JAMA Network Open最新文献

Importance: Despite the high prevalence of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC), the clinical impact of common KRAS mutations with different cytotoxic regimens is unknown. This evidence is important to inform current treatment and provide a benchmark for emergent targeted KRAS therapies in metastatic PDAC.

Objective: To assess the clinical implications of common KRAS G12 mutations in PDAC and to compare outcomes of standard-of-care multiagent therapies across these common mutations.

Design, setting, and participants: This retrospective cohort study obtained deidentified clinical data for 5382 patients from a nationwide (US-based) clinicogenomic database. The deidentified data originated from approximately 280 US cancer clinics (approximately 800 sites of care). Patients diagnosed with metastatic PDAC from February 9, 2010, to September 20, 2022, and with sufficient follow-up and treatment data were included.

Main outcomes and measures: Median overall survival (OS) and time to next treatment (TTNT) were calculated for each KRAS mutation group. Hazard ratios (HRs) were generated using multivariate Cox proportional hazards models for KRAS mutations and mutation-treatment combinations.

Results: A total of 2433 patients with PDAC were included in the analysis (mean age at first treatment, 67.0 [range, 66.0-68.0] years; 1340 male [55.1%]). Among 2023 patients with KRAS mutations, those with G12R had the longest median TTNT (6.0 [95% CI, 5.2-6.6] months) and the longest median OS (13.2 [95% CI, 10.6-15.2] months). Patients with KRAS G12D and G12V mutations had a significantly higher risk of disease progression (HRs, 1.15; [95% CI, 1.04-1.29; P = .009] and 1.16 [95% CI, 1.04-1.30; P = .01], respectively) and death (HRs, 1.29 [95% CI, 1.15-1.45; P < .001] and 1.23 [95% CI, 1.09-1.39; P < .001], respectively) compared with KRAS wild type. The FOLFIRINOX regimen (fluorouracil, irinotecan, oxaliplatin, and leucovorin) had a significantly lower risk of treatment progression and death than gemcitabine with (HRs, 1.19 [95% CI, [1.09-1.29; P < .001] and 1.18 [95% CI, 1.07-1.29; P < .001], respectively) or without (HRs, 1.37 [95% CI, 1.11-1.69; P = .003] and 1.41 [95% CI 1.13-1.75; P = .002], respectively) nab-paclitaxel across all patients.

Conclusions and relevance: In this cohort study of 2433 patients with PDAC, KRAS G12D and G12V mutations were associated with worse patient outcomes compared with KRAS wild type. KRAS G12R was associated with more favorable patient outcomes, and FOLFIRINOX was associated with better patient outcomes than gemcitabine-based therapies. These findings highlight the need for more effective systemic therapies for these groups of patients.

Importance: Despite guideline recommendations to use low-molecular-weight heparins (LMWHs) or direct oral anticoagulants in the treatment of most patients with acute pulmonary embolism (PE), US-based studies have found increasing use of unfractionated heparin (UFH) in hospitalized patients.

Objective: To identify barriers and facilitators of guideline-concordant anticoagulation in patients hospitalized with acute PE.

Design, setting, and participants: This qualitative study conducted semistructured interviews from February 1 to June 3, 2024, that were recorded, transcribed, and analyzed in an iterative process using reflexive thematic analysis. Interview participants were physicians in emergency medicine, hospital medicine (hospitalist), interventional cardiology, and interventional radiology. Participants were recruited using maximum variation sampling targeting UFH-dominant vs LMWH-dominant approaches in hospitalized patients with acute PE. We triangulated results with a group of interventional cardiologists and radiologists (interventionalists).

Main outcomes and measures: Common themes and factors associated with anticoagulant selection for hospitalized patients with acute PE. Reflexive thematic analysis was used to identify these themes and factors.

Results: Of the 46 interviewees (median [IQR] age, 43 [36-50] years; 33 who identified as men [71.7%]), 25 (54.3%) were emergency physicians, 17 (37.0%) were hospitalists, and 4 (8.7%) were interventionalists. Each interview lasted a median (IQR) of 29 (25-32) minutes. Prominent themes associated with anticoagulant selection included agnosticism regarding choice of anticoagulant, the inertia of learned practice, and therapeutic momentum after anticoagulation initiation. Institutional culture and support were factors associated with choice of the dominant anticoagulation strategy. Additionally, factors associated with UFH use were fear of decompensation and misperceptions regarding the pharmacology of anticoagulants and catheter-directed treatments.

Conclusions and relevance: In this qualitative study, physicians across a spectrum of specialties and geographical settings reported common barriers and facilitators to the use of guideline-concordant anticoagulation in patients hospitalized with acute PE, particularly agnosticism regarding choice of anticoagulant, inertia of learned practice, therapeutic momentum after anticoagulation initiation, and institutional culture and support. Future implementation efforts may consider targeting these domains.

Importance: Influenza vaccination remains the most important intervention to prevent influenza morbidity and mortality among nursing home residents. The additional effectiveness of recombinant influenza vaccine vs standard dose vaccines was demonstrated in outpatient older adults but has not been evaluated in nursing home populations.

Objective: To compare hospitalization rates among residents in nursing homes immunized with a recombinant vs a standard dose egg-based influenza vaccine.

Design, setting, and participants: This pragmatic cluster randomized trial assessed nursing home residents 65 years or older residing in a US facility for 100 or more days before the start of influenza season (October 1). The study was conducted across the 2019 to 2020 and 2020 to 2021 influenza seasons and randomly assigned nursing homes 1:1 within blocks categorized by proportion of Black residents and prior resident hospitalization rates. Medicare claims data were used to evaluate resident-level hospitalization outcomes. Enrollment and allocation to treatment groups began on July 20, 2019. Data analysis began on January 1, 2021, with primary end points finalized June 30, 2024.

Intervention: Nursing homes were cluster randomized to vaccinate all residents with recombinant quadrivalent influenza vaccine (RIV4) or standard egg-based quadrivalent inactivated influenza vaccine (IIV4).

Main outcome and measures: The primary outcome was respiratory-related hospitalization. Secondary outcomes included death and hospitalization due to any cause.

Results: A total of 144 565 person observations (mean [SD] age, 77.4 [13.1] years; 63.0% female) at 1078 nursing homes were included, with 72 005 residents in nursing homes randomized to provide RIV4 and 72 560 residents in nursing home randomized to provide IIV4. In total, 85.6% of the residents received influenza vaccination. Baseline resident characteristics were comparable across treatment groups. For the primary end point of respiratory-related hospitalizations, there were 1387 hospitalizations (1.9%) in the RIV4 group vs 1424 (2.0%) in the IIV4 group (hazard ratio, 1.01; 95% CI, 0.62-2.17). Hospitalization rates by vaccine were similar for other hospitalization outcomes and death, overall, and by season and subgroups (gender, race, and comorbidities).

Conclusions and relevance: In this cluster randomized trial of nursing homes, there was no significant difference between recombinant or standard dose vaccine for reducing hospitalizations associated with influenza illness. However, the COVID-19 pandemic restricting influenza activity along with poor vaccine match to circulating strains substantially limits the conclusions.

Trial registration: Clinicaltrials.gov Identifier: NCT03965195.

Importance: Mental health stigma is a considerable barrier to help-seeking among young people.

Objective: To systematically review and meta-analyze randomized clinical trials (RCTs) of interventions aimed at reducing mental health stigma in young people.

Data sources: Comprehensive searches were conducted in the CENTRAL, CINAHL, Embase, PubMed, and PsycINFO databases from inception to February 27, 2024. Search terms included "stigma," "mental health," "mental disorders," "adolescents," "youth," and "randomized controlled trial."

Study selection: Inclusion criteria encompassed RCTs involving interventions aimed at reducing mental health stigma among young people (aged 10-24 years). Studies had to report outcomes related to stigma or help-seeking behaviors. Exclusion criteria included grey literature and studies without results.

Data extraction and synthesis: Data were extracted independently by 7 authors (M.A.C., D.N., F.B., S.C., Á.I.L., J.C., V.M.) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed with the Cochrane risk-of-bias tool. Three-level multivariate meta-analyses were conducted to account for within-study correlations and to maximize data use. Standardized mean differences (SMDs) (Hedges g) and odds ratios (ORs) with 95% CIs were calculated. The data analysis was conducted from May 30 through July 4, 2024.

Main outcomes and measures: Primary outcomes included stigma-related knowledge, attitudes, behaviors, and general stigma. Help-seeking outcomes were categorized into attitudes, intentions, and behaviors. Secondary outcomes included self-efficacy and empowerment.

Results: A total of 97 studies were included in the systematic review, representing 43 852 young people (mean [IQR] age, 18.7 [15.8-21.3] years; mean [IQR] females, 59.2% [49.4%-72.0%]), and 74 studies were included in 3-level multivariate meta-analyses. Significant short-term effect sizes were found for stigma-related knowledge (SMD, 0.66; 95% CI, 0.43-0.89), attitudes (SMD, 0.38; 95% CI, 0.20-0.56), behaviors (SMD, 0.29; 95% CI, 0.13-0.45), and general stigma (SMD, 0.20; 95% CI, 0.06-0.34) and for help-seeking attitudes (SMD, 0.18; 95% CI, 0.09-0.28) and intentions (SMD, 0.14; 95% CI, 0.07-0.21). Social contact interventions had a greater influence on stigma-related behaviors than did educational approaches.

Conclusions and relevance: These findings suggest that interventions to reduce mental health stigma among youth are beneficial in the short term. Further high-quality RCTs with long-term follow-up are needed to better understand and enhance these interventions' outcomes.

Importance: Timely access to care is a key metric for health care systems and is particularly important in conditions that acutely worsen with delays in care, including surgical emergencies. However, the association between travel time to emergency care and risk for complex presentation is poorly understood.

Objective: To evaluate the impact of travel time on disease complexity at presentation among people with emergency general surgery conditions and to evaluate whether travel time was associated with clinical outcomes and measures of increased health resource utilization.

Design, setting, and participants: This retrospective cohort study used administrative statewide inpatient and emergency department databases with linkage across encounters, including nearly every inpatient or emergency department encounter in the states of Florida and California in 2021. Participants included adult patients who presented to an emergency department with 1 of 5 common emergency surgical conditions. Data were collected from January to December 2021 and analyzed from June to December 2023.

Exposure: The primary exposure was travel time from the patient's home to the facility where they initially received emergency care.

Main outcomes and measures: The primary outcome of interest was surgical disease complexity at the time of presentation to emergency care. Secondary outcomes included inpatient complications, mortality, and indicators of health system resource utilization. Multivariable logistic regression models were used, and adjusted odds ratios (aOR) and 95% CIs were reported.

Results: Among 190 311 adults with emergency general surgery conditions, 7138 (3.8%) lived further than 60 minutes from the facility where they sought emergency care. Longer travel times were associated with higher odds of complex disease presentation for travel time of more than 120 minutes vs 15 minutes or less (aOR, 1.28; 95% CI, 1.17-1.40). Patients with a travel time 60 minutes or more were more likely to require operative intervention (aOR, 1.17; 95% CI, 1.10-1.26), inpatient admission (aOR, 1.41; 95% CI, 1.33-1.50), interfacility transfer (aOR, 1.32; 95% CI, 1.15-1.51), and longer inpatient stay (adjusted mean difference, 0.47 days; 95% CI, 0.35-0.59), and had higher charges (adjusted mean difference, $8284; 95% CI, $5532-$11 035).

Conclusions and relevance: In this cohort study of patients with emergency surgical conditions, travel time to emergency care was associated with markers of delayed presentation and increased facility resource utilization. As opposed to static measures, such as rurality, travel time may serve as a more useful metric to inform policy efforts aimed at preserving access to care amidst rural hospital closures and regionalization.

Importance: Lung cancer in individuals who have never smoked (INS) is a growing global concern, with a rapidly increasing incidence and proportion among all lung cancer cases. Particularly in East Asia, opportunistic lung cancer screening (LCS) programs targeting INS have gained popularity. However, the sex-specific outcomes and drawbacks of screening INS remain unexplored, with data predominantly focused on women.

Objective: To compare LCS outcomes between Asian women and men with no smoking history.

Design, setting, and participants: This multicenter cohort study was conducted at health checkup centers in South Korea from 2009 to 2021. Participants included individuals aged 50 to 80 years with no smoking history who underwent low-dose computed tomography (LDCT) screening. Data were retrospectively analyzed from November 2023 to June 2024.

Exposures: Opportunistic LDCT screening for lung cancer.

Main outcomes and measures: Participants were followed up until December 2022 for the outcome of death. Lung cancer diagnosis, diagnostic characteristics, clinical course, and lung cancer-specific deaths (LCSD) were compared between women and men.

Results: A total of 21 062 participants (16 133 [76.6%] women and 4929 [23.4%] men) with a mean (SD) age of 59.8 (7.2) years were included. From baseline screening, 176 participants (139 women [0.9%] and 37 men [0.8%]) were diagnosed with lung cancer (screen-detected); 131 of 139 women (94.3%) and 33 of 37 men (89.2%) were diagnosed with stage 0 to I disease, with 133 of 139 women (95.7%) and 36 of 37 men (97.3%) having adenocarcinoma. There were no significant sex-based differences in stage or histologic type distribution. Among the 21 062 screened individuals, LCSD was reported in 8 women and 3 men during a mean (SD) follow-up of 83.8 (41.7) months. Multivariable analyses found no significant association between sex and cumulative hazards of lung cancer diagnosis (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.64-1.26] for men vs women) or LCSD (aHR, 1.06 [95% CI, 0.28-4.00] for men vs women). The estimated 5-year lung cancer-specific survival rate was 97.7% for women and 100% for men with screen-detected lung cancer, showing no significant sex differences.

Conclusions and relevance: In this cohort study of Asian individuals with no smoking history who underwent LDCT screening, no significant sex-based differences were detected in lung cancer diagnosis, stage distribution, or LCSD. These findings suggest that men and women who have never smoked would experience similar risks of overdiagnosis with little to no benefit when exposed to indiscriminate screening.

Importance: Sugar-sweetened beverage (SSB) excise taxes are popular policy interventions aimed at decreasing SSB purchasing and consumption to improve cardiometabolic health and generate revenue for public health initiatives. There is limited evidence that these taxes in the US are associated with weight-related outcomes in adults, a primary contributor to cardiometabolic health.

Objective: To determine the association between SSB excise taxes and adult body mass index (BMI) and proportion of adults with overweight or obesity among California cities and assess whether associations vary by demographic characteristics.

Design, setting, and participants: This cohort study compared California cities with SSB taxes (Albany, Berkeley, Oakland, and San Francisco) and demographically matched cities without SSB excise taxes from 6 years before the tax and 4 to 6 years after the tax from January 2009 through December 2020 using electronic health record data. Participants were Kaiser Permanente (KP) members aged 20 to 65 years at cohort entry with at least 1 pretax and 1 posttax BMI measurement. Data were analyzed from January 2021 to May 2023.

Exposure: Implementation of city-level SSB excise taxes.

Main outcomes and measures: Mean BMI and proportion of adults with overweight or obesity. Analysis used the differences-in-differences (DID) method.

Results: The cohort had a total of 1 044 272 members (178 931 participants in 4 cities with excise taxes; mean [SD] age, 39.7 [11.2] years; 99 501 [55.6%] female; 865 343 participants in 40 control cities without excise taxes; mean [SD] age, 39.9 [11.6] years; 480 155 [55.5%] female). DID estimates for mean BMI showed a modest decrease among adults aged 20 to 39 years (20-25 years: -0.30; 95% CI, -0.51 to -0.08; 26-39 years: -0.19; 95% CI, -0.37 to -0.20), female participants (-0.19; 95% CI, -0.26 to -0.11), and White participants (-0.19; 95% CI, -0.35 to -0.04) living in cities with SSB excise taxes. There was a statistically significant reduction in mean BMI in Berkeley (-0.16; 95% CI, -0.27 to -0.04). There were no overall differences in BMI or proportion with overweight or obesity.

Conclusions and relevance: In this cohort study, SSB excise taxes were associated with reduced mean BMI among adults in demographic subgroups, including in young adults who consumed the most SSBs, and in Berkeley. Future research should examine the mechanisms of these associations to inform how SSB taxes could be more equitable for weight-related outcomes.