Nevin Manimala

Klin Lab Diagn. 2022 Feb 23;67(2):97-100. doi: 10.51620/0869-2084-2022-67-2-97-100.

ABSTRACT

To identify new criteria for predicting the outcome of pregnancy in women with threatened preterm labor based on the establishment of the characteristics of differentiation and functional activity of memory T-cells in the population of CD8 + T-lymphocytes. The study involved 56 women with threatened preterm labor at 22-34 weeks of pregnancy. Depending on the outcome of pregnancy, patients were divided into 3 groups: Group I included 22 women by premature labor; group II – 34 women whose pregnancy ended by deliver at term. By tricolor flow cytofluorometry method the content of peripheral Tn, Tcm, Tem and Temra cells in CD8+ population was studied. Statistical analysis was carried out using programs «Statistica for Windows 13.0», «Microsoft Excel 2019» and «MedCalc 19.3». Patients with the threat of preterm birth were characterized by a significant increase in the relative content of CD8+ T-lymphocytes in the peripheral blood compared to the control group (p=0.001). When comparing this indicator in the subgroups of women with the threat of preterm birth, it was found that preterm birth was associated with significantly higher relative CD8 + lymphocyte counts (p=0.03) compared to the indicators of the subgroup of women who gave birth on time. When evaluating the results obtained, it was found that the percentage of CD8+Temra GranzymeB-producing cells in the group of patients with threatened preterm birth, whose pregnancy ended in preterm birth, was significantly lower than in the group of women who gave birth on time (p=0.003). The content of Tcm, Tem memory cells producing GranzymeB in the subgroups of women with pregnancy outcomes of timely and preterm birth did not have significant differences compared to the control group. Thus, the prediction of preterm birth is possible with a value of GranzymeB-producing CD8 + Tem equal to 8.2% or less (sensitivity-87.9%, specificity-85%, accuracy-87.9%). Thus, the identification of a new criterion will make it possible to predict preterm birth in a timely manner and promote the choice of optimal pregnancy management tactics, reasonable prevention of fetal respiratory distress syndrome and transfer of a woman to an obstetric hospital designed to provide high-tech care to premature newborns.

PMID:35192755 | DOI:10.51620/0869-2084-2022-67-2-97-100

Klin Lab Diagn. 2022 Feb 23;67(2):76-80. doi: 10.51620/0869-2084-2022-67-2-76-80.

ABSTRACT

Results of enzyme-linked immunosorbent assay of the soluble forms of PD-1/PD-L immune checkpoint receptor and ligand (sPD-1 and sPD-L1) in pretreatment blood serum of 88 breast cancer patients at various disease stages aged 30-83 years are presented. The control group included 55 practically healthy women aged 19-82 years. Serum sPD-1 and sPD-L1 levels in breast cancer patients highly significantly (p<0.0001) differ from control and these changes are opposite: soluble receptor level is more than 6-fold decreased, while soluble ligand concentration – 5.5 fold increased. Both markers separately, as well as their ratio demonstrate very high sensitivity (94-100%) and specificity (95-100%) in relation to healthy control. No statistically significant associations of sPD-1 and sPD-L1 levels with clinical stage, individual TNM system criteria, tumor histological structure, grade, receptor status, and molecular type were established. In particular, no significant peculiarities of the markers’ levels in triple negative breast cancer successfully treated with anti-PD-1/PD-L1 preparations were revealed. Long-term follow-up and dynamic studies of sPD-1 and sPD-L1serum levels in the course of treatment are required for evaluation of their independent from clinical and morphological factors prognostic significance and the possibility of application as low invasive tests for prediction and monitoring of corresponding targeted therapy efficiency.

PMID:35192751 | DOI:10.51620/0869-2084-2022-67-2-76-80

Genet Epidemiol. 2022 Mar;46(2):89-104. doi: 10.1002/gepi.22439. Epub 2021 Nov 22.

ABSTRACT

In this article, we propose the eigen higher criticism and the eigen Berk-Jones testing procedures to test the association between a single genetic variant and multiple correlated traits based on summary statistics from single-trait genome-wide association studies. Since the association pattern between each genetic variant and multiple traits varies across the whole genome, we further develop an omnibus (OMNI) test using the aggregated Cauchy association test to achieve more robust performance. The p values of our proposed tests can be computed analytically, thus, our methods are appealing in large-scale multiple phenotype association studies. Through extensive simulation studies, we found that all of our proposed tests can maintain the correct type I error rates and our proposed tests have greater power in certain settings. In addition, the OMNI test can always provide robust power performance across a wide range of scenarios. We apply the proposed tests to the Global Lipids Genetics Consortium summary statistics data set and identify additional genetic variants that were missed by the original single-trait analyses. We also develop an R package EBMMT publicly available at https://github.com/Vivian-Liu-Wei64/EBMMT.

PMID:35192735 | DOI:10.1002/gepi.22439

Genet Epidemiol. 2022 Feb 22. doi: 10.1002/gepi.22445. Online ahead of print.

ABSTRACT

Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample MR methods based on genome-wide association study summary level data, however, those methods could suffer from potential power loss or/and biased inference when the chosen genetic variants are in linkage disequilibrium (LD), and also have relatively large direct effects on the outcome whose distribution might be heavy-tailed which is commonly referred to as the idiosyncratic pleiotropy phenomenon. To resolve those two issues, we propose a novel Robust Bayesian Mendelian Randomization (RBMR) model that uses the more robust multivariate generalized $t$ -distribution to model such direct effects in a probabilistic model framework which can also incorporate the LD structure explicitly. The generalized $t$ -distribution can be represented as a Gaussian scaled mixture so that our model parameters can be estimated by the expectation maximization (EM)-type algorithms. We compute the standard errors by calibrating the evidence lower bound using the likelihood ratio test. Through extensive simulation studies, we show that our RBMR has robust performance compared with other competing methods. We further apply our RBMR method to two benchmark data sets and find that RBMR has smaller bias and standard errors. Using our proposed RBMR method, we find that coronary artery disease is associated with increased risk of critically ill coronavirus disease 2019. We also develop a user-friendly R package RBMR (https://github.com/AnqiWang2021/RBMR) for public use.

PMID:35192729 | DOI:10.1002/gepi.22445

Occup Med (Lond). 2022 Feb 22;72(2):99-104. doi: 10.1093/occmed/kqab154.

ABSTRACT

BACKGROUND: Medical education focuses on assessment, diagnosis and management of various clinical entities. The communication of this information, particularly in the written form, is rarely emphasized. Though there have been assessment tools developed to support medical learner improvement in this regard, none are oriented to occupational medicine (OM) practice.

AIMS: This study was aimed to develop and evaluate an assessment tool for consultation letters, by modifying a previously validated assessment tool to suit practice in OM.

METHODS: Using an iterative process, OM specialists added to the Consultation Letter Rating Scale (CLRS) of the Royal College of Physicians and Surgeons of Canada (henceforth abbreviated as RC) additional questions relevant to communication in the OM context. The tool was then used by two OM specialists to rate 40 anonymized OM clinical consultation letters. Inter-rater agreement was measured by percent agreement, kappa statistic and intraclass correlation.

RESULTS: There was generally good percent agreement (>80% for the majority of the RC and OM questions). Intraclass correlation for the five OM questions total scores was slightly higher than the intraclass correlations for the five RC questions (0.59 versus 0.46, respectively), suggesting that our modifications performed at least as well as the original tool.

CONCLUSIONS: This new tool designed specifically for evaluation of patient consultation notes in OM provides a good option for medical educators in a variety of practice areas in providing non-summative, low-stakes assessment and/or feedback to nurture increased competency in written communication skills for postgraduate trainees in OM.

PMID:35192724 | DOI:10.1093/occmed/kqab154

J Burn Care Res. 2022 Feb 22:irac023. doi: 10.1093/jbcr/irac023. Online ahead of print.

ABSTRACT

Burn injuries are a significant global public health concern. The psychological problems deserve more attention. Research has shown that reducing the stigma and improving the burn patient’s self-esteem are effective means to promote social reintegration. The aim of this study is to explore the relationship between stigma and self-esteem and to examine the independent factors that contribute to with the stigma of burns. The convenience sampling method was used in Guangzhou, China. A cross-sectional study was conducted using the Social Impact Scale, Rosenberg Self-Esteem Scale, and a sociodemographic questionnaire. Descriptive statistics, statistical inference, correlation testing, and regression analysis were used to analyze the data among 146 burn survivors. The p-value was set as 0.05. The mean score of SIS was 57.03 ± 6.762. Of the four components of the Social Impact Scale, social rejection had the highest mean score (21.72 ± 3.00). The mean Self-Esteem Scale score was 21.05 ± 2.492, markedly different from the general population. A moderate positive correlation (r = 0.546, p<0.001) was found between stigma and low self-esteem among burn victims. Multiple linear regression analysis identified residence, itching, and Self-Esteem Scale score as significant influencing factors, accounting for 38.5% of the total variance in stigma. Burn survivors reported moderate levels of stigma and low levels of self-esteem. Residence, itching, and Self-Esteem Scale score were significant influencing factors for stigma. To promote recovery of patients with burn injury, it is necessary to eliminate the stigma and improve their self-esteem.

PMID:35192722 | DOI:10.1093/jbcr/irac023

Sleep. 2022 Feb 22:zsac041. doi: 10.1093/sleep/zsac041. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Epilepsy is characterized by disrupted sleep architecture. Studies on sleep macro- and microstructure revealed that patients with epilepsy experience disturbed rapid eye movement (REM) sleep; however, no consensus has been reached on non-REM (NREM) sleep changes. Cyclic alternating pattern (CAP) is a marker of sleep instability that occurs only during NREM sleep. This meta-analysis investigated CAP differences between patients with epilepsy and healthy controls.

METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in searching PubMed, Embase, and Cochrane Central database for studies comparing polysomnographic sleep microstructures between patients with epilepsy and healthy controls. A meta-analysis using a random-effects model was performed. We compared CAP rates, percentages of phase A1, A2, A3 subtypes, and phase B durations between patients with epilepsy and healthy controls.

RESULTS: A total of 11 studies, including 209 patients with epilepsy and 197 healthy controls, fulfilled the eligibility criteria. Compared with healthy controls, patients with epilepsy had significantly increased CAP rates and decreased A1 subtype percentages, and patients with sleep-related epilepsy had increased A3 subtype percentages. Subgroup analyses revealed that antiseizure medications (ASMS) decreased CAP rates and increased phase B durations but did not affect the microstates of phase A in patients with sleep-related epilepsy.

CONCLUSIONS: This meta-analysis detected statistically significant differences in CAP parameters between patients with epilepsy and healthy controls. Our findings suggest patients with epilepsy experience NREM sleep instability. ASMs treatment may decrease NREM instability but did not alter the microstates of phase A.

PMID:35192721 | DOI:10.1093/sleep/zsac041

J Gerontol B Psychol Sci Soc Sci. 2022 Feb 22:gbac030. doi: 10.1093/geronb/gbac030. Online ahead of print.

ABSTRACT

OBJECTIVES: The paper seeks to examine the contribution of internal socioeconomic disparities in mortality to the United States international disadvantage in life expectancy at birth.

METHODS: Using individual death records from the US national vital statistics system for years 1982 to 2019 and data for other countries from the Human Mortality Database, we compare age-specific death rates and life expectancy between counties classified into ten socioeconomic categories and 20 high-income countries. We also calculate the number of years of life lost in each socioeconomic decile in relation to the comparison set.

RESULTS: There is a clear and increasing socioeconomic gradient of mortality in the United States but the growing divergence in internal mortality trends does not explain the rising gap between the country and its peers. In 2019, even American women in the most socioeconomically advantaged decile lived shorter lives while only the 10% men in the most affluent decile fared better than their peers. The long-standing US disadvantage in young adult mortality has been growing and the country previous advantage in mortality at ages 75 years and above has virtually disappeared for all but for Americans in the most affluent counties.

DISCUSSION: The similar age-pattern of differences in mortality rates between socioeconomic deciles and the comparison group suggests that the underlying factors might be the same. The roles of external causes (including drug overdoses) for middle-age adults and a slowing down in progress to control cardiovascular diseases at older ages at the national level are consistent with this pattern.

PMID:35192708 | DOI:10.1093/geronb/gbac030

Diabetes Care. 2022 Feb 22:dc211597. doi: 10.2337/dc21-1597. Online ahead of print.

ABSTRACT

OBJECTIVE: We investigated the association between interval changes in physical activity (PA) and dementia risk among patients with new-onset type 2 diabetes.

RESEARCH DESIGN AND METHODS: We identified 133,751 participants newly diagnosed with type 2 diabetes in a health screening (2009-2012), with a follow-up health screening within 2 years (2010-2015). PA level changes were categorized into continuous lack of PA, decreaser, increaser, and continuous PA groups. Dementia was determined using dementia diagnosis codes and antidementia drug prescriptions.

RESULTS: During the median follow-up of 4.8 years, 3,240 new cases of all-cause dementia developed. Regular PA was associated with lower risks of all-cause dementia (adjusted hazard ratio [aHR] 0.82; 95% CI 0.75-0.90), Alzheimer disease (AD) (aHR 0.85; 95% CI 0.77-0.95), and vascular dementia (VaD) (aHR 0.78; 95% CI 0.61-0.99). Increasers who started to engage in regular PA had a lower risk of all-cause dementia (aHR 0.86; 95% CI 0.77-0.96). Moreover, the risk was further reduced among those with continuous regular PA: all-cause dementia (aHR 0.73; 95% CI 0.62-0.85), AD (aHR 0.74; 95% CI 0.62-0.88), and VaD (aHR 0.62; 95% CI 0.40-0.94). Consistent results were noted in various subgroup analyses.

CONCLUSIONS: Regular PA was independently associated with lower risks of all-cause dementia, AD, and VaD among individuals with new-onset type 2 diabetes. Those with continuous regular PA and, to a lesser extent, those who started to engage in regular PA had a lower risk of dementia. Regular PA should be encouraged to prevent dementia in high-risk populations and those with new-onset type 2 diabetes.

PMID:35192690 | DOI:10.2337/dc21-1597

Age Ageing. 2022 Feb 2;51(2):afac012. doi: 10.1093/ageing/afac012.

ABSTRACT

OBJECTIVE: to evaluate the sensitivity, specificity and test-retest reliability of the Delirium Early Monitoring System-Delirium Observation Screening Scale (DEMS-DOSS).

DESIGN: prospective diagnostic accuracy study of a convenience sample of admitted older adults with DEMS-DOSS and reference standard assessments.

SETTING: 60-bed aged care precinct at a metropolitan hospital in Sydney, Australia.

PARTICIPANTS: 156 patients (aged ≥65 years old) were recruited to participate between April 2018 and March 2020. One hundred participants were included in the analysis.

MEASUREMENTS: Participants were scored on the DEMS-DOSS. Trained senior aged care nurses conducted a standardised clinical interview based on the Diagnostic and Statistical Manual of Mental Disorder (DSM)-IV delirium criteria, within two hours of DEMS-DOSS completion. The senior aged care nurse undertaking the DSM-IV interview was blinded to the results of the DEMS-DOSS.

RESULTS: Participants’ mean age was 84 (SD ±7.3) years and 39% (n = 39) had a documented diagnosis of dementia. Delirium was detected in 38% (n = 38) according to the reference standard. The DEMS-DOSS had a sensitivity of 76.3% and a specificity of 75.8% for delirium. The area under the receiver operating characteristics curve for delirium was 0.76. The test-retest reliability of the DEMS-DOSS was found to be high (r = 0.915).

CONCLUSION: DEMS-DOSS is a sensitive and specific tool to assist with monitoring new onset and established delirium in hospitalised older adults. Further studies are required to evaluate the impact of the monitoring tool on health outcomes.

PMID:35192683 | DOI:10.1093/ageing/afac012