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MODIFICATION OF THE TUMOR/INDUCED BYSTANDER EFFECT BY IRRADIATION UNDER COCULTIVATION OF LYMPHOCYTES FROM PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND LYMPHOCYTES FROM HEALTHY DONORS

Probl Radiac Med Radiobiol. 2021 Dec;26:248-259. doi: 10.33145/2304-8336-2021-26-248-259.

ABSTRACT

OBJECTIVE: Study the tumor-induced bystander effect of blood cells from chronic lymphocytic leukemia (CLL)patients on non-transformed bystander cells (peripheral blood lymphocytes (PBL) of conditionally healthy individ-uals) and the possibility of its modification after the impact of ionizing radiation.

MATERIALS AND METHODS: We carried out cocultivation and separate cultivation of blood samples from conditionallyhealthy volunteers and patients with CLL according to our technique. Using the Comet assay, the relative level ofDNA damage was evaluated.

RESULTS: A statistically significant increase (р < 0.001) in the level of DNA damage in PBL culture of conditionallyhealthy individuals after co-cultivation with malignant cells of CLL patients was observed. After irradiation, a drop in the level of cells with a high degree of DNA damage was noted, which was connected with an increase in the frequency of cells that were delayed in division at the S stage of the cell cycle. An increase in apoptotic activity in cultures of bystander cells was observed in all variants of the experiment (р < 0.001).

CONCLUSION: The influence of irradiated blood cells of patients with CLL results in an enhancement of the tumor-induced bystander effect manifestation in the PBL of conditionally healthy individuals.

PMID:34965552 | DOI:10.33145/2304-8336-2021-26-248-259

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Nevin Manimala Statistics

Clinical Pathway for Vaso-Occlusive Pain Reduces Hospital Admissions

J Healthc Qual. 2022 Jan-Feb 01;44(1):50-58. doi: 10.1097/JHQ.0000000000000292.

ABSTRACT

BACKGROUND: Vaso-occlusive pain leads to high acute care utilization among patients with sickle cell disease (SCD). Data suggest that clinical pathways (CPWs) reduce variation in the management of vaso-occlusive pain and improve clinical outcomes.

METHODS: We implemented and evaluated a CPW for vaso-occlusive pain at our institution using a before and after study design. The primary objective was to decrease acute care utilization among patients with SCD, which was assessed by the primary outcome measures of hospital length of stay (LOS), 30-day readmission rate, and total hospitalizations annually per patient. Secondary outcome measures were packed red blood cell transfusions, and acute chest syndrome incidence. Patient-controlled analgesia use and promethazine use were assessed to estimate CPW use.

RESULTS: Three hundred fourty-four admissions in 112 patients were analyzed, of which 193 admissions occurred pre-CPW and 151 admissions occurred post-CPW implementation. Post-CPW implementation, we observed a significant decrease in hospital admissions annually per patient, an increase in patient-controlled analgesia use, and a decrease in intravenous promethazine use. We observed trends toward decreased 30-day readmission rate and increased acute chest syndrome incidence, which were not statistically significant. No effect was found on hospital LOS.

CONCLUSIONS: Clinical pathway implementation at our institution reduced variation in management and decreased hospital admissions for vaso-occlusive pain.

PMID:34965539 | DOI:10.1097/JHQ.0000000000000292

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AGING OF THE CHORNOBYL CATASTROPHE SURVIVORS AND PROBLEMS OF THEIR MENTAL HEALTH SURVEY

Probl Radiac Med Radiobiol. 2021 Dec;26:162-187. doi: 10.33145/2304-8336-2021-26-162-187.

ABSTRACT

BACKGROUND: Depopulation processes in Ukraine have been affected by the Chornobyl catastrophe (ChC), but therate of demographic aging of survivors remains uncertain. Although the mental health disorders of the survivors arerecognized internationally, problems of their research remain unresolved. Thus, these areas of research are relevant.Objective is to determine the rate of demographic aging of survivors of the Chornobyl NPP (ChNPP) accident and toanalyze the state of their mental health survey, outlining solutions.

MATERIALS AND METHODS: Information and statistical sources for 1986-2019 of the Ministry of Health of Ukraine andthe State Statistics Service of Ukraine on the age of the ChC survivors are used. The results of previous own researchand other scientists using the data of the Clinical and Epidemiological Register (CER) of the State Institution«National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine»(NRCRM), the State Register of ChC survivors (SRU), and the Department of Radiation Psychoneurology, Institute ofClinical Radiology, NRCRM are integrated. Theoretical, general scientific, demographic and mathematical-statisticalresearch methods and documentary analysis are used.

RESULTS: It is shown that in 2018, compared to 1995, the number of the ChC survivors, who are under the supervi-sion of the Ministry of Health of Ukraine, decreased by almost 987 thousand. The part of people born from personsof the 1st-3rd accounting groups increased in the structure of survivors (from 13.1 % in 1995 to 13.6 %), and thisdecreased in persons living or lived in the territories subject to supervision (75.1 % and 63.1 %, respectively), butin evacuees and Chornobyl clean-up workers (liquidators) this did not change significantly. A high level of aging ofthe ChC survivors (except for the 4th group) is revealed: liquidators – 59.0 %; evacuees – 25.0 %, and residents ofradioactively contaminated territories (RCT) – 30.7 %. It has been proved that the countries of RCT differ signifi-cantly in the number of the ChC survivors and their structure. The increase in the post-accident period indicators ofthe level of aging and the average age of the RCT population indicates negative changes in age parameters and theneed to continue research to identify factors «responsible» for such changes. Long-term mental health disordersand neuropsychiatric effects in the ChC survivors have been identified – an excess of cerebrovascular pathology andneurocognitive deficits, especially in liquidators, which may indicate an accelerated aging. Radiation risks havebeen revealed for acute and chronic cerebrovascular pathology and organic mental disorders of non-psychotic andpsychotic levels. Neurophysiological and molecular-biological atypia of aging processes under an exposure to lowdoses of and low dose rate of ionizing radiation have been found. The psyche under the age of 40 years old at thetime of exposure is more vulnerable. Existing statistical and registry data underestimate the level of mental disor-ders in the population of Ukraine, including the ChC survivors by an order of magnitude.

CONCLUSIONS: The ChC survivors are aging in the country. The negative tendencies in age parameters of survival indi-cate the need to continue research to identify the factors «responsible» for such changes. Mental health disordersand neuropsychiatric effects in the ChC survivors are underestimated. It is necessary to create a national psychiatricregistry of Ukraine and long-term (lifelong) monitoring of survivors with well-planned clinical and epidemiologicalstudies of general and mental health with reliable dosimetric support based on national registries using the latest information technologies.

PMID:34965547 | DOI:10.33145/2304-8336-2021-26-162-187

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Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials

Psychother Psychosom. 2021 Dec 29:1-10. doi: 10.1159/000520554. Online ahead of print.

ABSTRACT

INTRODUCTION: Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose.

OBJECTIVE: This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder.

METHODS: A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031).

RESULTS: From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of -0.06 (-0.16 to 0.04) and -0.06 (-0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis.

CONCLUSION: Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

PMID:34965534 | DOI:10.1159/000520554

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Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray

Am J Nephrol. 2021 Dec 29:1-11. doi: 10.1159/000520998. Online ahead of print.

ABSTRACT

INTRODUCTION: The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN.

METHODS: We conducted a retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between December 2010 and September 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA were improved by adding the urinary glycan intensity.

RESULTS: Among 45 lectins, 3 lectins showed a significant improvement of the models: Amaranthus caudatus lectin (ACA) with the difference of c-statistics 0.038 (95% CI: 0.019-0.058, p < 0.001), Agaricus bisporus lectin (ABA) 0.035 (95% CI: 0.015-0.055, p < 0.001), and Maackia amurensis lectin (MAH) 0.035 (95% CI: 0.015-0.054, p < 0.001). In 3 lectins, each signal plus reference standard showed good reclassification (category-free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to the reference standard at the predefined threshold probability of 40%.

CONCLUSIONS: The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan analysis by ACA is a useful and robust noninvasive strategy for the diagnosis of IgAN.

PMID:34965524 | DOI:10.1159/000520998

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Occupational safety and health management of COVID-19 at a company in the Peruvian fishing sector

Arch Prev Riesgos Labor. 2021 Jul 15;24(3):240-251. doi: 10.12961/aprl.2021.24.03.02.

ABSTRACT

OBJECTIVE: To evaluate the occupational safety and health management of COVID-19 at a company in the Peruvian fishing sector Methods: The independent variable was occupational safety and health management, defined as the implementation of preventive and control measures in response to COVID-19. The dependent variable was defined as the number of detected COVID-19 cases and test positivity rate. We used a pre- (implementation phase) and post-test (following the implementation phase) study design. We performed a non-parametric inferential analysis to identify any significant pre- and post-test differences and any associations between the variables.

RESULTS: The company initiated a strategy to detect positive cases through the use of serological tests. During the first stage, 2329 tests were conducted, yielding a positivity rate of 71%. Once prevention and control actions were implemented, the positivity rate in August 2020 had decreased to 15.65%,, a statistically significant decrease (p<0.05), as well as its relationship to the measures implemented.

CONCLUSIONS: This occupational safety and health intervention significantly reduced the number of COVID-19 cases and positivity rate in this group of workers in the Peruvian fishing sector.

PMID:34965330 | DOI:10.12961/aprl.2021.24.03.02

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Vaccine response to SARS-CoV-2 in hospital workers

Arch Prev Riesgos Labor. 2021 Oct 15;24(4):383-403. doi: 10.12961/aprl.2021.24.04.05.

ABSTRACT

INTRODUCTION: The aim of this study was to measure anti-SARS-CoV-2 immunity of hospital workers after a completed 2-dose Pfizer-BionTech vaccination, and to examine factors potentially associated with immunity status. Side effects of the vaccine were also studied.

METHOD: This was a cross-sectional study of a representative sample of General University Hospital of Castellon workers, vaccinated with two doses in January and February 2021. We measured IgG antibodies against protein N (IgG-NP), IgM against protein S (IgM-S), and quantitative levles of IgG against protein S (IgG-Quant) one month after the last dose. We obtained information on demographic, risk factors, and vaccine side effects via a self-completed questionnaire. For the statistical analysis we used multiple regression models.

RESULTS: Two hundred seventy-five workers participated (96.8%, 275/284). Positive IgG-Quant, IgM-S, and IgG-NP were 99.6%, 14.9% and 4.4%, respectively. Adjusted IgG-Quant levels increased significantly with obesity, nonsmoking status, positive IgM-S, and/or IgG-NP. The prevalence of IgM-S was higher in males, and associated with the same factors as those for IgG-Quant. Among those with a history of COVD-19 infection, 42.9% did not have IgG-NP. Overall 86.5% of participants had side effects, which were associated with positive IgG-NP, high IgG-Quant levels, younger age, and being female.

CONCLUSIONS: All but one participant developed immunity. Those who had suffered from COVID-19 infection had higher antibody levels. A high proportion of participants had mild secondary effects, especially those with previous COVID-19 infection.

PMID:34965327 | DOI:10.12961/aprl.2021.24.04.05

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Semiparametric count data regression for self-reported mental health

Biometrics. 2021 Dec 29. doi: 10.1111/biom.13617. Online ahead of print.

ABSTRACT

”For how many days during the past 30 days was your mental health not good?” The responses to this question measure self-reported mental health and can be linked to important covariates in the National Health and Nutrition Examination Survey (NHANES). However, these count variables present major distributional challenges: the data are overdispersed, zero-inflated, bounded by 30, and heaped in five- and seven-day increments. To address these challenges-which are especially common for health questionnaire data-we design a semiparametric estimation and inference framework for count data regression. The data-generating process is defined by simultaneously transforming and rounding (star) a latent Gaussian regression model. The transformation is estimated nonparametrically and the rounding operator ensures the correct support for the discrete and bounded data. Maximum likelihood estimators are computed using an EM algorithm that is compatible with any continuous data model estimable by least squares. star regression includes asymptotic hypothesis testing and confidence intervals, variable selection via information criteria, and customized diagnostics. Simulation studies validate the utility of this framework. Using star regression, we identify key factors associated with self-reported mental health and demonstrate substantial improvements in goodness-of-fit compared to existing count data regression models.

PMID:34965306 | DOI:10.1111/biom.13617

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Risk Factors for COVID-19 transmission among healthcare workers

Arch Prev Riesgos Labor. 2021 Oct 15;24(4):370-382. doi: 10.12961/aprl.2021.24.04.04.

ABSTRACT

OBJECTIVE: Frontline healthcare workers are the first line of defense against Covid-19, resulting in a higher risk of infection. The objective of this study was to describe the impact of the SARS-CoV-2 infection and its associated risk factors among professionals working in a healthcare consortium that includes different centers.

METHODS: This was a retrospective analytical observational study of 2620 healthcare workers; the project period began with the declaration of the state of alarm in Spain (March 15, 2020) and ended on June 21, 2020. We estimated associations between the independent variables sex, age, seniority, professional category and work location and confirmed COVID-19 as the outcome variable. Bivariate study analysis was based on chi-square test and simple logistic regression with calculation of the odds ratio (OR) and 95% confidence interval (95%CI). Multivariate analysis was performed using multiple logistic regression. Statistical significance was set at p ≤0.05.

RESULTS: All frontline healthcare worker categories were at higher risk than non-patient-facing personnel. Nurses had the highest risk [OR, 14.03 (3.19-61.66)]. With respect to work location, and as compared to non-patient-facing personnel, working in the surgical-medical-hospitalization-clinic [OR 13.43 (1.7-106.12)] and socio-health center [OR 17.77 (2.19-144.04) posed the greatest risks.

CONCLUSIONS: The greatest risk of acquiring COVID-19 was among patient-facing healthcare professionals working in areas where COVID-19 was detected among patients admitted for other pathologies. This risk was higher than in those areas designated for the care of COVID-19 patients, possibly due to differences in the use of personal protective equipment.

PMID:34965326 | DOI:10.12961/aprl.2021.24.04.04

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Controlling forever love

PLoS One. 2021 Dec 29;16(12):e0260529. doi: 10.1371/journal.pone.0260529. eCollection 2021.

ABSTRACT

A stable and rewarding love relationship is considered a key ingredient for happiness in Western culture. Building a successful long-term relationship can be viewed as a control engineering problem, where the control variable is the effort to be made to keep the relationship alive and well. We introduce a new mathematical model for the effort control problem of a couple in love who wants to stay together forever. The problem can be naturally formulated as a dynamic game in continuous time with nonlinearities. Adopting a dynamic programming approach, a tractable computational formulation of the problem is proposed together with an accompanying algorithm to find numerical solutions of the couple’s effort problem. The computational analysis of the model is used to explore feeling trajectories, effort control paths, happiness, and stabilization mechanisms for different types of successful couples. In particular, the simulation analysis provides insight into the pattern of change of both marital quality and effort making in intact marriages and how they are affected by certain level of heterogamy in the couple.

PMID:34965275 | DOI:10.1371/journal.pone.0260529