Wald Method Research Articles

#3822 POLYOMAVIRUS INFECTION MONITORING BY QUANTITATIVE PCR IN KIDNEY RECIPIENTS AS AN INSTRUMENT FOR PREVENTING POSTTRANSPLANT COMPLICATIONS

Abstract Background and Aims Polyomaviruses (PyV) are ubiquitous human viral pathogens. BKV and JCV representing this viral family are common causative agents of viral complications among kidney recipients. Viral load higher than 1 × 107 copies/ml in urine (viruria) or 1 × 104 copies/ml in serum (viremia) in posttransplantation period may lead to polyomavirus-associated nephropathy (PVAN), hemorrhagic cystitis (HC) or even kidney transplant failure. The aim of the study was to assess PyV reactivation frequency in patients during 12 months after renal transplantation (RT) and to identify molecular subtypes of BKV and JCV. Method We examined 3207 samples of biological material (serum and urine) of 763 adult (>18 years) patients who underwent renal transplantation (RT) at the State Institution “Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology”, Healthcare institutions “Brest Regional Clinical Hospital”, “Vitebsk Regional Clinical Hospital Belarus”, “Mogilev Regional Clinical Hospital”. These patients were divided into 2 groups: group 1 included 394 patients examined only for BKV infection, group 2 – 356 recipients examined for both BKV and JCV infection. Serum and urine samples for regular monitoring were collected from patients before RT, every 2 weeks first 3 months, then at 6, 9, 12 months after RT. In the case of complication development samples from patients were collected later then 1-year monitoring period. PyV DNA was detected by real-time PCR. Viral DNAs from 17 BKV-positive and 11 JCV-positive patients were molecular typed by partial sequencing of VP1 genome region. Confidence intervals for the proportions were calculated using Wald's method. Results Results showed that BKV detection total frequency in the group 1 was 14.47% [11.32%; 18.3%], almost all patients developed viruria, only 2.54% [1.32%; 4.67%] had viremia. In the group 2 PyV DNA was detected in 46.07% [40.96%; 51.26%] of recipients: 19.10% [15.34%; 23.52%] had BKV infection, 19.94% [16.11%; 24.42%] – JCV, 7.02% [4.76%; 10.2%] – BKV+JCV mixed infection. Frequency of viremia was 6.74% [4.53%; 9.87%] in this group. Maximal BKV viral load levels reached 1.2 × 1012 copies/ml in urine and 5.9 × 107 copies/ml in serum. JCV loads were up to 3 × 109 copies/ml in urine and 1.2 × 108 copies/ml in serum. Then we analyzed frequency of PyV detection before RT and during the first year after RT among the 102 recipients. Results displayed on the Fig. 1 showed that the peak of PyV infection registration and the higher risk for patient had a place on the 1.5-2.5 months after RT. Quantitative monitoring of viral load in posttransplant period was the basis for the correction of the applied immunosuppressive therapy regimens in relation to the recipients with a high viral load (higher than 1 × 107 copies/ml in urine or 1 × 104 copies/ml in serum). The results of molecular typing showed that 17 BKV isolates belonged to subgroups Ib-2 and IVc-2 (12 and 5 isolates, respectively). Within subgroups Ib-2 isolates formed 3 clusters corresponding 3 separate genovariants. JCV isolates belonged to subtype 1A, 1B and 2A (7, 3 and 1 of isolates, respectively). The last one had 99% nucleotide sequence similarity with Greece and South Korea isolates. Conclusion Our data demonstrated an importance of PyV DNA monitoring of kidney recipients in the posttransplant period starting from the first days after RT to predict development of PyV complications as PVAN, HC or others by correcting the immunosuppressive therapy.

#3822 POLYOMAVIRUS INFECTION MONITORING BY QUANTITATIVE PCR IN KIDNEY RECIPIENTS AS AN INSTRUMENT FOR PREVENTING POSTTRANSPLANT COMPLICATIONS

Abstract Background and Aims Polyomaviruses (PyV) are ubiquitous human viral pathogens. BKV and JCV representing this viral family are common causative agents of viral complications among kidney recipients. Viral load higher than 1×107 copies/ml in urine (viruria) or 1×104 copies/ml in serum (viremia) in posttransplantation period may lead to polyomavirus-associated nephropathy (PVAN), hemorrhagic cystitis (HC) or even kidney transplant failure. The aim of the study was to assess PyV reactivation frequency in patients during 12 months after renal transplantation (RT) and to identify molecular subtypes of BKV and JCV. Method We examined 3207 samples of biological material (serum and urine) of 763 adult (>18 years) patients who underwent renal transplantation (RT) at the State Institution "Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology", Healthcare institutions "Brest Regional Clinical Hospital", "Vitebsk Regional Clinical Hospital Belarus", "Mogilev Regional Clinical Hospital". These patients were divided into 2 groups: group 1 included 394 patients examined only for BKV infection, group 2 – 356 recipients examined for both BKV and JCV infection. Serum and urine samples for regular monitoring were collected from patients before RT, every 2 weeks first 3 months, then at 6, 9, 12 months after RT. In the case of complication development samples from patients were collected later then 1-year monitoring period. PyV DNA was detected by real-time PCR. Viral DNAs from 17 BKV-positive and 11 JCV-positive patients were molecular typed by partial sequencing of VP1 genome region. Confidence intervals for the proportions were calculated using Wald's method. Results Results showed that BKV detection total frequency in the group 1 was 14.47% [11.32%; 18.3%], almost all patients developed viruria, only 2.54% [1.32%; 4.67%] had viremia. In the group 2 PyV DNA was detected in 46.07% [40.96%; 51.26%] of recipients: 19.10% [15.34%; 23.52%] had BKV infection, 19.94% [16.11%; 24.42%] – JCV, 7.02% [4.76%; 10.2%] – BKV+JCV mixed infection. Frequency of viremia was 6.74% [4.53%; 9.87%] in this group. Maximal BKV viral load levels reached 1.2×1012 copies/ml in urine and 5.9×107 copies/ml in serum. JCV loads were up to 3×109 copies/ml in urine and 1.2×108 copies/ml in serum. Then we analyzed frequency of PyV detection before RT and during the first year after RT among the 102 recipients. Results displayed on the fig.1 showed that the peak of PyV infection registration and the higher risk for patient had a place on the 1.5-2.5 months after RT. Quantitative monitoring of viral load in posttransplant period was the basis for the correction of the applied immunosuppressive therapy regimens in relation to the recipients with a high viral load (higher than 1×107 copies/ml in urine or 1×104 copies/ml in serum). The results of molecular typing showed that 17 BKV isolates belonged to subgroups Ib-2 and IVc-2 (12 and 5 isolates, respectively). Within subgroups Ib-2 isolates formed 3 clusters corresponding 3 separate genovariants. JCV isolates belonged to subtype 1A, 1B and 2A (7, 3 and 1 of isolates, respectively). The last one had 99% nucleotide sequence similarity with Greece and South Korea isolates. Conclusion Our data demonstrated an importance of PyV DNA monitoring of kidney recipients in the posttransplant period starting from the first days after RT to predict development of PyV complications as PVAN, HC or others by correcting the immunosuppressive therapy.

Predicting the tolerability of inhalation therapy as a stage of a personalized approach in the treatment of children with cystic fibrosis

Background. Considering the features of basic therapy for chronic inflammatory bronchopulmonary process in cystic fibrosis (CF), which includes almost daily inhalation of pharmacological drugs (mucolytics, hypertonic saline (HS), antibiotics), evaluation of their tolerability is relevant in practice. The purpose of the study is to create a prognostic scale convenient for use in practical medicine, which would predict development of bronchial hyperreactivity syndrome in children with CF, based on clinical and anamnestic data, the results of molecular genetic research and inhalation tests with increasing concentrations of HS to prescribe personalized treatment. Materials and methods. The results of clinical and anamnestic, microbiological, biochemical, molecular and genetic studies and inhalation tests with increasing concentrations of HS were analyzed in 40 children with CF. The creation of the predictive algorithm was based on the application of correlation analysis, receiver operating characteristic analysis, binary logistic regression, Wald and Kullback method. Results. Two prognostic models have been created that can be used at different stages of providing medical care. Model 1 was built for the ambulatory stage of providing medical care to patients with CF, considering clinical and anamnestic data, molecular genetic predictors, as well as clinical symptoms during inhalation tests with increasing concentrations of HS. This model also can be used in young children who cannot perform spirometry to assess their external breathing function. For the highly specialized medical care, model 2 was created, which considers indicators of spirometric data of inhalation tests with increasing concentrations of HS and the level of exhaled nitric oxide. Conclusions. The developed models make it possible to calculate with high probability the risk of developing bronchial hyperreactivity to perform a personalized selection of HS and choose preventive brocholytic therapy as needed.

Patient safety in emergency departments: a problem for health care systems? An international survey.

Patient safety in healthcare is one of the cornerstones of quality of care. The emergency department (ED) is by its very nature a place where errors and safety issues are liable to occur. The aim of the study was to assess health professionals' perception of the level of safety in EDs and to identify in which work domains safety appears most at risk. Between 30 January and 27 February 2023, a survey addressing the main domains of safety was distributed to ED health care professionals through the European Society of Emergency Medicine contact network. It addressed five main domains: teamwork, safety leadership, physical environment and equipment, staff/external teams, and organisational factors and informatics, with a number of items for each domain. Further questions about infection control and team morale were added. The Cronbach's alpha measure was calculated to assure internal consistency. A score was developed for each domain by adding the question's value using the following ranking: never (1), rarely (2), sometimes (3), usually (4), and always (5) and was aggregated in three categories. The calculated sample size needed was 1000 respondents. The Wald method was used for analysis of the questions' consistency and X2 for the inferential analysis. The survey included 1256 responses from 101 different countries; 70% of respondents were from Europe. The survey was completed by 1045 (84%) doctors and 199 (16%) nurses. It was noted that 568 professionals (45.2%) had less than 10 years' experience. Among respondents, 80.61% [95% confidence interval (CI) 78.42-82.8] reported that monitoring devices were available, and 74.7% (95% CI 72.28-77.11) reported that protocols for high-risk medication and for triage (66.19%) were available in their ED. The area of greatest concern was the disproportionate imbalance between needs and the availability of staff at times of greatest flow, considered sufficient by only 22.4% (95% CI 20.07-24.69) of doctors and 20.7% (95% CI 18.41-22.9) of nurses. Other critical issues were overcrowding due to boarding and a perceived lack of support from hospital management. Despite these difficult working conditions, 83% of the professionals said they were proud to work in the ED (95% CI 81.81-85.89). This survey highlighted that most health professionals identify the ED as an environment with specific safety issues. The main factors appeared to be a shortage of personnel during busy periods, overcrowding due to boarding, and a perceived lack of support from hospital management.

Specifying prior distributions in reliability applications

Especially when facing reliability data with limited information (e.g., a small number of failures), there are strong motivations for using Bayesian inference methods. These include the option to use information from physics‐of‐failure or previous experience with a failure mode in a particular material to specify an informative prior distribution. Another advantage is the ability to make statistical inferences without having to rely on specious (when the number of failures is small) asymptotic theory needed to justify non‐Bayesian methods. Users of non‐Bayesian methods are faced with multiple methods of constructing uncertainty intervals (Wald, likelihood, and various bootstrap methods) that can give substantially different answers when there is little information in the data. For Bayesian inference, there is only one method of constructing equal‐tail credible intervals—but it is necessary to provide a prior distribution to fully specify the model. Much work has been done to find default prior distributions that will provide inference methods with good (and in some cases exact) frequentist coverage properties. This paper reviews some of this work and provides, evaluates, and illustrates principled extensions and adaptations of these methods to the practical realities of reliability data (e.g., non‐trivial censoring).

Valor pronóstico de la perfusión cerebral por RM en el estudio inicial de los gliomas de alto grado

ObjectivesTo evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with high grade gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. Patients and methodsThe patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the lineal regression method.Those statistical analysis were carried out using the software SPSS v.17. ResultsThirty-eight patients were included (average age: 61.1years old). The general average survival period was 20.6months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV) >3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6months vs. 22.8months, P=.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. ConclusionsIt has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.

Comparison of 7 methods for sample size determination based on confidence interval estimation for a single proportion

To compare different methods for calculating sample size based on confidence interval estimation for a single proportion with different event incidences and precisions. We compared 7 methods, namely Wald, AgrestiCoull add z2, Agresti-Coull add 4, Wilson Score, Clopper-Pearson, Mid-p, and Jefferys, for confidence interval estimation for a single proportion. The sample size was calculated using the search method with different parameter settings (proportion of specified events and half width of the confidence interval [ω=0.05, 0.1]). With Monte Carlo simulation, the estimated sample size was used to simulate and compare the width of the confidence interval, the coverage of the confidence interval and the ratio of the noncoverage probability. For a high accuracy requirement (ω =0.05), the Mid-p method and Clopper Pearson method performed better when the incidence of events was low (P < 0.15). In other settings, the performance of the 7 methods did not differ significantly except for a poor symmetry of the Wald method. In the setting of ω=0.1 with a very low p (0.01-0.05), failure of iteration occurred with nearly all the methods except for the Clopper-Pearson method. Different sample size determination methods based on confidence interval estimation should be selected for single proportions with different parameter settings.

Bootstrapped artificial neural network model for uncertainty analysis in MELCOR simulation of severe accident

This study is concerned with uncertainty analysis of MELCOR simulation of a hypothetical severe accident initiated by station blackout (SBO) in a Nordic boiling water reactor (BWR). The hydrogen mass from cladding oxidation and the vessel failure timing in the accident are selected as the figures of merit (FOMs) in this study. As a conventional approach of uncertainty analysis, 456 cases with random sampling of 31 MELCOR input parameters are executed by the code to produce the empirical cumulative distribution functions (CDFs) and the empirical 95th percentiles of the FOMs. Given the sufficient sample cases, uncertainty analyses through two nonparametric methods at various orders, i.e., the Wilks' method and the Wald & Guba's method, can then be performed to obtain the distributions of 95/95 estimates (95th percentiles estimated at a 95% confidence level) of single FOM and two FOMs. However, the conventional approach turns out to be time consuming and computationally expensive since many sample cases require iterative tuning of MELCOR input to restart and finish calculations. To overcome this issue encountered in the conventional approach of uncertainty analysis, an alternative approach is developed in the present study, in which 150 and 170 MELCOR calculation cases are used to develop bootstrapped artificial neural network (ANN) models which predict single FOM and two FOMs, respectively. The bootstrapped ANN models are then employed in uncertainty analyses through the two nonparametric methods of 95/95 estimates mentioned above. The comparative results show that the alternative approach can reproduce the distributions of 95/95 estimates for both single FOM and two FOMs with less computational costs. Moreover, while the Wilks' method or the Wald & Guba's method at a very high order (e.g., 100th order) can be used in the alternative approach to produce 95/95 estimates closer to the empirical 95th percentile, it is practically impossible to do so in the conventional approach due to unaffordable computational cost of excessive MELCOR runs. Hence, it can be concluded that the alternative approach of uncertainty analysis is not only effective (much less MELCOR cases with least fixing of unsuccessful runs), but also enabling high-order nonparametric methods for 95/95 estimates.

The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and their influence on the NLR in NSCLC patients treated with immunotherapy

BackgroundPD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of KRAS mutations in these patients is unclear. Studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. Patients & methodsThis is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. ORR and safety were compared using Wald method. ResultsFrom 100 patients with known KRAS status, 50 were mutated (KRASMut). Mutation in TP53, STK11 and KEAP1 were present, and their status known in, respectively, 19/40 (47.5 %), 8/39 (20.5 %) and 4/38 (10.5 %) patients. STK11Mut and KEAP1Mut were associated with shorter overall survival when compared with wild type tumors (respectively median OS of 3.3 vs 20.4, p = 0.0001 and 10.1 vs 17.7, p = 0.24). When KRAS status was compounded with STK11/KEAP1, KRASMut trended to a better prognosis in STK11+KEAP1WT tumors (median OS 21.1 vs 15.8 for KRASWT, p = 0.15), but not for STK11+/-KEAP1Mut tumors. The NLR was strongly impacted by STK11 (6.0Mutvs 3.6WT, p = 0.014) and TP53 (3.2Mutvs 4.8WT, p = 0.048), but not by KEAP1 or KRAS mutations. ConclusionSTK11Mut and KEAP1Mut are adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11Mut but not by KEAP1Mut, suggesting differences in their resistance mechanism. In STK11-KEAP1WT tumors, KRASMut seem associated with improved survival in NSCLC patients treated with ICIs. MicroAbstractResponse of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known KRAS status. By accounting for different co-mutations, KRAS mutation was found to be associated with a better median overall survival in STK11 and KEAP1 wild-type tumors (21.1 vs 15.8, p = 0.15). NLR was impacted by STK11, but not KEAP1 mutation, suggesting a difference in their resistance mechanism.

Bayesian Computation for the Parameters of a Zero-Inflated Cosine Geometric Distribution with Application to COVID-19 Pandemic Data

A new three-parameter discrete distribution called the zero-inflated cosine geometric (ZICG) distribution is proposed for the first time herein. It can be used to analyze over-dispersed count data with excess zeros. The basic statistical properties of the new distribution, such as the moment generating function, mean, and variance are presented. Furthermore, confidence intervals are constructed by using the Wald, Bayesian, and highest posterior density (HPD) methods to estimate the true confidence intervals for the parameters of the ZICG distribution. Their efficacies were investigated by using both simulation and real-world data comprising the number of daily COVID-19 positive cases at the Olympic Games in Tokyo 2020. The results show that the HPD interval performed better than the other methods in terms of coverage probability and average length in most cases studied.

Pancreas fat content, insulin homeostasis and circulating endothelial microparticles inmale essential hypertensive patients.

Thepancreas fat contenthas been poorly investigated in essential hypertension. The authors aim to relatepancreas and liver fat contentwith parameters measuring insulin resistance, beta-cell function and also withmarkers ofendothelial dysfunction and platelet or endothelial cell destruction. The authors studied a group of 40malehypertensive patients with well-controlled blood pressure, maintaining a stable weight, and having not changed their medication during the last year. Pancreas fat content was correlated with HOMA-IR (r=.616, p<.001), HOMA-S (r=-.439, p<.005), beta cell function parameter (r=.457, p<.005), and QUICKI (r=.412, p<.01), whereas liver fat was not patients in thehighest quartileof pancreas fat content had more circulating endothelial microparticles than patients in the other quartiles (median 129 [94.3-200] vs. 60.9 [49.4-88.8], p=.002).However, patients in the highest quartile of the pancreas fat content distribution did not differ from the lowest in hyperemic response after ischemia nor circulating platelet microparticles count. Liver fat content was not related to any of the parameters studied. In a multivariate stepwise binary logistic regression analysis (Wald Method) circulating endothelial microparticles remain significantly associated with pancreas fat content after adjusting for confounding factors, such as tobacco, diabetes mellitus, hypercholesterolemia, or metabolic syndrome. Our results reflect that in essential hypertension,pancreas fat contentis superior toliver fatto study beta-cell functionality and insulin resistance. Moreover, the authors described for the first time thatpancreas fat content isrelated to endothelial cell destruction. Further studies are needed to confirm this point.

Modern Design and Analysis For Hit/Miss Probability of Detection Studies Using Profile Likelihood Ratio Confidence Intervals

To characterize the capability of an inspection system, indications from the system must be collected over a range of defect sizes. For flaw indications, insufficient sample size, overlap, or evenness between hit and miss indications may cause the probability of detection (POD) estimations to not exist or have high bias. Extensive simulations of representative Lognormal, Weibull, and Uniformly distributed data at varying levels of overlap, evenness, and sample size were fit using four modeling techniques: logistic regression, Firth’s Bias Adjusted Likelihood, the Lasso, and a ranked set sampling method from nonparametric statistics. Profile likelihood ratio confidence intervals were used instead of the standard Wald method to calculate a90/95. The probability of existence and the percent bias of the estimates provide recommendations for the ideal levels of overlap, evenness, modeling technique, and sample size requirements when designing a hit/miss POD study.

Federal innovation platform: reproductive health of 1st year students of Smolensk State Medical University

Aim. To study the state of reproductive health of female students of Smolensk State Medical University according to the 2020 monitoring data. To analyze the real picture of sexual life and reproductive health of first-year female students. To consider the necessity of including additional medical examinations in the dispensary monitoring plan.&#x0D; Materials and methods. We examined 507 first-year female students aged 1827 years at Smolensk State Medical University. The examination included the collection of complaints, general and obstetric-gynecological history, questionnaires, gynecological examination, general clinical examination, pelvic ultrasound, microscopic and oncocytological smears, pH-metry of vaginal secretions, colposcopy. Statistical data processing included methods of descriptive statistics. Construction of the 95% confidence interval was done according to the formula for fractions and frequencies by the Wald method. Significance of the difference between the studied features was assessed using Fisher's angle transformation. Statistical significance was considered at 95% (p0.05) and 99% (p0.01) probability. Statistical analysis of the results was performed in Microsoft Excel 2016 using the AtteStat 12.0.5.&#x0D; Results. The examination of female students of Smolensk State Medical University revealed reproductive health disorders and lack of awareness of modern contraceptives. The study concluded that an ultrasound examination of the ovarian tract, colposcopy, endocrinologist consultation, examination of hormonal background, and STI examination should be added to the plan of dispensary observation.&#x0D; Conclusion. The data obtained in the course of the present study indicate that modern first-year female students have an insufficient level of reproductive education that does not meet the requirements of our time. In our opinion, the scientific and practical project will help to increase competence and responsibility in health saving issues to improve and strengthen reproductive health, to develop and implement a set of measures in the form of clinical and diagnostic research of the reproductive system, informational and educational lectures on the prevention of abortion, infertility and other diseases, sexual education, and in the future to affect the demographic situation.

Risk factors of platelet refractoriness after thrombocyte concentrate transfusion in pediatric acute leukemia

Children with acute leukemia often require platelet transfusions, but the platelet count frequently doesn't reach a satisfactory response, which is known as platelet refractoriness. This study aimed to analyze the risk factors for platelet refractoriness after thrombocyte concentrate transfusion in children with acute leukemia. An analytical observational study with a prospective approach, with subjects with acute leukemia who met the inclusion and exclusion criteria, at Dr. Soetomo General Hospital. Analysis with Chi-square test; Odds Ratio (OR), 95% confidence interval, multivariate Backward Wald method with p&lt;0.05. There were 30 subjects, consisting of 19 subjects (63.3%) with platelet refractoriness, 11 subjects (36.7%) did not have platelet refractoriness. The significant differences factors are fever, splenomegaly, and antibiotic use with p values of 0.007; 0.004, and 0.049. There was no difference between gender, sepsis, heavy bleeding, chemotherapy, history of thrombocyte concentrate transfusion, and immature platelet fraction with the incidence of platelet refractoriness (p&gt;0.05). Splenomegaly had a 5.333 times greater probability of platelet refractoriness after thrombocyte concentrate transfusion compared to those without splenomegaly in children with acute leukemia, (p=0.008), (OR 5.333; 95% CI 1.554 – 18.304). Splenomegaly is a risk factor for platelet refractoriness after thrombocyte concentrates transfusion in children with acute leukemia.

Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study

BackgroundObservational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.MethodsTwo-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10−8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10−5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.ResultsBased on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 – 1.10, P = 1.67 × 10−4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75–0.93, P = 7.76 × 10−4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74–0.92, P = 4.15 × 10−4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.ConclusionOur findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.

Prevalence of attention-deficit/hyperactivity disorder and intellectual disability among children with hydrocephalus.

Little is known about the prevalence of attention-deficit/hyperactivity disorder (ADHD) in children with hydrocephalus. In this study, the authors assessed the prevalence of ADHD and its association with clinical and demographic factors, including intellectual disability (ID), a potential factor that can confound the diagnosis of ADHD. The authors conducted a cross-sectional study of children 6-12 years of age with hydrocephalus using parent telephone surveys. The Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) and the National Institute for Children's Health Quality (NICHQ) Vanderbilt Assessment Scale were used to screen for ID and ADHD, respectively. Among children without ID, the authors identified those with ADHD and calculated a prevalence estimate and 95% confidence interval (Wald method). Logistic regression analysis was conducted to compare children with ADHD with those without ADHD based on demographics, family income, parental educational, etiology of hydrocephalus, and primary treatment. As a secondary analysis, the authors compared subjects with ID with those without using the same variables. Multivariable analysis was used to identify factors with independent association with ADHD and ID. A total of 147 primary caregivers responded to the telephone questionnaire. Seventy-two children (49%) met the cutoff score for ID (CAIDS-Q). The presence of ID was significantly associated with lower family income (p < 0.001). Hydrocephalus etiology (p = 0.051) and initial treatment (p = 0.06) approached significance. Of children without ID (n = 75), 25 demonstrated a likely diagnosis of ADHD on the NICHQ, yielding a prevalence estimate of 0.33 (95% CI 0.22-0.44). No clinical or demographic variable showed significant association with ADHD. These data indicate that the prevalence of ADHD among children with hydrocephalus (33%) is higher than among the general population (estimated prevalence in Alabama is 12.5%). ID is also common (49%). Routine screening for ADHD and ID in children with hydrocephalus may help to ensure that adequate resources are provided to optimize functional outcomes across development.

Medication Adherence and Belief about Medication among Vietnamese Patients with Chronic Cardiovascular Diseases within the Context of Implementing Measures to Prevent COVID-19.

Background: Long-term adherence is crucial for optimal treatment outcomes in chronic cardiovascular diseases (CVDs), especially throughout the COVID-19 wide-spreading periods, making patients with chronic CVDs vulnerable subjects. Aim: To investigate the relationship between the characteristics, beliefs about prescribed medication, COVID-19 prevention measures, and medication adherence among patients with chronic CVDs. Methods: This is a cross-sectional study of outpatients with chronic CVDs in Southern Vietnam. The specific parts regarding the Beliefs about Medicines Questionnaires (BMQ—Specific) and the General Medication Adherence Scale (GMAS) were applied to assess the beliefs about and adherence to medication. The implementation measures to prevent COVID-19 in patients were evaluated according to the 5K message (facemask, disinfection, distance, no gathering, and health declaration) of the Vietnam Ministry of Health. A multivariable logistic regression with the Backward elimination (Wald) method was used to identify the associated factors of medication adherence. Results: A slightly higher score in BMQ-Necessity compared to BMQ-Concerns was observed. A total of 40.7% of patients were recorded as having not adhered to their medications. Patients’ behavior was most frequently self-reported by explaining their non-adherence (34.7%). Statistical associations were found between rural living place, unemployment status, no or only one measure(s) of COVID-19 prevention application, and medication adherence. Conclusion: During the COVID-19 spreading stage, patients generally showed a positive belief about medication when they rated the importance of taking it higher than its side effects. The data analysis suggested that rather than patients’ beliefs, the clinicians should consider the patient factors, including living place, employment, and the number of epidemic preventive measures applied for guiding the target patients for improving medication adherence.

Gender disparity in authorship of clinical trials leading to cancer drug approvals between 2008 and 2018: The glass ceiling of academic oncology.

11048 Background: Authorship, expressly premier positions (first, corresponding, or senior author), in peer reviewed journals is widely acknowledged as scientific credit in academia. Yet, gender inequities and biases pervade this facet of the scientific ecosystem. We reviewed the authorship of pivotal FDA trials that established the standards of care in oncology over the past decade with the goal of defining the magnitude of gender disparity in the most influential literature of the field in recent years. Methods: We collected and assessed data from the primary publication of 231 trials that enabled FDA drug approvals in hematology and oncology from July 2008 to June 2018. Author gender was assigned from listed names using statistical probability and confirmed using institutional websites and online databases (genderchecker database, biographical paragraphs, and social media). Authors where gender was not clearly identified (1.23%) were excluded. To account for equal authorship contribution, we included co-authors as distinct data points, and credit was given to reports for any women in premier authorship positions (first, corresponding, or senior author) to avoid overestimating disparity. Descriptive statistics were used, and 95% confidence intervals (95%CI) were reported using modified Wald method. Proportions were compared using Fisher-exact and Chi-squared test. Unadjusted P values of &lt; 0.05 were considered significant. Results: A total of 4664 (98.8%) authors were included in this analysis across 227 publications. Of these, 1287 (27.6%) were female with a median of 25.9% female authorship in total per trial. Female authorship was significantly higher for non-randomized (30.4% v 26.5% for randomized, P = 0.007) and phase 1/2 trials (29.9% v 26.3% for phase 3, P = 0.009) and varied with trial size (P &lt; 0.001), with the proportion greater in trials with ≤100 patients versus those with &gt; 500 patients. Female authorship in fields of breast and gynecological oncology was higher (41.3%) than other cancers (26.0%, P &lt; 0.001). Women were proportionally less likely to hold premier (9.2% v 18.2%, OR 0.46, 95%CI: 0.4 – 0.6, P &lt; 0.001), first (3.2% v 6.3%, OR 0.49, 95%CI: 0.3 – 0.7, P &lt; 0.001), senior (3.3% v 6.0%, OR 0.54, 95%CI: 0.4 – 0.8, P = 0.002) and corresponding (2.5% v 5.8%, OR 0.42, 95%CI 0.3 – 0.6, P &lt; 0.001) authorship but not second author role (4.1% v 5.1%, OR 0.80, 95%CI 0.6 – 1.1, P = 0.17). Conclusions: The under-representation of women in premier authorship positions in pivotal clinical trials, demonstrated in our study, serves as a barometer of a biased academic infrastructure, amplifying existing calls to address barriers that limit the full inclusion of women in oncology.

MO1016: Features of the Formation of Post-Infectious and Post-Vaccinal Humoral Immune Response to SARS-COV-2 in Kidney Recipients

BACKGROUNDThis paper presents the results of studying the characteristics of the antibody response in kidney recipients who are at high risk of severe COVID-19.METHODThe study of features of the formation of post-infectious anti-SARS-CoV-2 IgG was carried out in the group of kidney recipients (n = 171) with PCR confirmed diagnosis of COVID-19. Studies of the characteristics of post-vaccination immunity were carried out in a group of vaccinated recipients (n = 49) with Sputnik V (Russia) or Vero Cell (China).ELISA was used to detect IgG to S and N proteins of the SARS-CoV-2.Comparative studies used a simple randomized selection of immunocompetent COVID-19 patients (n = 163).Statistical data processing was carried out using the χ2 and Wald's methods.RESULTSIt was found that 30 days after the onset of clinical symptoms of COVID-19 in kidney recipients, IgG to S and/or N proteins of SARS-CoV-2 were detected in 89.5% (83.9%–93.3%) of them. The detection rate of IgG to the S protein was higher than that to the N protein [87.7% (81.9%–91.9%) and 62.0% (54.5%–68.9%), respectively). At the same time, the seroprevalence to the pathogen varied by age: in the 18–34-year-old group it was 77.7% (59.9%–88.9%), in the 50–64-year-old group it was 96.7% (88.2%–99.8%) and in the group >64 years old it was 80.0% (66.8%–89.0%). This trend of antibody production in older recipients correlated with the highest frequency of registration in them of moderate and severe forms [66.7% (56.4%–75.6%)]. Differences due to the severity of the disease were noted both in the frequency of detectable antibodies [80.3% (69.5%–88.0%) in recipients with a mild form of COVID-19 and 96.0% in recipients with a severe form of infection (P < .001)] and in the intensity of the formed anti-SARS-CoV-2 immunity. Thus, high values of PC (positivity coefficient) (>12) to S protein were recorded in 52.7% (39.8%–65.3%) and 63.2% (53.1%–72.2%) patients with mild and severe forms of COVID-19, respectively, which indicated a direct dependence of the production of antiviral antibodies on the severity of the infection. It was found that in 62.6% (55.1%–69.5%) of recovered recipients anti-SARS-CoV-2 IgG persisted for a period of 3 months from the onset of infection. In a significant proportion of recipients [42.8% (35.5%–50.2%)], antibodies were detected for up to 15 months. In general, the post-infectious antibody response in kidney recipients and immunocompetent patients had similar patterns of development. Despite the general mechanism of antibody production, in immunocompetent patients, the frequency of detection of antiviral antibodies (to N protein: 82.9% and to S protein: 91.2%), tension indicators (high values of PC to N protein: 51.0% and to S protein: 75.5%) and the duration of retention (in 50.3% at 15 months of monitoring) were slightly higher than the same parameters in recipients with COVID-19.In kidney recipients after immunization with Sputnik V and Vero Cell (n = 34), a rather low detection rate of antiviral IgG [52.9% (36.7%–68.6%) compared with a similar parameter (P < .001) in vaccinated immunocompetent individuals [96.8% (94.8%–98.1%)] was found. The seroprevalence in the group of recipients with hybrid immunity (after illness and vaccination, n = 15) was 86.7% (60.9%–97.5%). In a comparative analysis of the intensity of post-vaccination immunity, high values of PC to S protein (>12) were recorded in 44.0% (26.7%–62.9%) of recipients vaccinated with Sputnik V and 50.0% (31.4%–68.6%) of recipients vaccinated with Vero Cell. The inverse relationship was observed in immunocompetent individuals: 64.7% (58.1%–70.7%) for Sputnik V and 44.2% (36.8%–51.8%] for Vero Cell.CONCLUSIONThe patterns of antibody response to the causative agent in recipients with COVID-19 are comparable to those in immunocompetent patients, while for vaccinated recipients, a low frequency of detection of antiviral antibodies was shown, which indicates the need to continue research on the humoral immunity in people with vulnerable immunity in order to select the best tactics for COVID-19 immunization.

Hormonal Influence in Stress Urinary Incontinence During Pregnancy and Postpartum.

Hormonal changes have been proposed as an etiological factor of stress urinary incontinence (SUI) during pregnancy. Our main objective was to demonstrate the role of hormones in SUI development during pregnancy and postpartum. A prospective longitudinal study was designed. Primiparous women without previous urinary incontinence symptoms were included. Symptoms and Quality of Life (QoL) Questionnaires, physical examinations, and hormone concentration (progesterone, estradiol, and relaxin) were collected twice during pregnancy and three times during postpartum. Logistic regression models, with Wald's forward variable selection method, were used. Prevalence of SUI was 11% in the first trimester, 50% in the third trimester, and 16.4% at 6months postpartum. The risk of developing SUI throughout pregnancy is higher in women with higher progesterone concentration in the first trimester (OR 1.38, 95% CI 1.06-1.81, p < 0.05) and it is lower in women with stronger pelvic floor muscles in the first trimester (OR 0.35, 95% CI 0.17-0.72, p < 0.05). When occurred during pregnancy, SUI has a 14-fold higher risk of persistence 6months after birth. In addition, the severity of these symptoms is also an independent risk factor for SUI persistence at 6months postpartum (OR 1.41, 95% CI 1.15-1.73, p < 0.05). Quality of Life was affected for pregnant women with SUI symptoms. SUI is a highly prevalent condition during pregnancy, affecting the QoL of women in many areas. Higher concentration of progesterone can play a role in SUI development during pregnancy. The presence and severity of SUI during pregnancy are risk factors for the persistence of symptoms 6months postpartum. Sustaining an optimal pelvic floor muscle strength could prevent SUI during pregnancy.