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However, the risk of overdose due to the cumulative number of various recently used drug types remains unexplored. We estimated the risk of NFOD for different polysubstance use categories among PWID in Tijuana, Mexico.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data came from 661 participants followed for 2\u2009years in Proyecto El Cuete\u2010IV, an ongoing prospective cohort of PWID. A multivariable Cox model was used to assess the cumulative impact of polysubstance use on the time to NFOD. We used the Cochran\u2010Armitage test to evaluate a dose\u2013response relationship between number of polysubstance use categories and NFOD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed 115 NFOD among 1029.2 person\u2010years of follow\u2010up (incidence rate: 11.2 per 100 person\u2010years; 95% confidence interval [CI] 9.3\u201013.3). Relative to those who used one drug class, the adjusted hazard ratio of NFOD for individuals reporting using two drug classes was 1.11 (95% CI 0.69\u20101.79), three drug classes was 2.00 (95% CI 1.16\u20103.44) and for those reporting three compared to two was 1.79 (95% CI 1.09\u20102.97). A significant Cochran\u2010Armitage trend test (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.001) suggested a dose\u2013response relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusions<\/jats:title><jats:p>Polysubstance use was associated with increased risk of NFOD with a dose\u2013response relationship over 2\u2009years. We identified a subgroup of PWID at high risk of NFOD who reported concurrent use of opioids, stimulants and benzodiazepines. Prioritising tailored harm reduction and overdose prevention interventions for PWID who use multiple substances in Tijuana is needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dar.13305","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T10:06:52Z","timestamp":1622110012000},"page":"1340-1348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Risk of non\u2010fatal overdose and polysubstance use in a longitudinal study with people who inject drugs in Tijuana, Mexico"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-7798","authenticated-orcid":false,"given":"Carlos D.","family":"Rivera Saldana","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  La Jolla USA"},{"name":"School of Public Health San Diego State University  San Diego USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Abramovitz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  La Jolla USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith C.","family":"Meacham","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of California San Francisco  San Francisco USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Gonzalez\u2010Zuniga","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  La Jolla USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0083-7276","authenticated-orcid":false,"given":"Claudia","family":"Rafful","sequence":"additional","affiliation":[{"name":"Faculty of Psychology National Autonomous University of Mexico  Mexico City Mexico"},{"name":"Global Mental Health Research Center National Institute of Psychiatry  Mexico City Mexico"},{"name":"Centre for Urban Health Solutions St. Michael's Hospital  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudelia","family":"Rangel","sequence":"additional","affiliation":[{"name":"Department of Population Studies The College of the Northern Border  Tijuana Mexico"},{"name":"United States\u2010Mexico Border Health Commission  Tijuana Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffanie A.","family":"Strathdee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  La Jolla USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Cepeda","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  La Jolla USA"},{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2016.02.024"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugpo.2019.11.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugpo.2019.07.030"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.puhe.2007.02.016"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/003335491613100315"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2006.07.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.313.7069.1400b"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2016.303084"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6834a2"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2019.0013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.03.026"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dar.12524"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12913-018-3756-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2012.04.002"},{"key":"e_1_2_8_16_1","unstructured":"Instituto Nacional de Psiquiatri\u00e1 Ramo\u0144 de la Fuente Mu\u00f1iz (INPRFM) la Comisi\u00f3n Nacional Contra las Adicciones (CONADIC) Secretar\u00eda de Salud (SSA). 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