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A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans

Depth-dependent microbial succession and interspecies hydrogen transfer drive pit mud maturation in Chinese strong-flavor baijiu fermentation.

Microbial communities in fermentation pit mud play a key role in determining the quality of Chinese strong-flavor baijiu (CSFB). However, the ecological processes underlying pit mud maturation across spatial and temporal scales remain unclear. In this study, amplicon sequencing and metagenomic analyses were employed to investigate the taxonomic succession, community assembly, and metabolic functions of bacterial and archaeal communities during the transition from fresh pit mud (FPM) to new pit mud (NPM) and old pit mud (OPM). A pronounced depth-dependent succession pattern was observed, with 4 cm representing a critical ecological boundary separating distinct community structures and maturation trajectories. During surface-layer maturation, community assembly shifted from stochastic to deterministic processes, accompanied by homogeneous selection and increasing network complexity. In contrast, stochastic processes remained dominant throughout deep-layer maturation. Metagenomic analyses revealed a functional transition from lactate and acetate production, primarily associated with Lactobacillus in FPM and NPM, to butyrate and caproate production associated with Clostridium and Caproiciproducens in OPM. This functional transition was accompanied by enhanced amino acid metabolism, which was associated with the enrichment of Proteiniphilum and Aminobacterium. Notably, methanogen-mediated interspecies hydrogen transfer (IHT) emerged as a key ecological feature during pit mud maturation. In OPM, IHT networks primarily involving Methanobacterium and Methanosarcina linked methanogenesis with reverse β-oxidation through diverse hydrogen-transfer pathways, reinforcing metabolic interactions underlying caproate production. These findings provide new insights into the ecological mechanisms underlying pit mud maturation and offer a theoretical basis for the directed cultivation of high-quality pit mud in CSFB production.

Hydrogen

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans

Decoding bipotency: a transient regulatory state bridging totipotency and lineage commitment.

Early mammalian embryogenesis entails a coordinated transition from totipotency to the first lineage bifurcation, giving rise to embryonic lineages and the extra-embryonic trophectoderm. The mechanisms by which totipotency is resolved into lineage-primed states remain incompletely understood. Emerging evidence supports a non-binary model in which cells traverse a continuum of potency states, passing through a transient bipotent intermediate that retains both embryonic and extra-embryonic potential while exiting totipotency. Here, we synthesize recent advances in the mechanisms that establish, maintain, and resolve bipotency. We emphasize the coordinated roles of transposable elements, transcription factors, and signaling pathways in regulating this transition. We also highlight newly developed bipotent stem cell models and their implications in generating advanced embryo models in vitro. Notably, current insights are largely derived from mouse systems; given key differences between mouse and human early embryogenesis, extending these findings to human models remains a critical next step.

Animals

Transcription regulation of cell fate plasticity - from embryonic development to tissue regeneration.

Cell fate plasticity refers to the capacity of cells sharing the same genome to alter, reverse, or reconfigure their identity under physiological, pathological, or experimental conditions. This property underlies embryonic development, cellular reprogramming, and tissue regeneration, but becomes progressively restricted as lineage identity is stabilized. Embryonic development represents an intrinsic process of fate transitions, whereas reprogramming and regeneration reveal how differentiated cells can dedifferentiate or transdifferentiate under specific conditions. Across these contexts, plasticity is governed by multilayered regulatory networks involving transcription factors, epigenetic regulators, cofactors, and the core transcription machinery. Robust regulatory programs stabilize cell identity, whereas stochastic fluctuations in gene expression and chromatin state can prime cells for fate transitions, adding a tunable dimension to plasticity control. In this review, we synthesize recent advances in the regulation of cell fate plasticity across development, reprogramming, and regeneration, highlighting how transcription factors, epigenetic modifications, transcriptional cofactors, and core transcription machinery cooperate to control cell fate decisions and plasticity.

Animals

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

Journal Article

Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene

Workforce Representation in Ophthalmology Oral Board Examiners and Examinees.

PURPOSE: To evaluate the characteristics of the American Board of Ophthalmology (ABO) oral board examiners and examinees as well as trends in examiner and examinee gender over time. DESIGN: Retrospective cohort study. SUBJECTS: ABO oral board examiners and examinees. METHODS: We utilized data from the American Board of Ophthalmology (ABO) and Association of American Medical Colleges (AAMC) to assess board examiner and examinee demographic characteristics from 2011 to 2024. Examiner characteristics included gender, years of experience, initial certification year and average examiner score. Examinee characteristics included gender, years since residency graduation and exam outcome (pass/fail). We utilized logistic regression to examine temporal trends in examiner and examinee gender from 2013 to 2024. MAIN OUTCOME MEASURES: Gender distribution of examiners and examinees. RESULTS: Overall, the proportion of women examiners increased over the study period. Notably, the most pronounced increase occurred following the transition from in-person to virtual oral board exam administration in 2020, rising from 31.3% (95% CI: 24.1%-38.4%) in 2019 to 49.1% (95% CI: 43.8%-54.4%) in 2024 (p < .001). The percentage of women examinees remained stable (41.7% [95% CI: 37.6%-45.8%] in 2019; 37.5% [95% CI: 33.0%-42.0%] in 2024, p-value: .019). CONCLUSIONS: The representation of women among the ABO oral board examiners has increased significantly following the transition to virtual exams while the proportion of examinees remained stable. Strategies to increase flexibility in scheduling exams may be beneficial in continuing to improve examiner representation.

Humans

Sleep disturbances in children and adolescents with iron deficiency: Questionnaire-based and actigraphic findings.

OBJECTIVE: Iron deficiency (ID), without or with anemia (IDA), has been linked to restless sleep and sleep-related movement disorders in childhood, but objective correlates are incompletely defined. We aimed to describe caregiver-reported sleep disturbances, restless legs syndrome (RLS) - related symptoms, and actigraphic sleep patterns in children and adolescents with ID/IDA, and to compare these findings with available sleep-asymptomatic control datasets. We finally explored short-term changes after iron supplementation. METHODS: In this single-center pilot observational study, 31 children with ID/IDA underwent baseline clinical/laboratory assessment and caregiver-reported sleep evaluation with the Sleep Disturbance Scale for Children (SDSC) plus RLS-oriented items. Sixteen also completed home actigraphy, and 8 had follow-up after iron treatment prescribed in routine care. Baseline findings were compared with historical healthy control datasets without reported sleep disturbances; iron-status data were not available for the questionnaire control group; within-subject changes were explored in the follow-up subgroup. RESULTS: Compared with healthy controls, the ID/IDA cohort had higher SDSC total scores (43.97&#x202f;&#xb1;&#x202f;9.63 vs 34.61&#x202f;&#xb1;&#x202f;7.50; p&#x202f;<&#x202f;0.001), with significant differences in the subscales difficulty in initiating and maintaining sleep (DIMS), sleep-wake transition disorders (SWTD), and sleep hyperhidrosis (SHY). Ten of 31 screened children (32.25%) had clinically plausible RLS-related symptoms and higher SWTD scores. Actigraphy showed shorter sleep duration, lower sleep efficiency, longer wake after sleep onset, and greater fragmentation. After iron treatment, parent reported restlessness improved, whereas actigraphic parameters showed only partial normalization. CONCLUSIONS: Pediatric ID/IDA was associated with caregiver-reported and actigraphic sleep disruption, characterized by restless and fragmented sleep. These findings support systematic sleep assessment in children with low iron stores and consideration of iron status in the work-up of restless or nonrestorative sleep.

Humans

Gastric carcinoma classification in the WHO 6th edition (2026): Updated framework and emerging entities.

The sixth edition of the WHO Classification of Digestive System Tumours (2026) represents an important step in the continuing evolution of gastric carcinoma classification. While preserving morphology as the foundation of diagnosis, it incorporates advances in molecular pathology, genotype-phenotype correlations, tumour evolution, and predictive biomarker assessment. This review summarizes the development of the WHO classification from the third edition (2000) to the sixth edition (2026) and highlights its relationship with other major classification systems, including those of Laur&#xe9;n, Nakamura, and the Japanese Gastric Carcinoma Association (JGCA). Major histological categories remain largely unchanged; however, several important conceptual and diagnostic refinements have been introduced. These include recognition of crawling-type adenocarcinoma as a distinctive variant of tubular adenocarcinoma, subclassification of poorly cohesive carcinoma into signet-ring cell and non-signet-ring cell subtypes, introduction of the concept of pure signet-ring cell carcinoma, and increased emphasis on tumour evolution. The sixth edition also expands and refines the spectrum of uncommon gastric carcinoma subtypes, including gastric carcinoma with lymphoid stroma, AFP-producing carcinoma, micropapillary adenocarcinoma, gastric adenocarcinoma of fundic-gland type, and gastric sarcomatoid carcinoma. Crucially, molecular subgroups originally proposed by The Cancer Genome Atlas (TCGA) and actionable biomarkers-including HER2 (ERBB2), Claudin 18.2, mismatch repair deficiency/microsatellite instability (dMMR/MSI), and programmed death-ligand 1 (PD-L1)-have transitioned from research-based categories into essential tools for precision oncology. Rather than providing exhaustive diagnostic criteria, this review offers a conceptual framework and encourages consultation of the original WHO text for full details. These advances illustrate the transition of gastric carcinoma classification from a predominantly morphology-based system toward an integrated histomolecular framework that more closely links pathological diagnosis with tumour biology, prognostication, and therapeutic stratification.

Crawling-type adenocarcinoma

Exploring Primary Care Clinicians' Sexual and Reproductive Health Care Delivery to Male Adolescents and Young Adults.

INTRODUCTION: Despite existing guidance for adolescent sexual and reproductive health (SRH) care, male adolescent SRH care receipt is inadequate. Limited research has explored factors affecting clinicians' provision of SRH care to male adolescents, specifically. METHODS: This mixed-method study with 12 primary care clinicians included a brief survey assessing care delivery practices and confidence, followed by an in-depth interview to explore factors affecting SRH care delivery. RESULTS: Clinicians reported high confidence delivering male adolescent SRH care (mean &#xb1; SD: 8.31 &#xb1; 1.71 out of 10), but delivered only about half the recommended services (20 items out of 38). Factors influencing care delivery included gaps in education/training, assumptions about male SRH care, and behavioral constraints at various levels. DISCUSSION: Findings underscore the need to strengthen male adolescent SRH care by enhancing provider training, increasing clinic-level supports, and addressing structural barriers. CONCLUSIONS: Findings can inform strategies to improve the quality and comprehensiveness of SRH services for male adolescents in primary care settings.

Humans

Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N&#x2248;1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age

Nurse-led acute care post-operative interventions in adult cardiac surgery: a systematic review.

AIMS: The primary aim of this systematic review was to identify nurse-led clinical interventions evaluated in randomized controlled trials (RCTs) for adults who had undergone cardiac surgery. The secondary aim was to assess the effectiveness of these interventions on post-operative clinical and patient-reported outcomes during the acute inpatient phase. METHODS AND RESULTS: A systematic review was undertaken according to an a priori protocol using Joanna Briggs Institute (JBI) methodology and PRISMA guideline for reporting. Eligible studies were RCTs of adult (&#x2265;18 years) cardiac surgery, nurse-led inpatient interventions implemented immediately post-surgery and prior to discharge. Six databases were searched from inception to June 2025. Of 2690 records, 19 RCTs were eligible, representing 13 countries, and 3142 participants. Risk of bias varied, with only two low-risk trials. Interventions were grouped into seven domains: behavioural support; temperature management and comfort strategies; pain and symptom management; wound care; infection prevention; respiratory and pulmonary function; and post-operative recovery, mobilization, and hydration. Across these domains, nurse-led interventions were generally feasible, safe, and positively affected patient comfort, physiological stability, symptom relief, and aspects of functional recovery. CONCLUSION: Nurse-led inpatient interventions contribute meaningfully to inpatient post-operative recovery in cardiac surgery, although the broader cardiac surgical nursing scope is underrepresented in RCTs. This review provides a foundation for developing further high-quality research, peer-reviewed interdisciplinary practice guidelines, and strengthening the scope and recognition of cardiac surgical nursing as a distinct specialty. REGISTRATION: PROSPERO-CRD420251063851.

Humans

Clinical and Psychosocial Characteristics of Adult Primary Care IBS Patients: A Post hoc Analysis of the DOMINO Study.

BACKGROUND: The majority of irritable bowel syndrome (IBS) patients are diagnosed and managed in primary care, but this setting is underinvestigated to date. OBJECTIVE: The present study aimed to improve our understanding of IBS in primary care by evaluating the clinical and psychosocial characteristics of affected patients. METHODS: We performed a cross-sectional post hoc analysis of the DOMINO study, which enrolled 483 adult IBS patients newly diagnosed by primary care physicians. We investigated baseline demographics and questionnaires assessing Rome IV criteria and stool pattern subtype, symptom severity (IBS-SSS), quality of life (IBS-QoL), somatic symptom disorder (PHQ-12), depression (PHQ-9) and anxiety (GAD-7). RESULTS: 70% of the primary care diagnosed IBS patients fulfilled the Rome IV criteria (Rome+). The stool pattern subtype distribution according to the Rome IV diagnostic questionnaire was: 20% constipation (IBS-C), 33% diarrhea (IBS-D), 31% mixed (IBS-M) and 16% unclassified (IBS-U). Mean IBS-SSS was 268&#xa0;&#xb1;&#xa0;98, with 46% and 36% of cases reporting moderate and severe IBS-SSS, respectively. Rome&#xa0;+&#xa0;patients had, compared to Rome-, a significantly higher IBS-SSS, lower quality of life and higher psychosocial comorbidity. IBS-M, IBS-D and IBS-C participants scored significantly higher on IBS-SSS and IBS-QoL than IBS-U. Furthermore, IBS-M had significantly higher somatic symptom disorder and depression and anxiety levels compared with IBS-U. CONCLUSION: The majority of primary care IBS patients fulfilled the Rome IV criteria, were subtyped as IBS-D or IBS-M and were characterised by moderate or severe IBS-SSS. Rome+ and IBS-M participants had higher symptom severity, lower quality of life and higher psychosocial comorbidity. CLINICALTRIALS: gov, Number NCT04270487.

Adult

Impact of Integrated Continuous Team Midwifery Care on Breastfeeding Success within the Iranian Health System: A Randomized Controlled Trial.

INTRODUCTION: Supporting women during the perinatal period helps build confidence, strengthens early bonding between mother and baby, and encourages successful breastfeeding. Continuous midwifery care models are one of the ways that support women in this periods. OBJECTIVE: This study aimed to evaluate the effect of integrated continuous team midwifery care (ICTMC) in enhancing breastfeeding success in the Iranian health system. METHODS: In this randomized controlled trial, 200 low-risk primiparous women with a gestational age of less than 12 weeks were recruited from public health centers. Participants were randomly assigned to either the intervention group, which received continuous midwifery care throughout pregnancy, childbirth, and postnatal follow-up, or the control group, which received routine care. The primary outcomes were early skin-to-skin contact and breastfeeding success at the time of discharge and at 4-6 weeks postpartum. Data were analyzed using Stata, employing descriptive statistics, Chi-square, independent t-test, Phi/Cramer's V, and Cohen's d. The p < 0.05 is significant. Data were analyzed with SPSS 26. RESULTS: ICTMC groups were significantly more likely to initiate skin-to-skin contactearly skin-to-skin contact immediately after birth (92% vs. 74%, p < 0.001) and achieve successful breastfeeding at the discharge time (88% vs. 70%, p = 0.002) compared to the control group. At 6 weeks postpartum, breastfeeding success remained higher in the intervention group (82% vs. 65%, p = 0.004). CONCLUSION: Women with ICTMC, effectively support skin-to-skin contactearly mother-infant bonding and enhance breastfeeding success among low-risk primiparous women. Integrating this model into routine maternal care may improve perinatal outcomes.

Humans

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (&#x2265;18&#xa0;years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans

Linking women leaving jail to medications for opioid use disorder: Costs to implement pre-release telehealth and peer navigation services.

AIMS: Telehealth and peer navigation are feasible strategies for connecting women in the criminal-legal system with medications for opioid use disorder (MOUD), yet implementation costs are not well understood. This study conducted a microcosting analysis of two interventions for women leaving jail in Kentucky: pre-release, PreTreatment Telehealth with a MOUD provider (TH-Only) and PreTreatment Telehealth combined with peer navigation (TH+PN) through the Justice Community Opioid Innovation Network (JCOIN). METHODS: From the provider perspective, we estimated total start-up costs, total intervention costs, and average cost per participant. Women participating in the clinical trial were randomly assigned to TH-Only (n=299) or TH+PN (n=301). Start-up costs were incurred primarily in 2019 - 2020; intervention costs represent expenses in 2021 - 2023. Cost data were collected from study and agency financial records and interviews with research staff and analyzed using Microsoft Excel (version 16.90.2). RESULTS: Start-up costs were $36,320, comprising planning, meetings, travel, and supplies. The total cost of TH-Only was $60,767, representing 259 telehealth sessions with an average duration of 47 minutes. Total cost of TH+PN was $472,148 based on 270 telehealth sessions (48 minutes), 268 peer navigation (PN) sessions (30 minutes), and 12 weeks of PN support post-release per participant. Average cost per TH-Only participant was $235 and per TH+PN participant was $1,760. CONCLUSIONS: Telehealth may be a relatively low-cost approach for jails lacking on-site MOUD services. Although more costly, combining telehealth with PN may add value by supporting service continuity and facilitating linkage to treatment during the jail to community transition.

Humans

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units