Emanuele D'Amico

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-10-2017

DOI: 10.1212/WNL.0000000000004606

Abstract: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. In idual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7–1.4 p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3–4.3 p = 0.006 and HR 2.5, 95% CI 1.1–5.2 p = 0.032, respectively). The effect of lithium was different for UNC13A carriers ( p = 0.027), but not for C9orf72 carriers ( p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2–69.1) to 69.7% (95% CI 50.4–96.3). This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials.

Five insights from the Global Burden of Disease Study 2019

Publisher: Elsevier BV

Date: 10-2020

DOI: 10.1016/S0140-6736(20)31404-5

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS

Publisher: SAGE Publications

Date: 20-03-2018

DOI: 10.1177/1352458518763080

Abstract: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992–1995 and 2005–2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Publisher: Elsevier BV

Date: 10-2021

DOI: 10.1016/S1474-4422(21)00252-0

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Publisher: Elsevier BV

Date: 10-2020

DOI: 10.1016/S0140-6736(20)30977-6

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Publisher: Elsevier BV

Date: 2022

DOI: 10.1016/S1470-2045(21)00581-7

University Of Catania

Location: Italy

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Universidade Técnica De Lisboa Instituto Superior Técnico

Location: Portugal

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LNEC: Laboratório Nacional De Engenharia Civil

Location: Portugal

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EAPS (currently Safemode)

Location: Portugal

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Eawag: Swiss Federal Institute Of Aquatic Science And Technology

Location: Switzerland

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Imperial College London

Location: United Kingdom of Great Britain and Northern Ireland

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Universitätsklinikum Ulm

Location: Germany

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ULSS 17 Regione Veneto

Location: Italy

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Dipartimento Scienze Mediche E Chirurgiche

Location: Italy

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Columbia University

Location: United States of America

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Discovery Projects - Grant ID: DP210103704

Start Date: 2022

End Date: 12-2024

Amount: $390,000.00

Funder: Australian Research Council