Category: Statistics

Stroke. 2022 Aug 17:STROKEAHA122038838. doi: 10.1161/STROKEAHA.122.038838. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study is to examine the associations of Life’s Simple 7 (LS7) with risks of cerebral small vessel disease (CSVD) and its magnetic resonance imaging markers.

METHODS: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included in this study from 2017 to 2019. LS7 was analyzed as the total score, medical score (derived from the 3 metrics based on medical history and testing), and behavioral score (based on 4 metrics based on behaviors), and categorized as poor, intermediate, or ideal. A CSVD score or a modified CSVD score was derived from 4 magnetic resonance imaging markers (lacunes, microbleeds, perivascular spaces, and white matter hyperintensity) at baseline. Binary logistic regression or ordinal logistic regression model was used to estimate the relationship of LS7 scores with CSVD and magnetic resonance imaging markers.

RESULTS: A total of 3061 participants were included in this study. Compared with poor total LS7 score, ideal LS7 total score was associated with reduced adjusted odds of higher CSVD score (common odds ratio [cOR], 0.73 [95% CI, 0.58-0.90]) and higher modified CSVD score (cOR, 0.78 [95% CI, 0.64-0.95]). Compared with poor LS7 medical score, ideal LS7 medical score was associated with reduced adjusted odds of higher CSVD score (cOR, 0.65 [95% CI, 0.53-0.80]) and higher modified CSVD score (cOR, 0.67 [95% CI, 0.56-0.81]). Higher total LS7 score and LS7 medical score were associated with a lower risk of white matter hyperintensities and lacunes. Higher LS7 behavioral score was associated with lower risk of lacunes.

CONCLUSIONS: Ideal LS7 score, indicating excellent cardiovascular health, was associated with lower total CSVD burden. Optimizing the risk factors captured by LS7 may reduce the progression of CSVD.

PMID:35975667 | DOI:10.1161/STROKEAHA.122.038838

Stroke. 2022 Aug 17:101161STROKEAHA121037744. doi: 10.1161/STROKEAHA.121.037744. Online ahead of print.

ABSTRACT

BACKGROUND: Many methods have been suggested for analyzing the modified Rankin Scale (mRS). However, there lacks a unified approach to analysis and sample size determination that properly uses the ordinal nature of the data. We propose a simple method for CI estimation and corresponding sample size determination.

METHODS: We quantify treatment effect by the win probability (WinP) that a randomly selected patient in the treatment group has an equal or a better mRS score than a patient in the control group. Thus, a win probability of 0.5 means no effect, likened to a draw in competitive sports. We estimate the win probability and its SE based on the ranks of mRS scores, where tied scores are handled by average ranks. Corresponding methods for hypothesis testing, CI estimation, and sample size determination are derived. The methods are evaluated with a simulation study based on real data from 10 randomized stroke trials that used mRS as the outcome measure.

RESULTS: Simulation results demonstrated that the methods performed very well in terms of CI coverage, tail errors, and assurance to achieving the prespecified precision. Because the methods are very simple, we implemented them in an Excel spreadsheet, requiring only user inputs on frequencies of mRS scores in 2 comparison groups.

CONCLUSIONS: Sound statistical methods are important for the success of randomized stroke trials. The proposed methods and associated spreadsheet should prove useful for stroke researchers in the planning and analysis of randomized trials. Meta-analysis has also been made easy for trials with ordinal scores.

PMID:35975666 | DOI:10.1161/STROKEAHA.121.037744

Gut Liver. 2022 Aug 17. doi: 10.5009/gnl220005. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn’s disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab.

METHODS: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes.

RESULTS: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission.

CONCLUSIONS: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.

PMID:35975641 | DOI:10.5009/gnl220005

J Int Assoc Provid AIDS Care. 2022 Jan-Dec;21:23259582221121096. doi: 10.1177/23259582221121096.

ABSTRACT

Background: Drug adherence is the most significant in the progression of diseases. Thus, this study aimed to assess adherence and associated factors among seropositive people received treatment. Methods: Facility-based cross-sectional study was conducted in Jimma town public health facility from March to April 2019 on 385 selected participants. Systematic sampling technique was used to select study participants. The data were entered using Epi-data version 4.1 and analyzed by SPSS version 20 software. Variables with p-value of less than 0.25 in binary logistic regression were entered into the multivariable logistic regression to control cofounding A significance level of less than 0.05 was used in the final model to judge statistical significance. Results: The magnitude of adherence to antiretroviral treatment was 69.4%. Food security (AOR = 1.75 (95% CI;(1.01-3.0), substance abuse (AOR = 0.55 (95% CI;(0.32-0.96), Didn’t take other medications (AOR = 2.11(95%CI;(1.15-3.87), Good relationship with providers (AOR = 3.35(95%CI;(1.55-7.2), and irregular appointment (AOR = 0.19(95%CI; (0.11-0.34) were significantly associated. Conclusion: The magnitude of adherence to Anti-retroviral therapy was low compare to WHO. Food security, substance abuse, use of other medication, relationship with the health care providers, and irregular appointment were the factors associated. Treatment. Therefore, it is recommended that patients and health care workers enhance Antiretroviral Treatment adherence.

PMID:35975573 | DOI:10.1177/23259582221121096

Plant Genome. 2022 Aug 17:e20253. doi: 10.1002/tpg2.20253. Online ahead of print.

ABSTRACT

The growing demand for food and feed crops in the world because of growing population and more extreme weather events requires high-yielding and resilient crops. Many agriculturally important traits are polygenic, controlled by multiple regulatory layers, and with a strong interaction with the environment. In this study, 120 F₂ families of perennial ryegrass (Lolium perenne L.) were grown across a water gradient in a semifield facility with subsoil irrigation. Genomic (single-nucleotide polymorphism [SNP]), transcriptomic (gene expression [GE]), and DNA methylomic (MET) data were integrated with feed quality trait data collected from control and drought sections in the semifield facility, providing a treatment effect. Deep root length (DRL) below 110 cm was assessed with convolutional neural network image analysis. Bayesian prediction models were used to partition phenotypic variance into its components and evaluated the proportion of phenotypic variance in all traits captured by different regulatory layers (SNP, GE, and MET). The spatial effects and effects of SNP, GE, MET, the interaction between GE and MET (GE × MET) and GE × treatment (GE_Control and GE_Drought ) interaction were investigated. Gene expression explained a substantial part of the genetic and spatial variance for all the investigated phenotypes, whereas MET explained residual variance not accounted for by SNPs or GE. For DRL, MET also contributed to explaining spatial variance. The study provides a statistically elegant analytical paradigm that integrates genomic, transcriptomic, and MET information to understand the regulatory mechanisms of polygenic effects for complex traits.

PMID:35975565 | DOI:10.1002/tpg2.20253

J Clin Sleep Med. 2022 Aug 17. doi: 10.5664/jcsm.10240. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: This study evaluated sleep quality in relation to pain and pain-related impairment in adolescents and young adults (AYAs) with sickle cell disease (SCD). The purpose of this work was to examine whether increased age was associated with poorer sleep quality and pain and to examine the sleep quality-pain association in this age group.

METHODS: Eighty-nine AYAs with SCD between the ages of 13 and 25 completed ratings of sleep quality, overall pain, and two measures of pain-related impairment (pain impact and pain burden) as part of their clinical care. Retrospective chart reviews were completed to match ratings to demographic and medical characteristics. Correlations and multiple regression were used to examine associations between age, sleep quality, and pain variables, including an exploratory analysis of the sleep-pain association by age.

RESULTS: Increased age was associated with poorer sleep quality, worse overall pain, and higher pain burden. Poorer sleep quality was also associated with worse overall pain and pain burden. Using multiple regression, a small, but not statistically significant trend was observed for the interaction of increased age and strengthening of the sleep quality-pain burden association.

CONCLUSIONS: Sleep quality and pain are important challenges for AYAs with SCD that may persist or worsen with increased age. Early identification of these difficulties in pediatric populations as well as continued screening and intervention as adolescents transition into adult care is important. Additional longitudinal research is needed to better understand the progression of the sleep-pain relationship over time.

PMID:35975556 | DOI:10.5664/jcsm.10240

J Clin Sleep Med. 2022 Aug 17. doi: 10.5664/jcsm.10250. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) is a common and serious sleep disorder whose treatment remains challenging due to lack of adherence to approved therapies. Previous pharmacological studies addressing sleep-related upper airway muscle hypotonia suggested that the combination of atomoxetine and oxybutynin is effective in treating OSA. The current study is with aroxybutynin (AD109), a new enantiomerically pure form of oxybutynin with better safety profile compared to racemic oxybutynin.

METHODS: This was a randomized, double-blind, placebo-controlled, crossover study in patients with mild to moderate OSA. Each received low-dose AD109 (37.5/2.5mg), high-dose (75/2.5mg), and placebo at bedtime across three overnight periods in a randomized order. Adverse events were collected by telephone contact with participants during each washout period. The primary endpoint was change in Hypoxic Burden (HB) and secondary endpoint was apnea-hypopnea index (AHI).

RESULTS: Patients treated with both the high and low doses of AD109 had a statistically significant and clinically meaningful difference from placebo in HB. Median[IQR] HB for participants on placebo was 13.9[4.5-21.9]%min/h vs 2.3[0.1-10.5]%min/h for patients on the high dose (p<0.001) and to 7.3[2-12.5]%min/h on the low dose (p<0.01). AHI went from a median of 13.2[8.0-19.1] events/h on placebo reduced to 5.5[2.2 to 9.6] events/h on the high dose (p<0.001) and to 7.8[4-13.7] on the low dose (p<0.05). AD109 demonstrated a favorable safety profile.

CONCLUSIONS: This study provides further support that a pharmacological intervention for OSA, namely the combination of atomoxetine and aroxybutynin, offers promising results. Additional development of this compound and others is warranted.

CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT04631107; Title: AD109 Dose Finding in Mild to Moderate OSA; URL: https://clinicaltrials.gov/ct2/show/NCT04631107.

PMID:35975547 | DOI:10.5664/jcsm.10250

Clin Lab. 2022 Jul 1;68(7). doi: 10.7754/Clin.Lab.2021.211110.

ABSTRACT

BACKGROUND: Excessive inflammatory immune response during SARS-CoV-2 infection contributes to severe disease in COVID-19 patients. Recently, some researchers hypothesized that dysregulation of the bradykinin (BK) system may also play a role in the pathogenesis of severe disease. Des-Arg(9)-bradykinin (DABK), an active metabolite of BK, is responsible for vasodilatation and increased permeability in the lungs and regulated by angiotensin converting enzyme 2 (ACE-2). Viral inhibition of ACE-2 by SARS-CoV-2 increases DABK levels. Serum levels of this metabolite may be linked to disease severity in COVID-19 patients. In this study, it is aimed to investigate the prognostic value of serial measurement of serum DABK levels in severe COVID-19 patients.

METHODS: This prospective cohort study was conducted in hospitalized severe COVID-19 patients. Serum DABK levels of patients were serially measured on day 0, day 3 and day 5. Patients were categorized as cases with poor or good prognosis and critical or non-critical cases. Serum DABK levels of these patient groups were compared with paired sample t-test. Serum DABK levels on different days in the same patients were compared with repeated measures ANOVA tests.

RESULTS: There was no statistically significant difference in serum DABK levels measured at day 0, day 3, and day 5 between good and poor prognosis groups. DABK levels in critical and non-critical COVID-19 patients also did not show any significant difference.

CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.

PMID:35975542 | DOI:10.7754/Clin.Lab.2021.211110

Clin Lab. 2022 Jul 1;68(7). doi: 10.7754/Clin.Lab.2021.210910.

ABSTRACT

BACKGROUND: Candida auris is an opportunistic pathogen with multiple drug resistance. Therefore, researchers conducted a meta-analysis to review PCR’s ability to diagnose Candida auris to promote the development of accurate Candida auris diagnosis.

METHODS: Researchers systematically retrieved relevant articles from PubMed, Cochrane Library, Embase, and Web of Science. Then, researchers extracted the key data required for the study from the selected articles. Meta-DiSc 1.4 was used for the statistical analysis. RevMan 5.3 was employed to assess the quality of the included literature. A funnel plot can appraise whether the included articles have publication bias.

RESULTS: Five articles were included in the study. The results suggest that the pooled sensitivity and pooled specificity were 0.94 (95% CI: 0.92 – 0.95) and 0.99 (95% CI: 0.99 – 0.99), respectively. The positive and negative likelyhood ratios were 100.94 (95% CI: 47.51 – 214.47) and 0.07 (95% CI: 0.05 – 0.10), respectively. The diagnostic odds ratio was 1,814.70 (95% CI: 717.30 – 4,591.04), and the area under the SROC curve was 0.9935. Deek’s funnel plot indicated that there was no publication bias.

CONCLUSIONS: The results of the analysis indicate that PCR can become a valuable technique for the clinical diagnosis of Candida auris due to its excellent performance.

PMID:35975540 | DOI:10.7754/Clin.Lab.2021.210910

Clin Lab. 2022 Jul 1;68(7). doi: 10.7754/Clin.Lab.2021.210833.

ABSTRACT

BACKGROUND: Serum TSH reference intervals (RIs) are methodology, population, and age specific. However, the ethical and practical challenges restrict the establishment of pediatric RIs using conventional approaches and advocates the use of indirect data mining-based algorithms. This study was carried out to estimate the reference interval of neonatal serum TSH in Pakistani population using an indirect approach.

METHODS: A data mining of serum TSH results of neonates (≤ 1 month of age) from 2013 – 2018 was done. Two subgroups on the basis of age from birth to 5 days and 6 – 30 days were assessed. The German study group’s pre-validated indirect algorithm ‘KOSMIC’ was utilized for the statistical analysis.

RESULTS: A total of non-duplicate 82,299 neonatal serum TSH tests were retrieved over a period of 6 years, including 88% (n = 70,788) aged 0 – 5 days and 12% (n = 11,511) ranging from 6 days to 1 month. The estimated RIs for the first age partition was 0.7 (90% CI 0.6 – 0.8) to 15.5 (90% CI 12.9 – 16.2) and for the second group 0.7 (90% CI 0.5 – 0.9) to 7.8 (90% CI 6.1 – 9.9) µIU/mL.

CONCLUSIONS: This study revealed age related trends in serum TSH. The study advocates the need for population specific RIs owing to the significant variations noted on comparison with previously published literature. Precise RIs become vital particularly when serum TSH is undertaken as a confirmatory test for presumptive positive results on newborn screening for congenital hypothyroidism.

PMID:35975518 | DOI:10.7754/Clin.Lab.2021.210833