scholarly journals Hydroxychloroquine (HCQ): an observational cohort study in primary and secondary prevention of pneumonia in an at-risk population

2020 ◽  
Author(s):  
Alain Vanasse ◽  
Josiane Courteau ◽  
Yohann Chiu ◽  
André Cantin ◽  
Richard Leduc
Keyword(s):  
Cohort Study ◽  
Primary Prevention ◽  
Adverse Effects ◽  
Secondary Prevention ◽  
Observational Cohort Study ◽  
The Public ◽  
Positive Effects ◽  
Increased Risk ◽  
Observational Cohort ◽  
Public Drug

ABSTRACTBackgroundRecent studies suggest that hydroxychloroquine (HCQ) could be effective against COVID-19. It is reasonable to expect that if HCQ can prevent or reduce the adverse effects of influenza, it may also reduce the effects of COVID-19 in humans. The objective of this study was to test whether HCQ can prevent or reduce the risk and severity of influenza.MethodsThis is an observational cohort study using medico-administrative data from Québec. Patients included had at least one emergency department (ED) visit in 2012 or 2013, with a prior diagnosis of chronic conditions, and were admissible to the public drug insurance plan. Two sub-cohorts were considered depending on reasons for ED visit: other than influenza or pneumonia (primary prevention) and influenza or pneumonia (secondary prevention).ResultsIn the primary prevention analysis (n=417,353), patients taking HCQ (n=3,659) had an increased risk of hospitalization for pneumonia in the following year compared to those who did not (5.2% vs. 2.9%; adjusted OR=1.25, p=0.0079). In the secondary prevention analysis (n=27,152), patients taking HCQ (n=392), compared to those who did not had a modest and non-significant increased risk of hospitalization for pneumonia after 30 days (25.8% vs. 22.6%; adjusted OR=1.14, p=0.3177).InterpretationBased on the assumption that HCQ has similar effects on the COVID-19 as those observed on influenza, we can infer that it will not have positive effects on COVID-19. We should therefore act cautiously before initiating prospective interventional studies on the use of HCQ to reduce adverse effects of COVID-19.

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 Risk of QTc Interval Prolongation Associated With Circulating Anti‐Ro/SSA Antibodies Among US Veterans: An Observational Cohort Study

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Pietro Enea Lazzerini ◽  
Gabriele Cevenini ◽  
Yongxia Sarah Qu ◽  
Frank Fabris ◽  
Nabil El‐Sherif ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Small Sample ◽  
Observational Cohort Study ◽  
Current Evidence ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Increased Risk ◽  
Observational Cohort ◽  
Us Veterans

Background Anti‐Sjögren's syndrome‐related antigen A‐antibodies (anti‐Ro/SSA‐antibodies) are responsible for a novel form of acquired long‐QT syndrome, owing to autoimmune‐mediated inhibition of cardiac human ether‐a‐go‐go‐related gene‐potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample‐size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti‐Ro/SSA‐antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti‐Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate‐corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti‐Ro/SSA‐positive (8.3%). Subjects who were anti‐Ro/SSA‐positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26–2.21] for QTc >470/480 ms; 2.32 [1.54–3.49] for QTc >490 ms; 2.77 [1.66–4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT‐prolonging drugs were added to the model. Nevertheless, stepwise‐fully adjusted OR for the higher cutoffs remained significantly increased in anti‐Ro/SSA‐positive subjects, particularly for QTc >500 ms (2.27 [1.34–3.87]). Conclusions Anti‐Ro/SSA‐antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti‐Ro/SSA‐positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.

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 Fetal sex modifies the effect of maternal macronutrient intake on the incidence of small-for-gestational-age births: a prospective observational cohort study

2018 ◽  
Vol 108 (4) ◽  
pp. 814-820 ◽  
Author(s):  
A Mukhopadhyay ◽  
T Thomas ◽  
R J Bosch ◽  
P Dwarkanath ◽  
A Thomas ◽  
...  
Keyword(s):  
Cohort Study ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Observational Cohort Study ◽  
Prospective Observational Cohort Study ◽  
Macronutrient Intake ◽  
Fetal Sex ◽  
Increased Risk ◽  
Observational Cohort

Abstract Background Maternal macronutrient intake is likely to play a pivotal role in fetoplacental growth. Male fetuses grow faster and their growth is more responsive to maternal size. Objective We assessed the role of fetal sex in modifying the effect of maternal macronutrient intake on the risk of small-for-gestational-age (SGA) birth. Design This was a prospective, observational cohort study of 2035 births from an urban South Asian Indian population. Maternal intakes of total energy and macronutrients were recorded by validated food-frequency questionnaires. The interaction of trimester 1 macronutrient intake with fetal sex was tested on the outcome of SGA births. Results The prevalence of SGA was 28%. Trimester 1 macronutrient composition was high in carbohydrate and low in fat (means ± SDs—carbohydrate: 64.6% ± 5.1%; protein: 11.5% ± 1.1%; and fat: 23.9% ± 4.4% of energy). Higher carbohydrate and lower fat consumption were each associated with an increased risk of SGA [adjusted OR (AOR) per 5% of energy (95% CI): carbohydrate: 1.15 (1.01, 1.32); fat: 0.83 (0.71, 0.97)] specifically among male births (males: n = 1047; females: n = 988). Dietary intake of &gt;70% of energy from carbohydrate was also associated with increased risk (AOR: 1.67; 95% CI: 1.00, 2.78), whereas &gt;25% of energy from fat intake was associated with decreased risk (AOR: 0.61; 95% CI: 0.41, 0.90) of SGA in male births. Conclusions Higher carbohydrate and lower fat intakes early in pregnancy were associated with increased risk of male SGA births. Therefore, we speculate that fetal sex acts as a modifier of the role of maternal periconceptional nutrition in optimal fetoplacental growth.

scholarly journals Risk of human papillomavirus-related cancers among kidney transplant recipients and patients receiving chronic dialysis - an observational cohort study

2021 ◽  
Author(s):  
Lars Skov Dalgaard ◽  
Ulrik Fassel ◽  
Lars Jørgen Østergaard ◽  
Bente Jespersen ◽  
Ole Schmeltz Søgaard ◽  
...  
Keyword(s):  
Cohort Study ◽  
Human Papillomavirus ◽  
Incidence Rates ◽  
Observational Cohort Study ◽  
Excess Risk ◽  
Transplant Recipients ◽  
Increased Risk ◽  
Observational Cohort ◽  
Esrd Patients ◽  
Population Controls

Background Individuals with end-stage renal disease (ESRD) have excess risk of various cancer types. However, the total burden of human papillomavirus-related cancers remains unknown. Methods We performed a nationwide observational cohort study during 1994–2010. For each person with ESRD, we sampled 19 population controls (without ESRD) matched on age, gender and municipality. Participants were followed until first diagnosis of human papillomavirus-related cancer, death, emigration, or 31 December 2010, whichever came first. Human papillomavirus-related cancers were extracted from Danish medical administrative databases. We considered cancers of the cervix, vulva, vagina, penis, anus, and subsets of head and neck cancers as human papillomavirus-related. We calculated incidence rates of human papillomavirus-related cancer and used Poisson regression to identify risk factors for human papillomavirus-related cancer. Results Among 12,293 persons with ESRD and 229,524 population controls we identified 62 and 798 human papillomavirus-related cancers, respectively. Incidence rates of human papillomavirus-related- cancer were 102 per 100,000 person-years (95% confidence interval [CI]; 79.5-131) among persons with ESRD and 40.8 per 100,000 person-years (95% CI; 38.1-43.7) among population controls. ESRD patients had 4.54 (95% CI, 2.48-8.31) fold increased risk of anal cancer and 5.81 fold (95% CI; 3.36-10.1) increased risk of vulvovaginal cancer. Adjusted for age, comorbidity, and sex, ESRD patients had 2.41 (95% CI; 1.83-3.16) fold increased risk of any human papillomavirus-related cancer compared with population controls. Compared with dialysis patients renal transplant recipients had an age-adjusted non-significant 1.53 (95% CI, 0.91-2.58) fold higher risk of human papillomavirus-related cancer. Conclusions Persons with ESRD have excess risk of potentially vaccine-preventable human papillomavirus-related cancers.

scholarly journals Association of placental pathology and postpartum cardiovascular risk screening following preeclampsia: an observational cohort study

2021 ◽  
Author(s):  
Samantha Benton ◽  
Erika Mery ◽  
David Grynspan ◽  
Laura Gaudet ◽  
Graeme Smith ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Risk Score ◽  
Observational Cohort Study ◽  
Cvd Risk ◽  
Risk Screening ◽  
Cardiovascular Screening ◽  
Increased Risk ◽  
Observational Cohort

Objective: To determine the association between placental lesions and lifetime cardiovascular disease (CVD) risk screening at 6 months postpartum following preeclampsia (PE). Design: Observational cohort study. Setting: Tertiary care centres in Ottawa and Kingston, Ontario, Canada. Population: Women diagnosed with PE who received cardiovascular screening at 6 months postpartum. Methods: Placentas from women diagnosed with PE were evaluated for histopathological lesions according to a standardised synoptic data collection form with blinding to clinical outcomes apart from gestational age at delivery. At 6 months postpartum, each participant was screened for cardiovascular risk factors and a lifetime cardiovascular risk score was calculated. A risk score >35% was deemed high risk for lifetime CVD. Main Outcome Measures: The association between placental lesions and lifetime CVD risk was assessed using odds ratios (OR, 95% confidence intervals). Results: Of the 85 participants, 53 (62.4%) screened high-risk for lifetime CVD. High-risk women had more severe lesions of maternal vascular malperfusion (MVM). MVM lesions with a severity score >2 resulted in a 3-fold increased risk of screening high risk for lifetime CVD (OR 3.10 [1.20-7.92]). MVM lesion score >2 was moderately predictive of high-risk screening (AUC 0.63 [0.51,0.75]; sensitivity: 71.8% [54.6,84.4]; specificity: 54.7% [41.5,67.3]). When clinical data was added, the model’s predictive performance improved (AUC 0.73 [0.62,0.84] sensitivity 78.4% [65.4,87.5]; specificity 51.6% [34.8,68.0]). Conclusions: PE women with MVM are more likely to screen high-risk for lifetime CVD compared to women without these lesions. Placenta pathology may provide a unique modality to identify women for postpartum cardiovascular screening.

scholarly journals Effectiveness of Injectable Ibuprofen Salts and Indomethacin to Treat Patent Ductus Arteriosus in Preterm Infants: Observational Cohort Study

2018 ◽  
Vol 71 (1) ◽  
Author(s):  
Deonne Dersch-Mills ◽  
Belal Alshaikh ◽  
Amuchou S Soraisham ◽  
Albert Akierman ◽  
Kamran Yusuf
Keyword(s):  
Cohort Study ◽  
Adverse Effects ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Observational Cohort Study ◽  
End Points ◽  
Surgical Ligation ◽  
Observational Cohort ◽  
Patent Ductus

<p><strong>ABSTRACT</strong></p><p><strong>Background: </strong>There is no injectable ibuprofen product marketed to treat patent ductus arteriosus (PDA) in newborns in Canada. The authors’ institution has used ibuprofen arginine in the past. In the absence of published evidence supporting use of this salt form of ibuprofen for neonatal PDA, a retrospective analysis was undertaken.</p><p><strong>Objective: </strong>To compare the effectiveness and adverse effects of ibuprofen arginine, ibuprofen tromethamine, and indomethacin in the treatment of PDA.</p><p><strong>Methods: </strong>This retrospective observational cohort study, for patients admitted between 2009 and 2015, included preterm infants with symptomatic PDA who received at least one dose of injectable indomethacin, ibuprofen tromethamine, or ibuprofen arginine. Three effectiveness end points were analyzed: closure after one course of treatment, repeat medical treatment, and surgical ligation. The secondary end points included acute kidney injury, necrotizing enterocolitis, chronic lung disease, and time to full enteral feeding.</p><p><strong>Results: </strong>A total of 179 infants were included. There were no differences among groups in terms of closure after one course of treatment (37/54 [69%] with indomethacin, 42/70 [60%] with ibuprofen tromethamine, and 28/55 [51%] with ibuprofen arginine; <em>p </em>= 0.21) or surgical ligation (10/54 [19%] with indomethacin, 13/70 [19%] with ibuprofen tromethamine, and 12/55 [22%] with ibuprofen arginine; <em>p </em>= 0.88). However, there was a difference regarding use of a repeat course of treatment, ibuprofen arginine having the highest rate (8/54 [15%] with indomethacin, 18/70 [26%] with ibuprofen tromethamine, and 20/55 [36%] with ibuprofen arginine; <em>p </em>= 0.04). After adjustment for gestational age, the association between ibuprofen arginine and increased use of a repeat course of treatment remained significant. The groups did not differ with respect to adverse effects.</p><p><strong>Conclusion: </strong>These results highlight the potential for differences in effectiveness among various salt forms of injectable ibuprofen and indomethacin. Because of the small sample size and retrospective methodology, confirmation of the present results through a larger prospective study is needed.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte : </strong>Il n’y a pas sur le marché de produit injectable à base d’ibuprofène pour traiter la persistance du canal artériel (PCA) chez le nouveau-né au Canada. L’ibuprofène arginine a été utilisé auparavant dans l’établissement de santé des auteurs. En l’absence de données publiées appuyant l’utilisation de ce médicament sous forme de ce sel pour traiter la PCA chez le nouveau-né, une analyse rétrospective a été réalisée.</p><p><strong>Objectif : </strong>Comparer l’efficacité et les effets indésirables de l’ibuprofène arginine, de l’ibuprofène trométhamine et de l’indométhacine dans le traitement de la PCA.</p><p><strong>Méthodes : </strong>Cette étude de cohorte observationnelle rétrospective, au sujet de patients hospitalisés entre 2009 et 2015, incluait des nourrissons prématurés atteints d’une PCA symptomatique ayant reçu par injection au moins une dose d’indométhacine, d’ibuprofène trométhamine ou d’ibuprofène arginine. Trois paramètres d’évaluation de l’efficacité ont été analysés : la fermeture après un seul traitement, la répétition du traitement médical et la ligature chirurgicale. Les paramètres d’évaluation secondaires étaient les cas d’insuffisance rénale aiguë, d’entérocolite nécrosante et de maladie pulmonaire chronique ainsi que le temps pour atteindre l’alimentation entérale complète.</p><p><strong>Résultats : </strong>Au total, 179 nourrissons ont été admis à l’étude. Aucune différence n’a été relevée entre les groupes en ce qui touche à la fermeture après un seul traitement (37/54 [69 %] pour l’indométhacine, 42/70 [60 %] pour l’ibuprofène trométhamine et 28/55 [51 %] pour l’ibuprofène arginine; <em>p </em>= 0,21) ou à la ligature chirurgicale (10/54 [19 %] pour l’indométhacine, 13/70 [19 %] pour l’ibuprofène trométhamine et 12/55 [22 %] pour l’ibuprofène arginine; <em>p </em>= 0,88). Cependant, une différence a été observée pour ce qui est de la répétition du traitement et l’ibuprofène arginine a obtenu le taux le plus élevé (8/54 [15 %] pour l’indométhacine, 18/70 [26 %] pour l’ibuprofène trométhamine et 20/55 [36 %] pour l’ibuprofène arginine; <em>p </em>= 0,04). Après ajustement pour l’âge gestationnel, l’association entre l’utilisation de l’ibuprofène arginine et une augmentation du recours à un second traitement demeurait significative. Il n’y avait pas de différence entre les groupes en ce qui touche aux effets indésirables.</p><p><strong>Conclusion : </strong>Ces résultats soulignent la possible différence d’efficacité parmi les divers sels d’ibuprofène injectable et l’indométhacine. Cependant, en raison de la petite taille de l’échantillon et de l’emploi d’une méthodologie rétrospective, une étude prospective plus importante doit être menée pour confirmer les résultats de la présente étude.</p>

OS10.8.A The effectiveness of antiepileptic drug duotherapies in glioma patients: a multicenter observational cohort study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii14-ii14
Author(s):  
P B van der Meer ◽  
L Dirven ◽  
M Fiocco ◽  
M Vos ◽  
M C M Kouwenhoven ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Effects ◽  
Treatment Failure ◽  
Antiepileptic Drug ◽  
Observational Cohort Study ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Observational Cohort

Abstract BACKGROUND About 30% of glioma patients need an add-on antiepileptic drug (AED) due to uncontrolled seizures on AED monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV+VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in glioma patients. MATERIAL AND METHODS In this multicenter retrospective observational cohort study, treatment failure (i.e. replacement by or addition of a new AED, or withdrawal of an AED) for any reason was the primary outcome. Secondary outcomes included: 1) treatment failure due to uncontrolled seizures; and 2) treatment failure due to adverse effects. Time to treatment failure was defined as the time from the start of AED duotherapy until the time of treatment failure. Multivariable Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months. RESULTS A total of 1435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received AED duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV+VPA was prescribed in 66% (236/355) and other AED duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy versus LEV+VPA had higher risk of treatment failure for any reason (cause-specific hazard ratio [csHR]=1.50 [95%CI=1.07–2.12], p=0.020), treatment failure due to uncontrolled seizures (csHR=1.73 [95%CI=1.10–2.73], p=0.018). There were no differences in failure due to adverse effects (csHR=0.88 [95%CI=0.47–1.67]), p=0.703) between the two groups. CONCLUSION This observational cohort study suggests that LEV+VPA has better efficacy than other AED combinations. Similar toxicities were experienced in the two groups.

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