Nevin Manimala

Int Endod J. 2026 Jul 24. doi: 10.1111/iej.70236. Online ahead of print.

ABSTRACT

INTRODUCTION: This study evaluated whether the SCN9A rs6746030 (G>A; R1150W) polymorphism is associated with the clinical success or failure of pulpal anaesthesia following an inferior alveolar nerve block (IANB).

METHODS: In this prospective clinical genetic association study, 320 patients with symptomatic irreversible pulpitis in mandibular molars were recruited. Each patient received a standardized IANB with 2% lidocaine and 1:80000 epinephrine. Anaesthesia was considered successful if the Heft-Parker Visual Analogue Scale (HP-VAS) score was below 54 mm during access cavity preparation/instrumentation; scores of 54 mm or higher were classified as failures. Buccal swab samples were collected for genotyping of rs6746030 using a TaqMan SNP assay. Genotype distributions were compared between the success and failure groups. Statistical analysis included Hardy-Weinberg equilibrium testing, chi-square comparisons, and binary logistic regression with genotype, age and gender as predictors.

RESULTS: Out of 320 patients analysed, 199 experienced failed anaesthesia, while 121 achieved successful outcomes. A significant deviation from Hardy-Weinberg equilibrium was found in the failed anaesthesia group (p < 0.05), suggesting potential genetic influence, while the successful group showed no deviation (p = 0.99). Logistic regression revealed that patients with the AA genotype had significantly lower odds of successful anaesthesia (OR = 0.22; 95% CI: 0.049-0.993). No significant associations were observed for the GA genotype, age, or gender. The model’s predictive ability was limited, with an AUC of 0.53.

CONCLUSION: The rs6746030 polymorphism of SCN9A in its AA form is associated with a higher likelihood of IANB failure in mandibular molars with symptomatic irreversible pulpitis.

PMID:42495805 | DOI:10.1111/iej.70236

J Biopharm Stat. 2026 Jul 24:1-18. doi: 10.1080/10543406.2026.2699849. Online ahead of print.

ABSTRACT

Oncology dose optimization has moved beyond the maximum tolerated dose paradigm, yet many programs still implicitly target a threshold-style minimum effective dose (MED). In serious cancers, deliberately sub-therapeutic comparators are rarely ethical or approvable, so any sharp MED threshold is typically a fragile and only partially identifiable target. We propose a statistical and operational framework that reframes dose-finding as region-based optimization. First, we define a constraint-based Dose Optimization Region (DOR) where clinically meaningful benefit (potentially multi-endpoint and PD-informed) is credible, unacceptable toxicity is bounded, exposure targets are attainable within a prespecified window, and implementation is feasible. Second, within the DOR, we identify an Operational Optimal Dose (OOD) – a label-ready dosing strategy that integrates dose, schedule, exposure targets, and adjustmentrules – using comparative evidence across binary and time-to-eventendpoints, exposure – response (PK/PD) analyses, and time-to-event methods that account for delayed effects where follow-up allows. This approach turns regulatory evidence domains into region-definingconstraints and shifts the target from a single-point estimate to a strategy-level deliverable. It is intended to sit on top of conventional dose-finding designs and PK/PD modeling as a region-defining and reporting standard, rather than to replace existing methods. We illustrate its use with small-samplevisualizations based on pairwise superiority probabilities across in-region arms and with a real-world-inspired example to show how DOR→OOD can summarize the totality of evidence in practice. The framework provides statisticians and clinicians with practical design patterns and reporting checklists, aligning with contemporary regulatory expectations and supporting dose optimization in oncology, with potential adaptation to other therapeutic areas.

PMID:42495769 | DOI:10.1080/10543406.2026.2699849

Euro Surveill. 2026 Jul;31(29). doi: 10.2807/1560-7917.ES.2026.31.29.2600567.

NO ABSTRACT

PMID:42495763 | DOI:10.2807/1560-7917.ES.2026.31.29.2600567

J Investig Med. 2026 Jul 24:10815589261473281. doi: 10.1177/10815589261473281. Online ahead of print.

ABSTRACT

Obesity-related chronic inflammation, together with dyslipidemia, promotes gradually progressive microangiopathy all over the body. Retinal vascular network is a mirror for systemic diseases induced vascular complications. We aimed to explore the association between choroidal thickness and retinochoroidal microvascular changes and insulin resistance indices [Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and triglyceride glucose (TyG) index] in obese children. This exploratory pilot comparative study included 20 obese children (BMI >95th percentile) and 20 healthy normal weight children (BMI >5th, <85th percentile for age and sex) as controls. Optical coherence tomography angiography (OCTA) 6×6 mm scans was used to measure central macular thickness (CMT), choroidal thickness, foveal avascular zone, choriocapillaris flow area, and retinal superficial/deep vessel densities (SVD/DVD) in parafoveal and perifoveal sectors. Anthropometric measurements, lipid profile, HOMA-IR and TyG index were assessed and correlated to OCTA parameters. Obese children had significantly lower visual acuity and thinner choroid compared to normal weight children. OCTA showed significant reductions in SVD and DVD across multiple para-/perifoveal sectors in obese than normal weight children. There are statistically significant negative correlations between Waist/height ratio, insulin resistance indices and OCTA parameters particularly at DVD. Effect size analysis showed high difference in TyG index, whole and parafoveal DVD between obese and normal weight children. In conclusion, obesity may contribute to subclinical retinal and choroidal structural changes beginning at DVD particularly in those with central obesity and insulin resistance. OCTA provides a noninvasive tool for detection of subclinical retinal vascular changes in children with obesity.

PMID:42495759 | DOI:10.1177/10815589261473281

J Glob Health. 2026 Jul 24;16:04252. doi: 10.7189/jogh.16.04252.

ABSTRACT

BACKGROUND: The liver-kidney axis has been increasingly recognised as a potential pathway linking metabolic dysfunction to chronic kidney disease (CKD). However, longitudinal evidence from sub-Saharan African populations remains limited. We therefore aimed to prospectively investigate the association of baseline liver biomarkers with incident CKD and its components over six years in a transcontinental cohort of Ghanaians living in rural and urban Ghana and Amsterdam, the Netherlands.

METHODS: Using data from the prospective Research on Obesity and Diabetes among African Migrants cohort, we examined baseline liver biomarkers (gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the fatty liver index (FLI) in relation to incident CKD over approximately six years among Ghanaians in rural and urban Ghana and Amsterdam, The Netherlands. CKD was defined according to the Kidney Disease: Improving Global Outcomes 2021 criteria using race-free CKD-EPI equations. We used Poisson regression with robust standard errors to estimate adjusted incidence rate ratios (aIRRs) per standard deviation increases, adjusting for demographic, lifestyle, metabolic, and clinical factors. In fully adjusted models, we additionally accounted for longitudinal change (Δ) in liver biomarkers to isolate the association of baseline hepatic dysfunction with subsequent CKD risk.

RESULTS: Among 1,832 participants free of CKD at baseline (mean age of 45.9 years, 63% female), the incidence of CKD was 11%, the incidence of albuminuria was 9.7%, and the incidence of decreased estimated glomerular filtration rate (eGFR) was 2.3% over the follow-up period. Incident CKD was independently associated with higher baseline GGT (aIRR = 1.12; 95% confidence interval (CI) = 1.01-1.23), ALT (aIRR = 1.27; 95% CI = 1.04-1.50), and AST (aIRR = 1.20; 95% CI = 1.04-1.34). Associations were primarily driven by albuminuria, while we observed no significant associations for decreased eGFR. In exploratory analyses, elevated FLI was associated with incident CKD (aIRR = 1.92; 95% CI = 1.14-3.18 and albuminuria (aIRR = 2.15; 95% CI = 1.24-3.68), suggesting a broader metabolic-hepatic phenotype linked to early renal injury. Effect estimates remained materially consistent after inverse probability weighting to address differential follow-up.

CONCLUSIONS: In our study, markers of liver cell injury were associated with increased risk of CKD over six years in the African population. Our findings support a potential link between hepatic metabolic dysfunction and early renal injury, highlighting the need for integrated cardiometabolic risk assessment in sub-Saharan Africa.

PMID:42495747 | DOI:10.7189/jogh.16.04252

J Investig Med. 2026 Jul 24:10815589261473287. doi: 10.1177/10815589261473287. Online ahead of print.

ABSTRACT

Cardiovascular disease is the leading cause of death in women, who also experience worse outcomes after a cardiovascular event. Lifestyle factors such as diet, physical activity, and smoking influence the process of vascular aging. Therefore, the aim of this study was to examine the associations between lifestyle behaviors and various vascular parameters in women. A systematic search was conducted in different databases (PubMed, Scopus, Cochrane, and Web of Science) from their inception to April 2025. Standardised mean differences and their corresponding 95% confidence intervals for each outcome are presented in forest plots to assess the relationships between lifestyle behaviours and vascular parameters in women. All the statistical analyses were conducted via STATA 15 software. Twenty studies were included in the umbrella review. Flow-mediated dilation significantly improved following dietary and physical exercise interventions, particularly aerobic exercise and high-intensity interval training, whereas tobacco use was associated with a marked reduction. No significant effects were observed in terms of the relationship between physical exercise and the intima-media thickness. In contrast, various types of physical activity resulted in significant reductions in pulse wave velocity. This umbrella review demonstrates that lifestyle behaviours influence vascular parameters such as flow-mediated dilation and pulse wave velocity in women. However, further research is needed to provide more specific findings.

PMID:42495746 | DOI:10.1177/10815589261473287

J Investig Med. 2026 Jul 24:10815589261473288. doi: 10.1177/10815589261473288. Online ahead of print.

ABSTRACT

BACKGROUND: Body image disturbance (BID) affects physical and mental health, particularly in vulnerable populations like refugees. Syrian refugees in Jordan face unique challenges, including displacement and limited healthcare access, which may exacerbate BID. This study investigates BID, weight perception, and health behaviors among Syrian refugees in the Zaatari camp.

METHODS: A cross-sectional study was conducted among 487 Syrian refugees (61.4% males, 38.6% females) in the Zaatari camp between September and December 2022. Data collection involved Stunkard’s silhouettes and a health and lifestyle questionnaire. Statistical analysis was performed using IBM SPSS version 27.

RESULTS: Males had higher rates of overweight (23.8%) and obesity (8.6%) than females (15.4% and 3.1%, respectively). Among overweight participants, 71 females (14.5% of the total sample) and 109 males (22.3% of the total sample) perceived themselves as having an average weight, indicating underestimation of their weight status. Physical inactivity (26.1% females, 44.15% males) and poor dietary adherence (37.4% females, 59.3% males) were prevalent. Smoking was reported by (22.1%) of participants, primarily cigarette use among smokers (71.3%). Regarding perceived social influence, 109 overweight males (22.3%) and 69 overweight females (14.17%) reported that they believed their parents perceived them as being of average weight.

CONCLUSION: Targeted health education and culturally sensitive interventions are needed to address BID and promote healthier behaviors among Syrian refugees. Expanding education and integrating psychiatric and nutritional counseling could mitigate BID’s effects. Future research should explore sustainable, community-driven health solutions.

PMID:42495745 | DOI:10.1177/10815589261473288

J Glob Health. 2026 Jul 24;16:04208. doi: 10.7189/jogh.16.04208.

ABSTRACT

BACKGROUND: While frailty is a major public health concern in ageing populations, evidence on its relationship with hobby engagement among older adults remains limited. Existing studies have largely been limited to single-country settings and specific hobby types, with little evidence on cross-national generalisability or whether engagement frequency is associated with additional benefit.

METHODS: We conducted secondary analyses of harmonised longitudinal data from four nationally representative ageing cohorts conducted across 15 countries between 2010 and 2023: the China Health and Retirement Longitudinal Study, the English Longitudinal Study of Ageing, the US Health and Retirement Study, and the Survey of Health, Ageing and Retirement in Europe. We included participants aged ≥65 with baseline data on hobby engagement, frailty, and covariates, and who had frailty assessed at follow-up using the frailty index (FI). We used linear mixed models and random-effects meta-analyses to estimate the association between hobby engagement and FI, with average marginal effects (AMEs) and their 95% confidence intervals (CIs) reported. We further examined whether this association varied across subpopulations and whether higher engagement frequency was associated with additional benefits, and performed sensitivity analyses to assess the robustness of our findings.

RESULTS: Overall, 43,346 participants from 15 countries were included in the binary hobby-engagement analysis. The hobby engagement frequency analysis included 31,538 participants from 14 countries, as harmonisable information on engagement frequency was unavailable in ELSA. Hobby engagement was associated with lower FI (pooled AME = – 0.044; 95% CI = -0.054, -0.034; P < 0.001). Similar associations were consistently observed across age, education, smoking history, alcohol drinking, and physical activity levels, with AMEs from -0.032 to -0.058 and P-values <0.05, with no statistically significant interactions detected. Analyses by frequency suggested that hobby engagement at least monthly was associated with a significantly lower FI compared with less than once per month (pooled AME = 0.003; 95% CI = -0.006, -0.001; P = 0.028), but higher frequencies, either weekly (P > 0.05) or daily (P > 0.05), did not provide any additional benefits. Sensitivity analyses confirmed the robustness of our findings.

CONCLUSIONS: Hobby engagement was associated with lower subsequent FI among adults aged ≥65 years. The association appeared to plateau beyond a modest engagement level, suggesting that hobby engagement at an appropriate frequency may represent a generalisable and low-cost behavior associated with frailty risk.

PMID:42495743 | DOI:10.7189/jogh.16.04208

Stroke. 2026 Jul 24. doi: 10.1161/STROKEAHA.126.056127. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of postthrombectomy blood pressure (BP) management on the development of acute kidney injury (AKI) in patients with acute ischemic stroke remains largely unexplored.

METHODS: This secondary analysis of the OPTIMAL-BP trial (Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control) included patients with acute ischemic stroke due to large-vessel occlusion who achieved successful endovascular thrombectomy and had a systolic BP ≥140 mm Hg. Patients were randomized to intensive (target systolic BP <140 mm Hg) or conventional (target systolic BP 140-180 mm Hg) BP management for 24 hours. The outcomes were AKI within 7 days and within 2 days, defined according to the Kidney Disease: Improving Global Outcomes criteria. In addition, we examined the associations between AKI and functional independence at 3 months, defined as a modified Rankin Scale score of 0 to 2. Multivariable logistic regression analyses were performed with adjustment for age, sex, time from stroke onset to enrollment, baseline National Institutes of Health Stroke Scale score, and baseline estimated glomerular filtration rate.

RESULTS: Of 306 patients, 19 were excluded, and 287 patients were included in this analysis (mean age, 73.2 years; 117 [40.8%] women). AKI within 7 days occurred more frequently in the intensive management group than in the conventional group (20/147 [13.6%] versus 9/140 [6.4%]; adjusted odds ratio, 2.54 [95% CI, 1.10-6.35]). Most AKI events were stage 1 (20/29 [69.0%]). Early AKI within 2 days was also more common with intensive BP management. Patients with AKI had significantly lower rates of functional independence (4/29 [13.8%] versus 126/257 [49.0%]; adjusted odds ratio, 0.19 [95% CI, 0.05-0.55]) and higher stroke-related mortality at 3 months (11/29 [37.9%] versus 8/257 [3.1%]; adjusted odds ratio, 13.8 [95% CI, 4.14-49.64]). In a sensitivity analysis with equal creatinine ascertainment, the association with 48-hour AKI did not reach statistical significance (7/76 [9.2%] versus 2/66 [3.0%]; adjusted odds ratio, 4.20 [95% CI, 0.83-32.6]), although the absolute risk difference remained directionally consistent.

CONCLUSIONS: Intensive BP lowering after successful endovascular thrombectomy was associated with a higher risk of AKI, even when kidney injury was predominantly mild. In addition, AKI was associated with worse neurological outcomes. These findings suggest that AKI is an important marker of systemic hemodynamic vulnerability after aggressive postendovascular thrombectomy BP lowering.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04205305.

PMID:42495732 | DOI:10.1161/STROKEAHA.126.056127

J Arrhythm. 2026 Jul 22;42(4):e70366. doi: 10.1002/joa3.70366. eCollection 2026 Aug.

ABSTRACT

BACKGROUND: Electrical storm (ES) is a life-threatening manifestation of ventricular tachycardia (VT) associated with highmorbidity and mortality. Catheter ablation is an established therapy for VT, but the impact of ES on ablation outcomes remains uncertain.

METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 to compare VT ablation outcomes in patients with and without ES. PubMed, Cochrane Library, and ScienceDirect were searched from inception through January 2026. Eligible studies were comparative cohorts reporting periprocedural or long-term outcomes. Random-effects models were used to pool odds ratios (ORs), hazard ratios (HRs), and mean differences (MDs), with heterogeneity assessed using the I² statistic.

RESULTS: Six observational cohort studies including 3531 patients (1183 with ES and 2348 without ES) were included. Acute procedural endpoints, including post-ablation VT non-inducibility and residual inducible VT, were similar between groups. Periprocedural or in-hospital mortality was significantly higher in the ES group (OR 4.71, 95% CI 2.76-8.06), whereas complication rates, procedural duration, radiofrequency ablation time, and need for hemodynamic support did not differ significantly. During follow-up, ES was associated with higher all-cause mortality (OR 1.67, 95% CI 1.19-2.35) and greater VT recurrence in both arm-based (OR 1.45, 95% CI 1.11-1.91) and time-to-event analyses (HR 1.35, 95% CI 1.16-1.57).

CONCLUSIONS: VT ablation showed comparable acute procedural success and procedural safety in patients with and without ES. However, ES was associated with higher early and long-term mortality and greater VT recurrence, supporting its role as a marker of adverse prognosis.

PMID:42495726 | PMC:PMC13392503 | DOI:10.1002/joa3.70366