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Background: Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT., Methods: We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns., Results: 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66-428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg., Conclusions: On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Slow-release oral morphine (SROM) is used to manage pain, and as opioid agonist treatment (OAT). Between 2017 and 2021 in Canada, several drug shortages occurred for Kadian© (SROM-24). The purpose of this study was to evaluate the impact of these shortages on people's ability to remain on this medication., Methods: We conducted a retrospective population-based time series analysis of SROM-24 dispensed between January 1, 2014, and December 31, 2021, in Ontario, Canada. Using interventional autoregressive integrated moving average models (ARIMA) models, we evaluated the association between SROM-24 drug shortages and treatment discontinuation. Analyses were also stratified by the SROM-24 indication (pain or OAT)., Results: We identified 22,479 SROM-24 recipients, of which one-third (33.9%) were aged 65 or above and just over half (51.9%) were female. In our primary analysis of monthly SROM-24 discontinuation, we observed a significant sustained monthly increase following the shortages in November 2019 (+0.29%/month; 95% CI: 0.16%, 0.43%; p < .001) with significant sudden, temporary changes following the shortages in March 2020 (+2.00%; 95% CI: 0.95%, 3.05%; p < .001), July 2021 (+3.53%; 95% CI: 2.20%, 4.86%; p < .001), and August 2021 (+4.98%; 95% CI: 3.49%, 6.47%; p < .001). Similar results were observed in our stratified analyses, with sustained high rates of discontinuation among people accessing SROM-24 as OAT., Conclusions: The SROM-24 shortages resulted in significant treatment disruptions across all recipients. These findings have important implications for those with few treatment alternatives, including people using SROM-24 as OAT who are at risk of adverse outcomes following treatment disruptions., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: The opioid epidemic is an international public health concern. Pharmacists are in a strategic position to promote and implement effective opioid stewardship due to both their central role on health care teams and frequent interaction with patients. Despite this integral role, pharmacists do not have harmonized scopes of practice in opioid stewardship., Objectives: This scoping review was conducted to identify and critically review the role of pharmacists in opioid stewardship and identify future areas of study., Methods: The scoping review was conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases were searched for original, peer-reviewed research; PubMed (MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo., Results: In 92% of the included studies (n = 77), opioid stewardship interventions led by either a pharmacist or in an interdisciplinary team resulted in improvements in at least one outcome measure, with education and medication therapy adjustments being the most predominant activities. Other areas supported by evidence include community stakeholder education, policy and guideline setting, and risk assessment., Conclusion: This scoping review provides valuable insight into the various roles pharmacists can have in opioid stewardship. The findings from this review identified opioid stewardship activities that can make significant contributions towards reducing the impact of the opioid crisis. This review informs future research and has the potential to influence pharmacy practice on a national and international scale., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The opioid crisis is a worldwide public health concern. In North America, evidence suggests that the increase in opioid prescriptions correlates with the observed increase in opioid-related mortality and morbidity. Pharmacists are in a strategic position to promote effective opioid stewardship as they have a central role on healthcare teams. However, in many contexts, pharmacists do not have a harmonized scope of practice and no standardized opioid stewardship approach has been implemented., Objectives: A scoping review will be conducted to identify and summarize evidence on the role of pharmacists in opioid stewardship and identify areas for future study., Methods: The scoping review will be conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases will be searched which include PubMed, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo., Project Impact: The findings of this review will identify opioid stewardship activities that can contribute towards reducing the impact of the opioid crisis. Additionally, it will provide foundational strategies to promote policy level change and foster a harmonized scope of practice. This review has the potential to inform future research, impact pharmacy practice, and drive policy change., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To examine acute and residual mood and cognitive performance in young adult regular cannabis users following smoked cannabis., Methods: Ninety-one healthy young adults completed this double-blind, placebo-controlled, parallel-groups study. Participants were randomized to receive active (12.5% THC) or placebo cannabis with a 2:1 allocation ratio, and mood [Profile of Mood States (POMS)] and cognitive performance [Hopkins Verbal Learning Test - Revised (HVLT-R), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), grooved pegboard (GPB)] were assessed before and 1, 24, and 48 (h) after smoking cannabis ad libitum. High and Low THC groups were based on blood THC concentrations., Results: One hour after smoking cannabis, compared to Placebo, in both the High and Low THC groups, there were increases in POMS Arousal and Positive Mood, and in the High THC group only, increases in Confusion, Friendliness, and Elation, and a decrease in Fatigue. Increases in Friendliness and Elation in the High THC group remained significant for 24 h. The only significant acute effect of cannabis on cognition was a decrease in the percent of words retained in the HVLT-R in the High THC group compared to Placebo (mean difference = 15.8%, 95% CI = 3.6-28.0%, p = 0.006). Unexpectedly, compared to Placebo, both the High and Low THC groups improved in DSST performance at 48 h (p ≤ 0.016)., Conclusions: Under the present experimental conditions, in young regular cannabis users, smoking cannabis ad libitum had significant effects on mood, some of which persisted 24 h later, yet minimal effects on cognition, and no evidence of residual cognitive impairment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users., Methods: In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 min and 24 and 48 h after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate., Results: Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 min after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures., Conclusion: Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Opioid use disorder is a major health concern in North America. Currently, buprenorphine is one of the most common pharmacological interventions used to treat opioid use disorder. Despite increasing prevalence of opioid use disorder among females, little is known about sex considerations in relation to treatment with buprenorphine., Methods: CINAHL, PsycINFO, EMBASE, PubMed/MEDLINE and Cochrane Central were searched for randomized controlled trials examining buprenorphine maintenance versus other medication-assisted treatment, placebo, or withdrawal management to determine if there were any sex differences in treatment outcomes reported., Results: This review included 25 studies and found that only 52% included information related to sex differences in treatment outcomes or discussed any sex considerations in their studies. Of the 6,466 patients represented by these studies, only 26% were female. Of the studies conducting sex-specific analyses, seven studies examined treatment retention, five examined opioid use, two examined other substance use and one examined sexual risk behaviours. However, due to mixed findings, small sample sizes, and inability to conduct meta-analyses, no conclusive statements can be made about sex differences in these outcomes. None of the studies described sex differences in quality of life, legal involvement or mental and physical health., Conclusions: Low numbers of females have been included in randomized controlled trials examining buprenorphine compared to males. While sex differences in treatment outcomes were identified in this review, further research is needed in order to add to these findings. Future studies should include greater numbers of female participants and conduct sex-specific analyses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To characterize prescription opioid dependent patients in a methadone maintenance treatment (MMT) program, a detailed retrospective chart review of new admissions (1997-1999, n=178, mean age=34.5+/-0.7 years, 65% male) was conducted. At admission most patients (83%) had been using prescription opioids (+/-heroin). Four groups were identified: 24% had used prescription opioids only; 24% used prescription opioids initially and heroin later; 35% used heroin first and prescription opioids subsequently; and 17% had used heroin only (this group was significantly younger: mean age 26+/-1 years, P=0.0001). Subjects reported regular use of prescription opioids at higher than therapeutic dosages. For example, in the 'prescription opioid only' group the reported mean (+/-S.E.) number of codeine or oxycodone-containing tablets consumed daily was 23 (+/-6) tablets and 21 (+/-3) tablets, respectively. There were no significant differences found amongst the groups in measures of social stability. Those dependent on prescription opioids alone were less likely to use illicit non-opioid drugs or to be associated with injection drug use. Those that used prescription opioids only or initially were more likely to have ongoing pain problems and to be involved in psychiatric treatment. Further research is required to better elucidate the complex relationships between pain, mental health and addiction in order to develop optimal prevention and treatment strategies for prescription opioid dependence.

Previous reports have identified adrenal insufficiency in groups of patients with active pulmonary tuberculosis. To investigate this possibility, serum cortisol levels were measured in consecutive patients admitted to the hospital for investigation of active tuberculosis. Blood was drawn for cortisol determination promptly at the time of hospital admission, in the morning and afternoon before commencing chemotherapy for the suspected tuberculosis, and before the diagnosis was confirmed. Thirty-seven patients were assessed; 19 of these patients were subsequently proven to have active pulmonary tuberculosis, six had pulmonary disease caused by mycobacteria other than tuberculosis, and 12 had radiologic appearance indicating tuberculosis, accompanied by a significant tuberculin skin reaction but with negative sputum cultures and no change in roentgenographic appearance during the course of treatment. In evaluating the adrenocortical function, the morning and afternoon serum cortisol level was measured and the diurnal change in serum cortisol level (the difference between afternoon and morning levels) was calculated. There was no association of either morning cortisol levels or diurnal change in cortisol levels with age, gender, or race. There was no difference among the three groups in either cortisol determination. Although difference in morning cortisol levels between those with extensive as compared with limited disease was not statistically significant (p = 0.349 from analysis of variance), there was a significantly decreased diurnal change in cortisol levels in those with extensive disease as compared with those with limited disease (+2.7 +/- 188.3 vs -259.1 +/- 177.1). We conclude that patients in our hospital with active pulmonary tuberculosis do not exhibit decreased adrenocortical function as compared with groups of patients without active pulmonary tuberculosis.

Two patients with progressive sarcoidosis who had poor responses and side effects from corticosteroid therapy were treated with cyclosporine. Cyclosporine suppressed conventional markers of inflammation and there was clinical improvement in one patient, but the disease recurred when therapy was discontinued. The second patient who had diabetes mellitus developed unstable glucose metabolism when given cyclosporine. This unstable diabetes mellitus together with side effects of nausea and vomiting resulted in weight loss and inadequate serum therapeutic levels that was associated with a poor therapeutic response to the cyclosporine. The major side effects in both patients were headache and gastrointestinal symptoms, but there was no renal dysfunction. We conclude that while corticosteroids remain the mainstay of sarcoid therapy, when these drugs have not been successful for the skin manifestations of the disease, a trial of cyclosporine may be justified.

Regional residual volume to total lung capacity (RVr/TLCr) was measured with xenon 133 before and after methacholine challenge in 26 nonsmoking subjects (mean age 34 years). Eleven were normal control subjects and 15 were patients referred for methacholine challenge because of previous asthma-like symptoms. All had normal pulmonary function and normal RVr/TLCr distribution. Following methacholine challenge, RVr/TLCr increased in two control subjects and ten patients who also had decreases in FEV1 of greater than 20 percent. The RVr/TLCr changes were patchy, suggesting that the degree of bronchospasm varied between individual lung regions. The other 14 subjects did not have a 20 percent decrease in FEV1, but two controls and four patients had generalized increases in RVr/TLCr, while seven controls and one patient had no significant changes in RVr/TLCr. In all subjects, FEV1 and RVr/TLCr returned to the baseline level after salbutamol administration. The results indicate that methacholine can cause localized or diffuse effects on lung emptying and that bronchodilator completely reverses the bronchoconstriction induced by methacholine.

Clinical deterioration with features suggestive of asthma was seen in three patients following two to six months of drug therapy of primary tuberculosis. There was a poor clinical response to administered bronchodilators. Bronchoscopy in all three revealed culture-negative mycobacterial caseating granulomas. Corticosteroid therapy resulted in good clinical response, with resolution of the asthmatic symptoms and improvement in the expiratory flow rates. In our opinion these patients are clinically compatible with a hypersensitivity response to mycobacteria following antituberculosis therapy and release of tuberculosis antigens. Corticosteroid therapy is appropriate in this form of tuberculous disease.

A 24-year-old male with recurrent hemoptysis due to idiopathic pulmonary hemosiderosis and celiac sprue developed infranodal heart block necessitating implantation of a pacemaker. A possible common underlying mechanism is discussed.

An intraluminal carcinoid tumor obstructing the left mainstem bronchus produced hypoxemia through alteration in ventilation/perfusion matching. Studies of regional lung function using 133-xenon (133Xe) and a multiprobe computerized instrumentation system documented a reduction of perfusion to 22 percent and ventilation to 6 percent of the total. There was negligible washout of intravenously injected 133Xe from the left lung consistent with air trapping. Four days after left mainstem bronchial sleeve resection, perfusion, ventilation and washout of injected xenon had significantly improved and by four months postresection, all measurements were virtually normal, although complete restoration of perfusion in relation to ventilation was delayed. Regional lung function studied with a multiprobe system in this patient provided a clinical model for the study of ventilation and perfusion inter-relationships in large airway obstruction and demonstrated that a prolonged time may be required for return of perfusion to normal.

To evaluate the efficacy of a mild anxiolytic, alprazolam, in relieving dyspnea, we conducted a randomized, placebo-controlled double-blind study on patients with chronic obstructive lung disease. Twenty-four patients had alprazolam (0.5 mg bid) or placebo administered for one week, followed by placebo for one week, then either placebo or alprazolam for the third week. Assessment tests were performed at the outset, end of the first and second weeks, and finally end of the third week. The parameters measured were: pulmonary function, exercise testing on a bicycle ergometer, and the distance covered in a 12 minute walk. Subjective sensations of dyspnea at rest and during guarded exercise, as well as subjective feelings of calmness or anxiety were also recorded. There was no difference in mechanical lung function, but the PO2 tended to decrease and PCO2 to increase after alprazolam administration. The maximum exercise level attained and the distance covered in the 12 minute walk was unchanged. The subjective perception of dyspnea was the same before and after alprazolam, at rest and during exercise. We conclude that alprazolam is not effective in relieving exercise dyspnea in patients with obstructive lung disease.

Hypothalamic-pituitary-adrenal function in a well-defined, carefully selected group of 25 patients with extrinsic asthma was assessed by measuring plasma levels of adrenocorticotropic hormone (ACTH) and of 11-deoxycorticol after administration of metyrapone and by measuring the level of cortisol following stimulation with cosyntropin. No difference was demonstrated between asthmatic subjects and 20 normal age-matched controls. In addition, neither the response of the level of ACTH nor of 11-deoxycortisol correlated with the duration of asthma or the severity as assessed in 23 patients by tests of pulmonary function. We conclude that there is no abnormality in hypothalamic-pituitary-adrenal function in patients with extrinsic asthma, and we suggest that previous data suggesting such an abnormality may reflect heterogeneous groups of patients, inaccurate methods, and the variability of normal responses to ACTH and stimulation with metyrapone.