Nevin Manimala

Clin J Pain. 2025 Dec 10. doi: 10.1097/AJP.0000000000001351. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the relative efficacy of common non-pharmacological treatments for migraine and to determine the optimal dosage for physical exercise.

METHODS: We searched four databases up to January 2025 for randomized controlled trials of non-pharmacological interventions for migraine. A multilevel network meta-analysis, integrated with a dose-response analysis, was conducted to compare intervention efficacy and determine the optimal exercise dosage. Treatments were ranked by the Surface Under the Cumulative Ranking curve. Two independent reviewers extracted data and assessed the risk of bias.

RESULTS: Fifty-nine randomized controlled trials involving 10,020 participants (78.1%, female) were included. Neuromodulation techniques were most effective (Hedges’g=-0.61, 95% Credible Interval: -0.89 to -0.33), followed by physical exercise (Hedges’g=-0.42, 95% Credible Interval: -0.67 to -0.18) and mindfulness meditation (Hedges’g=-0.38, 95% Credible Interval: -0.63 to -0.12). The dose-response analysis for exercise indicated that while 100 metabolic equivalent (MET)-minutes per session was statistically effective, a minimum of 110 MET-minutes per session was required to achieve the Minimal Clinically Important Difference. Efficacy reached an optimal therapeutic plateau at 250-300 MET-minutes per session, achievable with 3-5 weekly sessions of 30-40 minutes.

DISCUSSION: Neuromodulation, physical exercise, and mindfulness meditation are promising non-pharmacological therapies for migraine. For physical exercise, a minimum dose of 110 MET-minutes per session is needed for clinically significant effects, with an optimal therapeutic window at 250-300 MET-minutes per session. Due to the low quality of primary evidence, these findings warrant cautious interpretation and require future validation.

PMID:41368711 | DOI:10.1097/AJP.0000000000001351

J Magn Reson Imaging. 2025 Dec 10. doi: 10.1002/jmri.70194. Online ahead of print.

ABSTRACT

BACKGROUND: Pathophysiological changes affect tissue cell composition and density. For example, neurodegenerative disorders and brain tumors are associated with cell loss and abnormal accumulation, respectively. In these scenarios, if monitored and tracked, tissue cellularity might be used to inform clinical diagnosis and management.

PURPOSE: To propose and evaluate a new marker of tissue cellularity, called susceptibility-Derived Cellularity Index (χDCI), that would be readily available for clinical applications with fast acquisition and at high resolution.

STUDY TYPE: Retrospective study.

POPULATION/SUBJECTS: 24 healthy subjects (7/17 M/F, 70 ± 11 years) and 21 patients with IDH-wild type glioblastoma (16/5 M/F, 65 ± 8 years).

FIELD STRENGTH/SEQUENCE: 3 T MRI sequences including 3D T1w pre- and post-contrast agent injection, 3D T2w, 3D FLAIR, 3D multi-echo gradient recalled echo, 2D diffusion weighted imaging.

ASSESSMENT: χDCI was computed based on parameters estimated with DECOMPOSE-QSM. The Neurite Density Index (NDI) was estimated with the NODDI model. T1w images were used for region of interest (ROIs) segmentations with FreeSurfer (i.e., cortical gray matter, white matter, thalamus, caudate, putamen, pallidum, hippocampus and amygdala). For the patients with glioblastoma, regions of contrast enhancement, necrosis, and edema were also included in the analysis.

STATISTICAL TESTS: Pearson’s correlation analysis between mean χDCI and NDI values in the ROIs was carried out separately for the two cohorts of participants (significance level = 0.05, after correction for multiple comparisons).

RESULTS: Significant correlations were observed between χDCI and NDI in white matter (r = 0.56) and putamen (r = 0.69) for the healthy participants. Significant positive correlations were also found in white matter (r = 0.6), pallidum (r = 0.48), putamen (r = 0.79), thalamus (r = 0.64) and edema (r = 0.69) for the patient cohort.

DATA CONCLUSION: χDCI is proposed as a marker of tissue cellularity. The significant associations between χDCI and NDI in several regions investigated in the present study support the potential of χDCI as a proxy of intracellular volume fraction.

TECHNICAL EFFICACY: Stage 1.

PMID:41368710 | DOI:10.1002/jmri.70194

JMIR Mhealth Uhealth. 2025 Dec 9;13:e63896. doi: 10.2196/63896.

ABSTRACT

BACKGROUND: Chronic noncommunicable diseases (NCDs) remain a leading health challenge worldwide, and reducing modifiable lifestyle risk factors is a key prevention strategy. Digital health interventions (DHIs) offer scalable, cost-effective tools to support healthy behaviors, but concerns persist about their equitable reach and uptake across population groups.

OBJECTIVE: This study aimed to examine how socioeconomic factors, health status, lifestyle behaviors, and attitudes and experiences related to the use of electronic services (e-services) are associated with the uptake of a DHI.

METHODS: In this cross-sectional study, we invited (through mail or SMS) a subgroup of 6978 participants aged 20-74 years from the population-based Healthy Finland survey to take part in a DHI. The DHI, delivered via the web-based BitHabit app, aimed to support the adoption of healthy lifestyle habits. Uptake was defined as successful registration, agreeing to the terms of use, and accepting the invitation to participate. Predictor variables were drawn from national registry and self-reported survey data and included socioeconomic status, health indicators, lifestyle behaviors, and attitudes and experiences related to the use of e-services. Adjusted logistic regression models were used to identify significant predictors of DHI uptake.

RESULTS: Of the final sample of 6975 participants, 1287 (18.5%) started using the DHI. Uptake was significantly higher among women (adjusted odds ratio [aOR] 1.69, 95% CI 1.49-1.93), middle-aged individuals (aOR 1.47, 95% CI 1.21-1.79), and those with higher income (aORs 1.76-1.97, 95% CIs 1.37-2.59) and more years of education (aOR 1.10, 95% CI 1.08-1.12). Healthier lifestyle indicators, including better diet quality (aOR 1.07, 95% CI 1.04-1.10), less frequent smoking or nonsmoking (aORs 1.59-2.29, 95% CIs 1.08-3.12), sleep (aOR 0.58, 95% CI 0.37-0.86), higher functional capacity (aOR 1.06, 95% CI 1.02-1.11), and good overall current health (aOR 1.46, 95% CI 1.15-1.89), were associated with increased likelihood of DHI uptake. The strongest predictors were related to the use of e-services: Individuals who used e-services (aORs 2.48-6.08, 95% CIs 1.19-11.92) reported higher competence to use e-services (aORs 2.00-4.10, 95% CIs 1.44-5.92), had low concerns about data security (aORs 1.37-1.76, 95% CIs 1.03-2.33), believed in the benefits of digital services (aOR 1.04, 95% CI 1.02-1.05), and had better internet connections had higher odds of uptake.

CONCLUSIONS: Our findings show that DHI uptake is associated with socioeconomic status, health and lifestyle factors, and, especially, individuals’ experience and attitudes toward e-services. Individuals with lower education levels, lower income, and poorer health and lifestyle habits are less likely to adopt DHIs, raising concerns about potential digital health inequities. These results underscore the need for targeted strategies to reduce barriers and ensure more equitable reach and engagement in future DHI implementations.

PMID:41364913 | DOI:10.2196/63896

JMIR Form Res. 2025 Dec 9;9:e74086. doi: 10.2196/74086.

ABSTRACT

BACKGROUND: Health systems are investing in mental health and well-being support tools and resources for health care workers (HCW). Considering the mental health strain facing HCWs, there is a need to optimize the current mental health delivery model.

OBJECTIVE: This study aimed to evaluate the usability and acceptability of a proactive digital mental health approach (Cobalt+;Penn Medicine), which included services proactively sent to HCWs via text messaging, including (1) monthly automated text messaging reminders and links to Cobalt, and (2) bimonthly text-message-based measures of depression and anxiety.

METHODS: This study used the System Usability Scale (SUS), Net Promoter Score (NPS), and open-ended questions to capture Cobalt+ participants who received proactive digital mental health tools and resources. Descriptive summary statistics were used for SUS and NPS outcome measures, and a chi-square test was used to detect group differences. Open-ended questions were analyzed using a qualitative open coding process by 2 coders. Research team members calculated interrater agreement (Cohen κ above 0.80).

RESULTS: A total of 162 of 642 HCWs randomized to Cobalt+ (25.2%) visited Cobalt due to a proactive text message and completed usability and acceptability measures. The mean age was 38.9 years, most were female (90.7%), 56.8% White, 53.1% married or partnered, and 34.6% engaged in shift work. The mean SUS score was 74.43 (median score 72.5). Participants said they mostly “browsed” the online mental health platform. Cobalt+ received an NPS of 13.7. When asked to elaborate on their experience, 2 categories (eg, positive and negative experiences) with 13 subcategories were identified. Most participants noted the brief process that helped prioritize mental health: “Forget otherwise. Puts in forefront of my mind,” and “Your texts do remind me to take stock of my current feelings.”

CONCLUSIONS: A proactive digital mental health approach may help overcome barriers in the uptake of services that are otherwise passively available to HCWs. This study demonstrated that the proactive approach is generally usable, modestly acceptable, and further supplemented by HCW feedback. These findings suggest the approach’s viability and the need for additional research toward improvement and broader implementation.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05028075; https://clinicaltrials.gov/study/NCT05028075.

PMID:41364911 | DOI:10.2196/74086

JMIR Form Res. 2025 Dec 9;9:e72440. doi: 10.2196/72440.

ABSTRACT

BACKGROUND: The process of accessing specialized medical training in Spain is a complex issue, involving not only the evaluation of medical knowledge acquired throughout university training but also the interaction of factors of a contextual and structural nature, which can influence the results obtained in the entrance examination. In this context, research on the variables that determine performance in this test is of great relevance form not only an academic but also a social and economic point of view. The interaction among factors such as academic performance, gender, nationality, and timing offers a unique opportunity to evaluate the functioning of the educational system at a critical moment in its recent history. Research that has focused specifically on access to specialized medical training has shown mixed results on how these factors impact examination performance.

OBJECTIVE: This study aimed to approximate the factors that determine failure in the entrance test for specialized medical training in Spain with the aim of better understanding the extent to which differences based on sex, nationality, and the context of the COVID-19 pandemic contribute to explaining such failure.

METHODS: We carried out econometric modeling of the final results obtained in the entrance examination to specialized medical training and identified the explanatory factors that determine the results, their relevance, effect, and significance. Econometric modeling provides a rigorous framework for estimating the causal effect of different variables on the final examination score. It helps identify not only which variables have an impact on performance but also to what extent they do so and under what conditions.

RESULTS: Based on the results obtained in the 2019-2021 test calls (7217 eliminated candidates), academic records (P<.001) and examination scores (P<.001), together with demographic factors including sex (P=.54) and nationality (P<.001), and calendar year (P<.001) were determinants of the behavior observed in the final results. Our results do not indicate whether being male or female favors or decreases the final grade obtained; however, being Spanish constitutes a relevant explanatory factor in our final results. The calendar effect, directly related to the COVID-19 pandemic, allows us to quantify the negative impact on the final results.

CONCLUSIONS: This study investigated the impact of factors such as sex, nationality, and the COVID-19 pandemic on access to specialized medical training in Spain. Empirically, not being Spanish acts as an unfavorable fixed characteristic in the baseline econometric model, but it becomes favorable when considering the candidate’s academic record. The impact of language is not perceived as a limiting factor; the test exclusively evaluates knowledge of medical content. The negative effects of the COVID-19 pandemic are visualized in the final scores.

PMID:41364909 | DOI:10.2196/72440

JMIR Form Res. 2025 Dec 9;9:e78489. doi: 10.2196/78489.

ABSTRACT

BACKGROUND: Research concerning the long-term health consequences of induced abortion is constrained by both the limitations in the availability of data necessary to construct complete reproductive histories, as well as the limitations in the analytical methods necessary to interpret them.

OBJECTIVE: This study aims to determine the association of induced abortion and the likelihood of a subsequent natural loss by applying the pregnancy outcome sequence (POS), a research construct that defines the number and order of all pregnancy outcomes (births, induced abortions, natural losses) in each woman’s reproductive history.

METHODS: Using the Medicaid Analytic eXtract files from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse, we identified a study population of 508 unique POSs, representing 5455 women, each of whom had 1 to 16 pregnancy outcomes, for a total of 14,198 pregnancies. We applied an exploratory iterative sequential analytical approach, which included aggregate POS correlation analysis, logistic multiple regression, and simultaneous CIs (Agresti and Tukey-Kramer methods). We also established counting methods to populate the data tables for each analytical phase.

RESULTS: Overall, we found evidence to conclude that both prior abortions and natural losses are significantly associated with the risk of subsequent natural losses. For abortion, there is evidence of a dose-response relationship from 0 to 3 abortions and the likelihood of subsequent natural loss. For natural loss, the risk of a subsequent natural loss is significant after 2 natural losses and between the first and second. There is no association of prior births, or any combination of birth/abortion or birth/natural loss, with the risk of subsequent natural loss. Limitations imposed by the skewed distribution of the number of total pregnancies per reproductive history, resulting in small cell sizes, and exclusion of important covariates, restrain assurance in the results.

CONCLUSIONS: The POS demonstrates that the order and combinations of pregnancy outcomes may result in varying conclusions that were previously undetectable. Therefore, further methodological development is indicated.

PMID:41364908 | DOI:10.2196/78489

Exp Physiol. 2025 Dec 9. doi: 10.1113/EP093300. Online ahead of print.

ABSTRACT

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that plays an important role in aldehyde detoxification. A large percentage (30-50%) of the East Asian population carry a single point mutation in the ALDH2 gene (ALDH2*2 variant) that causes a severe reduction or lack of ALDH2 enzyme activity, and leads to disrupted cellular homeostasis due to the accumulation of toxic reactive aldehydes. The ALDH2*2 variant has been associated with several degenerative diseases, with evidence suggesting a link to cardiovascular disease, potentially mediated by endothelial dysfunction. This, however, remains to be confirmed. We aimed to investigate whether the ALDH2*2 variant is associated with impaired endothelial function in young, healthy East Asians. Twenty-two participants were genotyped and divided into non-carriers (ALDH2*1/*1; n = 12; 7 females and 5 males; age = 23 ± 3 years; height = 167.4 ± 8.7 cm; body mass = 60.1 ± 9.0 kg) and carriers (ALDH2*1/*2 and ALDH2*2/*2; n = 10; 8 females and 2 males; age = 24 ± 5 years; height = 162.6 ± 10.1 cm; body mass = 62.1 ± 9.7 kg) of the ALDH2*2 allele. Endothelial function was assessed via flow-mediated dilation (FMD) following current guidelines. Carriers displayed lower FMD, either absolute or relative, which was not statistically significant but approached significance (unpaired t-test) (FMD%: non-carriers = 10.2 ± 1.9% vs. carriers = 8.1% ± 3.1%, P = 0.079, effect size: Cohen’s d = 0.82; FMD_abs: non-carriers = 0.32 ± 0.06 mm vs. carriers = 0.26 ± 0.09 mm, P = 0.082, effect size: Cohen’s d = 0.78). In conclusion, our data seem to suggest that the ALDH2*2 variant impairs endothelial function even in young and healthy individuals without the presence of other stressor agents. Future studies with larger sample size are necessary to confirm our findings.

PMID:41364906 | DOI:10.1113/EP093300

J Community Psychol. 2026 Jan;54(1):e70061. doi: 10.1002/jcop.70061.

ABSTRACT

Neighborhood environments may significantly impact psychological well-being, particularly in Black American communities where historical inequities and resilience factors intersect. This mixed-methods study investigates retrospective perceptions of childhood and current neighborhood social environments and their associations with loneliness and psychological distress in adulthood. Data were drawn from the Think PHRESH study, an ancillary project to the Pittsburgh Hill/Homewood Research on Neighborhood Change and Health (PHRESH). A mixed-methods design integrated survey data from 739 participants (77.5% female; mean age = 63.37) and qualitative interviews with 56 residents (60.7% female; mean age = 65.95). Measures assessed childhood and adulthood neighborhood social cohesion, collective child-rearing, current neighborhood safety, satisfaction, loneliness, and distress. A mixed-methods expansion approach was used, where qualitative themes informed quantitative model development. Thematic analysis was applied to qualitative data, and regression analyses examined associations between neighborhood factors and mental health. Participants reported significantly higher childhood social cohesion (M = 4.47, SD = 0.70) than adulthood (M = 3.22, SD = 0.69). Qualitative findings highlighted declines in community engagement and safety. Regression analyses showed greater current social cohesion (b = -0.61, SE = 0.25, p = 0.02), neighborhood safety (b = -0.48, SE = 0.21, p = 0.02), and satisfaction (b = -0.55, SE = 0.18, p = 0.002) were associated with lower distress, while higher satisfaction was linked to lower loneliness (b = -0.08, SE = 0.03, p = 0.002). Findings highlight the importance of policies that enhance neighborhood social environments, particularly in predominantly Black urban communities affected by structural inequities.

PMID:41364904 | DOI:10.1002/jcop.70061

JCO Oncol Pract. 2025 Dec 9:OP2500651. doi: 10.1200/OP-25-00651. Online ahead of print.

ABSTRACT

PURPOSE: Over 10 million jail admissions occur each year in the United States. Whether county-level incarceration shapes population-level cancer mortality remains unclear. We assessed county jail incarceration rates in relation to lung, liver, and colorectal cancer deaths.

METHODS: This ecological study linked county incarceration rates (1995-2018, Vera Institute) with age-adjusted cancer mortality from the National Vital Statistics System (2000-2019). Incarceration was grouped into lagged quartiles (Q1 lowest; Q4 highest). Pooled Poisson regression with county-clustered robust errors estimated adjusted incidence rate ratios (aIRRs) while controlling for sociodemographic, behavioral, health care, and structural factors. Sex- and race-stratified analyses and longer exposure lags tested robustness.

RESULTS: Relative to Q1, Q4 counties had higher mortality from lung (aIRR, 1.08 [95% CI, 1.04 to 1.12]), liver (aIRR, 1.10 [95% CI, 1.00 to 1.22]), and colorectal (aIRR, 1.09 [95% CI, 1.04 to 1.15]) cancers. Among men, liver cancer deaths rose 13% in Q4 (aIRR, 1.13 [95% CI, 1.03 to 1.24]). Black residents experienced elevated lung and colorectal mortality across all incarceration quartiles and a 29% increase in liver cancer deaths in Q4 (aIRR, 1.29 [95% CI, 1.04 to 1.61]); excess mortality among White residents emerged only in Q4 counties (all P < .05). Findings persisted in sensitivity analyses.

CONCLUSION: Counties with the highest jail incarceration rates had 7%-10% more lung, liver, and colorectal cancer deaths with disproportionate impacts on men and Black residents. Incarceration operates as a structural driver of cancer disparities; targeted prevention, screening, and treatment efforts are urgently needed in high-incarceration communities.

PMID:41364883 | DOI:10.1200/OP-25-00651

Diving Hyperb Med. 2025 Dec 20;55(4):391-397. doi: 10.28920/dhm55.4.391-397.

ABSTRACT

INTRODUCTION: Diving induced immersion diuresis predisposes divers to dehydration. Dehydration is considered a risk factor for decompression sickness (DCS) but there is very little evidence to prove it. Dehydration also potentially modifies venous gas emboli (VGE) formation and impairs endothelial function. The purpose of this study was to report the effects of fluid loss during a dive on the diver’s physiology.

METHODS: Nine divers performed a 45 metre fresh water (mfw) and a 100 mfw dive with predetermined dive profiles. Body weight was measured before and after the dive. Post-dive detection of VGE was performed according to the extended Eftedal-Brubakk scale. We also measured haematocrit and flow mediated dilation before and after the 100 mfw dives.

RESULTS: After a 68-minute dive to 45 mfw, median weight loss was -1.1 kg, (IQR -1.2, -1.0; range -2.0, -0.6), P = 0.009 and VGE were detected in all divers. After a 170-minute dive to 100 mfw, median weight loss was -1.5 kg (IQR -1.8, -1.1; range -2.2, -0.8), P = 0.009 and VGE were detected in seven divers. Weight loss after the dive was statistically significant and there was a negative correlation between weight loss and bubbling after the 45 mfw dives. None of the divers suffered any symptoms of DCS.

CONCLUSIONS: We found significant weight loss after both decompression dives but there were no clinical DCS symptoms in any of the divers. This study does not offer new evidence supporting the notion that dehydration increases decompression stress in divers.

PMID:41364863 | DOI:10.28920/dhm55.4.391-397