Tag: statistics

Genet Epidemiol. 2022 Feb 16. doi: 10.1002/gepi.22444. Online ahead of print.

ABSTRACT

Large-scale sequencing and genotyping data provide an opportunity to integrate external samples as controls to improve power of association tests. However, due to the systematic differences between genotyped samples from different studies, naively aggregating the controls could lead to inflation in Type I error rates. There has been recent effort to integrate external controls while adjusting for batch effect, such as the integrating External Controls into Association Test (iECAT) and its score-based single variant tests. Building on the original iECAT framework, we propose an iECAT-Score region-based test that increases power for rare-variant tests when integrating external controls. This method assesses the systematic batch effect between internal and external samples at each variant and constructs compound shrinkage score statistics to test for the joint genetic effect within a gene or a region, while adjusting for covariates and population stratification. Through simulation studies, we demonstrate that the proposed method controls for Type I error rates and improves power in rare-variant tests. The application of the proposed method to the association studies of age-related macular degeneration (AMD) from the International AMD Genomics Consortium and UK Biobank revealed novel rare-variant associations in gene DXO. Through the incorporation of external controls, the iECAT methods offer a powerful suite to identify disease-associated genetic variants, further shedding light on future directions to investigate roles of rare variants in human diseases.

PMID:35170803 | DOI:10.1002/gepi.22444

Genet Epidemiol. 2022 Feb 16. doi: 10.1002/gepi.22442. Online ahead of print.

NO ABSTRACT

PMID:35170805 | DOI:10.1002/gepi.22442

Environ Toxicol Chem. 2022 Feb 16. doi: 10.1002/etc.5309. Online ahead of print.

ABSTRACT

This project has generated a workflow based on non-target analysis (NTA) using Compound Discoverer (CD) v. 3.1 to characterize a set of source-discriminating compounds identified from water samples from locations in South Florida, particularly those describing a freshwater environment (Everglades-based), urban impacted areas (septic tank driven), and coastal (Biscayne Bay) endmembers in and around the Charles Deering Estate property in the Village of Palmetto Bay. Waters from an interconnected managed canal system were assessed to evaluate the influence of localized emissions. Septic tank effluents influence the water in many Southeast Florida environments due to their diminished onsite treatment capacity based on the limestone dominated geology and canal systems providing a relatively unobstructed connection pathway. Through a combination of high-resolution mass spectrometry (HRMS) and statistical analyses a set of tracers and indicators was determined (azelaic acid, decanophenone, galaxolidone, methyl violet, monoolein, metoprolol, and 1-stearoylglycerol). Tentatively identified compounds were generally assigned to various categories such as dyes, personal care products (PCPs), and pharmaceuticals. The NTA CD 3.1 compound data presented as Principal Component Analysis and Kendrick Mass Defect plots showed apparent differences between wastewater influenced sites and non-wastewater influenced sites along with the ranked “Top10” compounds found at each location. Waters from different locations were also compared using the presence of sucralose to further inform the NTA. The most septic influenced site contained 3,594 ± 94 ng/L of sucralose with concentrations declining steadily reaching the lowest concentrations in Biscayne Bay of 122 ± 94 ng/L. The sucralose concentrations provided further evidence of septic influence on this system. Sucralose was determined to be a conservative tracer between the freshwater and coastal sources and complimentary to other probable unique tracers of septic tank effluent identified by the NTA. This article is protected by copyright. All rights reserved.© 2022 SETAC.

PMID:35170796 | DOI:10.1002/etc.5309

J Ultrasound Med. 2022 Feb 16. doi: 10.1002/jum.15960. Online ahead of print.

ABSTRACT

OBJECTIVES: Ultrasound is useful in predicting arteriovenous fistula (AVF) maturation, which is essential for hemodialysis in end-stage renal disease patients. We developed ultrasound software that measures circumferential vessel wall strain (distensibility) using conventional ultrasound Digital Imaging and Communications in Medicine (DICOM) data. We evaluated user-induced variability in measurement of arterial wall distensibility and upon finding considerable variation we developed and tested 2 methods for semiautomated measurement.

METHODS: Ultrasound scanning of arteries of 10 subjects scheduled for AVF surgery were performed. The top and bottom of the vessel wall were tracked using the Kanade-Lucas-Tomasi (KLT) feature-tracking algorithm over the stack of images in the DICOM cine loops. The wall distensibility was calculated from the change of vessel diameter over time. Two semiautomated methods were used for comparison.

RESULTS: The location of points selected by users for the cine loops varied significantly, with a maximum spread of up to 120 pixels (7.8 mm) for the top and up to 140 pixels (9.1 mm) for the bottom of the vessel wall. This variation in users’ point selection contributed to the variation in distensibility measurements (ranging from 5.63 to 41.04%). Both semiautomated methods substantially reduced variation and were highly correlated with the median distensibility values obtained by the 10 users.

CONCLUSIONS: Minimizing user-induced variation by standardizing point selection will increase reproducibility and reliability of distensibility measurements. Our recent semiautomated software may help expand use in clinical studies to better understand the role of vascular wall compliance in predicting the maturation of fistulas.

PMID:35170801 | DOI:10.1002/jum.15960

J Adv Nurs. 2022 Feb 15. doi: 10.1111/jan.15178. Online ahead of print.

ABSTRACT

AIM: To evaluate the effectiveness of a nurse-led smartphone-based self-management programme (NSSMP) on improving self-efficacy, promoting diabetes self-care, increasing health-related quality of life (HRQoL) and decreasing HbA1c, acute complications and unplanned medical consultation for people with poorly controlled type 2 diabetes compared with a nurse-led diabetic service (NDS).

DESIGN: A two-arm randomized controlled trial with repeated measures was conducted.

METHODS: Participants were recruited from June 2018 to September 2020. Eligible participants were assigned to either the intervention or control group randomly. Participants assigned to intervention group received the 6-month NSSMP, while those in the control group received existing NDS provided by the study hospital. Outcomes were measured at baseline, and at 3 and 6 months from baseline.

RESULTS: A total of 114 participants were recruited. There were no significant interactions between group and time for all the outcomes except for blood glucose testing activities (F = 4.742, p = .015). Both groups had reduced HbA1c over 6 months. The intervention group had a lower HbA1c than the control group at follow-ups, but the differences were not statistically significant. None of the participants had acute diabetes complications at follow-up. Similarly, the differences in the number of unplanned medical consultation at 6-month follow-up between two groups were statistically insignificant.

CONCLUSION: The NSSMP is as effective as existing NDS provided by the study hospital in improving most of the outcomes. NSSMP can liberate valuable time for nurses to provide care to critically ill patients and supports healthcare resource constraints in the current COVID-19 pandemic.

IMPACT: The existing diabetes service is labour intensive as nurses are required to deliver education, follow-up telephone calls to trace blood sugar monitoring and provide therapeutic consultations and necessary referrals. The outbreak of COVID-19 pandemic has added further strain on the overworked professionals. NSSMP provides an alternative programme that is just as effective, to reduce nurses’ workload by delegating them back to the individuals through self-management strategies. This enables nurses to increase contact time with patients, and individuals to take onus of their disease through increased self-efficacy, facilitated by technology.

CLINICAL TRIAL: This study is registered under clinical registration number NCT03088475.

PMID:35170786 | DOI:10.1111/jan.15178

Lasers Surg Med. 2022 Feb 16. doi: 10.1002/lsm.23524. Online ahead of print.

ABSTRACT

BACKGROUND: A previous multi-center clinical study of low energy (20% power), single-pass helium plasma dermal resurfacing (HPDR) showed positive results but did not fully reveal the true potential of this novel technology. A second multi-center clinical study, reported herein, was therefore undertaken to evaluate efficacy and safety of high energy (40%), double pass HPDR for treatment of facial rhytids (ClinicalTrials.gov Identifier: NCT04185909).

METHODS: Fifty-five eligible subjects seeking improvement in facial rhytids were enrolled for study at one of four investigational sites. All subjects underwent full-face HPDR treatment. The forehead, nose, cheeks, and peri-oral treatment zones were treated at 40% power with two passes whereas the peri-orbital and jawline/mandibular zones were treated at 20% power (up to 40% for jawline/mandibular zone) and one or two passes. Photographic images of the face were captured using the VISIA-CR system. Three-month posttreatment Fitzpatrick Wrinkle and Elastosis Scale (FWS) scores were compared to baseline scores as determined by blinded independent photographic reviewers (IPRs) and study investigators.

RESULTS: Blinded IPRs and study investigators observed a ≥1-point FWS improvement in 100% of subjects with mean change in IPR FWS from baseline to the 90-day visit of -3.6 (±1.2). 96.4% of subjects indicated “improvement” in appearance at the 90-day visit utilizing the modified Global Aesthetic Improvement Scale. Evaluation of VISIA-CR data revealed statistically significant improvements in wrinkles, brown spots, and pore counts. Overall, 269 Adverse Events in 55 subjects were reported; most were mild-moderate in severity (99.3%), anticipated (86.2%), and of relatively short duration with most having resolved within 30 days (60.6%) of treatment.

CONCLUSION: Treatment of facial rhytids with high energy, double pass HPDR as detailed herein enables a marked improvement in FWS that parallels or surpasses competing technologies. VISIA-CR analysis demonstrates additional improvements in skin quality with statistically significant quantitative improvements in brown spots and enlarged pores as well as wrinkles. Effective rhytid effacement combines with high subject satisfaction and few unanticipated adverse events for a reasonable benefit-risk ratio.

PMID:35170772 | DOI:10.1002/lsm.23524

Clin Cardiol. 2022 Feb 16. doi: 10.1002/clc.23795. Online ahead of print.

ABSTRACT

BACKGROUND: Real-world data on atrial fibrillation (AF) ablation outcomes in obese populations have remained scarce, especially the relationship between obesity and in-hospital AF ablation outcome.

HYPOTHESIS: Obesity is associated with higher complication rates and higher admission trend for AF ablation.

METHODS: We drew data from the US National Inpatient Sample to identify patients who underwent AF ablation between 2005 and 2018. Sociodemographic and patients’ characteristics data were collected, and the trend, incidence of catheter ablation complications and mortality were analyzed, and further stratified by obesity classification.

RESULTS: A total of 153 429 patients who were hospitalized for AF ablation were estimated. Among these, 11 876 obese patients (95% confidence interval [CI]: 11 422-12 330) and 10 635 morbid obese patients (95% CI: 10 200-11 069) were observed. There was a substantial uptrend admission, up to fivefold, for AF ablation in all obese patients from 2005 to 2018 (p < .001). Morbidly obese patients were statistically younger, while coexisting comorbidities were substantially higher than both obese and nonobese patients (p < .01) Both obesity and morbid obesity were significantly associated with an increased risk of total bleeding, and vascular complications (p < .05). Only morbid obesity was significantly associated with an increased risk of ablation-related complications, total infection, and pulmonary complications (p < .01). No difference in-hospital mortality was observed among obese, morbidly obese, and nonobese patients.

CONCLUSION: Our study observed an uptrend in the admission of obese patients undergoing AF ablation from 2005 through 2018. Obesity was associated with higher ablation-related complications, particularly those who were morbidly obese.

PMID:35170775 | DOI:10.1002/clc.23795

J Periodontol. 2022 Feb 16. doi: 10.1002/JPER.21-0502. Online ahead of print.

ABSTRACT

BACKGROUND & AIM: The aim of this study was to test a non-submerged reconstructive approach for peri-implantitis osseous defects, by removing the prosthetic components, augmenting of the infraosseous bony compartment, and flap re-adaptation around the replaced healing abutments, without obtaining a primary wound closure.

METHODS: Twenty-nine implants in 24 patients were treated. Implant suprastructures were removed at the time of the intervention, to aid with the debridement process which included curettage, implantoplasty, air-power driven devices, and locally delivered antibiotics. The infraosseous part of peri-implant defects were augmented using a composite bone graft and an absorbable membrane to be secured around the replaced healing abutments without attempting to submerge the implants. After 8 months, direct peri-implant defect measurements were obtained to serve as the primary outcome. Secondary outcomes included of radiographic bone changes, and probing depth (PD) and bleeding on probing (BOP) changes at 12 months.

RESULTS: At the time of the surgical re-entry (8 months), a statistically significant clinical and radiographic defect fill was observed (average of 2.33 mm, and 1.63 mm, respectively). Approximately 3 months after crown replacement, 12 months from the surgical intervention, a significant PD (1.51 mm) and BOP (65%) reduction were also noted.

CONCLUSIONS: Considering its limitations, the utilized non-submerged approach (with removal of implant crowns) led to significant improvements in clinical (defect fill, PD, BOP) and radiographic outcomes. This article is protected by copyright. All rights reserved.

PMID:35170752 | DOI:10.1002/JPER.21-0502

Am J Clin Nutr. 2022 Feb 16:nqac047. doi: 10.1093/ajcn/nqac047. Online ahead of print.

ABSTRACT

BACKGROUND: High glycemic index (GI) diets have been linked to elevated risk of cardiometabolic diseases. One possible underlying mechanism comes from high GI diet’s potential to promote lipid peroxidation.

OBJECTIVES: We aim to evaluate whether and to what extent dietary carbohydrate quality and quantity are associated with systemic levels of lipid peroxidation in females.

DESIGN: In this cross-sectional analysis of 2163 middle-aged females, a subset of the Shanghai Women’s Health Study, we measured lipid peroxidation biomarkers F2-isoprostanes (F2-IsoPs) and its metabolite 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M) in urine. The quality of carbohydrate was defined by dietary GI, assessed using a validated food-frequency questionnaire via in-person interviews. A multivariable linear regression model with restricted cubic spline functions was used to evaluate the association of measured biomarkers with carbohydrate intake and dietary GI.

RESULTS: After adjustment for potential confounding factors such as cigarette smoking, BMI, comorbidities among others, we found that F2-IsoP-M concentrations were positively associated with both carbohydrate intake and dietary GI. Carbohydrate intake and dietary GI were weakly correlated (r = 0.12). When further mutually adjusted for the two factors, the positive association with F2-IsoP-M remained statistically significant for GI (P = 0.004) but not for carbohydrate intake (P = 0.50). Compared with those in the 10th percentile of dietary GI, fold-increases (95% CI) in F2-IsoP-M concentrations for those in the 30th, 50th, 70th, and 90th percentiles were 1.03 (1.00, 1.07), 1.06 (1.01, 1.10), 1.09 (1.03, 1.14), and 1.13 (1.05, 1.21), respectively. Moreover, there appeared a threshold regarding the association between dietary GI and F2-IsoP-M concentrations, with the dose-effect slope of GI being 2.3-times greater when GI ≥ 75 relative to GI < 75.

CONCLUSIONS: This study provides evidence that the quality of dietary carbohydrate may be more important than the quantity of the intake with regard to systemic lipid peroxidation.

PMID:35170729 | DOI:10.1093/ajcn/nqac047

Nicotine Tob Res. 2022 Feb 16:ntac043. doi: 10.1093/ntr/ntac043. Online ahead of print.

ABSTRACT

INTRODUCTION: Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allows for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown.

METHODS: We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior vs. combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURC) Study (1,091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent).

RESULTS: PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04-1.37], p=0.0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51-0.99], p=0.045).

CONCLUSIONS: PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors.

IMPLICATIONS: There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize use of polygenic risk scores in clinical care.

PMID:35170738 | DOI:10.1093/ntr/ntac043