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.
Importance: In the US, reliance on over-the-counter (OTC) and prescription medications has important public health implications. Understanding the prevalence of medication use, overall and by specific medication, aids in regulatory decision-making and pharmacoeconomic evaluations and informs measures of benefits and risks.
Objective: To estimate the current prevalence of OTC and prescription medication use in the US adult population.
Design, setting, and participants: This survey study analyzed data collected via a population-based, online survey of the US adult population (June 2023 to April 2024). Participants were volunteer online panelists aged 18 years and older.
Exposure: Use of any OTC or prescription medication.
Main outcomes and measures: The primary outcome was prevalence of OTC and prescription medication use (overall and by specific medication), stratified by sex and age. Prevalence estimates were generated by calculating the proportion of the population reporting the key outcomes.
Results: Of the 21 000 participants, 11 171 (53.2%) were female, and the mean (SD) age was 47.9 (17.5) years. Past-7-day prevalence of OTC or prescription medication use was 62.3% (13 073 individuals). The use of 5 or more medications was reported by 3425 participants (16.3%), and 690 (3.3%) reported taking 10 or more medications. Although use was higher among female individuals (7442 participants [66.6%]) than among male individuals (5631 participants [57.3%]), the patterns of increasing use and increasing number of medications with age were similar. The past-7-day prevalence of OTC medication use (9657 participants [46.0%]) was similar to that of prescription medications (9719 participants [46.3%]). Acetaminophen (6184 participants [29.4%]), ibuprofen (4693 participants [22.3%]), and aspirin (3323 participants [15.8%]) were the most reported medications used in the past 7 days. Six of the 10 most prevalent medications reported were available OTC. The most reported prescription medications were atorvastatin (1342 participants [6.4%]), lisinopril (1163 participants [5.5%]), levothyroxine (1086 participants [5.2%]), and amlodipine (965 participants [4.6%]).
Conclusions and relevance: In this 2023 to 2024 study, nearly 2 of 3 US adults reported medication use in the past 7 days. Past-7-day prevalence of OTC and prescription medication use was similar, demonstrating the reliance on these therapies and highlighting the importance of accessibility. Medication-specific prevalence allows for a better understanding of actual use and the ability to estimate potential benefits and risks associated with medication access or regulatory changes. Continued monitoring is necessary to measure the benefits and risks of regulatory decisions or other market changes that may affect medication access or use.
Importance: Albumin supplementation may reduce mortality in patients with septic shock; however, data from randomized clinical trials are limited.
Objective: To assess the impact of albumin administration on outcomes in patients with septic shock.
Design, setting, and participants: This multicenter, open-label randomized clinical trial was conducted between October 21, 2019, and May 2, 2022. Patients from 23 intensive care units in Germany enrolled within 24 hours of the onset of septic shock were followed up for outcome data up to 90 days. The statistical trial report was completed and filed with the federal authorities in December 2023; additional analyses were completed in October 2024. The study was terminated prematurely due to low enrollment rates.
Interventions: Protocol group patients received 20% albumin to maintain serum albumin levels of at least 3.0 g/dL for up to 28 days during their intensive care unit admission. The control group received standard fluid administration with crystalloids.
Main outcomes and measures: The primary end point was 90-day mortality; secondary end points included 28-day, 60-day, intensive care unit and in-hospital mortality, organ dysfunction or failure, total amount of fluid administration and total fluid balance while in the intensive care unit, duration of intensive care and hospital stays, and frequency of adverse events.
Results: Of 440 randomized patients (median [IQR] age, 69 [59-78] years; 290 [65.9%] male), 222 received albumin and 218 received standard fluids. Baseline characteristics were comparable. Ninety-day mortality was 43.3% (91 of 210) in the albumin group vs 45.9% (96 of 209) in controls (relative risk, 0.94; 95% CI, 0.76-1.17; P = .71). No significant differences were observed for secondary end points.
Conclusions and relevance: In this randomized clinical trial of patients with septic shock, albumin administration was safe but did not improve 90-day survival. As this trial was prematurely terminated, results remain inconclusive and additional studies are recommended.
Trial registration: ClinicalTrials.gov Identifier: NCT03869385.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：