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Nevin Manimala Statistics

The ultrasound gap in de-resuscitation trials: A systematic review of physiological assessment deficits

Ultrasound J. 2026 Aug 26;18(1):18750. doi: 10.5826/tuj.2026.18750.

ABSTRACT

BACKGROUND: Fluid overload is associated with increased mortality in critically ill patients, yet de-resuscitation trials frequently report negative or inconclusive results. This systematic review examines the relationship between parameter objectivity, ultrasound utilization, and trial outcomes in de-resuscitation research.

METHODS: We conducted a comprehensive systematic review of randomized controlled trials investigating de-resuscitation interventions in critically ill adults. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Statistical analysis included comparison of ultrasound versus non-ultrasound studies and pooled outcome analysis.

RESULTS: 13 studies were identified which randomised 2495 patients. Of the included studies, 4 (30.8%) performed some form of ultrasound assessment. However, only 1 study (7.7%) explicitly used ultrasound to guide de-resuscitation interventions. However, it did not achieve significant fluid separation between the control and interventional arm. No studies achieved positive hard clinical outcomes (mortality reduction or major morbidity reduction) from de-resuscitation interventions. However, several studies successfully achieved their stated primary endpoints: fluid balance separation was achieved in 7 of 13 studies (53.8%), feasibility objectives were met in 3 studies, and improvements in secondary endpoints including ventilator-free days and time to extubation were demonstrated in select studies. These findings suggest that achieving targeted fluid balance changes does not necessarily translate to improved clinical outcomes.

CONCLUSIONS: Current research is characterized by a significant ‘ultrasound gap,’ where the theoretical benefits of POCUS are not yet integrated into interventional trials. Future research must bridge this gap using standardized, physiology-driven protocols.

PMID:42644856 | DOI:10.5826/tuj.2026.18750

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Nevin Manimala Statistics

Endothelin Receptor Antagonists in Resistant Hypertension and Proteinuric Kidney Disease: Receptor Strategy and Volume Management

J Clin Hypertens (Greenwich). 2026 Aug;28(8):e70353. doi: 10.1111/jch.70353.

ABSTRACT

This narrative review examines how endothelin receptor antagonists (ERAs) can be used at the intersection of difficult-to-control hypertension, chronic kidney disease (CKD), and albuminuria or proteinuria. For clinicians, the central question is not receptor selectivity alone, but whether a specific agent, indication, dose, background therapy, and monitoring plan can deliver meaningful blood-pressure or kidney benefit without unacceptable fluid retention. Pulmonary arterial hypertension established the pharmacology and major safety liabilities of the class; the current implementation questions for hypertension and kidney specialists arise in systemic hypertension and proteinuric kidney disease. Aprocitentan is the first and only ERA approved for hypertension; in PRECISION, the approved 12.5-mg once-daily dose reduced placebo-corrected 24-h ambulatory systolic blood pressure by 4.2 mm Hg, with reductions of 4.2 to 5.9 mm Hg across the studied doses. In IgA nephropathy (IgAN), sparsentan reduces proteinuria and slows estimated glomerular filtration rate (eGFR) decline. Atrasentan has an established antiproteinuric effect and a favorable eGFR slope, although the prespecified week-136 eGFR contrast in the final ALIGN analysis did not reach statistical significance. Zibotentan plus dapagliflozin remains investigational. Across these settings, successful ERA use depends on careful patient selection, indication-specific interpretation of the evidence, optimized diuretic and cardiorenal therapy, and early surveillance for edema, anemia, liver-test abnormalities, and pregnancy risk, with treatment interruption or discontinuation when clinically significant volume expansion or other serious safety signals occur.

PMID:42644854 | DOI:10.1111/jch.70353

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Nevin Manimala Statistics

The Cox-Aalen Rate Model for Recurrent Events With an Informative Terminal Event

Stat Med. 2026 Sep;45(20-22):e70726. doi: 10.1002/sim.70726.

ABSTRACT

Recurrent event data arise frequently in many clinical and observational studies. In this article, we propose a Cox-Aalen rate model to analyze recurrent event data with a terminal event, where the covariate effects are additive, time-varying, and dependent on a latent variable nonparametrically. The association between recurrent and terminal events is fully nonparametric, and a proportional hazards model is specified for the terminal event. To estimate the model parameters, an estimating equation approach is developed and kernel-smoothing techniques are employed to estimate the conditional expectations in the estimating equation. The asymptotic properties of the proposed estimators are derived, and the finite sample performance is evaluated through simulation studies. An application to medical cost data for chronic heart failure patients is presented.

PMID:42644838 | DOI:10.1002/sim.70726

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Nevin Manimala Statistics

Sleep Quality and Falls Risk in the ELSA Study: A Cross-Sectional and Prospective Cohort Study

Brain Behav. 2026 Aug;16(8):e71719. doi: 10.1002/brb3.71719.

ABSTRACT

BACKGROUND: With aging populations, falls represent a significant public health challenge. Previous studies suggest that poor sleep quality may increase fall risk, but evidence among adults aged 50 years or older in the UK remains limited. The present study sought to investigate the associations between sleep quality, falls, and new-onset falls, along with potential underlying mechanisms.

METHODS: Data from the English Longitudinal Study of Ageing were analyzed. Cross-sectional associations between sleep quality and falls were assessed at baseline, and prospective analyses evaluated new-onset falls over a 4-year follow-up period between Wave 4 and Wave 8. Sleep quality was measured using the Jenkins Sleep Scale. Logistic regression models and restricted cubic spline (RCS) analyses were used to evaluate associations and dose-response relationships, respectively. Machine learning approaches were applied to identify risk factors for falls, and mediation analyses explored potential underlying pathways.

RESULTS: In the cross-sectional analysis, 9,734 participants were included (mean age, 68.11 years; 54.34% were female), of whom 2,446 reported falls. After adjustment for covariates, poorer sleep quality was independently associated with greater odds of falls (OR = 1.07, 95% CI: 1.05-1.09, p < 0.0001). In the prospective analysis, 3,224 participants were included (mean age, 68.32 years; 53.16% were female), of whom 1,452 reported new-onset falls. Findings were similar to those observed in the cross-sectional analysis (OR = 1.04, 95% CI: 1.01-1.07, p < 0.05). RCS analyses revealed an increase in fall risk as sleep quality worsened (p-overall < 0.05). LASSO regression and the Boruta algorithm identified depressive symptoms as key variables across different study designs. Mediation analyses indicated that depressive symptoms mediated 28.24% and 28.20% of the associations of sleep quality with falls and new-onset falls, respectively.

CONCLUSIONS: Poor sleep quality is significantly associated with a greater risk of falls among adults aged 50 or older. Depressive symptoms may partially mediate this association. Interventions addressing both sleep quality and depressive symptoms may help reduce falls in this population.

PMID:42644837 | DOI:10.1002/brb3.71719

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Nevin Manimala Statistics

Race, ethnicity, and prior colorectal screening test use in CONFIRM colonoscopy vs fecal immunochemical testing trial participants

JNCI Cancer Spectr. 2026 Aug 26:pkag080. doi: 10.1093/jncics/pkag080. Online ahead of print.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) outcomes vary by both race and ethnicity, and screening test use may contribute to this variation. We examined the association of race, ethnicity, and associated factors with CRC screening test use in a setting where financial barriers to screening are mitigated.

METHODS: Survey information was gathered from US Veteran participants (N = 50,125) when enrolled into a randomized trial comparing screening colonoscopy to annual fecal immunochemical testing (FIT) in the prevention of CRC mortality. The primary exposures of interest were the participants’ self-identified race and ethnicity, with adjustment for variables capturing access to care. Multivariable logistic regression, stratified by site and age, was used to assess the relationship between exposures of interest and prior use of any CRC screening test, prior colonoscopy, and prior fecal occult blood test (FOBT, including FIT) use.

RESULTS: Screening test use was common (N = 28,330, 56.5%) with more Veterans reporting prior FOBT (N = 20,386, 40.7%) than prior colonoscopy (N = 12,671, 25.3%). In multivariable analysis, Black participants were more likely (odds ratio (OR), 1.06; 95% confidence interval (CI) 1.01-1.12) to have had any prior screening relative to White persons and this finding was driven by more frequent FOBT use relative to White persons (OR, 1.16; 95% CI 1.10-1.23). There was no association between Hispanic ethnicity (relative to White persons) on the primary outcomes.

CONCLUSIONS: In this cohort, prior screening test use was common, with observed variation in overall test use by race, but not ethnicity. Further study of CRC screening test use in diverse populations are needed.

CLINICALTRIALS.GOV ID: NCT#05612347.

PMID:42644818 | DOI:10.1093/jncics/pkag080

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Nevin Manimala Statistics

A retrospective study of planned and achieved rotational changes of maxillary canines with clear aligner therapy

Am J Orthod Dentofacial Orthop. 2026 Aug 25:S0889-5406(26)00324-0. doi: 10.1016/j.ajodo.2026.05.016. Online ahead of print.

ABSTRACT

INTRODUCTION: This retrospective study aimed to assess the accuracy of planned moderate-to-severe rotation changes (≥5°) of maxillary canines with the Invisalign (Align Technology, Tempe, Ariz) appliance. The secondary aim was to evaluate the influence of the planned rotation direction on the accuracy.

METHODS: Digital models representing the initial malocclusion, the planned occlusions, and the achieved occlusions after the wear of an initial series of Invisalign aligners by adult patients were measured using metrology software. A method to define rotation directions was formulated. The sample was then divided into 5 categories by rotation type: mesial-in, mesial-out, distal-in, distal-out, and combination rotations. This categorization enabled subsequent analyses to determine whether the planned rotation directions were met and whether rotation direction influenced accuracy.

RESULTS: A total of 114 maxillary canines from 75 patients satisfied the inclusion criteria. Overall, the mean accuracy of the planned rotation was 64%. Rotation direction had no statistically significant influence on the accuracy of the planned rotations. Planned rotation directions were achieved in 77% of the maxillary canines evaluated. Combination rotations demonstrated the greatest variability, with 51% rotating in a direction other than that planned. A 1° increase in rotational velocity per aligner correlated with a 5.35° shortfall in the accuracy of this rotation (P < 0.05).

CONCLUSIONS: The achieved rotation of maxillary canines after the wear of an initial series of Invisalign aligners differed from the planned movements in both magnitude and direction for planned rotations of ≥5°. A method for classifying rotation types was developed, which may facilitate further research to guide clinicians and optimize treatment outcomes.

PMID:42644777 | DOI:10.1016/j.ajodo.2026.05.016

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Nevin Manimala Statistics

Price Elasticity of Demand for Alcoholic Beverages in India: Analysis Based on the NSSO’s Household Consumption Expenditure Survey 2022-2023 and 2023-2024

Drug Alcohol Rev. 2026 Sep;45(6):e70243. doi: 10.1111/dar.70243.

ABSTRACT

INTRODUCTION: Taxation of alcohol is an important policy instrument to combat the ill-effects of excessive alcohol consumption and raise revenues for governments. However, there is a need for studies exploring the demand price elasticity of different alcohols in Indian contexts amid changes in consumption habits, taxes and structure of the alcohol market. This paper examines the price and cross-price elasticity of demand for beer and foreign liquor in India using the latest surveys.

METHODS: Household Consumption Expenditure Surveys of 2022-2023 to 2023-2024 is used to estimate the elasticity. Unit values based on Deaton’s approach that leverages the geographic variation in unit values are utilised. Beer and foreign liquor were analysed jointly, with country liquor treated as a potential substitute.

RESULTS: The price elasticity of beer and foreign liquor is found to be statistically significant and inelastic. Own-price elasticity is recorded to be around -0.27 and -0.25 in 2022-2023 and around -0.18 and -0.17 in 2023-2024. Income elasticity is positive and increased from 0.42 to 0.63 in 2022-2023 to 0.55-0.80 in 2023-2024. Significant cross-price effects between foreign liquor and country liquor exist in 2022-2023; however, they became weaker and largely insignificant in 2023-2024.

DISCUSSION AND CONCLUSIONS: The above results show that the demand for alcoholic beverages in India is inelastic. Thus, the excise duties can be used by governments as instruments for increasing revenues and decreasing demand. The weakening of cross-price effects over time suggests reduced substitution between country liquor and higher-taxed alcoholic beverages.

PMID:42644770 | DOI:10.1111/dar.70243

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Nevin Manimala Statistics

Bunny Burrito Restraint for Computed Tomography in Conscious Rabbits: An Effective Alternative

Vet Radiol Ultrasound. 2026 Sep;67(5):e70230. doi: 10.1111/vru.70230.

ABSTRACT

Computed tomography (CT) is a critical diagnostic tool in rabbits. Traditional CT imaging often requires sedation or general anesthesia, posing inherent risks such as mortality and gastrointestinal complications. An effective physical restraint method could enhance patient safety, reduce costs, and improve accessibility to CT imaging. This study evaluates the effectiveness of the well-known bunny burrito restraint technique as an alternative to the plexiglass chamber method for conducting CT examinations in conscious rabbits. A retrospective multicenter observational study was conducted on 93 client-owned rabbits undergoing CT between March 2021 and December 2023. Cases were classified into three restraint groups: bunny burrito (n = 36), plexiglass chamber (n = 47), and sedation (n = 10). CT image quality was assessed on the basis of motion artifacts, positioning, and stability across different acquisitions. Statistical analyses, including logistic regression, were performed to compare the two physical restraint methods. The bunny burrito technique had significantly lower motion artifacts in pre-contrast acquisition (p = 0.02), better positioning in the dental disease subgroup (p = 0.03), and better stability in early post-contrast period (p = 0.04, wide confidence interval) compared to the plexiglass chamber group. Image quality was similar between bunny burrito and sedation in descriptive results. No complications were reported during or after CT examinations. In conclusion, the bunny burrito method is an effective and safe restraint method for CT imaging in conscious rabbits that shows advantages over the plexiglass chamber in specific imaging contexts. It minimizes sedation-related risks with simplified equipment. This method represents a valuable advancement in veterinary diagnostic imaging.

PMID:42644764 | DOI:10.1111/vru.70230

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Nevin Manimala Statistics

Integrative Multi-Omics-Informed Analysis Identifies Insulin Therapy-Associated Loci Implicated in Osteoarthritis Susceptibility

Chem Biol Drug Des. 2026 Aug;108(2):e70384. doi: 10.1111/cbdd.70384.

ABSTRACT

Integrative genetic approaches can combine Mendelian randomization, variant annotation, pathway-level interpretation, and exploratory cellular measurements to investigate complex disease mechanisms. However, the relationship between genetic liability to insulin medication use and osteoarthritis (OA) remains incompletely characterized GWAS summary statistics for insulin medication use were obtained from the UK Biobank insulin medication-use dataset. Insulin therapy-associated SNPs were selected using a suggestive significance threshold (p < 5 × 10-6) and clumped (r2 < 0.001, 10,000 kb). Two-sample Mendelian randomization (MR) was performed using the inverse-variance weighted (IVW) method as the primary analysis, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses included Cochran’s Q test, MR-Egger intercept, MR-PRESSO global test, and leave-one-out analysis. Insulin-associated genetic variants were functionally annotated using Ensembl VEP, ANNOVAR, FUMA, and Open Targets Genetics, and mapped genes were subjected to exploratory GO biological process and KEGG pathway enrichment analysis. A separate exploratory cellular experiment was performed in the immortalized human chondrocyte cell line TC28a2 using insulin treatment followed by Safranin O staining, RT-qPCR, western blotting, and ELISA. After SNP selection and harmonization, 56 instrument-outcome associations were retained, comprising 29 SNPs in the ukb-a-106 OA dataset and 27 SNPs in the ukb-b-14,486 OA dataset. IVW analysis suggested an association between genetic liability to insulin medication use and increased OA susceptibility (ukb-a-106: OR = 1.195, 95% CI = 1.062-1.344, p = 0.003; ukb-b-14,486: OR = 1.179, 95% CI = 1.066-1.305, p = 0.001). Sensitivity tests did not detect statistically significant heterogeneity or directional horizontal pleiotropy; however, indication-related genetic liability, correlated pleiotropy, and biologically plausible alternative pathways remain important concerns. Seven mapped genes were used for exploratory enrichment analysis. In a separate exploratory cellular experiment, insulin-treated TC28a2 cells under high-glucose conditions showed reduced proteoglycan staining, increased matrix-degrading and inflammatory markers, and reduced NRF2 protein expression. This study suggests an association between genetic liability to insulin medication use and OA susceptibility and provides exploratory functional-annotation and cellular observations for further investigation.

PMID:42644749 | DOI:10.1111/cbdd.70384

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Nevin Manimala Statistics

Mapping Indoor and Outdoor Environmental Radiation Exposure at a Nigerian Tertiary Institution: Evidence from Federal College of Education, Gombe, Gombe State. Nigeria

Health Phys. 2026 Aug 26. doi: 10.1097/HP.0000000000002212. Online ahead of print.

ABSTRACT

Natural background ionizing radiation from terrestrial and cosmic sources results in continuous exposure of the population, particularly in educational environments where staff and students spend prolonged periods indoors and outdoors. Monitoring ambient gamma radiation and associated health risks is therefore essential for ensuring radiological safety and regulatory compliance. This study assesses background gamma radiation levels and corresponding radiological risk indices within the Federal College of Education (Technical), Gombe, Gombe State, Nigeria. Indoor and outdoor ambient gamma dose rates were measured at selected campus locations using a calibrated Radiation Alert Inspector Geiger-Muller detector. Measurements were conducted at a height of 1 m above ground level in accordance with UNSCEAR guidelines, with geographic coordinates recorded using a GPS receiver. Absorbed dose rate (ADR), annual effective dose equivalent (AEDE), and excess lifetime cancer risk (ELCR) were calculated using standard conversion factors and appropriate occupancy coefficients. Descriptive statistics were applied to evaluate spatial variability and compare results with international recommended reference levels. Indoor absorbed dose rates ranged from 15.00 to 46.67 nGy h-1, while outdoor values ranged from 15.00 to 40.00 nGy h-1. The mean indoor AEDE (0.227 mSv y-1) was higher than the outdoor mean (0.049 mSv y-1), primarily due to differences in occupancy factors. All estimated AEDE and ELCR values remained below the ICRP-recommended reference level of 1 mSv y-1 for public exposure, with spatial analysis revealing localized variability but no abnormal radiation hotspots. The findings indicate that ambient gamma radiation levels within the campus are within global background ranges and pose no significant radiological health risk. Regular monitoring is recommended to ensure sustained radiological safety in educational environments.

PMID:42644743 | DOI:10.1097/HP.0000000000002212