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Strategies prescribers and pharmacists use to identify and mitigate adverse drug reactions in inpatient and outpatient care: a cognitive task analysis at a US Veterans Affairs Medical Center
(BMJ, 2022-02-21) Nguyen, Khoa Anh; Militello, Laura G.; Ifeachor, Amanda; Arthur, Karen J.; Glassman, Peter A.; Zillich, Alan J.; Weiner, Michael; Russ-Jara, Alissa L.; Medicine, School of Medicine
Objective: To develop a descriptive model of the cognitive processes used to identify and resolve adverse drug reactions (ADRs) from the perspective of healthcare providers in order to inform future informatics efforts SETTING: Inpatient and outpatient care at a tertiary care US Veterans Affairs Medical Center.
Participants: Physicians, nurse practitioners and pharmacists who report ADRs.
Outcomes: Descriptive model and emerging themes from interviews.
Results: We conducted critical decision method interviews with 10 physicians and 10 pharmacists. No nurse practitioners submitted ADR incidents. We generated a descriptive model of an ADR decision-making process and analysed emerging themes, categorised into four stages: detection of potential ADR, investigation of the problem's cause, risk/benefit consideration, and plan, action and follow-up. Healthcare professionals (HCPs) relied on several confirmatory or disconfirmatory cues to detect and investigate potential ADRs. Evaluating risks and benefits of related medications played an essential role in HCPs' pursuits of solutions CONCLUSIONS: This study provides an illustrative model of how HCPs detect problems and make decisions regarding ADRs. The design of supporting technology for potential ADR problems should align with HCPs' real-world cognitive strategies, to assist fully in detecting and preventing ADRs for patients.
Genetic Influence Underlying Brain Connectivity Phenotype: A Study on Two Age-Specific Cohorts
(Frontiers Media, 2022-02-07) Cong, Shan; Yao, Xiaohui; Xie, Linhui; Yan, Jingwen; Shen, Li; Alzheimer’s Disease Neuroimaging Initiative; Electrical and Computer Engineering, School of Engineering and Technology
Background: Human brain structural connectivity is an important imaging quantitative trait for brain development and aging. Mapping the network connectivity to the phenotypic variation provides fundamental insights in understanding the relationship between detailed brain topological architecture, function, and dysfunction. However, the underlying neurobiological mechanism from gene to brain connectome, and to phenotypic outcomes, and whether this mechanism changes over time, remain unclear.
Methods: This study analyzes diffusion-weighted imaging data from two age-specific neuroimaging cohorts, extracts structural connectome topological network measures, performs genome-wide association studies of the measures, and examines the causality of genetic influences on phenotypic outcomes mediated via connectivity measures.
Results: Our empirical study has yielded several significant findings: 1) It identified genetic makeup underlying structural connectivity changes in the human brain connectome for both age groups. Specifically, it revealed a novel association between the minor allele (G) of rs7937515 and the decreased network segregation measures of the left middle temporal gyrus across young and elderly adults, indicating a consistent genetic effect on brain connectivity across the lifespan. 2) It revealed rs7937515 as a genetic marker for body mass index in young adults but not in elderly adults. 3) It discovered brain network segregation alterations as a potential neuroimaging biomarker for obesity. 4) It demonstrated the hemispheric asymmetry of structural network organization in genetic association analyses and outcome-relevant studies.
Discussion: These imaging genetic findings underlying brain connectome warrant further investigation for exploring their potential influences on brain-related complex diseases, given the significant involvement of altered connectivity in neurological, psychiatric and physical disorders.
COVID-19-Induced Graves' Disease
(Springer Nature, 2022-02-15) Ghareebian, Hagop; Mariash, Cary; Medicine, School of Medicine
COVID-19, a multi-system disease, could potentially play a role in thyroid dysfunction. New reports show a prevalence of COVID-related thyroiditis. Recent studies suggest that there may be a higher risk of thyroiditis in the setting of SARS-CoV-2, and several cases of Graves’ disease have been reported in individuals with SARS-CoV-2, although the incidence of such findings and their relationship to COVID-19 is unknown. In this report, we present Graves’ hyperthyroidism in a 48-year-old African American male who was admitted to the hospital for complaints of cough, fatigue, and palpitations. He tested positive for SARS-CoV-2 and was found to have suppressed thyroid-stimulating hormone (TSH) and an elevated free T4. The patient had no prior history of thyroid disease. Initially, it was thought to be a case of viral thyroiditis, and he was discharged on prednisone. However, he was found to have positive thyroid-stimulating immunoglobulin (TSI) and a diffuse increase in flow on doppler ultrasound of the thyroid. Subsequently, he was started on anti-thyroid medications with significant improvement. What is unique about this case is that, unlike other described cases in the literature where there was a relapse of a known Graves' disease after COVID-19 disease, our patient did not have a history or symptoms of thyroid disease prior to this event, which should raise the concern about possible activation of Graves' disease after SARS-CoV-2 infection through an autoimmune pathway. In our opinion, physicians, particularly endocrinologists, must be aware of this condition and keep it in mind as a potential differential diagnosis when encountering a similar clinical scenario.
Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer's disease
(Wiley, 2022) Jun, Gyungah R.; You, Yang; Zhu, Congcong; Meng, Gaoyuan; Chung, Jaeyoon; Panitch, Rebecca; Hu, Junming; Xia, Weiming; The Alzheimer’s Disease Genetics Consortium; Bennett, David A.; Foroud, Tatiana M.; Wang, Li-San; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Au, Rhoda; Lunetta, Kathryn L.; Ikezu, Tsuneya; Stein, Thor D.; Farrer, Lindsay A.; Medical and Molecular Genetics, School of Medicine
Introduction: The apolipoprotein E (APOE) ɛ2 allele reduces risk against Alzheimer's disease (AD) but mechanisms underlying this effect are largely unknown.
Methods: We conducted a genome-wide association study for AD among 2096 ɛ2 carriers. The potential role of the top-ranked gene and complement 4 (C4) proteins, which were previously linked to AD in ɛ2 carriers, was investigated using human isogenic APOE allele-specific induced pluripotent stem cell (iPSC)-derived neurons and astrocytes and in 224 neuropathologically examined human brains.
Results: PPP2CB rs117296832 was the second most significantly associated single nucleotide polymorphism among ɛ2 carriers (P = 1.1 × 10-7 ) and the AD risk allele increased PPP2CB expression in blood (P = 6.6 × 10-27 ). PPP2CB expression was correlated with phosphorylated tau231/total tau ratio (P = .01) and expression of C4 protein subunits C4A/B (P = 2.0 × 10-4 ) in the iPSCs. PPP2CB (subunit of protein phosphatase 2A) and C4b protein levels were correlated in brain (P = 3.3 × 10-7 ).
Discussion: PP2A may be linked to classical complement activation leading to AD-related tau pathology.
Processed Electroencephalogram Monitoring and Postoperative Delirium: A Systematic Review and Meta-Analysis
(2018) MacKenzie, Kristen K.; Britt-Spells, Angelitta M.; Sands, Laura P.; Leung, Jacqueline M.
BACKGROUND: Postoperative delirium complicates approximately 15 to 20% of major operations in patients at least 65 yr old and is associated with adverse outcomes and increased resource utilization. Furthermore, patients with postoperative delirium might also be at risk of developing long-term postoperative cognitive dysfunction. One potentially modifiable variable is use of intraoperative processed electroencephalogram to guide anesthesia. This systematic review and meta-analysis examines the relationship between processed electroencephalogram monitoring and postoperative delirium and cognitive dysfunction.
Methods: A systematic search for randomized controlled trials was conducted using Ovid MEDLINE, PubMed, EMBASE, Cochrane Library, and Google search using the keywords processed electroencephalogram, Bispectral Index, postoperative delirium, postoperative cognitive dysfunction. Screening and data extraction were conducted by two independent reviewers, and risk of bias was assessed. Postoperative delirium combined-effect estimates calculated with a fixed-effects model were expressed as odds ratios with 95% CIs.
Results: Thirteen of 369 search results met inclusion criteria. Postoperative cognitive dysfunction data were excluded in meta-analysis because of heterogeneity of outcome measurements; results were discussed descriptively. Five studies were included in the quantitative postoperative delirium analysis, with data pooled from 2,654 patients. The risk of bias was low in three studies and unclear for the other two. The use of processed electroencephalogram-guided anesthesia was associated with a 38% reduction in odds for developing postoperative delirium (odds ratio = 0.62; P < 0.001; 95% CI, 0.51 to 0.76).
Conclusions: Processed electroencephalogram-guided anesthesia was associated with a decrease in postoperative delirium. The mechanism explaining this association, however, is yet to be determined. The data are insufficient to assess the relationship between processed electroencephalogram monitoring and postoperative cognitive dysfunction.