Category: Statistics

JAMA Netw Open. 2026 Feb 2;9(2):e2557361. doi: 10.1001/jamanetworkopen.2025.57361.

ABSTRACT

IMPORTANCE: The requirement for in-person, often daily, attendance at opioid treatment programs (OTPs) makes travel times a barrier to methadone treatment. Research on methadone accessibility has primarily focused on travel via personal vehicle, and there is uncertainty about public transit travel time to methadone treatment.

OBJECTIVE: To estimate travel time via personal vehicle vs public transit to methadone treatment in the state of Connecticut.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included geospatial analysis of median travel time to nearest OTP via personal vehicle and public transit from all census block groups (CBGs). This study took place in the state of Connecticut in 2023. Participants were all CBGs in Connecticut.

EXPOSURES: Participants were characterized by racial and ethnic demographics; household income; car ownership; urban, suburban, or rural designations; and per-capita opioid overdose deaths.

MAIN OUTCOMES AND MEASURES: The primary outcome was the median travel time to nearest OTP by via personal vehicle and public transit. Spatial error models using k-nearest neighbor spatial weight matrices were estimated to assess the associations between sociodemographic characteristics and travel times for each transportation mode (personal vehicle vs public transit) at the CBG level.

RESULTS: From the centroids of the 2702 CBGs in Connecticut, the median (IQR) travel time to the closest OTP was 11.0 (7.5-16.3) minutes by personal vehicle and 41.7 (31.0-49.5) minutes via public transit, with 1431 CBGs (53%) lacking access to public transit or having high public transit times (>60 minutes or no trip available). Travel times via public transit increased along the urban-rural gradient and across CBGs with an increasing percentage of non-Hispanic White residents. Median (IQR) travel times to an OTP from the 489 CBGs with the highest per-capita overdose death rates were 8.2 (5.9-11.7) minutes by personal vehicle and 37.6 (27.8-48.5) minutes by public transit, with 166 (34%) lacking public transit access.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study of barriers to access to methadone treatment suggest that areas with high overdose death rates, low car ownership, and high public transit travel times should be targets for interventions (eg, mobile services or greater use of take-home doses for patients) to lower travel-based barriers to methadone. Current federal statutes and regulations governing methadone provision are the greatest barrier, as they directly require often daily transit to opioid treatment clinics. Reducing this barrier requires policy changes.

PMID:41632474 | DOI:10.1001/jamanetworkopen.2025.57361

JAMA Netw Open. 2026 Feb 2;9(2):e2557415. doi: 10.1001/jamanetworkopen.2025.57415.

ABSTRACT

IMPORTANCE: As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies.

OBJECTIVE: To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, at 26 hospitals in 20 US states. Case patients presented with COVID-19-like illness and positive SARS-CoV-2 nucleic acid or antigen test results; control patients had COVID-19-like illness but tested negative for SARS-CoV-2.

EXPOSURE: Receipt of a 2024-2025 COVID-19 vaccine at least 7 days before illness onset.

MAIN OUTCOMES AND MEASURES: Main outcomes were COVID-19-associated hospitalization and severe in-hospital outcomes (supplemental oxygen therapy, acute respiratory failure, intensive care unit admission, and invasive mechanical ventilation or death). Logistic regression was used to estimate the odds of vaccination in case and control patients, adjusting for demographics, clinical characteristics, and enrollment region. The VE was estimated as (1 – adjusted odds ratio) × 100%.

RESULTS: A total of 8493 patients (median [IQR] age, 66 [54-76] years; 4338 female [51.1%]), including 1888 case patients with COVID-19 (among whom 951 [50.4%] had successful whole-genome sequencing, including 348 [36.6%] with KP.3.1.1, 218 [22.9%] with XEC, and 134 [14.1%] with LP.8.1 infections) and 6605 control patients were enrolled. Vaccine effectiveness against COVID-19-associated hospitalization was 40% (95% CI, 27%-51%), and protection was sustained through 90 to 179 days after vaccination. Vaccine effectiveness was higher against the most severe outcome of invasive mechanical ventilation or death at 79% (95% CI, 55%-92%). It was 49% (95% CI, 25%-67%) against hospitalization with KP.3.1.1, 34% (95% CI, 4%-56%) against XEC, and 24% (95% CI, -19% to 53%) against LP.8.1, with increasing median time since dose receipt among vaccinated case patients due to sequential circulation patterns (60, 89, and 141 days, respectively). The VE was similar against lineages with spike protein S31 deletion (41% [95% CI, 22%-56%]) and T22N and F59S substitutions (37% [95% CI, 9%-57%]).

CONCLUSIONS AND RELEVANCE: In this multicenter, case-control analysis of VE, 2024-2025 COVID-19 vaccines may have provided protection against hospitalizations and severe in-hospital outcomes as multiple JN.1 descendant lineages circulated. Monitoring COVID-19 VE, including stratifying by SARS-CoV-2 lineage and spike protein mutations, remains important to guide COVID-19 vaccine composition and recommendations.

PMID:41632473 | DOI:10.1001/jamanetworkopen.2025.57415

JAMA Netw Open. 2026 Feb 2;9(2):e2557546. doi: 10.1001/jamanetworkopen.2025.57546.

ABSTRACT

IMPORTANCE: Depression and factors reflecting neighborhood social structure (ie, socioeconomic deprivation, ethnic heterogeneity, residential mobility, and urbanicity) have each been linked to criminal convictions. However, how the association between depression and crime varies across different neighborhood types, and the extent to which it reflects unmeasured familial confounding, remains unclear.

OBJECTIVE: To examine whether the association between depression and violent and nonviolent criminal convictions varies across neighborhood types, and to assess the extent to which unmeasured familial factors contribute to the association.

DESIGN, SETTING, AND PARTICIPANTS: This population-based matched cohort and sibling-comparison study used data from Swedish national registers from 1986 to 2020. Follow-up spanned from 2001 to 2020. Statistical analyses were performed from January to November 2025. The cohort included individuals with a diagnosis of depression, each matched to 5 population controls without depression by birth year, sex, and neighborhood type.

EXPOSURE: Outpatient depression diagnosis (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F32-F33.9) recorded from 2001 to 2020.

MAIN OUTCOMES AND MEASURES: The primary outcomes were violent and nonviolent criminal convictions after diagnosis, identified through the National Crime Register. Conditional logistic regression estimated odds ratios (ORs) across 4 neighborhood types (resource-limited, rural low-diversity, urban professional, and urban affluent neighborhoods), with sibling comparisons used to assess familial confounding.

RESULTS: Among 571 470 matched individuals, 95 245 (36 297 male [38.1%]; median [IQR] age at first diagnosis, 20 [17-24] years) had depression. Depression was associated with increased odds of both violent and nonviolent convictions across all neighborhood types in unadjusted models. After adjustment for prior convictions, substance use disorder, and attention-deficit/hyperactivity disorder, associations remained significant in all but resource-limited neighborhoods (violent conviction OR, 1.14 [95% CI, 0.97-1.33]; nonviolent conviction OR, 1.01 [95% CI, 0.92-1.11]). A second sample included 42 585 individuals with depression and their full siblings without depression (total, 85 170 individuals). Sibling comparisons showed partial attenuation, indicating that familial confounding accounted for some, but not all, of the associations. Sibling-matched estimates were largely consistent with fully adjusted general population-matched estimates (eg, violent convictions in rural low-diversity neighborhoods: sibling-matched OR, 1.50 [95% CI, 1.33-1.69] vs general population-matched OR, 1.51 [95% CI, 1.39-1.65]).

CONCLUSIONS AND RELEVANCE: In this cohort study of the Swedish general population, the association between depression and criminal convictions varied across neighborhood types and was partially explained by familial factors. These findings underscore the relevance of considering contextual and familial influences and may offer insights for prevention and intervention strategies responsive to neighborhood social environments.

PMID:41632471 | DOI:10.1001/jamanetworkopen.2025.57546

J Trauma Acute Care Surg. 2026 Jan 21. doi: 10.1097/TA.0000000000004896. Online ahead of print.

ABSTRACT

BACKGROUND: Previous trials have found a modest survival benefit from tranexamic acid (TXA) administration after polytrauma, but the early discrimination of the survival benefit observed suggests that the clinical effect of TXA may be multifactorial, not solely through bleeding reduction. Plasmin is known to directly cleave and activate complement proteins, and TXA can inhibit plasmin generation. We hypothesized that polytrauma patients who received TXA would demonstrate less complement activation compared with placebo controls.

METHODS: Patient plasma was obtained from 53 polytrauma patients enrolled in the Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Hemorrhage (PATCH) trial of prehospital TXA (1 g bolus plus 1 g drip over 8 hours) versus placebo in the emergency department, at 8 hours, and at 24 hours after admission. Complement activation and regulatory markers were measured via multiplex, and plasmin-antiplasmin levels via enzyme-linked immunosorbent assay. Pairwise comparisons of analytes between TXA and placebo at each time point were performed with significance set at p < 0.05.

RESULTS: The median age was 41.0 years (interquartile range, 28-57 years), 69.8% were male, the median Injury Severity Score was 38.0 (27.0-50.0), and all included patients were blunt mechanism. At early time points (emergency department and 8 hours), patients who received TXA did not demonstrate a reduction in C3a, C5a, sC5b-9, or plasmin-antiplasmin relative to placebo. At 24 hours, there was a significant increase in both C3a (274.0 vs. 416.6 ng/mL, p = 0.0024) and C5a (9.4 vs. 11.6 ng/mL, p = 0.0462) in the TXA group.

CONCLUSION: A 1 g bolus plus 1 g drip of TXA paradoxically increased complement activation at 24 hours in the TXA group. These findings support that TXA is essential in the inflammatory pathway after trauma. The delayed increase in complement may reflect the timing of TXA dosing and the shift to urokinase as the main plasminogen activator at later time points after injury. These results raise important questions about the optimal dosing of TXA in trauma patients.

PMID:41632465 | DOI:10.1097/TA.0000000000004896

AANA J. 2026 Feb 1;94(1):42-48. doi: 10.70278/AANAJ/.0000001057.

ABSTRACT

Obstetric anesthesia is an important subspecialty of anesthesia requiring specialized training to meet the distinctive needs of maternal care. Variations in obstetric anesthesia education create deficiencies for some nurse anesthesiologists upon graduation. The purpose of this study was to evaluate incorporating dedicated obstetric anesthesia rotation for nurse anesthesia residents at a northeastern university, focusing on training outcomes, preparedness, and perceptions of obstetric anesthesia as a subspecialty. Certified registered nurse anesthetists (CRNAs) graduated between 2018 and 2023 received a survey. Two groups were analyzed: with and without the obstetric rotation. The survey assessed clinical experience, obstetric anesthesia preparedness, and perceptions of obstetric anesthesia as a specialty using Likert-scale questions and open-ended feedback. Numerical data were analyzed using descriptive statistics, paired t-tests, and graphical representation. CRNAs with the obstetric rotation reported significantly fewer challenges meeting minimum epidural requirements, higher confidence in managing obstetric cases, and greater recognition of the importance of the training. In contrast, CRNAs without the rotation highlighted deficiencies in epidural training. An obstetric rotation is important to instill the confidence necessary for CRNAs to achieve full scope of practice capabilities. In addition to an obstetric specialty rotation, recommendations include advocacy for CRNA training, a focus on obstetric anesthesia subspecialty development, and access for educators to resources assisting in creating this rotation.

PMID:41632460 | DOI:10.70278/AANAJ/.0000001057

AANA J. 2026 Feb 1;94(1):36-41. doi: 10.70278/AANAJ/.0000001045.

ABSTRACT

Anxiety is a common preoperative occurrence in children having surgery, and it can compromise surgical results, have long-term psychological effects, and lead to future healthcare challenges. In the surgical setting, preoperative anxiety is frequently treated with a combination of pharmaceutical and nonpharmacological interventions. One nonpharmacological approach is the use of virtual reality (VR), a computer-generated environment accessed by headset or goggles. This evidence-based practice initiative utilized VR goggles to address the question: to what degree would previous research on virtual reality distraction in the preoperative area and in the operating room impact preoperative anxiety levels among pediatric patients undergoing surgery at an outpatient surgery center? A preoperative registered nurse assessed and scored the patient for preoperative anxiety utilizing the modified Yale preoperative anxiety scale (mYPAS) tool while a certified registered nurse anesthetist intraoperatively obtained a second mYPAS score. The findings demonstrated how VR goggles utilized preoperatively and intraoperatively improved patients’ anxiety with innovative technology indicating that results were clinically and statistically significant.

PMID:41632459 | DOI:10.70278/AANAJ/.0000001045

J Med Econ. 2026 Dec;29(1):308-318. doi: 10.1080/13696998.2026.2618930. Epub 2026 Feb 3.

ABSTRACT

OBJECTIVES: To assess all-cause healthcare resource utilization (HCRU) and costs among patients with α- or β-non-transfusion-dependent thalassemia (NTDT) vs. matched controls in the United States.

METHODS: Adults with ≥1 inpatient setting or ≥2 outpatient settings claims for α- or β‑thalassemia between January 1, 2013 and June 30, 2021 were identified from the Merative MarketScan Commercial/Medicare database. Patients with <8 transfusions or ≥6 weeks between any two adjacent transfusions in a 1-year period post-index date (date of first observed α- or β-thalassemia diagnosis code) were considered to have NTDT. Patients were required to have mean hemoglobin (Hgb) levels <10 g/dL during follow-up as an additional measure to ensure exclusion of patients with thalassemia trait. Each patient was matched with five controls based on age, sex, length of follow-up, availability of lab data, and payer type. All-cause HCRU and costs were assessed over ≥12 months post-index. Data were also analyzed for the non-transfusion-dependent α- and β-thalassemia subgroups.

RESULTS: A total of 149 patients with NTDT and Hgb levels <10 g/dL were matched with 745 controls. The mean follow-up period was approximately 3 years. All-cause inpatient admissions (48.3% vs. 16.5%; p < 0.001) and emergency room visits (61.1% vs. 39.1%; p < 0.001) during follow-up were higher with NTDT vs. controls, and total costs (total medical + outpatient pharmacy) were $29,107 per patient per year (PPPY) in patients with NTDT vs. $9,042 PPPY in controls (p < 0.001). Similar trends were seen in the subgroups of patients with non-transfusion-dependent α- and β-thalassemia vs. matched controls.

CONCLUSIONS: Patients with NTDT in the United States, including those with α- and β-thalassemia, have significantly higher all-cause HCRU and costs vs. matched controls. There is a need for effective treatment options to reduce the healthcare burden of NTDT and improve patient outcomes.

PMID:41632448 | DOI:10.1080/13696998.2026.2618930

Clin Drug Investig. 2026 Feb 3. doi: 10.1007/s40261-025-01507-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: This study evaluated the pharmacokinetics (PK), safety, and tolerability of TV-44749 in patients with schizophrenia or schizoaffective disorder. TV-44749 is a novel, long-acting, subcutaneous (SC) olanzapine injection designed to leverage the benefits of long-acting injectable treatment, reduce the risk for post-injection delirium/sedation syndrome (PDSS), and maintain the efficacy of olanzapine.

METHODS: In this open-label phase I study, patients completed an oral olanzapine treatment period followed by administration of TV-44749 single doses (SD cohort; 318 mg, 425 mg, or 531 mg) or multiple doses (MD cohort; three consecutive monthly doses of 283 mg or 566 mg). For the SD cohort, the follow-up period was up to 84 days (i.e., day 85) after TV-44749 administration. Patients in the MD cohort received TV-44749 on days 1, 29, and 57 over an 84-day treatment period and were followed until the end of the study. Evaluations included PK, adverse events (AEs), clinical assessments, and injection-site pain.

RESULTS: A total of 71 (SD, 42; MD, 29) patients each received ≥ 1 dose of TV-44749. Both cohorts had overall similar baseline characteristics. Following subcutaneous administration, TV-44749 reached clinically relevant plasma concentrations (≥ 10 ng/mL) within 1-2 days, with a maximum observed plasma drug concentration (Cmax) within 11-14 days, followed by a sustained release profile over the dosing period of 1 month. The mean beta half-life values ranged from 5 to 10 days, and the mean apparent terminal half-life range was 11-17 days. The systemic exposure (Cmax and area under the plasma concentration-time curve (AUC)) of olanzapine and its two major metabolites, 10N‑glucuronide and N-desmethyl olanzapine, increased in an approximate dose-proportional manner over the clinically relevant dose range of 283 mg through 566 mg. The relative bioavailability of TV-44749 SD and MD compared with oral olanzapine after single or multiple doses was 112% (90% confidence interval (CI) 97, 129%) and 95% (90% CI 86, 106%), respectively. There were no grade ≥3 adverse events, no serious treatment-related adverse events, no suspected or confirmed post-injection delirium/sedation syndrome events, and no deaths.

CONCLUSION: TV-44749 administration resulted in a sustained release profile and comparable exposure to daily therapeutic doses of oral olanzapine over a monthly dosing interval. The TV-44749 systemic safety profile was consistent with approved oral olanzapine. The local tolerability was acceptable, and there were no PDSS events. These results contributed to the dose selection of TV-44749 in a phase III study evaluating its efficacy and safety in adults with schizophrenia (SOLARIS; NCT05693935).

PMID:41632432 | DOI:10.1007/s40261-025-01507-x

Photochem Photobiol Sci. 2026 Feb 3. doi: 10.1007/s43630-025-00843-3. Online ahead of print.

ABSTRACT

The widespread presence of pharmaceuticals and antibiotics in aquatic environments poses a serious ecological and public health risk, necessitating effective removal strategies. This study investigates a Z-scheme Ag/Ag₃PO₄/g-C₃N₄ photocatalyst for the simultaneous photodegradation of sulfamethoxazole, trimethoprim, naproxen, and diclofenac under visible light, a topic that has not been previously reported. The photocatalyst was comprehensively characterized using XRD, XPS, FTIR, BET, FESEM-EDX, TEM, EIS, PL, and DRS. Among the synthesized variants, Ag/Ag₃PO₄/g-C₃N₄ (80%) exhibited the highest photocatalytic efficiency. Optimal operational parameters (pH 6, 30 min irradiation, and 1.170 g L⁻¹ catalyst dosage) were established using response surface methodology based on a central composite design. Under these conditions, complete pollutant removal was achieved, with a total organic carbon (TOC) reduction of 88.62% after 180 min. Kinetic studies followed a pseudo-first-order model, and scavenger tests identified photogenerated holes (h⁺) as the dominant reactive species. Transformation products were identified using LC/MS. The photocatalyst retained high activity after five reuse cycles, confirming its stability and reusability. The superior performance is attributed to the Z-scheme mechanism and silver-induced surface plasmon resonance (SPR). The integration of advanced nanostructuring, heterojunction interface engineering, and statistical optimization enables efficient degradation of pharmaceutical mixtures at environmentally relevant concentrations in real water samples, highlighting its strong potential for sustainable water purification applications.

PMID:41632422 | DOI:10.1007/s43630-025-00843-3

Dig Dis Sci. 2026 Feb 3. doi: 10.1007/s10620-026-09678-z. Online ahead of print.

ABSTRACT

BACKGROUND: Propofol is the most commonly used intravenous anesthetic for endoscopic surgery, although it comes with various adverse effects. Research indicates that Remimazolam, which is considered a safe general anesthetic, is being increasingly adopted as an alternative to propofol in clinical settings. Our meta-analysis sought to evaluate whether the rate of adverse reactions associated with Remimazolam in gastrointestinal endoscopic procedures is acceptable, and whether its surgical success rate is at least comparable to that of propofol.

METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched five electronic databases (PubMed, Scopus, Cochrane Library, Embase, and Web of Science) to identify eligible studies published up to January 2025. Using R version R.4.4, we reported outcomes as risk ratios (RRs) or mean differences (MDs) and confidence intervals (CIs). A P-value of ≤ 0.05 is considered statistically significant.

RESULTS: Our meta-analysis included 37 studies encompassing 8533 patients. The results, analyzed using a random effects model, demonstrated no statistically significant difference in induction time between the two sedative groups, with an overall MD of 0.11 min (95% [- 0.10; 0.31], p = 0.2977). Patients in the Remimazolam group experienced longer total sedation times than those receiving Propofol, with an MD of 1.84 min (95% CI [0.61; 3.07], p = 0.0033). The pooled analysis indicated low heterogeneity (I² = 4.2%). There was no statistically significant difference between the two sedatives in procedure time, with an MD of 0.16 (95% CI: [-0.13; 0.45], p = 0.2689). The pooled analysis displayed moderate heterogeneity (I² = 43.5%, p = 0.0052).

CONCLUSION: Remimazolam has demonstrated safety, showing a reduced incidence of hypotension, bradycardia, respiratory depression, and hypoxemia compared to propofol. However, efficacy outcomes including the induction time and total procedure time were comparable between the two groups. However, the results were heterogeneous, which could be due to variability in the perfumed procedures, co-analgesics or dosing.

PMID:41632411 | DOI:10.1007/s10620-026-09678-z