This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of “omics” technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health.

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Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome exhibited by infants born to mothers with opioid use disorder (OUD). The American College of Obstetricians and Gynecologists and other professional societies endorse opioid agonist pharmacotherapy (MATs) as the optimal treatment for OUD during pregnancy. This study focuses on impact of weaning of MAT drugs on the incidence of NAS and neonatal birth outcomes among babies born to women with opioid exposure. The study population included eighty-six pregnant women with OUD, divided in to weaning and non-weaning groups based on their choice to wean the MATs during pregnancy. Univariate analysis was performed between the clinical and demographic variables of both groups. Multivariate analysis was performed to find the association between outcome variables and predictor variables. All analyses were conducted using SAS version 9.4. The study identified a significant negative correlation (p-value: 0.0099) between weaning from MATs and NAS incidence. The study showed significant correlations of weaning with shorter LOS (p-value: 0.0036) and higher birth weights (p-value: 0.0408). Weaning emerged as a significant predictor for decreasing the incidence of NAS and improving the neonatal outcomes. Logistic regression confirmed weaning as a protective factor (odds ratio: 4.881 CI: 1.3, 18.1). The intricacies of weaning of MATs in the context of OUD during pregnancy present profound health and ethical considerations for both mothers and infants. The investigation into NAS incidence among infants born to women with OUD revealed a significant association with weaning from MATs during pregnancy. The study highlights the potential benefits of weaning, offering insights into optimized neonatal care and efficient healthcare resource utilization.

Opioid use disorder (OUD) impacts 5.6 million people in the US. Buprenorphine (BUP) is a commonly prescribed opioid medication used to treat OUD, including in pregnant women. However, opioid use during pregnancy is associated with poorer infant outcomes including reduced fetal growth, neurodevelopmental deficits, and neonatal opioid withdrawal syndrome (NOWS). Recent clinical data suggests that providing mothers with a lower dose of BUP may result in fewer negative outcomes in infants. Here, a preclinical rodent model of low-dose perinatal BUP exposure was used to study offspring health outcomes in the neonate, juvenile, and adolescent offspring. Dams were given clinically relevant doses of BUP prior to and throughout gestation, and continuing through weaning to mimic human doses and exposure. Although the lowest BUP dose still elicited signs of NOWS in offspring, there were fewer negative effects on overall brain morphology across the early lifespan than that of the higher BUP dose compared to controls.

La douleur chronique non cancéreuse (DCNC) est un phénomène complexe et des interventions multimodales qui abordent à la fois ses dimensions biologiques et psychosociales sont considérées comme l’approche optimale pour traiter ce type de désordre. La prescription d'opioïdes pour la DCNC a augmenté d’une façon fulgurante au cours des deux dernières décennies, mais les preuves supportant l'efficacité à long terme de ce type de médicament en termes de réduction de la sévérité de la douleur et d’amélioration de la qualité de vie des patients souffrant de DCNC sont manquantes. L'objectif de cette étude était d'investiguer dans un contexte de vraie vie l'efficacité à long terme des opioïdes pour réduire l’intensité et l’impact de la douleur et améliorer la qualité de vie reliée à la santé des patients souffrant de DCNC sur une période d’une année. Méthodes: Les participants à cette étude étaient 1490 patients (âge moyen = 52,37 (écart-type = 13,9); femmes = 60,9%) enrôlés dans le Registre Québec Douleur entre octobre 2008 et Avril 2011 et qui ont complété une série de questionnaires avant d'initier un traitement dans un centre multidisciplinaire tertiaire de gestion de la douleur ainsi qu’à 6 et 12 mois plus tard. Selon leur profil d'utilisation d'opioïdes (PUO), les patients ont été classés en 1) non-utilisateurs, 2) utilisateurs non persistants, et 3) utilisateurs persistants. Les données ont été analysées à l'aide du modèle d'équation d'estimation généralisée. Résultats: Chez les utilisateurs d’opioïdes, 52% en ont cessé la prise à un moment ou à un autre pendant la période de suivi. Après ajustement pour l'âge et le sexe, le PUO a prédit d’une manière significative l’intensité de la douleur ressentie en moyenne sur des périodes de 7 jours (p <0,001) ainsi que la qualité de vie physique (pQDV) dans le temps (p <0,001). Comparés aux non-utilisateurs, les utilisateurs persistants avaient des niveaux significativement plus élevés d'intensité de douleur et une moins bonne pQDV. Une interaction significative a été trouvée entre le PUO et le temps dans la prédiction de l’intensité de douleur ressentie à son maximum (p = 0,001), les utilisateurs persistants sont ceux rapportant les scores les plus élevés à travers le temps. Une interaction significative a aussi été observée entre le PUO et le type de douleur dans la prédiction de l'impact de la douleur dans diverses sphères de la vie quotidienne (p = 0,048) et de la mQDV (p = 0,042). Indépendamment du type de douleur, les utilisateurs persistants ont rapporté des scores plus élevés d'interférence de douleur ainsi qu’une moins bonne mQDV par rapport aux non-utilisateurs. Cependant, la magnitude de ces effets était de petite taille (d de Cohen <0,5), une observation qui remet en question la puissance et la signification clinique des différences observées entre ces groupes. Conclusion: Nos résultats contribuent à maintenir les doutes sur l'efficacité d’une thérapie à long terme à base d’opioïdes et remettent ainsi en question le rôle que peut jouer ce type de médicament dans l'arsenal thérapeutique pour la gestion de la DCNC. / Chronic non-cancer pain (CNCP) is a complex phenomenon and multimodal interventions that address both its biological and psychosocial dimensions are considered as the optimal approach for treating this type of disorder. Prescription of opioids for CNCP has dramatically increased over the past two decades but little is known about the long-term effectiveness of this type of medication for reducing pain severity and improving quality of life of CNCP patients. The objective of the present study was to investigate in a real life context the long-term effectiveness of opioids for reducing pain intensity and interference, and improving health-related quality of life in patients with CNCP over a one-year period. Methods: Participants were 1,490 patients (mean age = 52.37 (SD = 13.9); female = 60.9%) enrolled in the Quebec Pain Registry between October 2008 and April 2011 who completed a series of questionnaires before initiating treatment at a tertiary multidisciplinary pain management facility as well as 6 and 12 months thereafter. Based on their opioid use profile (OUP), patients were categorized into 1) non users, 2) non-persistent users, and 3) persistent users. Data were analyzed using generalized estimating equation models. Results: Among the users of opioids, 52% stopped taking them during the follow-up period. After adjusting for age and sex, patients’ OUP significantly predicted pain intensity felt during 7-day periods (p < 0.001) and physical quality of life (pQOL) over time p < 0.001). Compared to non-users, persistent users had significantly higher levels of pain intensity and poorer pQOL. A significant interaction was found between patients’ OUP and time in the prediction of worst pain intensity (p = 0.001) but the persistent users reported the highest pain scores across time. A significant interaction was also observed between patients’ OUP and type of pain in the prediction of pain interference (p = 0.048) and mental quality of life (mQOL) (p = 0.042). Irrespective of the type of pain they suffered, persistent users reported higher pain interference scores and lower mQOL compared to non users. However, all effect sizes were small (Cohen’s d < 0.5), thus questioning the power and clinical significance of these group differences. Conclusion: These results contribute to the debate by adding evidences on the effectiveness of long term opioid therapy and question the role this type of medication should play in the therapeutic arsenal for managing CNCP.

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Bakgrund: LARO i Sverige är omgärdat av strikta regler. Läkemedlen som används, däribland buprenorfin, intas dagligen övervakat av sjuksköterska de tre första månaderna och vidare till dess att patienten bedöms kunna ta läkemedlet på egen hand. Sedan 2018 finns buprenorfin som depotinjektion veckovis eller månadsvis, vilket innebär en ny omvårdnadssituation. Syfte: Att utforska sjuksköterskans perspektiv på införandet av buprenorfin som depotinjektion i LARO. Metod: Tolv semistrukturerade intervjuer av sjuksköterskor med erfarenhet av depotinjektioner buprenorfin i LARO. Resultat: Införandet av depotinjektioner innebar ett fokusskifte i behandling och omvårdnad med bland annat minskad kontroll och ökad tillit mellan sjuksköterska och patient. Behandlingen med depotinjektioner ansågs kunna öppna för ökad egenmakt för patienterna. LARO-enheternas organisatoriska förutsättningar påverkade hur de tagit sig an den nya behandlingsformen. Kunskap och samsyn efterfrågades. Slutsats: Depotinjektioner buprenorfin kan öppna upp för nya sätt att främja egenmakt i LARO. Det finns ett behov av forskning på området. / Background: Opioid substitution treatment in Sweden is strictly regulated. Medications like Buprenorphine are taken daily supervised by a nurse during the initial three months and thereafter until the patient is assessed to be trusted with self-administration. Prolonged-release injectable Buprenorphine has beenavailable since 2018 for weekly or monthly use. This has implications for nursing care and practices. Purpose: To explore the nurse’s perspective on introducing prolonged-release injectable buprenorphine in opioid substitution treatment. Method: Twelve semi-structured interviews were conducted with nurses experienced in treatment with prolonged-release injectable buprenorphine. Results: The introduction of injection treatment entailed a shift in focus regarding restrains, trust and patient empowerment. The care units’ approaches to the new treatment differed and was influenced by organisational conditions. Nurses requested more knowledge and consensus about the new treatment. Conclusion:Prolonged-release injectable formulations may enable new approaches to patientempowerment in opioid substitution treatment. Research in this field is required.

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