Dataset Information

Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan.

ABSTRACT: This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795, P?

SUBMITTER: Tzeng NS

PROVIDER: S-EPMC5935641 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan.

Tzeng Nian-Sheng NS Chung Chi-Hsiang CH Lin Fu-Huang FH Chiang Chien-Ping CP Yeh Chin-Bin CB Huang San-Yuan SY Lu Ru-Band RB Chang Hsin-An HA Kao Yu-Chen YC Yeh Hui-Wen HW Chiang Wei-Shan WS Chou Yu-Ching YC Tsao Chang-Huei CH Wu Yung-Fu YF Chien Wu-Chien WC

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20180401 2

This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2 ...[more]

PMID: 29488144

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Project description:BACKGROUND: Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores and encephalitis. Previous antiviral studies on herpes viruses have focussed on developing nucleoside analogues that can inhibit viral polymerase and terminate the replicating viral DNA. However, these drugs bear an intrinsic non-specificity as they can also inhibit cellular polymerase apart from the viral one. The present study is an attempt to elucidate the action mechanism of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus providing an evidence for its development as a novel anti-herpetic drug. RESULTS: Withaferin A was found to bind very similarly to that of the previously reported 4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617, Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning of the polymerase. A comparison of the conformation obtained from docking and the molecular dynamics simulations shows that substantial changes in the binding conformations have occurred. These results indicate that the initial receptor-ligand interaction observed after docking can be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favoured. CONCLUSIONS: We have performed docking and molecular dynamics simulation studies to elucidate the binding mechanism of prospective herbal drug withaferin A onto the structure of DNA polymerase of Herpes simplex virus. Our docking simulations results give high binding affinity of the ligand to the receptor. Long de novo MD simulations for 10 ns performed allowed us to evaluate the dynamic behaviour of the system studied and corroborate the docking results, as well as identify key residues in the enzyme-inhibitor interactions. The present MD simulations support the hypothesis that withaferin A is a potential ligand to target/inhibit DNA polymerase of the Herpes simplex virus. Results of these studies will also guide the design of selective inhibitors of DNA POL with high specificity and potent activity in order to strengthen the therapeutic arsenal available today against the dangerous biological warfare agent represented by Herpes Simplex Virus.

Project description:Background/objectiveIn previous reports, the usage of anticholinergic medications has been associated with an increased risk of dementia with prolonged usage or with a high Anticholinergic Cognitive Burden (ACB). This study aimed to investigate the association between anticholinergic medications and the risk of dementia using data from Taiwan's National Health Research Database (NHIRD).MethodsA total of 790,240 patients, with 197,560 patients receiving anticholinergic medications and 592,680 control patients (1:3) matched for sex, age, and index-year, were enrolled from the two million Longitudinal Health Insurance Dataset, a subdataset of the NHIRD, between 2000 and 2015. The time-dependent Cox regression analysis was used to explore the hazard ratio (HR) with a 95% confidence interval for the association between anticholinergics and the risk of dementia during the 15-year follow-up. The behavioral and psychological symptoms of dementia (BPSD) were recognized by the usage of psychotropics. The ACB ranged from zero to three, divided as score <1, 1-1.9, 2-2.9, 3-4.9,and ≧5. The sensitivity analysis was done by excluding the diagnoses of dementia in the first 2 or 4 years after anticholinergic usage.ResultsIn the anticholinergic usage cohort, the HR was 1.043 (95% CI = 0.958-1.212, p = 0.139) without a significant difference. The sensitivity analysis revealed no association between the usage of anticholinergics and the risk of dementia. Anticholinergic usage was not associated with BPSD. Male sex, patients of ages of 60-64 and ≧80, usage of antiparkinsonian medications, a history of Parkinson's disease, epilepsy, urinary incontinence, depression, bipolar disorder, and psychotic disorder were independent risk factors of dementia. Increased HRs for dementia were associated with an ACB ≥ 5 and an anticholinergic usage period ≥ 1,460 days.ConclusionIn this study, the usage of anticholinergics was not associated with the risk of dementia or BPSD in a 15-year follow-up study. However, patients with the male sex, patients with ages of 65-79 and ≧80, patients with some comorbidities, high ACB scores, and long anticholinergic treatment duration were associated with the risk of dementia.

Dataset Information

Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan.

Publications

Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan.

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