Tag: statistics

Nat Commun. 2021 Jul 7;12(1):4172. doi: 10.1038/s41467-021-24457-2.

ABSTRACT

Cell-free DNA (cfDNA) is attractive for many applications, including detecting cancer, identifying the tissue of origin, and monitoring. A fundamental task underlying these applications is SNV calling from cfDNA, which is hindered by the very low tumor content. Thus sensitive and accurate detection of low-frequency mutations (<5%) remains challenging for existing SNV callers. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this challenge. Furthermore, by leveraging cfDNA’s comprehensive coverage of tumor clonal landscape, cfSNV can profile mutations in subclones. In both simulated and real patient data, cfSNV outperforms existing tools in sensitivity while maintaining high precision. cfSNV enhances the clinical utilities of cfDNA by improving mutation detection performance in medium-depth sequencing data, therefore making Whole-Exome Sequencing a viable option. As an example, we demonstrate that the tumor mutation profile from cfDNA WES data can provide an effective biomarker to predict immunotherapy outcomes.

PMID:34234141 | DOI:10.1038/s41467-021-24457-2

Nat Commun. 2021 Jul 7;12(1):4192. doi: 10.1038/s41467-021-24485-y.

ABSTRACT

Most existing tools for constructing genetic prediction models begin with the assumption that all genetic variants contribute equally towards the phenotype. However, this represents a suboptimal model for how heritability is distributed across the genome. Therefore, we develop prediction tools that allow the user to specify the heritability model. We compare individual-level data prediction tools using 14 UK Biobank phenotypes; our new tool LDAK-Bolt-Predict outperforms the existing tools Lasso, BLUP, Bolt-LMM and BayesR for all 14 phenotypes. We compare summary statistic prediction tools using 225 UK Biobank phenotypes; our new tool LDAK-BayesR-SS outperforms the existing tools lassosum, sBLUP, LDpred and SBayesR for 223 of the 225 phenotypes. When we improve the heritability model, the proportion of phenotypic variance explained increases by on average 14%, which is equivalent to increasing the sample size by a quarter.

PMID:34234142 | DOI:10.1038/s41467-021-24485-y

Int Heart J. 2021 Jul 6. doi: 10.1536/ihj.20-772. Online ahead of print.

ABSTRACT

Previous studies have indicated that low-dose new generation of P2Y12 receptor antagonists may be more suitable compared with clopidogrel at a standard dose for the dual antiplatelet therapy (DAPT) for East Asian patients receiving percutaneous coronary intervention (PCI). However, there remains no consensus in clinical practice. Thus, in this study, we aimed to determine the efficacy and safety of low-dose P2Y12 receptor antagonists, compared to clopidogrel at a standard dose, in DAPT in East Asian patients after PCI. We systematically searched literatures for randomized controlled trials (RCT) comparing low-dose P2Y12 receptor antagonists with standard-dose clopidogrel for the treatment of East Asian patients undergoing PCI. The endpoints of efficacy include major adverse cardiac events (MACEs), all-cause mortality, and the number of target vessel revascularization. The indicators of safety include major and minor bleeding events. Heterogeneity was evaluated by I² statistic test. Begg’s and Egger’s tests were used to evaluate publication bias. In total, 2,747 subjects from 8 RCT studies were included. Low-dose new P2Y12 receptor antagonists, that is, ticagrelor or prasugrel, showed significantly lower incidence of MACEs, as compared with standard-dose clopidogrel, in the East Asian patients who are in DAPT after undergoing PCI. Further, no difference was noted for the risk of major and minor bleeding events. In East Asian patients undergoing PCI and receiving DAPT, the use of low-dose P2Y12 receptor antagonists, ticagrelor or prasugrel, has been determined to be superior than clopidogrel at standard dose; this has been evidenced by a lower incidence of MACEs without increasing the risk of bleeding.

PMID:34234075 | DOI:10.1536/ihj.20-772

Med Sci Monit. 2021 Jul 8;27:e931597. doi: 10.12659/MSM.931597.

ABSTRACT

BACKGROUND One treatment option for benign prostatic hyperplasia (BPH) is transurethral microwave thermotherapy (TUMT). Unfortunately, TUMT has been increasingly marginalized recently. The aim of this study was to evaluate erectile function and urinary symptoms in patients after TUMT for BPH and compare the results with those of patients on pharmacological treatment for BPH. MATERIAL AND METHODS The study group consisted of 840 patients with BPH treated with TUMT and a control group consisting of 1040 patients who underwent pharmacotherapy. Erectile dysfunction was evaluated using the International Index of Erectile Function-5 questionnaire and the Individual Postoperative Erectile Assessment (IPEA) questionnaire, which was created by the authors for this study. Urinary symptoms were evaluated using the International Prostate Symptom Score (IPSS) questionnaire. RESULTS More than 50% of all patients experienced an improvement in urinary symptoms after TUMT, compared with only approximately 30% in the control group. Differences in each of the IPSS symptom scales between the TUMT and control groups were statistically significant (P<0.031, P<0.041, and P<0.025 for mild, moderate, and severe symptoms, respectively). Improvement in erectile dysfunction after TUMT was also statistically significant (P<0.0001, P<0.0001, P<0.05 for mild, moderate, and severe erectile dysfunction, respectively). Based on the IPEA questionnaire, approximately 24% of the TUMT group reported significant improvement in erectile function, while a decrease in erectile function was reported in the control group. CONCLUSIONS TUMT may still be a valuable option in the treatment of BPH. TUMT may be especially suitable for patients who expect to improve urinary symptoms without decreasing erectile function.

PMID:34234095 | DOI:10.12659/MSM.931597

Dent Mater J. 2021 Jul 7. doi: 10.4012/dmj.2020-427. Online ahead of print.

ABSTRACT

The aim of the study was to investigate the wear of luting materials (Variolink Esthetic LC/DC, Multilink Automix, Panavia V5 paste) compared to a resin composite (Tetric EvoFlow) with an ACTA-machine (three-body-wear simulator) using steel and 3D-printed polymer wheels. Wear was measured (software Match3D) and statistically analyzed (ANOVA). Worn surface was examined with a field-emission-scanning-electron-microscope. Finite element analysis was carried out to analyze differences in the mechanical stress of the two different sample wheels. Using the steel wheel, Variolink Esthetic DC exhibited significantly less wear than Tetric EvoFlow after 200,000 cycles (p=0.037). Luting composites on polymer wheels exhibited significantly lower wear values compared to the steel wheels (p<0.001). Finite element analysis showed higher stresses for the steel wheel compared to the polymer wheel. Mechanical properties of the sample wheels had a high influence on wear properties. Dual- or auto-polymerizing materials seem to have a small advantage over the light-curing materials.

PMID:34234046 | DOI:10.4012/dmj.2020-427

Drug Discov Ther. 2021;15(3):156-161. doi: 10.5582/ddt.2021.01014.

ABSTRACT

A variable proportion of patients develop persistent/prolonged symptoms of Coronavirus Disease 2019 (COVID-19) infection (long COVID). We aimed to study the clinical predictors of persistent symptoms in patients with mild COVID-19 at 30 days post discharge (long COVID-19). We also tried to identify symptom clusters among mild COVID-19 patients. Fifty-seven patients admitted at a tertiary care centre after a positive RT-PCR report over a period of 2 months, were enrolled in the study. Details of presentation, history of illness, laboratory investigations and disease outcomes were recorded from documented medical records and discharge slip. The patients were contacted (telephonically) at 30 days after discharge and enquired regarding persistent symptoms, if any. Follow up data at 30 days post-discharge was available for 53 patients. Among them, the most common persistent symptom was fatigue (22.6%), followed by cough (9.4%) and myalgias (7.5%). There was a significant association of persistent symptoms with diarrhoea at presentation [OR 14.26 (95% CI 2.30-142.47; p = 0.009] and gap between symptom onset and admission [OR 1.40 (95% CI 1.08-1.93; p = 0.020] on multivariate logistic regression analysis. On cluster analysis, three phenotypes of mild COVID-19 were identified, which may have implications on monitoring and management. There appears to be a positive association of diarrhoea as a presenting manifestation and gap between symptom onset and admission with the persistence of symptoms classified as long COVID-19, even in mild illness. We also identified multiple phenotypes of mild COVID-19 illness, which warrant further exploration.

PMID:34234065 | DOI:10.5582/ddt.2021.01014

Drug Discov Ther. 2021;15(3):162-165. doi: 10.5582/ddt.2021.01043.

ABSTRACT

In the present study, to identify the clinical significance of the cytokeratin (CK) 20 staining pattern in Merkel cell carcinoma (MCC), we retrospectively analyzed the major clinicopathological and immunohistochemical characteristics of 12 cases of MCC. Typical dot-like pattern was seen in eight of our patients, while four patients showed peripheral staining pattern. Interestingly, all cases of MCC with dot-like CK20 tumor cells occurred in the head and neck region, while those with peripheral CK20 pattern tended to be located in other lesions (forearm, knee, or buttock): The difference of frequency in the head and neck regions was statistically significant. Dot-like CK20 staining pattern may therefore be resulted from ultraviolet exposure. Additionally, although without significance, metastasis was more frequent in those with dot-like CK20 than in peripheral CK20 staining: All patients with peripheral CK20 pattern had complete remission by surgical excision with or without radiation therapy. CK20 staining pattern may be a novel predictor of prognosis.

PMID:34234066 | DOI:10.5582/ddt.2021.01043

Glob Health Sci Pract. 2021 Jul 1;9(2):220-228. doi: 10.9745/GHSP-D-21-00233. Print 2021 Jun 30.

NO ABSTRACT

PMID:34234020 | DOI:10.9745/GHSP-D-21-00233

Respir Care. 2021 Jul 7:respcare.09191. doi: 10.4187/respcare.09191. Online ahead of print.

ABSTRACT

Background Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubations of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP.Methods: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care.Results: A total of 46 published and 4 unpublished observational studies that included 2994 patients were included, of which 921 patients were managed with APP, and 870 patients were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 patients treated with APP, and 852 patients treated with usual care), the intubation rate was 27%(95%CI, 19 to 37%), as compared to 30%(95%CI, 20 to 42%)(p=0.71), even when duration of application, use of adjunctive respiratory assist device (high flow nasal cannula or non-invasive ventilation) and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when treated with APP was compared with usual care (11% v.s. 22%), which was not statistically significant.Conclusions: APP was associated with improvement of oxygenation but did not reduce the intubation rate in patients with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation and mortality rate in these patients.

PMID:34234032 | DOI:10.4187/respcare.09191

BMJ Open. 2021 Jul 7;11(7):e047920. doi: 10.1136/bmjopen-2020-047920.

ABSTRACT

OBJECTIVES: This study is designed to identify different body mass index (BMI) trajectories of individuals aged 40-70 years and test the effect of distinct BMI trajectories on incident hypertension.

DESIGN: The accelerated longitudinal design was used for this study.

METHODS: The study drew data from the third to ninth China Health and Nutrition Surveys (CHNS), and 4697 participants were included between 1991 and 2015. As analysed, three distinct individual BMI trajectories were identified by the latent class growth mixed model (LCGMM). Then, BMI values and BMI slopes were worked out through calculation with LCGMM trajectory parameters and their primary derivatives, respectively. Later, Cox proportional hazard models were applied to examine BMI values and slopes, and find out the relationship between the said predicted data and incident hypertension for different classes.

RESULTS: Three different trajectory classes were identified, that is, low-stable class (n=3711), sharp-increasing class (n=282) and high-stable class (n=704). Compared with the low-stable class, the adjusted HRs (95% CI) were 1.321 (1.119 to 1.559) and 1.504 (1.322 to 1.711) for the sharp-increasing class and the high-stable class, respectively. The HR (95% CI) for BMI values rose from 1.081 (1.030 to 1.135) to 1.221 (1.171 to 1.273) while the HR (95% CI) for BMI slopes dropped from 1.154 (1.100 to 1.211) to 0.983 (0.943 to 1.025). That is, the HR for BMI slopes were higher than that for BMI values for the class aged 40-47 years.

CONCLUSION: These findings suggest that the calibrated BMI trajectories for the period from mid-life to elderly adulthood have a significant effect on the risk of incident hypertension. The period from age 40 to 47 years is critical and has positive implications for the early prevention of hypertension.

PMID:34233991 | DOI:10.1136/bmjopen-2020-047920