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Nevin Manimala Statistics

Causal link between oxidative stress and epilepsy: A two-sample Mendelian randomization study

Brain Behav. 2024 Jun;14(6):e3549. doi: 10.1002/brb3.3549.

ABSTRACT

BACKGROUND: Although a growing body of research has indicated a strong link between oxidative stress and epilepsy, the exact nature of their interaction remains elusive. To elucidate this intricate relationship, we conducted a bidirectional Mendelian randomization (MR) analysis employing two independent datasets.

METHODS: A two-sample MR analysis was performed using instrumental variables derived from genome-wide association study summary statistics of oxidative stress injury biomarkers (OSIB) and epilepsy. The OSIBs were selected from eight primary metabolic pathways associated with oxidative stress. Additionally, seven distinct epilepsy phenotypes were considered, which encompassed all epilepsy, generalized epilepsy, generalized tonic-clonic seizures, focal epilepsy, focal epilepsy with hippocampal sclerosis (focal HS), focal epilepsy with lesions other than HS (focal NHS), and lesion-negative focal epilepsy. Causal estimates were computed using the inverse-variance weighted method or the Wald ratio method, and the robustness of causality was assessed through sensitivity analyses.

RESULTS: For OSIB and epilepsy, 520 and 23 genetic variants, respectively, were selectively extracted as instrumental variants. Genetically predicted higher kynurenine level was associated with a decreased risk of focal epilepsy (odds ratio [OR] 1.950, 95% CI 1.373-2.528, p = .023) and focal NHS (OR 1.276, 95% CI 1.100-1.453, p = .006). For reverse analysis, there was a suggestive effect of focal NHS on urate (OR 1.19 × 1015, 95% CI 11.19 × 1015 to 1.19 × 1015, p = .0000746) and total bilirubin (Tb) (OR 4.98, 95% CI 3.423-6.543, p = .044). In addition, genetic predisposition to focal HS was associated with higher Tb levels (OR 9.83, 95% CI 7.77-11.888, p = .034).

CONCLUSION: This MR study provides compelling evidence of a robust association between oxidative stress and epilepsy, with a notable emphasis on a causal relationship between oxidative stress and focal epilepsy. Additional research is warranted to confirm the connection between oxidative stress and the risk of epilepsy and to unravel the underlying mechanisms.

PMID:38849979 | DOI:10.1002/brb3.3549

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Correlation between geriatric nutritional risk index and intradialytic hypotension in elderly patients undergoing maintenance hemodialysis: a case-control study

J Health Popul Nutr. 2024 Jun 7;43(1):80. doi: 10.1186/s41043-024-00551-1.

ABSTRACT

BACKGROUND: There is a correlation between nutritional status and treatment outcomes and long-term survival in MHD patients but there is limited research on the relationship between GNRI and IDH. This case-control study aimed to investigate the correlation between Geriatric Nutritional Risk Index (GNRI) and intradialytic hypotension (IDH) in elderly patients undergoing maintenance hemodialysis (MHD).

METHODS: This study was carried out on 129 cases of MHD patients with IDH and 258 non-IDH-controls in Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China, between June 2020 and May 2022. Professional researchers collected patients’ general information on gender, primary disease, dialysis-related indicators, anthropometric measures, laboratory biochemicals, and GNRI. Logistic regression analysis was used to evaluate the correlation between GNRI and IDH.

RESULTS: A total of 385 elderly MHD patients were included. Compared with GNRI Q4 group, the odds ratios for the risk of IDH in GNRI Q3 group, GNRI Q2 group, and GNRI Q1 group of elderly MHD patients were 1.227, 2.196, and 8.350, respectively, showing a significant downward trend (P-trend < 0.05). The area under the curve of GNRI for predicting IDH was 0.839 (95% CI: 0.799-0.879). Between different genders, a decrease in GNRI was closely related to an increase in IDH risk (P for trend < 0.05).

CONCLUSIONS: This research shows a significant association between GNRI and the incidence of IDH among elderly MHD patients and has an important warning effect. Encouraging the incorporation of GNRI assessment into the clinical assessment protocols of older patients with MHD may help to improve the nutritional status of those suffering from it and reduce the risk of IDH.

PMID:38849963 | DOI:10.1186/s41043-024-00551-1

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Nonlinear relationship between platelet count and 30-day in-hospital mortality in ICU acute respiratory failure patients: a multicenter retrospective cohort study

Eur J Med Res. 2024 Jun 8;29(1):312. doi: 10.1186/s40001-024-01909-1.

ABSTRACT

BACKGROUND: Limited evidence exists regarding the link between platelet count and 30-day in-hospital mortality in acute respiratory failure (ARF) patients. Thus, this study aims to investigate this association among ICU patients experiencing acute respiratory failure.

METHODS: We conducted a retrospective cohort study across multiple centers, utilizing data from the US eICU-CRD v2.0 database covering 22,262 patients with ARF in the ICU from 2014 to 2015. Our aim was to investigate the correlation between platelet count and 30-day in-hospital mortality using binary logistic regression, subgroup analyses, and smooth curve fitting.

RESULTS: The 30-day in-hospital mortality rate was 19.73% (4393 out of 22,262), with a median platelet count of 213 × 109/L. After adjusting for covariates, our analysis revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.99, 95% CI 0.99, 0.99). Subgroup analyses supported the robustness of these findings. Furthermore, a nonlinear relationship was identified between platelet count and 30-day in-hospital mortality, with the inflection point at 120 × 109/L. Below the inflection point, the effect size (OR) was 0.89 (0.87, 0.91), indicating a significant association. However, beyond this point, the relationship was not statistically significant.

CONCLUSION: This study establishes a clear negative association between platelet count and 30-day in-hospital mortality among ICU patients with ARF. Furthermore, we have identified a nonlinear relationship with saturation effects, indicating that among ICU patients with acute respiratory failure, the lowest 30-day in-hospital mortality rate occurs when the baseline platelet count is approximately 120 × 109/L.

PMID:38849948 | DOI:10.1186/s40001-024-01909-1

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Prevalence and factors associated with falls in older adults in a Middle Eastern population: a retrospective cross-sectional study

Public Health. 2024 Jun 6;233:54-59. doi: 10.1016/j.puhe.2024.04.011. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective was to determine the prevalence of falls and associated factors in older adults living in Qatar.

STUDY DESIGN: Cross-sectional study.

METHODS: This is a cross-sectional study of older adults aged ≥60 years with at least one encounter with primary health care corporation (PHCC) in Qatar during the period 2017-2022. Data on documented falls, demographic variables, and medical comorbidities were extracted from all PHCCs in Qatar. Descriptive and inferential statistics were used to address the aim of the study.

RESULTS: A total of 68,194 older adults had at least one encounter with PHCC. The median age was 65.0 years, 58.9% were males, and 32.6% were Qatari nationality. A higher percentage of falls was found in individuals with hypertension (80%), diabetes (74.2%), and dyslipidemia (48.9%), which were also the most prevalent comorbidities. The prevalence of falls was 6.7% (95% CI 6.6-6.9). Compared to individuals aged 60-69 years, individuals aged 70-79, 80-89, and 90-99 had increased odds of falls by 1.6 (95% CI 1.5, 1.8), 2.5 (95% CI 2.2, 2.8), and 2.6 (95% CI 2.0, 3.3), respectively. Females and individuals of Qatari nationality had increased odds of fall by 1.5 (95% CI 1.4, 1.6) and 1.2 (95% CI 1.1, 1.3), respectively. Orthostatic hypotension, syncope, Parkinson’s disease, and hip arthritis showed the strongest associations with falls.

CONCLUSIONS: Given the growing population of older adults in the Middle East and North African region, falls is a public health concern. The risk factors identified in this study suggest the need for proactive healthcare strategies tailored to the unique needs of older adult populations.

PMID:38848620 | DOI:10.1016/j.puhe.2024.04.011

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Fractionated radiotherapy after gross-total resection of spinal chordoma: a systematic review of survival outcomes using individualized patient data

J Neurosurg Spine. 2024 Jun 7:1-8. doi: 10.3171/2024.4.SPINE2491. Online ahead of print.

ABSTRACT

OBJECTIVE: Spinal chordoma treatment guidelines recommend resection. However, in patients in whom gross-total resection (GTR) is achieved, the benefits of radiation therapy (RT) are unclear. Therefore, the authors performed a systematic review to determine if RT is associated with postoperative progression-free survival (PFS) or overall survival (OS) after achieving GTR of spinal chordoma.

METHODS: The PubMed database was searched for studies including individualized data of patients undergoing GTR with or without RT for spinal chordoma. Patients < 18 years of age or those who underwent stereotactic body RT were excluded. Qualitative assessment was performed using Newcastle-Ottawa Scale guidelines. Log-rank tests for time-to-event data and a Cox proportional-hazards model were generated for a multivariable statistical model.

RESULTS: Complete data of 132 patients were retrieved, with 37 (28%) patients receiving adjuvant RT and 95 (72%) not receiving adjuvant RT. The mean follow-up was not statistically significantly different between those undergoing RT and not undergoing RT (54.02 months and 65.43 months, respectively). Patients were more likely not to undergo RT if their disease was located in the sacrum versus the mobile spine (p < 0.001). When controlling for age ≥ 65 years, male sex, disease location, and treatment year ≥ 2010, patients undergoing RT had similar PFS and OS when compared with those not undergoing RT on multivariable survival analysis (HR 0.935 [95% CI 0.703-2.340], p = 0.844 and HR 2.078 [95% CI 0.848-5.090], p = 0.110, respectively). However, age ≥ 65 years was associated with poorer OS in adjusted analyses (HR 2.761 [95% CI 1.185-6.432], p = 0.018) relative to patients < 65 years of age.

CONCLUSIONS: After achieving GTR of spinal chordoma, the utility of RT on PFS and OS remains unclear. Age ≥ 65 years appears to be associated with OS in spinal chordoma patients. Additional multicenter prospective studies are needed to determine the utility of RT in this patient population.

PMID:38848586 | DOI:10.3171/2024.4.SPINE2491

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White matter characteristics in children with cerebral palsy prior to selective dorsal rhizotomy: a multicenter diffusion tensor imaging study

J Neurosurg Pediatr. 2024 Jun 7:1-10. doi: 10.3171/2024.4.PEDS23589. Online ahead of print.

ABSTRACT

OBJECTIVE: The aims of this study were to 1) assess and quantify white matter (WM) microstructural characteristics derived from diffusion tensor imaging (DTI) in children with cerebral palsy (CP) prior to selective dorsal rhizotomy (SDR), and 2) investigate potential associations between WM diffusion properties and gross motor function and spasticity in children with spastic CP who underwent SDR.

METHODS: This study is a multisite study based on DT images acquired prior to SDR as well as postoperative outcome data. DTI data collected from two sites were harmonized using the ComBat approach to minimize intersite scanner difference. The DTI abnormalities between children with spastic CP and controls were analyzed and correlated with the severity of impaired mobility based on the Gross Motor Function Classification System (GMFCS). The improvement in gross motor function and spasticity after SDR surgery was assessed utilizing the Gross Motor Function Measure-66 (GMFM-66), the Modified Tardieu Scale (MTS), and the modified Ashworth scale (MAS). Alterations in these outcome measures were quantified in association with DTI abnormalities.

RESULTS: Significant DTI alterations, including lower fractional anisotropy (FA) in the genu of the corpus callosum (gCC) and higher mean diffusivity (MD) in the gCC and posterior limb of the internal capsule (PLIC), were found in children in the SDR group when compared with the age-matched control group (all p < 0.05). Greater DTI alterations (FA in gCC and MD in gCC and PLIC) were associated with lower mobility levels as determined based on GMFCS level (p < 0.05). The pre- to post-SDR improvement in motor function based on GMFM-66 was statistically significant (p = 0.006 and 0.002 at 6-month and 12-month follow-ups, respectively). The SDR efficacy was also identified as improving spasticity in lower-extremity muscle groups assessed with the MTS and MAS. Partial correlation analysis presented a significant association between pre- to post-SDR MTS alteration and DTI abnormalities.

CONCLUSIONS: The findings in the present study provided initial quantitative evidence to establish the WM microstructural characteristics in children with spastic CP prior to SDR surgery. The study generated data for the association between baseline DTI characteristics and mobility in children with CP prior to SDR surgery. The study also demonstrated SDR efficacy in improving motor function and spasticity based on the GMFM-66, MTS, and MAS, respectively, in association with DTI data.

PMID:38848583 | DOI:10.3171/2024.4.PEDS23589

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Employing Informatics Strategies in Alzheimer’s Disease Research: A Review from Genetics, Multiomics, and Biomarkers to Clinical Outcomes

Annu Rev Biomed Data Sci. 2024 Jun 7. doi: 10.1146/annurev-biodatasci-102423-121021. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is a critical national concern, affecting 5.8 million people and costing more than 250 billion annually. However, there is no available cure. Thus, effective strategies are in urgent need to discover AD biomarkers for disease early detection and drug development. In this review, we study AD from a biomedical data scientist perspective to discuss the four fundamental components in AD research: genetics (G), molecular multiomics (M), multimodal imaging biomarkers (B), and clinical outcomes (O) (collectively referred to as the GMBO framework). We provide a comprehensive review of common statistical and informatics methodologies for each component within the GMBO framework, accompanied by the major findings from landmark AD studies. Our review highlights the potential of multimodal biobank data in addressing key challenges in AD, such as early diagnosis, disease heterogeneity, and therapeutic development. We identify major hurdles in AD research, including data scarcity and complexity, and advocate for enhanced collaboration, data harmonization, and advanced modeling techniques. This review aims to be an essential guide for understanding current biomedical data science strategies in AD research, emphasizing the need for integrated, multidisciplinary approaches to advance our understanding and management of AD.

PMID:38848574 | DOI:10.1146/annurev-biodatasci-102423-121021

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Nevin Manimala Statistics

App Engagement as a Predictor of Weight Loss in Blended-Care Interventions: Retrospective Observational Study Using Large-Scale Real-World Data

J Med Internet Res. 2024 Jun 7;26:e45469. doi: 10.2196/45469.

ABSTRACT

BACKGROUND: Early weight loss is an established predictor for treatment outcomes in weight management interventions for people with obesity. However, there is a paucity of additional, reliable, and clinically actionable early predictors in weight management interventions. Novel blended-care weight management interventions combine coach and app support and afford new means of structured, continuous data collection, informing research on treatment adherence and outcome prediction.

OBJECTIVE: Against this backdrop, this study analyzes app engagement as a predictor for weight loss in large-scale, real-world, blended-care interventions. We hypothesize that patients who engage more frequently in app usage in blended-care treatment (eg, higher logging activity) lose more weight than patients who engage comparably less frequently at 3 and 6 months of intervention.

METHODS: Real-world data from 19,211 patients in obesity treatment were analyzed retrospectively. Patients were treated with 3 different blended-care weight management interventions, offered in Switzerland, the United Kingdom, and Germany by a digital behavior change provider. The principal component analysis identified an overarching metric for app engagement based on app usage. A median split informed a distinction in higher and lower engagers among the patients. Both groups were matched through optimal propensity score matching for relevant characteristics (eg, gender, age, and start weight). A linear regression model, combining patient characteristics and app-derived data, was applied to identify predictors for weight loss outcomes.

RESULTS: For the entire sample (N=19,211), mean weight loss was -3.24% (SD 4.58%) at 3 months and -5.22% (SD 6.29%) at 6 months. Across countries, higher app engagement yielded more weight loss than lower engagement after 3 but not after 6 months of intervention (P3 months<.001 and P6 months=.59). Early app engagement within the first 3 months predicted percentage weight loss in Switzerland and Germany, but not in the United Kingdom (PSwitzerland<.001, PUnited Kingdom=.12, and PGermany=.005). Higher age was associated with stronger weight loss in the 3-month period (PSwitzerland=.001, PUnited Kingdom=.002, and PGermany<.001) and, for Germany, also in the 6-month period (PSwitzerland=.09, PUnited Kingdom=.46, and PGermany=.03). In Switzerland, higher numbers of patients’ messages to coaches were associated with higher weight loss (P3 months<.001 and P6 months<.001). Messages from coaches were not significantly associated with weight loss (all P>.05).

CONCLUSIONS: Early app engagement is a predictor of weight loss, with higher engagement yielding more weight loss than lower engagement in this analysis. This new predictor lends itself to automated monitoring and as a digital indicator for needed or adapted clinical action. Further research needs to establish the reliability of early app engagement as a predictor for treatment adherence and outcomes. In general, the obtained results testify to the potential of app-derived data to inform clinical monitoring practices and intervention design.

PMID:38848556 | DOI:10.2196/45469

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Use of Mobile Technologies to Streamline Pretriage Patient Flow in the Emergency Department: Observational Usability Study

JMIR Mhealth Uhealth. 2024 Jun 7;12:e54642. doi: 10.2196/54642.

ABSTRACT

BACKGROUND: In emergency departments (EDs), triage nurses are under tremendous daily pressure to rapidly assess the acuity level of patients and log the collected information into computers. With self-service technologies, patients could complete data entry on their own, allowing nurses to focus on higher-order tasks. Kiosks are a popular working example of such self-service technologies; however, placing a sufficient number of unwieldy and fixed machines demands a spatial change in the greeting area and affects pretriage flow. Mobile technologies could offer a solution to these issues.

OBJECTIVE: The aim of this study was to investigate the use of mobile technologies to improve pretriage flow in EDs.

METHODS: The proposed stack of mobile technologies includes patient-carried smartphones and QR technology. The web address of the self-registration app is encoded into a QR code, which was posted directly outside the walk-in entrance to be seen by every ambulatory arrival. Registration is initiated immediately after patients or their proxies scan the code using their smartphones. Patients could complete data entry at any site on the way to the triage area. Upon completion, the result is saved locally on smartphones. At the triage area, the result is automatically decoded by a portable code reader and then loaded into the triage computer. This system was implemented in three busy metropolitan EDs in Shanghai, China. Both kiosks and smartphones were evaluated randomly while being used to direct pretriage patient flow. Data were collected during a 20-day period in each center. Timeliness and usability of medical students simulating ED arrivals were assessed with the After-Scenario Questionnaire. Usability was assessed by triage nurses with the Net Promoter Score (NPS). Observations made during system implementation were subject to qualitative thematic analysis.

RESULTS: Overall, 5928 of 8575 patients performed self-registration on kiosks, and 7330 of 8532 patients checked in on their smartphones. Referring effort was significantly reduced (43.7% vs 8.8%; P<.001) and mean pretriage waiting times were significantly reduced (4.4, SD 1.7 vs 2.9, SD 1.0 minutes; P<.001) with the use of smartphones compared to kiosks. There was a significant difference in mean usability scores for “ease of task completion” (4.4, SD 1.5 vs 6.7, SD 0.7; P<.001), “satisfaction with completion time” (4.5, SD 1.4 vs 6.8, SD 0.6; P<.001), and “satisfaction with support” (4.9, SD 1.9 vs 6.6, SD 1.2; P<.001). Triage nurses provided a higher NPS after implementation of mobile self-registration compared to the use of kiosks (13.3% vs 93.3%; P<.001). A modified queueing model was identified and qualitative findings were grouped by sequential steps.

CONCLUSIONS: This study suggests patient-carried smartphones as a useful tool for ED self-registration. With increased usability and a tailored queueing model, the proposed system is expected to minimize pretriage waiting for patients in the ED.

PMID:38848554 | DOI:10.2196/54642

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Assessing the efficacy of oral Tranexamic Acid as adjuvant of Topic Triple Combination Cream Therapy in Melasma: A Meta-Analysis of Randomized Controlled Trials

Clin Exp Dermatol. 2024 Jun 8:llae226. doi: 10.1093/ced/llae226. Online ahead of print.

ABSTRACT

INTRODUCTION: Melasma is a skin pigmentation disorder that lacks consistent treatment success despite various methods used. Tranexamic Acid (TXA) has shown hypopigmentation properties, but whether TXA administration should be combined with standard treatment or not, is still not clarified. We aimed to perform an investigation of oral TXA effectiveness and safety as an adjuvant of Triple Combination Cream (TCC) Therapy in melasma.

METHODS: We searched PubMed, EMBASE and Cochrane Central for studies comparing TCC plus adjuvant TXA to TCC therapy alone in patients with melasma. Outcomes of interest included change from the baseline of Melasma Area Severity Index (MASI) score, recurrence of melasma and adverse events. Statistical analysis was performed using R Studio 4.3.2.

RESULTS: Four trials, involving 480 patients were included. In the pooled analysis, the decrease from baseline in the MASI score (mean difference [MD] -3.10; 95% confidence interval [CI] -5.85 to -0.35) was significantly higher in patients treated with oral tranexamic acid as an adjuvant to TCC compared to TCC alone. Melasma recurrence (RR 0.28; 95% CI 0.16-0.49) was significantly lower in the group treated with TCC and TXA. Regarding erythema (RR 0.63; 95% CI 0.34-1.17) and burning (RR 0.59; 95% CI 0.30-1.17), there was no significant difference.

CONCLUSION: This meta-analysis demonstrated statistically significant benefits of TCC plus TXA combination treatment compared with TCC alone. Furthermore, the results suggest that the addition of TXA to TCC therapy may reduce melasma recurrence.

PMID:38848545 | DOI:10.1093/ced/llae226