Nevin Manimala

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

Cereb Cortex. 2026 Mar 3;36(3):bhag024. doi: 10.1093/cercor/bhag024.

ABSTRACT

Understanding how differences in brain structure relate to differences in cognition across the lifespan is essential for addressing age-related cognitive decline. Since age is strongly associated with both brain structure and cognition, predictive models often risk simply capturing age effects. To mitigate this risk, deconfounding is typically applied to remove the effects of age. Here, beyond treating age as a confound, we treat it as a moderator by estimating brain-cognition associations separately across age groups. This captures age-stratified changes in how brain structure and cognitive performance are statistically connected. For this view to hold, variations in brain structure linked to differences in cognitive performance in older subjects (eg related to disease) would differ from those in younger subjects. Using structural brain imaging data from the UK Biobank we found an asymmetry in generalisability: models trained on younger subjects successfully predicted cognition in older subjects, but models trained on older subjects failed to generalize to younger individuals. These findings reveal a trade-off between model specificity and generalisability, suggesting the optimal approach-whether age-specific or pooled-depends on the research or clinical goal for the target population.

PMID:41812241 | DOI:10.1093/cercor/bhag024

Genetics. 2026 Mar 11:iyag068. doi: 10.1093/genetics/iyag068. Online ahead of print.

ABSTRACT

Pool-seq (pooled sequencing) combines DNA from multiple individuals prior to sequencing, enabling population-level allele frequency estimation without individual genotyping. When employed in a case-control Genome Wide Association Study (GWAS) framework, pool-seq faces a fundamental power limitation: Errors on allele frequency estimates are inversely proportional to sequence coverage and are large at modest coverage levels. Although this power limitation is appreciated, modestly sized pool-seq GWAS lacking unambiguous hits are often interpreted as showing a polygenic genetic architecture. We illustrate that this inference is unwarranted using empirical data from a Drosophila zinc resistance mapping study. Despite achieving >700× sequencing coverage in case and control pools, a directly ascertained SNP-based GWAS failed to reveal clear evidence for major-effect loci. A unique feature of the dataset is that an advanced intercross multiparent population, with known founders, was employed as the GWAS population. We leverage this unique population structure, in a manner that would not be possible in an outbred panel, to carry out two additional GWASs using imputed haplotype- or SNP-frequency estimates, which in contrast uncover localized regions of major effect. The key difference between approaches lies in statistical power: directly ascertained SNP counts have errors inversely proportional to sequencing coverage, whereas known founder imputation-based approaches can be considerably more accurate. In outbred populations where imputation cannot be used to obtain more accurate allele frequency estimates, substantially higher coverage than currently envisioned may be required to reliably detect modest allele frequency shifts. This work highlights that insufficiently powered GWAS studies can mask simple genetic architectures and create the illusion of polygenicity through statistical noise alone.

PMID:41812229 | DOI:10.1093/genetics/iyag068

J Med Entomol. 2026 Mar 9;63(2):tjag017. doi: 10.1093/jme/tjag017.

ABSTRACT

Malaria remains a significant public health burden in Cameroon, with high prevalence in the North Region. The success of control strategies depends on community understanding and practices. This study assessed the knowledge, attitudes, and practices towards malaria and mosquitoes in the region. A community-based cross-sectional survey was conducted in 2021 using structured questionnaires with 500 households across 50 randomly selected villages. Descriptive statistics were used for analysis. Malaria awareness was universal (100%), nearly all respondents (99.6%) correctly identified mosquito bites as the primary transmission route. However, a significant misconception persisted, with 42.4% also attributing transmission to cold weather. Mosquito net use was nearly universal (99.6%; 96.2% used one the previous night), yet 90.4% reported misusing nets for other purposes (tying animals: 35.8%; fishing: 7.4%). Thus, there was a contradiction between the high rate of ITN ownership and their widespread misuse. Self-medication was the most common first response to symptoms (43.2%), primarily due to the perceived high cost of hospital care (39.6%) and perceived staff carelessness (14.3%). Only 19.0% sought treatment within 24 h of symptom onset. Use of complementary vector control methods was low, and 17 plant species were documented for malaria treatment. While general knowledge is high, critical gaps and detrimental practices persist. The findings reveal a stark divergence between high net ownership and widespread misuse, coupled with suboptimal treatment-seeking behavior. This underscores the urgent need for targeted health education to correct misconceptions, promote proper net use, and encourage timely treatment to enhance malaria control efficacy in the region.

PMID:41812226 | DOI:10.1093/jme/tjag017

JMIR Form Res. 2026 Mar 11;10:e86070. doi: 10.2196/86070.

ABSTRACT

BACKGROUND: Approximately 45% of individuals taking methadone or buprenorphine have chronic pain. These medications are commonly prescribed for chronic pain or opioid use disorder (OUD). To optimize pain management as well as reduce opioid-related symptoms (eg, craving) and risks (misuse and overdose), there is a critical need for a brief, effective, and accessible pain skills intervention for this population.

OBJECTIVE: This single-arm study aimed to examine the feasibility and preliminary efficacy of online Empowered Relief (ER), a 1-session pain relief skills class, for individuals with chronic pain taking methadone or buprenorphine for chronic pain or OUD.

METHODS: A priori feasibility criteria were defined as at least 75% of enrolled participants attending the ER class and the mean satisfaction rating of at least 8 on a 0-10 scale. Participants were recruited nationally across the United States. Out of the 69 enrolled participants, 55 attended the ER class. Self-report measures were collected at baseline, immediately post class, and at follow-up points of 2 weeks and months 1-3. Additionally, qualitative interviews were conducted in a small sample (n=14) to obtain in-depth participant feedback. Among the class attendees, 51 participants (27/51, 52.9% female; mean age 48.6, SD 12.2, range 28-71 years) completed at least one follow-up survey, and treatment outcomes were analyzed using repeated measures ANOVA, with missing data imputed using linear regression. This analytic sample consisted of 24 participants taking methadone and 27 participants taking buprenorphine; 43.1% (22/51) endorsed at least≥2 OUD symptoms within the past 12 months, meeting the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) diagnostic criteria for current OUD.

RESULTS: Feasibility was achieved with 79.7% (55/74) attendance and mean 8.6 (SD 2) ratings of treatment appraisal and satisfaction. Qualitative feedback demonstrated high acceptability of the class content and delivery, with suggestions for refinements. Repeated-measures ANOVAs and FDR-corrected post hoc tests revealed significant reductions at 1 month post-ER class (primary endpoint) in pain intensity (Cohen d=0.71), pain bothersomeness (Cohen d=0.54), and pain interference (Cohen d=0.61). At 3 months post-ER class, efficacy was maintained for pain intensity, pain bothersomeness, and pain interference (Cohen d=0.28, 0.44, and 0.48, respectively). No significant time effects were observed for pain catastrophizing, sleep disturbance, physical function, fatigue, depression, anxiety, social isolation, and opioid craving.

CONCLUSIONS: This study is the first to test ER in patients taking methadone or buprenorphine for pain or OUD. Findings showed feasibility, acceptability, and preliminary evidence of treatment efficacy. Participant feedback will inform future study designs. These findings support a randomized trial to fully evaluate the efficacy and scalability of ER in this population.

PMID:41812186 | DOI:10.2196/86070