Precision Medicine for Clinicians: The Future Begins Now

Mortality Risk in Older Adults: What the Nose Knows

Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis: Annals of Internal Medicine: Vol 171, No 9

Background: Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia. Purpose: To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia. Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews. Study Selection: Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia. Data Extraction: Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias. Data Synthesis: After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], −0.5 [95% credible interval {CrI}, −0.99 to −0.01]), massage and touch therapy (SMD, −0.75 [CrI, −1.12 to −0.38]), and music combined with massage and touch therapy (SMD, −0.91 [CrI, −1.75 to −0.07]) were clinically more efficacious than usual care. Recreation therapy (SMD, −0.29 [CrI, −0.57 to −0.01]) was statistically but not clinically more efficacious than usual care. Limitations: Forty-six percent of studies were at high risk of bias because of missing outcome data. Harms and costs of therapies were not evaluated. Conclusion: Nonpharmacologic interventions seemed to be more efficacious than pharmacologic interventions for reducing aggression and agitation in adults with dementia. Primary Funding Source: Alberta Health Services Critical Care Strategic Clinical Network. (PROSPERO: CRD42017050130)

Predicting 6-Month Mortality for Older Adults Hospitalized With Acute Myocardial Infarction: A Cohort Study: Annals of Internal Medicine: Vol 172, No 1

Background: Older adults with acute myocardial infarction (AMI) have higher prevalence of functional impairments, including deficits in cognition, strength, and sensory domains, than their younger counterparts. Objective: To develop and evaluate the prognostic utility of a risk model for 6-month post-AMI mortality in older adults that incorporates information about functional impairments. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01755052). Setting: 94 hospitals throughout the United States. Participants: 3006 persons aged 75 years or older who were hospitalized with AMI and discharged alive. Measurements: Functional impairments were assessed during hospitalization via direct measurement (cognition, mobility, muscle strength) or self-report (vision, hearing). Clinical variables associated with mortality in prior risk models were ascertained by chart review. Seventy-two candidate variables were selected for inclusion, and backward selection and Bayesian model averaging were used to derive (n = 2004 participants) and validate (n = 1002 participants) a model for 6-month mortality. Results: Participants' mean age was 81.5 years, 44.4% were women, and 10.5% were nonwhite. There were 266 deaths (8.8%) within 6 months. The final risk model included 15 variables, 4 of which were not included in prior risk models: hearing impairment, mobility impairment, weight loss, and lower patient-reported health status. The model was well calibrated (Hosmer–Lemeshow P > 0.05) and showed good discrimination (area under the curve for the validation cohort = 0.84). Adding functional impairments significantly improved model performance, as evidenced by category-free net reclassification improvement indices of 0.21 (P = 0.008) for hearing impairment and 0.26 (P < 0.001) for mobility impairment. Limitation: The model was not externally validated. Conclusion: A newly developed model for 6-month post-AMI mortality in older adults was well calibrated and had good discriminatory ability. This model may be useful in decision making at hospital discharge. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

To What Target Hemoglobin A1c Level Would You Treat This Patient With Type 2 Diabetes?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 171, No 7

In the United States, 9.4% of all adults—and 25% of those older than 65 years—have diabetes. Diabetes is the leading cause of blindness and end-stage renal disease and contributes to both microvascular and macrovascular complications. The management of patients with type 2 diabetes (T2D) is a common and important activity in primary care internal medicine practice. Measurement of hemoglobin A1c (HbA1c) provides an estimate of mean blood sugar levels and glycemic control. The optimal HbA1c target level among various persons with T2D is a subject of controversy. Guidelines regarding HbA1c targets have yielded differing recommendations. In 2018, the American College of Physicians (ACP) published a guideline on HbA1c targets for nonpregnant adults with T2D. In addition to a recommendation to individualize HbA1c target levels, the ACP proposed a level between 7% and 8% for most patients. The ACP also advised deintensification of therapy for patients who have an HbA1c level lower than 6.5% and avoidance of HbA1c-targeted treatment for patients with a life expectancy of less than 10 years. This guidance contrasts with a recommendation from the American Diabetes Association to aim for HbA1c levels less than 7% for many nonpregnant adults and to consider a target of 6.5% if it can be achieved safely. Here, 2 experts, a diabetologist and a general internist, discuss how to apply the divergent guideline recommendations to a patient with long-standing T2D and a current HbA1c level of 7.8%.

A Portrait of the Physician as a Young Man

The Accuracy of Google Translate for Abstracting Data From Non–English-Language Trials for Systematic Reviews

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians

Description: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations based on the current evidence of the benefits and harms of testosterone treatment in adult men with age-related low testosterone. This guideline is endorsed by the American Academy of Family Physicians. Methods: The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. Clinical outcomes were evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events. Target Audience and Patient Population: The target audience includes all clinicians, and the target patient population includes adult men with age-related low testosterone. Recommendation 1a: ACP suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function (conditional recommendation; low-certainty evidence). The discussion should include the potential benefits, harms, costs, and patient's preferences. Recommendation 1b: ACP suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter. Clinicians should discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function (conditional recommendation; low-certainty evidence). Recommendation 1c: ACP suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar. Recommendation 2: ACP suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition (conditional recommendation; low-certainty evidence).

Treatments for the Prevention and Management of Suicide: A Systematic Review: Annals of Internal Medicine: Vol 171, No 5

Background: Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016. Purpose: To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults. Data Sources: MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018. Study Selection: Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide. Data Extraction: One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. Data Synthesis: Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or crisis planning. The evidence for pharmacologic treatments suggests that ketamine reduces suicidal ideation with minimal adverse events compared with placebo or midazolam. Lithium reduces rates of suicide among patients with unipolar or bipolar mood disorders compared with placebo. However, no differences were observed between lithium and other medications in reducing suicide. Limitation: Qualitative synthesis of new evidence with existing meta-analyses, methodological shortcomings of studies, heterogeneity of nonpharmacologic interventions, and limited evidence for pharmacologic treatments and harms. Conclusion: Both CBT and DBT showed modest benefit in reducing suicidal ideation compared with TAU or wait-list control, and CBT also reduced suicide attempts compared with TAU. Ketamine and lithium reduced the rate of suicide compared with placebo, but there was limited information on harms. Limited data are available to support the efficacy of other nonpharmacologic or pharmacologic interventions. Primary Funding Source: U.S. Department of Veterans Affairs Veterans Health Administration. (PROSPERO: CRD42018104978)

Tools to Help Overcome Barriers to Cost-of-Care Conversations