Category: Nevin Manimala

JAMA Netw Open. 2026 Apr 1;9(4):e269347. doi: 10.1001/jamanetworkopen.2026.9347.

ABSTRACT

IMPORTANCE: The use of audiovisual aids in the consent process may improve comprehension and willingness to participate in research. However, data supporting this hypothesis are lacking.

OBJECTIVE: To determine the impact of audiovisual augmentation of the consent process on willingness to participate in research and on consent comprehension.

DESIGN, SETTING, AND PARTICIPANTS: The Personalizing Cardiovascular Health: A Population Approach to Promoting Cardiovascular Disease Resistance and Resilience Among Individuals With Obesity (RESILIENCE) nonrandomized cohort study embedded this multiarm randomized clinical trial to test different participant consent modalities. RESILIENCE recruited participants between September 2019 and March 2022, with the analysis for this randomized substudy conducted from July to December 2025. No follow-up was undertaken for this study. This component of the study was conducted exclusively virtually and completed online within a single large US academic health system.

INTERVENTIONS: Potential participants were randomized for this trial in a 1:1:1:1 allocation to receive consent information via (1) text-only (2) text and physician-featured video, (3) text and patient-featured video, or (4) text and animated video.

MAIN OUTCOMES AND MEASURES: The primary outcome was provision of consent to participate in the cohort clinical study. The secondary outcome was consent comprehension, based on a score of at least 5 of 7 on a follow-up comprehension survey. Robust log-linear Poisson regression was used to determine the relative risks (RRs) of outcomes in comparison with the text-only arm. Analyses were conducted with the evaluable population.

RESULTS: Of 1535 participants (968 [63.1%] female; 658 [42.9%] ≥60 years of age; 380 randomized to text-only, 386 to text and physician-featured video, 383 to text and patient-featured video, and 386 to text and animated video) who began the consent process, 888 (57.9%) overall gave consent to participate in the study. Patient consent rates were similar across the 4 consent delivery strategies (text only [comparator], 221 of 380 [58.2%]; text and physician video, 241 of 386 [62.4%]; RR, 1.07 [96% CI, 0.95-1.21]; text and patient video, 203 of 383 [53.0%]; RR, 0.91 [96% CI, 0.8-1.04]; and text and animated video, 223 of 386 [57.8%]; RR, 0.99 [96% CI, 0.88-1.13]). Among 884 individuals who consented and completed the consent comprehension survey, the rate of comprehension of the consent process was high 86.4% (n = 764) and did not vary among the intervention delivery strategies (text only, 193 of 221 [87.3%]; text and physician video, 207 of 241 [85.9%]; text and patient video, 177 of 203 [87.2%]; and text and animated video, 187 of 223 [83.9%]). Compared with the text-only arm, the RRs of consent comprehension were not different for the text and physician-featured video arm (RR, 1.00; [95% CI, 0.93-1.07]), the text and patient-featured video arm (RR, 1.00 [95% CI, 0.93-1.07]) and the text and animated video arm (RR, 0.96 [95% CI, 0.89-1.04]).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of virtual consent delivery, the rates of patient consent and consent comprehension were similar regardless of whether they were delivered by text only or text augmented by physician, patient, or animated videos. Further evaluation of these consent delivery processes across different study types and patient populations is suggested to optimize the recruitment of diverse, informed populations.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04551872.

PMID:42060306 | DOI:10.1001/jamanetworkopen.2026.9347

JAMA Netw Open. 2026 Apr 1;9(4):e269923. doi: 10.1001/jamanetworkopen.2026.9923.

ABSTRACT

IMPORTANCE: Approximately 1% of newborns receive advanced neonatal resuscitation interventions (ANRIs; consisting of endotracheal intubation, chest compressions, and epinephrine administration), the likelihood of which increases with known clinical factors. Associations of socioeconomic status (SES) and health system factors with ANRI are unknown.

OBJECTIVE: To examine the associations among maternal SES, remoteness of maternal residence, birth-site level of service, clinical factors, and ANRIs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used an administrative dataset of all live births at 34 weeks’ gestation or later between January 1, 2000, and December 31, 2020, in Alberta, Canada, a jurisdiction with universal health care and provincially coordinated Neonatal Resuscitation Program training. Hospital births and home births attended by registered midwives were included. Statistical analyses were conducted from August 1 to September 30, 2025.

EXPOSURES: Maternal SES (classified according to Pampalon Material Deprivation Index quintiles), remoteness of residence (categorized using the Statistics Canada Remoteness Index), birth-site level of service, and clinical factors (including maternal, intrapartum, and fetal or neonatal characteristics).

MAIN OUTCOMES AND MEASURES: The primary outcome was any ANRI. Secondary outcomes were individual interventions (endotracheal intubation, chest compression, epinephrine administration). Multivariable logistic regression with stepwise variable selection was used to examine associations between SES and health system factors and the primary outcome.

RESULTS: A total of 966 475 live births at 34 weeks’ gestation or later were analyzed, of whom 1.0% received ANRI. Neonates had a mean (SD) gestational age of 38.9 (1.48) weeks and included 494 835 males (51.2%); mothers had a mean (SD) age of 29.4 (5.46) years. Compared with level 2 birth sites, level 3 birth sites had lower odds of ANRI (odds ratio [OR], 0.57; 95% CI, 0.53-0.61) and all interventions. Births at level 1A sites (OR, 2.53; 95% CI, 1.99-3.15) and home births (OR, 1.44; 95% CI, 1.18-1.74) had higher odds of ANRI and chest compressions (OR, 7.32 [95% CI, 5.61-9.40] and 4.12 [95% CI, 3.29-5.11], respectively). All level 1 births (level 1C: OR, 0.54; 95% CI, 0.49-0.60; level 1B: OR, 0.52; 95% CI, 0.45-0.59; and level 1A: OR, 0.4 95% CI, 0.20-0.71) and home births (OR, 0.27; 95% CI, 0.16-0.43) were associated with lower odds of endotracheal intubations. There were no associations for maternal SES and maternal residence remoteness. The most significant clinical factors associated with ANRI were maternal general anesthesia (OR, 4.89; 95% CI, 4.47-5.34), lower gestational age (highest OR at 34 weeks: 3.60; 95% CI, 3.11-4.15), cesarean delivery (OR, 1.80; 95% CI, 1.60-2.02), meconium-stained amniotic fluid (OR, 2.05; 95% CI, 1.94-2.17), and macrosomia (OR, 1.83; 95% CI, 1.55-2.16).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, maternal SES and maternal residence remoteness were not associated with increased odds of ANRI, and birth sites with a lower level of service were associated with higher odds of chest compressions but lower odds of endotracheal intubations. Clinicians should be prepared to resuscitate neonates exposed to general anesthesia.

PMID:42060305 | DOI:10.1001/jamanetworkopen.2026.9923

JAMA Netw Open. 2026 Apr 1;9(4):e269930. doi: 10.1001/jamanetworkopen.2026.9930.

ABSTRACT

IMPORTANCE: Delays in hospital discharge to skilled nursing facilities (SNFs) are widely viewed by hospital administrators and policymakers as a significant contributor to hospital crowding and adverse patient outcomes. However, the extent to which regional SNF capacity is associated with hospital length of stay (LOS) is not well understood.

OBJECTIVES: To construct empirically derived hospital-SNF markets using a network science approach and to examine whether variation in SNF capacity within these markets is associated with hospital LOS.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used 2018 and 2019 Medicare fee-for-service claims linked with publicly available SNF data and included 3.34 million inpatient admissions discharged to SNFs from short-term hospitals in the US. Data were analyzed from October 1, 2024, to February 28, 2026.

EXPOSURES: Monthly mean SNF occupancy rates and nurse and therapy staffing levels within an empirically defined regional hospital-SNF market from a patient-sharing network analysis.

MAIN OUTCOMES AND MEASURES: The main outcome was hospital LOS. Linear regression models estimated associations between market-level SNF capacity measures and LOS, adjusting for patient characteristics, hospital-level postacute care demand, SNF organizational features, and time and hospital-SNF market fixed effects. Analyses were stratified by dual Medicare-Medicaid eligibility.

RESULTS: The study sample included 3.34 million Medicare inpatient admissions (mean [SD] age, 78.6 [11.3] years; 60.2% women) discharged to SNFs across 62 303 hospital-SNF dyads, and 421 empirically derived hospital-SNF markets. The mean (SD) hospital LOS was 6.9 (6.8) days (7.4 [7.8] days for dual-eligible patients and 6.7 [6.2] days for non-dual-eligible patients). Within markets, each additional nurse staffing hour per patient-day was associated with a 3.5% shorter LOS (95% CI, -5.5% to -1.4%); associations were also found among dual-eligible patients (-3.9% [95% CI, -6.7% to -0.9%) and non-dual-eligible patients (-3.2% [95% CI, -5.4% to -0.9%]). Differences in occupancy rates and therapy staffing within networks were not associated with differences in LOS after adjusting for patient, hospital, and network factors.

CONCLUSIONS AND RELEVANCE: Hospital-SNF markets defined by the strength of patient-sharing relationships provide a reproducible framework for examining postacute care capacity across payer populations. Within these markets, for the Medicare fee-for-service population, higher nurse staffing levels were associated with shorter hospital LOS. Strategies to reduce discharge delays and hospital crowding may require closer alignment between hospitals and highly connected SNFs to maintain adequate postacute care capacity.

PMID:42060304 | DOI:10.1001/jamanetworkopen.2026.9930

JAMA Netw Open. 2026 Apr 1;9(4):e269937. doi: 10.1001/jamanetworkopen.2026.9937.

ABSTRACT

IMPORTANCE: Identifying factors that explain differences in physical performance measures by race and region in the US and whether they are associated with changes over time could inform preventive strategies.

OBJECTIVE: To examine 10-year changes in physical performance across race and race-region among Black and White older adults and whether differences are explained by demographic, cardiovascular, socioeconomic, and cognitive factors.

DESIGN, SETTING, AND PARTICIPANTS: The prospective Atherosclerosis Risk in Communities (ARIC) cohort study recruited participants between 1987 and 1989. This study included participants from 4 US communities in North Carolina, Mississippi, Maryland, and Minnesota who underwent physical performance evaluations initiated in 2011 to 2013 (visit 5 examinations) and in 3 subsequent in-person examinations conducted over a 10-year period through 2022. Data were analyzed from January through May 2025.

EXPOSURE: Self-identified race and region.

MAIN OUTCOMES AND MEASURES: Physical performance was assessed using the Short Physical Performance Battery (SPPB; score range, 0-12, with higher scores indicating better performance). Multivariable generalized estimating equations estimated cross-sectional differences as well as differences in 10-year changes by race and by race and region, adjusting for demographic, cardiovascular, socioeconomic, and cognitive factors.

RESULTS: Among 5666 participants (mean [SD] age, 75.4 [5.1] years; 3258 [58%] women), 1233 (22%) self-identified their race as Black and 4433 (78%) self-identified their race as White. Adjusting for demographic, cardiovascular, socioeconomic, and cognitive factors explained observed cross-sectional differences in physical performance between Black participants and White participants. However, 10-year SPPB longitudinal declines were steeper for Black participants compared with White participants (absolute difference, -0.80 points; 95% CI, -1.19 to -0.41 points), even after adjusting for all factors that accounted for cross-sectional differences; this finding met the 0.50-point threshold for a clinically meaningful difference. Between-region declines within races also showed notable differences; for example, SPPB declines were steeper for White Maryland participants compared with White North Carolina participants (absolute difference, -1.14 points; 95% CI, -1.45 to -0.83 points), and declines were steeper for Black Mississippi participants compared with Black North Carolina participants (absolute difference, -1.72 points; 95% CI, -2.65 to -0.78 points).

CONCLUSIONS AND RELEVANCE: In this cohort study of older adults, meaningful racial differences in physical performance declines were not explained by commonly suggested drivers of performance differences. Other unmeasured regional features may explain racial differences in decline in physical performance and warrant investigation.

PMID:42060303 | DOI:10.1001/jamanetworkopen.2026.9937

JAMA Netw Open. 2026 Apr 1;9(4):e269948. doi: 10.1001/jamanetworkopen.2026.9948.

ABSTRACT

IMPORTANCE: Children who survive critical illness commonly experience long-term morbidities. Little is known about the association of critical illness with cognitive health due to lack of preillness and postillness assessments and an adequate comparison population.

OBJECTIVE: To use school-based testing to evaluate cognitive health outcomes among children treated in the pediatric intensive care unit (PICU) compared with non-PICU-exposed control students.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study used statewide academic data and propensity score matching of 1088 patients admitted to the only PICU in Arkansas from January 1, 2008, to December 31, 2018, as well as controls matched on sociodemographic and pre-PICU admission academic factors. Statistical analysis was performed from March 2024 to September 2025.

EXPOSURE: PICU admission.

MAIN OUTCOMES AND MEASURES: Primary outcomes were (1) return to standardized testing, assessed using multivariable logistic regression to assess the odds of having a standardized test within 2 years after PICU admission compared with controls, and (2) change in pre-PICU to post-PICU test scores for PICU patients compared with propensity-matched control students, assessed using multivariable linear regression.

RESULTS: In this case-control study of 1088 school-aged patients (mean [SD] age, 12.1 [1.6] years; 566 girls [52.0%]), fewer PICU patients than controls had test scores after admission for math (80.6% [874 of 1085] vs 86.5% [938 of 1085]; adjusted odds ratio [AOR], 0.64 [95% CI, 0.51-0.81]) and reading (81.1% [877 of 1081] vs 87.1% [941 of 1081]; AOR, 0.64 [95% CI, 0.51-0.82]). PICU patients’ preadmission z scores were below average in math (z = -0.23 [95% CI, -0.29 to -0.16]) and reading (z = -0.22 [95% CI, -0.29 to -0.15]) compared with Arkansas students in the same grade and year. In adjusted pre-post analyses, PICU patients had a small but significant decrease in reading relative to controls (-0.07 [95% CI, -0.14 to -0.01]). The change in math score was not statistically significant (-0.06 [95% CI, -0.13 to 0.003]).

CONCLUSIONS AND RELEVANCE: This study suggests that PICU patients were less likely to take standardized tests after discharge and that those who did had greater decreases in reading scores relative to matched controls. Future studies should identify risk factors for nonreturn to testing and score decrease.

PMID:42060302 | DOI:10.1001/jamanetworkopen.2026.9948

Biomed Res Int. 2026;2026(1):e6698526. doi: 10.1155/bmri/6698526.

ABSTRACT

The number of depression sufferers is increasing at an alarming rate around the world. As a result, the usage of antidepressant drugs is growing day by day. However, the effect of this medication on glucose homeostasis is not clear. We investigated the impact of a combined antidepressant drug flupentixol-melitracen on glucose levels and the expression of associated genes in Drosophila melanogaster. The flies were reared in control and treatment vials having standard and drug-treated food. The glucose oxidase method showed significantly reduced glucose levels in the treated Drosophila. The Ct values obtained from qPCR for the relative quantification of Drosophila insulin-like peptide (DILP) genes, DILP5 and DILP6, were analyzed using the 2^-ΔΔCT method. The DILP5 gene was expressed slightly higher in the antidepressant-treated group, though the expressions of the DILP genes appeared statistically insignificant. The current study suggests that anxiolytics and antidepressant drugs might be associated with the insulin signaling pathway, which is crucial for growth, glucose regulation, and other fundamental metabolic processes. Further study is required to determine the expression pattern of all DILP and other genes that might affect glucose homeostasis.

PMID:42060265 | DOI:10.1155/bmri/6698526

Arthroscopy. 2026 Apr 30. doi: 10.1002/arj.70207. Online ahead of print.

ABSTRACT

PURPOSE: To systematically evaluate capsulotomy techniques through patient-reported outcome measures, rates of revision arthroscopy, conversion to total hip arthroplasty, and achievement of clinically meaningful outcomes.

METHODS: PubMed, Scopus, and Embase databases were queried in June 2024 for studies that could be used to compare capsular management strategies primarily via patient-reported outcome measures at a minimum 2-year follow-up. Inclusion criteria consisted of patients who underwent primary hip arthroscopy for the treatment of femoroacetabular impingement, minimum 2-year follow-up, and reported capsulotomy type. Based on the capsular management technique performed, groups were defined as interportal capsulotomy with closure, T-capsulotomy with complete closure, periportal capsulotomy, or puncture capsulotomy. Heterogeneity was adjusted for using metaregression models.

RESULTS: Of the 1322 unique studies identified in our search, 8 studies (1961 hips) were included. The combined puncture capsulotomy and periportal capsulotomy group (mean difference range, 21.30-32.56) performed similarly to interportal capsulotomy with closure (mean difference range, 18.33-32.00) and T-capsulotomy with complete closure (mean difference range, 20.70-23.30) groups in modified Harris Hip Score (P = .274). This continued when evaluating revision and total hip arthroplasty rates (proportion range, 0.0-0.05 and 0.0-0.01, respectively). Metaregression adjustments found baseline modified Harris Hip Score significantly influences mean differences (adjusted mean difference, -0.53 [-0.83, -0.23], P = .0006). When considering the achievement rates of minimal clinically important difference, all capsulotomy methods were similar for modified Harris Hip Score; however, minimal clinically important difference thresholds had a significant influence of -0.46 (95% confidence interval, [-0.54, -0.39], P < .0001) based on a metaregression model.

CONCLUSIONS: Periportal and puncture capsulotomy techniques did not yield statistically different outcomes compared with traditional capsulotomy techniques that use capsular closure at 2-year follow-up.

LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

PMID:42060264 | DOI:10.1002/arj.70207

Prog Orthod. 2026 Apr 30;27(1):19. doi: 10.1186/s40510-026-00620-7.

ABSTRACT

BACKGROUND: Maxillary transverse deficiency is one of the most common issues encountered in orthodontic practice. Ideally, intervention should take place before the midpalatal suture has completely ossified, in order to take advantage of the patient’s active growth. In recent years, treatment with clear aligners has emerged as an alternative to fixed appliances, offering a new way to achieve expansion in paediatric patients.

OBJECTIVES: This systematic review aimed to analyse the predictability of movements induced by clear aligners in maxillary expansion, and to compare the effectiveness of the Invisalign First® system with conventional expansion appliances.

SEARCH METHODS: A systematic review was conducted by searching PubMed-Medline, Scopus, Embase, Web of Science and Cochrane databases.

ELIGIBILITY CRITERIA: Retrospective and prospective studies, as well as one randomised clinical trial, published between January 2021 and October 2025, which answered the PICO question, were included.

DATA EXTRACTION AND SYNTHESIS: The quality of the included studies and the risk of bias were assessed using ROBINS-I (Risk of Bias in Non-randomised Studies) and ROB2 (Risk of Bias 2). For the quantitative analysis, heterogeneity among the included studies was quantified using the I² statistic, and the results were presented in a forest plot. The Trim and Fill method was used to assess publication bias.

RESULTS: Following a review of 267 publications, 15 studies were ultimately included in the review, and seven in the meta-analysis. Statistically significant differences were reported for the following variables: intermolar distance (6-6) ( – 1.77 mm; -2.57; – 0.97 95%CI; – 4.35 Z-test, p < 0.0001); total palatal volume ( – 460.63 mm³; – 738.32; – 182.94 95%CI; – 3.25 Z-test, p = 0.0011); and arch perimeter ( – 1.75 mm; – 2.71; – 0.80 95%CI; – 3.59 Z-test, p = 0.0003). These results indicate that aligners produce significantly less skeletal transverse expansion than conventional expanders.

CONCLUSIONS: Clear aligners appear to be capable of producing maxillary expansion, mainly through dentoalveolar changes that are more evident in the anterior region and at the level of deciduous teeth. In patients presenting with more pronounced transverse deficiencies, conventional expanders seem to achieve greater skeletal and posterior transverse changes. However, given that most of the current evidence derives from retrospective studies with moderate risk of bias, these conclusions should be interpreted cautiously and confirmed by well-designed prospective research.

REGISTRATION NUMBER: CRD420250608558.

PMID:42060239 | DOI:10.1186/s40510-026-00620-7

Discov Oncol. 2026 Apr 30. doi: 10.1007/s12672-026-05086-x. Online ahead of print.

ABSTRACT

BACKGROUND: Chordoma is a rare malignant bone tumor with limited effective systemic treatment options. Conventional chemotherapy generally shows minimal benefit, highlighting the need for predictive preclinical models to explore therapeutic vulnerabilities. Patient-derived organoids (PDOs) have emerged as a promising three-dimensional culture system that preserves tumor architecture and molecular features while enabling functional testing. However, mechanistic studies linking pathway activity to drug response in chordoma PDOs remain limited.

METHODS: Fresh surgical specimens from five patients with primary spinal chordoma were used to attempt generation of three-dimensional PDO cultures, of which primary three-dimensional cultures were successfully established. Organoids were characterized by histology, immunohistochemistry, and quantitative PCR analysis of chordoma-associated markers. Functional drug screening was performed using a panel of clinically relevant agents in a representative PDO model, followed by dose-response testing of gemcitabine. The role of TP53 in drug response was examined using small interfering RNA-mediated knockdown, with assessment of cell viability, Ki-67 expression, and DNA-damage response-related proteins. Statistical analyses were performed using one-way analysis of variance, with p < 0.05 considered statistically significant.

RESULTS: The established PDOs recapitulated the histopathological and molecular characteristics of their matched primary tumors and maintained stable growth across six passages. Among the screened agents, gemcitabine showed the strongest growth-inhibitory effect in PDO-based functional assays. Dose-response experiments confirmed significant gemcitabine-induced growth suppression. Importantly, TP53 knockdown markedly attenuated gemcitabine-induced cytotoxicity, increased proliferative activity, and reduced activation of DNA-damage response signaling, indicating a TP53-dependent vulnerability.

CONCLUSIONS: This study establishes a spinal chordoma PDO platform for functional precision oncology. Our findings identify a TP53-dependent DNA-damage vulnerability engaged by gemcitabine in patient-derived three-dimensional models, supporting biomarker-informed hypothesis generation rather than routine chemotherapy in unselected patients. This PDO-based approach provides a translational framework for exploring pathway-defined therapeutic susceptibilities in rare tumors such as chordoma.

PMID:42060212 | DOI:10.1007/s12672-026-05086-x

Mol Biol Rep. 2026 Apr 30;53(1):702. doi: 10.1007/s11033-026-11884-x.

ABSTRACT

A central enigma in crop improvement lies in introducing beneficial traits without fitness trade-offs. Rice, the cornerstone of global food security, demands multifaceted genetic innovation to sustain yield, quality, and resilience in the face of mounting climatic constraints. With the global population projected to surpass ten billion, functional master regulators such as miRNAs stand out as transformative molecular tools, capable of orchestrating complex trait networks and offering a tangible path toward the next green revolution. These are robust fine-tuners that orchestrate a myriad of functional processes and provide a value addition in emerging technologies such as assisted breeding, genome editing, and genomic selection to make rice production feasible. Herein, we have provided a comprehensive synthesis and updates on functional miRNA-mediated agronomically advantageous trait improvement exclusively for rice. It represents the latest functional understanding of miRNAs and their involvement as signatures of domestication and divergence processes, in support of the previously established notion and recent updates on emerging miRNA-assisted resources and technologies, such as their application as artificial solutions for improving genotypes, coding, and dietary potentialities for environmental safeguards and innovative biotherapeutics. Recent updates signify their robust cross-kingdom communicators’ potential for multifaceted non-host dialoguing, and their integrative action relies on the coordination with other non-coding regulatory elements for various downstream trait regulation. Moreover, specific highlights refer to the application of miRNAs for rice agronomical trait improvements, broadly classified into three functional domains, viz., biotic and abiotic stresses and yield and quality traits. Such updated functional aspects of different miRNA modules would strengthen rice improvement by facilitating a foundation and future roadmap for miRNA-mediated trait discovery and improvement.

PMID:42060211 | DOI:10.1007/s11033-026-11884-x