Consensus-based recommendations for titrating cannabinoids and tapering opioids for chronic pain control.

AIMS: Opioid misuse and overuse have contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five-step modified Delphi process, we aimed to develop consensus-based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids. RESULTS: In patients with chronic pain taking opioids not reaching treatment goals, there was consensus that cannabinoids may be considered for patients experiencing or displaying opioid-related complications, despite psychological or physical interventions. There was consensus observed to initiate with a cannabidiol (CBD)-predominant oral extract in the daytime and consider adding tetrahydrocannabinol (THC). When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day. Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain and/or the cannabis dose has been optimised. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks. Clinical success could be defined by an improvement in function/quality of life, a ≥30% reduction in pain intensity, a ≥25% reduction in opioid dose, a reduction in opioid dose to <90 mg MED and/or reduction in opioid-related adverse events. CONCLUSIONS: This five-stage modified Delphi process led to the development of consensus-based recommendations surrounding the safe introduction and titration of cannabinoids in concert with tapering opioids.

Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in chronic pain patients.

PURPOSE: We investigated patients with chronic pain seeking medical cannabis. We assessed their demographics, patterns of cannabis use, and the long-term effectiveness of cannabis on their pain and functional domains. METHODS: This observational study enrolled patients between 8 September 2015 and 31 July 2018 from community-based cannabis clinics in Ontario, Canada. In addition to collecting demographic information, the primary outcomes studied were pain intensity and pain-related interference scores assessed at baseline, three, six, and 12 months. Using validated questionnaires, we also assessed anxiety, depression, quality of life (QoL), general health symptoms, neuropathic pain, self-reported opioid consumption, and adverse events. RESULTS: Of the 1,000 patients consented, 757 (76%) participated at one or more of the study time points. At six and 12 months, 230 (30.4%) and 104 (13.7%) of participants were followed up, respectively. Most participants were female (62%), Caucasian (91%), and sought cannabis for pain relief (88%). Time was a significant factor associated with improvement in pain intensity (P < 0.001), pain-related interference scores (P < 0.001), QoL (P < 0.001), and general health symptoms (P < 0.001). Female sex was significantly associated with worse outcomes than male sex including pain intensity (P < 0.001) and pain-related interference (P < 0.001). The proportion of individuals who reported using opioids decreased by half, from 40.8% at baseline to 23.9% at 12 months. CONCLUSION: Despite significant challenges to collecting long-term observational data on patients who attempted a trial of cannabis products, approximately one-third of patients in the cohort remained on medical cannabis for six months. In this cohort, pain intensity and pain-related interference scores were reduced and QoL and general health symptoms scores were improved compared with baseline.

RéSUMé: OBJECTIF: Nous avons étudié des patients souffrant de douleur chronique et cherchant à obtenir du cannabis médical. Nous avons évalué leurs données démographiques, leurs habitudes de consommation de cannabis et l'efficacité à long terme du cannabis sur leur douleur et leurs domaines fonctionnels. MéTHODE: Cette étude observationnelle a recruté des patients entre le 8 septembre 2015 et le 31 juillet 2018 dans des cliniques communautaires de cannabis en Ontario, au Canada. En plus de recueillir des renseignements démographiques, les critères d'évaluation principaux étudiés étaient l'intensité de la douleur et les scores d'interférence liés à la douleur évalués au début de l'étude et à trois, six et 12 mois. À l'aide de questionnaires validés, nous avons également évalué l'anxiété, la dépression, la qualité de vie (QdV), les symptômes généraux de santé, la douleur neuropathique, la consommation d'opioïdes rapportée et les effets indésirables. RéSULTATS: Sur les 1000 patients consentants, 757 (76 %) ont participé à un ou plusieurs des points d'analyse de l'étude. À six et douze mois, 230 (30,4 %) et 104 (13,7 %) patients ont participé, respectivement. La plupart des participants étaient des femmes (62 %) d'origine caucasienne (91 %) et cherchaient à soulager leur douleur avec du cannabis (88 %). Le temps était un facteur important associé à l'amélioration de l'intensité de la douleur (P < 0,001), aux scores d'interférence liés à la douleur (P < 0,001), à la QdV (P < 0,001), et aux symptômes de santé généraux (P < 0,001). Le sexe féminin a été significativement associé à des pronostics moins bons que le sexe masculin, y compris en matière d'intensité de la douleur (P < 0,001) et d'interférences liées à la douleur (P < 0,001). La proportion de personnes qui ont déclaré utiliser des opioïdes a diminué de moitié, passant de 40,8 % au début de l'étude à 23,9 % à 12 mois. CONCLUSION: Malgré des défis importants dans la collecte de données observationnelles à long terme concernant les patients qui participent à une étude sur les produits du cannabis, environ un tiers des patients de la cohorte ont continué à prendre du cannabis médical pendant six mois. Dans cette cohorte, l'intensité de la douleur et les scores d'interférence liés à la douleur ont été réduits, et les scores de QdV et de symptômes généraux de santé se sont améliorés par rapport au début de la période à l'étude.

Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials.

OBJECTIVE: To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. DATA SOURCES: In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. STUDY SELECTION: An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. CONCLUSION: There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.

Characteristics of chronic noncancer pain patients assessed with the opioid risk tool in a Canadian tertiary care pain clinic.

BACKGROUND: The Opioid Risk Tool (ORT) is a screening instrument for assessing the risk of opioid-related aberrant behavior in chronic noncancer pain (CNCP) patients. OBJECTIVE: This study aims to compare patient characteristics documented in the original ORT study with those identified in CNCP patients assessed using a physician-administered ORT in a tertiary care pain clinic in Toronto, Canada. METHODOLOGY: This was a descriptive cross-sectional study of 322 consecutive new patients referred over 12 months. Data extraction included ORT scores, demographics, pain ratings, opioid, and other medication use at point of entry, diagnosis, and other variables. Characteristics were compared with those described in the original ORT study. RESULTS: The total mean ORT scores of patients in this study were related to several demographic (gender, age, marital status, and country of birth) and nondemographic variables (employment status, cigarette smoking, and contribution of biomedical and/or psychological factors to presentation). Prevalence of characteristics noted in this patient sample differed substantially from that found in Webster and Webster as the basis for ORT scores. CONCLUSION: Significant differences existed between this study population and the patient sample from which the ORT was derived. Limitations of this study are discussed. We concur with the authors of the original study that the ORT may not be applicable in different pain populations and settings. Based on our findings, we encourage caution in interpreting the ORT in general CNCP settings until further studies are performed.

Characteristics of complex regional pain syndrome in patients referred to a tertiary pain clinic by community physicians, assessed by the Budapest clinical diagnostic criteria.

OBJECTIVE: The aim of this study was to describe the characteristics of patients referred with complex regional pain syndrome (CRPS) diagnosis to a tertiary care pain center. METHOD: Descriptive chart review study of all patients referred by family physicians or community specialists as having CRPS (2006-2010). Data extraction included demographics, pain ratings, and diagnosis utilizing the Budapest CRPS criteria. RESULTS: The study population consisted of 54 subjects (male [M] =7, female [F] =47). Only 27.7% were classified as CRPS by the clinical expert. Four additional subjects carrying other diagnoses but found to have CRPS were added to the analysis. The non-CRPS group consisted of 39 subjects (M=8, F=31) and the CRPS group of 19 (M=2, F=17). CRPS patients were statistically significantly more likely to 1) have suffered a fracture; 2) report symptoms in each of the four symptom categories, as well as signs in three or four categories collectively; and 3) have allodynia/hyperalgesia alone or in combination (85/90%) as compared with the non-CRPS group (23/25%, respectively). The non-CRPS group was much more likely to report no symptoms or signs at all in the different symptom and sign categories. Of the 39 non-CRPS patients, 74% had other diagnosable entities (1/3 suffering from specific neuropathic pain conditions, e.g., radiculopathy, diabetic neuropathy, etc. and 2/3 from discreet musculoskeletal entities), while 18% were diagnosed with psychogenic pain disorders including conversion reaction associated with immobility or paralysis. DISCUSSION: Besides fulfilling the Budapest CRPS diagnostic criteria, the most important other factor for diagnosing CRPS is the exclusion of a neuropathic, musculoskeletal, or non-biomedical condition accounting for the presentation.

Automated, Vision-Based Goniometry and Range of Motion Calculation in Individuals With Suspected Ehlers-Danlos Syndromes/Generalized Hypermobility Spectrum Disorders: A Comparison of Pose-Estimation Libraries to Goniometric Measurements.

Generalized joint hypermobility (GJH) often leads clinicians to suspect a diagnosis of Ehlers Danlos Syndrome (EDS), but it can be difficult to objectively assess. Video-based goniometry has been proposed to objectively estimate joint range of motion in hyperextended joints. As part of an exam of joint hypermobility at a specialized EDS clinic, a mobile phone was used to record short videos of 97 adults (89 female, 35.0 ± 9.9 years old) undergoing assessment of the elbows, knees, shoulders, ankles, and fifth fingers. Five body keypoint pose-estimation libraries (AlphaPose, Detectron, MediaPipe-Body, MoveNet - Thunder, OpenPose) and two hand keypoint pose-estimation libraries (AlphaPose, MediaPipe-Hands) were used to geometrically calculate the maximum angle of hyperextension or hyperflexion of each joint. A custom domain-specific model with a MobileNet-v2 backbone finetuned on data collected as part of this study was also evaluated for the fifth finger movement. Spearman's correlation was used to analyze the angles calculated from the tracked joint positions, the angles calculated from manually annotated keypoints, and the angles measured using a goniometer. Moderate correlations between the angles estimated using pose-tracked keypoints and the goniometer measurements were identified for the elbow (rho =.722; Detectron), knee (rho =.608; MoveNet - Thunder), shoulder (rho =.632; MoveNet - Thunder), and fifth finger (rho =.786; custom model) movements. The angles estimated from keypoints predicted by open-source libraries at the ankles were not significantly correlated with the goniometer measurements. Manually annotated angles at the elbows, knees, shoulders, and fifth fingers were moderately to strongly correlated to goniometer measurements but were weakly correlated for the ankles. There was not one pose-estimation library which performed best across all joints, so the library of choice must be selected separately for each joint of interest. This work evaluates several pose-estimation models as part of a vision-based system for estimating joint angles in individuals with suspected joint hypermobility. Future applications of the proposed system could facilitate objective assessment and screening of individuals referred to specialized EDS clinics.

Perceptions and Prevalence of Cannabis Use in Women With Inflammatory Bowel Disease of Reproductive Age: A Cross-Sectional Study.

Background: Many patients with inflammatory bowel disease (IBD) may use cannabis for relief of symptoms. During pregnancy, however, cannabis exposure may be associated with adverse pregnancy outcomes. We aimed to determine the prevalence and perceptions of cannabis use in women with IBD. Methods: Through recruitment at Mount Sinai Hospital and online platforms such as Twitter, women with IBD (age 18-45) were asked to complete anonymous surveys on demographics, cannabis use, perception of use during pregnancy, and discussing its use with healthcare providers (HCP). Categorical variables were reported as frequencies and compared across groups with the chi-square test. Results: One-hundred and two pregnant patients with IBD were included in this study, 19 (18.6%) reported using cannabis. Current users were more likely to report constant pain in the last 12 months and discuss its use with their HCP. Fifty-three (52.0%) women were unsure of the specific risks associated with cannabis use during pregnancy, and only 15 (14.7%) had ever discussed its use with their HCP. Those who had discussed cannabis use with their HCP were more likely to have prior IBD-related surgery, perceive its use unsafe during pregnancy, and be more likely to be using cannabis. Conclusion: Many women with IBD report uncertainty of the risks of cannabis use during pregnancy and the majority have never discussed cannabis use with their providers. With the increasing legalization of cannabis in many jurisdictions, it is imperative patients and healthcare providers discuss the risks and benefits of its use, particularly during vulnerable times such as pregnancy.

Opioids compared to placebo or other treatments for chronic low-back pain.

BACKGROUND: The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these medications remain unclear. This review is an update of a Cochrane review first published in 2007. OBJECTIVES: To determine the efficacy of opioids in adults with CLBP. SEARCH METHODS: We electronically searched the Cochrane Back Review Group's Specialized Register, CENTRAL, CINAHL and PsycINFO, MEDLINE, and EMBASE from January 2006 to October 2012. We checked the reference lists of these trials and other relevant systematic reviews for potential trials for inclusion. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that assessed the use of opioids (as monotherapy or in combination with other therapies) in adults with CLBP that were at least four weeks in duration. We included trials that compared non-injectable opioids to placebo or other treatments. We excluded trials that compared different opioids only. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data onto a pre-designed form. We pooled results using Review Manager (RevMan) 5.2. We reported on pain and function outcomes using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (95% CI). We used absolute risk difference (RD) with 95% CI to report adverse effects. MAIN RESULTS: We included 15 trials (5540 participants). Tramadol was examined in five trials (1378 participants); it was found to be better than placebo for pain (SMD -0.55, 95% CI -0.66 to -0.44; low quality evidence) and function (SMD -0.18, 95% CI -0.29 to -0.07; moderate quality evidence). Transdermal buprenorphine (two trials, 653 participants) may make little difference for pain (SMD -2.47, 95%CI -2.69 to -2.25; very low quality evidence), but no difference compared to placebo for function (SMD -0.14, 95%CI -0.53 to 0.25; very low quality evidence). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), examined in six trials (1887 participants), were better than placebo for pain (SMD -0.43, 95%CI -0.52 to -0.33; moderate quality evidence) and function (SMD -0.26, 95% CI -0.37 to -0.15; moderate quality evidence). One trial (1583 participants) demonstrated that tramadol may make little difference compared to celecoxib (RR 0.82, 95% CI 0.76 to 0.90; very low quality evidence) for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for either pain (SMD 0.21, 95% CI -0.03 to 0.45; very low quality evidence), or function (SMD -0.11, 95% -0.63 to 0.42; very low quality evidence). The included trials in this review had high drop-out rates, were of short duration, and had limited interpretability of functional improvement. They did not report any serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism). In general, the effect sizes were medium for pain and small for function. AUTHORS' CONCLUSIONS: There is some evidence (very low to moderate quality) for short-term efficacy (for both pain and function) of opioids to treat CLBP compared to placebo. The very few trials that compared opioids to non-steroidal anti-inflammatory drugs (NSAIDs) or antidepressants did not show any differences regarding pain and function. The initiation of a trial of opioids for long-term management should be done with extreme caution, especially after a comprehensive assessment of potential risks. There are no placebo-RCTs supporting the effectiveness and safety of long-term opioid therapy for treatment of CLBP.

Design, synthesis and pharmacological evaluation of 4-(piperazin-1-yl methyl)-N1-arylsulfonyl indole derivatives as 5-HT6 receptor ligands.

4-(Piperazin-1-yl methyl)-N(1)-arylsulfonyl indole derivatives were designed and synthesized as 5-HT(6) receptor (5-HT(6)R) ligands. The lead compound 6a, from this series shows potent in vitro binding affinity, good PK profile, no CYP liabilities and activity in animal models of cognition.

Synthesis and structure-activity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands.

5-Hydroxytryptamine 6 receptors (5-HT(6)R) are being perceived as the possible target for treatment of cognitive disorders as well as obesity. The present article deals with the design, synthesis, in vitro binding and structure-activity relationship of a novel series of tetracyclic tryptamines with the rigidized N-arylsulphonyl, N-arylcarbonyl and N-benzyl substituents as 5-HT(6) receptor ligands. The chiral sulphonyl derivatives 15a and 17a showed high affinity at 5-HT(6)R with the K(i) of 23.4 and 20.5 nM, respectively. The lead compound from the series 15a has acceptable ADME properties, adequate brain penetration and is active in animal models of cognition like Novel Object Recognition Task (NORT) and water maze.

Long term outcomes of chronic pain patients attending a publicly funded community-based interdisciplinary pain program in the Greater Toronto area: results of a practice-based audit.

BACKGROUND: Chronic pain management multi/interdisciplinary programs attempt to address all elements of the biopsychosocial model. The primary objective of this retrospective study (based on practice-based audit) was to determine the effectiveness of a patient-centered, comprehensive and intense interdisciplinary pain management program in a publicly funded community-based pain clinic in the Greater Toronto Area. METHOD: This retrospective longitudinal study was conducted on 218 carefully selected sequential chronic pain patients, with 158 completing a 3-4-month interdisciplinary program between January 2016 and December 2018. Data collected upon exit, at 6 months and 12 months post-discharge included demographic information, pain characteristics, emotional/functional status obtained by validated instruments and global impression of change (GIC). Additionally, social health outcomes (return to work or school) were retrieved through retrospective chart review. Means of pre-and post-program variables were compared to assess changes of each patient's "journey". RESULTS: Physical and mental/ emotional health outcomes at exit, 6 months and 12 months post-discharge, showed initial and sustained, statistically and clinically significant improvement from pre-treatment levels, with GIC (much/very much improved) reported as 77%, 58% and 76%, respectively. Additionally, a substantial positive change in social health outcomes was noted particularly in patients on disability (29%), part time workers gaining full time employment (55%), and students (71%) who improved their level of schooling. CONCLUSION: The study showed that careful patient selection in a community-based publicly funded interdisciplinary pain management program can produce significant improvement in pain, physical, mental/emotional health and social function, with sustained long-term outcomes.

Feasibility of video-based joint hypermobility assessment in individuals with suspected Ehlers-Danlos syndromes/generalised hypermobility spectrum disorders: a single-site observational study protocol.

INTRODUCTION: Ehlers-Danlos syndromes (EDS)/generalised hypermobility spectrum disorders (G-HSD) affect the connective tissue of the body and present with a heterogeneous set of symptoms that pose a challenge for diagnosis. One of the main diagnostic criteria of EDS/G-HSD is generalised joint hypermobility, which is currently assessed by clinicians during a physical exam. However, the practice for measuring joint hypermobility is inconsistent between clinicians, leading to high inter-rater variability. Often patients are misdiagnosed with EDS/G-HSD based on an incorrect hypermobility assessment, leading to increased referral rates and resource utilisation at specialised EDS clinics that results in unnecessary emotional distress for patients. An objective, validated and scalable method for assessing hypermobility might mitigate these issues and result in improved EDS/G-HSD patient care. METHODS AND ANALYSIS: This study will examine the use of videos obtained using a smartphone camera to assess the range of motion (ROM) and hypermobility of the joints assessed in Beighton score and more (spine, shoulders, elbows, knees, ankles, thumbs and fifth fingers) in individuals with suspected EDS/G-HSD. Short videos of participants will be captured as they undergo a formal assessment of joint hypermobility at the GoodHope EDS Clinic at Toronto General Hospital. Clinicians will measure the ROM at each joint using a clinical-grade goniometer to establish ground truth measurements. Open-source human pose-estimation libraries will be used to extract the locations of key joints from the videos. Deterministic and machine learning systems will be developed and evaluated for estimating the ROM at each joint. Results will be analysed separately for each joint and human pose-estimation library. ETHICS AND DISSEMINATION: This study was approved by the Research Ethics Board of the University Health Network in Toronto on 26 April 2022. Participants will provide written informed consent. Findings from this study will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05366114.

Indole-3-piperazinyl derivatives: novel chemical class of 5-HT(6) receptor antagonists.

N(1)-Arylsulfonyl-3-piperazinyl indole derivatives were designed and identified as a novel class of 5-HT(6) receptors ligands. All the compounds have high affinity and antagonist activity towards 5-HT(6) receptor. The compound 7a (K(i) = 3.4 nM, functional assay IC(50) = 310 nM) shows enhanced cognitive effect when tested in NORT and Morris water maze models. Synthesis, SAR and PK profile of these novel compounds constitute the subject matter of this Letter.

Chronic noncancer pain: characteristics of patients prescribed opioids by community physicians and referred to a tertiary pain clinic.

OBJECTIVE: To describe the characteristics of patients with chronic noncancer pain (CNCP) prescribed opioids by community physicians and referred to a tertiary pain clinic. DESIGN: Cross-sectional, descriptive study. SETTING: A tertiary care, hospital-based pain clinic in Toronto, Ont. PARTICIPANTS: A total of 455 consecutive patients newly referred to the pain clinic by community physicians. MAIN OUTCOME MEASURES: Data on demographic characteristics, pain ratings, and medication intake were obtained using standardized collection forms and retrospective chart review. Patients were classified by diagnosis: group 1 patients had biomedical disorders only, group 2 patients had biomedical disorders and psychological factors, and group 3 patients had psychological factors only. Patients were also categorized based on opioid use: no opioid use (NOU); low opioid use (LOU), with a daily morphine-equivalent dosage (MED) of 200 mg or less; or high opioid use (HOU), with a daily MED of more than 200 mg. RESULTS: In the general study population, 63% of patients were taking opioids, with 1 in 5 exceeding an MED of 200 mg daily. In group 1, 59% of patients used opioids and 10% had HOU; 66% of patients in groups 2 and 3 were taking opioids, with 21% and 26% classified as having HOU. The mean (SD) daily MED for groups 2 and 3 HOU patients combined was significantly higher than that of group 1 HOU patients: 575.7 (472.9) mg/d versus 284.9 (74.6) mg/d, respectively. Men were twice as likely as women to have HOU; Canadian-born patients were 3 times as likely as foreign-born patients to have HOU. Psychoactive drugs were coprescribed in 61% of LOU patients and 76% of HOU patients. Greater opioid use was associated with group 2 and 3 diagnoses, male sex, Canadian-born origin, and high pain scores. CONCLUSION: Our results indicate that male, Canadian-born CNCP patients presenting with psychological morbidity or comorbidity and reporting higher pain severity ratings were more likely to receive opioids. Additionally, many CNCP patients referred to our tertiary care pain clinic were receiving opioids in excess of a 200-mg/d MED. More studies are needed to determine which factors lead to high-dose opioid prescribing in a subset of this CNCP population.

Demographics, Pain Characteristics and Diagnostic Classification Profile of Chronic Non-Cancer Pain Patients Attending a Canadian University-Affiliated Community Pain Clinic.

INTRODUCTION: Little information exists regarding the characteristics of patients with chronic non-cancer pain (CNCP) attending Canadian pain clinics. The study describes the demographics, pain characteristics and the diagnostic classification profile of such patients attending a university-affiliated community-based pain clinic in the Greater Toronto Area. METHODS: Retrospective descriptive study based on 644 unique consecutive CNCP patients assessed between January 2016 and December 2017. RESULTS: The female/male ratio was 1.6:1; 80% were younger than 65 years; 43% held some form of employment (full-time, part-time or self employment); median pain duration was 3 years; car accidents and medical conditions accounted for 28 and 27% of pain onset, respectively; 34% had four or more distinct areas of pain; and low back pain (LBP) was the most prevalent site (66%), but was the sole site of pain in less than a third of these patients. Age was positively associated with LBP prevalence. Self-reported health service utilization (visits to the emergency room, pain physician or psychologist) increased with patient psychopathology. Cannabis was used by 15% of the cohort and opioids by 34.5%, with only one in six opioid users exceeding 90 mg of morphine equivalent dose per day. Comparison of our data to three previously published studies from other Canadian pain clinics demonstrated both similarities and substantial differences between the populations. CONCLUSION: Our study highlights regional differences between CNCP population phenotypes. Recognition of biomedical, psychological and socio-environmental factors affecting pain should be considered for patient stratification and rational approaches to treatment, as "one size treatment does not fit all".

Role of Single-Agent Methotrexate as a Neoadjuvant Chemotherapy in Oral Cavity Cancers.

Oral cancers are the most common cancer in India due to tobacco abuse in the form of chewing, smoking, and inhalation. Majority of these patients present late at advanced disease stage. Such patients have significant morbidity irrespective of the intent of treatment; the survival rate is very poor. To improve loco-regional control and survival, neoadjuvant chemotherapy has been started in many centers all over the world. To study the effect of injecting methotrexate as a single agent in (1) down-staging and increasing operability of oral cancers, (2) need for reconstructive surgery, and (3) recurrence. A total of 50 patients with biopsy-proven oral malignancy were selected over a period of 2 years from August 2014 to August 2016 for the study. Patients were subjected to weekly dose of injecting methotrexate 1 mg/kg given intravenously for 6 weeks. All patients underwent surgery after completing 6 cycles of methotrexate. A total 50 patients were started on inj. methotrexate of which 9 patients did not complete neoadjuvant chemotherapy. 53.7% of patients showed more than 50% decrease in tumor size. 29.26% of patients showed complete disappearance of cervical lymph nodes and 31.7% of patients showed more than 50% decrease in size of cervical lymph nodes. 48.78% of patients were managed with wide local excision with primary closure, decreasing the need of reconstructive surgery. 94.74% of patients did not show any recurrence in follow-up period of 1 year. Single agent methotrexate is effective in down-staging oral cancers, improving operability and decreasing morbidity and recurrence among patients.

The impact of polyol-containing chewing gums on dental caries: a systematic review of original randomized controlled trials and observational studies.

BACKGROUND: The authors conducted a systematic review of original studies that was designed to assess the impact of polyol-containing chewing gum on dental caries compared with the effect with no chewing gum. REVIEW METHODS: The authors searched MEDLINE, The Cochrane Library and Google Scholar up to May 2008 to identify peer-reviewed articles that compared polyol-containing chewing gum with no chewing gum. The authors extracted study characteristics, data on incremental dental caries and quality by consensus. Data on prevented fraction (PF) were pooled across studies. RESULTS: The results of 19 articles with data from 14 study populations showed that the use of xylitol, xylitol-sorbitol blend and sorbitol were associated with mean PF (95 percent confidence interval) of 58.66 percent (35.42-81.90), 52.82 percent (39.64-66.00) and 20.01 percent (12.74-27.27), respectively. For the sorbitol-mannitol blend, it was 10.71 percent (-20.50-41.93), which was not statistically significant. Sensitivity analyses confirmed the robustness of the findings. CLINICAL IMPLICATIONS: Although research gaps exist, particularly on optimal dosing and relative polyol efficacy, research evidence supports using polyol-containing chewing gum as part of normal oral hygiene to prevent dental caries.