Sex Bias and Genotype Influence on Opioid Safety Profile in Chronic Low Back Pain.

OBJECTIVES: The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Among potential modulators are the individual's genetic background and being female. Our aim was to evaluate sex bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), the most frequent chronic noncancer pain. METHODS: A 3-year prospective study was developed in opioid-naive CLBP patients. Data were self-reported by patients (pain [Visual Analogy Scale], adverse events [AEs], and health care resource utilization) and physicians (analgesic prescription, morphine equivalent daily dose, and suspected adverse drug reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without (control) together with patients' sex and genotype. Gene variants in OPRM1 (rs1799971), COMT (rs4680), ABCB1 (rs1045642), UGT2B7 (rs12233719 and rs7438135), KCNJ6 (rs2070995 and rs6517442), and CYP3A5*3 (rs776746) were assessed. The hospital ethics committee approved the study, and statistical analyses were performed with R, v.3.2.4. RESULTS: A total of 179 patients were included (64% female, mean pain intensity 73±16 mm), and 90% of them presented at least 1 AE (median of 3 (1 to 6) AEs/patient) with a rate of 5 AEs: 1 ADR without differences due to sex. However, there is a significant delay in referral of female patients (a mean of 6 years) to the Pain Unit, being significantly 3 to 5 times more likely to present sleep or psychiatric disorders. Meanwhile male individuals showed more sexual and reproductive system disorders. Genotypes influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related problems. CONCLUSIONS: Sex bias affects female patients resulting in a CLBP diagnostic delay and a different analgesic safety profile. Moreover, the individual's genetic background might be useful to predict certain AEs in opioid-naive patients under an opioid titration procedure. Addressing sex in necessary to resolve inequalities in health care access.

Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients.

The threats involved in the long-term opioid treatment of chronic non-cancer pain (CNCP) have increased notably. Strategies to identify at-risk patients are important because there is no clear evidence showing which screening or deprescription programmes are appropriate. Our aim was to evaluate the evidence provided by pharmacogenetics applied to predict an analgesic toxicity profile in prescription opioid use disorder (POUD) patients participating in an opioid deprescription programme. Pharmacogenetic markers were analysed in an observational, prospective deprescription programme for POUD patients (n = 88) treated for CNCP. It consisted of monitoring visits (baseline, follow-up and final), opioid rotation or discontinuation and the recording of adverse events and suspected adverse drug reactions (ADRs). Variants in OPRM1 (A118G), ABCB1 (C3435T), COMT (G472A), OPRD1 (T921C) and ARRB2 (C8622T) genes were tested by real-time PCR. Ethics committee approved the study. Wild-type OPRM1-AA genotype carriers reported a significantly higher number of adverse events than OPRM1-AG/GG (median [p25-75], 7 [5-11] vs 5 [3-9]), particularly gastrointestinal system events (90% vs 63%) such as nausea (33% vs 0%). Suspected ADRs (affecting 17% of the patients) were three times higher in males than in females (30% vs 11%). The deprescription programme was effective and safe, and it achieved a significant progressive reduction in the morphine equivalent daily dose, strong opioids and other analgesics' use, without causing any changes in pain intensity or opiate abstinence syndrome. OPRM1 gene polymorphisms could identify the risk of gastrointestinal adverse events in POUD patients. Deprescription programmes including pharmacogenetic analysis should be considered during the follow-up of this population.

Descriçäo de algumas características da populaçäo infantil em duas comunidades da cidade de Pelotas, RS / Epidemiologic inquiry about health conditions among children in two districs of the city of Pelotas, RS

Este trabalho foi um inquérito epidemiológico sobre as condiçöes de saúde infantil realizado em duas comunidades, Vila Real e Vila Farroupilha, situadas na cidade de Pelotas, RS, com o intuito de subsidiar as atividades desenvolvidas no Posto de Saúde Local. Nas crianças até 3 anos de idade foram coletadas informaçöes sobre gênero, idade, utilizaçäo de serviços de saúde (motivos e locais), peso ao nascer, percentual de crianças que frequentaram programas de puericultura, cobertura vacinal, duraçäo de amamentaçäo natural e se as mäes das crianças haviam feito prée-natal. Os questionários foram respondidos pelas próprias mäes. Entre as 149 crianças encontradas, verificou-se que a média mensal de consultas era de 1,3, estimando-se em 15,6 por ano, sendo que principal motivo de consultas foram Puericultura e Infecçöes das Vias Aéreas Superiores. Entre as crianças menores de um ano, 96 por cento estavam inscritas em Programas de Puericultura. Encontrou-se 10 por cento de crianças com baixo peso ao nascimento, Constatou-se que, embora 90 por cento das crianças iniciassem o aleitamento materno, 59 por cento era amamentada por menos de 6 meses. A cobertura vacinal foi de 89,2 por cento para BCG, 75,2 por cento para as vacinas antipoliomielite e DPT e 71,8 por cento para anti-sarampo. Este tipo de inquérito é rápido, barato, fácil de realizar e pode contribuir de forma objetiva para o aperfeiçoamento das açöes de saúde