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The global prevalence of horizontal strabismus: A systematic review and meta-analysis with a focus on ethnic variation.

The prevalence of the 2 types of horizontal strabismus, esotropia and exotropia, varies considerably between studies. This variability has been attributed to factors such as geography/environment, research methodology, age of study subjects, and/or ethnicity. Comprehensive estimates of regional and global prevalences of esotropia and exotropia are lacking, making it difficult to recognize true patterns, trends, and etiologies. We compile prevalences and ratios of esotropia to exotropia from 315 population-based studies and 374 clinic-based studies. We analyze data to assess effects of ethnicity, geography, age, and we identify generational changes of horizontal strabismus. Major ethnicities differ in patterns and ratios of esotropia and exotropia prevalence, not only in Caucasians and East Asians, but also Latinos/Hispanics, South Asians, Africans, and Native Americans. Compared to population-based studies, clinic-based studies underestimate exotropia frequency. By weighing prevalences according to the population size of ethnicities, we estimate the worldwide prevalence of horizontal strabismus in the current generation at 1.81% (138.5 million people), comprising 60.0 million people with esotropia (0.67%) and 87.5 million with exotropia (1.14%). In the previous generation, the worldwide prevalence of horizontal strabismus was 1.64% (86.5 million people), comprising 50.5 million with esotropia (0.96%) and 36.0 million with exotropia (0.68%). Esotropia and exotropia prevalences differ between generations within the same ethnicity, indicating that extrinsic factors can modify the underlying intrinsic (genetic) disposition.

Humans

Multi-omic biomarkers in cardiovascular disease: Discovery to clinical translation.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, necessitating improved risk stratification and early detection strategies. Multiomics approaches that integrate genomics, transcriptomics, proteomics, metabolomics, and epigenomics offer unprecedented opportunities for biomarker discovery and precision medicine in cardiovascular care. This narrative review examines the current landscape of multiomics biomarkers for CVD, tracing their evolution from discovery to clinical translation. We synthesize evidence from recent studies evaluating the clinical utility of integrated omics approaches across diverse cardiovascular conditions, including atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation. High-throughput proteomics has identified novel protein signatures that enhance cardiovascular risk prediction beyond traditional risk factors. Metabolomics has revealed pathway-specific biomarkers, including trimethylamine N-oxide and lipid species, associated with atherogenesis. Polygenic risk scores derived from genomic data demonstrate incremental value when combined with clinical risk scores. Multiomics biomarkers represent a transformative approach to cardiovascular risk assessment and disease management.

Humans

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma

Efficacy of a self-guided online resilience intervention for improving mental health among university students: A randomized controlled trial.

Epidemiological data indicates that university students are an at-risk population for the development of mental disorders. Online interventions have been proposed as promising tools for reducing barriers to treatment and establishing easily accessible health-care services promoting mental health and resilience. This study investigated the efficacy of a Learning Management System (LMS)-based self-guided online resilience intervention. 216 university students took part in a randomized controlled trial with an intervention and a waitlist control group and three measurement points (pre, post and follow-up). We conducted per-protocol (PP) and intention-to-treat (ITT) analyses with mental distress as primary outcome, and self-reported resilience and resilience factors as secondary outcomes. Further, attitudes towards online interventions, adherence, satisfaction and possible negative effects were explored. Satisfaction with the intervention was high and PP analyses (n = 150) revealed significant improvements in mental distress and self-compassion at post-test and acceptance at follow-up. No favourable effects were found for self-reported resilience and resilience factors. Adherence was low and ITT analyses revealed no significant effects. Overall, the study provides preliminary evidence for the LMS-based self-guided online intervention as a potentially valuable tool for university mental health services under optimal adherence conditions. Further research into determinants of adherence is needed to improve intervention reach.

Humans

Impact of a thermal care bundle on peri-operative hypothermia, surgical site infection, and readmissions in osteosynthesis patients: A randomised controlled trial.

BACKGROUND: Maintaining normothermia throughout the peri-operative period prevents the occurrence of complications related to hypothermia. OBJECTIVE: To determine the effect of a thermal care bundle with a short prewarming period on inadvertent peri-operative hypothermia (IPH), surgical site infection (SSI), and unplanned readmission among osteosynthesis patients, and to identify associated variables. DESIGN: Open-label, randomised controlled trial. SETTING: University hospital. PATIENTS: One hundred and forty-eight patients who underwent osteosynthesis surgery. INTERVENTION: The intervention group received the thermal care bundle, which consisted in prewarming patients 10 min before anaesthesia delivery and maintaining body temperature with a forced air device during surgery and the immediate postoperative period; in addition, the operating room environmental temperature was kept at 21 °C, and fluids were warmed to 38 °C. MAIN OUTCOME MEASURES: For the primary objective, hypothermia was defined as core body temperature below 36 °C and measured using the 3M Spot On zero heat flux sensor. Core temperature was recorded upon admission to the pre-operative holding area and subsequently every 30 min until postanaesthesia care unit (PACU) discharge. Secondary objectives were SSI and readmissions: a follow-up at 30 to 60 and 90 days was performed by the principal investigator. RESULTS: All 148 patients completed the study, and there were no significant differences between the groups at baseline. At the start of surgery, the incidence of hypothermia was significantly lower in the bundle group (1.3 vs. 9.9% among controls; odds ratio = 7.59, P  = 0.021). A significantly lower incidence of hypothermia was also observed at admission to the PACU (14.3% in the bundle group vs. 29.6% among controls; odds ratio = 2.07; P  = 0.024). Application of the bundle increased patients' core body temperature by 0.13 °C (95% confidence interval (CI), 0.003 to 0.254; P  = 0.045). Patients in the bundle group had a slightly lower observed incidence of wound infections requiring readmission (odds ratio = 0.35; 95% CI, 0.04 to 2.92), although this difference was not statistically significant ( P  = 0.332). CONCLUSIONS: The bundle reduces peri-operative hypothermia by up to 59%, but does not affect on SSI; factors like presurgery hospital stay, operating room and PACU occupancy were identified as risk factors for SSI. REGISTRATION: 21 July 2022: NCT05469958 (Clinical Trials.gov), first recruitment 15 August 2022.

Adult

Transcranial Photobiomodulation Variables Assessment Battery: Development and Validation.

Transcranial photobiomodulation (tPBM) response variability is partly driven by biophysical characteristics such as skin tone and hair properties that attenuate photon penetration, and by lifestyle factors including sleep quality, alcohol use, and nicotine consumption that disrupt the mitochondrial and vascular pathways on which tPBM acts. To date, no validated self-report tool exists to capture these moderators systematically. To address this gap, the tPBM Variables Assessment Battery was developed and psychometrically evaluated. It integrates adapted versions of established measures (Brief Pittsburgh Sleep Quality Index, E-cigarette Dependence Scale, Hair Scale Assessment PRO, Monk Skin Tone Scale, and Heaviness of Smoking Index), validated wellbeing evaluators (Ryff's Psychological Wellbeing), and custom measures (Hairstyle Classification, Hair Color Classification). Face and content validity met recommended expert thresholds, internal consistency was acceptable across adapted subscales, and criterion validity analyses confirmed meaningful associations between the lifestyle components and PROMIS-10 global health outcomes. The battery is low-burden, digitally deployable, and psychometrically defensible, offering a practical tool for characterizing the variables most likely to moderate tPBM response in home-use studies.

Humans

Outcomes at rapid diagnostic centres and the association between non-specific symptoms and cancer: A systematic review and meta-analyses of up to 21,392 patients.

INTRODUCTION: Cancer remains a leading cause of mortality and poses a significant public health challenge. Several non-specific symptoms (NSSs) often indicate non-serious disease but can also accompany malignancy even in the absence of organ-specific signs. Therefore, the aim of the study was to comprehensively delineate the association between the most common NSSs (weight loss, fatigue, pain and nausea/appetite loss) and cancer or non-cancer diagnoses. METHODS: Database searches of PubMed and Embase were conducted applying search criteria to identify studies that investigated common NSSs in cancer patients diagnosed through rapid diagnostic centres (RDCs). The quality of the included studies was assessed using a modified Newcastle-Ottawa Scale (NOS). For each symptom, pooled relative risks (RRs) with 95% confidence intervals were derived using random-effects meta-analysis. RESULTS: Eleven studies met the inclusion criteria. All studies were considered to be of high methodological quality. The most frequent disease locations for cancer entities included hematologic, lung and lower gastrointestinal. Together with miscellaneous, rheumatic, and musculoskeletal conditions, these were the most common for non-cancer diagnoses. Nausea/appetite loss showed a statistically significant association with cancer (RR=1.20, 95%-CI 1.07-1.35). Pain showed a non-significant association (RR=1.07, 95%-CI 0.75-1.53) with substantial between-study heterogeneity, and weight loss showed a non-significant inverse trend (RR=0.92, 95%-CI 0.84-1.02). Fatigue showed no association with cancer (RR=1.00, 95%-CI 0.85-1.18). DISCUSSION/CONCLUSION: NSSs may be valuable for cancer risk assessment, but the associations remain modest. The complexity of patients' clinical presentations suggests that additional factors likely influence the cancer risk. Future research should examine symptom combinations and, where data allow, perform subgroup analyses.

Humans

A systematic review and meta-analysis of the late positive potential and internalizing psychopathology.

The present study leveraged the Hierarchical Taxonomy of Psychopathology (HiTOP) framework to conduct a systematic meta-analysis to determine the association between the late positive potential (LPP) index of emotional reactivity and internalizing psychopathology. PRISMA guidelines were followed. Articles were identified through PubMed, APA PsycInfo, and Web of Science online platforms in May 2025. Included articles examined associations between the LPP to positive and/or negative stimuli and internalizing psychopathology. Risk of bias and publication bias were assessed. Results were examined for individual disorders, distress and fear subfactors, and the internalizing spectrum using two approaches: standard analyses that examined aggregate effects and hierarchical analyses that examined direct and indirect relationships. We conducted moderator analyses for sample, task design, LPP quantification, and psychopathology measurement. We included 63 studies across 5,360 participants (Mage = 19.65, SD = 11.1; 58.7% female). In standard meta-analyses, depression was associated with a smaller LPP to positive stimuli (r = -.06, 95% confidence interval [CI; -.12, -.003]). Specific phobia was associated with a larger LPP to negative stimuli (r = .21, 95% CI [.02, .37]). Distress was associated with a smaller LPP to both positive (r = -.12) and negative (r = -.11) stimuli when measured via clinical interview, and fear was associated with a larger LPP to negative stimuli (r = .10, 95% CI [.03, .16]). Hierarchical analyses indicated that the depression results were specific to the disorder, whereas the fear disorder-level results were due to the higher order fear subfactor. The LPP demonstrates discriminant relationships with distress and fear disorders and subfactors. Results were largely robust against methodological factors. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Humans

A risk-need-responsivity (RNR)-informed systematic review of needs during the pretrial period.

OBJECTIVE: Pretrial risk assessments are becoming increasingly popular in the United States. Despite the importance of assessing and intervening around "needs" in the risk-need-responsivity model, few pretrial risk assessments include comprehensive assessment of needs. We aim to provide a systematic review of the prevalence of and predictive utility of needs within the pretrial population. HYPOTHESES: There were no hypotheses given the nature of the study. METHOD: We conducted searches for articles in the EBSCO, ProQuest, and Google Scholar databases using key words related to 11 needs domains: antisocial personality, procriminal attitudes, procriminal associates, substance use, family/marital relationships, school/work, prosocial recreational activities, self-esteem, housing, mental health, and physical health. We identified 215 articles that reported on the prevalence of needs or explored their predictive associations with pretrial misconduct outcomes in adult populations. RESULTS: Overall, we find few comprehensive investigations of needs in the pretrial domain, apart from substance use. Variation in methodology and operationalization contributes to wide variability in prevalence estimates. We found only 15 articles that examined predictive associations between pretrial needs and outcomes, which were limited to investigations of behavioral health, employment, and housing needs. Substance use and housing needs emerged as the only consistent predictors of pretrial misconduct. CONCLUSIONS: Researchers should more directly assess the prevalence and predictive utility of needs within the pretrial period to bolster the evidence base for including these factors in pretrial risk assessments. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Humans

Flavoromics-based profiling reveals taste and aroma differences between infant formula and breast milk.

Flavor differences between infant formula (IF) and breast milk (BM) are considered a potential factor affecting infants' acceptance of IF. This experiment employs flavoromics combined with multivariate statistical analysis to systematically compare the flavor profiles of IF and BM. Electronic tongue analysis and amino acid correlation revealed that IF was characterised by pronounced saltiness and umami richness, whereas BM exhibited greater bitterness and astringency. Volatile compound profiling identified five key flavor constituents in IF, predominantly aldehydes such as hexanal and pentanal. In contrast, BM contained a broader array of compounds-including acids, aldehydes, and esters-resulting in a more complex flavor profile. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based metabolic pathway annotation, together with fatty acid profiling, suggested that some volatiles may be associated with lipid oxidation, Maillard reaction and sulfur-containing amino acid degradation pathways, offering a theoretical basis for the targeted optimisation of IF flavor.

Humans

Intraoperative indocyanine green near-infrared fluorescence imaging for assessing testicular viability in pediatric testicular torsion: A retrospective study.

OBJECTIVE: To evaluate the clinical efficacy of indocyanine green near-infrared fluorescence (ICG-NIRF) imaging versus conventional surgery for assessing testicular viability and guiding decision-making in pediatric testicular torsion (TT). METHODS: A retrospective analysis was performed on 225 pediatric patients undergoing emergency scrotal exploration for TT between January 2019 and January 2025. Patients were categorized into a conventional surgery group (n = 118) relying on visual grading and an ICG-NIRF imaging group (n = 107). Primary outcomes included intraoperative testicular preservation rates and postoperative success rates. Multivariate Cox regression was utilized to identify factors influencing testicular preservation. RESULTS: Baseline characteristics were comparable between groups. The ICG-NIRF group demonstrated a significantly higher intraoperative preservation rate (74.77% vs. 61.02%, p = 0.028) and postoperative success rate (88.75% vs. 69.44%, p = 0.003) compared to the conventional group. Additionally, the ICG-NIRF group exhibited significantly lower rates of secondary orchiectomy (1.25% vs. 9.72%, p = 0.027) and 6-month testicular atrophy (7.59% vs. 23.08%, p = 0.02). Multivariate analysis confirmed ICG-NIRF application as an independent protective factor for testicular preservation (HR = 0.556, p < 0.001). CONCLUSION: ICG-NIRF imaging provides an objective, real-time assessment of testicular perfusion, significantly improving testicular preservation rates and postoperative outcomes. This technique overcomes the subjectivity of conventional visual methods, offering substantial clinical value for fertility preservation in pediatric TT.

Humans

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70&#xa0;mg/dL]: 40-42.5 vs 40&#xa0;min; Level 2 [<54&#xa0;mg/dL]: 35-39.9 vs 35&#xa0;min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult

Lower urinary tract evaluation in children with cerebral palsy: A crossectional study.

INTRODUCTION: Cerebral palsy (CP) is a chronic, non-progressive motor disorder affecting voluntary movement and posture. Lower urinary tract (LUT) dysfunction is highly prevalent in children with CP. This study aims to evaluate LUT function in children with CP. MATERIAL AND METHODS: This cross-sectional study was conducted at a tertiary care hospital. Patients aged 5-18 years with established CP diagnosis were included. Evaluation included clinical history, physical examination, urinary ultrasonography with post-void residual (PVR) measurement, and urodynamic studies when indicated. Patients were categorized into three groups; group-1 (LUT dysfunction), group-2 (symptomatic), and group-3 (asymptomatic) for analysis. RESULTS: The study included 97 children with CP (41 girls, 56 boys; median age 8 years). Of the patients, 61.8% were ambulatory (GMFCS I-III) and 38.2% were non-ambulatory (GMFCS IV-V). At least one LUT symptom was detected in 75.3% of patients. Incontinence was the most common symptom at 69.1%. Incontinence prevalence was significantly higher in non-ambulatory patients (81.1% vs 61.7%, p = 0.044). Invasive urodynamics was performed in 19 patients, and LUT dysfunction was diagnosed in 89.5% of them (19.3% of the entire population). Prematurity rate was significantly higher in patients with LUT dysfunction (94.1% vs 64.8%, p = 0.017). Binary logistic regression analysis identified elevated PVR as the strongest independent risk factor for LUT dysfunction (OR = 108, p < 0.001). Abnormal urinary frequency (OR = 14.9, p = 0.022) and quadriplegia (OR = 10.3, p = 0.016) were other independent risk factors. ROC analysis determined the optimal cut-off value for PVR as 19 mL (sensitivity 58.82%, specificity 94.92%). In the intergroup analysis, multinomial logistic regression identified elevated PVR as the strongest predictor (Group-1 vs Group-2: OR = 101; Group-1 vs Group-3: OR = 24, both p < 0.003). Lower gestational age was also an independent risk factor in both comparisons (OR = 1.25-1.26, p < 0.020). DISCUSSION: This study demonstrates LUT dysfunction affects 19.3% of children with CP, strongly correlating with motor impairment severity. Elevated PVR emerged as the strongest independent predictor (OR = 108), offering a practical non-invasive screening tool. Our proposed urodynamic criteria achieved 94.7% diagnostic yield, enabling selective evaluation. Limitations include single-center design and cross-sectional methodology without longitudinal follow-up. These findings support integrating systematic urological assessment into standard CP care for early intervention. CONCLUSION: LUT dysfunction prevalence is high in children with CP, and symptom frequency increases with higher GMFCS levels. Elevated PVR is the strongest predictor, with a clinically applicable cut-off value of 19 mL. Particularly in quadriplegic, non-ambulatory, and premature patients, close follow-up and urodynamic evaluation when necessary should be performed with a multidisciplinary approach.

Humans

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding

Early Worsening of Diabetic Retinopathy Following Initiation of Hybrid Closed-Loop/Automated Insulin Delivery Systems in Type 1 Diabetes: A Systematic Review and Structured Study-Level Synthesis.

BACKGROUND: Hybrid closed-loop (HCL) systems achieve rapid, algorithm-driven improvements in glycaemia in type 1 diabetes (T1D). Paradoxically, rapid improvement in glycaemic control is associated with early worsening of diabetic retinopathy (EWDR), a phenomenon established in the intensive insulin therapy era. Whether HCL initiation carries a clinically meaningful EWDR risk is unknown. No systematic review has previously addressed this question. METHODS: A systematic review and structured quantitative synthesis was performed using study-level estimates only (PROSPERO CRD:420261391951). MEDLINE, SCOPUS and Web of Science were searched to 14th May 2026. Studies reporting retinal outcomes in people with T1D initiating any HCL system were eligible. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I and certainty of evidence using the GRADE framework. EWDR incidence was summarised using study-level proportions, and comparative studies were summarised using study-specific risk ratios for HCL versus control therapy. Given substantial heterogeneity in EWDR definitions, retinal assessment timing, follow-up duration, and comparator groups, no pooled or meta-analytic estimates were derived. RESULTS: Eight studies (n&#x2009;=&#x2009;1487 participants; 860 HCL users) were included; all were observational and six were retrospective. EWDR varied markedly with the timing of retinal assessment. In studies assessing the retina within &#x2264;&#x2009;12&#x2009;months of HCL initiation, EWDR rates ranged from 8.9% to 26.5%. Studies with longer follow-up reported lower rates of retinal worsening or incident DR, 6.7% at 24&#x2009;months and 6.1% over a mean follow-up of 4.9&#x2009;years, suggesting that these studies may capture background DR progression rather than true early worsening. Three comparative studies included 177 HCL users and 315 controls; EWDR study-specific risk ratios were directionally inconsistent, ranging from 0.32 to 1.51, and were therefore not pooled. The most consistently identified risk factors were higher baseline HbA1c and older age. The magnitude of HbA1c reduction was not a consistent predictor of EWDR in the HCL context, in contrast to pre-HCL era evidence. Risk of bias ranged from moderate to critical and certainty of evidence was very low for all outcomes. CONCLUSIONS: Study-defined retinal worsening was reported in a minority of participants. The current evidence base is dominated by retrospective studies, variable retinal assessment timing, and inconsistent EWDR definitions. Well-designed prospective studies with protocol-specified retinal surveillance anchored to HCL initiation are required to generate reliable incidence estimates, identify risk factors, determine visual consequences, and inform standardised screening guidance.

Humans

Impact of Contact Lens Use on Clinical Profile and Outcomes of Fungal Keratitis: An 8-Year Retrospective Study.

PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and noncontact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospective, comparative clinical cohort study. METHODS: A review of culture-proven fungal keratitis treated at a tertiary referral center between 2018 and 2025 was conducted. Cases were categorized as CL or non-CL-associated. Demographic, clinical, microbiological, treatment, and outcome data were analyzed and compared between groups. RESULTS: Thirty-seven eyes were included, comprising 16 CL and 21 non-CL cases. CL users presented earlier than non-CL patients (median 7 vs 14 days, P = .007) and had fewer associated ocular risk factors (31% vs 81%, P = .001). Baseline visual acuity and infiltrate size did not differ significantly between groups. Candida species were isolated in 21% cases, Fusarium in 16% and Aspergillus in 8%. Fusarium (19% vs 13%) and Candida (24% vs 19%) infections were slightly more frequent in non-CL cases. Overall, filamentous fungi were the predominant organism group. Topical voriconazole was the most frequently used antifungal agent (78%). All CL-associated cases resolved with medical therapy alone, with a median time to resolution of 38 days (IQR 22-58). In contrast, 76% of non-CL cases resolved medically (median 42 days, IQR 32-76), while 23% required therapeutic keratoplasty (P = .04). Final visual acuity was comparable between groups (logMAR 0.2 vs 0.5, P = .56). CONCLUSION: Contact lens-associated fungal keratitis is characterized by earlier presentation and fewer underlying ocular comorbidities, with favorable outcomes achieved through medical therapy alone. Despite similar microbiological profiles and treatment approaches, noncontact lens-associated fungal keratitis more frequently follows a complicated course requiring surgical intervention.

Humans

Understanding Suicide through Coroners' Narratives: implications for primary care from a mixed&#x2011;methods study of 157 Coroners' reports.

Suicide is a major public health concern, and general practice is often a recent point of contact before death. While mental illness is well recognised, the broader social and contextual factors influencing suicide risk remain under-reported in primary care and epidemiological research Aim To describe the demographic, clinical, and psychosocial characteristics of individuals who died by suicide, integrating coronial quantitative data with qualitative narrative accounts to identify implications for primary/ secondary care and public health. Design and setting Explanatory sequential mixed&#x2011;methods study of 157 consecutive deaths by suicide recorded by coroners (2018-19) across five English local authorities. Method Demographic, clinical, and social data were extracted from coroners' records and summarised descriptively. Narrative case summaries were coded and analysed thematically to identify contextual, relational, and service factors preceding death. Results Of 157 individuals: 79% were male; 65% lived in the most deprived IMD quintile; 85% had a diagnosed mental health condition; 62% had a long&#x2011;term physical illness; 41% had a previous suicide attempt. About half consulted a GP in the preceding three months; mental health featured in about half of those consultations. Common stressors were relationship breakdown (37.2%), housing instability (22.1%), and work pressures (18.2%). Seven interlinked themes were identified: Mental health; Alcohol/Substance use, Physical health; Social connectedness; Life course trauma, Socioeconomic and Structural Vulnerability; Healthcare access. Service transitions were key vulnerability points Conclusion Coroners' records offer important insights into the complex circumstances preceding suicide and highlight opportunities for GPs to recognise intersectional complexity and support integrated, cross-sector suicide prevention approaches.

General Practice