• Fernando Navarro-Mateu, María Rubio-Aparicio, Pedro Cayuela, Francisco-Javier Álvarez, Agustín Roca-Vega, María Dolores Chirlaque, María Luisa Cayuela, Mathilde Husky, Salvador Martínez, and Julio Sánchez-Meca.
• Unidad de Docencia, Investigación y Formación en Salud Mental (UDIF-SM), Servicio Murciano de Salud, c/ Lorca, n° 58, 30120, Murcia, Spain. fernando.navarro@carm.es.
• Syst Rev. 2019 Dec 1; 8 (1): 298.

BackgroundThe present protocol was designed for a systematic review and meta-analysis aimed at determining the association of telomere length with substance use disorders with the exclusion of nicotine addiction, and to identify potential moderators of the effect of telomere length. Such methodological information may provide guidance to improve the quality of future research on this important topic.MethodsPotential studies will be identified through electronic databases (PubMed/MEDLINE, EMBASE, PsycINFO, and Web of Science) up from inception onwards. The inclusion criteria will include published or unpublished observational studies (cohort, case-control, and cross-sectional studies) reporting telomere length in adult patients with substance use disorder compared with a control group. Non-human studies or other study designs such as reviews, case-only, family-based, and/or population studies with only healthy participants will be excluded, as well as those focused solely on nicotine addiction. The main outcome will be telomere length in adults with substance use disorder (primary) and, specifically, in those with alcohol use disorder (secondary). Two investigators will independently evaluate the preselected studies for possible inclusion and will extract data following a standardized protocol. Disagreements will be resolved by consensus. The risk of bias of all included studies will be assessed using the Newcastle-Ottawa Quality Assessment Scale for non-randomized studies. Data will be converted into standardized mean differences as effect size index, and random-effects models will be used for the meta-analysis. Cochran's Q statistic, I2 index, and visual inspection of the forest plot will be used to verify study heterogeneity. Subgroup analyses and meta-regressions will be conducted to ascertain heterogeneity. Several sensitivity analyses will be conducted to address the influence of potential confounding factors. Publication bias will be examined using the "funnel plot" method with Duval and Tweedie's trim-and-fill method and Egger test.DiscussionThis systematic review will assess the association of telomere length with substance use disorders aside from nicotine addiction.Systematic Review RegistrationPROSPERO registration number CRD42019119785.

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