Renda M et al. · Jul 1, 2026
Introduction Return to studies or employment, a major element of recovery after a first episode of psychosis (FEP), is out of reach of a significant proportion of patients. Specific programs such as Individual Placement Support (IPS) have been proposed to overcome this hurdle. While some early intervention programs include IPS, others must rely on IPS programs that are open to a wider range of patients. The aim of this paper was to explore the accessibility of IPS for FEP patients treated in such a context. Methods One hundred and eighty nine patients of an ongoing FEP cohort study who were treated at our program in the period where the IPS program was available and for whom sufficient data was available were included in the study. We assessed reasons for non-referral to RESSORT and compared baseline and outcome characteristics of patients who did or did not enter the program. Results A small minority of patients had access to RESSORT. Patients who entered RESSORT had better premorbid functioning and a higher degree of insight at baseline than the ones who did not enter the program. Patients who entered RESSORT had a significantly higher rate of return to premorbid PAS score, without significant difference on other dimensions of functioning. Conclusions When IPS programs are not embedded in early intervention programs, FEP patients have limited chances to access them. Integrating supported employment skills within the role of case managers may be a solution in programs where resources are lacking to develop an IPS program specifically dedicated to FEP patients.
Medicine
van der Gaag M et al. · Jul 1, 2026
Aims The staging model in psychiatry is heuristic and evolving, provoking debate and stimulating alternative views. This paper reviews major controversies in the field of staging and prevention of psychosis. Methods We review the literature on the classification model, the continuum model and the dynamic systems model applied to psychiatry. Other controversies are stigmatisation of early detection, the prevention paradox and the interpretation of data on prevention of transition to psychosis. Results DSM classifications still lack validity. The continuum model supports preclinical stages but has no discrete conversions to different stages of illness. The emerging dynamic systems model builds on the interaction of symptoms eliciting networks of symptoms, while at the same time it explains sudden catastrophic shifts (transitions) between different states of equilibrium. Stigmatisation of early psychosis can be balanced against the benefits of early interventions. The prevention paradox states that only a minority of first episode cases arises from the high-risk group. However, there are many reasons to combine indicated prevention with population-based preventive interventions. A long-lasting controversy is on the interpretation of the research data. Several meta-analyses are reviewed on methodological issues. Conclusion The staging model is adequate to conceptualise psychiatric disorders and the progress over time in more chronic stages. No one is suggesting that help-seeking patients with an ARMS should be denied access to psychosocial treatment and it is recommended and necessary to continue building age and stage specific services to treat them and continue with research into risk factors and helpful interventions.
Medicine
Mondelli MU et al. · Jul 1, 2026
Background and aims Herpes simplex virus (HSV) infection is common worldwide, but hepatic involvement is rare. HSV hepatitis is an uncommon yet frequently catastrophic cause of acute hepatitis and acute liver failure (ALF), accounting for Methods We describe three cases of HSV hepatitis presenting with distinct risk profiles and clinical manifestations and review the diagnostic and therapeutic challenges associated with this condition. Results Clinical presentation was nonspecific in all cases, and mucocutaneous lesions were absent or delayed, contributing to diagnostic uncertainty. All patients exhibited marked aminotransferase elevation with relatively modest hyperbilirubinemia ("anicteric hepatitis"), frequently accompanied by cytopenias and coagulopathy. Delayed recognition was associated with rapid clinical deterioration, whereas earlier initiation of intravenous acyclovir was associated with biochemical and clinical improvement. Diagnosis was established using polymerase chain reaction-based detection of HSV DNA in blood and tissue samples. Conclusions HSV hepatitis remains an under-recognized cause of ALF across a broad spectrum of immunocompromised and seemingly immunocompetent patients. Given the narrow therapeutic window and favourable safety profile of acyclovir, empiric intravenous antiviral therapy should be considered in patients with ALF of indeterminate aetiology while diagnostic testing is pending, particularly in high-risk clinical settings. Increased awareness of this overlooked diagnosis may improve outcomes and prevent avoidable mortality.
Medicine
Malkani R et al. · Jul 1, 2026
Objectives Ethical decision-making in veterinary practice and in animal welfare sectors can be particularly challenging. Decision-making is reported to be largely subjective with various influences biasing these decisions. To enhance the objectivity with ethical dilemmas and difficult decisions, the application of standardised tools is increasingly advocated. This study explores the utility of the Animal Welfare Assessment Grid (AWAG) as a decision-making tool in various sectors of dog welfare including veterinary medicine, shelter environments, and assistance dog organisations. Methods This was undertaken through an online mixed-methods questionnaire of clinicians using the AWAG in their workplace to assess dogs. A total of 38 respondents from a group of 99 veterinary and animal welfare professionals provided insights on the tool's functionality. Results Over 96% of respondents acknowledge the utility of the AWAG in aiding in decision-making and it is reported to facilitate discussions among colleagues and dog caregivers about welfare. While the overall sentiment towards the AWAG was predominantly positive, a minority of users expressed difficulties in using the tool, indicating areas where the tool could be further refined and improved. Clinical significance The results suggest that the AWAG serves as a valuable asset for veterinary clinicians and animal welfare professionals, aiding in the assessment of dogs' welfare and informing treatment and management decisions. By providing an instrument to aid in objective reasoning to the complex process of decision-making, this may help transform how welfare considerations are integrated into daily practice.
Biochemistry, Genetics and Molecular Biology
Jafarbeglou M. · Jul 1, 2026
Intranasal (IN) drug delivery has increasingly considered as an easy, practical and non-invasive alternative to parenteral administration in veterinary medicine, offering rapid systemic and potential nose-to-brain effects. The first part of this review systematically collected and synthesized published evidence on IN administration across animal species, while the second part critically analysed the anatomical, pharmacological and technical factors that determine its success and limitations. Part I consisted a total of 110 eligible studies published between 1991 and 2025, encompassing dogs, cats, rabbits, pigs, ruminants, birds and reptiles. IN delivery has been investigated for a range of purposes and produced clinically meaningful sedation, analgesia and drug reversal, often comparable to intramuscular administration but generally characterized by slower onset and greater variability among species. Despite encouraging and favourable results, IN delivery was not without limitations. Its effectiveness can be strongly influenced by species-specific nasal anatomy and physiology, formulation characteristics and dosing volume. Defensive reactions, poor tolerability, sneezing, nasopharyngeal irritations, hypersalivation or swallowing of the drug are frequently reported. Future progress requires species-specific case selection guidelines and dosing standards, pharmacokinetic validation and developing safe concentrated formulations. Transparent reporting and balanced assessment of both benefits and drawbacks are essential to ensure the safe, effective and ethically responsible integration of IN administration into veterinary anaesthesia and critical care practice.
Veterinary
Lim JZM et al. · Jul 1, 2026
Background Diabetic foot ulceration (DFU) and lower limb complications are highly prevalent in people with end-stage kidney disease (ESKD), particularly those receiving dialysis; however, the overall burden and outcomes remain incompletely characterised. This systematic review with narrative synthesis aimed to summarise study characteristics and evidence on the epidemiology of DFU in ESKD, including incidence, prevalence, wound healing outcomes, and associations with lower-extremity amputation (LEA) and mortality. Methods MEDLINE (via PubMed), EMBASE and the Cochrane Database of Systematic Reviews were searched from inception to 31 January 2026 for longitudinal and cross-sectional studies, including registry data, in adults with ESKD or on dialysis. Outcomes included DFU epidemiology, wound healing, revascularisation, LEA and mortality. Results The review included 64 observational studies. In dialysis-dependent populations, DFU incidence is high and increases with advancing renal impairment, often preceding dialysis initiation. Evidence on whether dialysis initiation itself increases DFU risk is limited and heterogeneous, although observational cohorts suggest a temporal association with haemodialysis initiation, particularly within the first 2 years. Data comparing haemodialysis and peritoneal dialysis are scarce. Wound healing outcomes were variable, with earlier recurrence observed, although multidisciplinary care improved healing, largely driven by perfusion and ulcer severity rather than renal function alone. Although based on observational and heterogeneous data, dialysis-dependent ESKD was frequently identified as an independent predictor of LEA after adjustment for confounders, with coexisting peripheral arterial disease, a key determinant of adverse limb outcomes. Mortality risk appeared to compound following amputation, with observational data suggesting high post-amputation mortality (approaching 50% at 2 years and 70% at 5 years), consistent with a shift towards limb loss rather than increased DFU occurrence. Interpretation is limited by study heterogeneity, observational design, limited long-term data on healing and recurrence, and inadequate stratification by dialysis modality. Conclusions Current evidence underscores substantial gaps in understanding the natural history and optimal management of diabetic foot disease in dialysis-dependent ESKD. Future research should prioritise well-designed prospective studies to delineate dialysis-specific risk pathways, incorporate robust stratification by dialysis modality, and evaluate interventions targeting ischaemia and limb preservation. Standardisation of outcome reporting, particularly for healing durability and recurrence, will be essential to enable meaningful comparisons and guide the development of tailored multidisciplinary care models for this high-risk population.
Medicine
Liu W et al. · Jul 1, 2026
Primary signet-ring cell carcinoma and poorly differentiated adenocarcinoma with poorly cohesive morphology in the cervix are rare conditions, and their clinicopathological features remain poorly described. This study defines primary cervical poorly differentiated adenocarcinomas meeting the diagnostic criteria for poorly cohesive carcinoma as outlined in the 2019 WHO Classification of Digestive System Tumors as 'HPV-associated cervical poorly cohesive carcinomas' (HPV-associated CPCC) and describe their clinicopathological and molecular features. Sixteen HPV-associated CPCC cases were analyzed and classified into three histological subtypes: signet-ring cell carcinoma (n = 4), not otherwise specified (n = 6), and mixed types (n = 6). All patients were Chinese (median age: 46 years; range: 30-66). Vaginal bleeding was the primary presenting symptom (100.0%). High-risk human papillomavirus (HPV) was identified in all tumors, with HPV-18 as the predominant genotype (n = 13), HPV-16 in two cases, and a single case exhibiting concurrent infection with HPV-16, -18, and -58. Overall, 56.3% presented with advanced-stage disease (International Federation of Gynecology and Obstetrics [FIGO] IIIB-IVB), frequently involving regional lymph nodes (56.3%) and distant sites (18.8%). Histopathological examination revealed diffuse stromal infiltration (100%), lymphovascular invasion (75.0%), necrosis (75.0%), and desmoplasia. Immunohistochemically, all cases showed p16 block positivity. Variable expression of antibody-drug conjugate targets was observed, with HER2-low expression (33.3%), and positive staining for Trop-2 (85.7%), nectin-4 (42.9%), and tissue factor (92.3%). During follow-up, disease-specific mortality was 50.0%. The 3-year overall survival rate was 56.3%, which was significantly lower in advanced-stage disease (45.0%) than in early-stage disease (75.0%). Whole-exome sequencing revealed low tumor mutational burden (median 1.28 Muts/Mb), recurrent mutations in AK1, ARHGAP39, KRT24, MICAL3, SLC6A9 (27.3%), KRAS, and KMT2C (18.2%), alongside MUC2 copy gain (63.6%) and bidirectional Y_RNA alterations (gain 54.5%/loss 45.5%). Collectively, HPV-associated CPCC represents a distinct and aggressive subtype characterized by distinctive histopathological features, a predominant association with HPV18, frequent presentation at advanced stages, and marked molecular and biomarker heterogeneity.
Medicine
Ji D et al. · Jul 1, 2026
Background Migrant youth are at disproportionate risk of mental health challenges. Overcoming barriers to accessing services requires large-scale data to inform policies and interventions. This study maps mental health outcome trends of migrant youth over 8 years. Methods Canadian Health Behavior in School-aged Children study data from 2014, 2018, and 2022 were analyzed for mental health outcome trends. Age-adjusted logistic regressions examined health across years stratified by migrant status, separately by sex. Using nonmigrants as the referent group and 2014 as the referent year, contrasts for disparities were examined across migrant status to test widening, narrowing, or stability in differences of outcome prevalences between migrant and nonmigrant youth. Results Health worsened from 2014 to 2022 among migrants, especially migrant girls. Compared to 2014, life satisfaction, health, and self-confidence for migrant youth dropped in 2022. Health complaints and feeling sad/hopeless increased in 2022 among girls. Migrant youth reported fewer health complaints than nonmigrants in 2018 and 2022. Implications Investment in free/affordable, culturally safe/relevant, confidential school-based mental health supports with avenues for community collaboration are recommended. Conclusions Mental health outcomes worsened from 2014 to 2022, especially among migrants and girls; however, migrant youth exhibit resilience to adversity.
Psychology
Pistone I et al. · Jul 1, 2026
Introduction Alcohol use disorder is a major public health issue, impacting health, well-being, relationships and work performance. In Sweden, employers are legally required to provide access to and cover the cost of alcohol treatment for individuals with alcohol use disorder. Employer-supported alcohol treatment is therefore rather common in Sweden; however, research on employees' experiences with this type of treatment remains unexplored. This qualitative study investigates how a group of Swedish employees who had received employer-supported alcohol treatment experienced workplace management before, during and after treatment. Method Interviews with 15 participants were analysed using thematic analysis, revealing three key themes. Results The first theme highlights that many participants viewed their employer as a lifeline, experiencing relief when they received support to seek help for their alcohol problems. The second theme captures employees' reliance on their employer's ability to handle the situation, emphasising the crucial role managers play in the process, with varying levels of competence and support. Third, participants often felt alone upon returning to work, facing a discrepancy between their expectations of support and the actual workplace support provided post-treatment. Discussion and conclusions The findings show how employer-supported treatment may facilitate access to care and workplace reintegration under relatively favourable circumstances, particularly when supported by managerial competence, clear routines and continued follow-up.
Medicine
Han Y et al. · Jul 1, 2026
Background Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance. Purpose To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment. Methods TUM-SAM integrates nnU-Net-based lesion detection with a tumor-adapted Med-SAM segmentation model to enable prompt-free, fully automated segmentation. Training used 301 patients (2548 lesions), and external evaluation used an independent cohort of 105 patients (397 lesions). Segmentation accuracy was benchmarked against DeepMedic and nnU-Net using Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (HD95). Two physicians contoured all external cases, and a third physician contoured a 20-patient subset for a blinded, tumor-level, multi-rater preference study. Pairwise contour preferences were analyzed using a Bradley-Terry probabilistic model to obtain bias-adjusted estimates of relative contour quality while accounting for rater-specific tendencies and case difficulty. Results In the external cohort, TUM-SAM achieved a lesion-wise detection sensitivity of 0.94 and outperformed DeepMedic and nnU-Net across all tumor sizes, with a mean DSC of 0.84 and HD95 of 1.9 mm (nnU-Net/DeepMedic: DSC 3.3 mm). Across voxel-wise evaluation, TUM-SAM's geometric performance fell within the range of inter-observer variability among physicians and was sensitive to reference construction. In contrast, in the blinded rater study, experts preferred TUM-SAM-generated contours over individual physician contours in 81-87% of raw comparisons; Bradley-Terry analysis yielded conservative, bias-corrected win probabilities of 55-56%, indicating consistent preference after adjustment for rater and case difficulty. Conclusion Using a bias-controlled, blinded multi-rater evaluation framework, TUM-SAM demonstrates brain metastasis segmentation quality that is consistently preferred by expert physicians, highlighting the limitations of agreement-based voxel-wise metrics under inter-observer variability. These findings underscore the dependence of conventional evaluation on reference definition and support preference-based assessment as a complementary approach for evaluating AI segmentation quality in BM MRI.
Medicine