"Macrodosing" Sublingual Buprenorphine and Extended-release Buprenorphine in a Hospital Setting: 2 Case Reports.

OBJECTIVES: To describe 2 case reports in which high-dose administration of sublingual buprenorphine/naloxone quickly stabilized fentanyl users who presented to the hospital. To discuss how early administration of extended-release buprenorphine, before the patient is discharged, may improve retention rates for outpatient buprenorphine treatment. METHODS: Two case reports of fentanyl users presented to the emergency department at the general hospital in Timmins, Canada are described. They were rapidly stabilized on high-dose sublingual buprenorphine/naloxone and then transitioned within 24 to 36 hours to buprenorphine extended-release subcutaneous injection. RESULTS: In both cases, their withdrawal symptoms quickly resolved, without sedation or precipitated withdrawal. Both patients followed up with the outpatient clinic for another injection of extended-release buprenorphine. CONCLUSIONS: High-dose sublingual buprenorphine/naloxone followed by early administration of extended-release buprenorphine quickly and safely relieved withdrawal symptoms in 2 fentanyl users who presented to the hospital emergency department. This novel approach shows promise in improving treatment retention rates for patients using fentanyl. Further research is required to evaluate the safety and effectiveness of this approach.

Characterizing safer supply prescribing of immediate release hydromorphone for individuals with opioid use disorder across Ontario, Canada.

BACKGROUND: In response to the ongoing overdose crisis, some clinicians in Canada have started prescribing immediate release hydromorphone (IRH) as an alternative to the toxic unregulated drug supply. This practice is often referred to as safer supply. We aimed to identify and characterize patients receiving safer supply IRH and their prescribers in Ontario. METHODS: Using provincial administrative health data, we identified individuals with opioid use disorder prescribed safer supply IRH from January 2016 to March 2020 and reported the number of initiations over time. We summarized demographic, health, and medication use characteristics among patients who received safer supply IRH, and examined select clinical outcomes including retention and death. Finally, we characterized prescribers of safer supply IRH and compared frequent and infrequent prescribers. RESULTS: We identified 534 initiations of safer supply IRH (447 distinct individuals) from 155 prescribers. Initiations increased over time with a peak in the third quarter of 2019 (103 initiations). Patients' median age was 42 (interquartile range [IQR] 34-50), and most were male (60.2%), urban residents, (96.2%), and in the lowest neighborhood income quintile (55.7%), with 13.9% having overdosed in the previous one year. The prevalence of HIV was 13.9%. The median duration on IRH was 272 days (IQR 30-1,244) and OAT was co-prescribed in 62.9% of courses. Death while receiving IRH or within 7 days of discontinuation was rare (≤5 courses;≤0.94 per person-year for each). CONCLUSIONS: Clinicians are increasingly prescribing safer supply IRH in Ontario. Patients prescribed safer supply IRH had demographic and clinical characteristics associated with high risk of death from opioid-related overdose. Short-term deaths among people receiving safer supply IRH were rare.

Valorization of renewable resources to functional oligosaccharides: Recent trends and future prospective.

Lignocellulosic wastes have the ability to be transformed into oligosaccharides and other value-added products. The synthesis of oligosaccharides from renewable sources bestow to growing bioeconomies. Oligosaccharides are synthesized chemically or biologically from agricultural residues. These oligosaccharides are functional food supplements that have a positive impact on humans and livestock. Non-digestible oligosaccharides, refered as prebiotics are beneficial for the colonic microbiota inhabiting the f the digestive system. These microbiota plays a crucial role in stimulating the host immune system and other physiological responses. The commonly known prebiotics, galactooligosaccharides (GOS), xylooligosaccharides (XOS), fructooligosaccharides (FOS), mannanooligosaccharides (MOS), and isomaltooligosaccharides (IOS) are synthesized either through enzymatic or whole cell-mediated approaches using natural or agricultural waste substrates. This review focusses on recent advancements in biological processes, for the synthesis of oligosaccharides using renewable resources (lignocellulosic substrates) for sustainable circular bioeconomy. The work also addresses the limitations associated with the processes and commercialization of the products.

Facilitating rapid access to addiction treatment: a randomized controlled trial.

BACKGROUND: Obtaining timely access to addiction medicine treatment for patients with substance use disorders is challenging and patients often have to navigate complex referral pathways. This randomized controlled trial examines the effect of providing an expedited pathway to addiction medicine treatment on initial treatment engagement and health care utilization. METHODS: Individuals with possible alcohol or opioid use disorder were recruited from three residential withdrawal management services (WMS). Subjects randomized to the Delayed Intervention (DI) group were given contact information for a nearby addiction medicine clinic; those randomized to the Rapid Intervention (RI) group were given an appointment at the clinic within 2 days and were accompanied to their first appointment. RESULTS: Of the 174 individuals who were screened, 106 were randomized to either the DI or RI group. The two groups were similar in demographics, housing status, and substance use in the last 30 days. In the 6-month period following randomization, 85% of the RI group attended at least one clinic appointment, compared to only 29% in the DI group (p < 0.0001). The RI group had a mean of 6.39 ED visits per subject in the 12 months after randomization, while the DI group had a mean of 13.02 ED visits per subject in the same 12-month period (p = 0.0469). Other health utilization measures did not differ between the two groups. CONCLUSION: Providing immediate facilitated access to an addiction medicine service resulted in greater initial engagement and reduced emergency department visits at 6 months. Trial registration This trial is registered at the National Institutes of Health (ClinicalTrials.gov) under identifier #NCT01934751.

Long-term treatment outcomes in a First Nations high school population with opioid use disorder.

OBJECTIVE: To assess for long-term positive effects of buprenorphine treatment (BT) on opioid use disorder (OUD) at a Nishnawbe Aski Nation high school clinic. DESIGN: Postgraduation telephone survey of high school students between March 2017 and January 2018. SETTING: Dennis Franklin Cromarty High School in Thunder Bay, Ont. PARTICIPANTS: All 44 students who had received BT in the high school clinic during its operation from 2011 to 2013 were eligible to participate. MAIN OUTCOME MEASURES: Current substance use, BT status, and social and employment status. RESULTS: Thirty-eight of the 44 students who had received BT in the high school clinic were located and approached; 32 consented to participate in the survey. A descriptive analysis of the surveyed indicators was undertaken. Almost two-thirds (n = 20, 62.5%) of the cohort had graduated from high school, more than one-third (n = 12, 37.5%) were employed full time, and most (n = 29, 90.6%) rated their health as "good" or "OK." A greater percentage of participants who continued taking BT after high school (n = 19, 61.3%) were employed full time (n = 8, 42.1% vs n = 4, 33.3%) and were abstinent from alcohol (n = 12, 63.2% vs n = 4, 33.3%). Participants still taking BT were significantly more likely to have obtained addiction counseling in the past year than those participants not in treatment (n = 9, 47.4% vs n = 1, 8.3%; P = .0464). CONCLUSION: The study results suggest that offering OUD treatment to youth in the form of BT in a high school clinic might be an effective strategy for promoting positive long-term health and social outcomes. Clinical treatment guidelines currently recommend long-term opioid agonist treatment as the treatment of choice for OUD in the general population; they should consider adding youth to the population that might also benefit.

Improving opioid guideline adherence: evaluation of a multifaceted, theory-informed pilot intervention for family physicians.

OBJECTIVES: Opioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians' knowledge and practices after completing the OSA package. DESIGN: We conducted a mixed-method evaluation using a pre-test and post-test design that involved the collection of both qualitative and quantitative data. SETTING: This research was conducted in the primary care setting in Ontario, Canada. PARTICIPANTS: We recruited a purposive sample of nine family physicians in Ontario who use long-term opioid therapy to treat patients with chronic pain. INTERVENTIONS: The OSA package included four components: an online knowledge test, an online learning programme, a safe medication practice self-assessment questionnaire and chart audit with feedback. OUTCOME MEASURES: Our measures included changes in knowledge, opioid safety practices and physicians' perspectives on the OSA package. RESULTS: We found statistically significant improvements between pre-test and post-test knowledge scores at both baseline and 6-month follow-up. Physicians' scores improved significantly on five of the seven core characteristics of the practice self-assessment questionnaire. On the chart audits, we observed an improvement in patient education between baseline and 6 months. Qualitative interviews showed that participants appreciated embedded resources in the OSA package. The completion of the package stimulated identification of gaps or deficits in practice and served as a useful reminder to discuss risk and safety with patients. Participants described the chart review as helpful in prompting discussions with their patients, identifying deficits and strengths and a 'primary motivator' for project participation. CONCLUSIONS: The OSA package has the potential to improve medication safety practices in primary care related to opioid monitoring and adherence to current opioid guidelines.

Buprenorphine in the emergency department: Randomized clinical controlled trial of clonidine versus buprenorphine for the treatment of opioid withdrawal.

OBJECTIVE: To compare buprenorphine to clonidine for the treatment of opioid withdrawal in the emergency department (ED) and to study the effect assigned treatment medication had on longer-term addiction treatment outcomes. DESIGN: Randomized controlled trial. SETTING: Toronto, Ont. PARTICIPANTS: Twenty-six patients presenting to the ED while in opioid withdrawal or soon to be in opioid withdrawal. MAIN OUTCOME MEASURES: Patients were randomized to receive either clonidine or buprenorphine treatment. Both groups also received a corresponding discharge prescription and information on how to follow up in the addictions rapid access clinic (RAC) within a few days. Participants were followed for 1 month with respect to attendance at the RAC and to opioid agonist treatment status. Outcome measures included attendance at the RAC within 5 days of the initial ED visit and opioid agonist treatment status at 1 month (as determined by clinic attendance or self-report during a follow-up telephone interview). RESULTS: Participants who received buprenorphine in the ED were more likely to be receiving opioid agonist treatment at the 1-month mark compared with those participants who received clonidine to treat their withdrawal (P = .011). CONCLUSION: When opioid withdrawal is treated with buprenorphine in the ED, patients are more likely to be receiving opioid agonist treatment and connected with addiction treatment 1 month later. TRIAL REGISTRATION NUMBER: NCT03174067 (ClinicalTrials.gov).

Buprenorphine unobserved "home" induction: a survey of Ontario's addiction physicians.

BACKGROUND: Ontario patients on opioid agonist treatment (OAT) are often prescribed methadone instead of buprenorphine, despite the latter's superior safety profile. Ontario OAT providers were surveyed to better understand their attitudes towards buprenorphine and potential barriers to its use, including the induction process. METHODS: We used a convenience sample from an annual provincial conference to which Ontario physicians who are involved with OAT are invited. RESULTS: Based on 85 survey respondents (out of 215 attendees), only 4% of Ontario addiction physicians involved in OAT routinely used unobserved "home" buprenorphine induction: 59% of physicians felt that unobserved induction was risky because it was against "the guidelines" and 66% and 61% respectively believed that unobserved "home" induction increased the risk of diversion and of precipitated withdrawal. CONCLUSIONS: Ontario addiction physicians largely report following the traditional method of bringing in patients for observed in-office buprenorphine induction: they expressed fear of precipitated withdrawal, diversion, and going against clinical guidelines. The hesitance in using unobserved induction may explain, in part, Ontario's reliance on methadone.

Enrichment and evaluation of galacto-oligosaccharides produced by whole cell treatment of sugar reaction mixture.

A process was developed for enrichment of galacto-oligosaccharides (GOS), synthesized from a whole cell driven system, from a sugar reaction mixture (SRM) containing non prebiotic sugars (monosaccharides and disaccharides) as impurities. SRM containing 38% (w/w of total carbohydrates) of GOS was enriched by 7 and 27%, attaining a purity of 45 and 65% respectively using Saccharomyces cerevisiae followed by Kluyveromyces lactis var. lactis treatment. The two cell types could be recycled for consecutive 12 and 10 cycles respectively. The microbial purified GOS (MPG) was characterized by mass spectrometry and quantitated by HPLC. MPG was further evaluated for its prebiotic potential on Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus casei Shirota and Saccharomyces boulardii. The growth profile and colony forming units were determined and compared with the profiles obtained on glucose, used as a control. MPG was efficiently utilized by L. acidophilus and L. plantarum which showed antimicrobial activity with zone of lysis (12 and 10 mm) against Escherichia coli and Citrobacter (14 and 9 mm) respectively and performed better than Vivinal (commercial GOS), fructo-oligosaccharides and inulin. The synergistic effect of the MPG with L. acidophilus and L. plantarum was found to be most effective against pathogens as compared to other tested commercial oligosaccharides.

Potential of in situ SSF laccase produced from Ganoderma lucidum RCK 2011 in biobleaching of paper pulp.

Production of laccase from Ganoderma lucidum RCK 2011 under solid-state fermentation (SSF) conditions was optimized using response surface methodology, resulting in an approximate eightfold increase compared to that in the unoptimized media. Further, the enzyme produced under SSF as whole fermented substrate (in situ SSF laccase) was found to be more stable than the in vitro enzyme (harvested by downstreaming processing of fermented wheat bran). Interestingly, the biobleaching potentials of both in situ and in vitro SSF laccases were comparable, saving 25% chlorine dioxide for achieving similar pulp brightness as obtained in the pulp treated chemically. The reduction in the demand of chlorine dioxide in the pulp bleaching sequence subsequently decreased the levels of adsorbable organic halogen (AOX) in the resulting effluents of the process by 20% compared to the effluents obtained from chemical bleaching sequence. Therefore, direct application of in situ SSF laccase in pulp biobleaching will be environmentally friendly as well as economical and viable for implementation in paper mills.

Primary care management of opioid use disorders: Abstinence, methadone, or buprenorphine-naloxone?

OBJECTIVE: To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance. SOURCES OF INFORMATION: PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included. MAIN MESSAGE: Both methadone and buprenorphine-naloxone are substantially more effective than abstinence-based treatment. Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose. For all patient groups, physicians should recommend methadone or buprenorphine-naloxone treatment over abstinence-based treatment (level I evidence). Methadone is preferred over buprenorphine-naloxone for patients at higher risk of treatment dropout, such as injection opioid users (level I evidence). Youth and pregnant women who inject opioids should also receive methadone first (level III evidence). If buprenorphine-naloxone is prescribed first, the patient should be promptly switched to methadone if withdrawal symptoms, cravings, or opioid use persist despite an optimal buprenorphine-naloxone dose (level II evidence). Buprenorphine-naloxone is recommended for socially stable prescription oral opioid users, particularly if their work or family commitments make it difficult for them to attend the pharmacy daily, if they have a medical or psychiatric condition requiring regular primary care (level IV evidence), or if their jobs require higher levels of cognitive functioning or psychomotor performance (level III evidence). Buprenorphine-naloxone is also recommended for patients at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepines or other sedating drugs, heavy drinkers, those with a lower level of opioid tolerance, and those at high risk of prolonged QT interval (level III evidence). CONCLUSION: Individual patient characteristics and preferences should be taken into consideration when choosing a first-line opioid agonist treatment. For patients at high risk of dropout (such as adolescents and socially unstable patients), treatment retention should take precedence over other clinical considerations. For patients with high risk of toxicity (such as patients with heavy alcohol or benzodiazepine use), safety would likely be the first consideration. However, the most important factor to consider is that opioid agonist treatment is far more effective than abstinence-based treatment.

Prise en charge des troubles de consommation d'opioïdes en première ligne: Abstinence, méthadone ou buprénorphine-naloxone?

OBJECTIF: Conseiller les médecins quant aux options thérapeutiques à recommander à des populations précises de patients : approche axée sur l'abstinence, traitement d'entretien par la buprénorphine-naloxone ou traitement d'entretien par la méthadone. SOURCES D'INFORMATION: Une recherche sur PubMed a été effectuée, et on a relevé dans les publications les données sur l'efficacité, l'innocuité et le profil d'effets indésirables de l'approche axée sur l'abstinence, du traitement par la buprénorphine-naloxone et du traitement par la méthadone. Les études d'observation et interventionnelles ont été incluses. MESSAGE PRINCIPAL: La méthadone et la buprénorphine-naloxone sont substantiellement plus efficaces que l'approche axée sur l'abstinence. La méthadone présente un taux de rétention plus élevé que la buprénorphine-naloxone, alors que la buprénorphine-naloxone présente un risque plus faible de surdose. Les médecins devraient recommander le traitement par la méthadone ou la buprénorphine-naloxone plutôt que l'approche axée sur l'abstinence, et ce, à tous les groupes de patients (données de niveau I). La méthadone est préférable à la buprénorphine-naloxone chez les patients qui présentent un risque élevé d'abandon, comme les usagers d'opioïdes par injection (données de niveau I). Les jeunes et les femmes enceintes qui font usage d'opioïdes par injection devraient aussi recevoir la méthadone d'abord (données de niveau III). Si la buprénorphine-naloxone est prescrite en premier, il faut faire passer rapidement le patient à la méthadone si les symptômes de sevrage, les fortes envies ou la consommation d'opioïdes persistent malgré une dose optimale de buprénorphine-naloxone (données de niveau II). La buprénorphine-naloxone est recommandée chez les usagers d'opioïdes sur ordonnance par voie orale socialement stables, surtout s'ils ont un emploi ou si leurs obligations familiales les empêchent de se rendre à la pharmacie tous les jours, s'ils ont une affection médicale ou psychiatrique exigeant des soins réguliers de première ligne (données de niveau IV), ou encore si leur emploi exige une fonction cognitive ou un rendement psychomoteur élevés (données de niveau III). La buprénorphine-naloxone est aussi recommandée chez les patients qui présentent un risque élevé de toxicité à la méthadone, tels que les personnes âgées, les personnes qui prennent de fortes doses de benzodiazépines ou d'autres sédatifs, les gros buveurs, les personnes dont la tolérance aux opioïdes est faible et les personnes à risque de prolongement de l'intervalle QT (données de niveau III). CONCLUSION: Il faut tenir compte des caractéristiques et des préférences individuelles des patients lors de la sélection d'un traitement de première intention par un agoniste des opioïdes. Chez les patients qui présentent un risque élevé d'abandon (adolescents et patients socialement instables), la rétention en traitement doit avoir préséance sur les autres considérations cliniques. Chez les patients qui présentent un risque élevé de toxicité (comme les usagers abusifs d'alcool ou de benzodiazépines), la sécurité a sans doute préséance. Ce qu'il importe le plus de considérer toutefois, c'est que le traitement par un agoniste des opioïdes est beaucoup plus efficace que l'approche axée sur l'abstinence.

Home visits in family medicine residency: evaluation of 8 years of a training program.

PROBLEM ADDRESSED: There has been a decline in family physicians providing home visits to housebound patients. OBJECTIVE OF PROGRAM: To increase family medicine residents' exposure to home visits; their comfort and skills in providing home visits; and their willingness to provide home visits after graduation. PROGRAM DESCRIPTION: Between 2000 and 2010, each family practice resident at St Joseph's Health Centre Family Medicine Teaching Unit in Toronto, Ont, was assigned at least 1 housebound patient to care for longitudinally over 2 years; the rationale for this was to increase the sense of "ownership" and responsibility among residents for their assigned homebound patients. Starting in 2003, until the program's conclusion in 2010, residents were asked to fill out surveys before and after the program to assess their comfort with and confidence in providing home visits, as well as their satisfaction with the program. Survey responses were analyzed for changes over the course of residency training. A total of 85 residents completed the home visit teaching program between 2003 and 2010 inclusive. CONCLUSION: While residents' willingness to provide home visits did not increase over the course of residency, their confidence in making housecalls did increase. There was also a trend toward increased confidence among residents in working with community agencies. Thus, having home visit patients be a part of resident practices might play an important role in increasing the likelihood that future family physicians will continue to care for their patients when those patients are no longer ambulatory.

Predictors of Opioid-Related Death During Methadone Therapy.

We aimed to examine pharmacologic, demographic and medical comorbidity risk factors for opioid-related mortality among patients currently receiving methadone for an opioid use disorder. We conducted a population-based, nested case-control study linking healthcare and coroner's records in Ontario, Canada, from January 31, 1994 to December 31, 2010. We included social assistance recipients receiving methadone for an opioid use disorder. Within this group, cases were those who died of opioid-related causes. For each case, we identified up to 5 controls matched on calendar quarter. The primary analysis examined the association between use of psychotropic drugs (benzodiazepines, antidepressants or antipsychotics) and opioid-related mortality. Secondary analyses examined the associations between baseline characteristics, health service utilization, comorbidities and opioid-related mortality. Among 43,545 patients receiving methadone for an opioid use disorder, we identified 175 (0.4%) opioid-related deaths, along with 873 matched controls. Psychotropic drug use was associated with a two fold increased risk of opioid-related death (adjusted odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2 to 3.5). Specifically, benzodiazepines (adjusted OR 1.6; 95% CI 1.1 to 2.5) and antipsychotics (adjusted OR 2.3; 95% CI 1.5 to 3.5) were independently associated with opioid-related death. Other associated factors included chronic lung disease (adjusted OR 1.7; 95% CI 1.2 to 2.6), an alcohol use disorder (adjusted OR 1.9; 95% CI 1.2 to 3.2), mood disorders (adjusted OR 1.8; 95% CI 1.0 to 3.2), and a history of heart disease (adjusted OR 5.3; 95% CI 2.0 to 14.0). Psychotropic drug use is associated with opioid-related death in patients receiving methadone. Mindfulness of these factors may reduce the risk of death among methadone recipients.

Transgalactosylation of lactose for synthesis of galacto-oligosaccharides using Kluyveromyces marxianus NCIM 3551.

Among a number of yeast strains screened for whole cell transgalactosylating activity, Kluyveromyces marxianus NCIM 3551 was found to be most suitable biocatalyst for production of galacto-oligosaccharides (GOS). Cell permeabilization lead to an efficient bioconversion by ß-galactosidase resulting in synthesis of GOS. A maximum GOS yield of 36% (w/w) of total sugars was achieved and the products consisted of tri- and tetra-galacto-oligosaccharides. A lactose conversion rate of 80% and productivity of 24g/L/h was obtained under the optimum conditions at lactose concentration of 20% (w/v), temperature 40°C, pH 6.5 and enzyme units after 3h of reaction time. Tetrasaccharides were the main component of the reaction mixture. The products were quantitated by HPLC and structurally characterized by mass spectrometry.

Prescribing smoked cannabis for chronic noncancer pain: preliminary recommendations.

OBJECTIVE: To offer preliminary guidance on prescribing smoked cannabis for chronic pain before the release of formal guidelines. QUALITY OF EVIDENCE: We reviewed the literature on the analgesic effectiveness of smoked cannabis and the harms of medical and recreational cannabis use. We developed recommendations on indications, contraindications, precautions, and dosing of smoked cannabis, and categorized the recommendations based on levels of evidence. Evidence is mostly level II (well conducted observational studies) and III (expert opinion). MAIN MESSAGE: Smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics (level II evidence). Smoked cannabis is contraindicated in patients who are 25 years of age or younger (level II evidence); who have a current, past, or strong family history of psychosis (level II evidence); who have a current or past cannabis use disorder (level III evidence); who have a current substance use disorder (level III evidence); who have cardiovascular or respiratory disease (level III evidence); or who are pregnant or planning to become pregnant (level II evidence). It should be used with caution in patients who smoke tobacco (level II evidence), who are at increased risk of cardiovascular disease (level III evidence), who have anxiety or mood disorders (level II evidence), or who are taking higher doses of opioids or benzodiazepines (level III evidence). Cannabis users should be advised not to drive for at least 3 to 4 hours after smoking, for at least 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective "high" (level II evidence). The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing 9% delta-9-tetrahydrocannabinol (level III evidence). Physicians should avoid referring patients to "cannabinoid" clinics (level III evidence). CONCLUSION: Future guidelines should be based on systematic review of the literature on the safety and effectiveness of smoked cannabis. Further research is needed on the effectiveness and long-term safety of smoked cannabis compared with pharmaceutical cannabinoids, opioids, and other standard analgesics.

Effect of a course-based intervention and effect of medical regulation on physicians' opioid prescribing.

OBJECTIVE: To examine the effects of an intensive 2-day course on physicians' prescribing of opioids. DESIGN: Population-based retrospective observational study. SETTING: College of Physicians and Surgeons of Ontario (CPSO) in Toronto. PARTICIPANTS: Ontario physicians who took the course between April 1, 2000, and May 30, 2008. INTERVENTION: A 2-day opioid-prescribing course with a maximum of 12 physician participants. Educational methods included didactic presentations, case discussions, and standardized patients. A detailed syllabus and office materials were provided. MAIN OUTCOME MEASURES: Participants were matched with control physicians using specific variables. The primary outcome was the rate of opioid prescribing, expressed as milligrams of morphine equivalent per quarter. RESULTS: One hundred thirty-eight course participants (120 family physicians, 15 specialists, and 3 physicians whose status was uncertain) were eligible for analysis. Of these, 68.1% were self-referred and 31.9% were referred by the CPSO. Overall, among physicians referred by the CPSO, the rate of opioid prescribing decreased dramatically in the year before course participation compared with matched control physicians. The course had no added effect on the rate of physicians' opioid prescribing in the subsequent 2 years. There was no statistically significant effect on the rate of opioid prescribing observed among the self-referred physicians. Among 15 of the self-referred physicians who, owing to the high quantities of opioids they prescribed, were not matched with control physicians, the rate of opioid prescribing decreased by 43.9% in the year following course completion. CONCLUSION: Physicians markedly reduced the quantities of opioids they prescribed after medical regulators referred them to an opioid-prescribing course. The course itself did not lead to significant additional reductions; however, a subgroup of physicians who prescribed high quantities of opioids might have responded to what was taught in the course.