scholarly journals Safety of hydroxychloroquine and darunavir or lopinavir in COVID-19 infection

2020 ◽  
Author(s):  
Etienne Meriglier ◽  
Claire Rivoisy ◽  
Mojgan Hessamfar ◽  
Noelle Bernard ◽  
Ines Aureau ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cohort Study ◽  
Clinical Practice ◽  
Combination Therapy ◽  
Observational Cohort Study ◽  
Potential Drug ◽  
Clinical Evaluations ◽  
History Of ◽  
Observational Cohort ◽  
Ecg Abnormalities

Abstract Background Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection. Objectives To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Methods This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines. Results Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2–6) days after starting treatment. All ECG abnormalities reversed 1–2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration. Conclusions Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease.

scholarly journals Antidepressant dose and the risk of deliberate self-harm

2014 ◽  
Vol 23 (4) ◽  
pp. 329-331 ◽  
Author(s):  
C. Barbui ◽  
S.B. Patten
Keyword(s):  
Cohort Study ◽  
Clinical Practice ◽  
Propensity Score ◽  
Adverse Effects ◽  
Suicidal Behaviour ◽  
Research Question ◽  
Observational Cohort Study ◽  
Panic Attacks ◽  
Observational Cohort ◽  
Self Harm

Although the mechanism by which antidepressants (ADs) may increase the risk of suicide-related outcomes is unknown, it has been hypothesised that some adverse effects, including akathisia, insomnia and panic attacks, as well as an early energising effect that might allow patients with depression to act on suicidal impulses, may have a key role. Considering that these adverse effects are dose-related, it might be hypothesised that the risk of suicidal behaviour is similarly related to the AD dose. This research question has recently been addressed by a propensity score-matched observational cohort study that involved 162 625 patients aged 10–64 years with a depression diagnosis who initiated therapy with citalopram, sertraline or fluoxetine. In this commentary, we discuss the main findings of this study in view of its methodological strengths and limitations, and we suggest possible implications for day-to-day clinical practice.

scholarly journals Genetic and pharmacological relationship between P-glycoprotein and increased cardiovascular risk associated with clarithromycin prescription: An epidemiological and genomic population-based cohort study in Scotland, UK

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003372
Author(s):  
Ify R. Mordi ◽  
Benjamin K. Chan ◽  
N. David Yanez ◽  
Colin N. A. Palmer ◽  
Chim C. Lang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Observational Cohort Study ◽  
Chronic Obstructive ◽  
Antibiotic Prescribing ◽  
Nucleotide Polymorphisms ◽  
Major Pathway ◽  
P Glycoprotein ◽  
Increased Risk ◽  
History Of ◽  
Observational Cohort

Background There are conflicting reports regarding the association of the macrolide antibiotic clarithromycin with cardiovascular (CV) events. A possible explanation may be that this risk is partly mediated through drug–drug interactions and only evident in at-risk populations. To the best of our knowledge, no studies have examined whether this association might be mediated via P-glycoprotein (P-gp), a major pathway for clarithromycin metabolism. The aim of this study was to examine CV risk following prescription of clarithromycin versus amoxicillin and in particular, the association with P-gp, a major pathway for clarithromycin metabolism. Methods and findings We conducted an observational cohort study of patients prescribed clarithromycin or amoxicillin in the community in Tayside, Scotland (population approximately 400,000) between 1 January 2004 and 31 December 2014 and a genomic observational cohort study evaluating genotyped patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study, a longitudinal cohort study of 18,306 individuals with and without type 2 diabetes recruited between 1 December 1988 and 31 December 2015. Two single-nucleotide polymorphisms associated with P-gp activity were evaluated (rs1045642 and rs1128503 –AA genotype associated with lowest P-gp activity). The primary outcome for both analyses was CV hospitalization following prescription of clarithromycin versus amoxicillin at 0–14 days, 15–30 days, and 30 days to 1 year. In the observational cohort study, we calculated hazard ratios (HRs) adjusted for likelihood of receiving clarithromycin using inverse proportion of treatment weighting as a covariate, whereas in the pharmacogenomic study, HRs were adjusted for age, sex, history of myocardial infarction, and history of chronic obstructive pulmonary disease. The observational cohort study included 48,026 individuals with 205,227 discrete antibiotic prescribing episodes (34,074 clarithromycin, mean age 73 years, 42% male; 171,153 amoxicillin, mean age 74 years, 45% male). Clarithromycin use was significantly associated with increased risk of CV hospitalization compared with amoxicillin at both 0–14 days (HR 1.31; 95% CI 1.17–1.46, p < 0.001) and 30 days to 1 year (HR 1.13; 95% CI 1.06–1.19, p < 0.001), with the association at 0–14 days modified by use of P-gp inhibitors or substrates (interaction p-value: 0.029). In the pharmacogenomic study (13,544 individuals with 44,618 discrete prescribing episodes [37,497 amoxicillin, mean age 63 years, 56% male; 7,121 clarithromycin, mean age 66 years, 47% male]), when prescribed clarithromycin, individuals with genetically determined lower P-gp activity had a significantly increased risk of CV hospitalization at 30 days to 1 year compared with heterozygotes or those homozygous for the non-P-gp–lowering allele (rs1045642 AA: HR 1.39, 95% CI 1.20–1.60, p < 0.001, GG/GA: HR 0.99, 95% CI 0.89–1.10, p = 0.85, interaction p-value < 0.001 and rs1128503 AA 1.41, 95% CI 1.18–1.70, p < 0.001, GG/GA: HR 1.04, 95% CI 0.95–1.14, p = 0.43, interaction p-value < 0.001). The main limitation of our study is its observational nature, meaning that we are unable to definitively determine causality. Conclusions In this study, we observed that the increased risk of CV events with clarithromycin compared with amoxicillin was associated with an interaction with P-glycoprotein.

scholarly journals Valproate v. lithium in the treatment of bipolar disorder in clinical practice: observational nationwide register-based cohort study

2011 ◽  
Vol 199 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Lars Vedel Kessing ◽  
Gunnar Hellmund ◽  
John R. Geddes ◽  
Guy M. Goodwin ◽  
Per Kragh Andersen
Keyword(s):  
Bipolar Disorder ◽  
Cohort Study ◽  
Clinical Practice ◽  
Hospital Admission ◽  
Psychiatric Hospital ◽  
Hospital Admissions ◽  
Observational Cohort Study ◽  
Hazard Ratio ◽  
Daily Clinical Practice ◽  
Observational Cohort

BackgroundValproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse.AimsTo compare the effect of valproate v. lithium for treatment of bipolar disorder in clinical practice.MethodAn observational cohort study with linkage of nationwide registers of all people with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed valproate or lithium in Denmark during a period from 1995 to 2006.ResultsA total of 4268 participants were included among whom 719 received valproate and 3549 received lithium subsequent to the diagnosis of bipolar disorder. The rate of switch/add on to the opposite drug (lithium or valproate), antidepressants, antipsychotics or anticonvulsants (other than valproate) was increased for valproate compared with lithium (hazard ratio (HR) = 1.86, 95% CI 1.59–2.16). The rate of psychiatric hospital admissions was increased for valproate v. lithium (HR = 1.33, 95% CI 1.18–1.48) and regardless of the type of episode leading to a hospital admission (depressive or manic/mixed). Similarly, for participants with a depressive index episode (HR = 1.87, 95% CI 1.40–2.48), a manic index episode (HR = 1.24, 95% CI 1.01–1.51) and a mixed index episode (HR = 1.44, 95% CI 1.04–2.01), the overall rate of hospital admissions was significantly increased for valproate compared with lithium.ConclusionsIn daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.

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