Category: Nevin Manimala

Biomed Chromatogr. 2021 Jun 10:e5194. doi: 10.1002/bmc.5194. Online ahead of print.

ABSTRACT

The current work describes development and validation of a stability-indicating UPLC method for the determination of Olmesaratan Medoxomil (OLM), Amlodipine Besylate (AMB), Hydrochlorothiazide (HCT) and their degradation products in the triple-combination tablet dosage form. The separation was achieved using Zorbax Eclipse plus C8 RRHD (100mm x 3.0 mm), 1.8μm column with gradient elution of mobile phase-A containing 0.02M of sodium phosphate buffer (pH 3.35) and mobile phase B as acetonitrile and water (90:10, v/v). The detector signal was monitored at UV 250 nm. Analytical performance of the optimized UPLC method was validated as per ICH guidelines. The linearity ranges for OLM, AMB and HCT were 0.59-240 μg/mL, 0.30-60 μg/mL and 0.37-150 μg/mL respectively with correlation coefficients >0.999. The dosage form was subjected to forced-degradation conditions of neutral, acidic, and alkaline hydrolysis, oxidation, thermal and photo degradation. The method is proved to be stability-indicating by demonstrating the specificity of the drugs from degradation products. Robustness of the method was evaluated through 2-level, 3-factorial design with multivariate approach. Statistical data analysis with best model fit p-value<0.05 from ANOVA test indicated that the individual factors influence is relatively higher than the interaction effects. The method was for the analysis of drug product.

PMID:34110035 | DOI:10.1002/bmc.5194

J Vet Diagn Invest. 2021 Jun 10:10406387211021865. doi: 10.1177/10406387211021865. Online ahead of print.

ABSTRACT

Estimation of the postmortem interval (PMI) is a poorly studied field in veterinary pathology. The development of field-applicable methods is needed given that animal cruelty investigations are increasing continually. We evaluated various histologic criteria in equine brain, liver, and muscle tissue to aid the estimation of PMI in horses, which is central to forensic investigations of suspicious death. After death, autolysis proceeds predictably, depending on environmental conditions. Currently, no field-applied methods exist that accurately estimate the PMI using histology in animals or humans through quantification of autolysis. Brain, liver, and skeletal muscle from 12 freshly euthanized horses were held at 22°C and 8°C for 72 h. Tissues were sampled at T0h, T1h, T2h, T4h, T6h, T12h, T24h, T36h, T48h, T60h, and T72h. For each tissue, we quantified 5 to 7 criteria associated with autolysis, based on the percentage of microscopic field involved. Each criterion was modeled, with temperature and time as independent variables. Changes were most predictable in liver and muscle over the first 72 h postmortem. The criteria for autolysis that were present most extensively at both temperatures were hepatocyte individualization and the separation of bile duct epithelium from the basement membrane. The changes that were present next most extensively were disruption of myofiber continuity, hypereosinophilia, and loss of striation. Brain changes were highly variable. The high statistical correlation between the parameter “autolysis” and the variables “time/temperature”, indicates that autolysis is progressive and predictable. Further investigation of these criteria is needed to establish histologic algorithms for PMI.

PMID:34109897 | DOI:10.1177/10406387211021865

Rev Neurol. 2021 Jun 16;72(12):411-418. doi: 10.33588/rn.7212.2020595.

ABSTRACT

AIM: The aim of this study is to determine whether there are any differences in the dream content in different sleep disorders and to describe their characteristics.

PATIENTS AND METHODS: We studied four sleep disorders: sleep apnoea and hypopnoea syndrome (SAHS), primary insomnia (PI), idiopathic REM sleep behaviour disorder (IRBD) and narcolepsy type I. Each patient was asked to keep a dream diary for two weeks. The content of the diaries was transcribed and analysed for length, mental content, complexity and threat. The results were compared to establish differences.

RESULTS: Eighty-nine patients were studied: 23 with SAHS without continuous positive airway pressure (CPAP) who had the highest number of dreams involving threats (32.5%); 19 with SAHS treated with CPAP who had the highest number of dreams involving objects (64.8%), descriptive elements (38%) and higher complexity (9.5%); 22 with primary insomnia who had the highest number of dreams with threatening events in the social sphere (57.7%); 12 with IRBD who had the highest number of dreams with failures (14%) and lower complexity (71.7%); and 13 with narcolepsy type I who had the highest number of dreams related to activities (84.3%) and threats to life (41.4%) These differences were statistically significant (p <0.05).

CONCLUSIONS: Different sleep disorders are associated with different dream contents, which would be translating different underlying neurological processes. These findings should be replicated in studies that analyse more patients and add a control group without sleep disorders.

PMID:34109996 | DOI:10.33588/rn.7212.2020595

Perfusion. 2021 Jun 10:2676591211023687. doi: 10.1177/02676591211023687. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400-600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement.

METHODS: Simultaneous ACT measurements were performed with the Hemochron Response^®, Hemostasis Management System Plus^® (HMS Plus^®) and Hemochron Signature^® systems.

RESULTS: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature^® 361.1 seconds (SD: 156.9), HMS Plus^® 412.8 seconds (SD: 180.9) and Hemochron Response^® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman’s test p < 0.01). For comparisons the Bland-Altman method was used, resulting the Hemochron Response^® has 61.7 seconds higher mean values than the Hemochron Signature^®, the Hemochron Response^® 10 seconds higher than the HMS Plus^® and the HMS Plus^® 51.7 seconds higher than the Hemochron Signature^®.

CONCLUSION: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.

PMID:34109886 | DOI:10.1177/02676591211023687

Benef Microbes. 2021 Jun 10:1-8. doi: 10.3920/BM2021.0008. Online ahead of print.

ABSTRACT

The aim of this study was to explore the preventive effect of probiotic supplements on the development of early childhood caries (ECC). We searched the PubMed, Google Scholar and Cochrane databases up to January 15, 2021. The authors screened the hits independently for relevance, extracted outcome data and assessed the risk of bias. We performed a random effects meta-analysis to pool and compare the incidence of ECC in children assigned to test or placebo groups, respectively. The authors included nine randomised controlled trials published between 2001 and 2021, involving 2,363 preschool children. We assessed two publications with a moderate risk of bias and seven with high risk of bias. The median caries incidence in the probiotic test groups was 8.5% compared with 17.5% in the placebo groups and this difference was statistically significant (P<0.001). A pooled random effects meta-analysis on caries incidence on subject level showed a small but statistically significant risk difference in favour of the probiotic intervention (-0.05, 95% confidence interval (CI) -0.10, -0.00; P<0.05). The mean difference in caries increment on tooth/surface level was -0.57, (95% CI -0.91, -0.23; P<0.01). In conclusion, we demonstrated a small but statistically significant preventive effect of probiotic supplements on ECC. However, the certainty of this finding was low due to the risk of bias, heterogeneity and inconsistencies across the studies. Further long-term randomised controlled trials with low risk of bias are required in order to answer the research question with a higher certainty.

PMID:34109895 | DOI:10.3920/BM2021.0008

J Prim Care Community Health. 2021 Jan-Dec;12:21501327211024417. doi: 10.1177/21501327211024417.

ABSTRACT

INTRODUCTION: The proportion of patients who are frequent attenders (FAs) varies from few percent to almost 30% of all patients. A small group of patients continued to visit GPs year after year. In previous studies, it has been reported that over 15% of all 1-year FAs were persistent frequent attenders (pFAs).

OBJECTIVES: This study aimed to identify typical features of pFAs from the textual content in their medical entries, which could help GPs to recognize pFAs easily and facilitated treatment.Methods: A retrospective register study was done, using 10 years of electronic patient records. The data were collected from Finnish primary health care centers and used to analyze chronic symptoms and diagnoses of pFAs and to calculate the inverse document frequency weight (IDF) of words used in the patient records. IDF was used to determine which words, if any, are typical for pFAs. The study group consisted of the 5-year pFAs and control group of 1-year FAs. The main background variables were age, gender, occupation, smoking habits, use of alcohol, and BMI.

RESULTS: Out of 4392 frequent attenders, 6.6% were pFAs for 3 years and 1.1% were pFAs for 5 years. Of the pFAs, 65% were female and 35% were male. The study group had significantly more depressive episodes (P = .004), heart failure (P = .019), asthma (P = .032), COPD (P = .036), epilepsy (P = .035), and lumbago (P = .046) compared to the control group. GPs described their 5-year pFAs by words related to lung and breathing issues, but there was no statistical difference to the 1-year FAs’ descriptions.

CONCLUSION: A typical pFA seems to be a woman, aged about 55 years with depressive episodes, asthma or COPD, and lower back pain. Physicians describe pFAs with ordinary words in patient records. It was not possible to differentiate pFAs from 1-year FAs in this way.

PMID:34109878 | DOI:10.1177/21501327211024417

Nat Commun. 2021 Jun 9;12(1):3505. doi: 10.1038/s41467-021-23556-4.

ABSTRACT

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.

PMID:34108472 | DOI:10.1038/s41467-021-23556-4

Med Sci Monit. 2021 Jun 10;27:e930151. doi: 10.12659/MSM.930151.

ABSTRACT

BACKGROUND The aim of this study was to assess the influence of socio-demographic and clinical factors on personality trait expression and their relationship with more intense interdialytic disorders and changes in health behaviors of patients with chronic kidney disease (CKD). MATERIAL AND METHODS A total of 200 participants were recruited for the research (84 women and 116 men; aged 61±12 years): 160 patients had CKD stage G4-G5 and 40 healthy participants constituted a control group. A diagnostic poll method was used in the research employing the following questionnaires to collect socio-demographic and clinical data: Health Behavior Inventory (IZZ), Personality Inventory (NEO-FFI), Beck Depression Inventory (BDI), and Researcher’s Questionnaire Test. RESULTS Statistically significant differences were found in the intensity of personal traits at different stages of treatment. The influence of factors resulting from CKD on the expression of personality traits increased with subsequent stages of treatment. Depression intensity was not connected with the expression of personality traits. A higher frequency of reported interdialytic disorders was significantly related to a higher degree of openness and conscientiousness and a lower degree of agreeableness. Increased extraversion, conscientiousness, and openness were significantly correlated with more intense health behaviors. CONCLUSIONS Personalities of patients with CKD changed with subsequent stages of treatment and were influenced by socio-demographic and clinical factors. Personalities affected the frequency of reported interdialytic disorders and health behaviors.

PMID:34108439 | DOI:10.12659/MSM.930151

Nat Commun. 2021 Jun 9;12(1):3506. doi: 10.1038/s41467-021-23655-2.

ABSTRACT

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term ‘variance stratification’. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from multiple studies. We describe a WGS-appropriate analysis approach, implemented in freely-available software, which allows study-specific variances and thereby improves performance in practice. We illustrate the variance stratification problem, its solutions, and the proposed diagnostic procedure, in simulations and in data from the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed), used in association tests for hemoglobin concentrations and BMI.

PMID:34108454 | DOI:10.1038/s41467-021-23655-2

J Trauma Acute Care Surg. 2021 Apr 8. doi: 10.1097/TA.0000000000003192. Online ahead of print.

ABSTRACT

BACKGROUND: Studies comparing mortality following massive transfusion (MT) with fresher versus longer-stored red blood cells (RBCs) have focused on trauma patients. The Australian and New Zealand Massive Transfusion Registry (ANZMTR) collects data on all adult MT cases (≥5 RBCs within 4 hours, any bleeding context, ≥ 18 years) at participating hospitals.

METHODS: 2007-2018 data from 29 hospitals were analyzed to quantify the association between mortality and RBC storage time in adult MT cases. We ran three logistic regression models separately on each of seven bleeding contexts, with in-hospital mortality as the outcome and, in turn, (1) mean storage time (STmean) quartiles, (2) proportion of RBCs ≥30 days old (propOLD), and (3) scalar age of blood index (SBI) as predictors.

RESULTS: 8,685 adult MT cases involving transfusion of 126,622 RBCs were analyzed with Australian and New Zealand data analyzed separately. Mean storage times for these cases were (by quartile in ascending order) Australia: 12.5 days (range: 3.1-15.5 days), 17.7 (15.5-19.9), 22.3 (19.9-24.9), 29.8 (24.9-41.7); New Zealand: 11.3 (3.6-13.7), 15.3 (13.7-16.8), 18.7 (16.8-20.7), 24.5 (20.7-35.6). The odds ratios comparing in-hospital mortality for each quartile to that of the control first quartile (freshest blood), proportion of longer-stored (≥30 days) RBCs, and SBI were not statistically significant across all bleeding contexts.

CONCLUSIONS: We find no correlation between in-hospital mortality and storage time of transfused RBCs in a large cohort of adult MT patients representing all bleeding contexts. These results are consistent with those of recent large multi-center trials.

LEVEL OF EVIDENCE: Level III (retrospective study with one negative criterion [heterogeneous population]).

PMID:34108423 | DOI:10.1097/TA.0000000000003192