Patterns in Mental Health– and Substance Use–Related Visits From 2003 to 2022 Among Registered Ontario Physicians

The Misplaced Push to Restrict Access to Gabapentin

Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes: Two Target Trial Emulation Studies: Annals of Internal Medicine: Vol 178, No 7

Background: Reduction of premature death and adverse cardiovascular outcomes is a key goal in type 2 diabetes management. Objective: To compare mortality and cardiovascular event risks in patients treated with semaglutide versus empagliflozin and, secondarily, dulaglutide versus empagliflozin. Design: Target trial emulation studies from observational data comparing semaglutide- or dulaglutide-treated patients with propensity score–matched patients treated with empagliflozin. Setting: Health care system of 703 academic and community clinical practices. Participants: Patients aged 45 years or older with type 2 diabetes treated from 1 January 2019 to 31 December 2024 with semaglutide, dulaglutide, or empagliflozin. Intervention: Initial treatment with semaglutide, dulaglutide, or empagliflozin. At baseline, concomitant treatment with other diabetes medication was permitted, excluding other glucagon-like peptide-1 receptor agonists or sodium–glucose cotransporter-2 inhibitors. Measurements: A composite of death, myocardial infarction (MI), or stroke was the primary outcome, and secondary composite outcomes included death or MI, MI or stroke, and individual cardiac events. Results: Patients treated with semaglutide (n = 7899) versus empagliflozin (n = 7899) were followed for a median of 2.2 years; the respective rates of the composite of death, MI, or stroke were 3.7% versus 4.5% at 2 years and 5.9% versus 6.9% at 3 years. Corresponding incidence rates for the composite outcome were 20.99 versus 23.56 per 1000 person-years, with a hazard ratio (HR) of 0.89 (95% CI, 0.78 to 1.02). The HRs for the individual outcomes were 0.97 (CI, 0.81 to 1.15) for death, 0.85 (CI, 0.68 to 1.05) for MI, and 0.62 (CI, 0.43 to 0.89) for stroke. Risks for dulaglutide- and empagliflozin-treated patients were similar for the composite outcome (HR, 1.03 [CI, 0.90 to 1.16]) and for death, MI, and stroke separately. Limitation: Observational study design, lack of data on cause-specific mortality, and residual confounding. Conclusion: Semaglutide treatment seems to confer some advantage over empagliflozin. This advantage was not observed for dulaglutide. Primary Funding Source: American Heart Association.

The Effect of the “Safety in Dementia” Online Tool to Assist Decision Making for Caregivers of Persons With Dementia and Access to Firearms: A Randomized Trial: Annals of Internal Medicine: Vol 177, No 12

Background: Caregivers face challenges (including competing desires to prevent injury, respect autonomy, and avoid conflict) when addressing firearm access by community-dwelling persons with Alzheimer disease and related dementias (ADRD). Objective: To test the effect of the online Safety in Dementia (SiD) decision aid on caregivers’ decision making about firearm access for people with ADRD. Design: Prospective 2-group randomized trial with longitudinal follow-up. (ClinicalTrials.gov: NCT05173922) Setting: United States. Participants: English- or Spanish-speaking caregivers (aged ≥18 years) of community-dwelling adults with ADRD and firearm access. Intervention: SiD versus a web-based information control. Measurements: The primary outcome was preparation for decision making about firearm access. The secondary outcome at follow-up was self-reported action to reduce access. Results: Among 500 participants enrolled between June 2022 and February 2024, the mean age was 47 years, 69% identified as female, half were the adult child or stepchild of the person with ADRD, and 99% chose study participation in English. Participant characteristics were similar by study group. For the primary outcome, SiD significantly increased preparation for decision making versus the control (69.8 vs. 64.8 out of 100; mean difference, 4.80 [95% CI, 0.53 to 9.07]; P = 0.024). There was no significant effect on actions to reduce firearm access at 2 weeks or 2 months. Limitation: The results may not be generalizable to non–English-speaking populations. Conclusion: The online SiD decision aid increased preparation for decision making about firearm access in this sample of ADRD caregivers in the United States. Use of such resources in clinical or community settings may support caregivers and people with ADRD in avoiding firearm injury or death. Primary Funding Source: National Institute on Aging, National Institutes of Health.

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.

Illuminating the Value of Palliative Care in Cancer: A Path to Incentivizing High-Value Cancer Care

Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine

Background: The evidence informing the harms of gabapentin use are at risk of bias from comparing users with nonusers. Objective: To describe the risk for fall-related outcomes in older adults starting treatment with gabapentin versus duloxetine. Design: New user, active comparator study using a target trial emulation framework. Setting: MarketScan (IBM) commercial claims between January 2014 and December 2021. Participants: Adults aged 65 years or older with diabetic neuropathy, postherpetic neuralgia, or fibromyalgia and without depression, anxiety, seizures, or cancer in the 365 days before cohort entry. Intervention: New initiation of treatment with gabapentin or duloxetine (comparator). Measurements: The primary outcome was the hazard of experiencing any fall-related visit in the 6 months after initiating gabapentin or duloxetine until discontinuation of treatment. Secondary outcomes were hazard of severe fall-related events defined as a fall associated with hip fracture or emergency department visit or hospitalization associated with a fall. Stabilized inverse probability of treatment weighting was used to adjust for baseline characteristics. Results: Our analytic cohort included 57 086 older adults with a diagnosis of interest initiating treatment with gabapentin (n = 52 152) or duloxetine (n = 4934). Overall median follow-up duration was 30 days (IQR, 30 to 90 days). Weighted cumulative incidence of a fall-related visit per 1000 person-years at 30, 90, and 180 days was 103.60, 90.44, and 84.44 for gabapentin users and 203.43, 177.73, and 158.21 for duloxetine users, respectively. At 6-month follow-up, incident gabapentin users had lower hazard of falls (hazard ratio, 0.52 [95% CI, 0.43 to 0.64]), but there was no difference in the hazards of experiencing severe falls. Results were similar across sensitivity and subgroup analyses. Limitation: Claims may contain fewer frail adults and undercount falls. Conclusion: Compared with incident use of duloxetine, incident use of gabapentin was not associated with increased fall-related visits. Primary Funding Source: None.

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)

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

Health Expenditures of Patients With Diabetes After Bariatric Surgery: Comparing Gastric Bypass and Sleeve Gastrectomy

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differ in their effects on body weight and risk for reoperation. However, it is unclear whether long-term health expenditures differ by procedure type in patients with diabetes. Objective: To compare health expenditures 3 years before and 5.5 years after bariatric surgery between patients with diabetes undergoing RYGB versus SG. Design: Retrospective cohort study using target trial emulation principles. Setting: Integrated health system. Patients: Patients with diabetes undergoing RYGB (n = 3147) or SG (n = 3510) from 2012 to 2019. Measurements: Total, inpatient, outpatient, and medication expenditures. Results: Characteristics of patients undergoing RYGB and SG were well balanced after weighting; 73% were female, average body mass index was 43.8 kg/m2, and average age was 50 years. Expenditures per 6-month period decreased by about 30% for both groups, from $4039.06 (95% CI, $3770.88 to $4326.31) 3 years before to $2441.13 (CI, $2151.07 to $2770.30) 5.5 years after RYGB and from $3918.37 (CI, $3658.75 to $4196.40) 3 years before to $2658.15 (CI, $2279.17 to $3100.16) 5.5 years after SG. Total expenditures after surgery did not differ between groups through 5.5 years (difference at 5.5 years, −$217.02 [CI, −$671.29 to $201.96]) except for the first 6 months, when expenditures were transiently higher in the RYGB group (difference, $564.32 [CI, $232.60 to $895.20]), driven by a higher inpatient admission rate. Otherwise, postsurgical outpatient and medication expenditures did not appear to differ between RYGB and SG. Limitation: Unobserved confounding. Conclusion: Overall expenditures decreased substantially in the postsurgical period, primarily due to reductions in pharmacy expenditures, with no differences between RYGB and SG except in the first 6 months after surgery. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.