Prevalence of Aspirin Use for Primary Prevention of Cardiovascular Disease in the United States: Results From the 2017 National Health Interview Survey

Social Cognition and the Aging Brain

Annals for Hospitalists Inpatient Notes - Just What the Doctor Ordered—Checklists to Improve Diagnosis

Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 171, No 12

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485)

Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 172, No 2

Background: MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models. Objective: To evaluate the efficacy, safety, and tolerability of MIV-711 in participants with symptomatic, radiographic knee osteoarthritis. Design: 26-week randomized, double-blind, placebo-controlled phase 2a study with a 26-week open-label safety extension substudy. (EudraCT: 2015-003230-26 and 2016-001096-73) Setting: Six European sites. Participants: 244 participants with primary knee osteoarthritis, Kellgren–Lawrence grade 2 or 3, and pain score of 4 to 10 on a numerical rating scale (NRS). Intervention: MIV-711, 100 (n = 82) or 200 (n = 81) mg daily, or matched placebo (n = 77). Participants (46 who initially received 200 mg/d and 4 who received placebo) received 200 mg of MIV-711 daily during the extension substudy. Measurements: The primary outcome was change in NRS pain score. The key secondary outcome was change in bone area on magnetic resonance imaging (MRI). Other secondary end points included cartilage thickness on quantitative MRI and type I and II collagen C-telopeptide biomarkers. Outcomes were assessed over 26 weeks. Results: Changes in NRS pain scores with MIV-711 were not statistically significant (placebo, −1.4; MIV-711, 100 mg/d, −1.7; MIV-711, 200 mg/d, −1.5). MIV-711 significantly reduced medial femoral bone area progression (P = 0.002 for 100 mg/d and 0.004 for 200 mg/d) and medial femoral cartilage thinning (P = 0.023 for 100 mg/d and 0.125 for 200 mg/d) versus placebo and substantially reduced bone and cartilage biomarker levels. Nine serious adverse events occurred in 6 participants (1 in the placebo group, 3 in the 100 mg group, and 2 in the 200 mg group); none were considered to be treatment-related. Limitation: The trial was relatively short. Conclusion: MIV-711 was not more effective than placebo for pain, but it significantly reduced bone and cartilage progression with a reassuring safety profile. This treatment may merit further evaluation as a disease-modifying osteoarthritis drug. Primary Funding Source: Medivir.

Altered Risk for Cardiovascular Events With Changes in the Metabolic Syndrome Status: A Nationwide Population-Based Study of Approximately 10 Million Persons: Annals of Internal Medicine: Vol 171, No 12

Background: Population-scale evidence for the association between dynamic changes in metabolic syndrome (MetS) status and alterations in the risk for major adverse cardiovascular events (MACE) is lacking. Objective: To investigate whether recovery from or development of MetS in a population is associated with an altered risk for MACE. Design: Nationwide cohort study. Setting: An analysis based on the National Health Insurance Database of Korea. Participants: A total of 27 161 051 persons who received national health screenings from 2009 to 2014 were screened. Those with a history of MACE were excluded. We determined the MetS status of 9 553 042 persons using the following harmonizing criteria: MetS-chronic (n = 1 486 485), MetS-developed (n = 587 088), MetS-recovery (n = 538 806), and MetS-free (n = 6 940 663). Measurements: The outcome was the occurrence of MACE, including acute myocardial infarction, revascularization, and acute ischemic stroke, identified from the claims database. The incidence rate ratios (IRRs) were calculated with adjustments for body mass index, comorbidity scores, previous metabolic variables, and other clinical or demographic variables. Results: At a median follow-up of 3.54 years, the MetS-recovery group (incidence rate, 4.55 per 1000 person-years) had a significantly lower MACE risk (adjusted IRR, 0.85 [95% CI, 0.83 to 0.87]) than that of the MetS-chronic group (incidence rate, 8.52 per 1000 person-years). The MetS-developed group (incidence rate, 6.05 per 1000 person-years) had a significantly higher MACE risk (adjusted IRR, 1.36 [CI, 1.33 to 1.39]) than that of the MetS-free group (incidence rate, 1.92 per 1000 person-years). Among the MetS components, change in hypertension was associated with the largest difference in MACE risk. Limitation: Limited assessment of mortality and short follow-up. Conclusion: Recovery from MetS was significantly associated with decreased risk for MACE, whereas development of MetS was associated with increased risk. Primary Funding Source: Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea.

2018 Cholesterol Clinical Practice Guidelines: Synopsis of the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline*

Description: In November 2018, the American Heart Association and American College of Cardiology (AHA/ACC) released a new clinical practice guideline on cholesterol management. It was accompanied by a risk assessment report on primary prevention of atherosclerotic cardiovascular disease (ASCVD). Methods: A panel of experts free of recent and relevant industry-related conflicts was chosen to carry out systematic reviews and meta-analyses of randomized controlled trials (RCTs) that examined cardiovascular outcomes. High-quality observational studies were used for estimation of ASCVD risk. An independent panel systematically reviewed RCT evidence about the benefits and risks of adding nonstatin medications to statin therapy compared with receiving statin therapy alone in persons who have or are at high risk for ASCVD. Recommendation: The guideline endorses a heart-healthy lifestyle beginning in childhood to reduce lifetime risk for ASCVD. It contains several new features compared with the 2013 guideline. For secondary prevention, patients at very high risk may be candidates for adding nonstatin medications (ezetimibe or proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) to statin therapy. In primary prevention, a clinician–patient risk discussion is still strongly recommended before a decision is made about statin treatment. The AHA/ACC risk calculator first triages patients into 4 risk categories. Those at intermediate risk deserve a focused clinician–patient discussion before initiation of statin therapy. Among intermediate-risk patients, identification of risk-enhancing factors and coronary artery calcium testing can assist in the decision to use a statin. Compared with the 2013 guideline, the new guideline gives more attention to percentage reduction in low-density lipoprotein cholesterol as a treatment goal and to long-term monitoring of therapeutic efficacy. To simplify monitoring, nonfasting lipid measurements are allowed.

Cost-Effectiveness Analysis of Lung Cancer Screening in the United States: A Comparative Modeling Study: Annals of Internal Medicine: Vol 171, No 11

Background: Recommendations vary regarding the maximum age at which to stop lung cancer screening: 80 years according to the U.S. Preventive Services Task Force (USPSTF), 77 years according to the Centers for Medicare & Medicaid Services (CMS), and 74 years according to the National Lung Screening Trial (NLST). Objective: To compare the cost-effectiveness of different stopping ages for lung cancer screening. Design: By using shared inputs for smoking behavior, costs, and quality of life, 4 independently developed microsimulation models evaluated the health and cost outcomes of annual lung cancer screening with low-dose computed tomography (LDCT). Data Sources: The NLST; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SEER (Surveillance, Epidemiology, and End Results) program; Nurses' Health Study and Health Professionals Follow-up Study; and U.S. Smoking History Generator. Target Population: Current, former, and never-smokers aged 45 years from the 1960 U.S. birth cohort. Time Horizon: 45 years. Perspective: Health care sector. Intervention: Annual LDCT according to NLST, CMS, and USPSTF criteria. Outcome Measures: Incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results of Base-Case Analysis: The 4 models showed that the NLST, CMS, and USPSTF screening strategies were cost-effective, with ICERs averaging $49 200, $68 600, and $96 700 per QALY, respectively. Increasing the age at which to stop screening resulted in a greater reduction in mortality but also led to higher costs and overdiagnosis rates. Results of Sensitivity Analysis: Probabilistic sensitivity analysis showed that the NLST and CMS strategies had higher probabilities of being cost-effective (98% and 77%, respectively) than the USPSTF strategy (52%). Limitation: Scenarios assumed 100% screening adherence, and models extrapolated beyond clinical trial data. Conclusion: All 3 sets of lung cancer screening criteria represent cost-effective programs. Despite underlying uncertainty, the NLST and CMS screening strategies have high probabilities of being cost-effective. Primary Funding Source: CISNET (Cancer Intervention and Surveillance Modeling Network) Lung Group, National Cancer Institute.

The Limitations of Poor Broadband Internet Access for Telemedicine Use in Rural America: An Observational Study

Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy: A Randomized Trial: Annals of Internal Medicine: Vol 171, No 6

Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Design: Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611) Setting: 40 U.S. clinical centers. Participants: 9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. Intervention: Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years. Measurements: Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a “global index” (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up. Results: The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age. Limitations: The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing. Conclusion: The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term. Primary Funding Source: The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs.