Should We Screen for Vitamin D Deficiency?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 165, No 11

The U.S. Preventive Services Task Force (USPSTF) recently issued guidelines on screening for vitamin D deficiency. The guidelines were based on randomized trials of vitamin D deficiency screening and treatment, as well as on case–control studies nested within the Women's Health Initiative. The USPSTF concluded that current evidence is insufficient to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults. Compared with placebo or no treatment, vitamin D was associated with decreased mortality; however, benefits were no longer seen after trials of institutionalized persons were excluded. Vitamin D treatment was associated with a possible decreased risk for at least 1 fall and the total number of falls per person but not for fractures. None of the studies examined the effects of vitamin D screening versus not screening on clinical outcomes. In this Grand Rounds, 2 prominent endocrinologists debate the issue of screening for vitamin D deficiency in a 55-year-old, asymptomatic, postmenopausal woman. They review the data on which the USPSTF recommendations are based and discuss the potential benefits and risks, as well as the challenges and controversies, of screening for vitamin D deficiency in primary care practice.

Development of the SaFETy Score: A Clinical Screening Tool for Predicting Future Firearm Violence Risk

Background: Interpersonal firearm violence among youth is a substantial public health problem, and emergency department (ED) physicians require a clinical screening tool to identify high-risk youth. Objective: To derive a clinically feasible risk index for firearm violence. Design: 24-month prospective cohort study. Setting: Urban, level 1 ED. Participants: Substance-using youths, aged 14 to 24 years, seeking ED care for an assault-related injury and a proportionately sampled group of non–assault-injured youth enrolled from September 2009 through December 2011. Measurements: Firearm violence (victimization/perpetration) and validated questionnaire items. Results: A total of 599 youths were enrolled, and presence/absence of future firearm violence during follow-up could be ascertained in 483 (52.2% were positive). The sample was randomly split into training (75%) and post–score-construction validation (25%) sets. Using elastic-net penalized logistic regression, 118 baseline predictors were jointly analyzed; the most predictive variables fell predominantly into 4 domains: violence victimization, community exposure, peer influences, and fighting. By selection of 1 item from each domain, the 10-point SaFETy (Serious fighting, Friend weapon carrying, community Environment, and firearm Threats) score was derived. SaFETy was associated with firearm violence in the validation set (odds ratio [OR], 1.47 [95% CI, 1.23 to 1.79]); this association remained (OR, 1.44 [CI, 1.20 to 1.76]) after adjustment for reason for ED visit. In 5 risk strata observed in the training data, firearm violence rates in the validation set were 18.2% (2 of 11), 40.0% (18 of 45), 55.8% (24 of 43), 81.3% (13 of 16), and 100.0% (6 of 6), respectively. Limitations: The study was conducted in a single ED and involved substance-using youths. SaFETy was not externally validated. Conclusion: The SaFETy score is a 4-item score based on clinically feasible questionnaire items and is associated with firearm violence. Although broader validation is required, SaFETy shows potential to guide resource allocation for prevention of firearm violence. Primary Funding Source: National Institute on Drug Abuse R01024646.

Cardiometabolic Abnormalities Among Normal-Weight Persons From Five Racial/Ethnic Groups in the United States: A Cross-sectional Analysis of Two Cohort Studies: Annals of Internal Medicine: Vol 166, No 9

Background: The relationship between body weight and cardiometabolic disease may vary substantially by race/ethnicity. Objective: To determine the prevalence and correlates of the phenotype of metabolic abnormality but normal weight (MAN) for 5 racial/ethnic groups. Design: Cross-sectional analysis. Setting: 2 community-based cohorts. Participants: 2622 white, 803 Chinese American, 1893 African American, and 1496 Hispanic persons from MESA (Multi-Ethnic Study of Atherosclerosis) and 803 South Asian participants in the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study. Measurements: Prevalence of 2 or more cardiometabolic abnormalities (high fasting glucose, low high-density lipoprotein cholesterol, and high triglyceride levels and hypertension) among normal-weight participants was estimated. Correlates of MAN were assessed by using log-binomial models. Results: Among normal-weight participants (n = 846 whites, 323 Chinese Americans, 334 African Americans, 252 Hispanics, and 195 South Asians), the prevalence of MAN was 21.0% (95% CI, 18.4% to 23.9%) in whites, 32.2% (CI, 27.3% to 37.4%) in Chinese Americans, 31.1% (CI, 26.3% to 36.3%) in African Americans, 38.5% (CI, 32.6% to 44.6%) in Hispanics, and 43.6% (CI, 36.8% to 50.6%) in South Asians. Adjustment for demographic, behavioral, and ectopic body fat measures did not explain racial/ethnic differences. After adjustment for age, sex, and race/ethnicity–body mass index (BMI) interaction, for the equivalent MAN prevalence at a BMI of 25.0 kg/m2 in whites, the corresponding BMI values were 22.9 kg/m2 (CI, 19.5 to 26.3 kg/m2) in African Americans, 21.5 kg/m2 (CI, 18.5 to 24.5 kg/m2) in Hispanics, 20.9 kg/m2 (CI, 19.7 to 22.1 kg/m2) in Chinese Americans, and 19.6 kg/m2 (CI, 17.2 to 22.0 kg/m2) in South Asians. Limitation: Cross-sectional study design and lack of harmonized dietary data between studies. Conclusion: Compared with whites, all racial/ethnic minority groups had a statistically significantly higher prevalence of MAN, which was not explained by demographic, behavioral, or ectopic fat measures. Using a BMI criterion for overweight to screen for cardiometabolic risk may result in a large proportion of racial/ethnic minority groups being overlooked. Primary Funding Source: National Institutes of Health.

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.

Pioglitazone: An Addition to Our Toolbox for Patients With Diabetes and Nonalcoholic Steatohepatitis?

Physician Decision Making and Clinical Outcomes With Laboratory Polysomnography or Limited-Channel Sleep Studies for Obstructive Sleep Apnea: A Randomized Trial: Annals of Internal Medicine: Vol 166, No 5

Background: The clinical utility of limited-channel sleep studies (which are increasingly conducted at home) versus laboratory polysomnography (PSG) for diagnosing obstructive sleep apnea (OSA) is unclear. Objective: To compare patient outcomes after PSG versus limited-channel studies. Design: Multicenter, randomized, noninferiority study. (Australian New Zealand Clinical Trials Registry: ACTRN12611000926932) Setting: 7 academic sleep centers. Participants: Patients (n = 406) aged 25 to 80 years with suspected OSA. Intervention: Sleep study information disclosed to sleep physicians comprised level 1 (L1) PSG data (n = 135); level 3 (L3), which included airflow, thoracoabdominal bands, body position, electrocardiography, and oxygen saturation (n = 136); or level 4 (L4), which included oxygen saturation and heart rate (n = 135). Measurements: The primary outcome was change in Functional Outcomes of Sleep Questionnaire (FOSQ) score at 4 months. Secondary outcomes included the Epworth Sleepiness Scale (ESS), the Sleep Apnea Symptoms Questionnaire (SASQ), continuous positive airway pressure (CPAP) compliance, and physician decision making. Results: Change in FOSQ score was not inferior for L3 (mean difference [MD], 0.01 [95% CI, −0.47 to 0.49; P = 0.96]) or L4 (MD, −0.46 [CI, −0.94 to 0.02; P = 0.058]) versus L1 (noninferiority margin [NIM], −1.0). Compared with L1, change in ESS score was not inferior for L3 (MD, 0.08 [CI, −0.98 to 1.13; P = 0.89]) but was inconclusive for L4 (MD, 1.30 [CI, 0.26 to 2.35; P = 0.015]) (NIM, 2.0). For L4 versus L1, there was less improvement in SASQ score (−17.8 vs. −24.7; P = 0.018), less CPAP use (4.5 vs. 5.3 hours per night; P = 0.04), and lower physician diagnostic confidence (P = 0.003). Limitation: Limited-channel studies were simulated by extracting laboratory PSG data and were not done in the home. Conclusion: The results support manually scored L3 testing in routine practice. Poorer outcomes with L4 testing may relate, in part, to reduced physician confidence. Primary Funding Source: National Health and Medical Research Council and Repat Foundation.

Chlorthalidone Versus Hydrochlorothiazide: A New Kind of Veterans Affairs Cooperative Study

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.

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.

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.