Tag: statistics

PLoS One. 2021 Jun 24;16(6):e0253335. doi: 10.1371/journal.pone.0253335. eCollection 2021.

ABSTRACT

The sequencing of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) remains a matter of controversy. This cohort study analyzed the overall survival (OS) and progression-free survival (PFS) of afatinib compared with erlotinib and gefitinib first-line. EGFRm+, advanced NSCLC patients treated with either afatinib, erlotinib or gefitinib were retrospectively analyzed. A total of 107 patients were included. There was no statistically significant difference in PFS among the 3 groups. In the ≥ 60 years age group, the afatinib group had longer survival compared to the gefitinib group (p = 0.01). Median OS were 19.1, 22.9, and 35.6 months for gefitinib, erlotinib, and afatinib groups, respectively, with statistical significance between the gefitinib and afatinib groups (p = 0.009). Patients on afatinib also had longer median OS than erlotinib and gefitinib pooled together (35.5 versus 21.4 months; hazard ratio = 0.54, p = 0.016), despite similar median PFS. In conclusion, afatinib is a better choice compared to gefitinib or erlotinib for EGFRm+ patients. The OS obtained with afatinib is just 3 months shorter than osimertinib in the FLAURA trial. Direct comparison studies with osimertinib are still needed to determine optimal sequencing.

PMID:34166400 | DOI:10.1371/journal.pone.0253335

PLoS Negl Trop Dis. 2021 Jun 24;15(6):e0009456. doi: 10.1371/journal.pntd.0009456. Online ahead of print.

ABSTRACT

BACKGROUND: Ethiopia has over 3,200 new cases of leprosy diagnosed every year. Prevention remains a challenge as transmission pathways are poorly understood. Susceptibility and disease manifestations are highly dependent on individual host-immune response. Nutritional deficiencies, such as protein-energy malnutrition, have been linked to reduced cell-mediated immunity, which in the case of leprosy, could lead to a higher chance of active leprosy and thus an increased reservoir of transmissible infection.

METHODOLOGY/PRINCIPAL FINDINGS: Between June and August 2018, recently diagnosed patients with leprosy and individuals without known contact with cases were enrolled as controls in North Gondar regional health centers. Participants answered survey questions on biometric data, demographics, socioeconomic situation, and dietary habits. Descriptive statistics, univariate, and multivariate logisitic regression examined associations between undernutrition, specifically body mass index (BMI), middle upper arm circumference (MUAC), and leprosy. Eighty-one participants (40 cases of leprosy, 41 controls) were enrolled (75% male) with an average age of 38.6 years (SD 18.3). The majority of cases were multibacillary (MB) (90%). There was a high prevalence of undernutrition with 24 (29.6%) participants underweight (BMI <18.5) and 17 (21%) having a low MUAC. On multivariate analysis, underweight was significantly associated with leprosy (aOR = 9.25, 95% CI 2.77, 30.81). Also found to be associated with leprosy was cutting the size of meals/skipping meals (OR = 2.9, 95% CI 1.0, 8.32) or not having enough money for food (OR = 10, 95% CI 3.44 29.06).

CONCLUSIONS/SIGNIFICANCE: The results suggest a strong association between leprosy and undernutrition, while also supporting the framework that food insecurity may lead to undernutrition that then could increase susceptibility to leprosy. In conclusion, this study highlights the need to study the interplay of undernutrition, food insecurity, and the manifestations of leprosy.

PMID:34166403 | DOI:10.1371/journal.pntd.0009456

PLoS One. 2021 Jun 24;16(6):e0253111. doi: 10.1371/journal.pone.0253111. eCollection 2021.

ABSTRACT

Mental wellness is an important topic among practicing veterinarians. Peer reviewed studies focusing on veterinary house officers’ wellbeing are lacking in veterinary medicine. The aim of this study was to assess wellbeing of house officers using validated surveys for anxiety, burnout, depression, and quality of life. A cross-sectional survey of 103 house officers (residents, interns, and fellows) was performed. Respondents were invited to voluntarily complete the online surveys. Anxiety, burnout, depression, and quality of life were assessed using the Generalized Anxiety Disorder (GAD-7), Maslach Burnout Inventory (MBI), Patient Health Questionnaire (PHQ-9), and Short Form-8 (SF-8), respectively. Descriptive statistics were calculated. For qualitative analysis, respondents were requested to rate their perception of the level of stress regarding various work-related stressors. The first survey was completed in 2017 with 60 respondents of which 51 (85%) identified as females and nine (15%) identified as males. The second survey was completed in 2018 with 43 respondents of which 35 (81.4%) identified as females and 8 (18.6%) identified as males. Respondents reported high levels of burnout characterized by high levels of emotional exhaustion and lack of personal accomplishment but reported mild levels of anxiety and depression. The mental component of their quality of life score was lower than the general US population, whereas the physical component score was consistent with the general US population. Respondents indicated moderate scores of stress for concerns regarding patient management, research, teaching, work-life balance, relationships, organizational skills, time management, finances, and the mental and emotional impact of the work environment. The high levels of burnout, and low mental quality of life in house officers require specific intervention programs to improve wellbeing.

PMID:34166405 | DOI:10.1371/journal.pone.0253111

PLoS Med. 2021 Jun 24;18(6):e1003692. doi: 10.1371/journal.pmed.1003692. Online ahead of print.

ABSTRACT

BACKGROUND: Existing predictive outcomes models for type 2 diabetes developed and validated in historical European populations may not be applicable for East Asian populations due to differences in the epidemiology and complications. Despite the continuum of risk across the spectrum of risk factor values, existing models are typically limited to diabetes alone and ignore the progression from prediabetes to diabetes. The objective of this study is to develop and externally validate a patient-level simulation model for prediabetes and type 2 diabetes in the East Asian population for predicting lifetime health outcomes.

METHODS AND FINDINGS: We developed a health outcomes model from a population-based cohort of individuals with prediabetes or type 2 diabetes: Hong Kong Clinical Management System (CMS, 97,628 participants) from 2006 to 2017. The Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model comprises of 13 risk equations to predict mortality, micro- and macrovascular complications, and development of diabetes. Risk equations were derived using parametric proportional hazard models. External validation of the CHIME model was assessed in the China Health and Retirement Longitudinal Study (CHARLS, 4,567 participants) from 2011 to 2018 for mortality, ischemic heart disease, cerebrovascular disease, renal failure, cataract, and development of diabetes; and against 80 observed endpoints from 9 published trials using 100,000 simulated individuals per trial. The CHIME model was compared to United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) and Risk Equations for Complications Of type 2 Diabetes (RECODe) by assessing model discrimination (C-statistics), calibration slope/intercept, root mean square percentage error (RMSPE), and R2. CHIME risk equations had C-statistics for discrimination from 0.636 to 0.813 internally and 0.702 to 0.770 externally for diabetes participants. Calibration slopes between deciles of expected and observed risk in CMS ranged from 0.680 to 1.333 for mortality, myocardial infarction, ischemic heart disease, retinopathy, neuropathy, ulcer of the skin, cataract, renal failure, and heart failure; 0.591 for peripheral vascular disease; 1.599 for cerebrovascular disease; and 2.247 for amputation; and in CHARLS outcomes from 0.709 to 1.035. CHIME had better discrimination and calibration than UKPDS-OM2 in CMS (C-statistics 0.548 to 0.772, slopes 0.130 to 3.846) and CHARLS (C-statistics 0.514 to 0.750, slopes -0.589 to 11.411); and small improvements in discrimination and better calibration than RECODe in CMS (C-statistics 0.615 to 0.793, slopes 0.138 to 1.514). Predictive error was smaller for CHIME in CMS (RSMPE 3.53% versus 10.82% for UKPDS-OM2 and 11.16% for RECODe) and CHARLS (RSMPE 4.49% versus 14.80% for UKPDS-OM2). Calibration performance of CHIME was generally better for trials with Asian participants (RMSPE 0.48% to 3.66%) than for non-Asian trials (RMPSE 0.81% to 8.50%). Main limitations include the limited number of outcomes recorded in the CHARLS cohort, and the generalizability of simulated cohorts derived from trial participants.

CONCLUSIONS: Our study shows that the CHIME model is a new validated tool for predicting progression of diabetes and its outcomes, particularly among Chinese and East Asian populations that has been lacking thus far. The CHIME model can be used by health service planners and policy makers to develop population-level strategies, for example, setting HbA1c and lipid targets, to optimize health outcomes.

PMID:34166382 | DOI:10.1371/journal.pmed.1003692

PLoS One. 2021 Jun 24;16(6):e0253499. doi: 10.1371/journal.pone.0253499. eCollection 2021.

ABSTRACT

BACKGROUND: Scientists across the world are working on innovating a successful vaccine that will save lives and end COVID-19 pandemic. World Health Organization (WHO) is working to make sure COVID-19 vaccines can be safely delivered to all those who need them. Indeed, the successful deployment and a sufficient uptake of vaccines is equally important. Acceptance and accessibility of such vaccine is a key indicator of vaccination coverage.

OBJECTIVE: This study aimed to assess the determinants of intention to receive COVID-19 vaccine among school teachers in Gondar City.

METHODS: An institution based cross-sectional study was conducted from December, 2020 to January, 2021. A total of 301 school teachers selected using stratified simple random sampling were included. Descriptive analysis such as medians, means, proportions, standard deviations and frequencies were computed. Linear regression analysis was done to identify factors associated with intention to receive COVID-19 vaccine. A p-value of less than 0.05 was used to declare statistical significance.

RESULTS: The median intention to receive COVID-19 vaccine was 3.33 with interquartile range of 2.67-4.0. Of the participants 54.8% had scored above the median of intention to receive COVID-19 vaccine score. 54% variance in intention to receive COVID-19 vaccine was explained by the independent variables. Being affiliated with other category of religion, bachelor degree educational status, perceived susceptibility, perceived benefit, perceived barrier, and cues to action were significantly associated with the intention to receive COVID-19 vaccine.

CONCLUSION: The median score of intention to receive COVID-19 vaccine was 3.33. Socio-demographic and health beliefs influenced the intention to receive the COVID-19 vaccine in the study participant. Policy makers and stakeholders should focus on strong health promotion about risks of the pandemic, benefit, safety, and efficacy of vaccination.

PMID:34166399 | DOI:10.1371/journal.pone.0253499

PLoS Comput Biol. 2021 Jun 24;17(6):e1009095. doi: 10.1371/journal.pcbi.1009095. Online ahead of print.

ABSTRACT

The effectiveness of immune responses depends on the precision of stimulus-responsive gene expression programs. Cells specify which genes to express by activating stimulus-specific combinations of stimulus-induced transcription factors (TFs). Their activities are decoded by a gene regulatory strategy (GRS) associated with each response gene. Here, we examined whether the GRSs of target genes may be inferred from stimulus-response (input-output) datasets, which remains an unresolved model-identifiability challenge. We developed a mechanistic modeling framework and computational workflow to determine the identifiability of all possible combinations of synergistic (AND) or non-synergistic (OR) GRSs involving three transcription factors. Considering different sets of perturbations for stimulus-response studies, we found that two thirds of GRSs are easily distinguishable but that substantially more quantitative data is required to distinguish the remaining third. To enhance the accuracy of the inference with timecourse experimental data, we developed an advanced error model that avoids error overestimates by distinguishing between value and temporal error. Incorporating this error model into a Bayesian framework, we show that GRS models can be identified for individual genes by considering multiple datasets. Our analysis rationalizes the allocation of experimental resources by identifying most informative TF stimulation conditions. Applying this computational workflow to experimental data of immune response genes in macrophages, we found that a much greater fraction of genes are combinatorially controlled than previously reported by considering compensation among transcription factors. Specifically, we revealed that a group of known NFκB target genes may also be regulated by IRF3, which is supported by chromatin immuno-precipitation analysis. Our study provides a computational workflow for designing and interpreting stimulus-response gene expression studies to identify underlying gene regulatory strategies and further a mechanistic understanding.

PMID:34166361 | DOI:10.1371/journal.pcbi.1009095

PLoS One. 2021 Jun 24;16(6):e0250768. doi: 10.1371/journal.pone.0250768. eCollection 2021.

ABSTRACT

BACKGROUND: Plantar fasciitis is the most common cause of pain in the plantar region of the heel, and extracorporeal shockwave therapy (ESWT) is an option used in cases where conservative treatment fails. Hyaluronic acid (HA), initially used for osteoarthrosis, is a treatment option because it has been applied to extra-articular regions, such as tendons, ligaments, and fascia. The aim of the present study will be to evaluate the outcomes of pain, function, and personal satisfaction after a single injection of HA and to compare the results with those of ESWT in patients with chronic plantar fasciitis.

METHODS: The study will include 80 patients who will be randomized to receive three sessions of ESWT (n = 40) or a single ultrasound-guided HA injection in the plantar fascia (n = 40). The outcomes will include the visual analog pain scale score, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Foot and Ankle Outcome Score (FAOS). All of the assessments will be performed at baseline and 3, 6, and 12 months after treatment. Statistical analysis will be performed using the repeated measures ANOVA (analysis of variance test) for primary and secondary outcomes and also Fisher’s Least Significant Difference, a Post-Hoc test. We will use R software for statistical analysis, randomization, and sample size calculation.

RESULTS: Recruitment and data collection will begin in November 2020, with completion scheduled for November 2022 and final publication available in March 2023.

CONCLUSION: This trial will evaluate the effects of a single ultrasound-guided HA injection for the treatment of chronic plantar fasciitis.

TRIAL REGISTRATION: Brazilian Clinical Trials Registry (Register Number: RBR-97vkx4) http://www.ensaiosclinicos.gov.br/rg/RBR-97vkx4/.

PMID:34166373 | DOI:10.1371/journal.pone.0250768

PLoS One. 2021 Jun 24;16(6):e0247908. doi: 10.1371/journal.pone.0247908. eCollection 2021.

ABSTRACT

To investigate the influence of bedding structure and different loading rates on the dynamic fracture characteristics and energy dissipation of Datong coal, a split Hopkinson bar was used to obtain the fracture characteristics of coal samples with different bedding angles. The process of crack initiation and propagation in Datong coal was recorded by the high-speed camera. The formula for the model I fracture toughness of the transversely isotropic material is obtained on the basis of the finite element method (FEM) together with the J-integral. By comparing the incident energy, absorbed energy, fracture energy and residual kinetic energy of Datong coal samples under various impact speeds, the energy dissipation characteristics during the dynamic fracture process of coal considering the bedding structure is acquired. The experimental results indicate that the fracture pattern of notched semi-circular bending (NSCB) Datong coal is tensile failure. After splitting into two parts, the coal sample rotates approximately uniformly around the contact point between the sample and the incident rod. The dynamic fracture toughness is 3.52~8.64 times of the quasi-static fracture toughness for Datong coal. Dynamic fracture toughness increases with increasing impact velocity, and the effect of bedding angle on fracture toughness then decreases. In addition, the residual kinetic energy of coal samples with the same bedding angle increases with the increase of impact speed. The energy utilization rate decreases continuously, and the overall dispersion of statistical data decreases gradually. In rock fragmentation engineering, the optimum loading condition is low-speed loading regardless of energy utilization efficiency or fracture toughness. These conclusions may have significant implications for the optimization of hydraulic fracturing process in coal mass and the further understanding of crack propagation mechanisms in coalbed methane extraction (CME). The anisotropic effect of coal should be fully considered in both these cases.

PMID:34166380 | DOI:10.1371/journal.pone.0247908

Angiol Sosud Khir. 2021;27(2):114-120. doi: 10.33529/ANGIO2021214.

ABSTRACT

Annually, up to 850 000 coronary aortic bypass graft operations are performed worldwide. Despite modern technical equipment ensuring a high level of safety of the procedure, currently important remains a problem related to intraoperative myocardial damage in using artificial circulation. Early detection and clinical assessment of myocardial ischaemia often present a difficult task. This article deals with clinical, instrumental and laboratory methods of diagnosis, aimed at verification of an intraoperative cardiac lesion associated with graft dysfunction in coronary artery bypass grafting. Isolated electrocardiographic and echocardiographic signs of myocardial ischaemia between the comparison groups did not differ significantly. Analysing the markers of myocardial lesions, statistically significant differences were obtained only after 48 hours which, from the point of view of saving viable myocardium, is an utterly long-term interval. Studying the findings of intraoperative flowmetry showed statistically significant dependence between velocity characteristics, pulse index of shunts and their patency on angiographic examination. Thus, only combination of diagnostic parameters makes it possible to detect myocardial damage related to shunt dysfunction. This enables early determination of indications for performing bypass angiography and selection of the required therapeutic policy. Timely coronary artery angiography makes it possible to reveal defects of shunts and to timely perform surgical correction, preventing myocardial infarction.

PMID:34166351 | DOI:10.33529/ANGIO2021214

Angiol Sosud Khir. 2021;27(2):121-126. doi: 10.33529/ANGIO2021218.

ABSTRACT

AIM: This study was undertaken to investigate the preoperative incidence and severity of intimal hypertrophy, as well as the level of blood supply of arterial and venous conduits for coronary artery bypass grafting.

MATERIAL AND METHODS: Segments of the internal thoracic artery and great saphenous vein (n=13) were harvested pairwise during coronary artery bypass grafting and were then visualized by scanning electron microscopy in back-scattered electrons. The analysis of the incidence and thickness of intimal hypertrophy, as well as the calculation of the number and the area of the vasa vasorum were performed using the programme ImageJ.

RESULTS: Intimal hypertrophy was more characteristic for the great saphenous vein as compared with the internal thoracic artery (9/13 (69.2%) and 7/13 (55.8%), respectively), although this difference did not reach statistical significance. The maximal-to-minimal neointimal thickness ratio correlated with the percentage of stenosis (r=0.875, p<0.0001), the area (r=0.45, p=0.023) and the number (r=0.47, p=0.015) of the vasa vasorum in the conduits, thus confirming the hypothesis on possible participation of these vessels in the development of intimal hypertrophy, with the area of the vasa vasorum being greater in the vessels with >10% stenosis (p=0.051). The number of the vasa vasorum in the great saphenous vein exceeded that in the internal thoracic artery (p=0.0005), with this difference remaining significant after adjustment for the area of the adventitia (p=0.027). The number of the vasa vasorum per the percentage of stenosis in the great saphenous vein also exceeded that in the internal thoracic artery (p=0.039) and more strongly correlated with intimal hypertrophy in the great saphenous vein as compared with that in the internal thoracic artery (r=0.53 and r=0.27, respectively).

CONCLUSION: Intimal hypertrophy correlates with the area and number of the vasa vasorum in conduits. The great saphenous vein is characterised by a larger number and higher density of the vasa vasorum as compared with the internal thoracic artery. The number of the vasa vasorum is correlated with stenosis of the great saphenous vein more closely than with stenosis of the internal thoracic artery. This may be suggestive of significant predisposition of the great saphenous vein to the onset of adventitial inflammation followed by the development of intimal hypertrophy.

PMID:34166352 | DOI:10.33529/ANGIO2021218