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Objective: As medical cannabis use increases in North America, establishing the safety profile of cannabis is a priority. The objective of this study was to assess rates of emergency department (ED) visits and hospitalizations due to poisoning by cannabis and cannabis-related mental health disorders among medically authorized cannabis patients in Ontario, Canada, between 2014 and 2017.Methods: This is a retrospective longitudinal study conducted among a cohort of patients who received an authorization to use cannabis for treating various health conditions in Ontario, Canada. The cannabis cohort was selected using data collected in participating Canadian cannabis clinics. Outcomes included: ED visit/hospitalization with a main diagnosis code for cannabis/cannabinoid poisoning; and ED visit/hospitalization with a main diagnosis code for mental/behavioural disorders due to cannabis use. The Spearman correlation and univariate Cox proportional hazard regression was utilized.Results: From 29153 patients who received medical authorization, 23091 satisfied the inclusion criteria. During a median follow-up of 240 days, 14 patients visited the ED or were hospitalized for cannabis poisoning – with an incidence rate of 8.06 per 10,000 person-years patients (95%CI: 4.8-13.6). A total of 26 patients visited the ED or were hospitalized for mental and behavioural disorders due to cannabis use- with an incidence rate of 15.0 per 10,000 person-years (95%CI: 10.2-22.0). Predictors of cannabis-related mental and behavioural disorders include prior substance use disorders (drugs and alcohol), other mental disorders, age, diabetes, and chronic obstructive pulmonary disease. Conclusions: The results suggest that the incidence of cannabis poisoning or cannabis-related mental and behavioural disorders was low among patients who were authorized to use cannabis to treat a health condition. Identified predictors can help to target patients with potential risk of the studied outcomes.

PURPOSE OF REVIEW An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms. Canadians have a legal framework for access to medical cannabis, which provides a unique perspective in a setting lacking robust clinical evidence. This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice. RECENT FINDINGS A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids, over 3 weeks, demonstrated improved average pain score. A large observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use, whereas the number of patients reporting good quality of life increased. SUMMARY Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management. However, there are relatively weak data pointing to clinical efficacy from clinical trial data to date. In Canada, the burgeoning cannabis industry has driven the population to embrace a medicine before clinical evidence. There remains a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis, compared with placebo and standard treatments for cancer-related symptoms.

Study Objective To identify predictive factors for opioid consumption following hysterectomy by determining the relationship between perioperative opioid requirements, preoperative pelvic pain scores and patient variables. Design A prospective cohort study. Setting Canadian tertiary care academic center. Patients or Participants The study included 191 women undergoing hysterectomy. Interventions Preoperatively, all patients completed the Pain Sensitivity Questionnaire (PSQ), Pain Catastrophizing Scale and the Numeric Rating Scale (NRS). Cumulative opioid consumption (COC), calculated in oral morphine equivalents (OME), was the sum of opioid consumption recorded during three time periods; (i) intraoperatively, (ii) recovery room, and (iii) first 24 hours postoperatively. Measurements and Main Results 191 women underwent hysterectomy, 68 vaginal (36%), 91 laparoscopic assisted (48%), and 32 open (17%). The mean age and body mass index were 50 (27–77) and 27 (17-64) kg/m2, respectively. Most hysterectomies (138, 73%) were performed in premenopausal women. The majority of all hysterectomies were for benign indications (166, 87%), and 40 (21%) were pain-related. Median COC for all hysterectomies was 75 mg OME, and median 24h postoperative COC was 16 mg OME. In multivariate analysis, preoperative NRS scores, PSQ minor scores, preoperative use of pain medication and an open approach were found to be significant predictors of increased COC. Each additional point on the PSQ minor mean score and preoperative NRS score was found to be associated with an increase of 4 and 2.5 mg OME, respectively. Patients with open hysterectomy consumed 59.75 mg OME more than minimally invasive surgery patients, when all other factors were equal. Each additional preoperative pain medication was associated with a 9 mg OME increase. Conclusion Predictors of cumulative postoperative opioid requirements for hysterectomy include preoperative NRS scores, PSQ minor scores, number of preoperative pain medications, and surgical approach. This information can be used to create a predictive calculator to individualize perioperative interventions, optimize postoperative pain management, and tailor opioid use.

Background. Patient decision aids (PtDAs) supplement advice from health care professionals by communicating the absolute risk or benefit of treatment options (i.e., X/100). As such, PtDAs have been amenable to binary outcomes only. We aimed to develop and test the validity of the Conversion to Risk Estimates through Application of Normal Theory (CREATE) method for estimating absolute risk based on continuous outcome data. Methods. CREATE is designed to derive an estimate of the proportion of those who experience a clinically relevant degree of change (CRDoC). We used a 2-stage validation process using real and simulated change score data, respectively. First, using raw data from published intervention trials, we calculated the proportion of patients with a CRDoC and compared that with our CREATE-derived estimate using chi-square tests of association. Second, 200,000 simulated distributions of change scores were generated with widely varying distribution characteristics. Actual and CREATE-derived estimates were compared for each simulated distribution, and relative differences were summarized graphically. Results. The absolute difference between the estimated and actual CRDoC did not exceed 5% for any of the samples based on real data. Applying the CREATE method to 200,000 simulated scenarios demonstrated that the CREATE method should be avoided for outcomes where the underlying distribution can be reasonably assumed to have high levels of skew or kurtosis. Conclusion. Our results suggest that standard statistical theory can be used to estimate continuous outcomes in absolute terms with reasonable accuracy for use in PtDAs; caution is advised if outcome summary statistics are assumed to have been derived from highly skewed distributions.

When August Wilson's play Ma Rainey's Black Bottom debuted in New York's Cort Theatre in the fall of 1984, it was received rather coolly by the critics, but quite warmly by its audiences. Early critical reception pigeonholed the work as an overdone piece on the problems of race in America. John Simon, the reviewer for New York magazine, wrote that what Wilson delivers in the work "is only intermittently drama, more often rousing monologues, and finally more melodramatically didactic than imaginatively satisfying." Simon concluded that, for all its strengths, the play "sorely misses the transformative spark" — he wished the playwright "[b]etter luck next time". Edwin Wilson, writing for The Wall Street Journal, observed that "There is an abundance of atmosphere and banter, and a strong racial statement, but not much of a play." After summarizing the plot, he proclaimed that "The theme of the play is racial injustice" and explained how that theme is executed; but he, like Simon, concluded that "polemics do not make a play". In its 17 October issue, Variety magazine introduced Ma Rainey's Black Bottom as yet another "tragedy of racial bigotry," and suggested that "its technical clumsiness and downbeat story make it a difficult Broadway box office proposition". Such hasty dismissals of Wilson's first Broadway production proved to be shallow and obtuse, as word-of-mouth raves generated a high volume of ticket sales and turned Ma Rainey into "the first hit of the season." The critics took a second look at Wilson and "his powerful play," which according to The New York Times was "reawakening audiences to the wonder and dimensions of drama". The production went on to be nominated for three Tony awards, including one for best play, and it won the New York Drama Critics Circle Award for Best Play of the 1984-85 season.

The Photofrin-resistant cell line (HT29-P14) was used in the present study to investigate the mechanism(s) involved in Photofrin-mediated photodynamic therapy (PDT). We compared gene expression profiles between the resistant cell line and its parental cell line (HT29) using DNA microarray analysis. A significant up-regulation of small heat shock protein 27 (Hsp27) was found in HT29-P14 cells. The elevated Hsp27 level may play an important role in the resistance of HT29-P14 to Photofrin-PDT. To test this hypothesis, we stably transfected HT29 cells with human Hsp27 complementary DNA. The potential role of Hsp27 in the resistance to PDT was examined in Hsp27-overexpressing cells. Stable trasnfected cells (H13) showed an increased survival after Photofrin-PDT, suggesting that the up-regulation of Hsp27 is related to the induced resistance to Photofrin-PDT. Phosphorylation of Hsp27 has been suggested to play an important role in cytoprotection. We have examined the phosphorylation activity of Hsp27 among the parental and resistant cells, as well as the overexpression cells. An elevated level of Hsp27 resulted in an increased ability of phosphorylation in both resistant and overexpressing cells after PDT. The activation of the phosphorylation of Hsp27 induced by PDT was not mediated by the p38 mitogen-activated protein kinase. These data suggest that Hsp27 may play an important role in mediating the adaptive response to Photofrin-PDT-induced oxidative stress and that the pathways leading to Hsp27 phosphorylation may contribute to the resistance of the cells to photooxidative damage.

Aurora is a short-pulse high-power krypton-fluoride laser system that serves as an end-to-end technology demonstration prototype for large-scale ultraviolet laser systems of interest for short wavelength inertial confinement fusion (ICF) studies. The system is designed to employ optical angular multiplexing and serial amplification by electron-beam-driven KrF laser amplifiers to deliver 248 nm, 5-ns duration multi-kilojoule laser pulses to ICF targets using a beam train of approximately 1 km in length.In this paper, we will discuss the goals for the system and summarize the design features of the major system components: front-end lasers, amplifier train, optical train, and the alignment and controls systems.

Background Refractory angina is a severe chronic disease, defined as angina which cannot be controlled by usual treatments for heart disease. This disease is frightening, debilitating, and difficult to manage. Many people suffering refractory have inadequate pain relief, continually revisit emergency departments for help, undergo repeated cardiac investigations, and struggle with obtaining appropriate care. There is no clear framework to help people understand the risks and benefits of available treatment options in Canada. Some treatments for refractory angina are invasive, while others are not covered by provincial health insurance plans. Effective care for refractory angina sufferers in Canada is critically underdeveloped; it is important that healthcare professionals and refractory angina sufferers alike understand the treatment options and their implications. This proposal builds on the recent Canadian practice guidelines for the management of refractory angina. We propose to develop a decision support tool in order to help people suffering from refractory angina make well-informed decisions about their healthcare and reduce their uncertainty about treatment options. Methods This project will be conducted in three phases: a) development of the support tool with input from clinical experts, the Canadian refractory angina guidelines, and people living with refractory angina, b) pilot testing of the usability of the tool, and c) formal preliminary evaluation of the effectiveness of the support tool to help people make informed decisions about treatment options. Discussion A decision support tool for refractory angina is needed and the available data suggest that by developing such a tool, we may be able to help refractory angina sufferers better understand their condition and the effectiveness of available treatment options (in their respective clinical settings) as well as their implications (e.g. risks vs. benefits). By virtue of this tool, we may also be able to facilitate identification and inclusion of patients’ values and preferences in the decision making process. This is particularly important as refractory angina is an intractable condition, necessitating that the selected course of treatment be lifelong. This study will yield a much needed patient decision aid for people living with refractory angina and pilot data to support a subsequent effectiveness study.