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This investigation addressed influences of CYP2B6 and CYP2C19 genetic polymorphisms on steady-state bupropion disposition, antidepressant outcomes and side effects, and evaluated influences of pharmacokinetic variability on pharmacogenetic results. This was a preplanned secondary analysis of a prospective, 24-week, randomized, double-blind, crossover trial which compared pharmacokinetics and antidepressant effects across brand and 3 generic bupropion XL 300 mg drug products in 70 participants with major depressive disorder in remission, who were genotyped for CYP2B6 and CYP2C19 polymorphisms. We measured steady-state enantiomeric plasma and urine bupropion and primary (hydroxybupropion, a bioactivation pathway), reduced, and secondary metabolites, clinical depression (Montgomery-Asberg depression rating scale), side effects, and influence of CYP2B6 and CYP2C19 polymorphisms on bupropion disposition and drug effects across all 4 drug products (pooled analysis). Results showed that CYP2B6 polymorphisms (CYP2B6∗6 allele and the 516G>T variant alone) had a significant influence on bupropion disposition, including apparent oral clearance and enantiomers hydroxylation. Since bioactivation via bupropion hydroxylation has therapeutic importance, CYP2B6 polymorphisms could be clinically relevant. However, there were no significant differences between CYP2B6∗6 or 516G>T gene groups in either depression or side effect scores, at baseline on patients' own bupropion, or during the crossover phase of 4 bupropion products. CYP2C19 polymorphisms had a small and clinically unimportant influence on bupropion minor metabolites and secondary metabolism, and no effect on depression or side effect scores. Results show that CYP2B6 polymorphisms significantly influenced bupropion enantiomers steady-state disposition, but not long-term antidepressant or side effects. These findings may have relevance for clinical pharmacogenetic testing in depression. SIGNIFICANCE STATEMENT: This pharmacogenetic study in major depressive disorder evaluated both pharmacokinetics and clinical effects. CYP2B6 polymorphisms (CYP2B6∗6 allele, 516G>T variant) had significant influence on steady-state bupropion enantiomers apparent oral clearance and hydroxylation, but there was no association between CYP2B6∗6 or 516G>T gene groups and either depression or drug side effects. CYP2C19 polymorphisms had a small and clinically unimportant influence on bupropion minor metabolites and secondary metabolism and no effect on depression or side effect scores. These results may have implications for genetic testing in bupropion pharmacotherapy of major depressive disorder.

Functional brain networks support human cognition, yet how individualized network architecture emerges in early childhood remains poorly understood. Averaging across participants can obscure age-specific organization and person-to-person differences, particularly in slowly developing association cortices. We developed an age-appropriate functional reference that captured common structure across toddlers without averaging away individual variability, enabling estimation of each child's networks from resting-state fMRI. Across cohorts of 8-60-month-old children, we found individualized network organization-including finer-scale subdivisions and emerging language lateralization-well before age five. Network layouts showed longitudinal stability, with greater consistency in sensory than association regions. Within-network connectivity was stronger and explained age-related variance when networks were defined using individualized rather than group-consensus topography. Left-lateralization of language networks tracked age-normalized verbal ability, linking early functional architecture to emerging cognition. These findings show that behaviorally relevant brain networks arise far earlier than previously recognized, providing a foundation for studying typical development and early biomarkers.

Ehlers-Danlos syndrome (EDS) is a group of inherited disorders affecting collagen and extracellular matrix proteins, which can cause skin hyperelasticity, joint hypermobility, atrophic scarring, and blood vessel fragility. Complications include joint dislocation, chronic pain, fatigue, functional gastrointestinal disorders, mast cell hyperactivity, orthostatic intolerance, anxiety disorders, and pelvic and bladder dysfunction, among others. This article discusses the orthopedic concerns and complications, diagnosis, genetic testing, and multidisciplinary approach to management in EDS patients. A comprehensive review of the literature in PubMed was performed, focusing on EDS and its orthopedic implications, diagnosis, genetic testing, and management. Search terms included EDS with/without diagnosis, orthopedics, and management. Peer-reviewed journals were prioritized. Each source's credibility, findings, and level of evidence were organized by theme to synthesize the information. Literature within 5 years was prioritized. However, given the little information available about EDS, this was expanded to include landmark and highly relevant sources. EDS patients often have weak spinal muscles, deformities, and reduced column support leading to joint instability, recurrent dislocations, and chronic pain. Diagnosis is primarily clinical, but identifying the type of EDS by the gene encoding the defect in collagen or other proteins is essential to guide management. Physical therapy, pain management, skin care, and nutrition form the cornerstone of EDS management. Orthopedic surgery to address orthopedic concerns such as joint stability is controversial due to the potential for complications and should be considered only after nonoperative medical treatments have failed. EDS presents unique considerations that must be addressed, especially when orthopedic intervention is being considered. Due to the unique symptom presentation, goals and care plans should be individualized. The orthopedic nurse plays a vital role throughout all phases of care and should be aware of the special considerations with patients with EDS. The focus of treatment should be on patient safety, symptom management, and the prevention of future injuries.

Investigation of the failure of shunts used to treat hydrocephalus has been a topic of research for several decades, though it is difficult to understand the role of heterogeneous patient ventriculomegaly shifts over time. In this work, we present the design, verification, and validation of a novel benchtop model of the human lateral and third ventricles. 3D models were rendered from MRI of pre-revision hydrocephalic patients (n = 6), printed in hollow High Impact Polystyrene (HIPS) molds, and injected with silicone rubber allowed to rotationally cure for three hours. Wall thickness of the ventricle models was measured via random point sampling (n = 300), assessing distribution of silicone rubber within the mold. One sample z-test was used to compare mean wall thickness to the target thickness of 1 mm. To visualize the inner volume post-hoc, expanding polyurethane foam was injected into ventricle models, creating negatives of the hollow molds. The negatives were 3D scanned and measured for frontal horn diameter, occipital horn diameter, Evan’s Index, Frontal-Occipital-Horn Ratio, and frontal horn volume. A single MRI was chosen for verification of repeatability (n = 11). Ventricular size was validated across models from patients (n = 6). Accuracy of ventricular expansion (indirect compliance assessment) was tested. For all tests, a confidence interval was set at 0.95 (α = 0.05). The verification methods indicated that low variance of experimental clinical values were observed between ventricle model replicates. Nominal-actual comparison results consistently showed similar datapoint displacement densities between models. Validation showed that most ventricle geometries fell within 5% of MRI measurements. A strong positive correlation was observed between internal pressure and volume (R2 = 0.9932). Experimental Frontal Horn and Occipital Horn Diameter measurements compared to clinical observations showed anatomical accuracy. This study validates and verifies a model of the human ventricular system with arbitrarily chosen heterogeneous patient ventricles of varying morphologies and volumes. Paired with a pump, this model can be used to recapitulate cerebrospinal fluid flow. We show the recreation of patient-specific clinical lateral ventricle characteristics of size, shape, and static compliance control necessary to study the influence of these parameters on shunt function. The manufacturing process has the capacity to create accurate benchtop models of the lateral and third ventricles with geometric detail that should be refined over time with additive systems accounting for cranial viscoelastic compliance and varying material properties with elastic and shear moduli more similar to brain. The online version contains supplementary material available at 10.1186/s12987-025-00742-w.

Engaging interest-holders in health care evidence syntheses may make evidence syntheses more relevant, useful, and accessible. However, the best way(s) to engage interest-holders within the evidence synthesis process remain unknown. A previous scoping review collated 291 publications that reported interest-holder engagement in evidence syntheses, but conclusions were limited due to poor reporting. In the present scoping review, our aim was to identify and collate up-to-date publications focussed on interest-holder engagement in healthcare evidence syntheses, describe reported methods of engagement, and compare the results with those from the previous review. We updated a scoping review, following JBI guidance, using a pre-published protocol that defined all key terminology in this field. We systematically searched five electronic databases (MEDLINE, CINAHL, EMBASE, PsycInfo, and SCOPUS). Searches were conducted from January 2016 to February 2024. Records were imported into Covidence and screened by pairs of independent reviewers, including any publications that reported engagement of interest-holders in evidence syntheses. We extracted and coded key data relating to the evidence synthesis topic and ACTIVE framework domains (who was engaged, when, and in what way). Two reviewers independently made a judgment of the comprehensiveness of the description of methods of engagement, using a "traffic-light" system, coding evidence syntheses with comprehensive descriptions as "green," brief or partial descriptions as "amber," and those with few details as "red"; disagreements were resolved through discussion. Additional detailed data relating to the engagement methods were extracted from "green" evidence syntheses. Any disagreements were resolved through discussion. Data were synthesized within tables, and narrative summaries were written to provide an overview of key methods of engaging interest-holders within the identified evidence syntheses. We identified 302 publications published since the previous review. Most (272/302, 90%) reported interest-holder engagement in a single evidence synthesis; of these, 74% (200/272) engaged patients and/or their carers, while 17% (46/272) engaged other interest-holders only, and the remainder (26/272, 9.6%) was unclear. Over three-quarters of the evidence syntheses were conducted either in the United Kingdom, United States, Canada, or Australia (215/272, 79%). Most often (113/272, 42%), interest-holders were engaged at both the initial (scope and question setting) and final (interpretation of results) review stages (referred to as a "top and tail" approach). Nineteen percent (51/272) were judged to provide a comprehensive ("green") description of one or more method(s) or approach(es) to engagement in an evidence synthesis, enabling detailed data extraction and description. Most: engaged patients/public members and other interest-holder groups (30/51, 59%); used a "closed" recruitment strategy (30/51, 59%); engaged interest-holders during the stage of interpretation of findings (39/51, 76%); had at least one interest-holder as a co-author (27/51, 52%). Interest-holders generally attended meetings at which no formal methods of engagement were used. It was common to engage interest-holders in multiple activities throughout the review process. Our international team from the MuSE consortium has updated a previous scoping review, compiling the latest evidence on interest-holder engagement in evidence syntheses. We collated 302 publications and described the methods of interest-holder engagement reported in 51 evidence syntheses that we judged provided the most comprehensive information. Interest-holders have been involved at all stages of the process, using a wide range of engagement approaches, but with no clear patterns linked to the type or focus of evidence syntheses. Most commonly, patients/public and professional interest-holders were both engaged, but around one-quarter of our examples only engaged patients/public members, and a small number only engaged professional interest-holders. We identified some distinct engagement strategies and have used these to inform a potential decision tool to support the selection of engagement strategies. We propose recommendations in relation to the conduct and reporting of interest-holder engagement in evidence syntheses and future research to advance this field.

Several radiological signs have been recognized as valuable adjuncts to clinical criteria in the diagnosis of normal pressure hydrocephalus (NPH). Certain magnetic resonance imaging (MRI) findings may also provide information on postoperative outcomes following ventricular shunting. However, the evidence remains inconclusive. We conducted a retrospective cohort study including patients from our institution's Clinical Care Center for NPH. Preoperative MRI findings-specifically Evan's Index (EI), callosal angle (CA), disproportionately enlarged subarachnoid space hydrocephalus (DESH), and periventricular white matter hyperintensities (PWMH)-were analyzed in relation to pre- and postoperative clinical status. The median age was 80 years (IQR 75-85), and 68.3% of patients were males. All patients exhibited gait disturbances, 93.3% cognitive impairment, and 83.3% urinary symptoms. Median EI was 0.35 (IQR 0.33-0.37) and median CA was 85.2° (IQR 80-90). DESH was present in 60% of patients, while PWMH were detected in 48.3%. At 1-month follow-up, gait improvement was observed in 66.6%, urinary improvement in 75.6%, and cognitive improvement in 83.0%; sustained at 12 months in 63.8%, 63.8%, and 69.0%, respectively. PWMH correlated with gait improvement (p = 0.04), and DESH with cognitive improvement at 12 months (p = 0.02). DESH and PWMH demonstrated domain-specific prognostic value in idiopathic NPH, whereas EI and CA showed limited predictive utility. Imaging parameters should be interpreted in conjunction with clinical evaluation for outcome prediction.

Pervasive marine pollution can have devastating effects on ocean health. Polychlorinated Biphenyls (PCB), Polycyclic Aromatic Hydrocarbons (PAH), and Organochlorine Pesticides (OCP) are particularly relevant given their high level of toxicity and carcinogenicity. These compounds originate from anthropogenic activity, therefore are often ubiquitous in coastal environments close to human sources. Marine turtles in coastal Florida (USA) are affected by fibropapillomatosis, a tumor-causing panzootic with highly debilitating symptoms. Despite repeated associations between fibropapillomatosis occurrence and carcinogenic pollution, the ecotoxicological status of high disease areas in Florida's Gulf coast has been unknown. Our study deployed passive sampling devices along a structured inshore-to-offshore coastal grid to generate the first comprehensive dataset on the concentration and diversity of oncogenic pollutants in Crystal River, Florida, where juvenile green turtles exhibit a fibropapillomatosis prevalence of 74%. Multiple OCP, PAH, and PCB compounds were detected for a total chemical concentration of 16,086.98 pg/L (Σ OCP 45.51 pg/L + Σ PAH 16,014.53 pg/L + Σ PCB 26.94 pg/L). Density and composition of carcinogenic pollution was found to be significantly lower offshore compared to inshore green turtle habitats (p = 0.02), suggesting multiple potential contamination sources along the coastline. The carcinogenic compounds detected have been shown to have associations with fibropapillomatosis in other parts of the world, as well as having wider ecosystem implications. Our work contributes to the body of knowledge correlating the emerging threat of harmful ocean pollution and marine wildlife diseases.

Stiffness is a key mechanical property of tendon, relevant to both injury and athletic performance. Traditionally, stiffness is measured as tendon elongation in response to applied loading (tensile stiffness), requiring specialized equipment and methods. The MyotonPRO, a handheld device that delivers a small, rapid perturbation and measures dynamic stiffness from the resulting tissue oscillations, has emerged as a fast, user-friendly alternative. However, it assesses stiffness perpendicular to the tendon's primary axis and may not be appropriate as a surrogate for tensile stiffness. Tensile stiffness of the Achilles tendon was obtained from 18 healthy individuals using a combination of 3D motion analysis, passive ankle rotations performed on a dynamometer, and ultrasonography. Dynamic stiffness was obtained at a neutral ankle angle under resting conditions from a standardized location superficial to the Achilles tendon mid-portion using the MyotonPRO. Regression analysis showed a low correlation (R2 = 0.17) between the two methods. Tensile stiffness was consistently greater than dynamic stiffness (114 ± 63 N/mm vs. 1.04 ± 0.27 N/mm). Bland-Altman analysis showed wide limits of agreement (-11.0 to 236.7 N/mm), and proportional bias (R2 = 1) reflected a difference in scale. The poor agreement suggests the two methods are not interchangeable. The discrepancy likely reflects fundamental differences in measurement orientation and tissue behavior due to tendon anisotropy. Caution is warranted when interpreting MyotonPRO-derived stiffness, which may not reflect the same functional properties captured by tensile measurements.

Practicing CBT skills outside of therapy sessions is a core component of effective treatment, yet meaningful engagement can be difficult during periods of elevated psychological distress. Smartphone-based ecological momentary interventions (EMIs) offer a promising approach to support real-time skill use, but most research has focused on frequency rather than quality of engagement. This study examined the quality of CBT skills practice in a 28-day smartphone-based EMI following inpatient discharge and explored its associations with internal context and intervention effectiveness. Twenty-three adults hospitalized for suicidal thoughts and behaviors participated, selecting and practicing one of three guided CBT skills exercises (Mindful Emotional Awareness, Countering Emotional Behavior, or Cognitive Flexibility) up to three times daily. A structured coding system was used to rate the completeness and relevance of 945 total exercises (0-2 scale). Quality varied primarily within individuals and was lower during moments of high suicidal intent and urge. When combining across all skills, quality was not associated with proximal change. However, higher-quality Countering Emotional Behavior practice predicted greater reductions in suicidal intent, and higher-quality Countering Emotional Behavior and Cognitive Flexibility practice predicted greater reductions in anger. These findings suggest that momentary distress can impact engagement quality, and that the short-term impact of skills practice may depend on both the specific CBT strategy and type of distress targeted. Understanding and enhancing engagement quality is a key step toward optimizing mobile interventions for individuals in the midst of psychological distress.

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Previous research has attempted to quantify presence in virtual environments using event-related potentials (ERPs). We contend, however, that previous efforts have fallen short of fully realizing this goal, failing to either (A) independently manipulate presence, (B) validate their measure of presence against traditional techniques, (C) adequately separate the constructs of presence and attention, and/or (D) implement a realistic and immersive environment and task. We address these shortcomings in an ERP experiment in which participants play an engaging target shooting game in virtual reality (VR). ERPs are time-locked to the release of a ball from a sling. We induce breaks in presence (BIPs) by freezing the ball's release on a minority of trials. Embodiment is manipulated by allowing manual manipulation of the sling with a realistic avatar in one condition (embodied condition) and passive manipulation with only controllers in another (non-embodied condition). We find, in line with our preregistered predictions, that the N2, the P3b, and the N400 are selectively sensitive towards embodied BIPs, information extraction, and BIPs regardless of embodiment, respectively. The pattern of findings carries significant implications for theories of presence, which have been seldom addressed in previous ERP investigations on this topic.

Treatment options for metastatic castration-resistant prostate cancer (mCRPC) include androgen receptor pathway inhibitors (ARPIs), taxanes, radium-223, Lu-PSMA, poly (ADP-ribose) polymerase inhibitors, and immunotherapy in select patients. Resistance to ARPIs and hormone-based therapies has been associated with AR-ligand-binding domain mutations that can lead to promiscuous stimulation by other steroid hormones. There is a need to explore alternative targets and develop next-generation ARPIs or combination therapies that overcome this resistance. We describe the rationale and design of the randomized phase III trials OMAHA-003 (NCT06136624) and OMAHA-004 (NCT06136650), which will evaluate the efficacy and safety of opevesostat, a steroidogenesis inhibitor, versus ARPI switch in previously treated mCRPC. Results may support opevesostat as a potential new treatment option for mCRPC.Clinical trial registration: www.clinicaltrials.gov identifiers are NCT06136624 and NCT06136650. OMAHA-003 and OMAHA-004 are clinical studies that will test opevesostat (MK-5684) in people with advanced prostate cancer. Opevesostat is a drug that stops the body from producing all types of steroid hormones that fuel prostate cancer. Opevesostat is taken by mouth as a tablet. Adult men who have prostate cancer that worsened during treatment with androgen deprivation therapy, a type of treatment that reduces sex hormone levels in the body, are eligible to take part in the studies. For participation in OMAHA-003, men will have prostate cancer that worsened during or after treatment with 1 androgen receptor pathway inhibitor, which is a newer therapy to reduce sex hormone levels, and 1 or 2 taxane-based chemotherapies for cancer that has spread from where it started. For participation in OMAHA-004, men will have prostate cancer that worsened during or after treatment with 1 androgen receptor pathway inhibitor for hormone-sensitive or castration-resistant prostate cancer that has or has not spread from where it started. Participants in the studies will be assigned to 1 of 2 groups to compare opevesostat (group 1) to currently available hormonal therapies (group 2), which work by decreasing the amount of male sex hormones in the body, to learn the effects on radiographic progression-free survival (how long people live without their cancer worsening); overall survival (how long people live after starting treatment); safety, such as common side effects; and quality of life, such as improvement in people’s daily living. Both studies will take place in locations around the world.

Age-related macular degeneration is a common ocular disease that causes vision loss in the elderly, with a complex set of risk factors and proposed mechanisms of pathogenesis. A powerful method for investigating changes in disease is metabolomics, by which small molecules can be identified and quantified simultaneously. We report here the metabolic analysis of human RPE-choroid tissue in aging and macular degeneration (AMD), as well as comparisons of human macular and extramacular RPE-choroid and neural retina. Levels of 215 metabolites were determined in young donors, AMD donors (early/intermediate, geographic atrophy, and neovascularization) and age-matched controls. The largest number of metabolite differences were observed between young and healthy aged controls, as opposed to between aged controls and any stage of AMD. Two notable metabolites found to be increased in aging choroids are trimethylamine N-oxide and uric acid, both of which were significant after Bonferroni correction. A mouse endothelial cell line treated with a high concentration of uric acid exhibited reduced migration in a wound closure assay. This study provides initial insights into the metabolome of human choroids in varying states of age and macular degeneration, as well as functional implications of these changes in the aging choroid.

Although desert dust is the most abundant atmospheric aerosol by mass, its longwave radiative effects remain unclear, obscuring the impacts of dust on weather and climate. Here, using a data-driven analytical model constrained by observations, we show that scattering and absorption of longwave radiation by dust heats the planet by +0.25 ± 0.06 W m⁻² (90% confidence). This is nearly twice the value simulated by current climate models, which omit longwave scattering and underrepresent super coarse dust (diameter > 10 μm). These omissions bias modeled surface energy fluxes, cloud responses, precipitation, and atmospheric circulation. At the global scale, the sign and magnitude of the net dust direct radiative effect remain uncertain, with additional work needed to constrain shortwave cooling effects. These findings show that improving the representation of dust interactions with longwave radiation can improve weather forecasting and is essential to resolve the role of dust in climate change.

We sought to identify efficient tumor molecular profiling strategies for patients with newly diagnosed stage III-IVA endometrial cancer. We constructed a decision tree model to compare molecular profiling strategies. We considered testing options of mismatch repair (MMR), p53, and HER2 immunohistochemistry (IHC), and next generation sequencing (NGS, assessing for MMR protein, TP53 and POLE mutations). Strategies included (1) MMR/p53: MMR/p53 IHC at diagnosis, with HER2 IHC if p53 abnormal and NGS reserved for first progression/recurrence; (2) Selective NGS: MMR/p53 IHC at diagnosis, with immediate NGS and HER2 IHC if p53 abnormal, otherwise NGS at recurrence; (3) Universal NGS: NGS and HER2 IHC at diagnosis for all. Molecular subtype prevalence and six-year recurrence-free survival by subtype were derived from the GOG-0258 randomized trial. Outcomes included costs (2024 US$), timely NGS results (results available at recurrence/progression), and unnecessary NGS (NGS performed in patients who remained recurrence-free). Universal NGS resulted in unnecessary NGS in 57% of patients who remained recurrence-free, compared with 7% under the Selective NGS strategy and 0% with MMR/p53. MMR/p53 was the least costly strategy (mean cost $3772), followed by Selective NGS ($4186) and Universal NGS ($6250). Compared with MMR/p53, Selective NGS cost $2571 per additional timely NGS result, while Universal NGS cost $7600 per additional timely NGS result compared with Selective NGS. Selective molecular profiling of newly diagnosed stage III-IVA endometrial cancers using MMR and p53 IHC with reflex to NGS for p53-abnormal tumors improves testing efficiency and reduces unnecessary NGS compared with universal upfront NGS testing.

What is known? Hip fractures are debilitating osteoporotic fractures that are increasingly pervasive in our aging population. SES has an overarching influence on health outcomes and well-being, having already been proven in other morbid diseases. What is new? Overall, this study demonstrates that hip fracture patients experience poorer perioperative quality of life at different time points based on SES, though both groups recuperate to attain comparable outcomes by 1 year. What is the impact? Our findings suggest that hip fracture prevention should be emphasised across all socioeconomic strata. Health policies and coverage should be re-examined in the aging population, especially the need for mental health support during immediate recovery. Hip fractures are increasingly prevalent in our fast-aging population, but effects of socioeconomic status (SES) on these patients' perioperative wellbeing are not well understood. This study aims to investigate the effect of SES, represented by hospital ward class, on perioperative function and health-related quality of life (HRQoL) in hip fracture patients. Four hundred forty-five hip fracture patients were prospectively followed up and categorised into private (PTE) and government-subsidised (SUB) ward classes as a surrogate for SES. Patients were evaluated using Parker Mobility Score (PMS), EuroQol-5 Dimensions (EQ-5D) and Short Form-36 (SF-36; including Physical Function [PF] and Mental Health [MH]) scores premorbidly, and postoperatively at 3 months, 6 months and 1 year. Group PTE scored significantly higher in PMS across all time points and in PF at 6 months (42.5 ± 27.3 vs 35.0 ± 29.1, p = 0.033) postoperatively. Group PTE also had superior EQ-5D scores at 3 (0.620 ± 0.282 vs 0.497 ± 0.325, p = 0.002) and 6 months (0.715 ± 0.268 vs 0.576 ± 0.334, p = 0.001) postoperatively. Group PTE had higher MH scores at 3 months (85.9 ± 15.0 vs 80.9 ± 18.1, p = 0.014) postoperatively, though its scores continued to decline by 6 months. Changes over time in EQ-5D scores favoured Group PTE (p = 0.016). Both groups had an overall decline at 3 months before gradually returning towards baseline at 1 year. This study highlights SES-based disparities in hip fracture patients perioperatively, though both groups converge to comparable outcomes by 1 year. Health policies should consider MH support during recovery for all, regardless of SES.

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British Columbia (BC), Canada, continues to experience persistently high rates of unregulated drug toxicity. While the presence of fentanyl in the drug supply is well-established, less is known about how fluctuations in its concentration may influence mortality at the population level. This study describes geographic variation and temporal trends in fentanyl concentrations across BC and assesses if they are associated with unregulated drug toxicity rates. Using a validated machine learning model that quantifies fentanyl and fluorofentanyl concentrations in unregulated opioid samples, we estimated concentrations in samples submitted to BC drug checking services from October 2018 to June 2025. We derived monthly median concentrations by geographic health service delivery area to determine historic monthly typical fentanyl strength. We then examined the relationship between fentanyl concentrations and unregulated drug toxicity mortality rates using a generalized additive mixed model (GAMM), accounting for regional heterogeneity, temporal trends, and autocorrelation. Median fentanyl concentrations varied geographically and temporally across the province, peaking provincially at 11.0% in mid-2023 before declining to 5.1% in early 2025. The GAMM estimated that, on average, each 1-percentage point increase in median fentanyl concentration was associated with a 0.072 increase in the monthly drug-related mortality rate per 100,000 population (p = 0.029). Quantifying fentanyl concentrations from point-of-care drug checking data enables detection of geographic and temporal patterns in the unregulated drug supply and their associations with drug-related mortality. This approach offers a tool for harm reduction, drug supply monitoring, and policy response during the ongoing drug toxicity crisis.

In this study, we sought to characterize the epidemiologic features of trauma in Eeyou Istchee and describe outcomes for patients referred to our institution. Our primary objectives were to better define the regional burden of injury, identify potentially hidden trauma mortality, and explore opportunities for injury prevention and trauma system optimization in this unique setting in northern Quebec. We conducted a retrospective review of our institutional trauma registry, identifying all trauma patients transferred to the Montreal General Hospital from Eeyou Istchee between 2012 and 2022. We extracted and analyzed patient demographics, mechanisms of injury, and outcomes. We also reviewed the coroner's reports for all trauma-related deaths in Eeyou Istchee over the same period. We used descriptive statistics for analysis. A total of 587 patients (aged 18 to 91 yr) were transferred, including 353 males (60.1%) and 234 females (39.9%). The highest number of transfers (n = 84, 14.3%) occurred in 2022. The most common mechanisms of injury were blunt trauma (n = 228, 38.8%) and falls (n = 163, 27.8%). We also observed motor vehicle collisions (n = 103, 17.5%) and penetrating trauma (n = 50, 8.5%), while 17 cases (2.9%) involved other mechanisms, and 26 (4.4%) were of unknown origin. Assault was reported by 211 (35.9%) patients. Of all patients, 146 (24.9%) were admitted, and 441 (75.1%) were discharged from the emergency department. Computed tomography was performed for 376 patients (85.3%), among whom 222 (59.0%) patients had no injuries identified. Coroner data identified 82 trauma-related deaths, including 61 males (74.4%) and 21 females (25.6%). Motor vehicle collisions were the most common cause of death (n = 23, 28.0%). The trauma-related mortality rate in Eeyou Istchee was 47.8 per 10 000 population, compared with 27.8 per 10 000 in the rest of Quebec, yielding a relative risk of 1.72. There is a marked disparity in trauma-related mortality between Eeyou Istchee and the rest of Quebec, with motor vehicle collisions representing the leading cause of trauma death. Strengthening partnerships with local communities in Eeyou Istchee is essential to enhance awareness, promote injury prevention, and improve trauma system effectiveness in the region. : Dans cette étude, nous avons cherché à cerner les caractéristiques épidémiologiques des traumas à Eeyou Istchee et à décrire les issues de ces traumas chez la patientèle dirigée vers notre établissement. Nos principaux objectifs consistaient à mieux connaître le fardeau régional des traumas, à déceler une mortalité par trauma possiblement occultée, ainsi qu’à explorer les possibilités en matière de prévention des blessures et d’optimisation du système de traumatologie dans le contexte particulier du Nord québécois. : Nous avons procédé à une revue rétrospective de notre registre institutionnel de traumatologie pour recenser toutes les victimes de traumas transférées de Eeyou Istchee à l’Hôpital général de Montréal entre 2012 et 2022. Nous avons extrait et analysé les données relatives aux caractéristiques démographiques, aux mécanismes de blessure, ainsi qu’aux issues. Nous avons également examiné les rapports du coroner concernant tous les décès liés à des traumas survenus à Eeyou Istchee durant la même période. Notre analyse reposait sur des statistiques descriptives. : Au total, 587 personnes (âgées de 18 à 91 ans) provenant d’Eeyou Istchee ont été transférées à notre établissement, dont 353 hommes (60,1 %) et 234 femmes (39,9 %). Le plus grand nombre de transferts a été recensé en 2022 (n = 84, 14,3 %). Les mécanismes de blessure les plus fréquents étaient les traumas contondants (n = 228, 38,8 %) et les chutes (n = 163, 27,8 %). Nous avons également observé des collisions de véhicules automobiles (n = 103, 17,5 %) et des traumas pénétrants (n = 50, 8,5 %); 17 cas (2,9 %) relevaient d’autres mécanismes traumatiques, et 26 cas (4,4 %) étaient d’origine inconnue. Des agressions avaient été signalées par 211 personnes (35,9 %). Sur l’ensemble des personnes transférées, 146 (24,9 %) ont été hospitalisées et 441 (75,1 %) ont reçu leur congé du service d’urgence. Un examen de tomodensitométrie a été réalisé chez 376 personnes (85,3 %); chez 222 (59,0 %) d’entre elles, aucune lésion n’a été décelée. Les données du coroner ont révélé 82 décès liés à des traumas, dont 61 touchaient des hommes (74,4 %), et 21, des femmes (25,6 %). Les collisions de véhicules automobiles constituaient la cause de décès la plus fréquente (n = 23, 28,0 %). Le taux de mortalité liée aux traumas à Eeyou Istchee s’élevait à 47,8 pour 10 000 personnes, comparativement à 27,8 pour 10 000 dans le reste du Québec, ce qui correspond à un risque relatif de 1,72. : Il existe une disparité marquée quant à la mortalité liée aux traumas entre Eeyou Istchee et le reste du Québec, où les collisions de véhicules automobiles sont la principale cause de décès. Le renforcement des partenariats avec les communautés d’Eeyou Istchee est essentiel pour améliorer la sensibilisation, promouvoir la prévention des blessures et renforcer l’efficacité du système de traumatologie dans la région.