Category: Statistics

Bull Math Biol. 2021 Aug 30;83(10):103. doi: 10.1007/s11538-021-00935-y.

ABSTRACT

We combine a systems pharmacology approach with an agent-based modelling approach to simulate LoVo cells subjected to AZD6738, an ATR (ataxia-telangiectasia-mutated and rad3-related kinase) inhibiting anti-cancer drug that can hinder tumour proliferation by targeting cellular DNA damage responses. The agent-based model used in this study is governed by a set of empirically observable rules. By adjusting only the rules when moving between monolayer and multi-cellular tumour spheroid simulations, whilst keeping the fundamental mathematical model and parameters intact, the agent-based model is first parameterised by monolayer in vitro data and is thereafter used to simulate treatment responses in in vitro tumour spheroids subjected to dynamic drug delivery. Spheroid simulations are subsequently compared to in vivo data from xenografts in mice. The spheroid simulations are able to capture the dynamics of in vivo tumour growth and regression for approximately 8 days post-tumour injection. Translating quantitative information between in vitro and in vivo research remains a scientifically and financially challenging step in preclinical drug development processes. However, well-developed in silico tools can be used to facilitate this in vitro to in vivo translation, and in this article, we exemplify how data-driven, agent-based models can be used to bridge the gap between in vitro and in vivo research. We further highlight how agent-based models, that are currently underutilised in pharmaceutical contexts, can be used in preclinical drug development.

PMID:34459993 | DOI:10.1007/s11538-021-00935-y

JAMA Netw Open. 2021 Aug 2;4(8):e2129041. doi: 10.1001/jamanetworkopen.2021.29041.

ABSTRACT

IMPORTANCE: Housing insecurity induced by evictions may increase the risk of contracting COVID-19.

OBJECTIVE: To estimate the association of lifting state-level eviction moratoria, which increased housing insecurity during the COVID-19 pandemic, with the risk of being diagnosed with COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included individuals with commercial insurance or Medicare Advantage who lived in a state that issued an eviction moratorium and were diagnosed with COVID-19 as well as a control group comprising an equal number of randomly selected individuals in these states who were not diagnosed with COVID-19. Data were collected from OptumLabs Data Warehouse, a database of deidentified administrative claims. The study used a difference-in-differences analysis among states that implemented an eviction moratorium between March 13, 2020, and September 4, 2020.

EXPOSURES: Time since state-level eviction moratoria were lifted.

MAIN OUTCOMES AND MEASURES: The primary outcome measure was a binary variable indicating whether an individual was diagnosed with COVID-19 for the first time in a given week with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code U07.1. The study analyzed changes in COVID-19 diagnosis before vs after a state lifted its moratorium compared with changes in states that did not lift it. For sensitivity analyses, models were reestimated on a 2% random sample of all individuals in the claims database during this period in these states.

RESULTS: The cohort consisted of 509 694 individuals (254 847 [50.0%] diagnosed with COVID-19; mean [SD] age, 47.0 [23.6] years; 239 056 [53.3%] men). During the study period, 43 states and the District of Columbia implemented an eviction moratorium and 7 did not. Among the states that implemented a moratorium, 26 (59.1%) lifted their moratorium before the US Centers for Disease Control and Prevention issued their national moratorium, while 18 (40.1%) maintained theirs. In a Cox difference-in-differences regression model, individuals living in a state that lifted its eviction moratorium experienced higher hazards of a COVID-19 diagnosis beginning 5 weeks after the moratorium was lifted (hazard ratio [HR], 1.39; 95% CI, 1.11-1.76; P = .004), reaching an HR of 1.83 (95% CI, 1.36-2.46; P < .001) 12 weeks after. Hazards increased in magnitude among individuals with preexisting comorbidities and those living in nonaffluent and rent-burdened areas. Individuals with a Charlson Comorbidity Index score of 3 or greater had an HR of 2.37 (95% CI, 1.67-3.36; P < .001) at the end of the study period. Those living in nonaffluent areas had an HR of 2.14 (95% CI, 1.51-3.05; P < .001), while those living in areas with a high rent burden had an HR of 2.31 (95% CI, 1.64-3.26; P < .001).

CONCLUSIONS AND RELEVANCE: The findings of this difference-in-differences analysis suggest that eviction-led housing insecurity may have exacerbated the COVID-19 pandemic.

PMID:34459904 | DOI:10.1001/jamanetworkopen.2021.29041

Arch Orthop Trauma Surg. 2021 Aug 30. doi: 10.1007/s00402-021-04135-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The guidelines regarding rehabilitation after pediatric anterior cruciate ligament reconstruction (ACLR) are sparse. The aim of the study was to retrospectively describe the long-term outcome regarding further surgery and with special emphasis on the revision rate after two different postoperative rehabilitation programs following pediatric ACLR.

MATERIAL AND METHODS: 193 consecutive patients < 15 years of age who had undergone ACLR at two centers, A (n = 116) and B (n = 77), in 2006-2010 were identified. Postoperative rehabilitation protocol at A: a brace locked in 30° of flexion with partial weight bearing for 3 weeks followed by another 3 weeks in the brace with limited range of motion 10°-90° and full weight bearing; return to sports after a minimum of 9 months. B: immediate free range of motion and weight bearing as tolerated; return to sports after a minimum of 6 months. The mean follow-up time was 6.9 (range 5-9) years. The mean age at ACLR was 13.2 years (range 7-14) years. The primary outcome measurement in the statistical analysis was the occurrence of revision. Multivariable logistic regression analysis was performed to investigate five potential risk factors: surgical center, sex, age at ACLR, time from injury to ACLR and graft diameter.

RESULTS: Thirty-three percent had further surgery in the operated knee including a revision rate of 12%. Twelve percent underwent ACLR in the contralateral knee. The only significant variable in the statistical analysis according to the multivariable logistic regression analysis was surgical center (p = 0.019). Eight percent of the patients at center A and 19% of the patients at B underwent ACL revision.

CONCLUSIONS: Further surgery in the operated knee could be expected in one third of the cases including a revision rate of 12%. The study also disclosed a similar rate of contralateral ACLR at 12%. The revision rate following pediatric ACLR was lower in a center which applied a more restrictive rehabilitation protocol.

LEVEL OF EVIDENCE: Case-control study, Level III.

PMID:34459955 | DOI:10.1007/s00402-021-04135-0

Health Policy Plan. 2021 Aug 30:czab109. doi: 10.1093/heapol/czab109. Online ahead of print.

ABSTRACT

Implementing context-appropriate neonatal and pediatric advanced life support management interventions has increasingly been recommended as one of the approaches to reduce under-five mortality in resource-constrained settings like Rwanda. One such intervention is ETAT+, which stands for Emergency Triage, Assessment and Treatment plus Admission care for severely ill newborns and children. In 2013, ETAT+ was implemented in Rwandan district hospitals. We evaluated the impact of the ETAT+ intervention on newborn and child health outcomes. We used monthly time series data from the DHIS2-enabled Rwanda Health Management Information System from 2012 to 2016 to examine neonatal and pediatric hospital mortality rate. Each hospital contributed data for 12 and 36 months before and after ETAT+ implementation, respectively. Using controlled interrupted time series analysis and segmented regression model, we estimated longitudinal changes in neonatal and pediatric hospital mortality rate in intervention hospitals relative to matched concurrent control hospitals. We also studied changes in case fatality rate specifically for ETAT+ targeted conditions. Our study cohort consisted of seven intervention hospitals and fourteen matched control hospitals contributing 142,424 neonatal and pediatric hospital admissions. After controlling for secular trends and autocorrelation, we found that the ETAT+ implementation had no statistically significant impact on the rate of all-cause neonatal and pediatric hospital mortality in intervention hospitals relative to control hospitals. However, the case fatality rate for ETAT+ targeted neonatal conditions decreased immediately following implementation by 5% (95% CI: -9.25, -0.77) and over time by 0.8% monthly (95% CI: -1.36, -0.25), in intervention hospitals compared with control hospitals. Case fatality rate for ETAT+ targeted pediatric conditions did not decrease following the ETAT+ implementation. While ETAT+ focuses on improving quality of hospital care for both newborns and children, we only found an impact on neonatal hospital mortality for ETAT+ targeted conditions that should be interpreted with caution given the relatively short pre-intervention period and potential regression to the mean.

PMID:34459893 | DOI:10.1093/heapol/czab109

J Vis Exp. 2021 Aug 14;(174). doi: 10.3791/61696.

ABSTRACT

Microplastics are an emerging global pollutant type that poses a great health threat to animals due to their uptake and translocation in animal tissues and organs. Ecotoxicological effects of microplastics on the development of bird embryos are not known. The bird egg is a complete development and nutrition system, and the entire embryo development occurs in the eggshell. Therefore, a direct record of bird embryo development under the stress of pollutants such as microplastics is highly limited by the opaque eggshell in traditional hatching. In this study, the effects of microplastics on quail embryo development were visually monitored by hatching without an eggshell. The main steps include the cleaning and disinfection of fertilized eggs, the incubation before exposure, the short-term incubation after exposure, and the sample extraction. The results show that compared with the control group, the wet weight and body length of the microplastics-exposed group displayed a statistical difference and the liver proportion of the whole exposed group significantly increased. Additionally, we evaluated external factors that affect the incubation: temperature, humidity, egg rotation angle, and other conditions. This experimental method provides valuable information on the ecotoxicology of microplastics and a novel way to study the adverse effects of pollutants on the development of embryos.

PMID:34459802 | DOI:10.3791/61696

Bioinformatics. 2021 Aug 30:btab614. doi: 10.1093/bioinformatics/btab614. Online ahead of print.

ABSTRACT

SUMMARY: Expression quantitative trait loci (eQTLs) characterize the associations between genetic variation and gene expression to provide insights into tissue-specific gene regulation. Interactive visualization of tissue-specific eQTLs or splice QTLs (sQTLs) can facilitate our understanding of functional variants relevant to disease-related traits. However, combining the multi-dimensional nature of eQTLs/sQTLs into a concise and informative visualization is challenging. Existing QTL visualization tools provide useful ways to summarize the unprecedented scale of transcriptomic data but are not necessarily tailored to answer questions about the functional interpretations of trait-associated variants or other variants of interest. We developed FIVEx, an interactive eQTL/sQTL browser with an intuitive interface tailored to the functional interpretation of associated variants. It features the ability to navigate seamlessly between different data views while providing relevant tissue- and locus-specific information to offer users a better understanding of population-scale multi-tissue transcriptomic profiles. Our implementation of the FIVEx browser on the EBI eQTL catalogue, encompassing 16 publicly available RNA-seq studies, provides important insights for understanding potential tissue-specific regulatory mechanisms underlying trait-associated signals.

AVAILABILITY AND IMPLEMENTATION: A FIVEx instance visualizing EBI eQTL catalogue data can be found at https://fivex.sph.umich.edu. Its source code is open source under an MIT license at https://github.com/statgen/fivex.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34459872 | DOI:10.1093/bioinformatics/btab614

Wiad Lek. 2021;74(7):1680-1686.

ABSTRACT

OBJECTIVE: The aim: The purpose of the research is to study the understanding of student pharmaceutical youth the eating behavior in the context of the EBW and obesity.

PATIENTS AND METHODS: Materials and methods: The material of the study was anonymous questionnaire survey the students of the pharmaceutical faculties from Ukraine.

RESULTS: Results: The results of the questionnaire were analyzed using methods of statistics, comparison and generalization. Almost 9 out of 10 respondents from both universities consider the reason of obesity a sedentary lifestyle and poor nutrition, and the most effective way to treat it is physical activity, though only 36.3% and 28.4% of students of the corresponding samples have it constantly.

CONCLUSION: Conclusions: The questionnaire showed a lack of eating behavior, of their knowledge of the basic issues of the EBW and obesity, as well as differences in personal perception and the desire for the practical implementation of queries regarding the weight of their body that may further affect the professional ability of young specialists in influencing the processes of formation and improving the quality of their lives and patients’ lives.

PMID:34459771

Wiad Lek. 2021;74(7):1699-1706.

ABSTRACT

OBJECTIVE: The aim of the study was to analyze and identify risk factors for the development of moderate and severe bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis in preterm neonates in intensive care unit and during any kind of respiratory support.

PATIENTS AND METHODS: Materials and methods: A simple retrospective-prospective blind controlled non-randomised study included 28-32 weeks of gestational age 122 newborns with respiratory distress syndrom, who were treated in the neonatal intensive care units of two medical institutions of Dnipro from 2016 to 2020. Among 122 children neonates were divided into two groups according to particularities of respiratory support, prior type of noinvasive ventilation and infusion volume per day. The uni-variate Cox regressions using clinical variables identified specific clinical variables associated with development of moderate and severe BPD, retinopathy of prematurity, necrotizing enterocolitis, mortality rate (based on odds ratio and 95% confidence interval (95% CI). Then, significant clinical variables were used to build a multivariate Cox regression models. by backwards elimination of non-significant clinical variables. To estimate discriminative ability of comorbidities predictors we conducted ROC-analysis.

RESULTS: Results: The patients with moderate and severe BPD significantly longer were mechanically ventilated and received О2 more than 30% in inhaled gas mixture, therefore every day of MV and/or additional oxygen >30% led to increase in probability of BPD development by 15% (p=0,01), АUC=0,78 (95% CI 0,66-0,89). Significant predictors of moderate and severe retinopathy of prematurity were body weight (AUC 0,64 (95% CI 0,51-0,77) (p=0.03), duration of non-invasive ventilation by NIV PC (AUC 0,68 (95% CI 0,54-0,83) (p <0.01), CPAP (AUC 0.63) (95% CI 0.49-0.76) (p = 0,04) and caffeine administration (AUC 0,68 (95% CI 0,59-0,77) (p=0.01). Patients who developed NEC had a statistically significantly lower daily infusion volume AUC 0,68 (0,59-0,77) p <0.01, later onset of enteral nutrition AUC 0,68 (95% CI 0,59-0,77) p <0.01, lower hemoglobin levels on the first, third and seventh days of life AUC 0,67 (95% CI 0,57-0,77) p <0.01, as well as the level of leukocytes AUC 0,65 (95% CI 0,56-0,75) p = 0,01 and platelet count AUC 0,67 (0,58-0,77) (p <0.01) during the first 7 days of life.

CONCLUSION: Conclusions: The results of the study revealed risk factors for intensive care in general and respiratory support in particular, which significantly increase the risk of developing comorbidities of prematurity. Among them are relatively controlled, it is the duration of mechanical ventilation and NIV, which increase the risk of BPD and retinopathy of prematurity. Other risk factors which we can manage include nutrition state, anemia and supplemental oxygen.

PMID:34459774

Arthroplast Today. 2021 Aug 18;10:175-179. doi: 10.1016/j.artd.2021.06.013. eCollection 2021 Aug.

ABSTRACT

BACKGROUND: Patients undergoing total joint arthroplasty have higher rates of anxiety, depression or anxiety and depression than the general population and higher costs of care, which lead to higher levels of postoperative dissatisfaction and readmission rates. We evaluated the readmission rates of patients undergoing total hip or knee arthroplasty with diagnoses of anxiety, depression, or both.

METHODS: Our hospital’s prospectively collected data from Michigan’s statewide total joint database were reviewed from 2013 to 2018. Rates of anxiety, depression or anxiety and depression were determined based on preoperative anxiolytic or antidepressant medications using National Drug Codes.

RESULTS: A total of 4107 cases were included. Of which 4.28% had a readmission within the 90-day global period, and 12% had a history of depression or anxiety or both. For the entire cohort, those on anxiolytic medication were 153% more likely to be readmitted than those not on medication (P = .017). When comparing total hip arthroplasty (THA) or total knee arthroplasty (TKA), patients taking anxiolytic medication and undergoing TKA were 120% more likely to undergo readmission within 90 days (P = .021). Patients on depression medication alone were not at increased risk of readmission in the TKA cohort (P = .991). For THA, neither diagnosis appeared a risk factor for readmission (P = .852).

CONCLUSIONS: Patients with depression, anxiety, or both undergoing TKA were at a statistically significant risk of readmission within 90 days compared with patients without these diagnoses. Anxiety and depression were both risk factors for readmission, but anxiety appeared to have a more significant impact. Patients undergoing THA on the other hand did not appear to share this risk profile.

PMID:34458530 | PMC:PMC8379358 | DOI:10.1016/j.artd.2021.06.013

Biomed Res Int. 2021 Aug 22;2021:9942873. doi: 10.1155/2021/9942873. eCollection 2021.

ABSTRACT

PURPOSE: Due to the excessive use of raw materials in diagnostic tools and equipment during the COVID-19 pandemic, there is a dire need for cheaper and more effective methods in the healthcare system. With the development of artificial intelligence (AI) methods in medical sciences as low-cost and safer diagnostic methods, researchers have turned their attention to the use of imaging tools with AI that have fewer complications for patients and reduce the consumption of healthcare resources. Despite its limitations, X-ray is suggested as the first-line diagnostic modality for detecting and screening COVID-19 cases.

METHOD: This systematic review assessed the current state of AI applications and the performance of algorithms in X-ray image analysis. The search strategy yielded 322 results from four databases and google scholar, 60 of which met the inclusion criteria. The performance statistics included the area under the receiver operating characteristics (AUC) curve, accuracy, sensitivity, and specificity.

RESULT: The average sensitivity and specificity of CXR equipped with AI algorithms for COVID-19 diagnosis were >96% (83%-100%) and 92% (80%-100%), respectively. For common X-ray methods in COVID-19 detection, these values were 0.56 (95% CI 0.51-0.60) and 0.60 (95% CI 0.54-0.65), respectively. AI has substantially improved the diagnostic performance of X-rays in COVID-19.

CONCLUSION: X-rays equipped with AI can serve as a tool to screen the cases requiring CT scans. The use of this tool does not waste time or impose extra costs, has minimal complications, and can thus decrease or remove unnecessary CT slices and other healthcare resources.

PMID:34458373 | PMC:PMC8390162 | DOI:10.1155/2021/9942873