Category: Statistics

AIDS. 2021 Mar 16. doi: 10.1097/QAD.0000000000002883. Online ahead of print.

ABSTRACT

OBJECTIVE: Efficacy and safety of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc.

DESIGN AND METHODS: Data from 1039 adults naive to CAB+RPV LA were pooled in a multivariable analysis to examine the influence of baseline viral and participant factors, dosing regimen, and drug concentrations on confirmed virologic failure (CVF) occurrence using a logistic regression model. In a separate model, baseline factors statistically associated with CVF were further evaluated to understand CVF risk when present alone or in combination.

RESULTS: Overall, 1.25% (n = 13/1039) of participants experienced CVF. Proviral RPV resistance-associated mutations (RAMs), HIV-1 subtype A6/A1, higher body mass index (BMI, associated with Week 8 CAB trough concentration), and lower Week 8 RPV trough concentrations were significantly associated (p < 0.05) with increased odds of CVF (all except RPV trough are knowable at baseline). Few participants (0.4%) with zero or 1 baseline factor had CVF. Only a combination of ≥2 baseline factors (observed in 3.4%; n = 35/1039) was associated with increased CVF risk (25.7%, n = 9/35).

CONCLUSIONS: CVF is an infrequent multifactorial event, with a rate of ∼1% in the LA arms across Phase 3 studies (FLAIR, ATLAS, and ATLAS-2 M) through Week 48. Presence of ≥2 of proviral RPV RAMs, HIV-1 subtype A6/A1, and/or BMI ≥30 kg/m2 was associated with increased CVF risk. These findings support the use of CAB+RPV LA in routine clinical practice.

PMID:33730748 | DOI:10.1097/QAD.0000000000002883

Int J Biostat. 2021 Jan 18. doi: 10.1515/ijb-2020-0059. Online ahead of print.

ABSTRACT

In allometric studies, the joint distribution of the log-transformed morphometric variables is typically symmetric and with heavy tails. Moreover, in the bivariate case, it is customary to explain the morphometric variation of these variables by fitting a convenient line, as for example the first principal component (PC). To account for all these peculiarities, we propose the use of multiple scaled symmetric (MSS) distributions. These distributions have the advantage to be directly defined in the PC space, the kind of symmetry involved is less restrictive than the commonly considered elliptical symmetry, the behavior of the tails can vary across PCs, and their first PC is less sensitive to outliers. In the family of MSS distributions, we also propose the multiple scaled shifted exponential normal distribution, equivalent of the multivariate shifted exponential normal distribution in the MSS framework. For the sake of parsimony, we also allow the parameter governing the leptokurtosis on each PC, in the considered MSS distributions, to be tied across PCs. From an inferential point of view, we describe an EM algorithm to estimate the parameters by maximum likelihood, we illustrate how to compute standard errors of the obtained estimates, and we give statistical tests and confidence intervals for the parameters. We use artificial and real allometric data to appreciate the advantages of the MSS distributions over well-known elliptically symmetric distributions and to compare the robustness of the line from our models with respect to the lines fitted by well-established robust and non-robust methods available in the literature.

PMID:33730771 | DOI:10.1515/ijb-2020-0059

Oncology. 2021 Mar 17:1-8. doi: 10.1159/000514404. Online ahead of print.

ABSTRACT

BACKGROUND: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients.

PATIENTS AND METHODS: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity.

RESULTS: Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer.

CONCLUSION: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.

PMID:33730723 | DOI:10.1159/000514404

Dermatology. 2021 Mar 17:1-8. doi: 10.1159/000514503. Online ahead of print.

ABSTRACT

BACKGROUND: A growing body of evidence links various biomarkers to atopic dermatitis (AD). Still, little is known about the association of specific biomarkers to disease characteristics and severity in AD.

OBJECTIVE: To explore the relationship between various immunological markers in the serum and disease severity in a hospital cohort of AD patients.

METHODS: Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, were divided into groups based on disease severity (SCORAD). Serum levels of a preselected panel of immunoinflammatory biomarkers were tested for association with disease characteristics. Two machine learning models were developed to predict SCORAD from the measured biomarkers.

RESULTS: A total of 160 patients with AD were included; 53 (33.1%) with mild, 73 (45.6%) with moderate, and 34 (21.3%) with severe disease. Mean age was 29.2 years (range 6-70 years) and 84 (52.5%) were females. Numerous biomarkers showed a statistically significant correlation with SCORAD, with the strongest correlations seen for CCL17/thymus and activation-regulated chemokine (chemokine ligand-17/TARC) and CCL27/cutaneous T cell-attracting-chemokine (CTACK; Spearman R of 0.50 and 0.43, respectively, p < 0.001). Extrinsic AD patients were more likely to have higher mean SCORAD (p < 0.001), CCL17 (p < 0.001), CCL26/eotaxin-3 (p < 0.001), and eosinophil count (p < 0.001) than intrinsic AD patients. Predictive models for SCORAD identified CCL17, CCL27, serum total IgE, IL-33, and IL-5 as the most important predictors for SCORAD, but with weaker associations than single cytokines.

CONCLUSIONS: Specific immunoinflammatory biomarkers in the serum, mainly of the Th2 pathway, are correlated with disease severity in patients with AD. Predictive models identified biomarkers associated with disease severity but this finding warrants further investigation.

PMID:33730733 | DOI:10.1159/000514503

Cerebrovasc Dis. 2021 Mar 17:1-9. doi: 10.1159/000514133. Online ahead of print.

ABSTRACT

INTRODUCTION: Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed.

METHODOLOGY: We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test.

RESULTS: For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades.

CONCLUSION: The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.

PMID:33730735 | DOI:10.1159/000514133

J Phys Condens Matter. 2021 Mar 17. doi: 10.1088/1361-648X/abef9b. Online ahead of print.

ABSTRACT

We explore glassy dynamics of dense assemblies of soft particles that are self-propelled by active forces. These forces have a fixed amplitude and a propulsion direction that varies on a timescale τp, the persistence timescale. Numerical simulations of such active glasses are computationally challenging when the dynamics is governed by large persistence times. We describe in detail a recently proposed scheme that allows one to study directly the dynamics in the large persistence time limit, on timescales around and well above the persistence time. We discuss the idea behind the proposed scheme, which we call “activity-driven dynamics”, as well as its numerical implementation.We establish that our prescription faithfully reproduces all dynamical quantities in the appropriate limit τp→ ∞. We deploy the approach to explore in detail the statistics of Eshelby-like plasticevents in the steady state dynamics of a dense and intermittent active glass.

PMID:33730708 | DOI:10.1088/1361-648X/abef9b

Eur Addict Res. 2021 Mar 17:1-9. doi: 10.1159/000513776. Online ahead of print.

ABSTRACT

INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.

METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.

RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).

CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.

PMID:33730716 | DOI:10.1159/000513776

Complement Med Res. 2021 Mar 17:1-8. doi: 10.1159/000514944. Online ahead of print.

ABSTRACT

BACKGROUND: Menopause and estrogen deprivation cause a rise in the number of urogenital tract complaints.

OBJECTIVE: This study was conducted to assess the effectiveness of ginseng on genitourinary syndrome.

METHODS: This randomized trial was conducted on 60 postmenopausal women with genitourinary syndrome. The participants were randomly allocated to ginseng and placebo groups twice daily for 4 weeks. Vaginal maturation index and vaginal pH were evaluated before and 4 weeks after intervention as the primary outcomes. Also, the atrophic vaginitis and incontinence questionnaires were completed before and after intervention as the secondary outcomes. The safety of intervention was assessed by the side effects checklist.

RESULTS: No significant differences were observed between the 2 groups in objective symptoms after the intervention, but the difference was statistically significant (p < 0.001) in terms of subjective symptoms of atrophic vaginitis. One case of insomnia and palpitation and 2 cases of hot flashes were reported in the intervention group, and 1 case of gastric discomfort and change in urine appearance was reported in the placebo group.

CONCLUSION: Ginseng only improved the patient-assessed symptoms and had no significant effect on the clinician-assessed outcomes. Further studies are required to determine the precise pharmacological mechanisms of ginseng on genitourinary syndrome.

PMID:33730722 | DOI:10.1159/000514944

J Colloid Interface Sci. 2021 Mar 2;593:21-31. doi: 10.1016/j.jcis.2021.02.076. Online ahead of print.

ABSTRACT

HYPOTHESIS: The objective is to noninvasively probe the local hydrocarbon dynamics at asphaltene/maltene interfaces to reveal the global characteristics of bitumen at increasing temperatures and under various mechanical constraints.

EXPERIMENTS: We propose multidimensional (1D and 2D) nuclear magnetic relaxation (NMR) experiments to characterize the dynamic properties of hydrocarbons for a set of bitumen from 40 to 180 °C. The convergence towards universal theoretical modelling of NMR relaxation experiments gives a comprehensive understanding of hydrocarbon transport in these very weakly permeable samples. Moreover, a multivariate statistical analysis allows for correlating these NMR relaxation data for all bitumen samples to the main empirical parameters by qualifying the bitumen grading, such as the penetrability, softening and fragility points over a large range of temperatures.

FINDINGS: These new experimental and theoretical multiscale approaches link hydrocarbon interfacial dynamics to the global characteristics of various bitumen types. This is critical for grading these universally encountered materials.

PMID:33730653 | DOI:10.1016/j.jcis.2021.02.076

Clin Psychol Rev. 2021 Feb 27;85:102003. doi: 10.1016/j.cpr.2021.102003. Online ahead of print.

ABSTRACT

People with psychosis are reported to be one of the most stigmatised minority groups in society. Mental health stigma can have a detrimental impact on quality of life (QoL), which is a meaningful outcome for service users experiencing psychosis and using mental health services. This paper provides the first systematic literature review, meta-analysis and quality appraisal of studies examining the association between stigma and subjective QoL in non-affective psychosis. An electronic database search identified 45 articles for inclusion. A random-effects meta-analysis of 37 independent samples (n = 5795) found a statistically significant association between higher stigma and lower subjective QoL of medium strength (r = -0.40, 95% CI: -0.45, -0.35). Separate meta-analyses demonstrated medium-to-large negative pooled effects for self-stigma (k = 25, r = -0.44, 95% CI:-0.49, -0.38), perceived stigma (k = 10, r = -0.32, 95% CI:-0.42, -0.21) and experienced stigma (k = 6, r = -0.30, 95% CI:-0.35, -0.24). A narrative summary of 12 studies suggested psychological mechanisms relating to self-concept and social networks may play an important mediating role in the association between stigma and QoL in psychosis. Psychological interventions should target improvements in these psychological processes to reduce the negative impact of stigma on QoL in psychosis. Further longitudinal research is needed to test theoretical models of causal pathways and explanatory mechanisms.

PMID:33730660 | DOI:10.1016/j.cpr.2021.102003