Importance: With blood-based phosphorylated tau biomarkers soon to be used for diagnosis of Alzheimer disease, analyzing tau levels in other conditions could enhance biomarker interpretability. Moreover, mechanisms of tau release into circulation remain unclear.
Objective: To evaluate concentrations of phosphorylated and nonphosphorylated tau variants in the blood of patients with multiple traumatic injuries on days 0, 1, 5, and 10 and investigate biological processes driving tau release.
Design, setting, and participants: This multiple-trauma cohort (injury severity score, ≥18) included 45 severely injured patients with (n = 27) and without (n = 18) moderate-to-severe traumatic brain injury on emergency computed tomographic imaging. Controls consisted of 24 healthy volunteers. Participants were recruited from December 1, 2013, to October 31, 2022. Blood samples were analyzed for brain-derived tau (BD-tau), total tau (t-tau), and phosphorylated tau 217 (p-tau217) and 231 (p-tau231) levels. Associations among tau concentrations, clinical data, and outcome (eg, Glasgow Coma Scale [GCS] score) were assessed. Data were analyzed from March 1, 2023, to September 30, 2024.
Exposures: Serum BD-tau, t-tau, p-tau217, and p-tau231 levels.
Results: A total of 214 serum samples were analyzed. Median age of the 45 patients was 48 (IQR, 33-60) years (35 [77.8%] male); median age of the 24 controls, 43 (IQR, 28-50) years (16 [66.7%] male). Median serum levels of tau variants were increased in patients with multiple traumatic injuries at day 0 compared with controls (t-tau: 43 [IQR, 21-95] vs 3 [IQR, 3-5] pg/mL; BD-tau: 78 [IQR, 30-343] vs 2 [IQR, 2-3] pg/mL; p-tau231: 61 [IQR, 21-79] vs 2 [IQR, 1-3] pg/mL; all, P < .001). Only median BD-tau levels remained elevated until day 10 (day 1, 25 [IQR, 14-69] pg/mL; day 5, 9 [IQR, 4-15] pg/mL; day 10, 8 [IQR, 4-18] pg/mL). Median tau levels at admission were higher in patients with lower GCS scores (BD-tau: 107 [ IQR, 59-838] vs 33 [IQR, 24-78] pg/mL [P = .01]; p-tau231: 76 [IQR, 36-114] vs 28 [IQR, 9-63] pg/mL [P = .02]). Elevated median tau levels were also observed in patients with hemorrhagic shock vs those without shock (eg, BD-tau on day 0: 113 [IQR, 78-378] vs 31 [IQR, 24-61] pg/mL; P = .002) and in nonsurvivors vs survivors with uncomplicated courses (eg, BD-tau on day 1: 92 [IQR, 22-527] vs 16 [IQR, 7-23] pg/mL; P = .009).
Conclusions and relevance: In this exploratory study among a cohort of patients with multiple traumatic injuries, levels of tau variants reflected both direct and indirect neurological injury, with BD-tau showing the most persistent elevation in the acute phase.
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.
Importance: Australia is leading the world in efforts to reduce tobacco use by implementing high cigarette taxes and restrictive regulations on nicotine vaping products. However, concerns have emerged that these policies may unintentionally drive the expansion of illicit tobacco and vaping markets, potentially undermining public health gains.
Objectives: To assess spatial and temporal changes in total nicotine, tobacco-derived nicotine, and illicit tobacco use across Australian regions of different remoteness from 2017 to 2023.
Design, setting, and participants: This longitudinal, cross-sectional wastewater study was performed from April 2017 to April 2023. Wastewater samples were collected from as many as 55 wastewater treatment plants (WWTPs) in Australia, including 3 remoteness levels: major cities, inner regional, and outer regional to remote areas. The selected WWTPs serve more than 50% of the Australian population.
Main outcomes and measures: Nicotine metabolites (cotinine and hydroxycotinine) and the tobacco-specific alkaloid (anabasine) were analyzed in wastewater samples using a validated liquid-chromatography tandem mass spectrometry method. Total nicotine and tobacco-derived nicotine consumption were back-estimated. Illicit tobacco use was identified in combination with the tobacco sales data.
Results: Wastewater samples collected across Australia, representing 14 million people, were analyzed for back-estimation. Total nicotine consumption declined fastest in outer regional to remote areas (-2.2% annually; 95% CI, -3.2% to -1.1%), followed by inner regional areas (-1.4% annually; 95% CI, -2.1% to -0.8%), and remained stable in major cities. By comparison, tobacco-derived nicotine consumption decreased faster in major cities (-5.0% annually; 95% CI, -8.3% to -1.9%) and inner regional areas (-9.8% annually; 95% CI, -12.5% to -7.3%) than in the outer regional to remote areas (-2.3% annually; 95% CI, -6.0% to 1.8%). Illicit tobacco use was estimated to have increased from 1350 to 3400 tons from 2017 to 2023.
Conclusions and relevance: In this cross-sectional study of wastewater surveillance in Australia, different trends of tobacco use were observed across regions, accompanied by increasing use of illicit tobacco and vaping products. These findings provide evidence for future tobacco and vaping control policies. Ongoing wastewater monitoring is essential for evaluating new tobacco and vaping product control measures implemented in 2024.
Importance: Current interpretation services for Deaf patients who use sign language are often ineffective or unacceptable. In-person interpretation is frequently unavailable, and while video remote interpreting (VRI) remains underused, its scalability may be a solution given interpreter shortages and cost barriers. Existing research focuses on user and interpreter preferences, leaving a critical gap in understanding how interpretation formats affect communication quality.
Objective: To evaluate the effectiveness of VRI in improving communication outcomes between Deaf patients and physicians compared with usual communication tools, such as self-arranging interpretation, lip-reading, note-taking, and the use of images.
Design, setting, and participants: This randomized clinical trial was conducted in Colombia at a public hospital from August 2023 to October 2024, involving Deaf adults who use Colombian Sign Language as their primary language. Participants were randomly assigned to either the control or intervention group. The data were analyzed between January and May 2025.
Interventions: Patients were divided into 2 groups: an intervention group that received a medical appointment via VRI and a control group that received one via the current standard of communication. Both the Deaf participants and the health care professionals were blinded to the allocation.
Main outcomes and measures: An assessment of communication using the Doctor-Patient Communication scale.
Results: Data were collected from 210 Deaf participants, including 123 (58.6%) women and 87 (41.4%) men, with a mean (SD) age of 42 (13) years (range, 18-84 years). Overall, 108 participants (51.4%) reported using VRI. The intervention revealed that having VRI did not always result in improved communication between Deaf individuals and physicians. While those using VRI were more likely to report positive outcomes in certain areas, such as being encouraged to express themselves (odds ratio, 1.90; 95% CI, 1.13-3.18; P = .02), there was no difference in other areas, such as understanding the doctor (OR, 1.33; 95% CI, 0.79-2.23; P = .28).
Conclusions and relevance: In this randomized clinical trial of VRI in the health care context, some aspects of clinical communication were improved, but others were not. This suggests that critical preconditions have to be met for this technology to achieve its intended impact.
Trial registration: ClinicalTrials.gov Identifier: NCT05966623.
Importance: Intravascular catheters are essential in health care but remain a major source of health care-associated infections. Optimal skin antisepsis before insertion is key, yet the most effective antiseptic agent, concentration, and formulation remain uncertain.
Objective: To determine the concentration and formulation of chlorhexidine gluconate (CHG) or povidone-iodine (PVI) associated with the lowest incidence of catheter-related infections (CRIs).
Data sources: PubMed, EMBASE, Cochrane Central, Scopus, Web of Science, and CINAHL were searched through January 7, 2025, without restrictions. Trial registries and reference lists of relevant studies and guidelines were reviewed.
Study selection: Randomized clinical trials (RCTs) comparing CHG- or PVI-based skin antisepsis before insertion of intravascular catheters were eligible if they reported at least 1 CRI outcome (catheter-related bloodstream infection [CRBSI], catheter tip colonization, or local infection). Two independent reviewers screened titles, abstracts, and full texts.
Data extraction and synthesis: Data were extracted independently by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed with the Cochrane risk of bias 2 tool. A random-effects network meta-analysis (NMA) was performed to estimate relative risks (RRs) with 95% CIs.
Main outcomes and measures: The primary outcomes were incidence of CRBSIs, catheter tip colonization, and local infections associated with CHG or PVI formulations.
Results: Sixteen RCTs (7803 patients; 11 985 catheters) met inclusion criteria. When compared with aqueous formulations, alcohol-based formulations were consistently associated with lower infections rates, with isopropyl alcohol being superior to ethanol. Compared with alcoholic PVI, alcoholic CHG was associated with lower CRBSIs (RR, 0.70 [95% CI, 0.45 to 1.08]), catheter tip colonizations (RR, 0.42 [95% CI, 0.37 to 0.48]), and local infections (RR, 0.40 [95% CI, 0.23 to 0.70]). High concentration CHG (1% or higher) further lowered CRBSIs (RR, 0.31 [95% CI, 0.19 to 0.52]) and colonization (RR, 0.36 [95% CI, 0.30 to 0.42]) compared with lower concentrations. Local adverse events were uncommon, slightly more frequent with alcohol-based formulations, and similar between CHG and PVI.
Conclusions and relevance: In this NMA of RCTs, high concentration CHG in isopropyl alcohol was associated with the lowest incidence of CRIs. These results suggest that alcoholic PVI and aqueous formulations should be reserved for situations in which CHG or alcohol cannot be used.
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