Treatment non-adherence among methadone maintenance patients and associated factors: a multicenter, cross-sectional study in Vietnam.

OBJECTIVE: This multicenter, cross-sectional study was conducted to investigate the prevalence of treatment non-adherence and its associated factors among methadone maintenance patients in Vietnam. METHODS: This secondary data analysis was conducted using the data from a previous study. Six hundred patients were interviewed face-to-face to collect data on their demographic characteristics and social support. Information about the treatment characteristics and patients' non-adherence was gathered from medical records and books monitoring their treatment process. Treatment non-adherence was defined as missing at least one methadone dose in the last three months. RESULTS: The overall prevalence of non-adherence was 45.7%. The average social support score of patients who completely adhered to treatment was significantly higher than that of those who did not (p < 0.001). In the multivariate logistic regression model, for each one-unit increase in social support (one score), treatment time (a year), and patient's monthly income (one million Vietnam dongs), the odds of non-adherence decreased by 28% (aOR = 0.72, 95%CI 0.59-0.88, p = 0.002), 15% (aOR = 0.85, 95%CI 0.80-0.91, p < 0.001) and 9% (aOR = 0.91, 95%CI 0.85-0.97, p = 0.004), respectively. Patients living in Son La (a mountainous province) were 1.72 times (95%CI 1.09-2.71) more likely to be non-adherent as compared to those in other areas (p = 0.020). As per univariate analyses, other associated factors could be age, education level, family monthly income, occupation, and opioid relapse (p < 0.001). CONCLUSIONS: A high non-adherence rate was found among Vietnamese methadone maintenance patients. Interventions involving social support, occupation, income, and education are needed to improve their treatment adherence.

Predictors of retention in heroin-assisted treatment in Denmark 2010-2018 - A record-linkage study.

INTRODUCTION: While randomized-controlled trials have shown that heroin-assisted treatment (HAT) is superior to methadone maintenance alone in treatment of refractory clients, little is known about client factors associated with retention in HAT in routine care. METHODS: This retrospective cohort study assessed predictors of retention in first treatment episode among a consecutive cohort of clients admitted to HAT in Denmark from 2010 to 2018, who could be matched to the Danish population register and for whom a Short Form Health Survey (SF-36) was available at admission (N = 432). The study derived predictors from client self-reports at intake and administrative data available in national registers. Cox proportional hazards regression modelled retention in treatment. RESULTS: The one-year retention rate was 69.63 % (95 % CI 65.06 %-73.74 %), and the median time in treatment was 2.45 years (95 % CI, 1.83-3.12). Bivariate analyses showed that retention was lower for clients who had recent cocaine or benzodiazepine use and among those who had experienced an overdose in the year prior to enrollment in HAT. Age below 40, recent illegal activity, poorer emotional wellbeing, previous residential treatment experience, and previous intensive outpatient treatment were also predictors of dropout from HAT. CONCLUSIONS: This observational study found that retention in HAT in routine care was similar to rates observed in randomized-controlled trials conducted in other countries. The results suggest that addressing polysubstance use as part of the HAT program may promote long-term retention, as may directing resources to certain subgroups identified at intake, including clients under 40 years and those who report recent criminal activity, emotional problems, or overdoses. The findings that previous residential treatment and intensive outpatient treatment were associated with dropout were unexpected.

Rituximab maintenance treatment outcomes in patients with relapsing neuromyelitis optica spectrum disorder: a monocentric retrospective analysis.

Some patients with neuromyelitis optica spectrum disorder (NMOSD) experience relapse after rituximab (RTX) treatment. In this retrospective study, we analyzed the recurrence-related clinical features, laboratory investigation results, and dosing protocol of 30 female patients with relapsing NMOSD with immunoglobulin G autoantibodies against aquaporin-4 and relapses during repeated 0.5 g RTX infusions as maintenance treatment. The median follow-up period was 6.62 years. Thirty-five episodes were observed, with myelitis being the most frequent. The median expanded disability status scale change score was 0.50. The recurrence rate decreased by 44.23%/year with RTX infusion. Approximately 85.71% of the patients showed relapse without RTX infusion within 10 months. Overall, RTX may be effective for relapsing NMOSD cases.

Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program.

Background: The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP). Methods: This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice. Results: Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died. Conclusion: Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.

Impact of opioid maintenance therapy in the community on re-incarceration in individuals with opioid use disorder-A linked cohort study.

INTRODUCTION: Studies have found associations between Opioid Agonist Maintenance Treatment during incarceration and reduced recidivism among recently released formerly incarcerated persons. However, the role of community-based Opioid Agonist Maintenance Treatment in reducing recidivism post-release remains less explored. This study examines whether pre-release arranged, prison-to-rehabilitation Opioid Agonist Maintenance Treatment in the community following release is associated with reduced rates and lengths of re-incarceration among justice-involved individuals with Opioid Use Disorder. METHODS: A retrospective matched cohort study was conducted using linked records of 208 individuals with a history of Opioid Use Disorder and treatment during their incarceration. The primary predictor variable was the duration of Opioid Agonist Maintenance Treatment, with re-incarceration rates and lengths of stay after re-incarceration being the primary outcomes examined. RESULTS: Analysis showed a significant decrease in re-incarcerations and or lengths of stay in prison among those who have been re-incarcerated and have undergone Opioid Agonist Maintenance Treatment in the community for >24 months. CONCLUSIONS: Maintaining Opioid Agonist Maintenance Treatment over 24 months may reduce re-incarcerations, and may be significantly associated with a reduction in the length of prison stay for re-incarcerated individuals. The effects were consistent across the overall population and the individuals receiving the treatment. Various other unmeasured factors, including judicial discretion, individual motivation, type of offense, and employment status, could influence this association.

Change in substance use among patients in opioid maintenance treatment: baseline to 1-year follow-up.

BACKGROUND: Individuals with opioid use disorder (OUD) often have concurrent use of non-opioid substances. When patients enter opioid maintenance treatment (OMT), less is known about outcomes regarding the use of other types of drugs. Here we aimed to investigate changes in substance use among patients entering outpatient OMT, from treatment initiation to 1-year follow-up. METHODS: We used data from the prospective Norwegian Cohort of Patient in OMT and Other Drug Treatment Study (NorComt). Among 283 patients who entered OMT at participating facilities across Norway, 179 were assessed at follow-up. Of these patients, 131 were in a non-controlled environment, and were included in the present analysis. The main outcome was change in substance use. Logistic regression analysis was applied to identify factors associated with abstinence from all substances (other than agonist medication) at follow-up. RESULTS: Along with opioid use, most patients reported polysubstance use prior to entering treatment. No significant differences were found in baseline characteristics between the included and non-included groups when examining attrition. At the 1-year follow-up, reduced substance use was reported. While in treatment, around two-thirds of patients continued using other drugs to varying degrees. At follow-up, about one-third of patients reported abstinence from all drugs, apart from the agonist medication. Factors related to abstinence included a goal of abstinence at baseline (OR = 5.26; 95% CI 1.14-19.55; p = 0.013) and increasing age (OR = 1.05; 95% CI 1.00-1.09; p = 0.034). CONCLUSIONS: The majority of patients entering OMT used other substances in addition to opioids. About one-third of patients reported abstinence at the 1-year follow up. Although the majority of patients continued co-use of other drugs while in treatment, for most substances, less than 10% reported daily use at follow-up, with the exception of cannabis which was used daily/almost daily by about 2 in 10. Higher age and treatment goal at the start of OMT were important factors related to reducing concomitant substance use during treatment. These findings suggest that many patients entering OMT are in need of treatment and support related to the use of other substances, to further improve prognosis. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).

Confidence in providing methadone maintenance treatment of primary care providers in Vietnam.

BACKGROUND: Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in rural mountainous areas. This study aims to investigate factors related to confidence in providing methadone treatment among primary care providers in Vietnam to inform good practice development. METHODS: We conducted a cross-sectional survey with 276 primary care providers who were physicians, physician assistants, nurses, pharmacists or dispensing staff from 67 communes in a mountainous province in Northern Vietnam. Using self-report scales, we measured providers' confidence in providing methadone treatment, beliefs in harm reduction, perceived work-related support, perceived stigma and risk in working with drug-using patients, and empathy towards this population. We used multiple linear regression analyses to explore factors associated with providers' confidence in providing methadone treatment in the whole sample and to compare two groups of providers who did and did not have experience providing methadone. Potential associated factors were measured at facility and provider levels. RESULT: 114 (41.3%) participants had previously experience in providing methadone treatment. Providers with methadone treatment experiences had higher confidence in and more accurate knowledge of methadone treatment, perceived less stigma of working with drug-using patients, and reported more work-related support than those without experiences. Higher medical education is associated with lower confidence in providing methadone treatment among providers without methadone experiences, but higher confidence among providers with methadone experiences. Better methadone knowledge was associated with greater confidence in providing methadone treatment among inexperienced providers but not among those with experiences. Receiving work-related support was associated with greater confidence in providing treatment in both groups, regardless of their past methadone experiences. CONCLUSION: In rural provinces where methadone treatment has been expanded to primary care clinics, interventions to improve primary care providers' confidence should benefit professionals with diverse experiences in providing methadone treatment. Continued training and support at work for providers is essential to ensuring quality in decentralized methadone treatment.

Different characteristics but comparable hypertension rates between two MMT "twin" clinics.

BACKGROUND: Patients in methadone maintenance treatment (MMT) may develop age-related medical problems. Objective: To compare hypertension prevalence and its risk factors between two MMT clinics, having similar treatment guidelines, but different characteristics, one from Tel Aviv (TA) and one from Las Vegas (LV). METHODS: Prevalence of hypertension (systolic ≥140 and or diastolic ≥90 mmHg BP) among all current 291 MMT patients in TA and 180 patients in LV were studied, including body mass index (BMI), drugs in urine, sociodemographic, and addiction history data. RESULTS: Hypertension prevalence was comparable in TA (35.4%) and LV (34.4%), however TA patients were older (55.9 ± 9.5 vs. 45.5 ± 13.3, p < 0.001), with fewer females (22 vs. 42.2%, p < 0.001), fewer obese (BMI ≥30) (24 vs. 40.9%, p < 0.001), higher cocaine (21 vs. 7.8%, p < 0.001), and lower cannabis (14.1 vs. 32.4%, p < 0.001) and amphetamines (0 vs. 33.5%) users. Logistic regression found higher BMI to characterize hypertension in both clinics, but in TA also negative urine cocaine, benzodiazepine, and opioids screen, while in LV older age (≥50 y), male gender, and negative urine cannabis screen. CONCLUSIONS: While TA was characterized with older patients, LV patients had a comparable hypertension rate, as obesity was more prevalent. No drug use was accompanied by higher BMI in TA and therefore associated with hypertension. Weight reduction, hypertension detection and treatment are recommended.

Prevalence of high impulsivity and its relation to sleep indices in opioid use disorder patients receiving methadone maintenance treatment.

BACKGROUND: The relation between impulsivity and sleep indices is not well determined in patients receiving methadone maintenance treatment (MMT). AIMS: to evaluate high impulsivity prevalence, its risk factors and relation with sleep indices. METHODS: a random MMT sample (n = 61) plus MMT current cocaine users (n = 20) were assessed for impulsivity (Barratt impulsivity scale [BIS-11] and Balloon Analogue Risk task [BART]), sleep quality (Pittsburg Sleep Quality Index [PSQI]), sleepiness (The Epworth sleepiness scale [ESS]), and substance in urine. RESULTS: 81 patients, aged 56.6 ± 10, 54.3% tested positive to any substance, 53.1% with poor sleep (PSQI>5) and 43.2% with daytime sleepiness (ESS >7) were studied. Impulsivity (BIS-11 ≥ 72) prevalence was 27.9% (of the representative sample), and 30.9% of all participants. These patients characterized with any substance and shorter duration in MMT with no sleep indices or other differences including BART balloon task performance (that was higher only in any substance than non-substance user group). However, impulsive score linearly correlated with daytime sleepiness (R = 0.2, p = 0.05). Impulsivity proportion was lowest among those with no cocaine followed by cocaine use and the highest in those who used cocaine and opiates (20.8%, 33.3% and 60% respectively, p = 0.02), as daily sleep (38.3%, 42.1% and 60%, p = 0.3) although not statistically significant. CONCLUSION: Daytime sleepiness correlated with impulsivity, but cocaine usage is the robust factor. Further follow-up is warranted to determine whether substance discontinuing will lead to a reduction in impulsivity, and improved vigilance. Sleep quality did not relate to daytime sleepiness and impulsivity and need further research.

Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.

Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.

B-cells depletion after treatment with rituximab predicts relapse of IgG4-related disease.

OBJECTIVES: B cell depletion therapy with rituximab is effective in most patients with IgG4-related disease (IgG4-RD) but requires repeated cycles to prevent disease flares. We here aimed to assess B cells after rituximab to predict relapse of IgG4-RD and guide retreatment. METHODS: Patients with active IgG4-RD included in this retrospective study fulfilled the ACR/EULAR Classification Criteria. Total CD19+ B cells, plasmablasts, naïve and memory B cells were measured on peripheral blood by flow-cytometry at baseline and six months after rituximab. All patients were treated with two 1 g infusions of rituximab 15 days apart and monitored for 48 months. Disease response was assessed using the IgG4-RD Responder Index. RESULTS: Thirty-three patients were included. Six months after rituximab, disease response was observed in all patients. Complete depletion of CD19+ B cells, plasmablasts, naïve and memory B cell depletion was achieved in 30%, 55%, 39%, and 42% of cases, respectively. Twenty-three relapses (70%) were observed at a median time of 24 months after rituximab. Relapse rate was significantly higher in patients who failed to achieve complete depletion of CD19+ cells (60% vs 17%, p= 0.02), naïve B cells (54% vs 15%, p= 0.01), or memory B cells (50% vs 16%, p= 0.03) six months after rituximab. The median relapse free survival time was shorter in patients who failed to achieve complete depletion of CD19+ cells (19 vs 38 months, p= 0.02), naïve B cells (16 vs 38 months, p= 0.01), or memory B cells (19 vs 38 months, p= 0.03) six months after rituximab. CONCLUSIONS: The degree of B cell depletion six months after rituximab may predict disease flare and may instruct on the pacing of B cell depletion therapy in IgG4-RD.

Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study.

OBJECTIVE: Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. METHODS: The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. RESULTS: Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. CONCLUSIONS: In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.

Extended-release versus oral buprenorphine as opioid maintenance treatment during pregnancy-maternal and neonatal outcomes.

OBJECTIVE: To get information on subcutaneous extended-release buprenorphine as opioid maintenance treatment during pregnancy, we compared it to orally administered buprenorphine and buprenorphine-naloxone treatments. We hypothesized that maternal and neonatal outcomes do not differ between the treatment groups. Study design In this population-based cohort study, 60 pregnant individuals receiving non-changed opioid maintenance treatment for opioid use disorder with a buprenorphine product from the time before conception to the time after delivery and their newborns were included. They were divided into three groups based on the pharmacotherapy with subcutaneous extended-release buprenorphine, sublingual buprenorphine, or buprenorphine-naloxone. Statistical analyses were conducted using Fischer's exact tests, ANOVA tests, and Kruskal-Wallis tests. All the statistical tests were two-tailed. RESULTS: The frequency of pregnancy or delivery complications did not significantly differ between the group receiving extended-release buprenorphine and the other groups. During pregnancy, 38 % of the women used illicit drugs concomitantly, with equal frequency in the extended-release buprenorphine group and the other groups. Of the neonates, 93 % were born full-term and 90 % got at least eight Apgar points in one minute age, without significant differences between the groups (p = 0.57). The need for pharmacotherapy for neonatal opioid withdrawal syndrome was the lowest in the extended-release buprenorphine group (25 %) and highest in the sublingual buprenorphine group (67 %). Still, the difference between the treatment groups did not reach statistical significance (p = 0.17). Among all neonates, the breastfed infants were less likely to receive pharmacotherapy for withdrawal symptoms than the formula-fed ones (p = 0.048). CONCLUSIONS: Extended-release buprenorphine with steady drug concentration seems to be a promising pharmacotherapy option during pregnancy for mothers. Maternal health during pregnancy may contribute to the well-being of newborns. Larger trials are urgently needed to confirm these results..

Experience of patients on methadone maintenance treatment receiving take-home methadone doses during COVID-19 pandemic: A multi-site study from India.

BACKGROUND: Methadone take-home doses for opioid dependence treatment are strictly regulated due to diversion and overdose concerns, so patients must visit the clinic daily for dispensing. This was also done in India until the COVID-19 pandemic, when lockdown restriction compelled take- home dispensing of methadone. This study examined experience of patients who received take- home methadone during COVID-19 pandemic in India. METHODS: Observational, cross-sectional design. We contacted all consenting methadone centres in India during the lockdown and selected those that provided take-home doses for the study. Patients who received daily methadone before the lockdown and take-home doses after were interviewed using a study-specific questionnaire. RESULTS: The study had 210 participants. Take-home methadone was dispensed for 2.5 days on average in each dispensing. When taking methadone at home, 3.3% split their dose 25% took less than the prescribed dose to save it for a rainy days, and 3.3% reported an overdose episode. Adherence improved in 58.6% participants after take-home methadone. Participants perceived many benefits from take-home methadone such as reduced hospital visits and travel time to collect methadone, improvement in work, and financial savings. About 54.3% participants reported storing their take-home doses safely, and 1.9% reported that their family consumed methadone by mistake. CONCLUSIONS: Take-home methadone was found to be beneficial to most participants in terms of time saved and improved productivity. Preconceived concerns of providing take-home methadone in terms of its overdose, diversion, or accidental ingestion by others are not commonly seen when individuals are provided take-home doses of methadone.

Intrauterine exposure to maternal opioid maintenance treatment and associated risk factors may impair child growth.

AIM: How maternal opioid maintenance treatment (OMT) affects children is under-researched. This population-based registry study investigated child growth and somatic health following intrauterine exposure to this treatment. METHODS: Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine-naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland. Appropriate statistical tests were used to compare the treatment groups. RESULTS: Of the 67 neonates, 52% were male, 96% were born full-term and 63% were treated for neonatal opioid withdrawal syndrome. Otherwise, the children were predominantly healthy, although relatively small: 22% were small for gestational age, the methadone group children being the smallest. Foetal exposure to maternal methadone treatment, illicit drugs, hepatitis C and smoking were associated with small for gestational age; the former two were also associated with later slower growth, especially head growth and weight gain (p < 0.001). However, 29% were overweight at 2 years. CONCLUSION: Using child growth as the outcome, we found that buprenorphine-naloxone and buprenorphine-monotherapy had equal effects as forms of maternal OMT. Exposure to multiple risk factors may harm foetal and subsequent growth. We recommend long-term follow-up of children exposed to maternal OMT.

Patient's and healthcare provider's experiences with Opioid Maintenance Treatment (OMT): a qualitative evidence synthesis.

BACKGROUND: Opioid Maintenance Treatment (OMT) is the gold standard for people with opioid dependence. However, drop-out rates are high, and many patients do not reach desired outcomes. Understanding patients' and healthcare providers' experiences with the treatment can provide valuable information to improve the quality of OMT and to increase acceptability and accessibility of services. The aim of this systematic review is to explore and synthesise the experiences of OMT among persons with opioid dependence and health care providers, to inform policy makers and practitioners on how to improve OMT outcomes. METHODS: We conducted a qualitative evidence synthesis. We systematically searched in electronic databases (CINAHL, Embase, MEDLINE, and nordic databases) and searched for grey literature. As we identified many studies that met our inclusion criteria, we purposively sampled a manageable number of studies to include in this review. Two researchers independently extracted and coded data from the included studies and used the Andersen's healthcare utilization model to organize and develop codes. We assessed the methodological limitations of the studies, and our confidence in the findings using GRADE CERQual. RESULTS: We retrieved 56 relevant studies and purposively sampled 24 qualitative studies of patients' and healthcare providers' experiences with OMT. Our analyses resulted in six main themes: (1) External stigma prevents engagement and retention in treatment, (2) Being identified as in OMT contributed to an increased experience of stigma (3) Inadequate knowledge and expertise among healthcare providers affected patients' treatment experiences, (4) Quality of communication between personnel and patients impacts patients' engagement with treatment and treatment outcomes, (5) Patients wanted help with many aspects of their lives not just medication, and (6) Balancing positive expectations of OMT with treatment stigma. We found that stigma was an overarching theme across these themes. CONCLUSION: Our findings suggest that OMT could be more beneficial for patients if treatment programs prioritize efforts to diminish societal and OMT provider stigma and find strategies to better address patient needs. Initiatives should focus on improving treatment knowledge among providers, encouraging the use of client perspectives, considering the context of family members, and establishing a more holistic and flexible treatment environment.

Does cannabis use substitute for opioids? A preliminary exploratory survey in opioid maintenance patients.

Various studies showed that people with substance use disorder use cannabis to reduce withdrawal or dose of their main drug. Using a questionnaire about their cannabis use, 118 participants in an opioid maintenance treatment (OMT) in Germany were examined regarding this strategy. 60% reported to use cannabis. Of those, 72% were using cannabis in the suggested way. Cannabis was used to substitute for, e.g., heroin (44.8%) and benzodiazepines (16.4%). We also asked for an estimation of how good cannabis was able to substitute for several substances (in German school grades (1 till 6)); heroin average grade: 2.6 ± 1.49. Besides that we asked about the idea of cannabis as "self-medication", e.g., to reduce pain (47%) and about negative consequences from cannabis use. Our results suggest to consider the use of cannabis by patients in OMT rather as a harm reduction strategy to reduce the intake of more dangerous drugs.

Fentanyl abuse proportion in methadone maintenance treatment, and patients' knowledge about its risks.

INTRODUCTION: Fentanyl is not yet routinely monitored among methadone maintenance treatment (MMT) patients in Israel. We aimed 1. to evaluate urine fentanyl proportion changes over 3 years and characterize patients' characteristics 2. To study patients' self-report on fentanyl usage, and compare knowledge about fentanyl risk, before and following brief educational intervention. METHODS: Fentanyl in the urine of all current MMT patients was tested every 3 months year between 2021 and 2023, and patients with positive urine fentanyl were characterized. Current patients were interviewed using a fentanyl knowledge questionnaire (effects, indications, and risks) before and following an explanation session. RESULTS: Proportion of fentanyl ranged between 9.8 and 15.1%, and patients with urine positive for fentanyl (September 2023) were characterized as having positive urine for pregabalin, cocaine, and benzodiazepine (logistic regression). Of the current 260 patients (87% compliance), 78(30%) self-reported of fentanyl lifetime use ("Ever"), and 182 "never" use. The "Ever" group had higher Knowledge scores than the "Never", both groups improved following the explanatory session (repeated measure). The "Ever" group patients were found with urine positive for cannabis and benzodiazepine on admission to MMT, they were younger, did not manage to gain take-home dose privileges and had a higher fentanyl knowledge score (logistic regression). CONCLUSIONS: In the absence of routine fentanyl tests, a high knowledge score, shorter duration in MMT, benzodiazepine usage on admission, and current cannabis usage, may hint of the possibility of fentanyl abuse.

Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study.

BACKGROUND: Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD. METHODS: The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022-2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients' courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling. DISCUSSION: The project's primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers. TRIAL REGISTRATION: The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK), ref.nr.:195733.

Change in self-reported somatic symptoms among patients in opioid maintenance treatment from baseline to 1-year follow-up.

BACKGROUND: High somatic comorbidity is common among patients in treatment for opioid use disorder (OUD). The present study aims to investigate changes in self-reported somatic health conditions and somatic symptoms among patients entering opioid maintenance treatment (OMT) programs. METHODS: We used data from the Norwegian Cohort of Patients in OMT and Other Drug Treatment (NorComt) study. Of 283 patients who entered OMT, 176 were included for analysis at a 1-year follow-up. Participants provided self-reported data during structured interviews on somatic conditions, somatic symptoms, substance use severity measures, and mental distress. A multivariable linear regression analysis identified factors associated with changes in the burden of somatic symptoms. RESULTS: Patients entering OMT reported a high prevalence of somatic conditions at the beginning of treatment, with 3 of 5 patients reporting at least one. The most prevalent condition was hepatitis C, followed by asthma and high blood pressure. Patients reported experiencing a high number of somatic symptoms. The intensity of these symptoms varied across a wide spectrum, with oral health complaints and reduced memory perceived as the most problematic. Overall, for the entire sample, there was no significant change in somatic symptoms from baseline to 1 year. Further analysis indicated that those who reported a higher burden of somatic symptoms at baseline had the greatest improvement at the 1-year follow-up. A higher number of somatic conditions and higher mental distress at baseline was associated with improvements in somatic symptoms burden at follow-up. CONCLUSIONS: Patients in OMT report a range of somatic conditions and somatic symptoms. Given the wide range of symptoms reported by patients in OMT, including some at high intensity levels, healthcare providers should take into consideration the somatic healthcare needs of individuals in OMT populations. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).