JAMA Network Open最新文献

Importance: Respiratory syncytial virus (RSV) may trigger cardiorespiratory events in adults.

Objective: To assess the risk of cardiorespiratory events in the 180 days following RSV-related hospitalization compared with a control period in adults.

Design, setting, and participants: This self-controlled case series study had an observation period from January 1, 2017, through March 31, 2024. Data were obtained from the deidentified Optum Market Clarity Dataset, including RSV-related hospitalization and associated outcomes, which were identified based on diagnosis codes. Adults with 1 or more RSV-related hospitalizations and 1 or more cardiorespiratory events (myocardial infarction [MI], stroke, chronic obstructive pulmonary disease [COPD] exacerbation, congestive heart failure [CHF] exacerbation, and arrhythmia) were included.

Exposure: RSV-related hospitalization.

Main outcomes and measures: A conditional Poisson regression model was fitted to compare the incidence of cardiorespiratory events during the risk period (ie, ≤180 days after RSV-related hospital index date) and control periods (ie, >21 days before or >180 days after the index date). Incidence rate ratios (IRRs) and 95% CIs were estimated and adjusted for time-varying covariates.

Results: A total of 11 887 patients (mean [SD] age, 69.4 [15.5] years; 7303 females [61.4%]) with RSV-related hospitalization were included. An increased risk was associated with each cardiorespiratory event during the first 14 days following RSV-related hospitalization, with the highest IRR estimates observed in the initial 7 days. For MI, the IRRs were 8.7 (95% CI, 6.7-11.2) during days 1 to 7, decreasing to 5.2 (95% CI, 3.7-7.2) during days 8 to 14 and 2.6 (95% CI, 1.6-4.3) during days 15 to 21. For stroke, the IRRs were 7.4 (95% CI, 5.5-10.1), 5.9 (95% CI, 4.2-8.3), and 3.7 (95% CI, 2.3-5.9) during the first 3 weeks with a similar pattern for CHF exacerbation (12.5 [95% CI, 10.5-14.8], 4.1 [95% CI, 3.1-5.5], and 2.4 [95% CI, 1.6-3.6], respectively). For COPD exacerbation and arrhythmia, the IRRs decreased during the first 3 weeks from 23.1 (95% CI, 20.2-26.5) through day 7 to 1.3 (95% CI, 0.8-2.4) during days 15 to 21 and from 16.5 (95% CI, 14.5-18.7) to 1.6 (95% CI, 1.1-2.5), respectively.

Conclusions and relevance: This study demonstrated that RSV, similar to influenza and SARS-CoV-2, was associated with an increased risk of cardiorespiratory events 2 weeks following RSV-related hospitalization, and some conditions had significant risk elevations up to 180 days after admission. The findings reinforce the need to increase RSV immunization in adults.

Importance: Before elective surgery, direct oral anticoagulants (DOACs) are discontinued following a standardized protocol. However, this could result in insufficient lowering of DOAC levels that could increase bleeding risk.

Objective: To estimate the proportion of patients with elevated DOAC levels at the time of elective surgery, evaluate factors associated with DOAC levels, and examine associated blood loss.

Design, setting, and participants: This cohort study (DOAC Level Prior to Incision [DALI]) assessed adult patients prescribed a DOAC (apixaban, dabigatran, or rivaroxaban) for any indication and at any dose, undergoing an elective procedure requiring DOAC interruption between May 27, 2018, and February 25, 2024, at 2 Dutch hospitals.

Exposure: Standardized interruption protocol (1 day before moderate- and 2 days before high bleeding-risk procedures) with interruption adjustments for the patient's kidney function.

Main outcomes and measures: Blood was drawn immediately before surgery to determine DOAC levels (by liquid chromatography-mass spectrometry). Proportions of preoperative DOAC levels of 30 ng/mL or higher and their 95% CIs were estimated, stratified by DOAC type and surgical bleeding risk. Factors associated with DOAC levels were identified through multivariable linear regression. Surgical blood loss and 30-day postoperative complications were described according to DOAC concentrations.

Results: The study was terminated after including 257 patients (100 receiving apixaban, 100 receiving rivaroxaban, and 57 receiving dabigatran due to the slow inclusion rate of those receiving dabigatran; median [IQR] age, 72 [66-78] years; 173 male [67%]); 212 patients (82%) underwent a high bleeding-risk operation. Preprocedural DOAC levels were 30 ng/mL or higher in 7.6% (95% CI, 4.9%-11.6%) of patients. Dabigatran and rivaroxaban had similar proportions, whereas 13.1% (95% CI, 7.8%-21.2%) of patients treated with apixaban had levels of 30 ng/mL or higher. Treatment with apixaban, decreased kidney function, and a shorter interruption time were associated with higher levels. Surgical blood loss (median [range], 0 [0-4250] mL) was not associated with DOAC levels. Twelve patients (4.7%; 95% CI, 2.7%-8.0%), who all had DOAC levels less than 30 ng/mL, experienced major bleeding.

Conclusions and relevance: In this cohort study, most patients following the current protocol had DOAC levels less than 30 ng/mL, although the proportion of patients with elevated levels was higher for apixaban. Preoperative DOAC levels were not associated with blood loss during surgery.

Importance: Current colorectal surveillance guidelines emphasize adenoma characteristics but overlook temporal, racial, and sex-based heterogeneity in recurrence risk, a gap that limits equitable and personalized care.

Objective: To evaluate the associations of demographic factors, obesity, and adenoma features with recurrence risk over time in a large longitudinal surveillance cohort.

Design, setting, and participants: This retrospective cohort study included adults who underwent their first colonoscopic polypectomy between January 1990 and July 2024 at a tertiary medical center.

Exposures: Demographic variables included race and ethnicity, sex, obesity (body mass index >30), family history of colorectal cancer (CRC) or polyps, and age at adenoma onset (<50 vs ≥50 years). Adenoma features included histology, size, number, and dysplasia.

Main outcomes and measures: The primary outcome was recurrence-free survival, defined as time from initial polypectomy to histologically confirmed recurrence. Time-varying coefficient Cox models were fitted to handle the nonconstant associations of exposure over the follow-up time. The follow-up time was categorized into 3 periods (less than 5 years, 5 to 10 years, and 10 or more years). The heterogeneity of exposure associations across the 3 follow-up periods was assessed with likelihood ratio tests.

Results: Among 59 667 patients (mean [SD] age, 60 years [11.2]; 29 401 [49.3%] female; 1007 [1.7%] Asian and Pacific Islander, 646 [1.1%] Hispanic, 5972 [10.0%] non-Hispanic Black, and 52 042 [87.2%] non-Hispanic White; median [IQR] follow-up, 4 [1-9] years), 17 596 (29.5%) experienced overall recurrence within 5 years. High-grade dysplasia demonstrated the largest early phase association (adjusted hazard ratio [aHR], 4.00; 95% CI, 3.56-4.50) with complete midterm and late attenuation, while villous histology exhibited biphasic patterns with early elevation (aHR, 2.89; 95% CI, 2.63-3.18) and late-phase (>10 years) reemergence (aHR, 2.71; 95% CI, 2.15-3.41). Obesity conferred persistent risk across all surveillance intervals (early: aHR, 1.16; 95% CI, 1.11-1.21; late: aHR, 1.22; 95% CI, 1.09-1.35). Female patients with high-risk adenomas exhibited marked late-term (>10 years) elevation exceeding male patients (female patients: aHR, 1.73; 95% CI, 1.43-2.08 vs male patients: aHR, 1.29; 95% CI, 1.06-1.58).

Conclusions and relevance: Both histopathologic features and demographic factors demonstrated distinct time-dependent patterns in adenoma recurrence, underscoring the need for surveillance strategies that account for temporal variation and population-specific risk profiles.

Importance: Prior drug safety studies investigating the risk of neuropsychiatric events (NPEs) after montelukast initiation have been limited by methodological issues, including incomplete confounder control and unmeasured outcomes associated with completeness of structured data, as well as events recorded only in unstructured clinical notes.

Objective: To examine the value associated with using linked claims and electronic health records (EHRs) (structured and unstructured data) while investigating the risk of any NPE among patients with asthma initiating montelukast compared with inhaled corticosteroids (ICSs).

Design, setting, and participants: This retrospective cohort study used Oracle EHR Real-World Data linked to a national US claims dataset (July 1, 2015, to June 30, 2022) to identify patients aged 6 to 80 years with asthma newly initiating montelukast or ICSs. The data were analyzed between December 13, 2022, and August 2, 2024.

Main outcomes and measures: The primary outcome of any NPE and covariates was assessed using the incremental addition of each data source: analysis 1, claims-only data; analysis 2, claims plus structured EHR data; and analysis 3, claims plus structured and unstructured EHR data. Cox proportional hazard regression models using propensity score-matched cohorts across data sources were used to examine the risk of any NPE by treatment initiation group.

Results: Among 109 076 patients (mean [SD] age at treatment initiation, 28.8 [20.5] years, 59.4% female), 39 665 (36.4%) initiated montelukast and 69 411 (63.6%) ICSs. Incidence rates per 100 person-years of the first postindex NPE increased with additional data sources for both montelukast and ICS users (analysis 1, 17.11 [95% CI, 16.86-17.36] vs 15.57 [95% CI, 15.34-15.80], respectively; analysis 2, 19.10 [95% CI, 18.83-19.38] vs 18.23 [95% CI, 17.97-18.50], respectively; analysis 3, 27.78 [95% CI, 27.43-28.13] vs 27.40 [95% CI, 27.06-27.75], respectively). Hazard ratios were attenuated across contributing data sources for analysis 1 (1.08 [95% CI, 1.05-1.11]), analysis 2 (1.04 [95% CI, 1.01-1.06]), and analysis 3 (1.01 [95% CI, 1.00-1.03]).

Conclusions and relevance: This cohort study found that clinical information from linked claims and structured and unstructured EHR data was associated with enriched measurement of patient and disease characteristics and enhanced completeness of evidence vs claims data alone. The findings, however, did not differ substantially across the incrementally contributing data sources or from prior studies. Drug safety and effectiveness studies should integrate information using clinical notes from EHRs with consideration of potential limitations, challenges, and necessary validation processes.

Importance: Alcohol-related liver disease (ALD) is the leading indication for liver transplant in the US; however, use of medications for alcohol use disorder (MAUDs) remains very low overall. Few studies have examined the use of MAUDs for patients with severe ALD, and lack of clinical knowledge around the benefits of MAUDs for severe ALD remains a barrier to their use.

Objective: To assess the association between use of MAUDs and mortality among patients with severe ALD referred for liver transplant.

Design, setting, and participants: This retrospective single-center cohort study was conducted at a tertiary referral center among 1309 patients with severe ALD referred for liver transplant between January 1, 2016, and December 31, 2022. Statistical analysis was performed from January 2023 to December 2025.

Exposure: Use of MAUDs, including US Food and Drug Administration-approved and off-label treatments.

Main outcomes and measures: The main outcome was all-cause mortality, as determined by clinical staff and documented in the electronic medical record.

Results: This study included 1309 patients (mean [SD] age, 57.1 [10.5] years; 989 men [75.6%]) and had a mean (SD) of 38 (25) months of follow-up. Use of MAUDs for at least 3 months was associated with 6.6% higher 1-year survival (SE, 0.02%) and 18.5% higher 3-year survival (SE, 0.03%). This association persisted in propensity score-adjusted multivariable Cox proportional hazards regression models, independent of Model for End-Stage Liver Disease score, liver transplant status, and other clinical factors (hazard ratio, 0.59; 95% CI, 0.39-0.92).

Conclusions and relevance: In this cohort study, use of MAUDs was associated with improved survival among patients with severe ALD. This finding highlights the need for improved access to MAUDs among patients with severe ALD.

Importance: Perinatal hypoxia is an important cause of cerebral palsy (CP). Although criteria for relevant perinatal hypoxia require both clinical and biochemical abnormalities, such as low Apgar score and low umbilical cord blood pH, most observational studies have considered only 1 of these measures.

Objective: To investigate the association of perinatal hypoxia assessed by Apgar score combined with umbilical cord blood pH with CP.

Design, setting, and participants: This registry-based cohort study was conducted nationwide in Denmark with follow-up until December 31, 2022. Analyses were performed from October 2024 to May 2025. All singleton newborns with a gestational age of 35 weeks or older without major malformations between January 1, 2004, and December 31, 2018, with at least 1 year of follow-up were included.

Exposure: Combinations of 5-minute Apgar score category (0-3, 4-6, and 7-10) and umbilical cord blood pH category (<7.00, 7.00-7.09, 7.10-7.19, and ≥7.20). Newborns with an Apgar score of 7 to 10 combined with a pH level of 7.20 or greater were considered as a reference group.

Main outcomes and measures: Any diagnosis of CP. Associations between Apgar score combined with pH level and CP were estimated with multivariable log-binomial regression. Severe CP was defined as Gross Motor Function Classification System level IV to V.

Results: The cohort included 825 159 newborns (422 409 male [51.2%]; 432 398 born at 39-40 weeks of gestation among 822 913 with gestational age data [52.5%]). Among 145 children with the lowest Apgar score (0-3) combined with the lowest pH level (<7.00), 22 individuals (15.2%) were diagnosed with CP, corresponding to an adjusted relative risk (aRR) of 159.0 (95% CI, 104.0-243.0). In 2463 children with a normal Apgar score (7-10) but the lowest pH level (<7.00), 14 individuals (0.6%) were diagnosed with CP (aRR, 6.1; 95% CI, 3.7-10.0). Among 388 children with the lowest Apgar score (0-3) combined with a normal pH level (≥7.20), 8 individuals (2.1%) were diagnosed with CP (aRR, 22.0; 95% CI, 11.0-44.0). Severe CP was observed in 31 of 63 children (49.2%) with CP and an Apgar score of 0 to 6 combined with a pH level less than 7.20 compared with 39 of 385 children (10.1%) with CP and a normal Apgar score and pH level (P < .001).

Conclusion and relevance: In this study, perinatal hypoxia assessed by clinical and biochemical measures was associated with CP risk, with a higher risk when both measures were abnormal. These findings may guide future identification for follow-up of children with perinatal hypoxia.

Importance: Despite nearly universal adherence to the Surgical Care Improvement Project (SCIP), surgical site infections (SSIs) persist. Compared with SCIP, which largely focuses on antibiotic timing, the Infectious Diseases Society of America (IDSA) guidelines provide a more comprehensive framework of antibiotic metrics, including procedure-specific antibiotic selection, weight-adjusted dosing, timing of the first dose, and appropriate redosing.

Objective: To assess whether nonadherence to each antibiotic administration metric of IDSA guidelines is associated with SSIs.

Design, setting, and participants: In this nationwide, multicenter, cross-sectional study, patients aged 18 years or older who underwent noncardiac surgeries involving a skin incision between January 1, 2014, and August 31, 2022, were included from merged data of the Multicenter Perioperative Outcomes Group, National Surgical Quality Improvement Program, and Michigan Surgical Quality Collaborative registries. Analyses were conducted between July 2, 2024, and April 24, 2025.

Exposure: Nonadherence to IDSA-defined antibiotic metrics.

Main outcomes and measures: The primary end point was SSI, defined as any superficial, deep tissue, or organ-space infection as recorded in the National Surgical Quality Improvement Program and Michigan Surgical Quality Collaborative registries. The association of nonadherence to IDSA guidelines (both overall and individually) was examined using hierarchical generalized linear mixed models.

Results: Of 134 413 eligible surgical cases, a total of 119 236 patients (mean [SD] age, 56.2 [15.9] years; 58.1% women) from 37 institutions met the inclusion criteria, among whom 6796 (5.7%) had incomplete covariate data. Failure to adhere to any IDSA metric was common in 26.1% of cases, with individual nonadherence rates as follows: 13.3% for antibiotic choice, 9.0% for weight-adjusted dosing, 3.0% for timing relative to incision, and 4.8% for correct intraoperative redosing interval. Overall, SSIs occurred in 4.4% of cases. After adjusted analysis, guideline-nonadherent antibiotic administration was significantly associated with SSIs (relative risk [RR], 1.34 [95% CI, 1.26-1.43]). Nonadherence to antibiotic choice (RR, 1.43 [95% CI, 1.33-1.53]) and failure to appropriately redose intraoperatively (RR, 1.12 [95% CI, 1.02-1.24]) were significantly associated with SSIs.

Conclusions and relevance: This cross-sectional study found that IDSA guideline nonadherence, including incorrect antibiotic choice and missed intraoperative redosing, was common and associated with increased SSI risk, despite high adherence to SCIP timing metrics. Improving adherence to IDSA-recommended antibiotic selection and redosing may meaningfully reduce SSIs.