Category: Statistics

Asia Pac J Clin Oncol. 2022 Apr 8. doi: 10.1111/ajco.13668. Online ahead of print.

ABSTRACT

BACKGROUND: Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients.

METHODS: Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of <0.05 was considered statistically significant.

RESULTS: A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p < 0.001), smoking (p = 0.003), more comorbidity (p = 0.014), kidney disease (p = 0.016), and lower baseline creatinine clearance (p < 0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p < 0.001). Patients who received carboplatin were associated with delay (p = 0.049) and hospitalization (p = 0.006), whereas cisplatin CCRT had more dose reduction (p = 0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p = 0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p < 0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p = 0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis.

CONCLUSIONS: Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.

PMID:35394108 | DOI:10.1111/ajco.13668

J Dermatol. 2022 Apr 8. doi: 10.1111/1346-8138.16384. Online ahead of print.

ABSTRACT

In 2020, 5% sofpironium bromide (ECCLOCK^® ) gel (hereinafter referred to as sofpironium) was approved in Japan for the topical treatment of primary axillary hyperhidrosis. A phase III study of sofpironium demonstrated the efficacy and safety of sofpironium; however, no study has assessed its early efficacy at <6 weeks after starting treatment. Therefore, to assess the earlier effectiveness of sofpironium, we conducted a 2-week, single-center, exploratory, prospective, observational study in Japanese patients with primary axillary hyperhidrosis. Patients aged ≥20 years and satisfying with a Hyperhidrosis Disease Severity Scale (HDSS) score of 3 or 4 at baseline were eligible for the study. The primary endpoint for the effectiveness was change in the proportion of patients with a HDSS score of 1, 2, 3, or 4 during the 2-week study period. In 80 patients included in the full analysis set (FAS), there were more women than men (93.8% vs. 6.3%), and the mean age (±standard deviation [SD]) was 33.3 ± 9.4 years. In the FAS, the proportion of patients with a HDSS score of 1 or 2 was 55.0% on day 7, and statistically significant changes were observed after day 3 compared to baseline (p < 0.05). Mean HDSS scores (±SD) were significantly decreased from baseline value of 3.5 ± 0.5 to 2.4 ± 0.9 on day 7 (p < 0.001). The median period for sofpironium treatment to achieve a HDSS score of 1 or 2 for a continuous 2 days was 6 days (95% confidence interval, 4-8). Safety was evaluated in 92 patients in the safety analysis set, and no adverse events were reported during the study period of 2 weeks. These results suggest that after 1-week treatment with sofpironium for patients with a HDSS score of 3 or 4, approximately 50% of the patients can achieve a HDSS score of 1 or 2, which is a clinically significant improvement for the patients.

PMID:35394087 | DOI:10.1111/1346-8138.16384

Vet Surg. 2022 Apr 8. doi: 10.1111/vsu.13814. Online ahead of print.

ABSTRACT

OBJECTIVE: Determine compression generated by lag and neutral screws over 12 h using two bone analogs.

STUDY DESIGN: Experimental study.

SAMPLE POPULATION: Bone analogs were made of composite synthetic bone (CSB) or three-dimensional printed polylactic acid (PLA). Analogs had a 2 mm exterior shell with a 10 mm thick internal layer of open-cell material.

METHODS: Bone analogs were opposed, making a 4-sided box with open ends. A central channel contained the sensor and the screws passed through it to engage both paired analogs. Four screw/analog conditions were tested: neutral and lag screw with bicortical engagement, neutral and lag screw with unicortical engagement. All screws were tightened to 2 Nm torque and compression values recorded at 0, 0.5, 1, 2, 6, and 12 h (six trials per condition). Medians were compared across groups for statistical significance.

RESULTS: There was no difference in median compression between lag and neutral bicortical screws. For PLA, greater median compression was generated by neutral (median 437 N) and lag (median 379 N) bicortical screws compared to neutral unicortical screws (median 208 N, p < .001); lag bicortical screws generated greater median compression than lag unicortical screws (median 265 N, p = .012). For CSB, lag bicortical screws (median 293 N) generated greater median compression than neutral unicortical screws (median 228 N, p = .008).

CONCLUSION: Lag and neutral screws generated similar compression. Bicortical screws had higher median compression than unicortical screws in bone analogs.

CLINICAL SIGNIFICANCE: Neutral screws generate compression in cancellous bone analogs that can be increased with bicortical bone engagement.

PMID:35394080 | DOI:10.1111/vsu.13814

Med Phys. 2022 Apr 8. doi: 10.1002/mp.15647. Online ahead of print.

ABSTRACT

PURPOSE: This study explored the feasibility of reducing the scan time of Patlak parametric imaging on the uEXPLORER.

METHODS: A total of 65 patients (27 females and 38 males, age 56.1±10.4) were recruited in this study. ¹⁸ F-FDG was injected and its dose was adjusted by body weight (4.07 MBq / kg).Total-body dynamic scanning was performed on the uEXPLORER Total-Body PET/CT scanner with a total scan time of 60 minutes from the injection. The image derived input function (IDIF) was obtained from the aortic arch. The voxelwise Patlak analysis was applied to generate the K_i images designated as G_IDIF with different acquisition times (20-60, 30-60, 40-60, and 44-60 min). The population-based input function (PBIF) was constructed from the mean value of the IDIF from the population, and K_i images designated as G_PBIF were generated using the PBIF. Non-localmeans (NLM) denoising was applied to the generated images to get two extra groups of (NLM-designated) images: G_IDIF+NLM and G_PBIF+NLM . Two radiologists evaluated the overall image quality, noise, and lesion detectability of the K_i images from different groups. The 20-60 min scans in G_IDIF were selected as the gold standard for each patient. We determined that image quality is at sufficient level if all the lesions can be recognized and meet the clinical criteria. K_i values in muscle and lesion were compared across different groups to evaluate the quantitative accuracy.

RESULTS: The overall image quality, image noise, and lesion conspicuity were significantly better in long time series than short time series in all 4 groups (all p<0.001). The K_i images in the G_IDIF and G_PBIF groups generated from 30-min scans showed diagnostic value equivalent to the 40-min scans of G_IDIF . While the image quality of the 16-min scans was poor, all lesions could still be detected. No significant difference was found between K_i values estimated with G_IDIF and G_PBIF in muscle and lesion regions (all p>0.5). After applying the NLM filter, The coefficient of variation could be reduced on the order of [1%, 15%, 19%,37%] and [110%, 125%, 94%, 69%] with four acquisition time schemes for lesion and muscle. The reduction percentage did not have a substantial difference in IDIF and PBIF group. The K_i images in the G_IDIF+NLM and G_PBIF+NLM groups generated from the 20-min acquisitions showed acceptable quality. All lesions could be found on the NLM processed images of the 16-min scans. No significant difference was found between K_i values produced with G_IDIF+NLM and G_PBIF+NLM in muscle and lesion regions(all p>0.7).

CONCLUSIONS: The K_i images generated by the PBIF-based Patlak model using a 20-min dynamic scan with the NLM filter achieved a similar diagnostic efficiency to images with G_IDIF from 40-min dynamic data, and there is no significant difference between K_i images generated using IDIF or PBIF (p>0.5). This article is protected by copyright. All rights reserved.

PMID:35394071 | DOI:10.1002/mp.15647

East Mediterr Health J. 2022 Mar 29;28(3):204-212. doi: 10.26719/emhj.22.007.

ABSTRACT

BACKGROUND: The main social contradictions in China have changed: the core concept is high quality development. Health care investment improves the health of residents and promotes regional economic growth.

AIMS: To analyse the direct and indirect economic effects of health expenditure during 2012-2018 and to test whether China’s investment in health care meets the requirements for high quality development.

METHOD: We selected spatial panel data reflecting the input and output of health resources. We used the knowledge production function and a model of spatial economics to conduct empirical analysis of 31 provinces to show the effects of health expenditure on economic growth.

RESULTS: Economic development (LnGDP) was the dependent variable; explanatory variables included health financial input (LnHI), health personnel input (LnHR), health assets (LnCW) and health insurance expenditure (LnHIE). The regression coefficients for indirect, direct and total effects of LnHI were 0.4346, 0.0623 and 0.4970 respectively (all statistically significant). The direct effect coefficient of LnHR (0.3343) was statistically significant. The regression coefficients for the indirect and total effects were -0.6779 and -0.3436, respectively. The direct, indirect and total effect regression coefficients for LnCW and LnHIE were all statistically significant.

CONCLUSION: Both LnHI and LnHIE positively promote economic growth within provinces and in neighbouring provinces, i.e. there are direct and indirect positive effects from investing in health care. Increasing the input of health care personnel can promote the economic growth of a province but not that of neighbouring provinces. Overall planning and coordinated development will facilitate high quality development and economic advancement.

PMID:35394052 | DOI:10.26719/emhj.22.007

Biometrics. 2022 Apr 8. doi: 10.1111/biom.13670. Online ahead of print.

ABSTRACT

Gene-environment (G×E) interactions have important implications to elucidate the etiology of complex diseases beyond the main genetic and environmental effects. Outliers and data contamination in disease phenotypes of G×E studies have been commonly encountered, leading to the development of a broad spectrum of robust regularization methods. Nevertheless, within the Bayesian framework, the issue has not been taken care of in existing studies. We develop a fully Bayesian robust variable selection method for G×E interaction studies. The proposed Bayesian method can effectively accommodate heavy-tailed errors and outliers in the response variable while conducting variable selection by accounting for structural sparsity. In particular, for the robust sparse group selection, the spike-and-slab priors have been imposed on both individual and group levels to identify important main and interaction effects robustly. An efficient Gibbs sampler has been developed to facilitate fast computation. Extensive simulation studies, analysis of diabetes data with SNP measurements from the Nurses’ Health Study and TCGA melanoma data with gene expression measurements demonstrate the superior performance of the proposed method over multiple competing alternatives. This article is protected by copyright. All rights reserved.

PMID:35394058 | DOI:10.1111/biom.13670

Med Mycol. 2022 Apr 8:myac026. doi: 10.1093/mmy/myac026. Online ahead of print.

ABSTRACT

COVID-19 associated pulmonary aspergillosis (CAPA) incidence varies depending on the country. Serum galactomannan quantification is a promising diagnostic tool since samples are easy to obtain with low biosafety issues. A multicenter prospective study was performed to evaluate the CAPA incidence in Argentina and to assess the performance of the lateral flow assay with digital readout (Sōna Aspergillus LFA) as a CAPA diagnostic and screening tool. The correlation between the values obtained with Sōna Aspergillus LFA and Platelia® EIA was evaluated. In total, 578 serum samples were obtained from 185 critically ill COVID patients. CAPA screening was done weekly starting from the first week of ICU stay. Probable CAPA incidence in critically ill patients was 10.27% (19/185 patients when LFA was used as mycological criteria) and 9% (9/100 patients when EIA was used as mycological criteria). We found a very good correlation between the two evaluated galactomannan quantification methods (overall agreement of 92.16% with a Kappa statistic value of 0.721). CAPA diagnosis (>0.5 readouts in LFA) were done during the first week of ICU stay in 94.7% of the probable CAPA patients. The overall mortality was 36.21%. CAPA patients’ mortality and length of ICU stay were not statistically different from for COVID (non-CAPA) patients (42.11% vs 33.13% and 29 vs 24 days, respectively). These indicators were lower than in other reports. LFA-IMMY with digital readout is a reliable tool for early diagnosis of CAPA using serum samples in critically ill COVID patients. It has a good agreement with Platelia® EIA.

PMID:35394043 | DOI:10.1093/mmy/myac026

Int Health. 2022 Apr 8:ihac015. doi: 10.1093/inthealth/ihac015. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational trophoblastic diseases (GTDs) may follow any form of pregnancy or a pregnancy loss. Early detection of GTDs is important, as some benign forms of the disease may progress into a chemoresistant and metastatic disease. This study aimed at determining the frequency of GTDs among women experiencing first trimester pregnancy loss and the associated patients’ characteristics.

METHODS: This was a cross-sectional study that included 200 conveniently sampled women who experienced first trimester pregnancy loss from January to December 2019 at a Regional Referral Hospital in central Tanzania. The specimen obtained from products of conception were collected, formalin-fixed and paraffin-embedded and submitted for histopathological evaluation, for which haematoxylin and eosin stain was used. Data were analysed using SPSS version 23.0. The χ2 test was used to determine the association between categorical variables. p-Values ˂0.05 were considered statistically significant.

RESULTS: Among 200 study participants, the overall frequency of GTDs was 42 (21%). Among those with GTDs, the most common histopathological diagnosis was partial hydatidiform mole (18 [42.9%]), followed by complete hydatidiform mole (17 [40.5%]) and choriocarcinoma (7 [16.5%]). In the studied participants, only increased human chorionic gonadotropin hormone levels were found to be statistically significantly associated with GTDs (p=0.000).

CONCLUSIONS: Results from this study suggest that routine histopathological evaluation of the products of conception is recommended in order to allow early detection of GTDs, including choriocarcinoma, which usually carries a poor prognosis. The histopathological reporting of choriocarcinoma among first trimester products of conception from Tanzania is novel.

PMID:35394041 | DOI:10.1093/inthealth/ihac015

Rheumatology (Oxford). 2022 Apr 8:keac219. doi: 10.1093/rheumatology/keac219. Online ahead of print.

ABSTRACT

OBJECTIVES: This follow-up study of the INSTinCTS (INjection vs SplinTing in Carpal Tunnel Syndrome) trial compared the effects of corticosteroid injection (CSI) and night splinting (NS) for the initial management of mild-to-moderate carpal tunnel syndrome (CTS) on symptoms, resource use, and carpal tunnel surgery, over 24 months.

METHODS: Adults with mild-to-moderate CTS were randomised 1:1 to a local corticosteroid injection or a night splint worn for 6 weeks. Outcomes at 12 and 24 months included the Boston Carpal Tunnel Questionnaire (BCTQ), hand/wrist pain intensity numeric rating scale (NRS), the number of patients referred for and undergoing CTS surgery, and healthcare utilisation. A cost-utility analysis was conducted.

RESULTS: 116 participants received a CSI and 118 a NS. The response rate at 24 months was 73% in the CSI arm and 71% in the NS arm. By 24 months, a greater proportion of the CSI group had been referred for (28% vs 20%) and undergone (22% vs 16%) CTS surgery compared with the NS group. There were no statistically significant between-group differences in BCTQ score or pain NRS at 12 or 24 months. CSI was more costly (mean difference £68o59 (95% CI: -120·84, 291·24)) with fewer quality-adjusted life-years (QALYs) than NS over 24 months (mean difference -0·022 (95% CI: (-0·093, 0·045)).

CONCLUSION: Over 24 months, surgical intervention rates were low in both groups, but less frequent in the NS group. Whilst there were no differences in the clinical effectiveness of CSI and NS, initial treatment with CSI may not be cost-effective in the long-term compared with NS.

PMID:35394019 | DOI:10.1093/rheumatology/keac219

Bioinformatics. 2022 Apr 8:btac199. doi: 10.1093/bioinformatics/btac199. Online ahead of print.

ABSTRACT

MOTIVATION: Single cell technologies play a crucial role in revolutionizing biological research over the past decade, which strengthens our understanding in cell differentiation, development, and regulation from a single-cell level perspective. Single-cell RNA sequencing (scRNA-seq) is one of the most common single cell technologies, which enables probing transcriptional states in thousands of cells in one experiment. Identification of cell types from scRNA-seq measurements is a fundamental and crucial question to answer. Most previous studies directly take gene expression as input while ignoring the comprehensive gene-gene interactions.

RESULTS: We propose scGraph, an automatic cell identification algorithm leveraging gene interaction relationships to enhance the performance of the cell type identification. ScGraph is based on a graph neural network to aggregate the information of interacting genes. In a series of experiments, we demonstrate that scGraph is accurate and outperforms eight comparison methods in the task of cell type identification. Moreover, scGraph automatically learns the gene interaction relationships from biological data and the pathway enrichment analysis shows consistent findings with previous analysis, providing insights on the analysis of regulatory mechanism.

AVAILABILITY: scGraph is freely available at https://github.com/QijinYin/scGraph and https://figshare.com/articles/software/scGraph/17157743.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35394015 | DOI:10.1093/bioinformatics/btac199