Nevin Manimala

Eur Urol Oncol. 2026 Mar 10:S2588-9311(26)00040-4. doi: 10.1016/j.euo.2026.02.003. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) with targeted biopsies improves detection of clinically significant prostate cancer (csPC), commonly defined as Gleason grade group (GG) ≥2. Current practice combines targeted and systematic biopsies, which increases csPC detection but also increases detection of insignificant PC (GG 1), which contributes to overdiagnosis. Perilesional sampling around MRI-visible lesions has been proposed as a strategy to mitigate targeting imprecision while limiting sampling outside the MRI lesion area and GG 1 detection. The primary objective is to determine the diagnostic performance of the experimental targeted + perilesional biopsy scheme for detection of csPC in comparison to the standard targeted + systematic biopsy scheme.

CLINICAL TRIAL DESIGN AND TIMEFRAME: TARGET is a prospective, multicentre, open-label, comparative clinical trial. Each patient acts as their own control, as each patient will undergo all three types of biopsy (targeted, perilesional, and systematic). The inclusion period will last for 21 mo, and the participation duration for each patient is 3 mo.

ENDPOINTS: The primary endpoint is the sensitivity and specificity of the targeted + perilesional scheme for csPC detection in comparison to the targeted + systematic scheme. Secondary endpoints include differences in the detection rate for insignificant PC (GG 1) and aggressive PC (GG ≥3) between the experimental and standard biopsy schemes.

DATA SOURCES AND STATISTICAL ANALYSIS PLAN: The data collected will include patient demographics and laboratory, radiology, and pathology reports. Analyses will be performed with SAS version 9.4 using a locked database.

STRENGTHS AND LIMITATIONS: Strengths include the prospective and multicentre design. The main limitation is the open-label design.

FUNDING: TARGET is funded by Ramsay Générale de Santé (Paris, France), and supported by the Prostate Cancer Committee of Association Française d’Uologie.

ETHICS AND TRIAL REGISTRATION: The trial was assessed by the CPP Ouest VI ethics committee and is registered on ClinicalTrials.gov as NCT07296042.

PATIENT SUMMARY: Our multicentre trial is comparing two different approaches for prostate biopsy to determine if sampling the area around lesions seen on an MRI (magnetic resonance imaging) scan can maintain the detection rate for clinically significant prostate cancer while reducing detection of low-risk disease.

PMID:41813528 | DOI:10.1016/j.euo.2026.02.003

Lancet Digit Health. 2026 Mar 10:100963. doi: 10.1016/j.landig.2025.100963. Online ahead of print.

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a life expectancy of only 3-5 years and few approved treatments. To identify drug repurposing candidates for the treatment of ALS, we analysed the electronic health records (EHRs) of a large cohort of military veterans with ALS.

METHODS: We analysed the EHRs of individuals in the US Veterans Health Administration (VHA) database who were diagnosed with ALS between Jan 1, 2009 and Dec 31, 2019 to assess medication effects. Individuals without recorded prescriptions after the date of diagnosis were excluded. Two sets of criteria were applied to ascertain exposure. Exposure criteria A were met if the dispense date or the end date of the medication was within 12 months of ALS diagnosis and the end date was at least 6 months after the dispense date. Exposure criteria B were met if there were at least two dispenses within 6 months before diagnosis and 12 months after diagnosis. Propensity score-matched control groups were generated on the basis of confounders included in the EHR, with methodology of potential outcomes used to infer treatment effects. The primary outcome was death. A standard Cox proportional hazards analysis was done to assess association with survival. Survival was defined as the time from diagnosis date recorded in the EHR to death reported in the Department for Veterans Affairs Vital Status File. Follow-up survival time was censored on Dec 31, 2020, for those alive on this date. Downstream protein targets of drugs with clinically significant effects were analysed using the protein-protein interaction networks-based algorithm PathFX.

FINDINGS: The EHRs of 11 003 individuals with ALS in the VHA database were appropriate for analysis. 162 medications with treatment groups of 30 or more individuals were identified. Among these 162 medications, 27 were associated with statistically significant changes (≥0·1) in the hazard ratio (HR) for death. 18 of the medications were associated with a reduced HR for death (prolonged survival), and nine were associated with an increased HR for death (reduced survival). Drugs associated with reduced HR included HMG-CoA reductase inhibitors (simvastatin, pravastatin, lovastatin, and atorvastatin), PDE5 inhibitors (vardenafil and sildenafil), and α-adrenergic antagonists (tamsulosin and terazosin). The medications associated with an increased HR were drugs used either in the management of clinical features of ALS associated with poor outcomes or in end-of-life care. PathFx analysis identified a complex of proteins interacting with several of the identified drugs.

INTERPRETATION: To our knowledge, this analysis is the largest EHR-based study for identifying drug repurposing candidates for ALS. We identified several drugs that warrant further assessment as therapeutic options in ALS, as well as a protein network complex that might serve as a therapeutic target for ALS.

FUNDING: Congressionally Directed Medical Research Programs, US Department of Defense.

PMID:41813498 | DOI:10.1016/j.landig.2025.100963

JMIRx Med. 2026 Mar 3;7:e73211. doi: 10.2196/73211.

ABSTRACT

BACKGROUND: The IT sector is growing and encompasses all professions, from leisure and recreation to hospitals and emergency response groups. IT professionals are experiencing increased threats (eg, ransomware attacks), but little is known about the relationship between these IT profession-specific stressors and the professionals’ mental health.

OBJECTIVE: This study aimed to (1) estimate the associations between IT profession-specific stressors and anxiety, depression, and stress, and (2) examine the role of mental health literacy (MHL) as a mediator of the relationship between depression, anxiety, stress, and help-seeking.

METHODS: Between February and May 2023, IT professionals working in the United States were surveyed online. Participants (n=357) reported demographic characteristics, MHL, mental health symptoms, and help-seeking intentions with the following scales: Mental Health Literacy in the Workplace (MHL-W), Center for Epidemiological Studies Depression-10 (CESD-10), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale-10 (PSS-10), and the Mental Help Seeking Intention Scale (MHSIS). Descriptive statistics, regression models, and mediation analyses were conducted for CESD-10, GAD-7, and PSS-10.

RESULTS: Respondents who had experienced ransomware attacks in the past year reported significantly higher symptoms of depression (odds ratio [OR] 1.85, 95% CI 1.07-3.22; P=.03). Past-year exposure to balancing security and usability was associated with lower odds of reported anxiety (OR 0.48, 95% CI 0.28-0.82; P=.008). Having made critical technology decisions with limited information in the past year was associated with higher perceived stress by 2.02 points on the PSS-10 scale (SE 0.84, 95% CI 0.37-3.66; P=.02), and working with limited resources in the past year increased perceived stress by 1.70 points (SE 0.84, 95% CI 0.04-3.35; P=.04) after adjusting for the covariates. MHL was found to partially mediate the relationship between depression and help-seeking, but not between anxiety or stress and help-seeking.

CONCLUSIONS: These findings provide insight into the workplace stressors that pose a greater psychological health risk for IT professionals. These results emphasize the important role of MHL in helping facilitate the connection between depressive symptoms and help-seeking.

PMID:41813447 | DOI:10.2196/73211

JMIR Res Protoc. 2026 Mar 9;15:e77786. doi: 10.2196/77786.

ABSTRACT

BACKGROUND: Multi-organ autoimmunity belongs to a group of ultrarare diseases characterized by complex autoimmune or autoinflammatory processes affecting multiple organs. In addition to adequate medical care for patients with multi-organ autoimmunity, the understanding of patients’ treatment preferences and the measurement of their health-related quality of life are essential for improving therapy for these patients.

OBJECTIVE: This study has three goals: (1) to compile a modular questionnaire package using established instruments to assess health-related quality of life and health status; (2) to develop, through a participatory process, and conduct psychometric testing of a new self-report questionnaire assessing patients’ treatment preferences; and (3) to evaluate quality of life and patients’ preferences in a longitudinal study.

METHODS: To address our goals, we are conducting a mixed methods study involving 300 adult patients undergoing treatment for multi-organ autoimmune diseases; the study includes qualitative interviews with patients and their physicians and a quantitative longitudinal study with 4 measurement time points (at study enrollment and at 3, 6, and 9 months later). We will address our first goal by conducting psychometric analyses to assess the applicability of the modularized questionnaire package to our target population. We will determine item characteristics and conduct exploratory factor analyses and internal consistency analyses with the scales used to assess generic and disease-specific quality of life, as well as disease-specific health status. To address our second goal, we will conduct (1) qualitative interviews with patients and their physicians to explore the preferences of our target population, (2) a 2-round Delphi study to select preferences that are highly relevant to most patients, (3) cognitive pretests to ensure the acceptability and comprehensibility of the scale items and instructions, and (4) psychometric analyses to guide item selection and evaluate the reliability and validity of the final scales.

RESULTS: This paper describes the protocol for the longitudinal cohort study of the research project Qualy-GAIN (German Multi-Organ Auto-Immunity Network), which was funded from January 2023 to December 2025. Data were collected at 4 measurement points from July 2024 to June 2025. First results are expected to be submitted for publication in spring 2026.

CONCLUSIONS: A result of this study will be a package of questionnaires that can be used to assess health-related quality of life, disease-specific health status, and treatment preferences. Due to the voluntary nature of participation and the low burden associated with participation, we believe that the benefits of the study outweigh potential risks. In case the questionnaires evaluated in this study prove to be reliable, valid, and useful in practice, they can be transferred to the routine treatment of patients with multi-organ autoimmune diseases to improve treatment and promote patient-centered care.

PMID:41813446 | DOI:10.2196/77786

JMIR Res Protoc. 2026 Mar 6;15:e82491. doi: 10.2196/82491.

ABSTRACT

BACKGROUND: Treatment-resistant depression (TRD), affecting approximately 20% to 30% of individuals with major depressive disorder, is associated with significant disability, reduced quality of life, and an increased risk of hospitalization and suicide. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation therapy, has demonstrated strong efficacy for TRD but is typically limited to research contexts or private clinics. Existing research on patient perspectives on rTMS is limited and largely retrospective, focusing on individuals who have already undergone treatment. As a result, little is known about the factors that influence patients’ decisions to accept or decline rTMS at the time of referral, particularly within real-world clinical settings.

OBJECTIVE: This study aims to address the gap in the literature by prospectively examining decision-making processes surrounding rTMS in a community hospital outpatient clinic.

METHODS: This prospective mixed methods cohort study will recruit 30 adults with TRD referred to a public rTMS clinic. Participants will be stratified based on their decision to opt in or out of treatment. Data collection will include hybrid card sorting interviews, self-report questionnaires (assessing depression, well-being, cognitive flexibility, decisional conflict, and health literacy), and medical chart reviews. Each participant will complete a baseline and 6-month follow-up interview and survey. Qualitative data will be analyzed using constant comparative analysis, informed by bounded rationality and prospect theory. Quantitative data will be analyzed using bivariate statistics and hierarchical cluster analysis to identify patterns in decision-making factors.

RESULTS: This study is being funded by a charitable donation from Jack and Pat Kay to Humber River Health, which is also supporting the establishment of the rTMS clinic, committed to in April 2024. Recruitment commenced in December 2025 and is expected to conclude in December 2026; no participants have been enrolled as of February 2026.

CONCLUSIONS: To the best of our knowledge, this is the first study to prospectively examine decision-making regarding rTMS in a real-world, publicly funded clinic including both individuals who initiate and those who decline treatment. The findings may inform the development of patient educational and engagement materials and highlight gaps in patient-physician communication during the rTMS decision-making process.

PMID:41813443 | DOI:10.2196/82491

JMIR Res Protoc. 2026 Mar 3;15:e84218. doi: 10.2196/84218.

ABSTRACT

BACKGROUND: The early detection of cognitive impairments in individuals with psychosis offers a means to support clinical and functional recovery. However, there are significant barriers to assessing cognition in clinical services, including lack of staff time, training, and confidence in administering assessments. We have developed the Cardiff Online Cognitive Assessment (CONCA), aiming to address these barriers, and here present the protocol to assess its acceptability as a clinical tool.

OBJECTIVE: The aim of this study is to conduct the early-stage testing of the CONCA as a clinical tool to determine whether it is acceptable to young people with a history of psychosis and to health professionals.

METHODS: This cross-sectional study will use a mixed methods approach. A total of 100 young people with a history of psychosis will complete the CONCA and an acceptability questionnaire. We will conduct qualitative interviews with a minimum of 20 participants with psychosis and 10 participants with professional experience of working in early intervention in psychosis services to explore opinions on the CONCA as a clinical tool, attitudes toward and barriers or facilitators of implementing the CONCA, and cognitive testing more generally in clinical services. Quantitative data will be analyzed using descriptive statistics and linear or logistic regression. Qualitative interviews will be analyzed using a deductive thematic analysis approach.

RESULTS: The enrollment of study participants started in July 2025 and is expected to end in October 2026. Data analysis is expected to be finalized by March 2027. As of September 15, 2025, we have enrolled 26 participants with psychosis in the quantitative arm of the study, and 4 participants with psychosis and 1 health professional in the qualitative arm.

CONCLUSIONS: Our results will provide new data on the acceptability of the CONCA and cognitive testing more generally among patients and clinicians, as well as identify barriers and facilitators to the CONCA’s implementation. This will provide the groundwork for a larger hybrid effectiveness-implementation study.

PMID:41813441 | DOI:10.2196/84218

Early Interv Psychiatry. 2026 Mar;20(3):e70166. doi: 10.1111/eip.70166.

ABSTRACT

INTRODUCTION: Quality of Life (QoL) is an important outcome measure for people with a first episode psychosis (FEP). Despite high numbers of patients being admitted to psychiatric hospitals following an FEP, the impact of hospital admission on outcome measures such as QoL is under-investigated. This study aimed to systematically review evidence of the impact of hospital admission on QoL in patients with an FEP.

METHODS: A systematic review was conducted in line with the PRISMA Guidelines. PsychINFO, Medline, CINAHL, and EMBASE were searched from 2000 to 2022, examining the impact of QoL for people with an FEP following a hospital admission. Quantitative, qualitative, and mixed methods studies were included in the search. Study quality was assessed using the Mixed Methods Assessment Tool. Data was analysed using narrative synthesis.

RESULTS: Seven hundred and eight two abstracts were found. Fifty-three full texts were reviewed. Data was extracted for eight articles. Across the eight studies, four discrete QoL measures were employed. Results showed that QoL scores were consistent over time, with little statistical change from baseline to follow-up. Across studies, participants reported low average QoL scores. Across studies, information on the treatment components and duration of hospital admission were scarce.

CONCLUSION: There is a relative paucity of studies that have examined QoL in relation to hospital admission. QoL scores remained consistent over time, suggesting that QoL is relatively well preserved at the first episode. Further research is needed on the impact of inpatient-based interventions in FEP.

PMID:41813438 | DOI:10.1111/eip.70166

JMIR Res Protoc. 2026 Mar 5;15:e82245. doi: 10.2196/82245.

ABSTRACT

BACKGROUND: Problematic digital media use (PDMU) among young people has been on the rise. PDMU is defined as excessive use of digital media, the internet, or electronic communication leading to user dysfunction and harm to other individuals. Evidence links excessive use of media with various mental health disorders, behavioral problems, substance abuse, poor sleep hygiene, and social dysfunction. This maladaptive behavior is pervasive among young people, yet there is a paucity of studies that comprehensively examine the phenomenon in this specific population.

OBJECTIVE: This systematic review seeks to examine the current global prevalence of PDMU among young adults aged 18 to 24 years, explore the extent of the issue across different regions of the world, and identify key factors contributing to its occurrence.

METHODS: The proposed systematic review will use the Prevalence Estimates Reviews – Systematic Review Methodology Group (PERSyst) methodology for systematic reviews of prevalence and incidence. A 3-step search strategy will be used covering 2020 to 2025, with no language restrictions. Nine sources will be searched: Embase (Elsevier), PubMed, PsycInfo (EBSCO), Web of Science Core Collection (Clarivate), Communication & Mass Media Complete (EBSCO), LILACS (VHL Search Portal), China National Knowledge Infrastructure, ProQuest Dissertations and Theses Global, and Google Scholar. Study selection will follow a 3-step process, including critical appraisal for methodological quality. Standardized data extraction tools will be used. Two reviewers will make decisions independently; conflicts will be resolved through consensus. Narrative synthesis will be conducted, and where possible, a meta-analysis will estimate PDMU prevalence with 95% CIs using a random-effects model. Heterogeneity will be assessed using the chi-square and I2 statistics. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to assess the certainty of the evidence.

RESULTS: The protocol was completed in July 2025. The comprehensive search of electronic bibliographic databases began in September 2025, followed by deduplication, screening, and selection of eligible studies. Title and abstract screening were completed in January 2026, and full-text review is ongoing. Data extraction and synthesis will be conducted between March and April 2026. The manuscript will be prepared and completed by August 2026, with plans to submit the manuscript for publication in September 2026.

CONCLUSIONS: The planned review contributes to the growing body of evidence on digital media use among young adults by highlighting its potential impact on overall well-being. To our knowledge, this is the first comprehensive synthesis focused specifically on this population. The findings are expected to highlight the need for routine screening and early intervention strategies to address the social, mental, and physical health risks associated with digital media overuse in young adulthood.

PMID:41813435 | DOI:10.2196/82245

JMIR Res Protoc. 2026 Mar 5;15:e86322. doi: 10.2196/86322.

ABSTRACT

BACKGROUND: Multiple myeloma (MM) is characterized by kidney deficiency, phlegm, and blood stasis as core findings, specifically in Traditional Chinese Medicine (TCM), and the kidney-tonifying, phlegm-resolving, and blood stasis-removing (KPR) method is a fundamental therapeutic approach for MM in TCM. Western medicine primarily focuses on targeted immunotherapy or chemotherapy for MM treatment, whereas TCM characterizes MM through distinct pathological patterns that directly correspond to immune microenvironment dysregulation. Emerging evidence implicates the PHD finger protein 19 (PHF19)/enhancer of zeste homolog 2 (EZH2)/trimethylated histone H3 at lysine 27 (H3K27me3) epigenetic axis in immune microenvironment dysregulation and MM progression. Notably, TCM “blood stasis” correlates with hypoxia-induced immune gene silencing in MM bone marrow, and KPR (a clinically validated TCM decoction with 16 herbs) acts on this axis via its active components that regulate EZH2 and epigenetic function, merging TCM syndrome differentiation with modern epigenetics. We have designed a randomized controlled trial (RCT) to investigate the mechanism of action and safety of the KPR method in MM.

OBJECTIVE: This RCT aims to assess whether a KPR herbal formula combined with standard bortezomib-based therapy improves the immune microenvironment via the PHF19-EZH2-H3K27me3 epigenetic axis to restore immune function in MM, providing a mechanistic basis for integrating TCM into evidence-based oncology care in relapsed or refractory patients.

METHODS: This is a single-center, prospective RCT involving patients with MM. It has been designed to test the hypothesis that the KPR formula epigenetically regulates the PHF19-EZH2-H3K27me3 axis to improve the immune microenvironment. Patients are randomly assigned in a 1:1:1 ratio to 3 groups (blank control group, Western medicine control group, and integrated TCM and Western medicine treatment group). All patients undergo 12 weeks of treatment and a 6-month follow-up. The primary outcome is the CD3+ T-cell ratio in bone marrow/peripheral blood, which is detected by flow cytometry. The secondary outcomes include quantified TCM syndrome scores, Western medicine efficacy evaluation criteria, complete blood count, bone marrow morphology, blood and urine immunoglobulin levels, quantitative M protein levels, free light chain levels, β2-microglobulin levels, and whole-body imaging findings. Statistical analysis involves linear mixed models for longitudinal data and Bonferroni correction to verify KPR’s immunomodulatory effects via the targeted epigenetic axis.

RESULTS: This study was funded in November 2023. Recruitment was initiated in March 2025 and is expected to be completed in February 2026. As of October 2025, 41 patients have been enrolled. Data collection is projected to end in October 2026. Data analysis has not yet been initiated, and the results are expected to be published in 2027.

CONCLUSIONS: This unique mechanistic RCT evaluating a TCM formula targeting the PHF19-EZH2-H3K27me3 axis in patients with MM will establish a biomarker-driven framework for integrating TCM with immunotherapy, offering novel strategies for treatment-refractory patients.

PMID:41813432 | DOI:10.2196/86322

JMIR Nurs. 2026 Mar 5;9:e77051. doi: 10.2196/77051.

ABSTRACT

BACKGROUND: The integration of digital health technologies (DHTs) in clinical practice is accelerating, creating a need for nursing students to develop digital competencies aligned with professional expectations. In Quebec, curricular reforms aim to enhance digital health literacy, but data are limited on students’ preparedness.

OBJECTIVE: This study aimed to assess nursing students’ perceptions, self-reported competencies, and willingness to engage with DHTs across different academic years.

METHODS: A cross-sectional descriptive survey assessing self-reported digital health competencies, attitudes, perceived training coverage, and intentions was conducted using an online questionnaire administered through Qualtrics. Participants (N=136) were recruited from 3 cohorts: first-year (group 1; n=58, 42.6%), second-year (group 2; n=55, 40.4%), and third-year (group 3; n=23, 16.9%) nursing students. Data were analyzed using descriptive statistics and ANOVAs, with post hoc analyses performed via SPSS.

RESULTS: Significant differences were observed among cohorts concerning digital competencies and access to digital tools. Compared with first-year students (group 1), third-year students (group 3) showed higher proficiency with electronic medical records (group 3: mean 3.29, SD 1.31; group 1: mean 2.59, SD 1.32; P=.01), virtual reality (group 3: mean 4.53, SD 1.11; group 1: mean 2.90, SD 1.44; P<.001), and clinical databases (group 3: mean 4.59, SD 1.00; group 1: mean 3.21, SD 1.55; P<.001). Despite positive attitudes toward DHTs across all groups, training coverage for most digital tools was perceived as low, with the highest levels reported for clinical databases (mean 2.97, SD 1.1). This underscored a substantial gap between institutional expectations and actual digital training across all cohorts.

CONCLUSIONS: This study highlights critical gaps in digital health training among nursing students, emphasizing the need for targeted curricular reforms such as the one currently underway at the Université de Montréal. These efforts represent a promising opportunity to better align educational content with the evolving demands of health care systems. Today, preparing students in digital competencies is no longer just advantageous but may soon become essential for the next generation of nurses to navigate and lead within technology-driven care environments.

PMID:41813428 | DOI:10.2196/77051