and highlight the similarities and differences to aid clinician decision making. Data Sources: Publications in MEDLINE and CINAHL between 3 May 2009 and 30 June 2016 were identified. On 30 June 2016, the Guidelines International Network International Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and Web sites of organizations responsible for guideline development were searched. Study Selection: 2 reviewers screened titles and abstracts to identify guidelines from Western countries containing recommendations for cardiovascular risk assessment for healthy adults. Data Extraction: 2 reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines for Research and Evaluation II instrument, and 1 extracted the recommendations. Data Synthesis: Of the 21 guidelines, 17 showed considerable rigor of development. These recommendations address assessment of total cardiovascular risk (5 guidelines), dysglycemia (7 guidelines), dyslipidemia (2 guidelines), and hypertension (3 guidelines). All but 1 recommendation advocates for screening, and most include prediction models integrating several relatively simple risk factors for either deciding on further screening or guiding subsequent management. No consensus on the strategy for screening, recommended target population, screening tests, or treatment thresholds exists. Limitation: Only guidelines developed by Western national or international medical organizations were included. Conclusion: Considerable discrepancies in cardiovascular screening guidelines still exist, with no consensus on optimum screening strategies or treatment threshold. Primary Funding Source: Barts Charity.

Screening for Dyslipidemia in Younger Adults: A Systematic Review for the U.S. Preventive Services Task Force

Background: Dyslipidemia may occur in younger adults (defined as persons aged 21 to 39 years) and is an important risk factor for cardiovascular disease. Screening might identify younger adults with asymptomatic dyslipidemia who may benefit from lipid-lowering therapies. Purpose: To update the 2008 U.S. Preventive Services Task Force review on dyslipidemia screening in younger adults. Data Sources: The Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE through May 2016, and reference lists. Study Selection: Randomized, controlled trials; cohort studies; and case–control studies on screening for or treatment of asymptomatic dyslipidemia in adults aged 21 to 39 years. Data Extraction: The plan was for 1 investigator to abstract data and a second to check their accuracy, and for 2 investigators to independently assess study quality; however, no studies met the inclusion criteria. Data Synthesis: No study evaluated the effects of lipid screening versus no screening, treatment versus no treatment, or delayed versus earlier treatment on clinical outcomes in younger adults. In addition, no study evaluated the diagnostic yield of alternative screening strategies (such as targeted screening of persons with a family history of hyperlipidemia vs. general screening) in younger adults. Limitation: No direct relevant evidence. Conclusion: Direct evidence on the benefits and harms of screening for or treatment of dyslipidemia in younger adults remains unavailable. Estimating the potential effects of screening for dyslipidemia in this population requires extrapolation from studies performed in older adults. Primary Funding Source: Agency for Healthcare Research and Quality.

Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study: Annals of Internal Medicine: Vol 167, No 4

Background: Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. Objective: To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Design: Retrospective cohort study. Setting: Primary care practices affiliated with 2 academic medical centers. Participants: Patients with a presumed adverse reaction to a statin between 2000 and 2011. Measurements: Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Results: Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. Limitations: The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Conclusion: Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Primary Funding Source: Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital.

The Anticipated Clinical and Economic Effects of 90–90–90 in South Africa

Background: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 global treatment target aims to achieve 73% virologic suppression among HIV-infected persons worldwide by 2020. Objective: To estimate the clinical and economic value of reaching this ambitious goal in South Africa, by using a microsimulation model of HIV detection, disease, and treatment. Design: Modeling of the “current pace” strategy, which simulates existing scale-up efforts and gradual increases in overall virologic suppression from 24% to 36% in 5 years, and the UNAIDS target strategy, which simulates 73% virologic suppression in 5 years. Data Sources: Published estimates and South African survey data on HIV transmission rates (0.16 to 9.03 per 100 person-years), HIV-specific age-stratified fertility rates (1.0 to 9.1 per 100 person-years), and costs of care ($11 to $31 per month for antiretroviral therapy and $20 to $157 per month for routine care). Target Population: South African HIV-infected population, including incident infections over the next 10 years. Perspective: Modified societal perspective, excluding time and productivity costs. Time Horizon: 5 and 10 years. Intervention: Aggressive HIV case detection, efficient linkage to care, rapid treatment scale-up, and adherence and retention interventions toward the UNAIDS target strategy. Outcome Measures: HIV transmissions, deaths, years of life saved, maternal orphans, costs (2014 U.S. dollars), and cost-effectiveness. Results of Base-Case Analysis: Compared with the current pace strategy, over 5 years the UNAIDS target strategy would avert 873 000 HIV transmissions, 1 174 000 deaths, and 726 000 maternal orphans while saving 3 002 000 life-years; over 10 years, it would avert 2 051 000 HIV transmissions, 2 478 000 deaths, and 1 689 000 maternal orphans while saving 13 340 000 life-years. The additional budget required for the UNAIDS target strategy would be $7.965 billion over 5 years and $15.979 billion over 10 years, yielding an incremental cost-effectiveness ratio of $2720 and $1260 per year of life saved, respectively. Results of Sensitivity Analysis: Outcomes generally varied less than 20% from base-case outcomes when key input parameters were varied within plausible ranges. Limitation: Several pathways may lead to 73% overall virologic suppression; these were examined in sensitivity analyses. Conclusion: Reaching the 90–90–90 HIV suppression target would be costly but very effective and cost-effective in South Africa. Global health policymakers should mobilize the political and economic support to realize this target. Primary Funding Source: National Institutes of Health and the Steve and Deborah Gorlin MGH Research Scholars Award.

Effectiveness of Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries Aged 70 to 79 Years: A Prospective Observational Study: Annals of Internal Medicine: Vol 166, No 1

Background: No randomized, controlled trials of screening colonoscopy have been completed, and ongoing trials exclude persons aged 75 years or older. The Medicare program, however, reimburses screening colonoscopy without an upper age limit. Objective: To evaluate the effectiveness and safety of screening colonoscopy to prevent colorectal cancer (CRC) in persons aged 70 to 74 and those aged 75 to 79 years. Design: Large-scale, population-based, prospective study. The observational data were used to emulate a target trial with 2 groups: colonoscopy screening and no screening. Setting: United States. Participants: 1 355 692 Medicare beneficiaries (2004 to 2012) aged 70 to 79 years at average risk for CRC who used Medicare preventive services and had no previous diagnostic or surveillance colonoscopies in the past 5 years. Measurements: 8-year risk for CRC and 30-day risk for adverse events. Results: In beneficiaries aged 70 to 74 years, the 8-year risk for CRC was 2.19% (95% CI, 2.00% to 2.37%) in the screening colonoscopy group and 2.62% (CI, 2.56% to 2.67%) in the no-screening group (absolute risk difference, −0.42% [CI, −0.24% to −0.63%]). Among those aged 75 to 79 years, the 8-year risk for CRC was 2.84% (CI, 2.54% to 3.13%) in the screening colonoscopy group and 2.97% (CI, 2.92% to 3.03%) in the no-screening group (risk difference, −0.14% [CI, −0.41 to 0.16]). The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1000 individuals (CI, 4.4 to 6.8) in the 70- to 74-year age group and 10.3 per 1000 (CI, 8.6 to 11.1) in the 75- to 79-year age group. Limitation: CRC-specific mortality was not available, but CRC incidence and stage were studied at diagnosis. Conclusion: Screening colonoscopy may have had a modest benefit in preventing CRC in beneficiaries aged 70 to 74 years and a smaller benefit in older beneficiaries. The risk for adverse events was low but greater among older persons. Primary Funding Source: National Institutes of Health.

The Effectiveness of Total Worker Health Interventions: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Background: The Total Worker Health (TWH) program of the National Institute for Occupational Safety and Health aims to advance worker well-being by integrating injury and illness prevention efforts with work-related safety and health hazard efforts. Purpose: To evaluate evidence on the benefits and harms of integrated TWH interventions. Data Sources: MEDLINE, Cochrane Library, and PsycINFO (January 1990 through September 2015); clinical trial registries; and reference lists. Study Selection: English-language studies that enrolled employed adults and compared integrated interventions with usual work practice, no intervention, or another intervention. Data Extraction: Dual abstraction and risk-of-bias (ROB) assessment. Data Synthesis: Ten of the 15 included studies had high ROB, primarily because of selection and attrition bias. Findings graded as having low strength of evidence (SOE) supported the effectiveness of TWH interventions for improving smoking cessation, as measured by self-reported 7-day abstinence over 22 to 26 weeks (2 randomized, controlled trials [RCTs]; n = 737), and increasing consumption of fruits and vegetables over 26 to 104 weeks (3 RCTs; n = 6056); results apply to populations of blue-collar manufacturing and construction workers. Findings graded as having low SOE supported the effectiveness of TWH interventions for reducing sedentary work behavior in office workers over 16 to 52 weeks (2 RCTs; n = 262). Evidence was insufficient or lacking for other outcomes of interest, such as rates of work injuries, quality of life, and harms. Limitation: Small, diverse body of evidence with many methodological limitations; possible publication bias. Conclusion: Integrated TWH interventions might improve health behaviors (for example, reduce tobacco use and sedentary behavior and improve diet) of workers, but effects of these interventions on injuries and overall quality of life are not known. Primary Funding Source: Agency for Healthcare Research and Quality.