Accuracy of Cardiovascular Risk Prediction Varies by Neighborhood Socioeconomic Position: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 167, No 7

Background: Inequality in health outcomes in relation to Americans' socioeconomic position is rising. Objective: First, to evaluate the spatial relationship between neighborhood disadvantage and major atherosclerotic cardiovascular disease (ASCVD)–related events; second, to evaluate the relative extent to which neighborhood disadvantage and physiologic risk account for neighborhood-level variation in ASCVD event rates. Design: Observational cohort analysis of geocoded longitudinal electronic health records. Setting: A single academic health center and surrounding neighborhoods in northeastern Ohio. Patients: 109 793 patients from the Cleveland Clinic Health System (CCHS) who had an outpatient lipid panel drawn between 2007 and 2010. The date of the first qualifying lipid panel served as the study baseline. Measurements: Time from baseline to the first occurrence of a major ASCVD event (myocardial infarction, stroke, or cardiovascular death) within 5 years, modeled as a function of a locally derived neighborhood disadvantage index (NDI) and the predicted 5-year ASCVD event rate from the Pooled Cohort Equations Risk Model (PCERM) of the American College of Cardiology and American Heart Association. Outcome data were censored if no CCHS encounters occurred for 2 consecutive years or when state death data were no longer available (that is, from 2014 onward). Results: The PCERM systematically underpredicted ASCVD event risk among patients from disadvantaged communities. Model discrimination was poorer among these patients (concordance index [C], 0.70 [95% CI, 0.67 to 0.74]) than those from the most affluent communities (C, 0.80 [CI, 0.78 to 0.81]). The NDI alone accounted for 32.0% of census tract–level variation in ASCVD event rates, compared with 10.0% accounted for by the PCERM. Limitations: Patients from affluent communities were overrepresented. Outcomes of patients who received treatment for cardiovascular disease at Cleveland Clinic were assumed to be independent of whether the patients came from a disadvantaged or an affluent neighborhood. Conclusion: Neighborhood disadvantage may be a powerful regulator of ASCVD event risk. In addition to supplemental risk models and clinical screening criteria, population-based solutions are needed to ameliorate the deleterious effects of neighborhood disadvantage on health outcomes. Primary Funding Source: The Clinical and Translational Science Collaborative of Cleveland and National Institutes of Health.

The Importance of the Childhood Immunization Schedule for Internal Medicine

Surgery Versus Watchful Waiting for First Metatarsophalangeal Joint Osteoarthritis: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 0, No 0

Background: Hallux rigidus, or osteoarthritis of the first metatarsophalangeal joint (MTPJ), causes pain and functional limitation. No randomized trials have compared surgery with the natural course of the disease. Objective: To compare first MTPJ arthrodesis—a widely used surgical intervention—with watchful waiting in reducing walking-related pain in symptomatic hallux rigidus at 12 months after randomization. Design: Single-center, parallel-group, randomized, controlled, superiority trial with 12-month follow-up. (ClinicalTrials.gov: NCT04590313) Setting: Orthopedic department of a tertiary care hospital in Finland. Participants: Adults aged 40 years or older with radiographically confirmed (Coughlin–Shurnas grade I to III) hallux rigidus with symptoms over a year and a walking pain score of 4 or higher on a numerical rating scale (NRS) of 0 to 10 were eligible. Exclusion criteria included type 1 diabetes mellitus, rheumatoid arthritis, and hallux valgus angle greater than 15°. Intervention: Participants were randomly assigned in a 1:1 ratio to surgery with first MTPJ arthrodesis using lag-screw and dorsal plating or to watchful waiting. Measurements: The primary outcome was walking-related pain (NRS of 0 to 10) at 12 months. The prespecified minimal clinically important difference was 1.7 points. Results: Between November 2021 and June 2024, 90 patients were randomly assigned (45 per group). The mean age was 58.1 years, and 89 participants completed the 12-month follow-up. At 12 months, the observed mean walking-related pain was 1.3 in the arthrodesis group and 5.7 in the watchful waiting group (adjusted mean difference, −5.0 points [95% CI, −6.1 to −3.9 points]), exceeding the prespecified minimal clinically important difference and favoring arthrodesis. Limitation: Single-center design. Conclusion: Among adults aged 40 years or older with painful hallux rigidus, first MTPJ arthrodesis provides a superior and clinically significant reduction in walking-related pain at 12 months compared with watchful waiting. Primary Funding Source: Suomen Lääketieteen Säätiö Foundation, Finland.

The Role of Telemedicine on Interhospital Transfer Outcomes: A Systematic Review: Annals of Internal Medicine: Vol 179, No 7

Background: Interhospital transfers are essential to ensure access to appropriate levels of care, yet many transfers are potentially avoidable, leading to unnecessary resource use and patient burden. Purpose: To determine the association between telemedicine and interhospital transfer rates among patients considered for an interhospital transfer. Data Sources: Five databases were searched from database inception to 20 January 2026. Study Selection: Studies including patients considered for transfer between hospitals, studies comparing telemedicine with usual care, and studies reporting interhospital transfers rates. Data Extraction: Two independent reviewers extracted data and assessed risk of bias. The primary outcome was interhospital transfer rate; the secondary outcome was death. Grouping by patient population, clinical indication for transfer, setting, and intervention characteristic was done. Data Synthesis: Thirty-three studies representing 609 188 patients were included. Given substantial clinical and methodological heterogeneity, a structured narrative synthesis was done. Telemedicine was commonly associated with lower transfer rates in adult (13 of 17 adult only studies) and pediatric (4 of 5 studies) populations, across clinical indication for transfer (medical [9 of 14 studies] versus surgical [6 of 7 studies] versus acute care conditions [7 of 12 studies]), and rural (9 of 16 studies) and urban (9 of 10 studies) settings. Variation in the transfer rate changes was driven by differences in confounder adjustment, comparator definitions, and study design. Telemedicine was associated with lower or unchanged mortality in most studies that assessed mortality (15 of 17 studies). Limitation: Included studies were mostly observational with risk for confounding, with high heterogeneity driven by variability in study populations, telemedicine models, comparator groups, clinical contexts, and methodological approaches. Conclusion: Telemedicine may support appropriate triage and reduce potentially avoidable interhospital transfers, with no adverse association on mortality, contributing to safe and efficient transfer decision making. Primary Funding Source: None. (PROSPERO: CRD42023493486)

Continuing Glucagon-Like Peptide-1 Receptor Agonists Into the First Trimester of Pregnancy and Pregnancy Outcomes: A Target Trial Emulation Study Using Claims Information: Annals of Internal Medicine: Vol 179, No 7

Background: Glucagon-like peptide-1 receptor agonist (GLP-1RA) use has increased among women of reproductive age, but limited data exist on safety in pregnancy. Objective: To estimate the risk for nonlive birth, abnormal fetal growth, and major congenital malformation (MCM) with GLP-1RA dispensing in early pregnancy. Design: In an observational cohort of pregnant women aged 16 to 55 years with a GLP-1RA dispensation in the 90 days before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: continuation of dispensing into the first trimester (≥1 further dispensation), or noncontinuation. Setting: Merative MarketScan U.S. insurance claims data (2011 to 2024). Participants: 3572 pregnancies (41.1% [n = 1467] among women with type 2 diabetes). Measurements: Risk for nonlive birth was estimated using a weighted Kaplan–Meier estimator. Among live-birth pregnancies linked to infants, the weighted prevalence of MCM, small for gestational age (SGA), and large for gestational age (LGA) was estimated. Results: The weighted risk for nonlive birth was 29.7% with continuation and 27.1% with noncontinuation (adjusted risk ratio, 1.09 [95% CI, 0.98 to 1.23]). Among 2529 live-birth pregnancies, 1443 (57.1%) received at least 1 GLP-1RA dispensation after LMP and 1499 (829 continuers) were linked to an infant. Weighted prevalence ratios for continuation versus noncontinuation were 1.29 (CI, 0.82 to 2.06) for SGA, 1.08 (CI, 0.84 to 1.40) for LGA, and 1.21 (CI, 0.83 to 1.82) for MCM. Limitation: Potential residual confounding by prior glycemic control. Conclusion: Risks for nonlive birth, SGA, LGA, and MCM were not definitively higher with continuation of GLP-1RAs into early pregnancy. However, estimates for MCM and SGA were imprecise and were compatible with both no increased risk and clinically relevant differences in risk. Primary Funding Source: National Institutes of Health.

Weekly and Biweekly Treatment With Bofanglutide Versus Semaglutide in Chinese Patients With Type 2 Diabetes: A Phase 2b Randomized Clinical Trial: Annals of Internal Medicine: Vol 179, No 8

Background: Bofanglutide is a novel glucagon-like peptide-1 receptor agonist under development for type 2 diabetes mellitus (T2DM) and overweight and obesity. Objective: To evaluate the efficacy and safety of bofanglutide compared with semaglutide. Design: Phase 2b, randomized, open-label, active-controlled trial. (ClinicalTrials.gov: NCT06256549) Setting: Multicenter (37 sites in China). Participants: Adults with T2DM who were drug-naive or receiving stable oral antidiabetic drugs (glycated hemoglobin A1c [HbA1c], 7.0% to 11.0%). Intervention: Participants were randomly assigned 1:1:1:1:1 to 1 of 5 treatment groups: bofanglutide titrated to targets of 12, 18, or 24 mg (biweekly [once every 2 weeks; Q2W]); bofanglutide titrated to 24 mg (once weekly [QW]); or semaglutide titrated to 1 mg QW. Measurements: Change in HbA1c level from baseline to week 24 (primary end point), secondary efficacy end points, and safety. Results: Overall, 272 participants were enrolled, with a mean age of 50.8 years, HbA1c level of 8.35%, and body mass index of 27.9 kg/m2. At week 24, HbA1c level change from baseline was −1.87% (95% CI, −2.11% to −1.63%), −2.28% (CI, −2.54% to −2.03%), and −1.94% (CI, −2.19% to −1.69%) for bofanglutide 12, 18, 24 mg Q2W, respectively; −2.32% (CI, −2.57% to −2.06%) for bofanglutide 24 mg QW; and −1.60% (CI, −1.85% to −1.35%) for 1 mg of semaglutide QW. Corresponding treatment differences versus semaglutide were −0.27% (CI, −0.61% to −0.08%), −0.68% (CI, −1.04% to −0.33%), −0.34% (CI, −0.70% to 0.02%), and −0.72% (CI, −1.08% to −0.36%), respectively. Gastrointestinal adverse events (GIAEs) (mostly grade 1 or 2 in severity) occurred in 81.8% to 87.3% and 51.9% of participants in the bofanglutide and semaglutide groups, respectively. Hypoglycemia occurred in 0% to 3.8% versus 1.9%, with no severe hypoglycemia. Limitation: Open-label, short duration, only Chinese participants. Conclusion: Meaningful reductions in HbA1c levels were seen with bofanglutide in patients with T2DM; GIAEs were the most common and generally manageable. Primary Funding Source: Gan & Lee Pharmaceuticals.

Vaporized Nicotine Products for Smoking Cessation Among People Experiencing Social Disadvantage: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 8

Background: Vaporized nicotine products (VNPs) are more effective than nicotine replacement therapy (NRT) for smoking cessation in general populations, but their effectiveness among low socioeconomic groups is largely unknown. Objective: To examine whether VNPs are more effective than NRT for smoking cessation among people experiencing social disadvantage. Design: Two-group, open-label, randomized trial with blinded outcome ascertainment. (Australian New Zealand Clinical Trials Registry ACTRN12621000076875) Setting: Australia, between March 2021 and December 2022. Participants: 1045 adults who smoked daily, were willing to quit smoking, and were receiving a government pension/allowance (proxy for social disadvantage). Intervention: Participants were randomly assigned (1:1) to either a free 8-week supply of NRT or VNPs, and all participants received text-message support. Measurements: The primary outcome was 6-month continuous smoking abstinence verified using a carbon monoxide breath test at 7-month follow-up. Analysis included randomly assigned participants in accordance with Russell Standard criteria and the intention-to-treat principle. Results: Among 1045 randomly assigned participants, 866 (82.9%) completed final follow-up. The verified 6-month continuous abstinence rate was 9.6% (50 of 523) in the NRT group and 28.4% (148 of 522) in the VNP group (posterior risk difference estimate, 18.7% [95% credible interval, 14.1% to 23.3%]; >99% posterior probability that VNP is superior). Self-reported adverse events occurred less frequently in the VNP group (355 events among 237 participants) compared with the NRT group (442 events among 278 participants; incident rate ratio, 0.75 [95% CI, 0.65 to 0.88]; P < 0.001). Limitations: Biochemical verification method tested short-term exposure to cigarette smoke. Conclusion: Findings indicate that VNPs were more effective than NRT for smoking cessation in this population. Given the challenges for cessation among these socially disadvantaged populations, VNPs present a promising treatment option for this priority group. Primary Funding Source: Australian National Health and Medical Research Council.

Effectiveness of Psychological Therapies for Depression During the Perinatal Period: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 178, No 12

Background: Perinatal depression can have a deleterious impact on mothers and infants. Purpose: To evaluate psychological therapies for perinatal depression. Data Sources: 6 databases from January 2000 to March 2025. Study Selection: Randomized controlled trials (RCTs) of psychological therapies for people with depression during pregnancy and up to 1 year postpartum. Data Extraction: 6 researchers extracted study data and assessed the risk of bias and strength of evidence (SoE). Data Synthesis: Forty-four RCTs were included. Cognitive behavioral therapy (CBT; k = 25, n = 2962) was probably more effective than treatment as usual (TAU) in reducing depressive symptoms by an equivalent −1.7 points (95% CI, −2.0 to −1.3 points) on the Edinburgh Postnatal Depression Scale (EPDS; range, 0 to 30 points) (moderate SoE) and may have greater recovery rates from depressive symptoms (relative risk [RR], 1.7 [CI, 1.3 to 2.3]) (low SoE). Behavioral activation (k = 3, n = 508) may be more effective than TAU in reducing depressive symptoms by an equivalent −1.5 EPDS points (CI, −2.6 to −0.5 points) (low SoE). There may be no differences in depressive symptoms between CBT and counseling (k = 3, n = 226; EPDS, −0.5 [CI, −1.5 to 0.5]) or counseling and TAU (k = 3, n = 247; EPDS, −0.8 [CI, −2.6 to 1.0) (low SoE). Interpersonal therapy (IPT; k = 9, n = 1003) was probably more effective than TAU in reducing depressive symptoms by an equivalent −1.7 EPDS points (CI, −2.9 to −0.5 points) (moderate SoE) and may have greater recovery rates from depressive symptoms (RR, 1.2 [CI, 0.97 to 1.5]) (low SoE). Limitations: Participants were not blinded to treatment, study variation in country, interventions, populations, or reducing SoE. Differences may not be clinically important. Conclusion: For treatment of perinatal depression, CBT, behavioral activation, and IPT may be effective. Primary Funding Source: Agency for Healthcare Research and Quality (AHRQ).

Patient Navigation to Improve Colonoscopy Completion After an Abnormal Stool Test Result: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 178, No 5

Background: Patient navigation is a recommended practice of the Guide to Community Preventive Services; little is known about whether it improves colonoscopy completion for adults who have received an abnormal stool test result. Objective: To determine whether patient navigation delivered to persons with an abnormal stool test result increased follow-up colonoscopy completion (primary) at 1 year. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT03925883) Setting: A federally qualified health center (n = 32 clinics) in Washington state. Patients: Persons aged 50 to 75 years with an abnormal fecal test result in the prior month. Intervention: A 6-topic, telephone-based patient navigation program delivered by bilingual (English and Spanish) clinical staff. Measurements: Receipt of follow-up colonoscopy at 1 year (primary); time to colonoscopy receipt (secondary); and program effectiveness by patient characteristics, including patients’ probability of obtaining a colonoscopy without navigation, derived using health record data (secondary). Results: Of 985 participants enrolled (mean age, 61 years [SD, 6.8]; 170 [18%] had a Spanish-language preference listed in the medical record), 967 were included in the primary intention-to-treat analysis (479 in patient navigation, 488 in usual care). Receipt of follow-up colonoscopy was higher in the patient navigation group than in the usual care group (55.1% vs. 42.1%; risk difference, 13.0 percentage points [95% CI, 6.5 to 19.4 percentage points]). The intervention effect was not moderated by patients’ probability of obtaining a colonoscopy without navigation. Limitation: The study was primarily done during the height of the COVID-19 pandemic, which created additional barriers to colonoscopy at the health system and patient levels. Conclusion: These findings support the effectiveness of patient navigation for follow-up colonoscopy completion. Primary Funding Source: National Cancer Institute.

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