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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.

Objectives Poisoning from psychoactive drugs and substance use disorders (SUD) have been reported among non-medical cannabis users. However, little is known about medical cannabis users and their risk for poisoning and/or development of SUD. This study assessed the risk of emergency department (ED) visits or hospitalization for 1) poisoning by psychoactive drugs and 2) mental/behavioural disorders due to the use of psychoactive drugs and other substances, in medically authorized cannabis patients in Ontario, Canada from 2014–2017. Methods A cohort study of adult patients authorized for medical cannabis that were matched to population-based controls. ED visit/hospitalization were assessed with a main diagnostic code for: 1) poisoning by psychoactive drugs; 2) mental and behavioural disorder due to psychoactive drugs or other substance use. Conditional Cox proportional hazards regressions were conducted. Results 18,653 cannabis patients were matched to 51,243 controls. During a median follow-up of 243 days, the incidence rate for poisoning was 4.71 per 1,000 person-years (95%CI: 3.71–5.99) for cases and 1.73 per 1,000 person-years (95% CI: 1.36–2.19) for controls. The adjusted hazard ratio (aHR) was 2.45 (95%CI: 1.56–3.84). For mental/behavioural disorders, the incident rates were 8.89 (95% CI: 7.47–10.57) and 5.01 (95% CI: 4.36–5.76) in the cannabis and the controls group. The aHR was 2.27 (95%CI: 1.66–3.11). No difference was observed between males and females ( P-value for interaction > 0.05). Conclusions Our study observed a short-term increased risk of ED visit/hospitalization for poisoning or for mental/behavioural disorders (from use of psychoactive drugs and other substances)- in medically authorized cannabis patients.

Background The opioid overdose epidemic in Canada and the United States has become a public health crisis - with exponential increases in opioid-related morbidity and mortality. Recently, there has been an increasing body of evidence focusing on the opioid-sparing effects of medical cannabis use (reduction of opioid use and reliance), and medical cannabis as a potential alternative treatment for chronic pain. The objective of this study is to assess the effect of medical cannabis authorization on opioid use (oral morphine equivalent; OME) between 2013 and 2018 in Alberta, Canada. Methods All adult patients defined as chronic opioid users who were authorized medical cannabis by their health care provider in Alberta, Canada from 2013 to 2018 were propensity score matched to non-authorized chronic opioid using controls. A total of 5373 medical cannabis patients were matched to controls, who were all chronic opioid users. The change in the weekly average OME of opioid drugs for medical cannabis patients relative to controls was measured. Interrupted time series (ITS) analyses was used to assess the trend change in OME during the 26 weeks (6 months) before and 52 weeks (1 year) after the authorization of medical cannabis among adult chronic opioid users. Results Average age was 52 years and 54% were female. Patients on low dose opioids ( 100), showed a significant decrease over 6 months (− 435.5, 95% CI: − 596.8 to − 274.2) compared to controls. Conclusions This short-term study found that medical cannabis authorization showed intermediate effects on opioid use, which was dependent on initial opioid use. Greater observations of changes in OME appear to be in those patients who were on a high dosage of opioids (OME > 100); however, continued surveillance of patients utilizing both opioids and medical cannabis is warranted by clinicians to understand the long-term potential benefits and any harms of ongoing use.

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.

Background: Despite the same surgical approach, up to 40% of patients develop chronic postsurgical pain (CPSP) following cardiac surgery, whereas the rest are chronic pain free. This variability suggests that CPSP is controlled partially through genetics, but the genes for CPSP are largely unknown. Aims: The aim of this study was to identify potential CPSP phenotypes by comparing patients who developed CPSP following cardiac surgery vs. those who did not. Methods: A research ethics board–approved, cross-sectional study of post–cardiac surgery pain was conducted at Toronto General Hospital from 2011 to 2015. Patients were recruited to complete a short survey of chronic pain scores and the Short-Form McGill Pain Questionnaire–2. A subset of patients completed a longer survey of eight validated pain phenotyping questionnaires and/or four psychophysical assessments. All surveys and psychophysical testing were conducted after surgery. Patients were stratified by presence of chronic pain and groups were compared using descriptive statistics. Results: Six hundred forty-three patients completed the short form survey. The mean postsurgery assessment time was 41.5 (SD = ±25.1) months. Over a quarter (27.8%) reported CPSP at the chest as a consequence of their surgery. Of patients reporting CPSP, 46.6% reported mild pain (0–3), 35.8% reported moderate pain (4–7), and 17.6% reported severe pain (7–10) in accordance with the numerical rating scale. Patients with moderate and/or severe CPSP were younger, had a greater body mass index, and had higher anxiety sensitivity, pain catastrophizing, and somatization scores. Conclusions: Chronic pain levels after cardiac surgery are associated with anxiety, catastrophizing, and sensory abnormalities in body parts outside the field innervated by injured nerves, indicating the presence of widespread central sensitization to incoming sensory inputs from intact nerves.

Objectives Despite increasing rates of legalization of medical cannabis worldwide, the current evidence available on its effect on mental health outcomes including anxiety is of mixed results. This study assesses the effect of medical cannabis on generalized anxiety disorder 7-item (GAD-7) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada. Methods An observational cohort study of adults authorized to use medical cannabis. The GAD-7 was administered at the time of the first visit to the clinic and subsequently over the follow-up time period of up to 3.2 years. Overall changes in GAD-7 scores were computed (mean change) and categorized as: no change (Results A total of 37,303 patients had initial GAD-7 scores recorded and 5,075 (13.6%) patients had subsequent GAD-7 follow-up scores. The average age was 54.2 years (SD 15.7 years), 46.0% were male, and 45.6% noted anxiety symptoms at the baseline. Average GAD-7 scores were 9.11 (SD 6.6) at the baseline and after an average of 282 days of follow-up (SD 264) the average final GAD-7 score recorded was 9.04 (SD 6.6): mean change −0.23 (95% CI, −0.28 to −0.17, t[5,074]: −8.19, p-value Conclusions Overall, there was a statistically significant decrease in GAD-7 scores over time (in particular, in the 6–12-month period). However, this change did not meet the threshold to be considered clinically significant. Thus, we did not detect clinical improvements or detriment in GAD-7 scores in medically authorized cannabis patients. However, future well-controlled clinical trials are needed to fully examine risks or benefits associated with using medical cannabis to treat anxiety conditions.

Summary Until recently, the belief that adequate pain management was not achievable while patients remained on buprenorphine was the impetus for the perioperative discontinuation of buprenorphine. We aimed to use an expert consensus Delphi-based survey technique to 1) specify the need for perioperative guidelines in this context and 2) offer a set of recommendations for the perioperative management of these patients. The major recommendation of this practice advisory is to continue buprenorphine therapy in the perioperative period. It is rarely appropriate to reduce the buprenorphine dose irrespective of indication or formulation. If analgesia is inadequate after optimisation of adjunct analgesic therapies, we recommend initiating a full mu agonist while continuing buprenorphine at some dose. The panel believes that before operation, physicians must distinguish between buprenorphine use for chronic pain (weaning/conversion from long-term high-dose opioids) and opioid use disorder (OUD) as the primary indication for buprenorphine therapy. Patients should ideally be discharged on buprenorphine, although not necessarily at their preoperative dose. Depending on analgesic requirements, they may be discharged on a full mu agonist. Overall, long-term buprenorphine treatment retention and harm reduction must be considered during the perioperative period when OUD is a primary diagnosis. The authors recognise that inter-patient variability will require some individualisation of clinical practice advisories. Clinical practice advisories are largely based on lower classes of evidence (level 4, level 5). Further research is required in order to implement meaningful changes in practitioner behaviour for this patient group.

Study Objective To determine sociodemographic, surgical, and psychologic risk factors, including pain sensitivity, for persistent postsurgical pain (PPSP) after hysterectomy. Design A prospective cohort study. Setting Canadian academic medical center. Patients Patients (N = 200) who underwent hysterectomy (vaginal, laparoscopic, robotic, or open) between 2013 and 2014. Interventions Participants completed preoperative questionnaires assessing baseline pain scores and psychologic factors, including the Pain Sensitivity Questionnaire, Brief Pain Inventory Interference Items, the Beck Depression Inventory, the Numeric Rating Scale (NRS), and the Pain Catastrophizing Scale. Pain was recorded 1 and 24 hours postoperatively using the NRS. Patients were reassessed at 6 weeks postoperatively and completed the Brief Pain Inventory Interference Items, Patient Global Impression of Change, and the NRS. Patients who reported pain at 6 weeks were reassessed at 12 weeks using the above-mentioned questionnaires. Measurements and Main Results Of 200 study participants, 58 (32%) met the definition for PPSP (NRS ≥ 1 at 12 weeks), and 11 (6.1%) met the definition for moderate to severe postsurgical pain (NRS ≥ 4 at 12 weeks). Risk factors for PPSP included baseline pain scores, depression, pain catastrophizing, uterine mass, open surgical approach, acute postoperative pain, history of chronic pain, and having a hysterectomy due to pain. Multivariate regression analysis revealed that depression, pain catastrophizing, open surgical approach, and acute postoperative pain at 1 hour represent independent predictors of PPSP. Pain sensitivity was not associated with PPSP but was associated with acute and severe acute (NRS≥4) pain at 24 hours. Conclusion Patients at risk for PPSP after hysterectomy can be identified preoperatively using validated questionnaires. This information can be used to guide targeted perioperative interventions to mitigate their risk.

Background: The opioid overdose epidemic in Canada and the United States has become a public health crisis - with exponential increases in opioid-related morbidity and mortality. Recently, there has been an increasing body of evidence focusing on the opioid-sparing effects of medical cannabis use (reduction of opioid use and reliance), and medical cannabis as a potential alternative treatment for chronic pain. The objective of this study is to assess the effect of medical cannabis authorization on opioid use (oral morphine equivalent; OME) between 2013-2018 in Alberta, Canada.Methods: All adult patients defined as chronic opioid users who received medical cannabis authorization in the province of Alberta from 2013-2018 were propensity score matched to non-authorized chronic opioid using controls. 5373 medical cannabis patients were matched to controls, who were all chronic opioid users. The change in the weekly average OME of opioid drugs for medical cannabis patients relative to controls was measured. Interrupted time series (ITS) analyses was used to assess the trend change in OME during the 26 weeks (6 months) before and 52 weeks (1 year) after the authorization of medical cannabis among adult chronic opioid users.Results: Average age was 52 years and 54% were female. Patients on low dose opioids (100), showed a significant decrease over 6 months (-435.5, 95% CI: -596.8 to -274.2) compared to controls. Conclusions: This short-term study found that medical cannabis authorization showed intermediate effects on opioid utilization, which was dependent on initial opioid use. Greater observations of changes in OME appear to be in those patients who were on a high dosage of opioids (OME>100); however, continued surveillance of patients utilizing both opioids and medical cannabis – is warranted by clinicians to understand the long-term potential benefits and any harms of ongoing use.

Background With increasing numbers of countries/jurisdictions legalizing cannabis, cannabis impaired driving has become a serious public health concern. Despite substantive research linking cannabis use with higher rates of motor vehicle crashes (MVC), there is an absence of conclusive evidence linking MVC risk with medical cannabis use. In fact, there is no clear understanding of the impact of medical cannabis use on short- and long-term motor vehicle-related healthcare visits. This study assesses the impact of medical cannabis authorization on motor vehicle-related health utilization visits (hospitalizations, ambulatory care, emergency department visits, etc) between 2014 and 2017 in Ontario, Canada. Methods A matched cohort study was conducted on patients authorized to use medical cannabis and controls who did not receive authorization for medical cannabis – in Ontario, Canada. Overall, 29,153 adult patients were identified and subsequently linked to the administrative databases of the Ontario Ministry of Health, providing up to at least 6 months of longitudinal follow-up data following the initial medical cannabis consultation. Interrupted time series analyses was conducted to evaluate the change in rates of healthcare utilization as a result of MVC 6 months before and 6 months after medical cannabis authorization. Results Over the 6-month follow-up period, MVC-related visits in medical cannabis patients were 0.50 visits/10000 patients (p = 0.61) and − 0.31 visits/10000 patients (p = 0.64) for MVC-related visits in controls. Overall, authorization for medical cannabis was associated with an immediate decrease in MVC-related visits of − 2.42 visits/10000 patients (p = 0.014) followed by a statistically significant increased rate of MVC-related visits (+ 0.89 events/10,000 in those authorized medical cannabis) relative to controls in the period following their authorization(p = 0.0019). Overall, after accounting for both the immediate and trend effects, authorization for medical cannabis was associated with an increase of 2.92 events/10,000 (95%CI 0.64 to 5.19) over the entire follow-up period. This effect was largely driven by MVC-related emergency department visits (+ 0.80 events/10,000, p Conclusions Overall, there was an association between medical cannabis authorization and healthcare utilization, at the population level, in Ontario, Canada. These findings have public health importance and patients and clinicians should be fully educated on the potential risks. Continued follow-up of medically authorized cannabis patients is warranted to fully comprehend long-term impact on motor vehicle crash risk.

An increasing number of patients with opioid use disorder (OUD) are treated with opioid agonist-antagonists such as buprenorphine/naloxone. Perioperative management of patients on buprenorphine/naloxone is inconsistent and remains a controversial topic with mismanagement posing a significant risk to the long-term health of these patients. We performed a systematic literature search involving Medline, Medline In-Process, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science (Clarivate), Scopus (Elsevier), CINAHL (EbscoHosst), and PubMed (NLM). Eighteen studies were included in the final sample, including one controlled study and four observational studies . Neither the controlled study nor the observational studies assessed addiction treatment retention, harm reduction, or long-term mortality rates as primary or secondary outcomes. Of the observational studies, authors showed equivalent peri- and postoperative pain control among buprenorphine continued patients. All but one authors described adequate analgesia among the case reports in which buprenorphine ≤ 16 mg sublingually (SL) daily was continued during the perioperative period. Long-term harm reduction was not reported with only three case reports including any long-term abstinence or relapse rates. The current understanding of the risks and benefits of continuing or stopping buprenorphine perioperatively is limited by a lack of high-quality evidence. Observational studies and case reports indicate no evidence against continuing buprenorphine perioperatively, especially when the dose is < 16 mg SL daily. In patients with significant potential for relapse, such as those with a recent history of OUD, the discontinuation of buprenorphine should have a strong rationale supported by patient and surgical preferences. Future studies require standardized reporting of median doses, details on the route of delivery, dosing schedules and any dosing changes, and rates of addiction relapse, including long-term morbidity and mortality where possible.

As countries progressively embrace the legalization of both medicinal and recreational cannabis, there remains a significant knowledge gap when it comes to the perioperative uses of cannabis, as well as the management of cannabis users. This review summarizes the information available on the subject based on existing published studies. Articles outlining the physiological changes occurring in the human body during acute and chronic use of cannabis (outside the context of anesthesia) are also taken into consideration as understanding these changes allows a more calculated approach to better anticipate patients' needs in the perioperative setting. Common questions facing the anesthesiologist at each phase of the perioperative period will be addressed and a systematic approach to the effect of cannabinoids on various organ systems will also be presented. Issues unique to cannabis use such as cannabis withdrawal syndrome and alterations in post-operative pain processing will also be discussed. To date, the number of studies available for guidance is small and study designs are markedly heterogenous, if not limited, making conclusions challenging. While the currently available information can assist in making decisions, further studies of larger scale are eagerly anticipated to help guide future patient care.

IntroductionThe ongoing opioid epidemic has necessitated increasing prescriptions of buprenorphine, which is an evidence-based treatment for opioid use disorder, and also shown to reduce harms associated with unsafe opioid administration. A systematic review of perioperative management strategies for patients taking buprenorphine concluded that there was little guidance for managing buprenorphine perioperatively. The aim of this project is to develop consensus guidelines on the optimal perioperative management strategies for this group of patients. In this paper, we present the design for a modified Delphi technique that will be used to gain consensus among patients and multidisciplinary experts in addiction, pain, community and perioperative medicine.Methods and analysisA national panel of experts identified by perioperative, pain and/or addiction systematic review authorship established an international profile in perioperative, pain and/or addiction research, community clinical excellence and by peer referral. A steering group will develop the first round with a list of indications to be rated by the panel of national experts, patients and allied healthcare professionals. In round 1, the expert panel will rate the appropriateness of each individual item and provide additional suggestions for revisions, additions or deletions. The definition of consensus will be seta priori. Consensus will be gauged for both appropriateness and inappropriateness of treatment strategies. Where an agreement is not reached and items are suggested for addition/deletion/modification, round 2 will take place over teleconference in order to obtain consensus.Ethics and disseminationInstitutional research ethics board provided a waiver for this modified Delphi protocol. We plan on developing a national guideline for the management of patients taking buprenorphine in the perioperative period that will be generalisable across three sets of preoperative diagnoses including opioid use disorder and/or co-occurring pain disorders. The findings will be published in peer-reviewed publications and conference presentations.

The purpose of this study is to examine the relationship between immediate post-surgical flap position and subsequent probing depth measurements following osseous surgery.Twenty-four patients treatment planned for osseous surgery after completion of initial therapy and re-evaluation were enrolled. Pressure molded stents were fabricated to serve as a reference for probing depth and relative attachment level measurements prior to surgery. After osseous recontouring was completed, flaps were sutured and compressed, and bone sounding measurements were made as designated by the stent. Patients returned at 3- and 6 months for repeat measurements of probing depth and attachment level.Twenty-four patients completed surgical treatment and follow-up measurements with a total of 402 treated sites. A statistically significant moderate correlation between immediate post-surgical bone sounding measurements and subsequent probing depth was found at 6 months (R = 0.56, P 0.001). There was no significant difference between this correlation at 3 and 6 months. The probability of having 6 month probing depth ≤3 mm was 93.5% when the surgical flap was placed within 3 mm of the alveolar crest (286/306 sites) as opposed to 50% when the surgical flap was3 mm away from the alveolar crest (48/96 sites). Interproximal sites were significantly more likely (P 0.01) to have probing depths 3 mm at 3 and 6 months.Results suggest a statistically significant relationship between immediate post-surgical flap placement and subsequent probing depths. Positioning the surgical flap more closely to the alveolar crest when performing osseous surgery resulted in shallower probing depths at 3 and 6 months.

BackgroundThe impact of medical cannabis on healthcare utilisation between 2014 and 2017 in Ontario, Canada. With cannabis legalisation in Canada and some states in the USA, high-quality longitudinal cohort research studies are of urgent need to assess the impact of cannabis use on healthcare utilisation.MethodsA matched cohort study of 9925 medical cannabis authorised adult patients (inhaled (smoked or vaporised) or orally consumed (oils)) at specialised cannabis clinics, and inclusion of 17 732 controls (not authorised) between 24 April 2014 and 31 March 2017 from Ontario, Canada. Interrupted time series and multivariate Poisson regression analyses were conducted. Medical cannabis impact on healthcare utilisation was measured over 6 months: all-cause physician visits, all-cause hospitalisation, ambulatory care sensitive conditions (ACSC)-related hospitalisations, all-cause emergency department (ED) visits and ACSC-related ED visits.ResultsFor medical cannabis patients compared with controls, there was an initial (within the first month) increase in physician visits (additional 4330 visits per 10 000 patients). However, a numerical reduction was noted over the 6-month follow-up, and no statistical difference was observed (p=0.126). Likewise, in hospitalisations and ACSC ED visits, there was an initial increase (44 per 10 000 people, pConclusionsAn initial increase (within first month) in healthcare utilisation may be expected among medical cannabis users that appears to wane over time. Proactive follow-up of patients using medical cannabis is warranted to minimise initial risks to patients and actively assess potential benefits/harms of ongoing use.

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.

Objectives To determine the relationship between persistent postsurgical pain following hysterectomy and preoperative pelvic pain scores and patient variables, to identify patients at higher risk of persistent postsurgical pain. Methods A prospective cohort study of 200 women undergoing hysterectomy at a tertiary care academic hospital was conducted. Preoperatively, all patients completed the Pain Sensitivity Questionnaire (PSQ), Brief Pain Inventory Interference Items (BPI-II) and the Numeric Rating Scale (NRS). Postoperatively, the NRS was used to record pain scores at 1 and 24 hours, 6 and 12 weeks. Opioid consumption over the first 24 hours was recorded. Results 200 women underwent hysterectomy (72 vaginal (36%), 92 laparoscopic assisted (46%) and 36 open (18%)). Mean age and BMI were 50 (27–77) and 27 (17–64) kg/m2, respectively. Most hysterectomies (144, 72%) were performed in premenopausal status for benign indications (175, 88%), 42 (24%) of which were pain-related. Pain at 24h significantly correlated with PSQ scores (r=0.21, p Conclusions Predictors of persistent postsurgical pain include preoperative pelvic pain and correlate significantly with PSQ and BPI-II scores. This information can be used to individualize perioperative interventions to minimize the risk of developing persistent postsurgical pain.

The purpose of this case report is to describe a patient with a preoperative complex pain syndrome who underwent liver transplantation and was able to reduce his opioid consumption significantly following the initiation of treatment with medical cannabis.A 57-yr-old male with a history of hepatitis C cirrhosis underwent liver transplantation. Preoperatively, he was taking hydromorphone 2-8 mg⋅day(-1) for chronic abdominal pain. Postoperatively, he was given intravenous patient-controlled analgesia through which he received hydromorphone 30 mg⋅day(-1). Our multidisciplinary Transitional Pain Service was involved with managing his moderate to severe acute postsurgical pain in hospital and continued with weaning him from opioid medications after discharge. It was difficult to wean the patient from opioids, and he was subsequently given medical cannabis at six weeks postoperatively with remarkable effect. By the fifth postoperative month, his use of opioids had tapered to 6 mg⋅day(-1) of hydromorphone, and his functional status was excellent on this regimen.Reductions in opioid consumption were achieved with the administration of medical cannabis in a patient with acute postoperative pain superimposed on a chronic pain syndrome and receiving high doses of opioids. Concurrent benefits of initiating medical cannabis may include improvements in pain profile and functional status along with reductions in opioid-related side effects. This highlights the potential for medical cannabis as an adjunct medication for weaning patients from 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.

Background and Objectives Chronic low back pain related to degenerative spondylosis is commonly managed by the radiofrequency ablation of sensory nerves. Fluoroscopic guidance has been considered mandatory to ensure placement of the active tip of the cannula parallel to the nerve to provide adequate neurolysis. Conversely, analgesic (or diagnostic) blockade is usually accomplished by placing the needle perpendicular to the nerve using either fluoroscopy or ultrasound (US) guidance. The recently introduced disposable equipment of internally cooled radiofrequency allows the denervation procedure to be performed similarly to the routine diagnostic block. Consequently, US may now potentially be used for image-guided radiofrequency neurotomy. We sought to compare the accuracy using a novel US-based technique with the traditional fluoroscopy-guided placement. Methods The proof of concept study was performed using a magnetic positioning US-guided system. The precision of needle placements was compared with the standard fluoroscopic guidance. The primary outcome of this study was defined as the procedural accuracy. Procedural and radiation exposure time was also recorded. In addition, projected operational expenses were calculated. Results Ultrasound-guided procedural accuracy reached 97%. Both the imaging and procedure times were similar between the 2 forms of imaging guidance. Of significant importance, the US-guided approach (no radiation exposure) was quantitatively advantageous over fluoroscopy-guidance, which required an average of 170 seconds of radiation per procedure. Thus, the US method seems to be cost effective. Conclusions A magnetic positioning system allows accurate and quick US-guided placement of radiofrequency cannula to the desired anatomical targets, sparing patients and personnel from exposure to ionized radiation.

Background and Objectives Intercostal nerve (ICN) injections are routinely performed under anatomic landmark or fluoroscopic guidance for acute and chronic pain indications. Ultrasound (US) is being used increasingly to perform ICN injections, but there is lack of evidence to support categorically the benefits of US over conventional techniques. We compared guidance with US versus anatomic landmarks for accuracy and safety of ICN injections in cadavers in a 2-phase study that included evaluation of deposition of injected dye by dissection and spread of contrast on fluoroscopy. Methods A cadaver experiment was performed to validate US as an imaging modality for ICN blocks. In the first phase of the study, 12 ICN injections with 2 different volumes of dye were performed in 1 cadaver using anatomic landmarks on one side and US-guidance on the other (6 injections on each side). The cadaver was then dissected to evaluate spread of the dye. The second phase of the study consisted of 74 ICN injections (37 US-guided and 37 using anatomic landmarks) of contrast dye in 6 non-embalmed cadavers followed by fluoroscopy to evaluate spread of the contrast dye. Results In the first phase of the study, the intercostal space was identified with US at all levels. Injection of 2 mL of dye was sufficient to ensure compete staining of the ICN for 5 of 6 US-guided injections but anatomic landmark guidance resulted in correct injection at only 2 of 6 intercostal spaces. No intravascular injection was found on dissection with either of the guidance techniques. In the second phase of the study, US-guidance was associated with a higher rate of intercostal spread of 1 mL of contrast dye on fluoroscopy compared with anatomic landmarks guidance (97% vs 70%; P = 0.017). Conclusions Ultrasound confers higher accuracy and allows use of lower volumes of injectate compared with anatomic landmarks as a guidance method for ICN injections in cadavers. Ultrasound may be a viable alternative to anatomic landmarks as a guidance method for ICN injections.

To compare the self-perceived sleepiness of Canadian anesthesia residents providing modified on-call duties (12-16 h) vs. traditional on-call duties (24 h).A 25-item online survey was distributed to all Canadian anesthesia residents who, at that time, were on anesthesia rotations. The survey assessed resident demographics, perceived work patterns, and sleepiness, as well as their opinions on resident work hour reform. Self-perceived sleepiness was quantified using the validated Epworth sleepiness scale (ESS).Three hundred eight of 400 (77%) eligible Canadian anesthesia residents completed the survey. Forty-three percent of residents who worked traditional on-call (duration 24.1 +/- 0.5 h) shifts and 48% of residents who worked modified on-call (duration 15.5 +/- 1.8 h) shifts met ESS criteria for excessive daytime sleepiness. Overall mean ESS scores did not differ significantly between the traditional (9.1 +/- 4.9) and the modified call groups (9.5 +/- 4.8). Residents with an on-call frequency ofor=1:4 days or those who sleptor=2 h while on call perceived themselves as significantly more sleepy (P = 0.045 and P = 0.008, respectively). Six percent of residents admitted to taking "something other than caffeine" to stay awake on call.Many anesthesia residents do exhibit excessive daytime sleepiness, with a similar incidence for those working within either modified or traditional call systems. Our study suggests that sleepiness may be reduced by scheduling on-call duties no more frequently than one in every five nights and by ensuring that residents sleep more than 2 h while on call.

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.

Media attention to celebrities during the 2004 U.S. presidential campaign was substantial. This article traces some of the more remarkable celebrity roles throughout the campaign. Through an account of journalistic experience, the authors provide evidence of the way celebrity spectacle dominated much of the campaign rhetoric in the 2004 election. Analysis of what to expect in the future suggests only increased attention to the role of celebrities in U.S. politics as the line between information and entertainment is blurred.

Our approach to examine the mechanism(s) of action for photodynamic therapy (PDT) has been via the generation of PDT-resistant cell lines. In this study we used three human cell lines, namely, human colon adenocarcinoma (HT29), human bladder carcinoma and human neuroblastoma. The three photosensitizers used were Photofrin, Nile Blue A and aluminum phthalocyanine tetrasulfonate. The protocol for inducing resistance consisted of repeated in vitro photodynamic treatments with a photosensitizer to the 1-10%-survival level followed by regrowth of single surviving colonies. Varying degrees of resistance were observed. The three induced variants of the HT29 cell line were the most extensively studied. Their ratios of increased survival at the LD90 level range between 1.5- and 2.62-fold more resistant.

Background— Homeless people represent an extremely disadvantaged group in North America. Among older homeless men, cardiovascular disease (CVD) is the leading cause of death. The objective of this study was to examine cardiovascular risk factors in a representative sample of homeless adults and identify opportunities for improved risk factor modification. Methods and Results— Homeless persons were randomly selected at shelters for single adults in Toronto. Response rate was 79%. Participants (n=202) underwent interviews, physical measurements, and blood sampling. The mean age of participants was 42 years, and 89% were men. The prevalence of smoking among homeless subjects (78%; 95% confidence interval [CI], 72% to 84%) was significantly higher than in the general population (standardized morbidity ratio [SMR], 254; 95% CI, 216 to 297). Hypertension, high cholesterol, and diabetes were not more prevalent than in the general population but were often poorly controlled. Homeless men were significantly less likely to be overweight or obese than men in the general population (SMR, 79; 95% CI, 63 to 98). Cocaine use in the last year was reported by 29% of subjects (95% CI, 23% to 36%). CVD was reported by 15% of subjects, fewer than one third of whom reported taking aspirin or cholesterol-lowering medication. According to multiple-risk-factor equations, the median estimated 10-year absolute risk of myocardial infarction or coronary death among homeless men aged 30 to 74 years was 5% (interquartile range, 3% to 9%). Conclusions— Cardiovascular risk factor modification is suboptimal among homeless adults in Toronto, despite universal health insurance. Multiple risk factor equations may underestimate true risk in this population because of inadequate accounting for factors such as cocaine use and heavy smoking.

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.

Background Chronic stable angina (CSA) has a major negative impact on health-related quality of life (HRQL) including poor general health status, psychological distress, and inability to self-manage. Methods We used meta-analysis to assess the effectiveness of self-management interventions for improving stable angina symptoms, HRQL and psychological well-being. Nine trials, involving 1,282 participants in total, were included. We used standard inverse-variance random-effects meta-analysis to combine the trials. Heterogeneity between trials was evaluated using chi-square tests for the tau-squared statistic and quantified using the I2 statistic. Results There was significant improvement in the frequency of angina symptoms (Seattle Angina Questionnaire [SAQ], symptom diary) across trials, standardized mean difference (SMD): 0.30 (95% Confidence interval [CI] 0.14, 0.47), as well as reduction in the use of sublingual (SL) nitrates, SMD: -0.49 (95% CI -0.77, -0.20). Significant improvements for physical limitation (SAQ), SMD: 0.38 (95% CI 0.20, 0.55) and depression scores (Hospital Anxiety and Depression Scale), SMD: -1.38 (95% CI -2.46, -0.30) were also found. The impact of SM on anxiety was uncertain due to statistical heterogeneity across trials for this outcome, I2 = 98%. SM did not improve other HRQL dimensions including angina stability, disease perception, and treatment satisfaction. Conclusions SM interventions significantly improve angina frequency and physical limitation; they also decrease the use of SL nitrates and improve depression in some cases. Further work is needed to make definitive conclusions about the impact of SM on cardiac-specific anxiety.

This paper reviews the literature on the time series modelling of earnings from its beginnings around 1970 through to the 1990s. The paper focuses first on the evidence reported in that part of the literature which analysed the time series properties of earnings without reference to an explicitly stated earnings-based valuation model and outlines the motivations underlying that literature. It then shows that recent theoretical developments in the construction of earnings-based valuation models incorporating the time series properties of earnings have provided an important new impetus to the time series modelling of earnings.

Objectives Implanted peripheral nerve stimulation is one of the earliest developed methods of neuromodulation for the treatment of chronic neuropathic pain. It is traditionally performed by surgical exposure and implantation of a paddle lead. Ultrasound-guided percutaneous placement of cylindrical leads has been proposed as an alternative. However, those leads are fragile and prone to migration. Minimally invasive paddle lead implantation may improve long-term results while minimizing surgical insult. A feasibility laboratory study was performed. Materials and Methods Ultrasound-guided placements of a narrow paddle lead were performed in the upper and lower extremities of a human cadaver. Ultrasonography was used to record the lead position relative to the target nerves. Dissections were performed, and digital photography was completed. Anatomic images were analyzed. Results All experiments were successfully accomplished. Although ultrasound localization of the upper extremity nerves was straightforward and clear, all procedural steps were technically easier at the lower extremity. For the latter, fewer attempts were required to maintain the lead in the desired tissue plane. Ultrasound revealed an acoustic shadowing of the underlying nerves in both the short- and long-axis views by the inserted lead. All dissections revealed a parallel to the nerve lead placement with at least four contacts facing the nerve. The lead appeared to be more mechanically stable at the lower extremity. Conclusions This anatomic study confirmed technical feasibility of percutaneous placement of a narrow paddle-type lead for the peripheral nerve stimulation that may potentially improve stimulation and reduce migrations.

Technical proficiency in anesthesia has historically been determined subjectively. The purpose of this study was to establish the construct validity for the Imperial College Surgical Assessment Device (ICSAD), a measure of hand motion efficiency, as an objective assessment tool for technical skill performance, by examining its ability to distinguish between operators of different levels of experience performing a labour epidural. Concurrent validity for the ICSAD was investigated by comparison to a validated task specific checklist (CL) and global rating scale (GRS).A single blinded, prospective, controlled study design compared three groups of subjects: novice residents (30 epidurals), experienced residents (100 epidurals), and staff anesthesiologists (500 epidurals). Performance was measured using the ICSAD (number of movements, path length, time) and scores from a CL and GRS graded by examiners blinded to the level of training. Data were analyzed by multivariate analysis of variance (MANOVA).Twenty-nine subjects were recruited. Novice residents had longer path lengths compared to experienced residents (P = 0.031) and staff anesthesiologists (P = 0.0004), made more movements (P = 0.012) and took more time than staff (P = 0.009). Novice residents scored significantly worse on the GRS compared to experienced residents (P = 0.029) and staff (P = 0.01) and had significantly lower CL scores compared to staff (P = 0.003).Construct and concurrent validity for the ICSAD was established for a regional anesthesia technique by demonstrating that it can distinguish between operators of different levels of experience and by comparing it to the current standards of technical skill assessment.

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.

Photodynamic therapy (PDT) invokes a number of cellular responses. Other studies have shown that PDT induces transcription and translation of heat shock proteins (Hsps). The expression of mitochondrial heat shock protein, Hsp60, was measured following in vitro Photofrin-mediated PDT in the colon cancer cell line HT29 and its PDT-induced resistant variant HT29-P14 as well as the radiation-induced fibrosarcoma cells RIF-1 and its PDT-induced resistant variant, RIF-8A. Basal levels of Hsp60 were found to be similar in the two murine cell lines. In the human model, the resistant HT29-P14 cell line showed a small increase in basal levels relative to its parental population. Incubation with Photofrin® (PII) alone or photosensitization caused a significant increase in Hsp60 levels in all cell lines as determined by flow cytometry. A dose-dependent and temporal relationship for PDT response was observed, maximum levels were detected 6–8 h post PDT, at which time, Hsp60 induction was found to be significantly greater in the two resistant variants. Induction in the RIF cells was also found to be greater after incubation with PII alone at the highest doses tested. These results indicate that the presence of PII and the subsequent oxidative stress of PDT can induce Hsp60 and implicated it as a common factor that may contribute to the resistance observed in the induced resistant cells.

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.

The Los Alamos National Laboratory KrF Aurora laser optical system is described. Conceptual, first-order, and detailed designs are presented for the major 248-nm ultraviolet optical, subsystems. In Aurora, a 5-ns front-end pulse is replicated and time encoded into a 96-beam, 480-ns pulse train, angle encoded, amplified, and then time and angle decoded so that all the 5-ns pulses arrive at the target plane simultaneously. The encoder and the centered optical system that directs the pulse train through the amplifiers have been installed, on major alignment system has been built and tested, and most decoder optical components have been designed and ordered. The plan is to have the entire optical system installed and initial integration completed by October 1987.