Little Miracles

Mammography Screening Preferences Among Screening-Eligible Women in Their 40s: A National U.S. Survey: Annals of Internal Medicine: Vol 177, No 8

Background: The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years. Although many women welcome this change, some may prefer not to be screened at age 40 years. Objective: To conduct a national probability-based U.S. survey to investigate breast cancer screening preferences among women aged 39 to 49 years. Design: Pre–post survey with a breast cancer screening decision aid (DA) intervention. (ClinicalTrials.gov: NCT05376241) Setting: Online national U.S. survey. Participants: 495 women aged 39 to 49 years without a history of breast cancer or a known BRCA1/2 gene mutation. Intervention: A mammography screening DA providing information about screening benefits and harms and a personalized breast cancer risk estimate. Measurements: Screening preferences (assessed before and after the DA), 10-year Gail model risk estimate, and whether the information was surprising and different from past messages. Results: Before viewing the DA, 27.0% of participants preferred to delay screening (vs. having mammography at their current age), compared with 38.5% after the DA. There was no increase in the number never wanting mammography (5.4% before the DA vs. 4.3% after the DA). Participants who preferred to delay screening had lower breast cancer risk than those who preferred not to delay. The information about overdiagnosis was surprising for 37.4% of participants versus 27.2% and 22.9% for information about false-positive results and screening benefits, respectively. Limitation: Respondent preferences may have been influenced by the then-current USPSTF guideline. Conclusion: There are women in their 40s who would prefer to have mammography at an older age, especially after being informed of the benefits and harms of screening. Women who wanted to delay screening were at lower breast cancer risk than women who wanted screening at their current age. Many found information about the benefits and harms of mammography surprising. Primary Funding Source: National Cancer Institute.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 177, No 6

Background: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. Design: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436) Setting: 8 cities in China. Participants: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. Intervention: VMMC. Measurements: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. Results: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. Limitation: Few HIV seroconversions and limited follow-up period. Conclusion: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. Primary Funding Source: The National Science and Technology Major Project of China.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease: A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials: Annals of Internal Medicine: Vol 177, No 7

Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. Primary Funding Source: National Institutes of Health. (PROSPERO: CRD42022307589)

Progressive Resistance Training or Neuromuscular Exercise for Hip Osteoarthritis: A Multicenter Cluster Randomized Controlled Trial: Annals of Internal Medicine: Vol 177, No 5

Background: Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). However, randomized controlled trials providing evidence for the optimal exercise type are lacking. Objective: To investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance in patients with hip OA. Design: Multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. (ClinicalTrials.gov: NCT04714047) Setting: Hospitals and physiotherapy clinics. Participants: 160 participants with clinically diagnosed hip OA were enrolled from 18 January 2021 to 28 April 2023 and randomly assigned to PRT (n = 82) or NEMEX (n = 78). Intervention: Twelve weeks of PRT or NEMEX with 2 supervised 60-minute group sessions each week. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. Measurements: The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Results: The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, −0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX (difference, −0.7 [CI, −5.3 to 4.0] points). For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX (difference, 2.3 [CI, −3.0 to 7.6] points). Limitation: Participants and physiotherapists were not blinded. Conclusion: In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL. Primary Funding Source: Independent Research Fund Denmark.

Sodium–Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 177, No 10

Background: Both sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. Objective: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). Design: Target trial emulation study. Setting: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. Patients: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. Measurements: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score–matched cohort adjusted for confounders. Results: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was −0.91 percentage point (95% CI, −2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). Limitation: Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. Conclusion: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. Primary Funding Source: Ministry of Food and Drug Safety of South Korea.

Effect of Weight Loss Interventions on the Symptomatic Burden and Biomarkers of Polycystic Ovary Syndrome: A Systematic Review of Randomized Controlled Trials: Annals of Internal Medicine: Vol 177, No 12

Background: Polycystic ovary syndrome (PCOS) is common in women of reproductive age and is associated with obesity. Clinical guidelines recommend weight loss, but the impact on the clinical manifestations of PCOS is unclear. Purpose: To quantify the effect of weight loss interventions on clinical features of PCOS, compared with usual care. Data Sources: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, and trial registries were searched from inception through June 2024. Study Selection: Randomized controlled trials comparing interventions aiming to reduce weight against usual care, including lower-intensity weight loss interventions in people with PCOS. Conversations with people with PCOS informed the outcomes. Data Extraction: Pairs of independent reviewers screened studies, extracted data, and assessed risk of bias (RoB). Outcomes included glycemic control (Homeostasis Model Assessment for Insulin Resistance [HOMA-IR], fasting insulin and glucose), hormonal markers (free androgen index [FAI] and other sex hormones), menstrual frequency, hirsutism, and PCOS-related quality of life (QoL). Pooled mean differences were obtained from random-effects meta-analysis with Knapp–Hartung adjustment. Data Synthesis: Primary analyses included 29 comparisons with 1529 participants: 13, 12, and 4 comparisons were judged as high, some, or low RoB, respectively. Twelve used behavioral interventions, 9 used glucagon-like peptide-1 (GLP1) agonists, and 8 used other weight loss medications. Weight loss interventions were associated with significantly greater improvements in HOMA-IR (mean difference, −0.45 [−0.75 to −0.15]; I 2 = 24%), FAI (mean difference, −2.03 [−3.0 to −1.07]; I 2 = 48%), and menstrual frequency (mean difference, 2.64 [0.65 to 4.63]; I2  = 43%). There was no evidence that weight loss interventions were associated with clinically or statistically significant improvements in hirsutism, QoL, or other sex hormones, which may be due to the limited power of the available data. Limitation: There was high statistical heterogeneity in the interventions, comparators, and outcomes, largely unexplained by sensitivity and subgroup analyses. Conclusion: Weight loss interventions were associated with improvements in some important features of PCOS and should be considered as a routine treatment option for people with PCOS. Primary Funding Source: National Institute for Health and Care Research School for Primary Care Research. (PROSPERO: CRD42022367488)

A Framework for Considering the Value of Race and Ethnicity in Estimating Disease Risk

Background: Accounting for race and ethnicity in estimating disease risk may improve the accuracy of predictions but may also encourage a racialized view of medicine. Objective: To present a decision analytic framework for considering the potential benefits of race-aware over race-unaware risk predictions, using cardiovascular disease, breast cancer, and lung cancer as case studies. Design: Cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey), 2011 to 2018, and NLST (National Lung Screening Trial), 2002 to 2004. Patients: U.S. adults. Measurements: Starting with risk predictions from clinically recommended race-aware models, the researchers generated race-unaware predictions via statistical marginalization. They then estimated the utility gains of the race-aware over the race-unaware models, based on a simple utility function that assumes constant costs of screening and constant benefits of disease detection. Results: The race-unaware predictions were substantially miscalibrated across racial and ethnic groups compared with the race-aware predictions as the benchmark. However, the clinical net benefit at the population level of race-aware predictions over race-unaware predictions was smaller than expected. This result stems from 2 empirical patterns: First, across all 3 diseases, 95% or more of individuals would receive the same decision regardless of whether race and ethnicity are included in risk models; second, for those who receive different decisions, the net benefit of screening or treatment is relatively small because these patients have disease risks close to the decision threshold (that is, the theoretical “point of indifference”). When used to inform rationing, race-aware models may have a more substantial net benefit. Limitations: For illustrative purposes, the race-aware models were assumed to yield accurate estimates of risk given the input variables. The researchers used a simplified approach to generate race-unaware risk predictions from the race-aware models and a simple utility function to compare models. Conclusion: The analysis highlights the importance of foregrounding changes in decisions and utility when evaluating the potential benefit of using race and ethnicity to estimate disease risk. Primary Funding Source: The Greenwall Foundation.

Does Racial Bias Play a Role in Internal Medicine Resident Knowledge Evaluations?

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation: A Nationwide Cohort Study: Annals of Internal Medicine: Vol 177, No 8

Background: Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. Objective: To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. Design: Population-based cohort study. Setting: Two U.S. claims data sets (Medicare and Optum’s de-identified Clinformatics Data Mart Database [2013 to 2022]). Participants: 1:1 propensity score (PS)–matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. Measurements: Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. Results: Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). Limitation: Nonrandomized treatment selection. Conclusion: Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. Primary Funding Source: National Institutes of Health.