Nevin Manimala

Eur J Pediatr. 2026 Jun 23;185(7):518. doi: 10.1007/s00431-026-07195-9.

ABSTRACT

Children with asthma commonly present with multiple allergic comorbidities; however, the quantitative dose-response relationship between cumulative allergic burden and lung function has not been established in pediatric populations. This retrospective cross-sectional study included 264 treatment-naive children with asthma aged 4-16 years. An allergy burden score (ABS) was constructed using a cumulative disease count strategy incorporating allergic rhinitis, atopic dermatitis, food allergy, drug allergy, and family history of allergic disease. Multivariable linear regression and restricted cubic spline (RCS) analyses assessed dose-response relationships between ABS and FEV₁% predicted. Bootstrap-based statistical decomposition examined the contribution of type 2 inflammatory markers, and logistic regression assessed the odds of lung function abnormality. In the fully adjusted model, each 1-point increase in ABS was associated with a 3.03% decrease in FEV₁% predicted (95% CI: – 3.77 to – 2.29; P < 0.001). RCS analysis indicated significant nonlinearity (P for nonlinearity < 0.001), with accelerated decrease at ABS ≥ 3. Type 2 inflammatory markers accounted for only 2.7% of the statistically decomposed total association. Each 1-point increase in ABS was associated with 43% higher odds of lung function abnormality (adjusted OR = 1.43, 95% CI: 1.07-1.94).

CONCLUSION: A dose-response association exists between cumulative allergic comorbidity burden and lung function impairment in treatment-naive children with asthma. Peripheral type 2 inflammatory markers explain only a small proportion of this association, suggesting additional contributing mechanisms. The ABS may warrant further evaluation as a simple clinical indicator for identifying children with greater lung function impairment, pending prospective multicenter validation.

TRIAL REGISTRATION: Not applicable. As a retrospective cross-sectional study, this research analyzed existing medical records without prospective assignment of interventions by the research team, and therefore does not meet the WHO criteria for clinical trial registration.

WHAT IS KNOWN: • Allergic comorbidities are prevalent in children with asthma and associated with worse clinical outcomes. The quantitative dose-response relationship between cumulative allergic burden and lung function has not been established in pediatric populations.

WHAT IS NEW: • Each 1-point increase in the Allergy Burden Score (ABS) was associated with a 3.03% decrease in FEV1% predicted, with a nonlinear threshold effect at ABS ≥ 3. Type 2 inflammatory markers collectively accounted for only 2.7% of the total association, suggesting that mechanisms beyond peripheral type 2 inflammation may be involved.

PMID:42337151 | DOI:10.1007/s00431-026-07195-9

Eur J Pediatr. 2026 Jun 23;185(7):519. doi: 10.1007/s00431-026-07124-w.

ABSTRACT

Childhood disability is a significant health concern with profound implications for caregivers’ well-being. This study examines the association between children’s cumulative disability profile, encompassing disability status, types, and multiplicity, and caregivers’ health-related quality of life (HRQoL) in a cross-sectional Australian setting. Utilising data from the Longitudinal Study of Australian Children (LSAC), this study examined the association between children’s cumulative disability profile and caregivers’ cross-sectional HRQoL. Caregivers’ HRQoL was assessed using the Assessment of Quality of Life-8 Dimensions (AQoL-8D) instrument. Multivariable linear regression models were estimated to assess these associations, adjusting for sociodemographic and economic covariates. Overall, 25% of children experienced at least one form of disability. A significant lower mean utility score was observed (mean difference = 0.034; 95% confidence interval [CI], [0.018, 0.050]; p < 0.001) among caregivers of children with disabilities compared with caregivers of children without disabilities. After adjusting for covariates, caregivers of children with disabilities had significant lower utility (β = – 0.0230; 95% CI, [- 0.0376, – 0.0084]; p = 0.002), physical super dimension (β = – 0.0339; 95% CI, [- 0.0497, – 0.0182]; p < 0.001), and psychological super dimension (β = – 0.0181; 95% CI, [- 0.0353, – 0.0009]; p = 0.039) scores than caregivers of children without disabilities. Similarly, children experiencing physical, sensory, psychosocial disabilities, or multiple coexisting disabilities were associated with lower HRQoL among their caregivers compared with caregivers of children without disabilities.

CONCLUSION: Childhood disability is associated with a lower HRQoL for the caregivers. These findings highlight the need for targeted support services, particularly for families caring for children with physical, sensory, psychosocial, and multiple disabilities, and provide estimates of reductions in health state utility scores to inform future cost-utility analyses of caregiver-focused interventions.

WHAT IS KNOWN: • Caregivers of children with disabilities report lower health-related quality of life (HRQoL) and significantly higher caregiving time demands than caregivers of children without disability. • Despite these recognised challenges, there is a paucity of population-level evidence in the Australian context on how specific child cumulative disability profiles, including status, types, and multiple coexisting conditions, are associated with caregiver cross-sectional HRQoL.

WHAT IS NEW: • Using a nationally representative Australian cohort, this study identifies a significant disparity in health state utility scores between caregivers of children with disabilities and caregivers of children without disabilities. • Beyond overall cumulative disability status, specific categories (physical, sensory, and psychosocial), and the presence of multiple coexisting disabilities are significantly associated with lower caregivers’ HRQoL across both physical and psychological dimensions. • The findings provide specific estimates of reductions in health state utility scores, which are essential for informing future cost-utility analyses of targeted policy interventions for Australian families.

PMID:42337140 | DOI:10.1007/s00431-026-07124-w

Phys Med. 2026 Jun 23;148:105863. doi: 10.1016/j.ejmp.2026.105863. Online ahead of print.

ABSTRACT

PURPOSE: Patient-specific quality assurance (PSQA) for VMAT treatments represents a significant workload. This study presents an integrated approach combining plan complexity metrics with statistical process control (SPC) to safely reduce PSQA burden while maintaining robust process monitoring.

MATERIAL AND METHODS: We analyzed 557 consecutive patients (695 VMAT plans, 1650 arcs). MCSv and SAS were combined into a composite modulation index (CMI). Spearman correlation analysis identified the optimal gamma criterion among 22 configurations, with Bonferroni correction across 220 pairwise tests. Statistical distribution analysis determined tolerance limits using the percentile-equivalent method. ROC analysis established a complexity threshold for PSQA exemption, validated on an independent cohort of 267 patients.

RESULTS: High correlation was observed between (1 – MCSv) × SAS(7.5 mm) and 3%/1.5 mm local gamma criterion (r_S = -0.74, p < 10^-11). The beta distribution provided superior fit to PSQA data across all standard goodness-of-fit metrics (KS = 0.155 vs 0.229-0.235; AD = 34.3 vs 147-160) compared to normal, lognormal, and gamma distributions. Control and action limits were established at 78.1% and 66.5%, and ROC analysis demonstrated excellent discriminative performance (AUC = 0.90, 95% CI: 0.87-0.92). A complexity threshold of 0.131 achieved 100% sensitivity (95% CI: 93.4%-100.0%). Independent validation confirmed perfect sensitivity with zero false negatives. Eight months of clinical implementation achieved 26% workload reduction with no safety incidents.

CONCLUSIONS: This methodology demonstrates that integrating complexity metrics with appropriate statistical modeling and SPC enables safe, clinically validated PSQA workload reduction while maintaining rigorous quality standards and continuous process monitoring.

PMID:42335518 | DOI:10.1016/j.ejmp.2026.105863

Musculoskelet Sci Pract. 2026 Jun 17;85:103604. doi: 10.1016/j.msksp.2026.103604. Online ahead of print.

ABSTRACT

BACKGROUND: Femoroacetabular Impingement Syndrome (FAIS) is a prominent source of non-arthritic hip pain and is highly prevalent in young active populations. Decisions to undergo surgery are significant in nature and require proper understanding of potential benefits and risks.

OBJECTIVE: To develop and user-test a patient decision aid comparing non-surgical management and hip arthroscopy for FAIS with an additional military-related section.

DESIGN: Mixed-methods.

METHOD: The initial draft of the decision aid was developed by a multidisciplinary steering group. An iterative process of semi-structured interviews, re-drafting and further interviews provided feedback on the decision aid. The interviews were analysed reflexively using thematic analysis for qualitative findings. Acceptability questionnaires were analysed using descriptive statistics for quantitative findings.

RESULTS: We interviewed 27-participants; 13 clinicians (6 physiotherapists, 3 orthopaedic surgeons, 2 general practitioners, 1 sports medicine doctor, 1 anaesthesia pain physician) and 14 patients. Most participants rated the decision aid’s acceptability as good-to-excellent. Participants agreed on most aspects of the decision aid including the introduction, treatment options, comparison of outcomes and questions to consider asking a health professional. Participants agreed on including more information on the treatment options and provide more long-term outcomes comparing the options. Our decision aid met all 6 of the International Patient Decision Aid Standards qualifying criteria.

CONCLUSION: Our decision aid was considered a useful tool that may help patients choose an appropriate treatment option for the management of FAIS. A clinical trial evaluating the impact of the decision aid on decision making for patients considering surgery for FAIS is needed.

PMID:42335507 | DOI:10.1016/j.msksp.2026.103604

Pregnancy Hypertens. 2026 Jun 23;45:101492. doi: 10.1016/j.preghy.2026.101492. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare echocardiographic hemodynamic parameters between pregnant women with and without preeclampsia evaluated at high altitude.

STUDY DESIGN: We conducted an observational cross-sectional study including pregnant women evaluated at a tertiary referral center located at 2640 m above sea level. Participants were classified according to the presence or absence of preeclampsia, diagnosed using International Society for the Study of Hypertension in Pregnancy criteria. All participants underwent standardized transthoracic echocardiography following international guidelines. Conditions known to significantly affect maternal hemodynamics were excluded.

RESULTS: A total of 105 pregnant women were included (35 with preeclampsia and 70 controls). Women with preeclampsia had higher cardiac output (median 5.18 L/min (IQR 3.90-6.04) vs. 4.52 L/min (IQR 3.67-5.15); p = 0.045) and higher left ventricular stroke volume (median 62.80 mL (IQR 53.04-71.41) vs. 55.65 mL (IQR 50.24-62.80); p = 0.019) compared with controls. Systemic vascular resistance was lower in the preeclampsia group, although the difference was not statistically significant (median 1243.36 dyn·s·cm^-5 (IQR 1057.32-1594.65) vs. 1418.58 dyn·s·cm^-5 (IQR 1234.44-1717.41); p = 0.06). Left ventricular systolic function and indexed chamber volumes were similar between groups.

CONCLUSIONS: Among pregnant women evaluated at high altitude, preeclampsia was associated with higher cardiac output and stroke volume, accompanied by mild alterations in diastolic filling, without significant differences in ventricular structure or systolic function. These findings underscore the heterogeneity of maternal hemodynamic presentation in preeclampsia and support further investigation of maternal cardiovascular adaptation in high-altitude settings.

PMID:42335505 | DOI:10.1016/j.preghy.2026.101492

Gait Posture. 2026 Jun 18;130:110264. doi: 10.1016/j.gaitpost.2026.110264. Online ahead of print.

ABSTRACT

BACKGROUND: Independent outdoor ambulation is a key rehabilitation goal after stroke, but it is unclear whether instrumented gait analysis adds prognostic information beyond conventional clinical measures.

RESEARCH QUESTION: Do spatiotemporal gait parameters provide incremental predictive value beyond clinical assessments-independent of admission Functional Ambulation Category (FAC)-for outdoor ambulation in subacute stroke patients?

METHODS: We retrospectively analysed 137 subacute stroke inpatients with admission FAC 2-3 (89 outdoor, 48 indoor-only ambulators at discharge); one patient was excluded for an implausible step time. Admission FAC was excluded from candidate predictors to avoid overlap with the outcome. Hierarchical logistic regression compared a clinical model (Motricity Index [MI], time since onset) with one adding GAITRite-derived spatiotemporal parameters, using likelihood-ratio and DeLong tests with Firth-penalised sensitivity analysis.

RESULTS: Model 1 achieved near-perfect discrimination (AUC = 0.995, 95% CI 0.984-0.999). Adding affected-side single- and double-support percentages (Model 2) significantly improved fit (likelihood-ratio χ² = 9.39, p = 0.009; AUC = 0.998); the AUC difference was not significant by DeLong’s test (p = 0.262). Firth-penalised analyses produced concordant, stable coefficients. MI and gait velocity were the strongest single predictors (both AUC = 0.981); bootstrap optimism was ≤ 0.002.

SIGNIFICANCE: Beyond a near-perfect clinical model, affected-side support-phase parameters add statistically detectable model information (improved fit and calibration) rather than a clinically decisive gain in discrimination, which is constrained by a ceiling effect. Their value is best understood as quantifying paretic-limb weight-bearing and balance-related gait quality not captured by bedside scales, in subacute stroke inpatients with admission FAC 2-3. The Youden cut-offs (MI ≥ 40, velocity ≥ 32.1 cm/s, single support ≥ 29.7%) are hypothesis-generating and require external validation before clinical use.

PMID:42335499 | DOI:10.1016/j.gaitpost.2026.110264

J Psychiatr Res. 2026 Jun 22;201:225-230. doi: 10.1016/j.jpsychires.2026.06.025. Online ahead of print.

ABSTRACT

INTRODUCTION: Major depressive disorder (MDD) is strongly associated with suicidal ideation, a major predictor of suicide attempts and completed suicide. Transcranial magnetic stimulation (TMS) has shown promise in improving suicidal ideation, though the generalizability of these findings to routine clinical practice remains uncertain. This study evaluated whether TMS exposure was associated with recurrent suicidal ideation among adults with moderate-to-severe MDD using real-world electronic health record data.

METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adults with moderate-to-severe MDD and documented suicidal ideation who received TMS were compared with matched patients not exposed to TMS. Propensity score matching and Kaplan-Meier and Cox proportional hazards analyses were performed. A landmark sensitivity analysis excluding outcomes within the first 30 days after index was conducted to address potential immortal time bias.

RESULTS: After matching, 1193 patients per cohort were included. Recurrent suicidal ideation occurred in 22.5% of TMS-exposed patients versus 33.9% of controls (HR 0.584, 95% CI 0.500-0.681; p < 0.001). In the landmark sensitivity analysis, recurrent suicidal ideation occurred in 17.5% of the TMS cohort and 14.5% of controls, and the association was no longer statistically significant (HR 1.203, 95% CI 0.954-1.516; p = 0.118).

CONCLUSION: The initially observed association between TMS exposure and lower recurrent suicidal ideation attenuated substantially after landmark sensitivity analysis addressing potential immortal time bias. These findings do not provide robust evidence that TMS independently reduces recurrent suicidal ideation in adults with moderate-to-severe MDD.

PMID:42335495 | DOI:10.1016/j.jpsychires.2026.06.025

J Psychiatr Res. 2026 Jun 6;201:198-206. doi: 10.1016/j.jpsychires.2026.05.037. Online ahead of print.

ABSTRACT

BACKGROUND: Late-life depression (LLD) is a growing public health concern in aging populations. Although digital mindfulness interventions show promise for depression, anxiety, and insomnia, their efficacy and electroencephalogram (EEG) correlates in older adults with LLD remain unclear. This study evaluated the FocusZen Mindfulness Stress Reduction System, a digital mindfulness intervention with EEG feedback, in mild-to-moderate LLD.

METHODS: Fifty-four participants with mild-to-moderate LLD were randomly assigned to a 6-week intervention group (n = 27; daily FocusZen sessions) or a control group (n = 27; general health education). The primary outcome was the change in HAMD-17 score. Secondary outcomes included anxiety, sleep quality, cognition, and frontal EEG spectral activity. Data were analyzed using mixed-effects models and intention-to-treat principles.

RESULTS: The intervention group demonstrated significant reductions in depressive symptoms [HAMD-17: F(3, 132.69) = 8.83, P < 0.001], anxiety [HAMA: F(3, 129.95) = 8.34, P < 0.001], and sleep disturbances [PSQI: F(3, 128.91) = 5.55, P = 0.01], alongside improved cognition [MOCA: F(3, 133.19) = 5.14, P = 0.01]. Response and remission rates were higher in the intervention group. Exploratory EEG analysis showed increased frontal theta [F(1.96, 43.12) = 25.28, P < 0.001] and alpha activity [F(1.44, 31.73) = 22.92, P < 0.001].

CONCLUSIONS: FocusZen-based digital mindfulness reduced depressive, anxiety, and sleep symptoms and improved cognition in mild-to-moderate LLD, potentially accompanied by enhanced frontal theta and alpha activity.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2400086063; https://www.chictr.org.cn/.

PMID:42335492 | DOI:10.1016/j.jpsychires.2026.05.037

J Psychiatr Res. 2026 Jun 17;201:190-197. doi: 10.1016/j.jpsychires.2026.06.021. Online ahead of print.

ABSTRACT

Previous studies have linked opioid use to altered metabolic profiles, but findings have been inconsistent and mechanisms remain unclear. One potential mechanism involves increased adiposity, leading to chronic low-grade inflammation that elevates metabolic risk. Here, we examined metabolic profiles in individuals with opioid use disorder (OUD) and matched non-OUD controls, focusing on the sequential mediating roles of BMI and inflammation. Data from individuals with OUD (n = 281) and non-OUD (n = 246) were drawn from a natural history screening protocol from the National Institute on Alcohol Abuse and Alcoholism intramural program. Groups were matched on age, sex, race, ethnicity, socioeconomic status, and education via propensity score matching. Metabolic measures included body mass index (BMI), hemoglobin A1c (HbA1c), and lipid profiles, with lipid imbalance indexed by the atherogenic index of plasma (AIP). Inflammatory markers included C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Individuals with OUD had significantly higher BMI (F_1,481 = 12.9, p < 0.001), higher HbA1c (F_1,481 = 10.5, p = 0.001), lower high-density lipoprotein cholesterol (HDL-C; F_1,481 = 46.2, p < 0.001), higher low-density lipoprotein cholesterol (LDL-C; F_{1, 481} = 11.9, p < 0.001), and higher AIP (F_1,481 = 20.7, p < 0.001) compared to non-OUD. Inflammatory markers were also elevated in individuals with OUD, including CRP (F_1,481 = 9.4, p = 0.002) and ESR (F_1,481 = 7.4, p = 0.007),and statistically mediated group differences in AIP and HbA1c, respectively. Our results are consistent with prior evidence of metabolic dysfunctions in individuals with OUD and suggest inflammation as a contributing mechanism. Targeting metabolic health and inflammation may offer new avenues for improving long-term health outcomes in OUD.

PMID:42335491 | DOI:10.1016/j.jpsychires.2026.06.021

Ticks Tick Borne Dis. 2026 Jun 23;17(4):102675. doi: 10.1016/j.ttbdis.2026.102675. Online ahead of print.

ABSTRACT

Illinois is known to have established populations of four vector tick species of human health concern: Ixodes scapularis, Dermacentor variabilis, Amblyomma americanum, and Amblyomma maculatum. These ticks can transmit pathogens causing eight reportable tick-borne diseases (TBDs): anaplasmosis, babesiosis, ehrlichiosis, Lyme disease, spotted fever group rickettsioses (SFG rickettsioses), Powassan virus disease, Heartland virus disease, and Bourbon virus disease. The incidence of these diseases is spatially varied and has been changing over time. The purpose of this research is to describe factors associated with human incidence of the various tick-borne diseases in Illinois and to compare this to factors associated with canine seroprevalence to similar tick-borne diseases. All cases of tick-borne diseases in humans reported to the Illinois Department of Public Health (IDPH) between 2004 (when reporting began) and 2022 were reviewed (n = 6423), with all county-level seropositivity and canine test data reported by the Companion Animal Parasite Council between 2009 (when reporting began) and 2022. Descriptive statistics were performed to identify spatial and temporal variation. Comparison with known risk factors was conducted using zero-inflated spatiotemporal modeling for anaplasmosis, ehrlichiosis, Lyme disease, and SFG rickettsioses in humans and anaplasmosis, ehrlichiosis, and Lyme disease in dogs. Every county in Illinois reported at least one case of a human TBD from 2004 to 2022. Most reported cases were in males (61%), white (71%), and non-Hispanic (64%) residents over 40 years of age (56%). On average, the annual number of human cases increased by 23 cases every year (95% CI: 15, 31), despite large year-to-year fluctuations, with 343 in 2022 and 645 in 2021. The spatial hotspots were noted in southern Illinois for human TBDs associated with A. americanum, and D. variabilis, and for dog exposure associated with A. americanum. Hotspots were also noted in northern Illinois for diseases and exposure associated with I. scapularis for both humans and dogs and across the 2004-2022 study period. Case incidence was higher in rural counties, counties with higher deer harvests, and counties with lower median household income. These findings can be used to guide public health efforts that target self-prevention strategies to decrease the risk of a tick bite and tick-borne diseases in Illinois and are applicable in similar midwestern states with expanding TBD risk.

PMID:42335481 | DOI:10.1016/j.ttbdis.2026.102675