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Nevin Manimala Statistics

Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization

J Clin Endocrinol Metab. 2022 Mar 20:dgac171. doi: 10.1210/clinem/dgac171. Online ahead of print.

ABSTRACT

BACKGROUND: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause.

OBJECTIVES: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian Randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men.

DESIGN: Two-sample MR, using both cohort data as well as summary statistics, with four methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression.

PARTICIPANTS: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available GWAS were pooled for the different analyses.

MAIN OUTCOME MEASURES: CHD, CHD risk factors and ANM.

RESULTS: Across different methods of MR no association was found between genetically determined reproductive aging and CHD risk in women (Relative Risk Estimate (RRE)IVW=0.99, 95% confidence interval (CI):0.97;1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging.

CONCLUSION: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.

PMID:35306566 | DOI:10.1210/clinem/dgac171

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Nevin Manimala Statistics

The Effect of Linked Color Imaging for Adenoma Detection. A Meta-analysis of Randomized Controlled Studies

J Gastrointestin Liver Dis. 2022 Mar 19;31(1):67-73. doi: 10.15403/jgld-4027.

ABSTRACT

BACKGROUND AND AIMS: The effect of linked color imaging (LCI) compared with white light imaging (WLI) is conflicting. The aim of this meta-analysis is to compare the efficacy of LCI versus WLI for the adenoma detection.

METHODS: PubMed, Embase, Google Scholar and Cochrane Library were searched up to the end of Aug 18, 2021. All randomized controlled trials (RCTs) comparing LCI with WLI were included. Dichotomous data were pooled to obtain the relative risk (RR) with a 95% confidence interval (CI), whereas continuous data were pooled using a mean difference (MD) with 95%CI.

RESULTS: A total of 10 RCTs involving 5,510 patients were included. The use of LCI was associated with a statistically significant improvement in adenoma detection rate (ADR), polyp detection rate (PDR), mean adenomas per patient (MAP) and mean polyp per patient (MPP) when compared to WLI (ADR: RR=1.15, 95%CI: 1.07-1.23, p=0.0001, PDR: RR=1.15, 95%CI: 1.08-1.22, p<0.0001; MAP: MD=0.18, 95%CI: 0.09- 0.28, p=0.0002; MPP: MD=0.13, 95%CI: 0.01, 0.25, p=0.03). When stratified by size, LCI group had a higher detection rate of small adenomas (<10 mm) than the WLI group. Besides, LCI showed a significant decrease in adenoma miss rate (AMR) when compared to WLI. There were no statistically significant differences between the two groups in advanced ADR (AADR), sessile serrated lesion detection rate (SDR), cecal intubation rate, insertion time, and withdrawal time.

CONCLUSIONS: The pooled evidence suggests that LCI can significantly improve the detection of ADR, especially for small adenomas (<10 mm). Moreover, the AMR were significantly lower using LCI compared with WLI.

PMID:35306544 | DOI:10.15403/jgld-4027

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Nevin Manimala Statistics

Blood Metabolomic Signatures to Identify Bacterial Infection in Patients with Decompensated Cirrhosis

J Gastrointestin Liver Dis. 2022 Mar 19;31(1):40-47. doi: 10.15403/jgld-4034.

ABSTRACT

BACKGROUND AND AIMS: Bacterial infections are associated with high mortality rates in patients with decompensated cirrhosis. Early diagnosis with the available diagnostic tools is challenging. Metabolomics is a novel technique with a widespread application in hepatology. The aims of our study were to find new biomarkers for decompensated cirrhosis and for those with overlapping bacterial infections.

METHODS: 43 patients with compensated and 54 patients with decompensated cirrhosis were enrolled in the study. In patients with decompensation, a complete infectious workup was performed at admission. Blood and ascitic fluid were collected and stored at -80° C until performing the metabolomic analysis. Statistical analysis was performed using the Metaboanalyst 4.0 software.

RESULTS: 36 patients (66%) in the decompensated group were infected. Among them, 15 had multiple infections; thus, finally, 52 infections were diagnosed. The main metabolic pathways affected in patients with decompensated cirrhosis were those related to lipid metabolism, involving acylcarnitines, stearic acid derivatives, and 12/15 HETE-GABA. N-oleoyl ethanolamine was the most promising biomarker for bacterial infection diagnosis. Moreover, prostaglandin E2/D2/H2 and N-oleoyl alanine levels were higher in Gram- positive infections and ceramides (d16:2/18:0), in Gram-negative infections, respectively. L-phenylalanine (m/z=166.09) and lysophosphatidylethanolamine (18:3/0:0) were the two most relevant identified ascitic biomarkers for spontaneous bacterial peritonitis diagnosis.

CONCLUSIONS: The lipid and energetic metabolic pathways were the most affected in patients with decompensated cirrhosis and those with overlapping infections.

PMID:35306561 | DOI:10.15403/jgld-4034

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Nevin Manimala Statistics

Clinical Relevance of Anti-Gliadin Seropositivity in the Ageing Population: A Long-term Follow-up Study

J Gastrointestin Liver Dis. 2022 Mar 19;31(1):11-17. doi: 10.15403/jgld-4025.

ABSTRACT

AIMS: To explore if anti-gliadin antibody (AGA) positivity is associated with overall mortality or morbidity and especially with the development of coeliac disease during long-term gluten exposure.

METHODS: The study population comprised 130 persistently AGA-positive but transglutaminase-2 (anti- TG2) -negative and 52 persistently AGA- and anti-TG2 -negative subjects aged 64-88 years. HLA-typing for DQ2 and DQ8 (coeliac-type HLA) was performed on the AGA-positives. The medical records of the study population were reviewed to compare mortality and morbidity during a long-term follow-up of 12-13 years since the initial antibody analysis.

RESULTS: Mortality or cumulative prevalence of gastroenterological, autoimmune, psychiatric, cardiovascular or any malignant diseases did not differ statistically between the AGA-positives and the AGA-negatives. Neurological diseases were more common in the AGA-negative group (p=0.017), but there was no statistical difference between the prevalence of any particular neurological diseases. Coeliac-type HLA in AGA-positive subjects did not influence mortality or morbidity. However, during the last six to seven years the incidence of immunological diseases was more common in the AGA-positive subjects without coeliac-type HLA than in those with coeliac-type HLA, or in the AGA-negative group (p=0.020). None of the persistently AGA-positive subjects developed clinically diagnosed coeliac disease.

CONCLUSIONS: Gliadin antibody positivity without coeliac disease does not predict mortality or morbidity in the ageing population continuing to consume gluten for over ten years.

PMID:35306543 | DOI:10.15403/jgld-4025

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Nevin Manimala Statistics

A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing

Br J Cancer. 2022 Mar 19. doi: 10.1038/s41416-022-01779-6. Online ahead of print.

ABSTRACT

BACKGROUND: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type).

METHODS: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life).

RESULTS: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27-0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24-0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93-1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66-2.44], p = 0.47).

CONCLUSION: PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response.

REGISTRATION NUMBER: The study is registered with PROSPERO, registration number CRD42020223768.

PMID:35306539 | DOI:10.1038/s41416-022-01779-6

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Nevin Manimala Statistics

Parameters from site classification to harmonize MRI clinical studies: Application to a multi-site Parkinson’s disease dataset

Hum Brain Mapp. 2022 Mar 19. doi: 10.1002/hbm.25838. Online ahead of print.

ABSTRACT

Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson’s disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE-p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site-effects quantitatively and allow the harmonization of data. This method is user-friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites.

PMID:35305545 | DOI:10.1002/hbm.25838

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Nevin Manimala Statistics

Advancement in the contemporary clinical diagnosis and treatment strategies of insomnia disorder

Sleep Med. 2022 Mar 1;91:124-140. doi: 10.1016/j.sleep.2022.02.018. Online ahead of print.

ABSTRACT

This review is intended to provide an updated summary of, but not limited to, classification, etiopathogenesis, diagnosis, and treatment strategies for insomnia disorder. The severity of insomnia symptoms irrespective of co-existing primary medical condition/s in the studied patients classified insomnia as ‘insomnia disorder’ to prioritize the clinical attention on insomnia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The frequency and duration of symptoms further divided insomnia into chronic, short-term, and other insomnia disorder (International Classification of Sleep Disorders, Third Edition). This disorder is a phenomenal state of hyperarousal developed and perpetuated by environmental, behavioral, cognitive, genetic, socioeconomic, preexisting medical factors. Overarching physiological, cortical, behavioral, and cognition changes in hyperarousal manifest insomnia disorder. It, sometimes, leads to the co-occurrence of other chronic medical condition/s. The contemporary diagnosis of insomnia disorder needs to consider modified diagnostic criteria, growing evidence on insomnia disorder symptoms, associated factors, co-existing medical condition/s (if any) to identify the subjective severity of insomnia disorder and design a treatment plan. The recommended treatment strategies include cognitive-behavioral therapy for insomnia (CBTI) and pharmacotherapy. However, CBTI lacks accessibility, qualified facilitators, and pharmacotherapy has limitations like side effects, physiological tolerance/dependence. The investigation of phytocompounds subdued these drawbacks of existing treatments as some compounds showed anti-insomniac potential. Furthermore, complementary alternative medicines (CAMs) like mindfulness-based practices, acupuncture, listening to music, Yogasanas, Pranayama, digital cognitive behavioral therapy for insomnia (dCBTI) during bedtime proved supportive in insomnia disorder treatment.

PMID:35305527 | DOI:10.1016/j.sleep.2022.02.018

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Longitudinal analysis of aging in place at TigerPlace: Resident function and well-being

Geriatr Nurs. 2022 Mar 16;45:47-54. doi: 10.1016/j.gerinurse.2022.02.030. Online ahead of print.

ABSTRACT

This paper reports on a longitudinal eight-year analysis (2011-2019) of trajectory of function and well-being residents of TigerPlace Aging in Place (AIP) model of care. Residents were routinely assessed using standard health assessment instruments. Average scores from each measure were examined for changes or trends in resident function; decline over time was calculated. Scores for depression, mental health subscale Short Form Health Survey-12 (SF-12) remained stable over time. Mini Mental State Exam declined to mild dementia range (21-24). Physical measures SF-12 physical health subscale, ADLs, and IADLs declined slightly, while fall risk increased over time. When yearly trends in AIP were modeled with a referent group there was no significant worsening of functioning. The length of stay for TigerPlace residents continued to remain stable at nearly 30 months. Residents maintained function in the environment of their choice longer at cost less than nursing homes, and just above residential care cost.

PMID:35305514 | DOI:10.1016/j.gerinurse.2022.02.030

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Nevin Manimala Statistics

Evaluation of pulmonary function and exercise capacity after COVID-19 pneumonia

Heart Lung. 2022 Mar 11;54:1-6. doi: 10.1016/j.hrtlng.2022.03.004. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals who suffer from coronavirus disease 2019 (COVID-19) pneumonia may experience pulmonary dysfunction during the chronic period due to pulmonary parenchymal damage after acute disease.

OBJECTIVES: The aim of the present study was to evaluate the pulmonary function and exercise capacity of patients treated for COVID 19 pneumonia after discharge.

METHODS: In this cross-sectional study, 79 people who were hospitalized with COVID-19 between March and October 2020 were evaluated at least two months after discharge. A pulmonary function test and a six-minute walk test were administered to the individuals included in the study.

RESULTS: Restrictive-type disorder was detected in 21.5% of the individuals who were evaluated at least two months after discharge. The forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC) values of the pulmonary function tests were significantly lower in the individuals with severe/critical clinical disease compared to those with moderate disease (p = 0.004 and p = 0.001, respectively). Although the six-minute walk test (6MWT) distances were lower in the severe/critical group than in the moderate group, the difference was not statistically significant (p > 0.05).

CONCLUSIONS: Individuals who are discharged after hospitalization for COVID-19 pneumonia may develop a restrictive type of pulmonary dysfunction. Therefore, survivors of COVID-19 pneumonia should be evaluated for pulmonary function and rehabilitation needs and should be provided with treatment as required.

PMID:35305515 | DOI:10.1016/j.hrtlng.2022.03.004

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Nevin Manimala Statistics

Hippocampal and auditory contributions to speech segmentation

Cortex. 2022 Feb 23;150:1-11. doi: 10.1016/j.cortex.2022.01.017. Online ahead of print.

ABSTRACT

Statistical learning has been proposed as a mechanism to structure and segment the continuous flow of information in several sensory modalities. Previous studies proposed that the medial temporal lobe, and in particular the hippocampus, may be crucial to parse the stream in the visual modality. However, the involvement of the hippocampus in auditory statistical learning, and specifically in speech segmentation is less clear. To explore the role of the hippocampus in speech segmentation based on statistical learning, we exposed seven pharmaco-resistant temporal lobe epilepsy patients to a continuous stream of trisyllabic pseudowords and recorded intracranial stereotaxic electro-encephalography (sEEG). We used frequency-tagging analysis to quantify neuronal synchronization of the hippocampus and auditory regions to the temporal structure of words and syllables of the learning stream. We also analyzed the event-related potentials (ERPs) of the test to evaluate the role of both regions in the recognition of newly segmented words. Results show that while auditory regions highly respond to syllable frequency, the hippocampus responds mostly to word frequency. Moreover, ERPs collected in the hippocampus show clear sensitivity to the familiarity of the items. These findings provide direct evidence of the involvement of the hippocampus in the speech segmentation process and suggest a hierarchical organization of auditory information during speech processing.

PMID:35305505 | DOI:10.1016/j.cortex.2022.01.017