Category: Statistics

Nucleic Acids Res. 2022 Jan 21:gkac019. doi: 10.1093/nar/gkac019. Online ahead of print.

ABSTRACT

The application of single-cell RNA sequencing (scRNAseq) for the evaluation of chemicals, drugs, and food contaminants presents the opportunity to consider cellular heterogeneity in pharmacological and toxicological responses. Current differential gene expression analysis (DGEA) methods focus primarily on two group comparisons, not multi-group dose-response study designs used in safety assessments. To benchmark DGEA methods for dose-response scRNAseq experiments, we proposed a multiplicity corrected Bayesian testing approach and compare it against 8 other methods including two frequentist fit-for-purpose tests using simulated and experimental data. Our Bayesian test method outperformed all other tests for a broad range of accuracy metrics including control of false positive error rates. Most notable, the fit-for-purpose and standard multiple group DGEA methods were superior to the two group scRNAseq methods for dose-response study designs. Collectively, our benchmarking of DGEA methods demonstrates the importance in considering study design when determining the most appropriate test methods.

PMID:35061903 | DOI:10.1093/nar/gkac019

PLoS One. 2022 Jan 21;17(1):e0262866. doi: 10.1371/journal.pone.0262866. eCollection 2022.

ABSTRACT

Pectus excavatum (PE) is one of the most frequently reported chest deformities. However, limited studies are available with regard to its CT scan findings in cats. In the present research computed tomographic images of the thoraxes of 14 cats diagnosed with PE has been reviewed. This is one of the first studies exploring the use of CT to characterise PE in animals. The aim of this study was to present characteristic CT features of PE in cats. The introduction of new criteria for better assessing thoracic wall deformity-a correction index (CI) and an asymmetry index (AI)-was also proposed. The study revealed a high variety of morphological features of PE in cats. It was demonstrated that among the 14 cats: cranial PE (an atypical location) occurred in seven cats while seven cats had typical (caudal) PE, long PE occurred in five cats, while short PE had nine cats. Of the 14 cats included in the study eight showed symmetric PE, and asymmetric PE was found insix. Thoracic asymmetry was found in six cats. Six cats had sternal torsion. Based on the Vertebral Index moderate or severe PE was revealed in 11 animals. In the group of cats studied the CI ranged from 12.20 to 32.11. The magnitude of AI did not exceed 10% in any of the cats studied. The study confirmed statistically significant differences in the CI values between groups of cats with different degrees of PE severity (p = 0.02). CT examination showed many PE features that have not been discussed so far. The main benefit of CT examination is its ability to reveal asymmetric PE, thoracic asymmetry and sternal torsion. CI and AI provided a clinically useful tool to quantify thoracic wall deformity in order to obtain comparable results between cats with PE.

PMID:35061860 | DOI:10.1371/journal.pone.0262866

Eur J Cardiovasc Nurs. 2022 Jan 21:zvab131. doi: 10.1093/eurjcn/zvab131. Online ahead of print.

ABSTRACT

BACKGROUND: Internet-based cognitive behavioural treatment (iCBT) has shown positive short-term effects on depression in patients with cardiovascular disease (CVD). However, knowledge regarding long-term effects and factors that may impact the effect of iCBT is lacking.

AIMS: This study therefore sought (i) to evaluate the effect of iCBT on depression in CVD patients at 6- and 12-month follow-ups and (ii) to explore factors that might impact on the effect of iCBT on change in depression at 12-month follow-up.

METHODS AND RESULTS: A longitudinal follow-up study of a randomized controlled trial evaluating the effects of a 9-week iCBT programme compared to an online discussion forum (ODF) on depression in CVD patients (n = 144). After 9 weeks, those in the ODF group were offered the chance to take part in the iCBT programme. The Patient Health Questionnaire (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale-self-rated version (MADRS-S) measured depression at baseline, 9 weeks, 6 months, and 12 months. Linear mixed model and multiple regression analysis were used for statistical computing. The iCBT programme significantly improved depression at 9-week follow-up and this was stable at 6- and 12-month follow-ups (PHQ-9 P = 0.001, MADRS-S P = 0.001). Higher levels of depression at baseline and a diagnosis of heart failure were factors found to impact the effect of iCBT on the change in depression.

CONCLUSION: A 9-week iCBT programme in CVD patients led to long-term improvement in depression. Higher levels of depression scores at baseline were associated with improvement in depression, whereas heart failure had opposite effect.

CLINICAL TRIAL: The trial is registered at ClinicalTrials.gov, NCT02778074.

PMID:35061868 | DOI:10.1093/eurjcn/zvab131

PLoS One. 2022 Jan 21;17(1):e0262827. doi: 10.1371/journal.pone.0262827. eCollection 2022.

ABSTRACT

INTRODUCTION: The potential role of medical students in raising awareness during public health emergencies has been acknowledged. To further explore their potentials as public educators and role models for the communities during the coronavirus disease 2019 (COVID-19) pandemic, this study aims to assess the knowledge, attitude, and practice of these students toward COVID-19.

METHODS: An online cross-sectional survey was conducted among undergraduate medical students in Indonesia. Socio-demographics characteristics, social interaction history, information-seeking behavior, as well as knowledge, attitude, and practice toward COVID-19 were collected through a self-reported questionnaire. A p-value of <0.05 indicated statistical significance.

RESULTS: Out of 4870 respondents, 64.9% had positive attitude and 51.5% had positive practice toward COVID-19, while only 29.8% had adequate knowledge. Knowledge was slightly positively correlated with attitude and practice (ρ = 0.074 and ρ = 0.054, respectively; both p<0.001), while attitude was weakly correlated with practice (ρ = 0.234, p<0.001). Several factors including age, sex, place of residence, institution type, academic level, family income, history of chronic illness, prior volunteering experience, and perceptual awareness on COVID-19 were significantly associated with either knowledge, attitude, and/or practice toward COVID-19. Furthermore, health institution’s and the government’s press releases, as well as health expert opinions were deemed as the most reliable sources of COVID-19-related information-yet trivially none of these sources were associated with knowledge, attitude, and practice in the study population.

CONCLUSION: Many undergraduate medical students in Indonesia had positive attitude and practice against COVID-19, yet only a few had adequate knowledge. This warrants further interventions to keep them updated with COVID-19 evidence to maximize their potentials in raising public awareness on COVID-19.

PMID:35061848 | DOI:10.1371/journal.pone.0262827

PLoS One. 2022 Jan 21;17(1):e0262928. doi: 10.1371/journal.pone.0262928. eCollection 2022.

ABSTRACT

A wealth of research suggests that sexual minority individuals experience stigma and lack of sexual minority specific competencies in mental health care, which could lead to less optimal treatment outcome. However, most related research suffers from methodological limitations, such as selected samples, retrospective design, or not assessing treatment outcome. To overcome some of these limitations, we explored if sexual minority patients have poorer treatment outcome and are less satisfied with treatment in a mental health care setting not specialized in sexual minority issues. The analytical sample comprised 5609 inpatients, including 11% sexual minority patients, from a German psychiatric clinic. Outcomes were improvement in well-being and depression from admission to discharge, and satisfaction with treatment judged at discharge. Nearly all sexual orientation differences were in a direction hinting at less improvement of depression and well-being and less satisfaction among sexual minority compared to heterosexual patients. However, the differences were generally small and not statistically significant. Stigma and lacking sexual orientation specific competency in healthcare may not be universally present or not as severe as studies with other research designs suggested. However, this needs to be investigated in more clinical settings by including sexual orientation as part of the routine assessment. Moreover, adequate sexual-minority specific competencies are important in any case, not just to prevent that sexual minority patients benefit less from treatment.

PMID:35061835 | DOI:10.1371/journal.pone.0262928

PLoS One. 2022 Jan 21;17(1):e0262822. doi: 10.1371/journal.pone.0262822. eCollection 2022.

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cancer type in China. Targeted therapies have been used to treat NSCLC for two decades, which is only suitable for a subgroup of patients with specific genetic variations. The aim of this study was to investigate the prevalence of genetic variations leading to sensitivity or resistance to targeted therapies in NSCLC, and their relationship with clinicopathological characteristics of the patients.

METHODS: Tumor samples were collected from 404 patients who were diagnosed to have NSCLC and underwent surgery, transthoracic biopsy, bronchoscopy biopsy, or pleural aspiration in Sichuan Provincial People’s Hospital from January 2019 to March 2020. Commercial amplification-refractory mutation system kits were used to detect targeted therapy-related genetic variations in those tumor samples. The prevalence of genetic variations and their relationship with patient clinicopathological characteristics were analyzed using statistical software, followed by subgroup analysis.

RESULTS: In all, 50.7% of the NSCLC patients had sensitive genetic variations to anti-EGFR therapies, and 4.9% of those patients had co-existing resistant genetic variations. Fusions in ALK, ROS1, or RET were found in 7.7% of the patients, including 2 patients with co-existing EGFR exon 19 deletion or L858R. EGFR exon 19 deletion and L858R were more common in female patients and adenocarcinoma. Further subgroup analysis confirmed the observation in female patients in adenocarcinoma subgroup, and in adenocarcinoma in male patients. In addition, smokers were more likely to have squamous cell carcinoma and KRAS mutation and less likely to have EGFR L858R, which were also confirmed after standardization of gender except KRAS mutations.

CONCLUSION: Nearly half of the NSCLC patients were eligible for anti-EGFR treatments. In NSCLC, female gender and adenocarcinoma may indicate higher chance of EGFR exon 19 deletion or L858R, and smoking history may indicate squamous cell carcinoma and EGFR L858R.

PMID:35061839 | DOI:10.1371/journal.pone.0262822

PLoS One. 2022 Jan 21;17(1):e0262715. doi: 10.1371/journal.pone.0262715. eCollection 2022.

ABSTRACT

BACKGROUND: Asthma and nonalcoholic fatty liver disease (NAFLD) are chronic diseases known to be associated with metabolic abnormalities. We aimed to clarify the association between NAFLD and asthma incidence in a large population-based cohort.

METHODS AND FINDINGS: We selected 160,603 individuals without comorbidities from the National Health Insurance Service-National Sample cohort between 2009 and 2014. NAFLD was defined using a surrogate marker, fatty liver index (FLI). During a median of 5.08 years’ follow-up, 16,377 subjects (10.2%) were newly diagnosed with asthma and categorized into three groups according to FLI. The cumulative incidence of asthma was higher in subjects with higher vs. lower FLIs (FLI < 30, 10.1%; 30 ≤ FLI < 60, 10.8%; FLI ≥ 60, 10.5%). Higher FLI was associated with an increased incidence of asthma (Hazard ratios (HR)highest vs. lowest FLI, 1.25; 95% CI, 1.15-1.36). The results using another definition of NAFLD, as measured by the hepatic steatosis index (HSI), were similar to the primary results. This association was more pronounced in women than in men (HR 1.46; 95% CI, 1.13-1.64 vs. HR 1.07; 95% CI, 0.94-1.20).

CONCLUSIONS: This study demonstrated that NAFLD, as measured by FLI and HSI, may influence the incidence rates of asthma in adults, especially in women.

PMID:35061826 | DOI:10.1371/journal.pone.0262715

PLoS One. 2022 Jan 21;17(1):e0262636. doi: 10.1371/journal.pone.0262636. eCollection 2022.

ABSTRACT

OBJECTIVES: Occupation is a poorly characterised risk factor for cardiovascular disease (CVD) with females and indigenous populations under-represented in most research. This study assessed associations between occupation and ischaemic heart disease (IHD) in males and females of the general and Māori (indigenous people of NZ) populations of New Zealand (NZ).

METHODS: Two surveys of the NZ adult population (NZ Workforce Survey (NZWS); 2004-2006; n = 3003) and of the Māori population (NZWS Māori; 2009-2010; n = 2107) with detailed occupational histories were linked with routinely collected health data and followed-up until December 2018. Cox regression was used to calculate hazard ratios (HR) for IHD and “ever-worked” in any of the nine major occupational groups or 17 industries. Analyses were controlled for age, deprivation and smoking, and stratified by sex and survey.

RESULTS: ‘Plant/machine operators and assemblers’ and ‘elementary occupations’ were positively associated with IHD in female Māori (HR 2.2, 95%CI 1.2-4.1 and HR 2.0, 1.1-3.8, respectively) and among NZWS males who had been employed as ‘plant/machine operators and assemblers’ for 10+ years (HR 1.7, 1.2-2.8). Working in the ‘manufacturing’ industry was also associated with IHD in NZWS females (HR 1.9, 1.1-3.7), whilst inverse associations were observed for ‘technicians and associate professionals’ (HR 0.5, 0.3-0.8) in NZWS males. For ‘clerks’, a positive association was found for NZWS males (HR 1.8, 1.2-2.7), whilst an inverse association was observed for Māori females (HR 0.4, 0.2-0.8).

CONCLUSION: Associations with IHD differed significantly across occupational groups and were not consistent across males and females or for Māori and the general population, even within the same occupational groups, suggesting that current knowledge regarding the association between occupation and IHD may not be generalisable across different population groups.

PMID:35061833 | DOI:10.1371/journal.pone.0262636

PLoS One. 2022 Jan 21;17(1):e0262733. doi: 10.1371/journal.pone.0262733. eCollection 2022.

ABSTRACT

This study aims at establishing specimens pooling approach for the detection of SARS-CoV-2 using the RT-PCR BGI and Sansure-Biotech kits used in Gabon. To validate this approach, 14 positive samples, stored at -20°C for three to five weeks were analyzed individually (as gold standard) and in pools of five, eight and ten in the same plate. We created 14 pools of 5, 8 and 10 samples using 40 μL from each of the selected positive samples mixed with 4, 7 and 9 confirmed negative counterparts in a total volume of 200 μL, 320 μL and 400 μL for the pools of 5, 8 and 10 respectively. Both individual and pooled samples testing was conducted according to the BGI and Sansure-Biotech RT-PCR protocols used at the Professor Daniel Gahouma Laboratory (PDGL). Furthermore, the pooling method was also tested by comparing results of 470 unselected samples tested in 94 pools and individually. Results of our experiment showed that using a BGI single positive sample with cycle threshold (Ct) value of 28.42, confirmed by individual testing, detection occurred in all the pools. On the contrary samples with Ct >31 were not detected in pools of 10 and for these samples (Ct value as high as 37.17) their detection was possible in pool of 8. Regarding the Sansure-Biotech kit, positive samples were detected in all the pool sizes tested, irrespective of their Ct values. The specificity of the pooling method was 100% for the BGI and Sansure-Biotech RT-PCR assays. The present study found an increase in the Ct values with pool size for the BGI and Sansure-Biotech assays. This trend was statistically significant (Pearson’s r = 0.978; p = 0,022) using the BGI method where the mean Ct values were 24.04±1.1, 26.74±1.3, 27.91±1.1 and 28.32±1.1 for the individual, pool of 5, 8 and 10 respectively. The testing of the 470 samples showed that one of the 94 pools had a positive test similar to the individual test using the BGI and Sansure-Biotech kits. The saving of time and economizing test reagents by using the pooling method were demonstrated in this study. Ultimately, the pooling method could be used for the diagnosis of SARS-CoV-2 without modifying the accuracy of results in Gabon. We recommend a maximum pool size of 8 for the BGI kit. For the Sansure-Biotech kit, a maximum pool size of 10 can be used without affecting its accuracy compared to the individual testing.

PMID:35061822 | DOI:10.1371/journal.pone.0262733

PLoS One. 2022 Jan 21;17(1):e0262601. doi: 10.1371/journal.pone.0262601. eCollection 2022.

ABSTRACT

BACKGROUND: Chronic pain is a common condition which causes patients much suffering and is very costly to society. Factors known to be associated with chronic pain include female gender, acute pain, depression, and anxiety. This study investigated whether stress, sleep disturbance, and physical inactivity were risk factors for developing chronic pain among young adults, and whether there were any interactions between these.

METHODS: This retrospective longitudinal study was based on an existing database from a cohort study on IT use and health, called Health 24 Years. A questionnaire was sent to students aged 19-24 in Sweden for five consecutive years, containing questions on pain, stress, sleep, physical activity, technology use, health, and more. In logistic regressions, stress, sleep, and physical activity at baseline were potential predictors of chronic pain one and four years later. In addition, a new variable including all possible interactions between potential predictors was created to test for effect modification between risk factors.

RESULTS: At the one-year follow-up, stress, non-restorative sleep, and physical inactivity showed odds ratios of 1.6 (95% CI: 1.0-2.4), 1.5 (95% CI: 1.0-2.3), and 1.8 (95% CI: 1.1-3.0) respectively after adjusting for confounders, the reference being non-stressed, having restorative sleep and being active. At the four-year follow-up, stress showed an adjusted odds ratio of 1.9 (95% CI: 1.3-2.9), while non-restorative sleep and physical inactivity were statistically insignificant. At the one-year follow-up, the interaction between risk factors were significant. The most clear example of this effect modification was to be inactive and not have -restorative sleep, compared to individuals who were active and had restorative sleep, showing an adjusted odds ratio of 6.9 (95% CI: 2.5-19.2) for developing chronic pain one year after baseline. This in comparison of odds ratios for only inactive respectively only non-restorative sleep being 1.7 (95% CI: 0.6-5.3) respectively 1.6 (95% CI: 0.7-3.5).

CONCLUSIONS: Stress, non-restorative sleep, and physical inactivity were risk factors for developing chronic pain one year after baseline, and stress were also a risk factor four years after baseline. These findings suggest that non-restorative sleep and inactivity are risk factors in the short term while stress is a risk factor in both the short and the long term. In addition to the independent effects of non-restorative sleep and inactivity, their combination seems to further increase the odds of chronic pain.

PMID:35061825 | DOI:10.1371/journal.pone.0262601