Category: Statistics

Diabet Med. 2022 Mar 30:e14837. doi: 10.1111/dme.14837. Online ahead of print.

ABSTRACT

AIM: Previous studies have focused on the association between ambient particulate matter and diabetes. However, the relationship between subacute exposure to occupational dust and diabetes has not been explored. We aimed to assess this relationship.

METHODS: Men who worked in dust-related process factories between January 2013 and December 2017 were recruited from a Korea Health Worker Examination Common Data Model cohort. A history of physician-diagnosed diabetes, use of an anti-diabetic drug, or a fasting blood glucose level of ≥7 mmol/L were considered the criteria to diagnose diabetes. Multivariable time-dependent Cox analysis estimated hazard ratios (HRs) and 95% CIs for incident diabetes associated with exposure to occupational dust exposure; interactions with lifestyle factors were analysed. Sensitivity analyses used propensity score matching and landmark analysis RESULTS: Among 5,141 male participants (median follow-up duration, 3.85 years), 349 participants had diabetes. Occupational dust exposure was related to an increased risk of diabetes in the time-dependent Cox analysis (entire cohort: HR 1.66 [95% CI 1.25-2.19], matched cohort: HR 1.65 [95% CI 1.22-2.24]). The findings showed the same direction in the landmark analysis (HR 1.42 [95% CI 1.01-1.99]).

CONCLUSIONS: A significant relationship exists between occupational dust exposure and increased risk of diabetes in male workers. Further studies should be conducted to confirm that occupational dust exposure is a possible risk factor for diabetes.

PMID:35352388 | DOI:10.1111/dme.14837

J Magn Reson Imaging. 2022 Mar 30. doi: 10.1002/jmri.28159. Online ahead of print.

ABSTRACT

BACKGROUND: Extracellular matrix expansion is a key pathophysiologic feature in heart failure and can be quantified noninvasively by cardiac magnetic resonance T₁ -mapping. Free water within the interstitial space of the myocardium, however, may also alter T₁ -mapping results.

PURPOSE: To investigate the association between systemic fluid status and T₁ -mapping by cardiac magnetic resonance.

STUDY TYPE: Prospective, observational single-center study.

POPULATION: Two-hundred eighty-five consecutive patients (44.4% female, 70.0 ± 14.9 years old) scheduled for cardiac MR due to various cardiac diseases.

SEQUENCE AND FIELD STRENGTH: 1.5-T scanner (Avanto Fit, Siemens Healthineers, Erlangen, Germany). For T₁ -mapping, electrocardiographically triggered modified-Look-Locker inversion (MOLLI) recovery sequence using a 5(3)3 prototype on a short-axis mid-cavity slice and with a four-chamber view was performed.

ASSESSMENTS: MR parameters including native myocardial T₁ -times using MOLLI and extracellular volume (MR-ECV) were assessed, and additionally, we performed bioimpedance analysis (BIA). Furthermore, demographic data and comorbidities were assessed.

STATISTICS: Wilcoxon’s rank-sum test, chi-square tests, and for correlation analysis, Pearson’s correlation coefficients were used. Regression analyses were performed to investigate the association between patients’ fluid status and T₁ -mapping results. A P-value <0.05 was considered statistically significant.

RESULTS: The mixed cohort presented with a mean overhydration (OH) of +0.2 ± 2.4 liters, as determined by BIA. By MR, native T₁ -times were 1038 ± 51 msec and MR-ECV was 31 ± 9%. In the multivariable regression analysis, only OH was significantly associated with MR-ECV (adj. beta: 0.711; 95% CI: 0.28 to 1.14) along with male sex (adj. beta: 2.529; 95% CI: 0.51 to 4.55). In linear as well as multivariable analysis, only OH was significantly associated with native T₁ times (adj. beta: 3.750; 95% CI: 1.27 to 6.23).

CONCLUSION: T₁ -times and MR-ECV were significantly associated with the degree of OH on BIA measurement. These effects were independent from age, sex, body mass index, and hematocrit. Patients’ volume status may thus be an important factor when T₁ -time and MR-ECV values are interpreted.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

PMID:35352420 | DOI:10.1002/jmri.28159

Br J Clin Pharmacol. 2022 Mar 29. doi: 10.1111/bcp.15330. Online ahead of print.

ABSTRACT

AIM: We aimed to investigate French pharmacovigilance data. The objective was to characterize psoriatic conditions occurred after BB exposure and bright to light a possible pharmacovigilance signal.

METHODS: Spontaneous reports of psoriatic conditions recorded in the French national Pharmacovigilance database (FPVD) between 1985 and 2019 were extracted. We performed a retrospective, descriptive analysis of reports linked to BB exposure. Association between psoriasis risk and BB exposure was assessed using a case/non-case study.

RESULTS: Two hundred and twenty-five reports of psoriatic conditions after BB exposure were recorded in the FPVD during the study period. Both, cardioselective and non-cardioselective, topical and systemic, BBs are involved. Therapeutic indication of BB was mainly hypertension Mean time to onset was 5 months and outcome was favorable in 68% after BB discontinuation. These features were concordant with those of literature reports. The reporting odds ratio (ROR) was 8.95 (95%CI 7.75 – 10.33).

CONCLUSION: We highlighted a statistically significant disproportionality which constitutes a pharmacovigilance signal. Psoriasis risk with BBs is a class effect. Increasing surveillance during the 1^st year of BB exposure is needed.

PMID:35352377 | DOI:10.1111/bcp.15330

Biometrics. 2022 Mar 30. doi: 10.1111/biom.13669. Online ahead of print.

ABSTRACT

Functional data are smooth, often continuous, random curves, which can be seen as an extreme case of multivariate data with infinite dimensionality. Just as component-wise inference for multivariate data naturally performs feature selection, subset-wise inference for functional data performs domain selection. In this paper, we present a unified testing framework for domain selection on populations of functional data. In detail, p-values of hypothesis tests performed on point-wise evaluations of functional data are suitably adjusted for providing a control of the family-wise error rate (FWER) over a family of subsets of the domain. We show that several state-of-the-art domain selection methods fit within this framework and differ from each other by the choice of the family over which the control of the FWER is provided. In the existing literature, these families are always defined a priori. In this work, we also propose a novel approach, coined threshold-wise testing, in which the family of subsets is instead built in a data-driven fashion. The method seamlessly generalizes to multidimensional domains in contrast to methods based on a-priori defined families. We provide theoretical results with respect to consistency and control of the FWER for the methods within the unified framework. We illustrate the performance of the methods within the unified framework on simulated and real data examples, and compare their performance with other existing methods. This article is protected by copyright. All rights reserved.

PMID:35352337 | DOI:10.1111/biom.13669

Folia Microbiol (Praha). 2022 Mar 30. doi: 10.1007/s12223-022-00968-3. Online ahead of print.

ABSTRACT

KlUpc2p, a transcription factor belonging to the fungal binuclear cluster family, is an important regulator of ergosterol biosynthesis and azole drug resistance in Kluyveromyces lactis. In this work, we show that the absence of KlUpc2p generates Rag^– phenotype and modulates the K. lactis susceptibility to oxidants and calcofuor white. The KlUPC2 deletion leads to increased expression of KlMGA2 gene, encoding an important regulator of hypoxic and lipid biosynthetic genes in K. lactis and also KlHOG1 gene. The absence of KlUpc2p does not lead to statistically significant changes in glycerol, corroborating the expression of KlGPD1 gene, encoding NAD⁺-dependent glycerol-3-phosphate dehydrogenase, that is similar in both the deletion mutant and the parental wild-type strain. Increased sensitivity of Klupc2 mutant cells to brefeldin A accompanied with significant increase in KlARF2 gene expression point to the involvement of KlUpc2p in intracellular signaling. Our observations highlight the connections between ergosterol and fatty acid metabolism to modulate membrane properties and point to the possible involvement of KlUpc2p in K. lactis oxidative stress response.

PMID:35352326 | DOI:10.1007/s12223-022-00968-3

Reprod Sci. 2022 Mar 29. doi: 10.1007/s43032-022-00922-1. Online ahead of print.

ABSTRACT

Peripartum depression is common and carries significant morbidity and mortality. This study aimed to identify modifiable psychological and biological factors that increase the risk for peripartum depression. In a prospective cohort study, pregnant women (n = 105) completed self-report assessments of mood (Edinburgh Postnatal Depression Scale-EPDS), anxiety (Generalized Anxiety Disorder Scale-GAD), and sleep disturbances (Pittsburgh Sleep Quality Index-PSQI) and provided a blood sample at 8-to-12 and 24-to-28 weeks of gestation and 6-to-8 and 10-to-12 weeks postpartum. During the study, 33.3% (35/105) of participants met criteria for depression (EPDS ≥ 10). Women with elevated PSQI (OR: 1.17; 95% CI 1.04-1.33) or GAD (OR: 1.33; 95% CI 1.18-1.48) scores at 8-12 weeks of gestation were significantly more likely to experience elevated depressive symptoms at subsequent assessments. Women with deficient vitamin D levels (≤ 20 ng/L) were more likely to report elevated depressive symptoms at follow-up assessments, although these findings were not statistically significant (OR: 2.40; 95% CI 0.92-6.27). Participation rates for postpartum assessments were low. Depressive and anxiety symptoms, and sleep disturbances were assessed through self-report measures. Sleep, anxiety, and potentially vitamin D disturbances in early pregnancy are associated with an increase in peripartum depression. Interventions aimed at reducing sleep and anxiety disturbances and ensuring adequate levels of vitamin D in pregnancy are potential therapeutic targets to reduce risk of peripartum depression.

PMID:35352331 | DOI:10.1007/s43032-022-00922-1

Atten Percept Psychophys. 2022 Mar 30. doi: 10.3758/s13414-022-02469-4. Online ahead of print.

ABSTRACT

Individuals can adjust their shift readiness, known as attentional flexibility, according to the statistical structure of the environment. However, the extent to which these modulations in attentional flexibility are associated with a global readiness to shift attention to any location versus an anticipated shift to a single location remains unknown. Across two experiments, participants shifted attention among three rapid serial visual presentation (RSVP) streams of alphanumeric characters in response to embedded visual cues and made button presses in response to targets at the cued location. We manipulated the likelihood that participants would receive a cue that signaled a shift between two of the streams across blocks of trials. The likelihood of a cued shift of attention to the third location was held constant across all blocks. Participants demonstrated smaller target detection shift costs (Experiments 1 and 2) and shorter saccade latencies (Experiment 1) when the overall likelihood of shifting was high than when the overall shift likelihood was low. Critically, we observed evidence of both global shift readiness and location-specific shift readiness in both experiments such that participants shifted attention to the most-likely-to-be cued location the fastest, but still demonstrated a difference in the time to shift attention to the unlikely location according to the overall shift likelihood. Our findings provide evidence that moment-by-moment changes in attentional flexibility are not limited to an expectation to shift to a single location, but rather reflect, in part, a location-independent state of control.

PMID:35352297 | DOI:10.3758/s13414-022-02469-4

Biol Trace Elem Res. 2022 Mar 30. doi: 10.1007/s12011-022-03212-8. Online ahead of print.

ABSTRACT

Celiac disease is a multisystem immune based disorder, caused by an immune-mediated reaction to ingested gluten with increasing prevalence in the USA. Celiac disease can cause a wide variety of symptoms, including gastrointestinal symptoms (diarrhea, abdominal distention, or abdominal pain), which may affect absorption of many nutritional components. All patients with celiac disease should remain on a strict and lifelong gluten-free diet, which are often low in certain trace elements such as zinc. On the other hand, zinc and copper as the essential trace elements have been hypothesized to help maintain optimum function of the immune system. Then, this study aims to examine the association between celiac disease seropositivity and serum zinc and copper levels. A nationally representative sample from National Health and Nutrition Examination Survey (2011-2014) was analyzed. Celiac disease seropositivity was determined using the tissue transglutaminase IgA antibody test (IgA-TTG). Multivariable linear regression models were performed with celiac disease seropositivity as a predictor and serum zinc and copper levels as outcome. The present study included 4732 participants (1398 children aged 6-19 years and 3334 adults aged ≥ 20 years). The weighted prevalence of celiac disease seropositivity was higher (11.6/1000) among children aged 6-19 years compared to that (6.3/1000) among adults aged ≥ 20 years. In the stratified analysis by age, the multivariable linear regression analysis revealed that among children aged 6-19 years, celiac disease seropositivity was associated with 5.32 (95% CI, – 9.71 to – 0.92) μg/dL lower serum zinc level, but not associated with serum copper level. However, the association between celiac disease seropositivity and serum zinc level was not statistically significant among adults aged 20 years or older. Future prospective studies are warranted to confirm these findings.

PMID:35352294 | DOI:10.1007/s12011-022-03212-8

Lifetime Data Anal. 2022 Mar 29. doi: 10.1007/s10985-022-09550-y. Online ahead of print.

ABSTRACT

This paper discusses the fitting of the proportional hazards model to interval-censored failure time data with missing covariates. Many authors have discussed the problem when complete covariate information is available or the missing is completely at random. In contrast to this, we will focus on the situation where the missing is at random. For the problem, a sieve maximum likelihood estimation approach is proposed with the use of I-spline functions to approximate the unknown cumulative baseline hazard function in the model. For the implementation of the proposed method, we develop an EM algorithm based on a two-stage data augmentation. Furthermore, we show that the proposed estimators of regression parameters are consistent and asymptotically normal. The proposed approach is then applied to a set of the data concerning Alzheimer Disease that motivated this study.

PMID:35352270 | DOI:10.1007/s10985-022-09550-y

Pharm Res. 2022 Mar 29. doi: 10.1007/s11095-022-03244-8. Online ahead of print.

ABSTRACT

BACKGROUND: Although kinase inhibitors (KIs) are generally effective, their use has a large impact on the current health care budget. Dosing strategies to reduce treatment costs are warranted. Boosting pharmacokinetic exposure of KIs metabolized by cytochrome P450 (CYP)3A4 with ritonavir might result in lower doses needed and subsequently reduces treatment costs. This study is a proof-of-concept study to evaluate if the dose of erlotinib can be reduced by co-administration with ritonavir.

METHODS: In this open-label, cross-over study, we compared the pharmacokinetics of monotherapy erlotinib 150 mg once daily (QD) (control arm) with erlotinib 75 mg QD plus ritonavir 200 mg QD (intervention arm). Complete pharmacokinetic profiles at steady-state were taken up to 24 h after erlotinib intake for both dosing strategies.

RESULTS: Nine patients were evaluable in this study. For the control arm, the systemic exposure over 24 h, maximum plasma concentration and minimal plasma concentration of erlotinib were 29.3 μg*h/mL (coefficient of variation (CV):58%), 1.84 μg/mL (CV:60%) and 1.00 μg/mL (CV:62%), respectively, compared with 28.9 μg*h/mL (CV:116%, p = 0.545), 1.68 μg/mL (CV:68%, p = 0.500) and 1.06 μg/mL (CV:165%, p = 0.150) for the intervention arm. Exposure to the metabolites of erlotinib (OSI-413 and OSI-420) was statistically significant lower following erlotinib plus ritonavir dosing. Similar results regarding safety in both dosing strategies were observed, no grade 3 or higher adverse event was reported.

CONCLUSIONS: Pharmacokinetic exposure at a dose of 75 mg erlotinib when combined with the strong CYP3A4 inhibitor ritonavir is similar to 150 mg erlotinib. Ritonavir-boosting is a promising strategy to reduce erlotinib treatment costs and provides a rationale for other expensive therapies metabolized by CYP3A4.

PMID:35352280 | DOI:10.1007/s11095-022-03244-8