Nevin Manimala

Pain Physician. 2025 Nov;28(6):519-526.

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is characterized by the destruction of the articular cartilage and narrowing of the joint space and bone formations around the joint due to mechanical, genetic, and inflammatory causes. The hip joints are some of the most commonly affected in OA. Hip OA is also known as coxarthrosis.

OBJECTIVES: This study aimed to compare the effects of conventional radiofrequency (RF) to those of intraarticular steroid treatment methods on pain, limitations, and quality of life in patients who had advanced OA of the hip and could not undergo surgery for any reason.

STUDY DESIGN: The study was designed as a randomized, prospective single-center study.

SETTING: A total of 40 patients with advanced primary hip OA who met the inclusion criteria were included in the study.

METHODS: Patients were randomized into 2 groups, each of which included 20 individuals. One group received conventional (thermal) radiofrequency ablation (RFA) to the femoral and obturator sensory branches of the hip, while the other group received intraarticular steroid injections in their hips. Scores on the Visual Analog Scale (VAS) and the physical-function component of the Medical Outcomes Study Short Form Health Survey (SF-36) were completed before, one month after, and 3 months after the procedure. The VAS was recorded both at rest and during activity. Each patient’s gender, body mass index (BMI), affected hip side, duration of pain, and previous treatments for the hip were recorded, as were the procedure-related complications each patient experienced.

RESULTS: Forty patients were followed up on for 3 months. The analysis revealed that at both one month and 3 months after treatment, the 2 groups of patients showed a significant improvement in their scores on the resting VAS, activity VAS, and physical-function component of the SF-36 from the pre-procedure values (P < 0.05). As for resting VAS scores in the hip intraarticular steroid injection (HIASI) group and activity VAS scores in the thermal radiofrequency ablation (TRFA) group, there was a statistically significant difference between the groups at one month and 3 months after the procedure, respectively (P < 0.05). This study found a statistically significant correlation between hip stage and age, but no significant correlation was found for gender and weight. No difference between the groups appeared in the complications related to the procedure at the 3-month follow-up.

LIMITATIONS: The follow-up period was relatively short. The sample size was small, and to avoid neuritis, a half dose of triamcinolone acetonide was given to the patients in the TRFA group.

CONCLUSIONS: Conventional RF is more effective at treating the symptoms of advanced coxarthrosis than are intraarticular steroids, based on observations of the activity in the 3-month follow-up of patients with the condition.

PMID:41337764

Pain Physician. 2025 Nov;28(6):511-518.

ABSTRACT

BACKGROUND: Post cardiac surgery pain remains a problem for a significant number of patients. While opioids have long been used for cardiac surgery pain control and hemodynamic stability, methods to improve pain control while also reducing reliance on opioids are desired. Intravenous lidocaine has shown promise for pain and opioid reduction in multiple operative settings, yet its role in cardiac surgery lacks conclusive data.

OBJECTIVE: To determine the effect of intravenous lidocaine on pain scores and opioid consumption in the first 48 hours post cardiac surgery.

STUDY DESIGN: Preplanned substudy of a single-center, double-blind, placebo-controlled, randomized controlled trial.

SETTING: This study was conducted in a tertiary/quaternary care academic hospital in the United States.

METHODS: Following institutional review board approval and informed consent, a total of 449 patients who met the inclusion criteria were enrolled and randomized to receive either a bolus of one mg/kg of lidocaine administered after anesthesia induction followed immediately by a continuous infusion at 48 mu-g/kg/min for the first hour, 24 mu-g/kg/min for the second hour, and 10 mu-g/kg/min for the next 46 hours (lidocaine group) or normal saline (placebo group). Primary outcomes were Visual Analog Scale (VAS) scores and opioid consumption in of morphine milligram equivalents at 24 and 48 hours post surgery. Secondary endpoints included the administration of other nonopiod analgesic medications, postoperative antiemetic medication use, intensive care unit length of stay, hospital length of stay, and time to return of bowel function. Univariable and multivariable regression analyses were performed.

RESULTS: A total of 215 patients who received a placebo and 218 patients who received lidocaine were evaluated. We observed a statistically significant difference in VAS pain score at postoperative 24 hours (adjusted mean difference -0.68; 95%CI, -1.23 to 0.13; P = 0.016) between patients treated with lidocaine vs placebo; however, no difference was observed at postoperative 48 hours. The cumulative opioid use in morphine milligram equivalents was not significant, both in univariable and multivariable analysis, at all timepoints between patients receiving lidocaine vs placebo. Among secondary outcomes, the only significant effect was a decrease in odds of acetaminophen use in the first postoperative 48 hours (adj. odds ratio 0.54; 95% CI 0.32 to 0.90, P = 0.018).

LIMITATIONS: Although pain scores were a preplanned outcome of the parent study, opioid consumption was not. Furthermore, postoperative pain management was not specifically standardized for this study.

CONCLUSIONS: We found that intravenous lidocaine resulted in a statistically significant decrease in VAS pain scores at 24 hours post cardiac surgery, with no difference in opioid consumption. While this pain benefit has been noted in other surgical patient populations, our findings are important since patients undergoing cardiac surgery are unique given the physiologic changes associated with cardiopulmonary bypass graft.

PMID:41337763

Pain Physician. 2025 Nov;28(6):495-510.

ABSTRACT

BACKGROUND: Observational studies have reported relationships among physical activity (PA), leisure sedentary behaviors (LSBs), lifestyle habits, and chronic pain (CP). However, these findings may be unreliable due to confounding biases.

OBJECTIVES: To evaluate the causal effects of PA, LSB, and lifestyle habits on CP.

STUDY DESIGN: This study performed a 2-sample Mendelian randomization to assess the causal effects of the 3 exposures of interest on MCP and evaluated the robustness of the results through a series of sensitivity analyses.

SETTING: The genetic instruments were obtained from UK Biobank, which provides publicly accessible genome-wide association studies (GWAS) summary statistics based on individuals of European ancestry.

METHODS: We used GWAS summary statistics of multisite chronic pain (MCP) in 387,649 individuals from the UK Biobank to identify genetically predicted MCP. Data on PA, LSBs, and lifestyle habits were derived from large GWAS datasets (n > 300,000). Causal effects were assessed by inverse variance weighted (IVW), MR-Egger, weighted median, maximum likelihood, and penalized weighted median. Sensitivity analyses, including MR-PRESSO, Cochran’s Q test, MR-Egger intercept, and leave-one-out analysis, were performed to evaluate the robustness of the MR results.

RESULTS: The results of univariable MR analyses indicated that genetically predicted computer use (OR = 0.905 [0.832, 0.984]) and strenuous sports or other exercises (SSOEs) (OR = 0.490 [0.361, 0.664]) reduced the risk of MCP. Watching television (OR = 1.320 [1.262, 1.380]) and smoking initiation (OR =1.164 [1.122, 1.207]) increased the risk of MCP. Reverse inference results showed that watching television (beta = 0.256 [0.170, 0.341]) and smoking initiation (OR = 1.475 [1.257, 1.732) were risk factors for MCP, while SSOEs (OR = 0.900 [0.871, 0.931) and VPA (OR = 0.945 [0.900, 0.993]) reduced the likelihood of MCP.

LIMITATIONS: This study was unable to use non-overlapping samples to assess the causal association in every 2-sample MR analysis due to the restriction of GWAS datasets, resulting in inevitable bias.

CONCLUSION: This study revealed that television-watching and smoking initiation increased the risk of CP, while computer use and vigorous PA served as protective factors.

PMID:41337762

JMIR Form Res. 2025 Dec 3;9:e80082. doi: 10.2196/80082.

ABSTRACT

BACKGROUND: Video games are becoming increasingly accessible and occupy a prominent position among students’ leisure activities. Recent studies have demonstrated that engagement with video games can facilitate the development of specific abilities, such as visuospatial skills and hand-eye coordination. Thus, it seemed relevant to investigate whether the practice of playing video games could enhance the technical capabilities of novice dental students.

OBJECTIVE: The objective of this study was to ascertain whether dental students who identified themselves as video game players exhibited differences in fundamental technical skills in comparison to students who identified as nonplayers. This preliminary study aimed to validate the methodology and measurement tools for a subsequent prospective study.

METHODS: Second-year dental students who were novices in the field of preclinical dental practice were divided into 2 groups: one designated nonplayers and the other players. The visual, motor, and cognitive coordination of the students was assessed using 3 different tests. The initial assessment focused on evaluating spatial ability, while the subsequent assessments addressed arm-hand coordination and the velocity of execution. The study data were collected in September 2021.

RESULTS: This study included 92 second-year dental students (mean age 19.49, SD 0.8 years). Thirty-seven students were placed in the player group (40%), while 55 were placed in the nonplayer group (60%). The findings showed no statistically significant differences between the two groups when the 3 distinct tests were administered. The nonplayer group made fewer mistakes on the test evaluating spatial ability (P=.051) and achieved a higher score on the modified Precision Manual Dexterity Test, which evaluates arm-hand coordination, compared to the player group (P=.17), but without statistical significance. The nonplayer group took more time to perform the pulpotomy during the third test, which evaluated execution speed, compared to the player group, again without significance (P=.87).

CONCLUSIONS: This study did not demonstrate significant differences between player and nonplayer dental students who participated in the study with regard to their fundamental technical abilities in a preclinical training environment. Nevertheless, it validated the feasibility of a methodology for a future longitudinal study to concentrate on the evolution of acquiring technical skills during preclinical training in these two populations. Consequently, further investigation is warranted to determine the potential impact of video games on the acquisition of surgical skills, including in dentistry.

PMID:41337749 | DOI:10.2196/80082

JMIR Med Inform. 2025 Dec 3;13:e78309. doi: 10.2196/78309.

ABSTRACT

BACKGROUND: Reusing long-term data from electronic health records is essential for training reliable and effective health artificial intelligence (AI). However, intrinsic changes in health data distributions over time-known as dataset shifts, which include concept, covariate, and prior shifts-can compromise model performance, leading to model obsolescence and inaccurate decisions.

OBJECTIVE: In this study, we investigate whether unsupervised, model-agnostic characterization of temporal dataset shifts using data distribution analyses through Information Geometric Temporal (IGT) projections is an early indicator of potential AI performance variations before model development.

METHODS: Using the real-world Medical Information Mart for Intensive Care-IV (MIMIC-IV) electronic health record database, encompassing data from over 40,000 patients from 2008 to 2019, we characterized its inherent dataset shift patterns through an unsupervised approach using IGT projections and data temporal heatmaps. We trained and evaluated annually a set of random forests and gradient boosting models to predict in-hospital mortality. To assess the impact of shifts on model performance, we checked the association between the temporal clusters found in both IGT projections and the intertime embedding of model performances using the Fisher exact test.

RESULTS: Our results demonstrate a significant relationship between the unsupervised temporal shift patterns, specifically covariate and concept shifts, identified using the IGT projection method and the performance of the random forest and gradient boosting models (P<.05). We identified 2 primary temporal clusters that correspond to the periods before and after ICD-10 (International Statistical Classification of Diseases, Tenth Revision) implementation. The transition from ICD-9 (International Classification of Diseases, Ninth Revision) to ICD-10 was a major source of dataset shift, associated with a performance degradation.

CONCLUSIONS: Unsupervised, model-agnostic characterization of temporal shifts via IGT projections can serve as a proactive monitoring tool to anticipate performance shifts in clinical AI models. By incorporating early shift detection into the development pipeline, we can enhance decision-making during the training and maintenance of these models. This approach paves the way for more robust, trustworthy, and self-adapting AI systems in health care.

PMID:41337748 | DOI:10.2196/78309

JMIR Form Res. 2025 Dec 3;9:e59951. doi: 10.2196/59951.

ABSTRACT

BACKGROUND: Migraines are a significant health concern affecting millions of individuals, often requiring habitual tracking of potential triggers to mitigate or predict episodes. Digital health tools such as mobile apps offer a scalable solution for personalized tracking and pattern recognition. Migraine Insight is one such app that facilitates daily logging to quantitatively assess individualized patterns of events preceding migraine onset. However, while various triggers have been reported in migraine literature, there is limited large-scale electronic user-driven data on the frequency and relative impact of specific triggers.

OBJECTIVE: This study aims to address this gap by analyzing user-reported data from Migraine Insight to identify the most frequently reported triggers and evaluate their potential associations with migraine onset.

METHODS: Food-associated migraine triggers were identified by performing a noninterventional, retrospective analysis of self-reported data obtained via the Migraine Insight app. A collaboration was made with the representatives of the Migraine Insight app to extrapolate the data needed for the study. A preliminary keyword list was assessed from a raw data set of 2605 data entry values, extracted from a 30-day period of September 19 to October 18, 2021, to identify high ranking self-reported events, classified by dietary habits, environmental conditions, body physiology, and medications. The variables examined included the following: dietary items, environmental conditions, body physiology, and electronics. Food items were combined into similar groups, considering variable spelling and descriptions of self-reported events. The association of migraine onset after consumption of top 5 dietary products was evaluated to establish the frequency of migraine episodes for all users who reported the items.

RESULTS: Collectively, food (n=353) and beverage (n=252) totaled the highest reported entries, with chocolate, wine, tea, coffee, and cheese as the highest ranked foods for prevalence of reporting across all users and for frequency of migraine onset for users who consumed the items within 48 hours. The 4 highest nonfood entries were altered sleep patterns (n=245), stress or anxiety (n=199), rain or storm conditions (n=192), and bright light or brightness (n=191). Statistical analysis showed that chocolate was the only food trigger significantly associated with migraines (P=.003 vs 50%; P=.04 vs average). Consumption of tea approached significance (P=.051), while consumption of coffee, cheese, and wine were not significant. These findings suggest that chocolate is the most consistent dietary trigger.

CONCLUSIONS: High-risk foods, environmental conditions, stress, and lighting with highest prevalence reporting have previously been reported in medical literature, implicating that a migraine tracking app is a valid alternative to paper-based diaries.

PMID:41337743 | DOI:10.2196/59951

Cancer Rep (Hoboken). 2025 Dec;8(12):e70383. doi: 10.1002/cnr2.70383.

ABSTRACT

OBJECTIVES: Penile squamous cell carcinoma (PSCC) is the most common penile cancer, accounting for ≥ 95% of cases, though it accounts for < 1% of all malignancies in men in the United States. We report an updated, stage-stratified analysis of the efficacy of surgery, radiation, and chemotherapy, including adjuvant and neoadjuvant chemoradiation, with further analysis of demographic and clinical factors.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, patients with PSCC diagnosed between 2000 and 2018 were identified. Five-year overall survival Cox regression analysis as well as univariate Kaplan-Meier analysis were performed, stratified by demographic and treatment variables.

RESULTS: Two thousand seven hundred eight patients with PSCC were identified, with 57.8% being older than 65 years at diagnosis and 94.2% undergoing surgical intervention. With multivariate analysis, increasing disease stage (p < 0.001), age < 65 years (p < 0.001), lower disease grade (p < 0.001) were all associated with increased survival, while treatment with chemotherapy or radiotherapy was both associated with decreased survival (p = 0.002 and < 0.001, respectively). On univariate analysis, less invasive surgery was associated with increased survival among patients with low-grade, local (p < 0.001) or regional (p = 0.03) disease. Among those with high-grade disease, local excision was associated with increased survival (p = 0.008), though among those with regional disease no survival difference was seen (p = 0.86). Patients with regional disease saw increasing survival with four or more lymph nodes dissected (69% vs. 61%, respectively; p = 0.002).

CONCLUSIONS: Surgical management of penile SCC remains the mainstay treatment, and less invasive surgery is associated with noninferior or improved 5-year overall survival regardless of disease stage and grade. Patients with regional disease had increased survival when four or more lymph nodes were dissected. Future analysis of these trends stratified by disease subhistology and more granular analysis of the role of lymphadenectomy are warranted.

PMID:41337679 | DOI:10.1002/cnr2.70383

Environ Sci Technol. 2025 Dec 3. doi: 10.1021/acs.est.5c05810. Online ahead of print.

ABSTRACT

The role of particulate matter (PM) in the bidirectional relationship between cardiovascular disease (CVD) and mood disorders remains unclear. This UK Biobank-based study included participants without prior CVD or mood disorders at baseline with complete data. Outcomes included CVD and mood disorder incidences, comorbidity, and mortality. During a median 13.8-year follow-up, among 358,119 participants, 145,406 developed CVD, 27,318 mood disorders, 15,443 comorbidity, and 26,703 deaths. Multistate analysis showed PM_2.5 exposure significantly increased risks of progression in both trajectories. For trajectory 1, each IQR increase in PM_2.5 was associated with HRs (95% CI) of 1.219 (1.216-1.222), 1.080 (1.070-1.091), and 1.033 (1.013-1.053) for progression from baseline to CVD, CVD to comorbidity, and comorbidity to death, respectively. For trajectory 2, each IQR increase in PM_2.5 was associated with HRs (95% CI) of 1.227 (1.218-1.237), 1.024 (1.009-1.040), and 1.033 (1.013-1.053) for progression from baseline to mood disorders, mood disorders to comorbidity, and comorbidity to death, respectively. Similarly, PM₁₀ exposure showed weaker positive associations than PM_2.5. Lipoproteins and fatty acid metabolites primarily mediated disease progression in these trajectories. Our results demonstrated PM exposure contributes to progression from CVD and mood disorders to comorbidity and mortality, with different mediating metabolites identified at each stage of progression. These results highlight both the importance of PM control and the potential of metabolic pathways as targets for early intervention.

PMID:41337673 | DOI:10.1021/acs.est.5c05810

Neuro Endocrinol Lett. 2025 Nov 25;46(5):265-269. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aims to evaluate the prevalence and characteristics of scoliosis in asthenic children diagnosed with mitral valve prolapse (MVP).

MATERIAL AND METHODS: This study aims to characterize scoliosis prevalence and examine relationships with mitral valve morphology, regurgitation severity, and skeletal phenotypes (pectus excavatum, hypermobility, skin laxity) in asthenic children with primary MVP based on echocardiographic findings. Individuals with known systemic connective tissue disorders were excluded. Scoliosis was assessed radiographically using Cobb angle measurements with a threshold of ≥10° for diagnosis. Statistical analysis was performed using SPSS 26.0.

RESULTS: The study included 49 asthenic children (25 females, 24 males) aged 9 to 17 years who were diagnosed MVP. The mean age of participants was 13.2 ± 2.2 years. Physical examination revealed pectus excavatum in 46.9%, joint hypermobility in 39%, and skin laxity in 16.3% of patients. Scoliosis (Cobb ≥10°): 47% (23/49, [95% CI: 33-61%]); potential scoliosis (5-10°): 27% (13/49, [95% CI: 16-40%]); any abnormal curvature: 73% (36/49, [95% CI: 59-84%]). Valve morphology: diffuse thickening 61% (30/49); localized elongation 39% (19/49). No significant association between scoliosis and valve morphology (p > 0.05) or MR severity (p > 0.05). Pectus excavatum significantly associated with elongated valve structure (p = 0.001). Pectus excavatum was significantly more common in patients with an elongated, straight valve structure (p = 0.001).

CONCLUSIONS: High scoliosis prevalence (47%) in asthenic MVP children is independent of cardiac severity, suggesting intrinsic skeletal tissue vulnerability. Neuroendocrine and immune mechanistic investigation warranted.

PMID:41337646

Funct Plant Biol. 2025 Dec 3:FP25301. doi: 10.1071/FP25301. Online ahead of print.

ABSTRACT

Agricultural productivity is increasingly constrained by water scarcity, which affects nearly one-quarter of cultivated land and is projected to intensify due to climate change and escalating freshwater demands. Melatonin is widely recognized as a potent biostimulant that plays a crucial role in mitigating various abiotic stresses, particularly drought, across many plant species. This study demonstrates that exogenous application of melatonin (150 μM; foliar spray) confers protection to Phaseolus vulgaris under moderate water deficit (40% field capacity). A randomized complete block design comprising four treatment groups (n = 30 seedlings per group, five replicates) was employed to systematically evaluate morphological, physiological, biochemical, and molecular responses. Melatonin applications at 21 and 28 days after sowing significantly enhanced shoot elongation, leaf area expansion, and photosynthetic efficiency. Biochemically, melatonin markedly increased the activities of key antioxidant enzymes (SOD, CAT, and POD), reduced ROS accumulation, elevated proline content by 24%, and decreased electrolyte leakage by 18%, thereby improving osmotic balance and maintaining membrane integrity. Genomic stability was assessed using ISSR and RAPD markers, revealing that melatonin substantially attenuated drought-induced DNA damage. Marker analysis further demonstrated differential sensitivity, while key statistical indices including polymorphism information content (PIC), effective multiplex ratio (EMR), and resolving power (RP) exhibited strong linear associations, reinforcing the reliability of molecular diagnostics. Collectively, these results highlight melatonin’s multifaceted role in enhancing water deficit resilience through integrated regulation of physiological homeostasis, oxidative stress mitigation, and genome protection. The findings support melatonin’s practical potential as a low-cost, environmentally compatible strategy for improving legume performance in water-deficit environments.

PMID:41337642 | DOI:10.1071/FP25301