JAMA Network Open最新文献

Importance: Tranexamic acid (TXA) is associated with improved survival following trauma in prior prehospital trials, shaping clinical practice. The Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport (STAAMP) trial did not find a difference in mortality between TXA and placebo. A bayesian approach that incorporates prior clinical evidence may better characterize the impact of TXA.

Objective: To evaluate the probability of mortality benefit associated with prehospital TXA in trauma.

Design, setting, and participants: This quality improvement study used a post hoc bayesian analysis of data from the STAAMP trial, a prospective, multicenter, double-masked, placebo-controlled, phase 3 randomized clinical trial conducted at level I trauma centers in the US from May 1, 2015, to October 31, 2019. Patients at risk for hemorrhage within approximately 2 hours of injury were randomized to receive prehospital TXA or placebo. The data analysis was performed between January 1, 2024, and December 31, 2025.

Main outcomes and measures: The primary outcome was 30-day mortality assessed using frequentist statistics. Bayesian hierarchical logistic regression models were built to estimate the posterior probability of mortality associated with TXA. The prior distributions were informed by Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage 2 (CRASH-2) and Prehospital Antifibrinolytics for Traumatic Coagulopathy and Hemorrhage (PATCH-Trauma) trial data, and the influence of prior selection, sample size, and varying risk thresholds was also evaluated.

Results: Of 903 STAAMP patients analyzed (median [IQR] age, 39 [26-55] years; 668 male [74.0%]), 447 received TXA and 456 received placebo. The majority of patients (n = 760 [84.2%]) sustained blunt injuries, with a median injury severity score of 12 (IQR, 5-22). In the frequentist analysis, the 30-day mortality rates were 8.1% and 9.9% for the TXA and placebo groups, respectively (hazard ratio, 0.81; 95% CI, 0.59-1.11). Using bayesian models, the estimated posterior risk ratios were 0.91 (95% credible interval [CrI], 0.85-0.97) with a CRASH-2 prior, 0.80 (95% CrI, 0.65-0.97) with a PATCH-Trauma prior, and 0.82 (95% CrI, 0.52-1.23) under a noninformative prior. The results were robust across confounders, site clustering, and alternative priors. The posterior probability that TXA reduced mortality ranged from 84% to 99%.

Conclusions and relevance: This quality improvement study using a post hoc bayesian reanalysis of the STAAMP trial suggested a high probability that prehospital TXA would improve survival. Bayesian methods may offer refined inference and support clinical decision-making in prehospital trauma care.

Importance: Esophageal squamous cell carcinoma (ESCC) carries a poor prognosis, stressing the need for preventive measures. A decreased risk of ESCC among metformin users has been suggested, but evidence is limited.

Objective: To assess whether metformin use, given its potential anticancer properties, is associated with risk of ESCC.

Design, setting, and participants: This population-based case-control study set between 1994 and 2023 looked at data from all 5 Nordic countries (ie, Denmark, Finland, Iceland, Norway, and Sweden). Participants were patients newly diagnosed with ESCC during the study period, and each was compared with 10 times as many control participants randomly selected from the general population (matched by age, sex, calendar year, and country).

Exposures: Use of metformin vs nonuse.

Main outcomes and measures: Conditional logistic regression provided odds ratios (OR) with 95% CIs for the association between metformin use and the development of ESCC. In addition to the matching, the ORs were adjusted for tobacco smoking, alcohol overconsumption, use of nonsteroidal anti-inflammatory drugs or aspirin, and use of statins. A dose-response analysis was conducted among participants with at least 5 years of observation time, based on the defined daily dose during the 5-year period.

Results: This study included 13 050 case patients with ESCC (8030 men [61.5%] and 5020 women [38.5%], diagnosed at a median age of 70 years [IQR, 62-77 years]), and 130 500 age- and sex-matched control participants. Metformin use was associated with a 36% lower odds of ESCC compared with nonuse (OR, 0.64; 95% CI, 0.59-0.69). The odds were especially lower in participants with a higher dosage of metformin (>1278 defined daily dose in 5 years: OR, 0.52; 95% CI, 0.44-0.61).

Conclusions and relevance: In this case-control study, metformin use was associated with substantially lower odds of ESCC. This finding should prompt investigations of metformin as a preventive option in high-risk individuals and as a potential future therapeutic agent for ESCC.

Importance: Peripheral intravenous (PIV) vasopressors are increasingly used but remain associated with adverse events (AEs). Quantifying the incidence of these AEs is essential to guide clinical decision-making regarding PIV vasopressor use.

Objective: To assess the incidence of AEs and avoidance of central venous catheter (CVC) placement after PIV vasopressor administration in adults with hypotension, shock, or critical illness.

Data sources: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to December 13, 2025, using medical subject headings and keywords related to peripheral vasopressors.

Study selection: Eligible studies included critically ill adults receiving vasopressors via PIV catheters and reported AEs and/or CVC avoidance.

Data extraction and synthesis: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 2 investigators independently extracted data and assessed risk of bias. A random-effects model was used, and proportions were pooled using a generalized linear mixed model.

Main outcomes and measures: The primary end point was the pooled incidence of AEs as the proportion among total catheters, and the secondary end point was the pooled proportion of CVC avoidance.

Results: Forty-nine studies including 33 060 catheters were analyzed. The pooled minor AE incidence was 2.6% (95% CI, 1.4%-4.7%) for norepinephrine, 0.0% (95% CI, 0.0%-24.6%) for epinephrine, 2.9% (95% CI, 1.8%-4.8%) for phenylephrine, 1.4% (95% CI, 0.3%-5.9%) for dopamine, 0.5% (95% CI, 0.1%-1.8%) for vasopressin, and 0.9% (95% CI, 0.1%-11.5%) for metaraminol. When considering all vasopressors collectively, the pooled minor AE incidence was 2.3% (95% CI, 1.5%-3.7%). Regarding major AEs, 30 venous thromboembolism events occurred, all in the 4 studies (8.1%) using midline catheters (1126 total catheters), with a pooled incidence of 1.4% (95% CI, 0.4%-5.4%). In contrast, only 1 major AE (a tissue necrosis event) was reported in 43 studies (87.8%) using short PIV catheters (29 596 total catheters), with a pooled incidence of 0.0% (95% CI, 0.0%-0.0%). CVC avoidance ranged from 0% to 100%, with a pooled proportion of 59.7% (95% CI, 46.4%-71.7%) in 38 studies (77.6%) including 15 371 catheters.

Conclusions and relevance: In this systematic review and meta-analysis of adult patients, AE incidence was low after short-term vasopressor administration through PIV catheters, particularly short catheters. These findings suggest that PIV administration might reduce the need for CVC placement with appropriate monitoring.

Importance: Current data on Candida bloodstream infection (candidemia) in solid organ transplant recipients (SOTRs) are constrained by small sample sizes. Further research may inform targeted prevention strategies for early intervention.

Objective: To determine the incidence and outcomes of candidemia in SOTRs.

Design, setting, and participants: A population-based cohort study using a provincewide mycology laboratory dataset of patients aged 18 or more years from Ontario, Canada, who received an organ allograft between January 1, 2011, and September 30, 2022, with follow-up through December 31, 2023, and linked to administrative health care data.

Exposure: Organ transplant.

Main outcomes and measures: The primary outcome was candidemia incidence, estimated using the Kaplan-Meier method, with differences across SOTRs evaluated via the log-rank test. The secondary outcome was all-cause mortality, evaluated using a Cox proportional hazards regression model with candidemia as a time-dependent variable. Analyses were adjusted for relevant covariates.

Results: This study included 10 249 SOTRs (median age, 57 [IQR, 46-64] years; 63.9% male), with kidney transplants representing the majority (59.8%). Candidemia occurred in 135 patients, with Candida albicans as the most frequent species (41.5%), followed by Nakaseomyces (Candida) glabrata (28.1%) and C parapsilosis (11.9%). The cumulative probability of candidemia was 0.87% (95% CI, 0.69%-1.05%) at 1 year, 1.33% (95% CI, 1.09%-1.57%) at 5 years, and 1.67% (95% CI, 1.34%-2.00%) at 10 years. Lung transplant recipients had the highest 10-year cumulative probability at 4.17% (95% CI, 2.96%-5.39%; log-rank P < .001). Median time to candidemia was 34 (IQR, 18.5-354) days in recipients of thoracic allografts and 174 (IQR, 20-836) days in recipients of abdominal allografts. Thirty-day mortality was 39.3% (53 of 135) and 90-day mortality was 47.4% (64 of 135) in patients with candidemia. Candidemia was associated with an increase in mortality (adjusted hazard ratio [AHR], 6.85; 95% CI, 5.59-8.39; P < .001). Fluconazole-susceptible isolates were associated with an increase in mortality (AHR, 8.45; 95% CI, 6.42-11.14; P < .001) as were fluconazole-resistant Candida isolates (AHR, 11.86; 95% CI, 6.13-22.93; P < .001).

Conclusions and relevance: In this cohort study of SOTRs, candidemia was an uncommon complication after organ transplant, with lung transplant recipients at the highest risk. Candidemia was associated with increased mortality. Further research is needed to better identify vulnerable subpopulations and to develop targeted strategies for early intervention.

Importance: The APOL1 M1 (p.N264K) variant protects against G2-associated APOL1 focal segmental glomerulosclerosis (FSGS) and chronic kidney disease (CKD). However, the utility of knowing an individual's M1 status in guiding kidney disease diagnosis and other clinical scenarios remains underexplored.

Objective: To test 2 hypotheses: (1) in patients with APOL1 high-risk (HR) genotype kidney disease with at least 1 G2 allele, M1 can distinguish APOL1 CKD from non-APOL1 CKD; (2) in people with APOL1 low-risk (LR) genotypes, M1 is independently associated with protection against FSGS and CKD.

Design, setting, and participants: Retrospective case-control study using data from 2 tertiary care hospitals (Columbia University Irving Medical Center and Mass General Brigham Biobank) and population-based data (the UK Biobank [UKB], Electronic Medical Records and Genomics [eMERGE-III], and All of Us [AoU]). Participants were individuals with a diagnosis of FSGS or steroid-resistant nephrotic syndrome (SRNS), individuals with CKD, and controls.

Exposures: Exposures included the M1 variant (p.N264K) obtained from exome or genome sequencing data, sex, and genetic ancestry.

Main outcome and measure: The main outcome was the presence or absence of kidney disease, defined as FSGS or non-FSGS CKD, compared with non-kidney disease controls. Association between the M1 variant and disease status was assessed using odds ratios (ORs).

Results: A total of 107 696 individuals (54 994 [51.1%] female; 8779 [8.2%] with African ancestry, 78 475 [72.9%] with European ancestry, and 16 129 [15.0%] with multiethnic ancestry), including 3460 with FSGS or SRNS, 24 382 with non-FSGS CKD kidney disease, and 79 854 controls were enrolled in the discovery cohort. In the APOL1-HR group (1413 participants), M1 was significantly inversely associated with FSGS or SRNS cases compared with controls without kidney disease (OR, 0.20; 95% CI, 0.04-0.63; P = 3.69 × 10-3). Among individuals with CKD with APOL1-HR genotypes, M1 was 4 times more frequent in those whose CKD was not due to FSGS or SRNS. Importantly, electronic health record and biopsy review identified an alternative, non-APOL1 cause for CKD in nearly all APOL1-HR-M1 cases. There was no association between individuals with APOL1-LR genotypes with M1 and protection against CKD or FSGS.

Conclusions and relevance: In this case-control study of 107 696 individuals, presence of an APOL1-HR genotype M1 was significantly associated with protection against kidney disease, suggesting that it may have a role as a genetic modifier. Patients with CKD with an APOL1-HR genotype and M1 should be evaluated for an alternative and potentially treatable cause of their CKD.