Mechanical evaluation of a threaded interference interlocking mechanism for angle-stable intramedullary nailing.

OBJECTIVE: To assess the fatigue and load-to-failure mechanical characteristics of an intramedullary nail with a threaded interference design (TID) in comparison to a commercially available veterinary angle-stable nail with a Morse taper bolt design (I-Loc) of an equivalent size. METHODS: 10 single interlocking screw/bolt constructs of TID and I-Loc implants were assembled using steel pipe segments and placed through 50,000 cycles of simulated, physiologic axial or torsional loading. Entry torque, postfatigue extraction torque, and 10th, 25,000th, and 50,000th cycle torsional toggle were assessed. Each construct was then loaded to failure in the same respective direction as fatigue testing. Four complete constructs of each design were then assessed using a synthetic bone analog with a 50-mm central defect via nondestructive torsional and axial loading followed by axial load to failure. RESULTS: All constructs were angle stable at all time points and withstood fatigue loading. Median insertional torque, extraction torque-to-insertion torque ratio, and torsional yield load were 33%, 33%, and 72.5% lower, respectively, for the TID interlocking screws. No differences in torsional peak load, torsional stiffness, axial yield load, axial stiffness, or axial peak load were identified. No differences in complete construct angle stability, torsional stiffness, axial peak load, axial stiffness, or axial yield load were identified. CLINICAL RELEVANCE: The TID had an inferior torsional yield load when compared to I-Loc implants but generated angle stability and sustained simulated physiologic fatigue loading. The TID may be a suitable mechanism for generating angle stability in interlocking nails.

Benzodiazepine use in medical cannabis authorization adult patients from 2013 to 2021: Alberta, Canada.

BACKGROUND: Benzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential "sparing effects" of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada. METHODS: A propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis. RESULTS: Over the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (- 0.08 DDE, 95% CI: - 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, - 0.04 DDE, 95% CI: - 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: - 0.009 to 0.12) per patient was noted. CONCLUSIONS: This short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use. HIGHLIGHTS: • Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada. • Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

Medical cannabis authorization and risk of emergency department visits and hospitalization due to psychotic disorders: A propensity score-matched cohort study.

Despite evidence showing that recreational cannabis use is associated with a higher risk of psychotic disorders, this risk has not been well characterized for patients using medical cannabis. Therefore, this study assessed the risk of emergency department (ED) visits and hospitalization for psychotic disorders (the study outcome) among adult patients authorized to use medical cannabis. We performed a retrospective cohort study on patients authorized to use medical cannabis in a group of Ontario cannabis clinics between 2014 and 2019. Using clinical and health administrative data, each patient was matched by propensity scores to up to 3 population-based controls. Conditional Cox proportional hazards regressions were used to assess the risk. Among 54,006 cannabis patients matched to 161,265 controls, 39 % were aged ≤50 years, and 54 % were female. Incidence rates for psychotic disorders were 3.00/1000 person-years (95%CI: 2.72-3.32) in the cannabis group and 1.88/1000 person-years (1.75-2.03) in the control group. A significant association was observed, with an adjusted hazard ratio of 1.38 (95%CI: 1.19-1.60) in the total sample and 1.63 (1.40-1.91) in patients without previous psychotic disorders. The results suggest that cannabis authorization should include a benefit-risk assessment of psychotic disorders to minimize the risk of events requiring emergency attention.

A Prospective Cohort Study of Acute Pain and In-Hospital Opioid Consumption After Cardiac Surgery: Associations With Psychological and Medical Factors and Chronic Postsurgical Pain.

BACKGROUND: Understanding the association of acute pain intensity and opioid consumption after cardiac surgery with chronic postsurgical pain (CPSP) can facilitate implementation of personalized prevention measures to improve outcomes. The objectives were to (1) examine acute pain intensity and daily mg morphine equivalent dose (MME/day) trajectories after cardiac surgery, (2) identify factors associated with pain intensity and opioid consumption trajectories, and (3) assess whether pain intensity and opioid consumption trajectories are risk factors for CPSP. METHODS: Prospective observational cohort study design conducted between August 2012 and June 2020 with 1-year follow-up. A total of 1115 adults undergoing cardiac surgery were recruited from the preoperative clinic. Of the 959 participants included in the analyses, 573 completed the 1-year follow-up. Main outcomes were pain intensity scores and MME/day consumption over the first 6 postoperative days (PODs) analyzed using latent growth mixture modeling (GMM). Secondary outcome was 12-month CPSP status. RESULTS: Participants were mostly male (76%), with a mean age of 61 ± 13 years. Three distinct linear acute postoperative pain intensity trajectories were identified: "initially moderate pain intensity remaining moderate" (n = 62), "initially mild pain intensity remaining mild" (n = 221), and "initially moderate pain intensity decreasing to mild" (n = 251). Age, sex, emotional distress in response to bodily sensations, and sensitivity to pain traumatization were significantly associated with pain intensity trajectories. Three distinct opioid consumption trajectories were identified on the log MME/day: "initially high level of MME/day gradually decreasing" (n = 89), "initially low level of MME/day remaining low" (n = 108), and "initially moderate level of MME/day decreasing to low" (n = 329). Age and emotional distress in response to bodily sensations were associated with trajectory membership. Individuals in the "initially mild pain intensity remaining mild" trajectory were less likely than those in the "initially moderate pain intensity remaining moderate" trajectory to report CPSP (odds ratio [95% confidence interval, CI], 0.23 [0.06-0.88]). No significant associations were observed between opioid consumption trajectory membership and CPSP status (odds ratio [95% CI], 0.84 [0.28-2.54] and 0.95 [0.22-4.13]). CONCLUSIONS: Those with moderate pain intensity right after surgery are more likely to develop CPSP suggesting that those patients should be flagged early on in their postoperative recovery to attempt to alter their trajectory and prevent CPSP. Emotional distress in response to bodily sensations is the only consistent modifiable factor associated with both pain and opioid trajectories.

Application of organoselenium in inhibiting Candida albicans biofilm adhesion on 3D printed denture base material.

PURPOSE: Denture Stomatitis, a chronic mucosal inflammation associated with Candida albicans, is common among denture wearers. Several health conditions have been linked to chronic Candida infections. The complex, multifactorial nature of denture stomatitis requires the continuous pursuit of effective long-term solutions. The present in vitro study investigated the effect of incorporating organoselenium into 3D-printed denture base resin on C. albicans adhesion and biofilm formation. MATERIALS AND METHODS: Thirty disks were fabricated using 3D-printed denture base resin and assigned to three experimental groups (10/group): disks without organoselenium (control), disks with 0.5% organoselenium (0.5%SE), and disks with 1% organoselenium (1%SE). Each disk was incubated with approximately 1 × 106 cells/mL of C. albicans for 48 h. Microbial viability (CFU/mL) was quantified by the spread plate method, while Confocal laser scanning microscopy and scanning electron microscope were performed for quantifying the biofilm thickness and examining biofilm morphology, respectively. Data were analyzed using One-way ANOVA with Tukey's multiple comparisons test. RESULTS: CFU/mL was significantly (p < 0.05) higher in Control when compared with 0.5%SE and 1%SE, but no significant difference between 0.5%SE and 1%SE. A similar trend was observed with biofilm thickness except that there was no significant difference between the Control and 0.5%SE. There was C. albicans biofilm adhesion on the Control disks, with yeast cells and hyphae formation, whereas on 0.5%SE and 1%SE, there was inhibition of yeast cells transition to hyphae formation. CONCLUSIONS: Incorporation of organoselenium into 3D-printed denture base resin was effective in reducing C. albicans biofilm formation and growth on denture base material.

Risk of depressive disorders associated with medical cannabis authorization: A propensity score matched cohort study.

There is an increase in the medical use of cannabis. However, the safety of medical cannabis, particularly for mental health conditions, has not yet been clearly established. Thus, this study assessed the risk of emergency department (ED) visits and hospitalization for depressive disorders among medical cannabis users. We conducted a retrospective longitudinal cohort study of patients who received medical authorization to use cannabis from 2014 to 2019 in Ontario, matched (1:3 ratio) to population-based controls using propensity scores. Conditional Cox regressions were used to assess the association between cannabis authorization and the outcome. A total of 54,006 cannabis-authorized patients and 161,265 controls were analyzed. Approximately 39% were aged under 50 years, 54% were female, and 16% had a history of anxiety or mood disorders. The adjusted hazard ratio (aHR) for depressive disorders was 2.02 (95%CI: 1.83-2.22). The aHR was 2.23 (1.95-2.55) among subjects without prior mental health disorders. The interaction between sex (or age) and exposure was not significant. In conclusion, medical cannabis authorization was associated with an increased risk of depressive disorders. This finding highlights the need for a careful risk-benefit assessment when authorizing cannabis, particularly for patients who seek cannabis to treat a depressive condition.

Mechanical evaluation of canine sacroiliac joint stabilization using two short screws.

OBJECTIVE: To assess the feasibility and mechanical stability of sacroiliac (SI) joint stabilization using 2 short 3.5 mm cortical screws, each spanning an average of 23% of the width of the sacral body. STUDY DESIGN: Cadaveric experimental study. SAMPLE POPULATION: Twenty-four canine pelvis specimens. METHODS: Pelvis specimens were prepared by disarticulation of the left SI joint and osteotomy of the left pubis and left ischium, and stabilized using a single long lag screw (LLS), 2 short lag screws (SLS) or 2 short positional screws (SPS). Computed tomography (CT) imaging was used to determine standardized screw lengths for each group and was repeated following implant insertion. Specimens were secured within a servohydraulic test frame and loaded through the acetabulum to simulate weight bearing under displacement control at 4 mm/min for 20 mm total displacement. Group mechanical testing data were compared. RESULTS: Peak load, yield load, and stiffness were more than 2 times greater in both the SLS and SPS groups when compared with the LLS group. No mechanical difference was identified between the short-screw groups. CONCLUSION: Sacroiliac luxation fixation using 2 short screws created a stronger, stiffer construct when compared with fixation using a single lag screw spanning 60% of the width of the sacral body. No mechanical advantage was observed between short screws inserted in positional vs. lag fashion. CLINICAL SIGNIFICANCE: Sacroiliac luxation fixation using 2 short screws creates a mechanically superior construct with a larger region of acceptable implant positioning and potentially reduced risk of iatrogenic injury compared with conventional fixation.

Incidence and Predictors of Cannabis-Related Poisoning and Mental and Behavioral Disorders among Patients with Medical Cannabis Authorization: A Cohort Study.

OBJECTIVE: As medical cannabis use increases in North America, establishing its safety profile 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 cohort study of patients who received medical cannabis authorization in Ontario, Canada, using data collected in participating cannabis clinics. Outcomes included ED visit/hospitalization with a main diagnosis code for: cannabis/cannabinoid poisoning; and mental/behavioral disorders due to cannabis use. Cox proportional hazard regressions were utilized to analyze the data. RESULTS: From 29,153 patients who received medical authorization, 23,091 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 (95% CI: 4.8-13.6). A total of 26 patients visited the ED or were hospitalized for mental and behavioral 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 behavioral disorders include prior substance use disorders, 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 behavioral disorders was low among patients who were authorized to use cannabis for medical care. Identified predictors can help to target patients with potential risk of the studied outcomes.

Generalized Anxiety Disorder 7-Item (GAD-7) Scores in Medically Authorized Cannabis Patients-Ontario and Alberta, Canada.

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 (<1 point); improvement; or worsening-over time. 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 <0.001). A total of 4,607 patients (90.8%) had no change in GAD-7 score from their initial to final follow-up, 188 (3.7%) had a clinically significant decrease, and 64 (1.3%) noted a clinically significant increase in their GAD-7 scores. 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.

Substance Use Disorders and Psychoactive Drug Poisoning in Medically Authorized Cannabis Patients: Longitudinal Cohort Study.

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.

Medical cannabis authorization and the risk of cardiovascular events: a longitudinal cohort study.

BACKGROUND: Cannabis is increasingly used for therapeutic purpose. However, its safety profile is not well known. This study assessed the risk of cardiovascular-related emergency department (ED) visit and hospitalization in adult patients authorized to use medical cannabis in Ontario, Canada from 2014 to 2017. METHODS: This is a longitudinal cohort study of patients who received medical cannabis authorization and followed-up in cannabis clinics, matched to population-based controls. The primary outcome was an ED visit or hospitalization for acute coronary syndrome (ACS) or stroke; and secondary outcome was for any cardiovascular event. Conditional Cox proportional hazards regression was used to assess the association between cannabis authorization and risk. RESULTS: 18,653 cannabis patients were matched to 51,243 controls. During a median follow-up of 242 days, the incidence rates for ACS or stroke were 7.19/1000 person-years and 5.67/1000 person-years in the cannabis and controls group, respectively- adjusted hazard ratio (aHR) of 1.44 (95% CI 1.08-1.93). When stratified by sex, the association was only statistically significant among males: aHR 1.77 (1.23-2.56). For the secondary outcome (any CV events), the aHR was 1.47 (1.26-1.72). The aHR among males and females were 1.52 (1.24-1.86) and 1.41 (1.11-1.79), respectively. Tested interaction between cannabis authorization and sex was not significant (p > 0.05). CONCLUSIONS: Medical cannabis authorization was associated with an increased risk of ED visits or hospitalization for CV events including stroke and ACS.

Gaps in evidence for the use of medically authorized cannabis: Ontario and Alberta, Canada.

BACKGROUND: With legal access to medical cannabis in Canada since 2001, there is a need to fully characterize its use at both the individual and population levels. We draw on data from Canada's largest cohort study of medical cannabis to identify the primary reasons for medical cannabis authorization in Canada from 2014 to 2019 in two major provinces: Alberta (AB) and Ontario (ON), and review the extent that evidence supports each indication. METHODS: Self-reported baseline assessments were collected from adult patients in ON (n = 61,835) and AB (n = 3410) who were authorized medical cannabis. At baseline, sociodemographic, primary medical information, and validated clinical questionnaires were completed by patients as part of an individual assessment. Patients' reasons for seeking medical cannabis were compared to published reviews and guidelines to assess the level of evidence supporting medical cannabis use for each condition. RESULTS: Medical cannabis use in both AB and ON was similar in both demographic and reason for authorization. The most common reasons for medical cannabis authorization were: (1) pain (AB = 77%, ON = 76%) primarily due to chronic musculoskeletal, arthritic, and neuropathic pain, (2) mental health concerns (AB = 32.9%, ON = 38.7%) due to anxiety and depression, and (3) sleep problems (AB = 28%, ON = 25%). More than 50 other conditions were identified as reasons for obtaining authorization. CONCLUSION: In both AB and ON, the majority of reasons for medical cannabis authorization are not substantiated by clinical evidence to fully support its efficacy for long-term use. Ongoing epidemiological studies on medical cannabis on these treatments are warranted to fully outline its treatment benefits or risks.

Predictors of Persistent Postsurgical Pain After Hysterectomy-A Prospective Cohort Study.

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.

Opioid use in medical cannabis authorization adult patients from 2013 to 2018: Alberta, Canada.

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 (< 50 OME) had an increase in their weekly OME per week (absolute increase of 112.1 OME, 95% CI: 104.1 to 120.3); whereas higher dose users (OME > 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.

Cohort study of medical cannabis authorization and motor vehicle crash-related healthcare visits in 2014-2017 in Ontario, Canada.

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 < 0.001). 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.

Changes in patient health questionnaire (PHQ-9) scores in adults with medical authorization for cannabis.

BACKGROUND: Legal access to medical cannabis is increasing world-wide. Despite this, there is a lack of evidence surrounding its efficacy on mental health outcomes, particularly, on depression. This study assesses the effect of medical cannabis on Patient Health Questionnaire (PHQ-9) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada. METHODS: An observational cohort study of medically authorized cannabis patients in Ontario and Alberta. Overall change in PHQ-9 scores from baseline to follow-up were evaluated (mean change) over a time period of up to 3.2 years. RESULTS: 37,338 patients from the cohort had an initial PHQ-9 score recorded with 5103 (13.7%) patients having follow-up PHQ-9 scores. The average age was 54 yrs. (SD 15.7), 46% male, 50% noted depression at baseline. The average PHQ-9 score at baseline was 10.5 (SD 6.9), following a median follow-up time of 196 days (IQR: 77-451) the average final PHQ-9 score was 10.3 (SD 6.8) with a mean change of - 0.20 (95% CI: - 0.26, - 0.14, p-value < 0.0001). Overall, 4855 (95.1%) had no clinically significant change in their PHQ-9 score following medical cannabis use while 172 (3.4%) reported improvement and 76 (1.5%) reported worsening of their depression symptoms. CONCLUSIONS: Although the majority showed no clinically important changes in PHQ-9 scores, a number of patients showed improvement or deteriorations in PHQ-9 scores. Future studies should focus on the parallel use of screening questionnaires to control for PHQ-9 sensitivity and to explore potential factors that may have attributed to the improvement in scores pre- and post- 3-6 month time period.

Cannabis and cannabinoids in cancer pain management.

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.

Macrophage Effects on Mesenchymal Stem Cell Osteogenesis in a Three-Dimensional In Vitro Bone Model.

As musculoskeletal (MSK) disorders continue to increase globally, there is an increased need for novel, in vitro models to efficiently study human bone physiology in the context of both healthy and diseased conditions. For these models, the inclusion of innate immune cells is critical. Specifically, signaling factors generated from macrophages play key roles in the pathogenesis of many MSK processes and diseases, including fracture, osteoarthritis, infection etc. In this study, we aim to engineer three-dimensional (3D) and macrophage-encapsulated bone tissues in vitro, to model cell behavior, signaling, and other biological activities in vivo, in comparison to current two-dimensional models. We first investigated and optimized 3D culture conditions for macrophages, and then co-cultured macrophages with mesenchymal stem cells (MSCs), which were induced to undergo osteogenic differentiation to examine the effect of macrophage on new bone formation. Seeded within a 3D hydrogel scaffold fabricated from photocrosslinked methacrylated gelatin, macrophages maintained high viability and were polarized toward an M1 or M2 phenotype. In co-cultures of macrophages and human MSCs, MSCs displayed immunomodulatory activities by suppressing M1 and enhancing M2 macrophage phenotypes. Lastly, addition of macrophages, regardless of polarization state, increased MSC osteogenic differentiation, compared with MSCs alone, with proinflammatory M1 macrophages enhancing new bone formation most effectively. In summary, this study illustrates the important roles that macrophage signaling and inflammation play in bone tissue formation.

Cohort study of medical cannabis authorisation and healthcare utilisation in 2014-2017 in Ontario, Canada.

BACKGROUND: The 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. METHODS: A 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. RESULTS: For 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, p<0.05) but no statistical difference after follow-up (p=0.34). Conversely, no initial increase in all-cause ED visits was observed with a slight decrease (19 visits per 10 000 patients, p=0.014) in follow-up. CONCLUSIONS: An 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.

Post-surgical flap placement following osseous surgery: A short-term clinical evaluation.

BACKGROUND: The purpose of this study is to examine the relationship between immediate post-surgical flap position and subsequent probing depth measurements following osseous surgery. METHODS: 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. RESULTS: 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 was >3 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. CONCLUSIONS: 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.