Category: Statistics

J Gastrointestin Liver Dis. 2021 Dec 21;30(4):446-455. doi: 10.15403/jgld-3681.

ABSTRACT

BACKGROUND AND AIMS: Colorectal adenomas are precursor lesions for colorectal cancer (CRC), a major cause of cancer-related death. Despite all molecular insights, there are still unknown variables in the development of CRC as well as uncertainties regarding adenoma recurrence after resection. We aimed to characterize the expression of docking protein 1 (DOK1) and myotubularin-related protein 7 (MTMR7), which share inhibiting functions on EGFR-RAS-signalling, a major oncogenic driver in CRC, and their association with clinical variables and adenoma recurrence.

METHODS: This observational study is based on clinical data obtained from patients who underwent routine endoscopy and consecutive follow-up examinations. Immunohistochemistry was conducted both in dysplastic tissue and adjacent non-dysplastic mucosa followed by microscopical assessment. Recurrence was differentiated between local, segmental and distant relapse.

RESULTS: A total of 56 patients (23 females) gathering 96 adenomas/polyps were included. 36 patients experienced a metachronous lesion, 23 patients had simultaneous lesions in their index endoscopy. Female patients showed lower levels of MTMR7 in adenomas (p=0.0318). Adenomas of young patients showed lower DOK1 than those of older patients (p=0.0469). Big adenomas showed a higher expression of DOK1 than small lesions (p=0.0044). In serrated lesions, DOK1 was reduced (p=0.0026) and correlated with the quantity of lesions (p < 0.001). MTMR7 was significantly reduced in distant (p=0.05) and local segmental recurrence (p=0.0362), while DOK1 showed higher expression in recurrence (p=0.0291).

CONCLUSIONS: We found ambivalent results regarding the role of the markers as potential tumor suppressors, implying a context-dependent function of these molecules which might change in the course of time. DOK1 may play an inhibiting role in the serrated pathway. Remarkably, molecular markers have the potential to predict recurrence, since a combined expression analysis of high DOK1 and low MTMR7 correlated with the likelihood of segmental adenoma recurrence.

PMID:34941983 | DOI:10.15403/jgld-3681

PLoS One. 2021 Dec 23;16(12):e0261575. doi: 10.1371/journal.pone.0261575. eCollection 2021.

ABSTRACT

BACKGROUND: Local relapse of oral squamous cell carcinoma in non-involved mucosal surgical margins indicated possibility of field alteration in the margins, which could be predicted with certain biomarkers. The objectives were to evaluate the expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins and the association of clinicopathological prognosticators with local relapse in oral squamous cell carcinoma.

METHODS: Surgical margins from the study (relapse) group (n = 23), control (non-relapse) group (n = 32) and normal oral mucosa (n = 5) were immunohistochemically stained using Ki-67, Cornulin and ISG15 antibodies. Association between expression of markers and clinicopathological prognosticators with local relapse in oral squamous cell carcinoma was analyzed statistically.

RESULTS: The study group surgical margins demonstrated significantly decreased Cornulin expression (p = 0.032). Low Cornulin expression was significantly associated with local relapse (p = 0.004) and non-tongue primary tumor (p = 0.013). Although not significantly associated with local relapse, expression of Ki-67 was significantly reduced in female patients (p = 0.041). Age above 57.5 years, Chinese & Indian ethnicity, alcohol consumption, epithelial dysplasia in surgical margins, and type III and IV patterns of invasion of tumor were also significantly related to local relapse. Regression analysis showed low expression of Cornulin (p = 0.018), and increased patient’s age (p = 0.008) were predictors of local relapse in oral squamous cell carcinoma, with 34-fold risk and 18-fold risk, respectively. Expression of Ki-67 and ISG15 did not show significant association with local relapse in oral squamous cell carcinoma.

CONCLUSION: Low expression of Cornulin is an independent predictor of relapse in oral squamous cell carcinoma.

PMID:34941961 | DOI:10.1371/journal.pone.0261575

PLoS One. 2021 Dec 23;16(12):e0261703. doi: 10.1371/journal.pone.0261703. eCollection 2021.

ABSTRACT

Vonoprazan, a potassium-competitive acid blocker, is expected to be superior to proton pump inhibitors (PPIs) in preventing post-endoscopic submucosal dissection (ESD)-induced gastric bleeding. However, the results of randomized controlled trials (RCTs) and observational studies on the efficacy of vonoprazan have been inconsistent. This study aimed to evaluate the effectiveness of vonoprazan in antithrombotic drug users, a population that has been excluded from RCTs. Treatment effects were assessed using cross-design synthesis, which can be adjusted for differences in study design and patient characteristics. We used data from an RCT in Japan (70 patients in the vonoprazan group and 69 in the PPI group) and an observational study (408 patients in the vonoprazan group and 870 in the PPI group). After matching, among the antithrombotic drug users in the observational study, post-ESD bleeding was noted in 8 out of 86 patients in the vonoprazan group and 18 out of 86 patients in the PPI group. After pooling the data from the RCT and observational study, the risk difference for antithrombotic drug users was -14.6% (95% CI: -22.0 to -7.2). CDS analysis suggested that vonoprazan is more effective than PPIs in preventing post-ESD bleeding among patients administered antithrombotic medications.

PMID:34941937 | DOI:10.1371/journal.pone.0261703

PLoS One. 2021 Dec 23;16(12):e0261844. doi: 10.1371/journal.pone.0261844. eCollection 2021.

ABSTRACT

BACKGROUND: The rapid development of COVID-19 vaccines has brought an unprecedented focus on public attitudes to vaccines, with intention to accept a COVID-19 vaccine fluctuating during the pandemic. However, it is unclear how the pandemic may influence attitudes and behaviour in relation to vaccines in general. The aim of the current study is to examine older adults’ changes in vaccination attitudes and behaviour over the first year of the pandemic.

METHODS: In February-March 2020 (before the first COVID-19 national lockdown in the UK), 372 older adults (aged 65+) provided sociodemographic information, self-reported influenza vaccine uptake, and completed two measures of vaccination attitudes: the 5C scale and the Vaccination Attitudes Examination Scale. One-year later, following rollout of COVID-19 vaccines to older adults, participants provided information on their COVID-19 and influenza vaccine uptake in the previous 12 months, and completed the 5C and VAX scales again. Paired samples t-tests were used to examine changes in vaccination attitudes over time.

RESULTS: Almost all participants (98.7%) had received at least one dose of a COVID-19 vaccine, and a significant increase in influenza uptake was identified (83.6% in 2020 to 91.6% in 2021). Complacency, mistrust of vaccine benefit, concerns about commercial profiteering, and constraints to vaccination had significantly decreased between Time 1 and Time 2, and collective responsibility had significant increased. However, calculation and worries about unforeseen future effects had increased, indicating that participants now perceived higher risks related to vaccination and were taking a more deliberative information-seeking approach.

CONCLUSION: The results show significant changes in vaccination attitudes across the pandemic. These changes suggest that while older adults became less complacent about the importance of vaccines, concerns about potential risks associated with vaccination increased. It will be important for public health communication to address these concerns for all vaccines offered to this group.

PMID:34941951 | DOI:10.1371/journal.pone.0261844

PLoS One. 2021 Dec 23;16(12):e0261684. doi: 10.1371/journal.pone.0261684. eCollection 2021.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world.

METHODS: This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone.

RESULTS: Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48-0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone.

CONCLUSIONS: Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.

PMID:34941933 | DOI:10.1371/journal.pone.0261684

PLoS One. 2021 Dec 23;16(12):e0261120. doi: 10.1371/journal.pone.0261120. eCollection 2021.

ABSTRACT

Data-based instruction (DBI) is an ongoing process to utilize students’ data for determining when and how to intensify intervention. It is an educational approach that is suggested as effective to enhance achievements of struggling learners, particularly for those who did not respond to intensive intervention in usual ways. In Korea, DBI was introduced and applied for students with learning difficulties especially since 2000 when the first Korea curriculum-based measurement (CBM) was developed as the name of Basic Academic Skills Assessment. Despite a number of studies accumulated since then, there has been a lack of research that examined the level of evidence-based practice (EBP) of DBI research. Thus, the present study sought to synthesize the DBI research so far in Korea by analyzing the effectiveness of DBI for school-aged students with learning difficulties via meta-analysis and evaluating the quality of the research. In this study, a total of 32 single-subject design studies were used. Multilevel meta-analysis revealed that the mean effect size of DBI was statistically significant (B = 1.34) and there was significant variance across participants in effect sizes. The results from the conditional model showed that exceptionality type, the number of sessions, and the length of each session were significantly accountable for the variability of effect sizes. In addition, the results of the qualitative analysis revealed the acceptable quality of the overall DBI research with some limitations. Based on these findings, implications and study limitations were discussed.

PMID:34941909 | DOI:10.1371/journal.pone.0261120

PLoS One. 2021 Dec 23;16(12):e0261746. doi: 10.1371/journal.pone.0261746. eCollection 2021.

ABSTRACT

OBJECTIVE: Women living with HIV (WLWH) experience psychosocial stress related to social-structural vulnerabilities. To investigate neuroendocrine pathways linking stress and increased cardiovascular disease risk among WLWH, we evaluated associations between psychosocial stress (i.e., perceived stress, posttraumatic stress, and experiences of race- and gender-based harassment) and a composite neuroendocrine biomarker index among WLWH and women without HIV.

METHODS: In 2019-2020, Women’s Interagency HIV Study participants in Washington, DC completed a questionnaire and provided blood and 12-hour overnight urine samples for testing of serum dehydroepiandrosterone sulfate (DHEA-S) and urinary free cortisol, epinephrine, and norepinephrine. Psychosocial stress was measured using the Perceived Stress Scale, PTSD Checklist-Civilian Version, and Racialized Sexual Harassment Scale. Latent profile analysis was used to classify participants into low (38%), moderate (44%), and high (18%) stress groups. Composite biomarker index scores between 0-4 were assigned based on participants’ number of neuroendocrine biomarkers in high-risk quartiles (≥75th percentile for cortisol, epinephrine, and norepinephrine and ≤25th percentile for DHEA-S). We evaluated associations between latent profile and composite biomarker index values using multivariable linear regression, adjusting for socio-demographic, behavioral, metabolic, and HIV-related factors.

RESULTS: Among 90 women, 62% were WLWH, 53% were non-Hispanic Black, and median age was 55 years. In full multivariable models, there was no statistically significant association between psychosocial stress and composite biomarker index values among all women independent of HIV status. High (vs. low) psychosocial stress was positively associated with higher mean composite biomarker index values among all monoracial Black women (adjusted β = 1.32; 95% CI: 0.20-2.43), Black WLWH (adjusted β = 1.93; 95% CI: 0.02-3.83) and Black HIV-negative women (adjusted β = 2.54; 95% CI: 0.41-4.67).

CONCLUSIONS: Despite a null association in the overall sample, greater psychosocial stress was positively associated with higher neuroendocrine biomarker concentrations among Black women, highlighting a plausible mechanism by which psychosocial stress could contribute to cardiovascular disease risk.

PMID:34941922 | DOI:10.1371/journal.pone.0261746

PLoS One. 2021 Dec 23;16(12):e0260937. doi: 10.1371/journal.pone.0260937. eCollection 2021.

ABSTRACT

Data from the 2016-17 Multiple Indicator Cluster Survey from Nigeria are used to study the relationship between child stature, mother’s years of education, and indicators of early childhood development (ECD). The relationships are contrasted between two empirical approaches: the conventional approach whereby control variables are selected in an ad-hoc manner, and the double machine-learning (DML) approach that employs data-driven methods to select controls from a much wider set of variables and thus reducing potential omitted variable bias. Overall, the analysis confirms that maternal education and the incidence of chronic malnutrition have a significant direct effect on measures of early childhood development. The point estimates based on the ad-hoc specification tend to be larger in absolute value than those based on the DML specification. Frequently, the point estimates based on the ad-hoc specification fall inside the confidence interval of the DML point estimates, suggesting that in these cases the omitted variable bias is not serious enough to prevent making causal inferences based on the ad-hoc specification. However, there are instances where the omitted variable bias is sufficiently large for the ad hoc specification to yield a statistically significant relationship when in fact the more robust DML specification suggests there is none. The DML approach also reveals a more complex picture that highlights the role of context. In rural areas, mother’s education affects early childhood development both directly and indirectly through its impact on the nutritional status of both older and younger children. In contrast, in urban areas, where the average level of maternal education is much higher, increases in a mother’s education have only a direct effect on child ECD measures but no indirect effect through child nutrition. Thus, DML provides a practical and feasible approach to reducing threats to internal validity for robust inferences and policy design based on observational data.

PMID:34941902 | DOI:10.1371/journal.pone.0260937

PLoS One. 2021 Dec 23;16(12):e0260730. doi: 10.1371/journal.pone.0260730. eCollection 2021.

ABSTRACT

This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005-2007 and between 2008-2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances.

PMID:34941887 | DOI:10.1371/journal.pone.0260730

PLoS One. 2021 Dec 23;16(12):e0259877. doi: 10.1371/journal.pone.0259877. eCollection 2021.

ABSTRACT

The shape of phylogenetic trees can be used to gain evolutionary insights. A tree’s shape specifies the connectivity of a tree, while its branch lengths reflect either the time or genetic distance between branching events; well-known measures of tree shape include the Colless and Sackin imbalance, which describe the asymmetry of a tree. In other contexts, network science has become an important paradigm for describing structural features of networks and using them to understand complex systems, ranging from protein interactions to social systems. Network science is thus a potential source of many novel ways to characterize tree shape, as trees are also networks. Here, we tailor tools from network science, including diameter, average path length, and betweenness, closeness, and eigenvector centrality, to summarize phylogenetic tree shapes. We thereby propose tree shape summaries that are complementary to both asymmetry and the frequencies of small configurations. These new statistics can be computed in linear time and scale well to describe the shapes of large trees. We apply these statistics, alongside some conventional tree statistics, to phylogenetic trees from three very different viruses (HIV, dengue fever and measles), from the same virus in different epidemiological scenarios (influenza A and HIV) and from simulation models known to produce trees with different shapes. Using mutual information and supervised learning algorithms, we find that the statistics adapted from network science perform as well as or better than conventional statistics. We describe their distributions and prove some basic results about their extreme values in a tree. We conclude that network science-based tree shape summaries are a promising addition to the toolkit of tree shape features. All our shape summaries, as well as functions to select the most discriminating ones for two sets of trees, are freely available as an R package at http://github.com/Leonardini/treeCentrality.

PMID:34941890 | DOI:10.1371/journal.pone.0259877