Nevin Manimala

JAMA Netw Open. 2025 Dec 1;8(12):e2545274. doi: 10.1001/jamanetworkopen.2025.45274.

ABSTRACT

IMPORTANCE: Prescribing cascades are an underrecognized driver of polypharmacy among older adults (aged ≥65 years). The clinical decision-making processes underlying cascades and their downstream consequences are poorly understood.

OBJECTIVE: To explore clinical reasoning leading to prescribing cascades and downstream outcomes (eg, falls, electrolyte abnormalities) via the exemplar gabapentinoid (gabapentin and pregabalin)-loop diuretic (LD) cascade.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study randomly selected medical records from a cohort of US veterans aged 66 years or older between January 1, 2013, and August 31, 2019, who potentially experienced the gabapentinoid-LD prescribing cascade. The medical record review and data analysis were performed between October 24, 2023, and July 22, 2025.

EXPOSURES: Initiation of gabapentinoid and LD.

MAIN OUTCOMES AND MEASURES: Abstractors evaluated clinical documentation in the 30 days prior to and 60 days after LD initiation to evaluate decision-making processes and potential downstream outcomes of the gabapentinoid-LD cascade. Secondary analyses examined whether a dementia diagnosis was associated with clinician decision-making and patient outcomes.

RESULTS: The analytic cohort comprised 120 patients (mean [SD] age, 73.9 [7.1] years; 116 male [96.7%]; 106 [88.3%] taking ≥5 long-term medications). Documentation of a differential diagnosis for edema was noted in 73 patients (60.8%), most commonly referencing congestive heart failure (n = 47 [39.2%]) and/or venous stasis (n = 16 [13.3%]). Gabapentinoids were rarely noted in the differential (n = 4 [3.3%]). The majority of clinicians documented the indication for LD (n = 116 [96.7%]), most commonly for lower-extremity edema (n = 104 [86.7%]), congestive heart failure (n = 16 [13.3%]), and/or dyspnea (n = 15 [12.5%]). In the 60 days following LD initiation, 28 patients (23.3%) experienced 37 events potentially attributable to LD initiation. The most common downstream events were worsening kidney function (n = 9 [7.5%]), orthostasis (n = 7 [5.8%]), electrolyte abnormalities (n = 6 [5.0%]), and falls (n = 5 [4.2%]). Six patients (5.0%) were evaluated in the emergency department and/or hospital for potential downstream events. Documentation of differential diagnoses, indications, actions taken regarding gabapentinoids, and downstream events generally did not vary between patients with and without dementia.

CONCLUSIONS AND RELEVANCE: This cohort study found that among older veterans who received LD following gabapentinoid initiation and experienced a potential gabapentinoid-LD prescribing cascade, clinicians almost never explicitly considered gabapentinoid adverse drug effects in their treatment of edema. These findings suggest that potential downstream harms of this overlooked prescribing cascade are common, underscoring the importance of addressing prescribing cascades in clinical practice.

PMID:41329486 | DOI:10.1001/jamanetworkopen.2025.45274

JAMA Netw Open. 2025 Dec 1;8(12):e2546166. doi: 10.1001/jamanetworkopen.2025.46166.

ABSTRACT

IMPORTANCE: Maternal vitamin D level during pregnancy has been repeatedly reported to be associated with early childhood caries (ECCs) in offspring, yet the conclusions remain inconsistent.

OBJECTIVE: To evaluate the association between maternal vitamin D status in different trimesters during pregnancy and offspring dental caries.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was based on the Zhoushan Pregnant Women Cohort, which enrolled pregnant women between August 2011 to May 2021, and followed up on their offspring until November 2022, at Zhoushan Maternal and Child Health Hospital in Zhoushan, Zhejiang Province, China. Data were analyzed from October 2024 to April 2025.

EXPOSURES: Maternal plasma 25-hydroxyvitamin D (25[OH]D) levels measured in the first, second, and third trimesters and vitamin D deficiency (VDD).

MAIN OUTCOMES AND MEASURES: The primary outcome was offspring ECCs. Secondary outcomes included the decayed, missing, or filled teeth (dmft, with lowercase term denoting primary, instead of permanent, dentition) index and caries rate (the ratio of dmft to number of erupted teeth).

RESULTS: The cohort included 4109 mother-offspring pairs (maternal median [IQR] age, 29.0 [27.0-32.0] years; offspring gestational age at birth, 39.0 [38.0-40.0] weeks; 2121 males [51.6%]), of whom 960 children had ECCs and 3149 did not. Higher maternal 25(OH)D levels were associated with reduced odds of ECCs in offspring (first trimester odds ratio [OR], 0.98 [95% CI, 0.97-0.99], false discovery rate [FDR]-adjusted P = .009; second trimester OR, 0.98 [95% CI, 0.97-0.99], FDR-adjusted P = .001; third trimester OR, 0.99 [95% CI, 0.98-1.00], FDR-adjusted P = .009), while Cox proportional hazards regression models showed protective benefits of 25(OH)D levels against ECC risk throughout all trimesters. Categorical analyses suggested elevated odds of ECCs in offspring of mothers with vitamin D insufficiency, VDD, or severe VDD compared with the vitamin D sufficiency group, although the statistical significance of some associations was attenuated after FDR correction. Moreover, higher maternal 25(OH)D levels (μg/mL) were associated with lower dmft scores (third trimester: β [SE] = -9.97 [3.97]; P = .01) and caries rate (third trimester: β [SE] = -50.87 [19.78]; P = .01). Generalized estimation equation models also confirmed the inverse associations.

CONCLUSIONS AND RELEVANCE: In this cohort study, maternal 25(OH)D levels throughout pregnancy were inversely associated with odds of offspring ECCs. These findings support the potential benefit of vitamin D supplementation before or during pregnancy in reducing the risk and severity of childhood dental caries.

PMID:41329485 | DOI:10.1001/jamanetworkopen.2025.46166

JAMA Netw Open. 2025 Dec 1;8(12):e2546213. doi: 10.1001/jamanetworkopen.2025.46213.

ABSTRACT

IMPORTANCE: Low-value care has been recognized as a pernicious phenomenon that increases health care costs and contributes to suboptimal care delivery. Low-value surgery may be less likely in systems that used salaried reimbursement as opposed to fee-for-service.

OBJECTIVE: To explore the association of reimbursement model with low-value surgery among a battery of elective procedures.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used TRICARE health care claims to compare rates of low-value surgery over fiscal years 2016 to 2023. Participants included patients aged 10 years and older who underwent acromioplasty, partial knee meniscectomy, shoulder rotator cuff repair, wrist arthroscopy, or ankle arthroscopy. Data were analyzed from January to May 2025.

EXPOSURE: Direct vs private sector care.

MAIN OUTCOMES AND MEASURES: The primary outcome was the comparison of low-value care in patients in direct care vs private-sector care. An interaction between environment of care and year of surgery was retained in all models. Multivariable logistic regression analyses were used to adjust for case mix. Secondary analyses were limited to non-active-duty individuals to account for differences in low-value care for each surgical procedure.

RESULTS: A total of 304 908 procedures were included. The mean (SD) patient age was 47.2 (12.9) years, with 189 648 (62%) male patients. Partial meniscectomy was the most common surgical procedure (128 363 procedures [42%]), followed by acromioplasty (87 721 procedures [29%]). The percentage of low-value surgery in direct care was 20%, compared with 35% in the private-sector (χ22,304 908 = 90007.01; P < .001). After adjusting for case mix, the private sector demonstrated significantly greater odds of low-value surgery (odds ratio [OR], 1.41; 95% CI, 1.38-1.45). Low-value surgery was significantly lower in each respective sector for 2020 to 2023 compared with 2016 to 2019 (direct care: OR, 0.78; 95% CI, 0.73-0.83; private sector: OR, 0.93; 95% CI, 0.91-0.96).

CONCLUSIONS AND RELEVANCE: In this cohort study of 304 908 surgical procedures, direct care evinced a significantly lower likelihood of low-value surgery in both 2016 to 2019 and 2020 to 2023. These findings support the contention that changing clinician reimbursement models from fee-for-service to salaried is associated with lower rates of low-value care.

PMID:41329484 | DOI:10.1001/jamanetworkopen.2025.46213

Strabismus. 2025 Dec 2:1-8. doi: 10.1080/09273972.2025.2579178. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate the long-term efficacy of the Cambridge Visual Stimulator (CAM) in pediatric amblyopia, by comparing outcomes of standard occlusion therapy alone versus occlusion combined with CAM.

METHODS: In this retrospective cohort, 112 patients (112 eyes) aged ≤10 years with strabismic or anisometropic amblyopia were assigned to one of two groups. Group 1 (n = 64) received three hours/day of occlusion therapy; Group 2 (n = 48) received the same occlusion regimen plus a supervised 5-day CAM course (six rotating high-contrast spatial-frequency disks, 18 minutes daily). Best-corrected visual acuity was recorded in logMAR at baseline, 6 months, and 12 months. Within-group improvements were analyzed using the Wilcoxon signed-rank test, and between-group differences with the Mann – Whitney U test. P-value of <0.05 was considered statistically significant.

RESULTS: Both groups showed significant acuity gains at 6 and 12 months versus baseline (p < .001 for all comparisons). Numerically, Group 2 improved more (6 months: -0.137 ± 0.231 vs. -0.127 ± 0.196; 12 months: -0.192 ± 0.267 vs. -0.190 ± 0.225), but these differences did not reach significance (6 months p = .402; 12 months p = .883).

CONCLUSION: Occlusion therapy markedly enhances visual acuity in amblyopic children, whereas adjunctive CAM yields only limited additional benefit. Prospective, larger-scale trials are needed to determine whether specific subgroups – such as treatment-resistant cases – may derive clinically meaningful gains from CAM.

PMID:41329471 | DOI:10.1080/09273972.2025.2579178

Eur J Orthop Surg Traumatol. 2025 Dec 2;36(1):33. doi: 10.1007/s00590-025-04605-w.

ABSTRACT

BACKGROUND: In shoulder arthroscopy, visual clarity is essential for safe and efficient procedures, yet intraoperative bleeding often compromises the surgical field. Several randomized studies have demonstrated that adding epinephrine to irrigation fluid significantly reduces bleeding and enhances visual clarity. This meta-analysis synthesizes findings from multiple studies to critically evaluate the overall efficacy and safety of epinephrine in improving intraoperative visualization during arthroscopic shoulder surgery.

METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Google Scholar for studies published up to September 8, 2025. Eligible studies included randomized controlled trials and comparative observational studies evaluating the effect of epinephrine added to irrigation fluid during shoulder arthroscopy in adults. Primary outcomes included surgeon-rated visual clarity (scored on a 1-to-10 scale) and the incidence of increased pump pressure. Secondary outcomes included operative time, irrigation fluid volume used, and mean arterial pressure.

RESULTS: Six studies met the inclusion criteria, including 422 adult patients undergoing arthroscopic shoulder surgery. Epinephrine use was associated with significantly improved surgeon-reported visual clarity, with a mean difference of 2.32 (95% CI 0.32-4.32; p = 0.02) compared to controls. The epinephrine group also had a significantly lower likelihood of requiring increased pump pressure (risk ratio = 0.39; 95% CI 0.27-0.57; p < 0.001). While trends toward reduced operative time (MD = – 4.38 min; 95% CI: – 10.41 to 1.64; p = 0.15) and lower irrigation fluid volume (MD = – 0.83 L; 95% CI: – 2.04 to 0.37; p = 0.18) were observed, these differences were not statistically significant. No significant differences in mean arterial pressure were found between groups (p > 0.05).

CONCLUSION: In the studies reviewed, epinephrine in irrigation fluid during arthroscopic shoulder surgery significantly increases visual clarity. Based on surgical and patient-specific factors, this should be taken into consideration for arthroscopic shoulder procedures.

PMID:41329443 | DOI:10.1007/s00590-025-04605-w

Phys Eng Sci Med. 2025 Dec 2. doi: 10.1007/s13246-025-01677-0. Online ahead of print.

ABSTRACT

To compare dose to the organ at risk (OAR) and target coverage of carbon-ion beam, protons, and photons for patients with head and neck cancer. Treatment plans for carbon-ion pencil beam scanning (C-PBS) (64 Gy (RBE) in 16 fractions), proton pencil beam scanning (P-PBS), and volumetric modulated arc therapy (VMAT) (70 Gy in 35 fractions for P-PBS and VMAT) were generated and compared using different dose constraints per treatment modality. Dose metrics (e.g. D95,V20) were analyzed. Statistical significance was assessed by the Wilcoxon signed-rank test. Also, we investigated howmany normal tissues were irradiated above the constraint after achieving the planning goals (pass rate) in the OARs. C-PBS outperformed P-PBS and VMAT in PTV coverage (p = 0.01 for both); however, P-PBS and VMAT did not differ substantially from each another (p = 0.35). C-PBS was superior in limiting the dose to the OAR. The pass rates for C-PBS, P-PBS, and VMAT were 94%, 81%, and 69%, respectively. C-PBS demonstrated superior performance compared to VMAT and P-PBS in terms of dose conformation to the target volume and normal tissue sparing, and achieved the highest pass rate in meeting dose constraints.

PMID:41329435 | DOI:10.1007/s13246-025-01677-0

J Orthop Traumatol. 2025 Dec 2;26(1):74. doi: 10.1186/s10195-025-00896-1.

ABSTRACT

BACKGROUND: Robotic-assisted unicompartmental knee arthroplasty (UKA) has gained popularity for its potential to improve implant precision and reduce surgical errors. However, comparative evidence on short-term outcomes versus conventional UKA is lacking. Thus, the purpose of this study was to compare the short-term outcomes of robotic-assisted versus conventional UKA using a nationally representative database.

METHODS: The Nationwide Readmissions Database 2016-2020 was retrospectively examined to identify adult patients who received an elective UKA. After applying exclusion criteria and 1:2 propensity score matching (PSM), 8310 patients were included in the analysis. Outcomes included in-hospital complications, implant malposition or failure, perioperative fracture, length of hospital stay (LOS), hospital costs, and 30- and 90-day readmission rates. Multivariable regression analyses were performed to adjust for residual confounding factors.

RESULTS: Robotic-assisted UKA was associated with significantly lower complication rates compared with conventional UKA (3.7% versus 13.2%, p < 0.001). Specifically, robotic-assisted procedures had reduced risks of implant malposition or failure (odds ratio [OR] = 0.08; 95% confidence interval [CI]: 0.05-0.13; p < 0.001) and perioperative fracture (OR = 0.18; 95% CI 0.04-0.76; p = 0.020). No significant differences were observed in LOS, total hospital costs, or readmission rates at 30 and 90 days.

CONCLUSIONS: Robotic-assisted UKA is associated with improved short-term surgical safety, including fewer complications, particularly, reduced implant malposition and perioperative fractures. However, broader hospital metrics such as LOS, cost, and readmissions were comparable between the two approaches. Further prospective studies are needed to validate these findings and assess long-term outcomes and cost-effectiveness.

LEVEL OF EVIDENCE: Level III.

CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

PMID:41329432 | DOI:10.1186/s10195-025-00896-1

Clin Rheumatol. 2025 Dec 2. doi: 10.1007/s10067-025-07862-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the prevalence of kinesiophobia and central sensitization and the association of kinesiophobia and central sensitization with clinical variables in patients with gout.

METHOD: This cross-sectional study included patients with gout and age- and gender-matched individuals. All participants were assessed by using the Tampa Scale of Kinesiophobia (TSK), Central Sensitization Inventory (CSI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), and International Physical Activity Questionnaire-Short Form (IPAQ-SF). Disease-related clinical variables, Gout Activity Score (GAS), and Health Assessment Questionnaire-Disability Index (HAQ-DI) were also recorded.

RESULTS: The frequency of kinesiophobia and central sensitization in patients with gout was 62.3% and 33.8%, respectively. TSK, CSI, and HADS scores were higher, and SF-36 and IPAQ-SF scores were lower in patients with gout than in controls. Patients with kinesiophobia statistically had higher GAS, CSI, HADS, and HAQ-DI scores and lower subscores of SF-36 (except emotional role) and total IPAQ-SF scores than the non-kinesiophobia group. GAS, TSK, HADS, and HAQ-DI scores were found to be higher, and SF-36 and total IPAQ-SF scores were lower in patients with central sensitization compared to those without central sensitization. TSK and CSI scores had significant positive correlations with each other (ρ = 0.650) and with pain, GAS, HADS-D, HADS-A, and HAQ-DI scores (ρ ranged from 0.414 to 0.702). According to the regression analyses, the CSI score appeared to determine the severity of kinesiophobia.

CONCLUSIONS: Kinesiophobia and central sensitization frequently accompany patients with gout. These were associated with increased pain intensity, decreased quality of life, impaired emotional health, functionality, and physical activity. Key Points • The frequency of central sensitization and kinesiophobia accompanying patients with gout is considerable. • Mental health plays a fundamental role in influencing central sensitization in gout. • Central sensitization was independently associated with kinesiophobia. • These close associations lead to challenges in optimizing management, functionality, physical activity level, and quality of life in gout.

PMID:41329430 | DOI:10.1007/s10067-025-07862-6

Clin Rheumatol. 2025 Dec 2. doi: 10.1007/s10067-025-07859-1. Online ahead of print.

ABSTRACT

BACKGROUND: While stress is associated with the exacerbation of rheumatoid arthritis (RA), empirical evidence linking specific, acute real-world stressors to objective inflammatory markers and clinical symptoms remains limited. This study investigated the short-term effects of a defined occupational stressor-24-h hospital duty-on C-reactive protein (CRP) levels and pain in a patient with RA.

METHODS: A 40-day prospective, within-subject observational study was conducted on a male participant with stable, low disease activity RA. During this period, the participant completed six 24-h duty shifts. A total of 20 high-sensitivity CRP blood tests were performed, and daily self-reported data on pain and stress/fatigue were collected. Fisher’s exact test was used to compare the proportion of CRP-positive samples ( exact tedL) obtained within 2 days after a duty shift to those from all other periods. Spearman correlation analysis was employed to evaluate the relationships between CRP levels, pain intensity, and fatigue.

RESULTS: CRP levels showed statistically significant, strong positive correlations with both pain intensity (rho = 0.68, p < 0.001) and fatigue (rho = 0.74, p < 0.001). The CRP positivity rate was 63.6% (7/11) within 2 days following a 24-h duty shift, which was significantly higher than the rate of 0% (0/9) during non-post-duty periods (p = 0.0067). Furthermore, even minimal elevations in CRP were associated with substantial increases in pain intensity.

CONCLUSION: This single-case study provides preliminary evidence that acute, real-world occupational stress can trigger a significant increase in systemic inflammation (CRP) and associated clinical symptoms in RA. These findings underscore the importance of stress management in RA care and suggest that clinically meaningful disease activity may persist even when CRP levels are normal (< 0.50 mg/dL) or only minimally elevated.

PMID:41329429 | DOI:10.1007/s10067-025-07859-1

J Autism Dev Disord. 2025 Dec 2. doi: 10.1007/s10803-025-07146-7. Online ahead of print.

ABSTRACT

PURPOSE: Empathy has become a key area of research in children with autism spectrum disorder (ASD) in recent years. However, the neural characteristics of empathy in children with ASD remain controversial. To advance the understanding of the neural mechanism of ASD’s empathy and test the classic empathy imbalance hypothesis, it is necessary to explore the cognitive-affective empathy in young children with ASD from another electrophysiological perspective in detail.

METHODS: The present study explored the specific neural characteristics of children with ASD and typically developing children under cognitive empathy and affective empathy via simultaneous EEG recording of social animation, which would be able to capture reliable and effective evidence in children with ASD.

RESULTS: The present study mainly revealed that the ASD group had abnormal electrophysiological characteristics under cognitive empathy, including increased functional connectivity in the θ band and abnormalities in the microstate classes C and D. Incidentally, this study also roughly found that the severity of autism symptoms was significantly correlated with the β-band amplitude of certain brain regions when viewing cognitive empathy clips, whereas the severity of autism symptoms was significantly correlated with the θ-band amplitude when viewing affective empathy clips.

CONCLUSION: The present study supported the empathy imbalance hypothesis in young children with ASD and might indicate that children with ASD have distinct neural characteristics related to cognitive empathy and affective empathy processing. Future studies can combine eye movement measurements while watching animations, and further longitudinal studies on the electrophysiological characteristics of empathy in children with ASD.

PMID:41329424 | DOI:10.1007/s10803-025-07146-7