Wald Method Research Articles

Gender differences in periodontal pocket microflora in patients with chronic generalized periodontitis

Background: Periodontal disease, the primary cause of tooth loss, is a critical public health concern with a considerable impact on quality of life. It is of interest to explore gender differences in the course of inflammatory periodontal diseases, as well as the prospects of their personalized treatment and prevention in males and females. Aim: To assess the dental health and quantitative composition of periodontal pocket microflora in periodontitis patients, taking into account gender differences. Materials and Methods: The study included 39 patients with moderate chronic generalized periodontitis aged 40–60 years. The diagnosis was made using both primary and secondary dental diagnostic tools. The study had two groups: males (41%, n=16) and females (59%, n=23). The following parameters were assessed: oral hygiene index (OHI-S), severity of gingival inflammation (PMA), and quantitative composition of periodontal pocket microflora (DENTOSCREEN, “Lytech” Co. Ltd., Russia), taking into account gender differences. The study findings were statistically processed using Microsoft Office Excel 2016 with Data Analysis and AtteStat 12.0.5 add-ins. The Shapiro–Wilk test was used. The data are presented as median and interquartile range: Me [Q1; Q3]. The frequency of microorganisms is presented as percentage of the mean and standard error of the mean. The confidence interval was calculated using the Wald method, according to the formula for proportions and frequencies. For small values, the Wald method with Agresti–Coull correction was used. Samples were compared using the following tests: the Mann–Whitney U test was used for quantitative data and Fisher’s angular transformation (φ*emp) for frequency (nominal) attributes. Significant differences were defined as a probability 95% (p 0.05). Results: The quantitative composition of periodontal pocket microflora in patients with moderate periodontitis revealed significant gender differences, as demonstrated by an increase in the count of Fusobacterium nucleatum and Prevotella intermedia, as well as the frequency of Porphyromonas gingivalis, in males compared to females (φ*emp=1.736; p 0.05). Dental health indices confirmed the hypothesis of significant differences between males and females in terms of plaque index (OHI-S) and РМА. In males, poor oral hygiene was reported in 93.7% cases, which was significantly higher (φ*emp=2.04; p 0.05) than in females (69.6%). Moderate gingival inflammation was more prevalent in males, while mild gingival inflammation was more prevalent in females (p 0.05). Conclusion: The study findings emphasize the importance of oral hygiene in the prevention of chronic periodontitis and can be used to improve complex treatment algorithms for patients with periodontal diseases. This includes more frequent dental check-ups and professional oral care sessions, as well as oral hygiene training and monitoring, in males compared to females. Diagnosis by polymerase chain reaction allows for the identification and quantitative determination of DNA from periodontopathogenic bacteria at low concentrations, as well as the justification of treatment algorithms and prediction of treatment outcomes.

Predictions of live birth in IVF programs of patients with recurrent implantation failure

BackgroundWhen a high-quality embryo is implanted into the uterus, but the pregnancy is not established as shown by the ultrasound visualization of an intrauterine gestational sac, this is known as “implantation failure.” Cases when more than two times implantation failure occurred was defined as recurrent implantation failure (RIF). Additional testing is done at this stage of infertility treatment to avoid a repeat of the same result with a future in vitro fertilization (IVF) effort. Aim of the studyThe study aimed to evaluate predictive value of using embryo transfer personalization because of the implantation window study in combination with preimplantation genetic testing in patients with recurrent implantation attempts. MethodsBriefly describe the main methods or treatments applied: Ninety-three infertile women make up the sample for this prospective cohort study. In regard to treatment results, the study intends to assess the predictive importance of patient characteristics, screening indicators, and several features of IVF cycles, such as the quantity, quality, and developmental stage of the transferred embryos. Statistical methods employed include the calculation of the median (Me) and interquartile range (IQR) for continuous variables. The Mann-Whitney U test was used to discern differences between unrelated samples, while categorical variables were presented as absolute and percentage values. The Pearson’s Chi-squared test assessed differences between groups. Logistic regression, utilizing both enter and backward Wald methods, was applied to establish associations with binary outcomes. ResultsThe integration of individualized embryo transfer and preimplantation genetic testing (PGT) significantly enhanced the likelihood of live births by 3.4 times in patients experiencing recurrent implantation failure (RIF), with a statistical significance of p = 0.026. In contrast, employing PGT alone increased the probability of live births by 1.5 times; however, this result was not statistically significant (p = 0.439). The predictive model for live birth in patients with RIF, based on our study findings, is defined as follows: the probability of live birth = 1.936 + [1.014 if PGT-A embryos are utilized for transfer] + [1.742 if endometrial preparation is tailored according to the Wellbeing Index (WI)] − [1.860 in cases of secondary infertility] − [1.891 when a male factor is involved]. ConclusionsThe determination of the implantation window (IW) and PGT of the embryo are efficient methods of live birth achievement for patients with RIF.

Prognostic determinants in patients with heart failure with reduced ejection fraction after a first hospitalisation for acute heart failure. COMFE registry

Abstract Introduction The clinical characteristics and determinants for prognosis of patients with a first hospitalisation for heart failure (HF) with reduced left ventricular ejection fraction (LVEF <40%) are poor described and show heterogeneous results that need major investigation. Purpose The aim of our study was to identify the clinical characteristics, prognosis and their main determinants in a prospective registry of patients with HF and reduced LVEF with a first hospital admission for acute heart failure, prognosis and their main determinants in a prospective registry in these patients. Methods We carried out a prospective registry in 2 University Hospitals of patients admitted to cardiology department due to first-time HF hospitalisation with reduced LVEF. 231 admitted consecutively between March 2021 and September 2022 were included, with a mean follow-up of 381 days. Continuous variables were represented as median (interquartile range) and categorical variables as percentage %. A multivariate logistic regression was performed in which age, sex, comorbidities, treatment, rhythm at discharge and improvement in LVEF were included; and using the Wald method, the predictors of rehospitalization and/or death were identified. Data were analysed using SPSS v. 25.0. Results The main baseline characteristics are shown in Table 1. The population had a median age of 71 years, 75% were men, with a high prevalence of arterial hypertension (HBP) (69%) and hyperlipidemia (57%). Quadruple therapy (Na-Glucose cotransporter 2 inhibitor [SGLT2i], Beta-Blocker, mineralocorticoid receptor antagonist [MRA] and angiotensin receptor-neprilysin inhibitor [ARNI], angiotensin converting enzyme inhibitor [ACEi] or Angiotensin-II receptor blocker [ARB]) was achieved in 57% at discharge. The dynamics of NTproBNP was studied from admission to completed up-titration, observing an average reduction of 37% and 32% met the criteria for improved LVEF after. The etiology is described in Figure 1a, with ischemic heart disease being the most represented (31%). Multivariate Cox regression for the combined event of readmission/death from any cause showed that treatment with SGLT2i (OR 0,48 [CI 95%: 0,23-0,98 p:0,04]) and Beta-Blocker (OR 0,35 [CI 95%: 0,14-0,87 p:0,02]) at discharge and improved LVEF (OR 0,33 [CI 95%: 0,15-0,72 p:0,006]) were protective predictors against the event; but diabetes mellitus (DM) was a predictor of a worse prognosis (OR 2,9 [CI 95%: 1,52-5,5 p:0,001]) Fig. 1b. Conclusions Patients with a first admission for HF with reduced LVEF constitute a heterogeneous clinical group. Improvement in LVEF after drug up-titration and treatment with SGLT2i and Beta-blocker are independently associated with a better prognosis. Our findings may have implications for their clinical management.Table 1Figure 1

EARLY MANIFESTATIONS OF HEART FAILURE AND ACTIVITY OF SYSTEMIC INFLAMMATION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION DEPENDING ON RISK FACTORS

Acute myocardial infarction and heart failure (HF) resulting from this condition remain complex and not fully understood problems in cardiology. It is important to detect early manifestations of HF and optimize treatment to prevent pathological myocardial remodeling and the occurrence of adverse events. The increase in systemic inflammation activity (SIA) and the presence of comorbidities in patients contribute to the development of HF. The aim of the study- to investigate the impact of risk factors (RF) such as arterial hypertension (AH), diabetes mellitus (DM), history of COVID-19, and obesity on the occurrence of HF and SIA in patients with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention. Materials and Methods. The study involved 50 patients from the cardiology and reperfusion therapy department of St. Panteleimon Hospital in Lviv (66,00 (52,43-78,35) % men and 34,00 (21,65-47,57) % women), with an average age of 62,01±10,30 years. Blood levels of NT-proBNP (a biomarker of HF) and C-reactive protein (CRP) (a biomarker of SIA) were analyzed on the day of hospitalization for STEMI (the first day from the onset of clinical symptoms, stenting of the infarct-related coronary artery). Results were evaluated using descriptive statistical analysis methods (mean and standard deviation; median and percentile, fractions and their 95 % confidence intervals, calculated by the Wald and Fisher methods), unpaired Student's t-test, and Pearson correlation analysis. Results. The average NT-proBNP levels in the studied patients were 0,50 (0,30; 2,60) ng/ml, and CRP levels were 10,50 (6,00; 20,80) IU/ml (p<0,05, compared to normal parameters). NT-proBNP levels significantly (p<0,05) exceeded the upper reference limit in the presence of AH (0,50 (0,30; 3,30) ng/ml); DM (0,61 (0,30; 4,37) ng/ml); history of COVID-19 (0,61 (0,32; 3,36) ng/ml) (as well as without this RF – 0,49 (0,15; 1,37) ng/ml); obesity (0,31 (0,19; 380) ng/ml). The average NT-proBNP levels in patients with a history of COVID-19 were significantly (p<0,05) higher compared to those in patients without it. CRP levels in blood were significantly (p<0,05) higher than normal values in patients with AH (11,05 (5,60; 25,90) IU/ml); DM (15,20 (7,06; 25,20) IU/ml) (as well as without this RF – 9,50 (5,54; 18,20) IU/ml); history of COVID-19 (12,52 (8,20; 19,65) IU/ml) (as well as without it in history – 9,99 (5,60; 20,06) IU/ml); obesity (9,63 (6,52; 35,00) IU/ml) (as well as without this RF – 10,50 (5,81; 18,40) IU/ml). Average CRP levels in patients with DM and a history of COVID-19 were significantly (p<0,05) higher compared to those without these RFs. The correlation between NT-proBNP and CRP levels was direct – strong in the presence of DM (r=0,78; p=0,012) and history of COVID-19 (r=0,70; p=0,001), medium strength in patients with AH (r=0,55; p=0,0004). Conclusions. In patients with STEMI who underwent myocardial revascularization, early manifestations of HF and a significant increase in SIA occur within the first day of the disease, promoted by such risk factors as AH, DM, history of COVID-19, and obesity. In the presence of DM and history of COVID-19, CRP should be considered an early marker of HF occurrence alongside NT-proBNP, as indicated by a strong direct correlation between these indicators in this category of individuals.

Mortality Rate of COVID-19 With Comorbid Pneumonia in a Rural Area.

A myriad of risk factors and comorbidities have been determined to influence COVID-19 mortality rates; among these is pneumonia. This study considers pneumonia as a risk factor for increased mortality in patients admitted with COVID-19 in a rural healthcare system. We predicted that the presence of pneumonia of any kind would increase mortality rates in patients admitted with COVID-19. A retrospective observational study was conducted using data collected from hospitals in the Freeman Health System (FHS) located in Joplin and Neosho, Missouri. Data were collected between April 1, 2020, and December 31, 2021. Using International Classification of Diseases, Tenth Revision (ICD-10) codes, the investigators identified five distinct patient populations: patients with COVID-19 and pneumonia due to COVID-19 (P1); patients with COVID-19 but without pneumonia due to COVID-19 (P2); patients with COVID-19 and any type of pneumonia (P3); patients with COVID-19 but without any type of pneumonia (P4); and patients without COVID-19 and with any type of pneumonia (P5). In order to understand how pneumonia influences COVID-19 outcomes, the investigators used Wald's method and a two-sample proportion summary hypothesis test to determine the confidence interval and to compare the mortality rates between these populations, respectively. The population of patients with COVID-19 and any type of pneumonia (P3) and the population of patients with COVID-19 and pneumonia due to COVID-19 (P1) showed the highest mortality rates. The population of patients with COVID-19 but without any type of pneumonia (P4) had the lowest mortality rate. The data revealed that having pneumonia combined with COVID-19 in any patient population led to a higher mortality rate than COVID-19 alone. Mortality rates were higher among COVID-19 patients with pneumonia compared to COVID-19 patients without pneumonia. Additionally, pneumonia, by itself, was found to have a higher mortality rate compared to COVID-19 alone.

Fibrinogen to albumin ratio's prognostic value in ischemic stroke patients who underwent mechanical thrombectomy.

<p>Fibrinogen to albumin ratio (FAR) is thought to have a predictive effect in diseases such as cancer and myocardial infarction. We aimed to elucidate the prognostic value of FAR in ischemic stroke patients who underwent mechanical thrombectomy.</p>. <p>A total of 103 patients hospita&shy;lized for acute stroke who underwent me&shy;cha&shy;nical thrombectomy within 6 hours of symp&shy;toms&rsquo; outset have been analyzed retro&shy;spectively. Stroke severity was interpreted via the National Institutes of Health Stroke Scale (NIHSS) score during the neurological examination. Recanalization success after mechanical thrombectomy was evaluated with the TICI score (Thrombolysis in Cerebral Infarction scale), and 2b &ndash; 3 patients were recorded as those with recanalization. The patients&rsquo; modified Rankin scale (mRS) at discharge and at the end of the third month were recorded.&nbsp;</p>. <p>&nbsp;Statistically significant differen&shy;ces were observed in age, admission blood glucose, glomerular filtration rate and FAR according to the mRS scores of the patients in the third month (p&lt;0.05). Significant va&shy;riab&shy;les in the risk factor analysis were re-evaluated in the multivariate model. The best model was determined using the backward Wald method in the multivariate model, and it was determined that differences in age, admission blood glucose, and FAR were significant.</p>. <p>FAR can be used as a novel, effective, economical, and practical biomarker in patient with acute ischemic stroke who underwent mechanical thrombectomy.</p>.

Association of Oxidative Stress on Cognitive Function: A Bidirectional Mendelian Randomisation Study.

The purpose of this study was to investigate the relationship between oxidative stress and cognitive function, encompassing cognitive performance, intelligence, memory, reaction time, speech and vision by a bidirectional Mendelian randomisation study. Independent genetic variants associated with glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin (PRDX), sulfhydryl oxidase (SOX) and thyroid peroxidase (TPO) were explored using a genome-wide association study (GWAS). The inverse variance weighted (IVW) or Wald ratio method was employed to ascertain the relationship between antioxidant enzymes and cognitive function. The MR analyses indicated that the MR effect estimates of GST (β = 0.0352, P = 0.0047, FDR = 0.0164) and TPO (β = 0.0531, P = 0.0003, FDR = 0.0021) were significantly associated with cognitive performance elevation. Furthermore, genetically predicted GST (β = 0.0334, P = 0.0043, FDR = 0.0151) and TPO (β = 0.0496, P = 0.0031, FDR = 0.0151) were found to be associated with high intelligence. Additionally, there were also some associations of SOX (β = 0.0243, P = 0.0283, FDR = 0.066) on high cognitive performance, TPO (β = 0.1189, P = 0.0315, FDR = 0.2205) on larger maximum digits remembered correctly, and SOX (β = - 0.2435, P = 0.0395, FDR = 0.1185) on reaction time. Nevertheless, the associations between antioxidant enzymes and speech and linguistic disorders, as well as visual disturbances, were not significant. We did not find reverse causation between antioxidant enzymes and cognitive function traits. This study provides evidence of potential causal relationships between oxidative stress and cognitive function.

Cross-Sectional Study of Flood Damage Assumptions in Medical Facilities Using Geographic Information Systems.

Introduction Floods not only directly damage medical facilities but also hinder access to medical facilities, potentially disrupting local medical services. The scale of damage that medical facilities suffer from floods in Japan is unknown. In this study, we assessed the potential impact of floods on Japanese healthcare facilities by facility characteristics. Methods We conducted a cross-sectional study involving medical facilities registered in the Japan Medical Association Regional Medical Information System. Geographic data for the inundation area was obtained from open data of the Japanese government. Facilities that overlap with flooded areas were designated as affected facilities. The primary outcomes were the percentage of damaged facilities and beds. We calculated odds ratios (OR) and 95% confidence intervals (95%CI) using the Wald method to assess the impact of disaster base hospital designation on damage extent. Results We included 140,826 general clinics and 8,126 hospitals, which had 137,731 and 1,483,347 beds, respectively. The planned scale of flooding is estimated to affect 8.0% of general clinics and 10.8% of their beds. For hospitals, these figures were 8.8% and 7.8%, respectively. The maximum potential scale of flooding is estimated to affect 23.6% of general clinics and 23.9% of their beds. For hospitals, these figures were 22.5% and 20.6%, respectively. At the planned scale of flooding, there was no difference found in therate of damaged facilities between disaster base hospitals and non-disaster base hospitals, and the rate of damaged beds was lower at non-disaster base hospitals (OR = 0.92, 95%CI = 0.71-1.18 for damaged facilities and OR = 0.79, 95%CI = 0.78-0.80 for damaged beds). At the maximum potential scale of flooding, there was no difference found in the expected damage between disaster base hospitals and non-disaster base hospitals (OR = 1.14, 95%CI = 0.95-1.38 for damaged facilities and OR = 0.99, 95%CI = 0.98-1.00 for damaged beds). Conclusion In Japan, floods can hinder nationwide medical functions, particularly in certain regions. Healthcare professionals should assess potential flood damage in advance and ensure that their workplace's business continuity plan includes appropriate countermeasures.

Efficient and Reliable Estimation of Knowledge Graph Accuracy

Data accuracy is a central dimension of data quality, especially when dealing with Knowledge Graphs (KGs). Auditing the accuracy of KGs is essential to make informed decisions in entity-oriented services or applications. However, manually evaluating the accuracy of large-scale KGs is prohibitively expensive, and research is focused on developing efficient sampling techniques for estimating KG accuracy. This work addresses the limitations of current KG accuracy estimation methods, which rely on the Wald method to build confidence intervals, addressing reliability issues such as zero-width and overshooting intervals. Our solution, rooted in the Wilson method and tailored for complex sampling designs, overcomes these limitations and ensures applicability across various evaluation scenarios. We show that the presented methods increase the reliability of accuracy estimates by up to two times when compared to the state-of-the-art while preserving or enhancing efficiency. Additionally, this consistency holds regardless of the KG size or topology.

Determination of predictive factors in families of girls with menstrual disorders comorbid with endocrine system pathology

Objective — to determine predictive factors in the families of girls with menstrual disorders comorbid with endocrine system pathology. Materials and methods. The genealogical analysis was carried out in the families of 47 girls with oligomenorrhea (OM) and 44 girls with abnormal uterine bleeding (AUB) comorbid with endocrine system pathology. The comparison group consisted of the pedigrees of 30 families of healthy girls living in Kharkiv and Kharkiv Region. During the genealogical study, we observed the principles of the Declaration of Helsinki, the Council of Europe Convention for the Protection of Human Rights and Dignity of the Human Being, and the relevant laws of Ukraine. The Student’s t­test was used to determine the significance of the differences between the signs. The predictive implications of the studied signs were determined by the Wald method with informativity estimation using the Kullback criterion. Results and discussion. Hereditary burden of reproductive, gynecological non­inflammatory, endocrine diseases and environmental factors was identified in the families of girls with OM and AUB comorbid with endocrine pathology: pernicious habits and stress in the mothers of sick girls before and during pregnancy, threatened miscarriage. Risk factors for the sick girls included artificial feeding of a girl, stress, traumatizing of a girl, and prolonged use of the Internet and gadgets. Among non­communicable diseases in relatives of sick girls, the most common were gynecological non­inflam­matory diseases when compared with the relatives of girls with AUB and healthy girls (p &lt; 0.001), while relatives of healthy girls mostly suffered from nervous system disorders (p &lt; 0.05). Common and distinct predictive signs in the families of girls with OM and AUB and comorbid endocrine pathology have been identified. Conclusions. The predictive factors in the families of girls with OM and AUB have been identified, the use of which will allow forming high-risk groups as regards the high risk of menstrual disorders based on the genealogical analysis.

Interactions with humans reduce the success of foraging for anthropogenic food by capuchin monkeys (Sapajus libidinosus) in Brasília National Park, Brazil.

The progressive growth of urban environments has increasingly forced populations of nonhuman primates to coexist with humans in many cities, which has resulted in problems such as behavioral alterations, conflicts with humans, and threats to the health of the monkeys, due to their consumption of anthropogenic foodstuffs. These anthropogenic foods, which are rich in calories, are the principal driver of the proximity between humans and primates, even though the acquisition of these foods tends to be risky for the monkeys and involve a variety of challenges derived from specific features of the urban environment. The present study evaluated the success/risk relationship of foraging for anthropogenic food by tufted capuchins (Sapajus libidinosus) in Brasília National Park. The data were analyzed using a binary logistic regression, with the backward-stepwise Wald method, to investigate the factors related to the foraging success of the capuchins, considering variables such as their sex and age, the type of approach and its context, and interactions with humans. The capuchins were influenced by the anthropogenic context, which affected their foraging strategies and diet. Interactions with humans reduced the success of foraging for anthropogenic foods. Conflicts between humans and the capuchins were common, especially in the context of access to food. The capuchins thus preferred to access feeding resources directly, probably due to the reduced human interference, which resulted in greater foraging success for unattended food brought by park visitors and the raiding of trash cans. Based on the observed behavior patterns, a number of measures can be proposed to mitigate these conflicts. These recommendations include not bringing food into areas frequented by the capuchins, not reacting to approaching animals, and removing all trash generated during a visit. A cleaning team dedicated to the maintenance of the visitation area free of anthropogenic waste is also be recommended.

Static black hole in minimal Horndeski gravity with Maxwell and Yang-Mills fields and some aspects of its thermodynamics

In this work we obtain a static spherically symmetric charged black hole solution in the framework of minimal Horndeski gravity with additional Maxwell and Yang-Mills fields. The obtained solution is examined; in particular, its asymptotics are studied. Thermodynamics of the black hole is investigated, namely, we use an effective surface gravity to derive black hole temperature. To obtain the first law of black hole thermodynamics, the Wald method is applied. We also use the extended thermodynamics approach, namely, it allows us to derive the Smarr relation, Gibbs free energy, and the thermal equation of state. The study of thermal values in the extended space shows rich phase behavior, in particular, the domain where the first-order phase transition takes place and the critical point with the second-order phase transition. We also study thermal behavior near the critical point, obtain critical exponents, and analyze the Ehrenfest equations at the critical point. Finally, we calculate the Prigogine-Defay ratio confirming the conclusion about the second-order phase transition at the critical point. Published by the American Physical Society 2024

Likelihood-based inferences for active-arm trial with counterfactual incidence based on recency assay

Abstract Objectives The approach of using HIV recency assay to estimate the counterfactual incidence rate is being used as the primary efficacy method in a few ongoing large-scale HIV pre-exposure prophylaxis (PrEP) trials, and the current available approach for the inference is based on the Wald method that leverages the asymptotic distribution of the estimators. One issue with the Wald test is that it does not work well when the number of HIV infections are small in the active arm, and it fails to work when there are zero HIV infections. As future long-acting PrEP products are becoming more efficacious, it is very likely that a small or zero number of infections will be observed in HIV prevention trials, especially for subgroup analyses or interim analyses, hence there is a pressing need to develop inference methods that work under such scenarios. Methods It is well known that when the sample size is small to moderate, likelihood ratio tests are more reliable than Wald tests in terms of actual error probabilities coming close to matching nominal levels. In this manuscript we derive the likelihood ratio test and the likelihood-based confidence intervals for HIV prevention trials based on recency assays. Results Compared with the Wald test, the proposed method works when there are zero infections. Additionally, unlike the Wald test, the p-value from the likelihood ratio test is an increasing function with respect to the number of infections, which is a desirable property as otherwise it will cause confusions. Conclusions For HIV PrEP trials based on recency assay, the likelihood-based p-value and confidence interval can be preferable to the Wald based inference methods when the number of HIV infections is expected to be small.

Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease.

Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2-sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome-wide association study of 8293 European participants. Summary-level data on CAD were derived from a large genome-wide association study (71 602 cases and 260 875 controls). We used the inverse-variance-weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR-Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni-adjusted level of significance (P<1.79×10-3). The odds ratio was 1.20 (95% CI, 1.08-1.33; P=6.83×10-4) per 1-SD increase in macrophage migration inhibitory factor. Colocalization analyses supported our MR findings. Additionally, we found suggestive evidence between the genetic effects of stem cell growth factor-β and the risk of CAD (odds ratio, 0.95 [95% CI, 0.91-0.98]; P=0.007). Our findings suggested a risk-increasing effect of macrophage migration inhibitory factor level on the development of CAD. The roles of these inflammatory factors for CAD warrant further investigation.

Debate on the oncologic potential of sex steroid preparations

Background. Thanks to numerous worldwide studies, the significant contribution of the hormonal component to the oncological risks of the organs of the female reproductive system is beyond doubt. Of great interest is the analysis of world research on the oncological potential of hormonal drugs, namely COCs and MGT, since this issue continues to be one of the most complex and controversial.&#x0D; Aim. This study aimed to contribution of hormonal factors to the development of cancer of the female reproductive system, namely breast, cervical, endometrial and ovarian cancers.&#x0D; Materials and Methods. The study was conducted on the basis of the Center of Gynecology and Reproductive Technologies of the FSAU “National Medical Research Center “Treatment and Rehabilitation Center” of the Ministry of Health of the Russian Federation, the Department of Oncogynecology of the University Clinical Hospital No. 4 of the I.M. Sechenov First Moscow State Medical University. The analysis of medical documentation for the period from January 2015 to December 2021 was carried out. The study included 1842 patients with verified oncological disease of the female reproductive system, who had a history of taking hormonal drugs of the following pharmacological groups: hormonal contraceptives, menopausal hormone therapy drugs. The age of all patients ranged from 26 to 83 years (mean age 51.98±10.3 years). The control group consisted of 611 patients without oncological diseases, who have a history of indications for taking hormonal drugs of these pharmacological groups.&#x0D; Results. When assessing the effect of the duration of MGT intake on the risk of developing breast cancer, it was found that MGT intake for a total of more than 6 years was associated with a higher risk of developing breast cancer (HR 1.18; CI 1.02–1.36; p 0.001). Using the Wald method, we found that the probability of developing breast cancer is associated with a BMI of more than 25 kg/m2 and long-term intake of combined MGT for a total of more than 6 years. When assessing the effect of the duration of MGT intake on the risk of developing RTM, it was found that MGT intake for a total of more than 6 years was associated with a higher risk of developing RTM (HR 1,432; CI 1,172–1,750; p 0.001). Using the Wald method, we found that the probability of developing RTM is associated with the presence of a BMI of more than 25 kg/m2, prolonged MGT intake for a total of more than 6 years and the presence of endometrial hyperplastic processes, adenomyosis, hypertension in the anamnesis. When assessing the effect of the duration of COC intake on the risk of developing breast cancer, it was found that taking COC for a total of more than 7 years was associated with a higher risk of developing breast cancer (HR 1.68; CI 1.1–2.5; p=0.010). According to the Wald method, it was revealed that the probability of developing breast cancer is associated with the presence of HPV type 16, a BMI of more than 25 kg/m2 and prolonged intake of COCs for a total of more than 7 years. When assessing the effect of the duration of MGT intake on the risk of developing PC, it was found that MGT intake for a total of more than 9 years was associated with a higher risk of developing PC (HR 1.65; CI 1.2–2.3; p=0.010). Using the Wald method, we found that the probability of developing RYA is associated with the presence of a BMI of more than 25 kg/m2, MGT intake and the presence of endometrial hyperplastic processes in the anamnesis.&#x0D; Conclusions. With prolonged use of sex steroids, there is a tendency to increase the risk of developing cancer of the female reproductive system. Careful follow-up and limitation of the duration of taking sex steroids in risk groups will reduce carcinogenic risks.

Prediction Model with Validation for Polioseronegativity in Malnourished Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Malnutrition is identified as a risk factor for insufficient polio seroconversion in the context of a vaccine-derived poliovirus (VDPV) outbreak-prone region. In the Democratic Republic of Congo (DRC), underweight decreased from 31% (in 2001) to 26% (in 2018). Since 2004, VDPV serotype 2 outbreaks (cVDPV2) have been documented and were geographically limited around the Haut-Lomami and Tanganyika Provinces. To develop and validate a predictive model for poliomyelitis vaccine response in malnourished infants, a cross-sectional household study was carried out in the Haut-Lomami and Tanganyika provinces. Healthy children aged 6 to 59 months (n=968) were enrolled from eight health zones (HZ) out of 27, in March 2018. We performed a bivariate and multivariate logistics analysis. Final models were selected using a stepwise Wald method, and variables were selected based on the criterion p < 0.05. The association between nutritional variables, explaining polio seronegativity for the three serotypes, was assessed using the receiver operating characteristic curve (ROC curve). Factors significantly associated with seronegativity to the three polio serotypes were underweight, non-administration of vitamin A, and the age group of 12 to 59 months. The sensitivity was 10.5%, and its specificity was 96.4% while the positive predictive values (PPV) and negative (PNV) were 62.7% and 65.3%, respectively. We found a convergence of the curves of the initial sample and two split samples. Based on the comparison of the overlapping confidence intervals of the ROC curve, we concluded that our prediction model is valid. This study proposed the first tool which variables are easy to collect by any health worker in charge of vaccination or in charge of nutrition. It will bring on top, the collaboration between the Immunization and the Nutritional programs in DRC integration policy, and its replicability in other low- and middle-income countries with endemic poliovirus.

Causal effects of genetically vitamins and sepsis risk: a two-sample Mendelian randomization study

BackgroundIn recent years, observational studies have been conducted to investigate the potential impact of vitamins on sepsis. However, many of these studies have produced inconsistent results. Our Mendelian randomization (MR) study aims to evaluate the causality between vitamins and sepsis from a genetic perspective.MethodsOur MR study was designed following the STROBE-MR guidelines. Genetic instrumental variables for vitamins including folate, vitamin B12, B6, A (Retinol), C, D, and K were obtained from previous genome-wide association studies (GWAS) and MR studies. Five different sepsis severity levels were included in the analysis. The genetic instrumental variables were screened for potential confounders using PhenoScanner V2. MR analysis was performed using MR-egger, inverse-variance weighted multiplicative random effects (IVW-RE), inverse-variance weighted multiplicative fixed-effects (IVW-FE), and wald ratio methods to assess the relationship between vitamins and sepsis. Sensitivity analysis was performed using the MR-egger_intercept method, and the MR-PRESSO package and Cochran’s Q test were used to evaluate the heterogeneity of the instrumental variables.ResultsOur MR study found no statistically significant association between vitamins and sepsis risk, regardless of the type of vitamin (P-value > 0.05). The odds ratios (ORs) for folate, vitamin B6, vitamin B12, vitamin A, vitamin D, vitamin K, and vitamin C were 1.164 (95% CI: 0.895–1.514), 0.987 (95% CI: 0.969–1.005), 0.975 (95% CI: 0.914–1.041), 0.993 (95% CI: 0.797–1.238), 0.861 (95% CI: 0.522–1.42), 0.955 (95% CI: 0.86–1.059), and 1.049 (95% CI: 0.911–1.208), respectively. Similar results were observed in subgroups of different sepsis severity levels.ConclusionsOur MR study found no evidence of a causal association between vitamins and sepsis risk from a genetic perspective. Further randomized controlled trials are necessary to confirm these results.

A Retrospective Analysis of Hyperlipidemia and COVID-19 Outcomes Investigated in a Rural Midwestern Population.

Background COVID-19 is a respiratory disease caused by SARS-CoV-2, a coronavirus discovered in 2019. Its impact on the world continues to be studied due to the significant death toll of the disease. As the COVID-19 pandemic remains ongoing, examining theassociation ofCOVID-19 with comorbidities andresulting mortality is necessary. This study focuses on population health outcomes with COVID-19 infection and hyperlipidemia (total cholesterol greater than or equal to 200 mg/dL) as a comorbidity, including potential associations with age and sex. Methods As a retrospective analytical study, patients were divided into three populations based on COVID-19 and/or hyperlipidemia based on the International Classification of Diseases, Tenth Edition (ICD-10) codes reported in the electronic medical record system at Freeman Health System (FHS) in Southwest Missouri from April 1, 2020, to December 31, 2021. Wald's methods and two sample proportion summary hypotheses with confidence intervals (CIs) were used for comparison. The populations were subdivided and analyzed for age and sex differences. Results Patients with both COVID-19 and hyperlipidemia had a higher mortality rate than patients with COVID-19 and without hyperlipidemiaand patients with hyperlipidemia and without COVID-19; patients with COVID-19 and without hyperlipidemia had a higher mortality rate than patients with hyperlipidemia and without COVID-19. All comparisons across these populations were statistically significant (p-value < 0.05). While increased age was associated with increased mortality in all groups, sex was not predictive in this regard. Conclusion Our study provides insights into variables affecting COVID-19 outcomes in a rural Midwestern population by showing how the comorbidity hyperlipidemia contributes to increased mortality.

RISK-ORIENTED PREDICTION OF PREGNANCY LOSS PATHOLOGY BASED ON A PERSONALIZED APPROACH

The increase in the frequency of pregnancy loss and the negative prognostic trend with the probable development of the demographic crisis in connection with the martial law in Ukraine and the mass migration of the female population provoked by it, requires the search for all possible ways of prevention and prophylactic of this pathology.&#x0D; Aim. Development and scientific substantiation of a risk-oriented model of prevention of pregnancy loss.&#x0D; Material and Methods. In the course of creating a model for determining the probability of the appearance of symptoms of pregnancy loss, we used a step-by-step method of logistic regression with the gradual exclusion of unreliable signs according to the Wald method.&#x0D; Results and Discussion. In the process of sociological research, the importance of 30 risk factors was analyzed, and 14 factors were singled out from among them using the logistic regression method, which, when combined, have a probable impact on the development of pregnancy loss. Namely: emotional strain/stress in everyday life, first ultrasound and biochemical screening, history of herpes type 1, chlamydial infection, COVID-19, tonsillitis, allergic rhinitis/sinusitis, autoimmune thyroiditis, presence of type I diabetes, use of artificial insemination, wine consumption, additional use of folic acid and drugs, marital status, and computer work. Among these 14 factors, three have a preventive effect, while the other 11 increase the risk of developing the pathology of pregnancy loss. This preventive model is reliable (p&lt;0.001) and was transformed into the application "Individual prediction of the occurrence of pregnancy loss pathology" created for the Android platform, which provides 95.5% accuracy of the prediction of the occurrence of pregnancy loss pathology.&#x0D; Conclusions. The personalized preventive model can be applied by general practitioners/family doctors and obstetrician-gynecologists in order to form risk groups among pregnant women and prevent the occurrence of pregnancy loss pathology.

Causal associations between gut microbiota and urological tumors: a two-sample mendelian randomization study

BackgroundDysbiosis of gut microbiota has been linked to numerous diseases, including cancer. The unique role of gut microbiota in urological tumors is gaining prominence. However, it is still controversial whether the dysbiosis of gut microbiota should be one of the etiological factors of bladder cancer (BCa), prostate cancer (PCa) or kidney cancer (KCa).Materials and methodsThe microbiome genome-wide association study (GWAS) from the MiBioGen consortium (18,340 samples of 24 population-based cohorts) was utilized as the exposure data. Additionally, outcomes data (951 BCa cases and 307,092 controls; 1,631 KCa cases and 238,678 controls; 79,148 PCa cases and 61,106 controls) were extracted from the GWAS of the FinnGen and PRACTICAL consortia. To detect the potential causative bacterial traits for BCa, PCa, and KCa, a two-sample Mendelian randomization (MR) analysis was performed, employing the inverse-variance weighted or Wald ratio method. Sensitivity analyses were subsequently conducted to explore the robustness of the primary results. Finally, the reverse MR analysis was undertaken to mitigate the reverse causation.ResultsThis study suggested that Bifidobacterium (p = 0.030), Actinobacteria (p = 0.037 for phylum, 0.041 for class), and Ruminococcustorques group (p = 0.018), exhibited an association with an increased risk of BCa using either the inverse-variance weighted or Wald ratio method. By utilizing the Wald ratio method, Allisonella (p = 0.004, p = 0.038) was associated with a decreased risk of BCa and PCa, respectively. Furthermore, Ruminococcustorques group (p = 0.028) and Erysipelatoclostridium (p = 0.048) were causally linked to an elevated risk of KCa.ConclusionsThis MR study supports that genetically predicted gut microbiota is causally related to BCa, PCa and KCa. Additionally, distinct bacterial traits are identified in relation to each tumor type.