Category: Statistics

Transbound Emerg Dis. 2021 Jul 28. doi: 10.1111/tbed.14263. Online ahead of print.

ABSTRACT

Existing models about the dynamics of COVID-19 transmission often assume the mechanism of virus transmission and the form of the differential equations. These assumptions are hard to verify. Due to the biases of country-level data, it’s inaccurate to construct the global dynamic of COVID-19. This research aims to provide a robust data-driven global model of the transmission dynamics. We apply Sparse Identification of Nonlinear Dynamics (SINDy) to model the dynamics of COVID-19 global transmission. One advantage is that we can discover the nonlinear dynamics from data without assumptions in the form of the governing equations. To overcome the problem of biased country-level data on the number of reported cases, we propose a robust global model of the dynamics by using maximin aggregation. Real data analysis shows the efficiency of our model. This article is protected by copyright. All rights reserved.

PMID:34320273 | DOI:10.1111/tbed.14263

N Engl J Med. 2021 Jul 28. doi: 10.1056/NEJMp2110468. Online ahead of print.

NO ABSTRACT

PMID:34320282 | DOI:10.1056/NEJMp2110468

J Eur Acad Dermatol Venereol. 2021 Jul 28. doi: 10.1111/jdv.17551. Online ahead of print.

ABSTRACT

BACKGROUND: Hidradenitis suppurativa (HS), a chronic, recurrent, debilitating skin disease, is characterized by painful, inflammatory, subcutaneous lesions of the axilla, inguinal, and anogenital regions. Overall prevalence of HS is ~1%, and impact of disease on patient quality of life (QoL) and healthcare resource utilization (HRU) is high.

OBJECTIVES: To estimate the real-world effectiveness of adalimumab (Humira^® ) treatment in patients with moderate to severe HS on disease severity, pain, QoL, work productivity, and HRU.

METHODS: HARMONY (Effectiveness of Adalimumab in Moderate to Severe HidrAdenitis SuppuRativa Patients – a Multi cOuNtry studY in Real Life Setting) is a multicenter, postmarketing observational study in adult patients with moderate to severe HS. Disease severity and QoL parameters were evaluated using validated measures at 12-week intervals over 52 weeks of treatment. The primary endpoint was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR: ≥50% reduction in abscess and inflammatory nodule count, with no increase in abscess and draining fistula counts relative to baseline) at 12 weeks. Secondary endpoints were HiSCR at 24, 36, and 52 weeks and changes in QoL parameters and work productivity assessments. Analyses were conducted using as-observed data.

RESULTS: The proportion of patients reaching the primary HiSCR endpoint was 70.2% (n=132/188 enrolled) and remained ≥70% until study completion. There were statistically significant (P<0.0001) reductions in worst and average skin pain. All of the QoL measures evaluated improved significantly (P<0.0001) by 12 weeks of adalimumab treatment, as did work productivity assessments (P<0.05), and there was a ~50% decrease in HRU between baseline and week 52. Adalimumab was well tolerated.

CONCLUSIONS: In this real-world setting, adalimumab treatment of moderate to severe HS resulted in decreased disease severity and improvements in QoL and productivity. Response to adalimumab was rapid (within 12 weeks) and sustained (52 weeks). No unexpected safety signals were reported.

PMID:34320249 | DOI:10.1111/jdv.17551

Int J Clin Pract. 2021 Jul 28:e14653. doi: 10.1111/ijcp.14653. Online ahead of print.

ABSTRACT

The T.O.HO. scoring system was developed to predict stone-free status after flexible ureterenoscopy (fURS) lithotripsy applied for ureter and renal stones. This study aimed to perform the external validation of the T.O.HO. score in the Turkish population and propose a modification for this system.

MATERIAL METHODS: Patients who underwent fURS for kidney and ureteral stones between January 2017 and January 2020 were retrospectively analyzed. The patient and stone characteristics and perioperative findings were noted. The T.O.HO. score was externally validated and compared with the STONE score. Stone-free parameters were evaluated with the multivariate analysis. Based on the results of this analysis, the T.O.HO. score was modified and internally validated.

RESULTS: A total of 621 patients were included in the study. The stone-free rate was determined as 79.8% (496/621) after fURS. The regression analysis showed that stone area had better predictive power than stone diameter (p=0.025). Lower pole (reference), middle pole [odds ratio (OR)=0.492 p=0.016] and middle ureteral (OR=0.227, p=0.024) localizations, stone density (OR=1.001, p<0.001), and stone volume (OR = 1.008, p <0.001) were determined as independent predictive markers for stone-free status. Based on the effect size of the stone surface area in the nomogram, stone volume was divided into five categories, at 1-point intervals. The AUC values of the T.O.HO., STONE, and modified T.O.HO. score in predicting stone-free status were calculated as 0.758, 0.634, and 0.821, respectively. The modified T.O.HO. created by adding stone volume was statistically significantly superior to the original version (ROC curve comparison, p < 0.001).

CONCLUSION: The T.O.HO. score effectively predicted stone-free status after fURS. However, Modified T.O.HO. SS showed the best predictive performance compared with original T.O.HO. SS.

PMID:34320257 | DOI:10.1111/ijcp.14653

J Oral Rehabil. 2021 Jul 28. doi: 10.1111/joor.13235. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about the effect of the type of splint material, Heat-Cured PMMA (HC) or Chemical-Cured PMMA (CC) on the wear of opposing tooth surfaces.

OBJECTIVE: The aim of this in-vitro study was to evaluate two-body wear of dentin, enamel, glass-ceramic or one of four resin composites when opposing splint materials, namely ProBase HC and CC.

METHODS: The two-body wear of bovine dentine, bovine enamel, glass-ceramic IPS e.max CAD (EMAX) and four composites (Filtek Z250 (Z250), Clearfil AP-X (AP-X), Clearfil Majesty Posterior (CMP), Filtek Supreme XTE (FSE)) opposing three antagonists (HC and CC and stainless steel as control) were evaluated in the ACTA wear machine. In addition, all the surfaces were evaluated with scanning electron microscopy.

RESULTS: The highest average wear was observed in the case of dentin. The lowest average wear was found EMAX. In every case -except for EMAX – the wear rate was higher with HC than with CC (all differences being statistically significant).

CONCLUSIONS: The level of wear of enamel, dentin and various resin composites was higher in contact with HC than in CC, the wear of dentin being the highest. In the case of a patient with no or little tooth wear or whose teeth are restored with composite material or glass-ceramic, the splint HC might be preferred because of its better durability. However, when the splint is in contact with opposing dentin preservation of the dentin CC might be the best choice.

PMID:34320246 | DOI:10.1111/joor.13235

Biom J. 2021 Jul 28. doi: 10.1002/bimj.202000256. Online ahead of print.

ABSTRACT

Chromatin dynamics are central to the regulation of gene expression and genome stability. In order to improve understanding of the factors regulating chromatin dynamics, the genes encoding these factors are deleted and the differential gene expression profiles are determined using approaches such as RNA sequencing. Here, we analyzed a gene expression dataset aimed at uncovering the function of the relatively uncharacterized chromatin regulator, Set4, in the model system Saccharomyces cerevisiae (budding yeast). The main theme of this paper focuses on identifying the highly differentially expressed genes in cells deleted for Set4 (referred to as Set4 Δ mutant dataset) compared to the wild-type yeast cells. The Set4 Δ mutant data produce a spiky distribution on the log-fold changes of their expressions, and it is reasonably assumed that genes which are not highly differentially expressed come from a mixture of two normal distributions. We propose an adaptive local false discovery rate (FDR) procedure, which estimates the null distribution of the log-fold changes empirically. We numerically show that, unlike existing approaches, our proposed method controls FDR at the aimed level (0.05) and also has competitive power in finding differentially expressed genes. Finally, we apply our procedure to analyzing the Set4 Δ mutant dataset.

PMID:34320248 | DOI:10.1002/bimj.202000256

Hepatology. 2021 Jul 28. doi: 10.1002/hep.32074. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Wilson disease (WD) is an autosomal recessive disorder caused by ATP7B gene mutations leading to pathologic accumulation of copper in the liver and brain. Adoption of initial treatments for WD was based on empiric observations. These therapies are effective, but there are still are unmet needs for which new treatment modalities are being developed. Randomized controlled phase 3 studies are lacking for current WD treatments.

APPROACH AND RESULTS: The first Wilson Disease Aarhus Symposium (May 2019) included a workshop on randomized clinical trial (RCT) design. The authors of the paper were organizers or presented during this workshop and this article presents their consensus on the design of clinical trials for WD, addressing trial population, treatment comparators, inclusion and exclusion criteria and treatment endpoints. To achieve adequate recruitment of patients with this rare disorder, the study groups should include all clinical phenotypes and treatment-experienced as well as treatment-naive patients.

CONCLUSIONS: The primary study endpoint should be clinical or a composite endpoint until appropriate surrogate endpoints are validated. Standardization of clinical trials will permit pooling of data and allow for better treatment comparisons, as well as reduce the future numbers of patients needed per trial.

PMID:34320232 | DOI:10.1002/hep.32074

Mov Disord. 2021 Jul 28. doi: 10.1002/mds.28732. Online ahead of print.

ABSTRACT

BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility.

OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach.

METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal.

RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10^-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10^-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10^-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823).

CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.

PMID:34320236 | DOI:10.1002/mds.28732

J Gerontol B Psychol Sci Soc Sci. 2021 Jul 28:gbab141. doi: 10.1093/geronb/gbab141. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine distributional effects of the 2008 recession and subsequent recovery across generational cohorts.

METHODS: Using data from the Survey of Consumer Finances (2007-2016), we constructed a measure of economic well-being accounting for income, household size and annuitized value of assets. We examine trajectories of adjusted income and inequality, using Gini coefficients and income shares by decile, for the overall population and by cohort during the recession and recovery.

RESULTS: Inequality declined temporarily during the recession, but reached new highs during the recovery. During recovery, population-level increases in economic resources were not reflected among below-median households, as the more concentrated financial assets rose while broader-based home equity and employment fell or remained stagnant. Inequality measures increased for cohorts in their primary working years (Generation-X and Baby Boomers), but not among the younger Millennials, who were at early stages of education, workforce entry and household formation.

DISCUSSION: The study illustrates an integrative approach to analyzing cumulative dis/advantage by considering interactions between historically consistent macro-level events, such as economic shocks or policy choices affecting all cohorts, and the persistent life-course processes that tend to increase heterogeneity and inequality as cohorts age over time. Although recovery policies led to rapid recovery of financial asset values, they did not proportionately reach those below the median or their economic resource-types. Results suggest that in a high-inequality environment, recovery policies from economic shocks may need tailoring to all levels of resources in order to achieve more equitable recovery outcomes and prevent exacerbating cohort inequality trajectories.

PMID:34320206 | DOI:10.1093/geronb/gbab141

Neurosurgery. 2021 Jul 28:nyab250. doi: 10.1093/neuros/nyab250. Online ahead of print.

ABSTRACT

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) represent options to treat many patients with carotid stenosis. Although randomized trial data are plentiful, estimated rates of morbidity and mortality for both CEA and CAS have varied substantially.

OBJECTIVE: To evaluate rates of adverse outcomes after CAS and CEA in a large national database.

METHODS: We analyzed 84 191 adult patients undergoing elective, nonemergent CAS (n = 81 361) or CEA (n = 2830), from 2011 to 2018, in the American College of Surgeons’ National Surgical Quality Improvement Program database. Odds of adverse outcomes (30-d rates of stroke, myocardial infarction (MI), cardiac arrest, prolonged length of stay (LOS), readmission, reoperation, and mortality) were evaluated in propensity-matched (n = 2821) cohorts through logistic regression.

RESULTS: In the propensity-matched cohorts, CAS had increased odds of periprocedural stroke (odds ratio [OR] 1.97, 95% CI 1.32-2.95) and decreased odds of cardiac arrest (OR 0.33, 95% CI 0.13-0.84) and 30-d reoperation (OR 0.59, 95% CI 0.44-0.80) compared to CEA. Relative odds of MI, prolonged LOS, discharge to destination other than home, 30-d readmission, or 30-d mortality were statistically similar. In the unmatched patient population, rates of adverse outcomes with CEA were constant over time; however, for CAS, rates of stroke increased over time. In both the matched and unmatched patient cohorts, patients 70 yr and older had lower rates of post-procedural stroke with CEA, but not with CAS, compared to younger patients.

CONCLUSION: In a propensity-matched analysis of a large, prospectively collected, national, surgical database, CAS was associated with increased odds of periprocedural stroke, which increased over time. Rates of MI and death were not significantly different between the 2 procedures.

PMID:34320217 | DOI:10.1093/neuros/nyab250