Molecular Imaging Versus Adrenal Vein Sampling for the Detection of Surgically Curable Primary Aldosteronism: A Prospective Within-Patient Trial: Annals of Internal Medicine: Vol 178, No 3

Background: Primary aldosteronism (PA) causes hypertension and is potentially surgically curable when it is caused by a unilateral aldosterone-producing adrenal adenoma (APA). Adrenal vein sampling (AVS) is required to guide surgery, but it is invasive, is technically difficult, and has limited availability. Objective: To determine whether the accuracy of post-dexamethasone [11C]metomidate ([11C]MTO) positron emission tomography–computed tomography, a diagnostic test for APAs, is superior or noninferior to the accuracy of AVS in predicting outcomes from unilateral adrenalectomy, and whether [11C]MTO is interchangeable with its longer-half-life analogue, para-chloro-2-[18F]fluoroethyletomidate ([18F]CETO). Design: Prospective within-patient comparison of diagnostic interventions. (ClinicalTrials.gov: NCT02945904) Setting: Three referral centers. Participants: 174 patients with PA desiring surgery if a unilateral source of PA was diagnosed. Intervention: [11C]MTO and AVS in 169 patients, plus [18F]CETO in the final 31. Measurements: International consensus criteria for biochemical and clinical success at 6 and 24 months after surgery; κ statistic and Bland–Altman analyses comparing predictions of surgical outcomes by [11C]MTO and [18F]CETO. Results: Eighty-nine of 169 (52.7%), 78 of 169 (46.2%), and 43 of 169 (25.4%) patients were predicted to have unilateral PA by [11C]MTO, AVS, or both, respectively. One hundred of 169 (59.1%) were assigned to adrenalectomy by the multidisciplinary team; primary outcome data were available for 156 of 169. Predictions were most accurate for complete or partial biochemical success ([11C]MTO, 71.3% [95% CI, 61.0% to 80.1%]; AVS, 62.8% [CI, 52.2% to 72.6%]) and least accurate for complete clinical success (home blood pressure <135/85 mm Hg off treatment). The 95% CIs around differences between accuracies crossed zero, excluding superiority for [11C]MTO, but not the prespecified lower bound of −17%, allowing [11C]MTO to be declared noninferior to AVS. [18F]CETO and [11C]MTO agreed in 29 of 31 patients (κ = 0.85 [CI, 0.68 to 1.00]). Limitation: The accuracy of [11C]MTO could be assessed only in the surgical group. Conclusion: Molecular imaging is an accurate, noninvasive alternative to AVS. Primary Funding Source: National Institute for Health and Care Research.

Development and Evaluation of a Comprehensive Prediction Model for Incident Coronary Heart Disease Using Genetic, Social, and Lifestyle–Psychological Factors: A Prospective Analysis of the UK Biobank

Background: Clinical risk calculators for coronary heart disease (CHD) do not include genetic, social, and lifestyle–psychological risk factors. Objective: To improve CHD risk prediction by developing and evaluating a prediction model that incorporated a polygenic risk score (PRS) and a polysocial score (PSS), the latter including social determinants of health and lifestyle–psychological factors. Design: Cohort study. Setting: United Kingdom. Participants: UK Biobank participants recruited between 2006 and 2010. Measurements: Incident CHD (myocardial infarction and/or coronary revascularization); 10-year clinical risk based on pooled cohort equations (PCE), Predicting Risk of cardiovascular disease EVENTs (PREVENT), and QRISK3; PRS (Polygenic Score Catalog identification: PGS000018) for CHD (PRSCHD); and PSSCHD from 100 related covariates. Machine-learning and time-to-event analyses and model performance indices. Results: In 388 224 participants (age, 55.5 [SD, 8.1] years; 42.5% men; 94.9% White), the hazard ratio for 1 SD increase in PSSCHD for incident CHD was 1.43 (95% CI, 1.38 to 1.49; P < 0.001) and for 1 SD increase in PRSCHD was 1.59 (CI, 1.53 to 1.66, P < 0.001). Non-White persons had higher PSSCHD than White persons. The effects of PSSCHD and PRSCHD on CHD were independent and additive. At a 10-year CHD risk threshold of 7.5%, adding PSSCHD and PRSCHD to PCE reclassified 12% of participants, with 1.86 times higher CHD risk in the up- versus down-reclassified persons and showed superior performance compared with PCE as reflected by improved net benefit while maintaining good calibration relative to the clinical risk calculators. Similar results were seen when incorporating PSSCHD and PRSCHD into PREVENT and QRISK3. Limitation: A predominantly White cohort; possible healthy participant effect and ecological fallacy. Conclusion: A PSSCHD was associated with incident CHD and its joint modeling with PRSCHD improved the performance of clinical risk calculators. Primary Funding Source: National Human Genome Research Institute.

Development and Validation of Body Mass Index–Specific Waist Circumference Thresholds in Postmenopausal Women: A Prospective Cohort Study: Annals of Internal Medicine: Vol 178, No 8

Background: A 2020 consensus statement proposed body mass index (BMI)–specific waist circumference (WC) thresholds to improve patient care. Objective: To determine whether stratifying BMI categories by BMI-specific WC thresholds improves mortality risk prediction. Design: Prospective cohort study. Setting: Women’s Health Initiative multicenter, population-based U.S. study, with enrollment from 1993 to 1998 and follow-up through 2021. Participants: 139 213 postmenopausal women aged 50 to 79 years were included in a development cohort (n = 67 774) and 2 external validation cohorts. Validation Cohort 1 had high prevalence of overweight or obesity (n = 48 335), and Validation Cohort 2 included diverse, geographically separate centers (n = 23 104). Measurements: Height, weight, and WC measured at enrollment. BMI categories were normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), obesity-1 (30 to <35 kg/m2), obesity-2 (35 to <40 kg/m2), and obesity-3 (≥40 kg/m2), with further stratification by prespecified WC thresholds (≥80, ≥90, ≥105, ≥115, and ≥115 cm, respectively). Mortality was ascertained annually and was supplemented with serial National Death Index queries. Ten- and 20-year mortality prediction models that included BMI categories were compared to models with BMI categories stratified by WC thresholds using c-statistics and continuous net reclassification improvement (NRI). Results: Over a median of 24 years of follow-up, 69 297 participants died. Multivariable-adjusted mortality risk was consistently greater for BMI categories with large WC than those with normal WC. Compared with women with normal weight and normal WC, women with normal or overweight BMI but large WC (hazard ratios [HRs], 1.17 [95% CI, 1.12 to 1.21] and 1.19 [CI, 1.15 to 1.24], respectively) had risk similar to those with obesity-1 but normal WC (HR, 1.12 [CI, 1.08 to 1.16]). Mortality associated with obesity-1 and large WC (HR, 1.45 [CI, 1.35 to 1.55]) was similar to that with obesity-3 and normal WC (HR, 1.40 [CI, 1.28 to 1.54]). Models with BMI-specific WC thresholds improved discrimination and risk stratification at 10 years for Validation Cohort 1; c-statistics improved by 0.7% (CI, 0.3% to 1.0%) to 61.3% (CI, 60.2% to 62.5%), and continuous NRI was 20.4% (CI, 17.3% to 23.6%). Results were mixed for Validation Cohort 2; risk stratification improved (continuous NRI, 12.3% [CI, 8.5% to 16.0%]), but not discrimination. Results were similar at 20 years. Limitation: The study did not include men or younger women. Conclusion: Further stratifying BMI categories by WC thresholds modestly improved mortality risk stratification, with larger WC predicting greater mortality, although the degree of improvement varied by cohort. Discrimination did not improve consistently. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Complementary and Alternative Therapies for Genitourinary Syndrome of Menopause: An Evidence Map: Annals of Internal Medicine: Vol 177, No 10

Background: Women seeking nonhormonal interventions for vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM) may seek out complementary and alternative medicine or therapies (CAMs). Purpose: To summarize published evidence of CAMs for GSM. Data Sources: Ovid MEDLINE, EMBASE, and CINAHL from inception through 11 December 2023. Study Selection: Randomized controlled trials (RCTs) 8 weeks or more in duration that evaluated the effectiveness or harms of CAMs for postmenopausal women with GSM and reported 1 or more outcomes of interest, with sample sizes of 20 or more participants randomly assigned per group. Data Extraction: Data were abstracted by 1 reviewer and verified by a second. Data Synthesis: An evidence map approach was used to organize and describe trials. Studies were organized by type of intervention, with narrative summaries for population, study characteristics, interventions, and outcomes. Fifty-seven trials were identified that investigated 39 unique interventions. Studies were typically small (n < 200), and most were done in Iran (k = 24) or other parts of Asia (k = 9). Few trials evaluated similar combinations of populations, interventions, comparators, or outcomes. Most studies (k = 44) examined natural products (that is, herbal or botanical supplements and vitamins), whereas fewer reported on mind and body practices (k = 6) or educational programs (k = 7). Most studies reported 1 or 2 GSM symptoms, mainly sexual (k = 44) or vulvovaginal (k = 30). Tools used to measure outcomes varied widely. Most trials reported on adverse events (k = 33). Limitations: Only English-language studies were used. Effect estimates, risk of bias, and certainty of evidence were not assessed. Conclusion: There is a large and heterogeneous literature of CAM interventions for GSM. Trials were small, and few were done in North America. Standardized population, intervention, comparator, and outcomes reporting in future RCTs are needed. Primary Funding Source: Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42023400684)

Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians (Version 1, Update Alert 2)

In many mental health and some somatic disorders, efficacy of therapist-guided remote CBT and in-person CBT does not differ

Source Citation Zandieh S, Abdollahzadeh SM, Sadeghirad B, et al. Therapist-guided remote versus in-person cognitive behavioural therapy: a systematic review and meta-analysis of randomized controlled trials. CMAJ. 2024;196:E327-E340. 38499303

Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians

Background: Various treatments for preventing episodic migraine are available. Purpose: To evaluate the comparative effectiveness and harms of pharmacologic prevention of episodic migraine, focusing on treatments already determined to be superior to placebo. Data Sources: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until April 2024. Study Selection: Randomized trials evaluating selected efficacious pharmacologic treatments in adults with episodic migraine. Selection was done independently by 2 reviewers. Data Extraction: Data were extracted by 1 reviewer and checked by a second. Risk of bias and certainty of the evidence were assessed using the Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, respectively. Data Synthesis: Sixty-one studies (20 680 patients) evaluating 16 treatments were included. Nineteen studies had low risk of bias. All selected treatments were deemed efficacious against placebo on the basis of previous systematic reviews. In network meta-analyses, calcitonin gene–related peptide antagonist monoclonal antibodies (CGRP-mAbs) probably resulted in fewer discontinuations due to adverse events than topiramate (risk difference, −16.2% [95% CI, −18.4% to −12.8%]; moderate-certainty evidence), and CGRP-mAbs may result in less migraine-related disability and improved quality of life compared with gepants (mean differences, −4.12 [CI, −9.30 to 1.05] and 2.25 [CI, −0.85 to 5.34], respectively; low-certainty evidence). For other outcomes and comparisons, there was moderate- or low-certainty evidence of no clinically important differences, uncertain evidence, or no evidence. Limitations: Limited literature was available to determine the minimal important differences. The number of head-to-head comparisons of treatments was limited. Conclusion: No high-certainty evidence favored one pharmacologic treatment for prevention of episodic migraine over another. Evidence was mostly insufficient or of low certainty. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42023414305)

Type 2 Diabetes

Type 2 diabetes (T2D) is a prevalent disease that increases risk for vascular, renal, and neurologic complications. Prevention and treatment of T2D and its complications are paramount. Many advancements in T2D care have emerged over the past 5 years, including increased understanding of the importance of early intensive glycemic control, mental health, social determinants of health, healthy eating patterns, continuous glucose monitoring, and the benefits of some drugs for preventing cardiorenal disease. This review summarizes the evidence supporting T2D prevention and treatment, focusing on aspects that are commonly in the purview of primary care physicians.

Screening for Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death. Screening has been proven to reduce both cancer incidence and cancer-related mortality. Various screening tests are available, each with their own advantages and disadvantages and varying levels of evidence to support their use. Clinicians should offer CRC screening to average-risk persons aged 50 to 75 years; starting screening at age 45 years remains controversial. Screening may be beneficial in select persons aged 76 to 85 years, based on their overall health and screening history. Offering a choice of screening tests or sequentially offering an alternate test for those who do not complete screening can significantly increase participation.

Travel Medicine

International travel can cause new illness or exacerbate existing conditions. Because primary care providers are frequent sources of health advice to travelers, they should be familiar with destination-specific disease risks, be knowledgeable about travel and routine vaccines, be prepared to prescribe chemoprophylaxis and self-treatment regimens, and be aware of travel medicine resources. Primary care providers should recognize travelers who would benefit from referral to a specialized travel clinic for evaluation. Those requiring yellow fever vaccination, immunocompromised hosts, pregnant persons, persons with multiple comorbid conditions, or travelers with complex itineraries may warrant specialty referral.