Naldemedine’s role in relieving opioid-induced constipation among patients on opioid agonist treatment

Purpose As deaths from the illicit drug poisoning crisis continue to rise in Canada, increasing the number of healthcare professionals qualified to effectively prescribe opioids could be beneficial. The willingness of family medicine residents to undertake structured training in prescribing opioids for Opioid Agonist Treatment (OAT) and pain management have not been well described. Materials and methods Family medicine residents (n = 20) in British Columbia, Canada, were asked about their experience with and willingness to enrol in OAT training. Informed by the Consolidated Framework for Implementation Research, data were analysed thematically using NVivo software. Results Four themes were identified: (1) challenges to training implementation, (2) feelings and attitudes on prescribing practices, (3) helpful learning spaces and places of substance use training, and (4) recommendations for implementing training. Preparedness, exposure, and supportive learning environments for substance use education increased willingness to pursue OAT accreditation, while ineffective learning experiences, mixed feelings about opioid prescribing, and lack of protected time were the most common reasons for unwillingness. Conclusions Protected time and a range of clinical experiences appear to facilitate residents’ willingness to complete OAT and opioid training. Implementation strategies to enhance the uptake of OAT accreditation in family medicine residency must be prioritised.

Background and AimsThe individual‐level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established, but there is less evidence on population‐level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in the community and prisons on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation.DesignDynamic modeling.Setting and participantsA cohort of 49 359 individuals who ever received OAT in NSW from 2001 to 2018.MeasurementsReceipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1–9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata: (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1–12 months ago. The model incorporated elevated mortality post‐release from prison and OAT impact on reducing mortality and incarceration.FindingsAmong the cohort, mortality was 0.9 per 100 person‐years, OAT coverage and retention remained high (> 50%, 1.74 years/episode). During 2001–20, we estimate that OAT provision reduced overdose and other cause mortality among the cohort by 52.8% [95% credible interval (CrI) = 49.4–56.9%] and 26.6% (95% CrI =22.1–30.5%), respectively. We estimate 1.2 deaths averted and 9.7 life‐years gained per 100 person‐years on OAT. Prison OAT with post‐release OAT‐linkage accounted for 12.4% (95% CrI = 11.5–13.5%) of all deaths averted by the OAT program, primarily through preventing deaths in the first month post‐release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% (95% CrI = 0.8–2.0%) and 3.0% (95% CrI = 2.1–5.3%) of deaths, respectively.ConclusionThe community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population‐level overdose and all‐cause mortality in the past 20 years, partially due to high retention.

Source: Piske M, Homayra F, Min JE, et al. Opioid use disorder and perinatal outcomes. Pediatrics. 2021;148(4):e2021050279. doi: 10.1542/peds.2021-050279Investigators from multiple institutions in Canada conducted a retrospective study to evaluate perinatal outcomes in infants born to mothers with opioid use disorder (OUD). For the study, they linked multiple databases to identify mothers with OUD diagnosed before delivery or in the puerperium period with completed pregnancies between April 1, 2000 and March 31, 2019 in British Columbia, Canada. Data abstracted on mothers included age, parity, gestational age, receipt of opioid agonist treatment, timing of treatment (before pregnancy, during pregnancy but not until delivery, or until delivery), type of opioid agonist treatment (methadone, slow release oral morphine [SROM], buprenorphine/naloxone), use of other psychotropic drugs during pregnancy (selective serotonin reuptake inhibitors [SSRIs], benzodiazepines, antipsychotics, and stimulants), tobacco use, and alcohol use. Newborn outcomes included low birth weight (<2,500 g), prematurity (<37 weeks), and neonatal abstinence syndrome (NAS) diagnosis (based on ICD-9 and ICD-10 codes). Descriptive statistics were used to evaluate these outcomes and assess trends over the study period. Linear mixed effects models were used to compare outcomes in babies whose mothers used opioid agonist treatment until delivery and in those who discontinued treatment in pregnancy, and in mothers treated with buprenorphine/naloxone or SROM vs methadone. Models were adjusted for maternal age, parity, use of psychotropic drugs, and alcohol and tobacco use.A total of 4,574 women were diagnosed with OUD, with 6,693 deliveries and 6,720 live births during the study period. Opioid agonist treatment during pregnancy was documented for 2,824 deliveries (42%), and prescriptions for psychotropic drugs were identified during pregnancy in 2,684 (37%) deliveries. During the study period, the number of cases of OUD in pregnancy increased from 166 in 2000–2001 to 513 in 2018–2019. Rates of use of opioid agonist treatment remained stable during the treatment period; 94.7% of opioid agonist treatment was with methadone. Among the infants born to mothers with OUD, 16% were low birth weight, 24% were born premature, and 2,496 (36.8%) were diagnosed with NAS. In the multivariate models, continued opioid agonist treatment through delivery, compared to treatment discontinuation during pregnancy, was associated with an increased risk of NAS in the infant (odds ratio [OR], 4.7; 95% CI, 3.6, 6.1), but decreased risk of preterm birth (OR, 0.6; 95% CI, 0.4, 0.8) and low birth weight (OR, 0.4; 95% CI, 0.2, 0.7). Compared to methadone, treatment with buprenorphine/naloxone or SROM was associated with lower risks of preterm delivery (OR, 0.6; 95% CI, 0.3, 0.9), low birth weight (OR, 0.6; 95% CI, 0.4, 0.9) and NAS (OR, 0.6; 95% CI, 0.4, 0.9).The authors conclude the incidence of perinatal OUD in British Columbia more than tripled over a 20-year period.Dr Von Kohorn has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The documented increases in OUD during pregnancy and NAS in Canada mirror the US experience, where a recent national estimate of OUD in pregnancy was 8.2 per 1,000 births, and NAS was 7.3 per 1,000 births.1 (See AAP Grand Rounds. 2018;39[4]:47.)2 The current investigators found a rate of prematurity of 24% among infants born to mothers with OUD, which is more than double the population rate in the US.3 In multivariate models the authors demonstrate that treatment with opioid agonists, particularly non-methadone medications, significantly and substantially was associated with a reduced chance of prematurity.Despite the increase in OUD during pregnancy, the results of the current study show that the proportion of pregnant women with OUD who receive treatment remains stable and low, with less than half receiving opioid agonist treatment. The results of prior studies have shown similarly poor rates of opioid agonist treatment, with even less behavioral therapy.4 One barrier to uptake or continuation of opioid agonist treatment during pregnancy has been doubt about the strength of the evidence for improved outcomes with opioid agonist treatment during pregnancy. The current study overcomes many limitations of prior studies, and the results substantiate the association of opioid agonist treatment for those with OUD in pregnancy with improved outcomes.The evidence presented reinforces the need to make opioid agonist therapy more accessible to pregnant women with OUD. Since more than 90% of participants in the current study also had a coexisting mental health and other substance use diagnosis, interventions that increase holistic, multidisciplinary treatment may be optimal. Despite growing evidence for the superiority of buprenorphine and other non-methadone medications, methadone remains a common treatment.5 Improved access to non-methadone medications can help increase uptake.4OUD in pregnancy has increased substantially. Although treatment with opioid agonist medications improves outcomes, the proportion of those receiving treatment during pregnancy remains low.

Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in opioid agonist treatment is unclear. We investigated the joint association of prescribed dosage of opioid agonist treatment and patient-perceived dosage adequacy with risk of HCV infection among people who inject drugs. We followed prospectively people who inject drugs at risk of acquiring HCV infection (who were RNA negative and HCV-antibody negative or positive) in Montréal, Canada (2004-2017). At 6-month, then 3-month intervals, participants were tested for HCV antibodies or RNA, and completed an interviewer-administered behavioural questionnaire, reporting the following: current exposure to opioid agonist treatment (yes/no), prescribed dosage either high (methadone ≥ 60 mg/d or buprenorphine ≥ 16 mg/d) or low, and perceived dosage adequacy (adequate/inadequate). We then assigned participants to 1 of 5 exposure categories: no opioid agonist treatment, high dosage of opioid agonist treatment perceived to be adequate, high dosage perceived to be inadequate, low dosage perceived to be adequate or low dosage perceived to be inadequate. To estimate associations between categories of opioid agonist treatment dosage and incident HCV infection, we conducted Cox regression analyses, adjusting for multiple confounding factors. Of 513 participants (median age 35.0 yr, 77.6% male), 168 acquired HCV over 1422.6 person-years of follow-up (incidence 11.8/100 person-years, 95% confidence interval [CI] 10.1-13.7). We observed a gradient in the relative risks of HCV infection across categories of opioid agonist treatment dosage. Compared with people who inject drugs not receiving opioid agonist treatment, adjusted hazard ratios were 0.43 (95% CI 0.23-0.84) for those receiving high dosages perceived to be adequate, 0.61 (95% CI 0.25-1.50) for those receiving high dosages perceived to be inadequate, 1.22 (95% CI 0.74-2.00) for those receiving low dosages perceived to be adequate and 1.94 (95% CI 1.11-3.39) for those receiving low dosages perceived to be inadequate. Risk of HCV infection varies considerably according to dosage of opioid agonist treatment and patient-perceived adequacy, with associations indicating both protective and harmful effects relative to no exposure to opioid agonist treatment.

Willingness to pay for opioid agonist treatment among opioid dependent people who inject drugs in Ukraine

BackgroundOpioid use disorder is a public health problem and treatment variability, coverage and accessibility poses some challenges. The study’s objective is to review the impact of interim opioid agonist treatment (OAT), a short-term approach for patients awaiting standard OAT, in terms of treatment retention, access to standard OAT, quality of life and satisfaction with treatment.MethodWe conducted a systematic review searching MEDLINE, EMBASE, PsycINFO, and CENTRAL up to May 2020. Due to variability between studies and outcome measurements, we did not pool effect estimates and reported a narrative synthesis of findings rating their certainty according to GRADE.ResultsWe identified 266 unique records and included five randomized trials with some limitations in risk of bias and one observational study limited by selection bias. The studies assessed similar approaches to interim OAT but were compared to three different control conditions. Four studies reported on treatment retention at 4 months or less with no significant differences between interim OAT and waiting list or standard OAT. Two studies reported treatment retention at 12 months with no differences between interim OAT and standard OAT. Two trials assessed access to standard OAT and showed significant differences between interim OAT and waiting list for standard OAT. We rated the quality of evidence for these outcomes as moderate due to the impact of risk of bias. Data on quality of life or satisfaction with treatment was suboptimal.ConclusionsInterim OAT is likely more effective than a waiting list for standard OAT in access to treatment, and it is probably as effective as standard OAT regarding treatment retention.PROSPERO registration CRD42018116269.

BackgroundPrevalence of substance use disorders, especially opioid use disorders, is high in patients admitted into forensic psychiatric settings. Opioid agonist treatment is a safe, well-established, and effective treatment option for patients that suffer from opioid dependence. Surprisingly, data on the availability and practice of opioid agonist treatment (OAT) options in German Forensic Clinics for Dependency Diseases is rare. Furthermore, essential data on the prevalence of critical incidents such as violent behavior, relapse, or escape from the clinic are missing for this particular treatment setting.Materials and methodsWe conducted an observational study on all forensic addiction treatment units in Germany (Sect. 64 of the German Criminal Code). A questionnaire on the availability and practice of OAT was sent to all Forensic Clinics for Dependency Diseases in Germany. Following items were assessed: availability and the total number of patients that received an OAT in 2018, available medication options, specific reasons for start and end of OAT, number of treatments terminated without success, number of successful treatments, and critical incidents such as violent behavior, relapse, escape and reoffending. We compared the forensic clinics that offered OAT with those that did not offer this treatment option. The data were analyzed descriptively. Mean and standard deviation was calculated for metric scaled variables. For categorical variables, absolute and relative frequencies were calculated. The two groups (OAT vs. Non-OAT institutions) were compared concerning the given variables by either using Fishers exact test (categorical variables), t-test (normally distributed metric variables), or Wilcoxon-test (metric variables not normally distributed).ResultsIn total, 15 of 46 Forensic Clinics for Dependency Diseases participated in the study (33%). In total, 2,483 patients were treated in the participating clinics, 18% were relocated into prison due to treatment termination, and 15% were discharged successfully in 2018. 275 critical incidents were reported: violence against a patient (4%), violence against staff (1.6%), escape (4.7%) and reoffending in (0.5%). In seven clinics treating 1,153 patients, an OAT was available. OAT options in forensic clinics were buprenorphine/naloxone, buprenorphine, methadone, and levomethadone. Regarding critical incidents and successful discharge, no differences were detected in the clinics with or without an OAT. In the clinics that offered an OAT, we found a significantly higher rate of treatment termination without success (p < 0.007) in comparison to clinics without an OAT program. Ninety-nine patients received an OAT, and this treatment was ended due to illegal drug abuse (57%), refusal to give a urine drug sample (71%), and cases where the OAT was given away to other patients (85%).ConclusionIn Forensic Clinics for Dependency Diseases in Germany, OAT is not available in every institution, and thus, access is limited. Critical incidents such as violent behavior against staff or patients and escape are not uncommon in these forensic treatment settings. Further studies are needed to enhance the understanding of OAT practice and the risks for patients and staff.

Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. To estimate the association of time receiving OAT with mortality. The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.

Introduction Correctional populations with opioid use disorder experience increased health risks during community transition periods. Opioid Agonist Treatment (OAT) can reduce these risks, but retention is a key challenge. This study addresses a knowledge gap by describing facilitators and barriers to OAT engagement among federal correctional populations released into the community in Ontario, Canada. Methods This article describes results from a longitudinal mixed-methods study examining OAT transition experiences among thirty-five individuals released from federal incarceration in Ontario, Canada. Assessments were completed within one year of participants’ release. Data were thematically analyzed. Results The majority (77%) of participants remained engaged in OAT, however, 69% had their release suspended and 49% returned to custody. Key facilitators for OAT engagement included flexibility, positive staff rapport, and structure. Fragmented OAT transitions, financial OAT coverage, balancing reintegration requirements, logistical challenges, and inaccessibility of ‘take-home’ OAT medications were common barriers. Conclusions Post-incarceration transition periods are critical for OAT retention, yet individuals in Ontario experience barriers to OAT engagement that contribute to treatment disruptions and related risks such as relapse and/or re-incarceration. Additional measures to support community OAT transitions are required, including improved discharge planning, amendments to OAT and financial coverage policies, and an expansion of OAT options.

State criminal justice policy context and opioid agonist treatment delivery among opioid treatment admissions, 2015

Buprenorphine and methadone are highly effective first-line medications for opioid agonist treatment (OAT) but are not acceptable to all patients. We aimed to assess the uptake of slow-release oral morphine (SROM) as second-line OAT among medically ill, hospitalised patients with opioid use disorder who declined buprenorphine and methadone. This study included consecutive hospitalised patients with untreated moderate-to-severe opioid use disorder referred to an inpatient addiction medicine consultation service, between June 2018 and September 2019, in Nova Scotia, Canada. We assessed the proportion of patients initiating first-line OAT (buprenorphine or methadone) in-hospital, and the proportion initiating SROM after declining first-line OAT. We compared rates of outpatient OAT continuation (i.e., filling outpatient OAT prescription or attending first outpatient OAT clinic visit) by medication type, and compared OAT selection between patients with and without chronic pain, using χ2 tests. Thirty-four patients were offered OAT initiation in-hospital; six patients (18%) also had chronic pain. Twenty-one patients (62%) initiated first-line OAT with buprenorphine or methadone. Of the 13 patients who declined first-line OAT, seven (54%) initiated second-line OAT with SROM in-hospital. Rates of outpatient OAT continuation after hospital discharge were high (>80%) and did not differ between medications (P=0.4). Patients with co-existing chronic pain were more likely to choose SROM over buprenorphine or methadone (P=0.005). The ability to offer SROM (in addition to buprenorphine or methadone) increased rates of OAT initiation among hospitalised patients. Increasing access to SROM would help narrow the opioid use disorder treatment gap of unmet need.

To quantify the association between opioid agonist treatment (OAT) and overdose death by age group; test the hypothesis that across different age groups, opioid overdose mortality is lowest during OAT with buprenorphine compared with time out of treatment or OAT with methadone; and test associations between OAT and opioid overdose mortality in the presence of chronic circulatory, respiratory, liver and kidney diseases. Retrospective observational cohort study using linked administrative data. New South Wales, Australia. A total of 37 764 people prescribed OAT, 1 August 2002 and 31 December 2017. OAT exposure, opioid overdose mortality and key confounders were measured using linked population data sets on OAT entry and exit, hospitalization, mental health care, incarceration and mortality. ICD-10 codes were used to define opioid overdose mortality and chronic disease groups of interest. Relative to time out of treatment, time in OAT was associated with a lower risk of opioid overdose death across all age groups and chronic diseases. Among people aged 50 years and older, there was weak evidence that buprenorphine may be associated with greater protection against opioid overdose death than methadone [generalized estimating equation (GEE) adjusted incident rate ratio (aIRR) = 0.47; 95% confidence interval (CI) = 0.21, 1.02; marginal structural models (MSM) aIRR = 0.49; 95% CI = 0.17, 1.41]. Buprenorphine was associated with greater protection against overdose death than methadone for clients with circulatory (MSM aIRR = 0.27; 95% CI = 0.11, 0.67) or respiratory (MSM aIRR = 0.26; 95% CI = 0.07, 0.94) diseases, but not liver (MSM aIRR = 0.59; 95% CI = 0.14, 2.43) or kidney (MSM aIRR = 1.16; 95% CI = 0.31, 4.36) diseases. Opioid agonist treatment (OAT) appears to reduce mortality risk in people with opioid use disorder who are older or who have physical comorbidities. Opioid overdose mortality during OAT with buprenorphine appears to be lower and reduced in clients with circulatory and respiratory diseases compared with OAT with methadone.

25 Core decompression by laser osteoperforation: a new and minimal invassive modality for treatment of avascular necrosis (AVN) of femoral head. A preliminary report

Determinants of willingness to enroll in opioid agonist treatment among opioid dependent people who inject drugs in Ukraine

PurposeLong-acting injectable buprenorphine (LAI BUP) is a novel opioid agonist treatment (OAT) medication with several benefits for patients, OAT units, and society. We present a case series of fatalities in OAT with LAI BUP.MethodsThis was an audit of OAT patient records, supplemented with results of post-mortem (PM) investigation. We started with all deaths (N = 604) between 2018 and 2020 in Finland with a buprenorphine or norbuprenorphine finding in PM toxicology and with known substance use history or concomitant findings of illicit drugs. We then examined the patient records of the 43 individuals in OAT at the time of death. We analyzed information on OAT medication, OAT structure, and performance, including concomitant substance use, and PM findings.ResultsTen LAI BUP patients died during the study period, all of them in 2020, out of the 18 patients receiving some OAT that year. Among the LAI BUP patients, four died from buprenorphine poisoning. Eight patients had PM findings of abused drugs, always including unprescribed benzodiazepines. Two patients showed signs of additional buprenorphine use of which their OAT unit was unaware. Three patients were classified as non-compliant with OAT but had received no extra support to tackle their situation. Visits to the OAT clinic had mainly occurred only on injection days.ConclusionsLAI BUP comprised 56% of OAT medication among all deceased OAT patients in 2020. Despite its recognized benefits, LAI BUP treatment was associated with deaths. Psychosocial support among the deceased LAI BUP patients seemed inadequate.