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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., Competing Interests: Dr. Steinhart has received education grants from Abbvie, Celgene (BMS), Janssen, Arena (Pfizer), Genentech/Roche, and Takeda; Has served as a consultant for Abbvie, BioJAMP, Fresenius Kabi, McKesson, Organon, Pfizer, Takeda, Lilly, Amgen, BMS, Janssen, Mylan Pharmaceuticals, Pendopharm, Sandoz, Viatris; Has attended educational events sponsored by Abvvie, BMS, Organon, Takeda, Amgen, Janssen, and Pfizer. Dr. Tandon has attended educational events supported by Takeda and Janssen. Other authors have no conflict of interest to report., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

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., (© 2023 The Authors.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022. The Author(s).)

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"., (© 2021. The Author(s).)

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.

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., Competing Interests: Compliance with Ethical StandardsThe authors declare that they have no conflict of interest.

As scientific endeavors and data analysis become increasingly collaborative, there is a need for data management systems that natively support the versioning or branching of datasets to enable concurrent analysis, cleaning, integration, manipulation, or curation of data across teams of individuals. Common practice for sharing and collaborating on datasets involves creating or storing multiple copies of the dataset, one for each stage of analysis, with no provenance information tracking the relationships between these datasets. This results not only in wasted storage, but also makes it challenging to track and integrate modifications made by different users to the same dataset. In this paper, we introduce the Relational Dataset Branching System, Decibel, a new relational storage system with built-in version control designed to address these shortcomings. We present our initial design for Decibel and provide a thorough evaluation of three versioned storage engine designs that focus on efficient query processing with minimal storage overhead. We also develop an exhaustive benchmark to enable the rigorous testing of these and future versioned storage engine designs.

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.

The relative ease of collaborative data science and analysis has led to a proliferation of many thousands or millions of versions of the same datasets in many scientific and commercial domains, acquired or constructed at various stages of data analysis across many users, and often over long periods of time. Managing, storing, and recreating these dataset versions is a non-trivial task. The fundamental challenge here is the storage-recreation trade-off : the more storage we use, the faster it is to recreate or retrieve versions, while the less storage we use, the slower it is to recreate or retrieve versions. Despite the fundamental nature of this problem, there has been a surprisingly little amount of work on it. In this paper, we study this trade-off in a principled manner: we formulate six problems under various settings, trading off these quantities in various ways, demonstrate that most of the problems are intractable, and propose a suite of inexpensive heuristics drawing from techniques in delay-constrained scheduling, and spanning tree literature, to solve these problems. We have built a prototype version management system, that aims to serve as a foundation to our DataHub system for facilitating collaborative data science. We demonstrate, via extensive experiments, that our proposed heuristics provide efficient solutions in practical dataset versioning scenarios.

While there have been many solutions proposed for storing and analyzing large volumes of data, all of these solutions have limited support for collaborative data analytics , especially given the many individuals and teams are simultaneously analyzing, modifying and exchanging datasets, employing a number of heterogeneous tools or languages for data analysis, and writing scripts to clean, preprocess, or query data. We demonstrate DataHub, a unified platform with the ability to load, store, query, collaboratively analyze, interactively visualize, interface with external applications, and share datasets. We will demonstrate the following aspects of the DataHub platform: (a) flexible data storage, sharing, and native versioning capabilities : multiple conference attendees can concurrently update the database and browse the different versions and inspect conflicts; (b) an app ecosystem that hosts apps for various data-processing activities : conference attendees will be able to effortlessly ingest, query, and visualize data using our existing apps; (c) thrift-based data serialization permits data analysis in any combination of 20+ languages , with DataHub as the common data store : conference attendees will be able to analyze datasets in R, Python, and Matlab, while the inputs and the results are still stored in DataHub. In particular, conference attendees will be able to use the DataHub notebook - an IPython-based notebook for analyzing data and storing the results of data analysis.

Fondaparinux sodium is a synthetic low-molecular-weight heparin (LMWH). This medication is an anticoagulant or a blood thinner, prescribed for the treatment of pulmonary embolism and prevention and treatment of deep vein thrombosis. Its determination in the presence of related impurities was studied and validated by a novel ion-pair HPLC method. The separation of the drug and its degradation products was achieved with the polymer-based PLRPs column (250 mm × 4.6 mm; 5 μm) in gradient elution mode. The mixture of 100 mM n-hexylamine and 100 mM acetic acid in water was used as buffer solution. Mobile phase A and mobile phase B were prepared by mixing the buffer and acetonitrile in the ratio of 90:10 (v/v) and 20:80 (v/v), respectively. Mobile phases were delivered in isocratic mode (2% B for 0-5 min) followed by gradient mode (2-85% B in 5-60 min). An Evaporative Light Scattering Detector (ELSD) was connected to the LC system to detect the responses of chromatographic separation. Further, the drug was subjected to stress studies for acidic, basic, oxidative, photolytic, and thermal degradations as per ICH guidelines and the drug was found to be labile in acid, base hydrolysis, and oxidation, while stable in neutral, thermal, and photolytic degradation conditions. The method provided linear responses over the concentration range of the LOQ to 0.30% for each impurity with respect to the analyte concentration of 12.5 mg/mL, and regression analysis showed a correlation coefficient value (r(2)) of more than 0.99 for all the impurities. The LOD and LOQ were found to be 1.4 µg/mL and 4.1 µg/mL, respectively, for fondaparinux. The developed ion-pair method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness.

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., (Wiley Periodicals, Inc.)

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., (Wiley Periodicals, Inc.)

Study Design: Systematic review and meta-analysis., Objective: To assess the efficacy of opioids in adults with chronic low back pain (CLBP)., Summary of Background Data: Opioids for CLBP has increased dramatically. However, the benefits and risks remain unclear., Methods: We updated a 2007 Cochrane Review through October 2012 of randomized controlled trials from multiple databases. Use of noninjectable opioids in CLBP for at least 4 weeks was compared with placebo or other treatments; comparisons with different opioids were excluded. Outcomes included pain and function using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (CIs), and absolute risk difference with 95% CI for adverse effects. Study quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation criteria., Results: Fifteen trials (5540 participants), including twelve new, met the criteria. Tramadol was better than placebo for pain (SMD, -0.55; 95% CI, -0.66 to -0.44) and function (SMD, -0.18; 95% CI, -0.29 to -0.07). Compared with placebo, transdermal buprenorphine decreased pain (SMD, -2.47; 95% CI, -2.69 to -2.25), but not function (SMD, -0.14; 95% CI, -0.53 to 0.25). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), were better than placebo for pain (SMD, -0.43; 95% CI, -0.52 to -0.33) and function (SMD, -0.26; 95% CI, -0.37 to -0.15). One trial demonstrated little difference with tramadol compared with celecoxib for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for pain or function. Reviewed trials had low to moderate quality, high drop-out rates, short duration, and limited interpretability of functional improvement. No serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism) were reported., Conclusion: There is evidence of short-term efficacy (moderate for pain and small for function) of opioids to treat CLBP compared with placebo. The effectiveness and safety of long-term opioid therapy for treatment of CLBP remains unproven.

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.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

Objective: This project was undertaken to develop a rapid method for obtaining a widespread sample of patient views on the efficacy and side-effects of antidepressants., Method: A Web-based method is described for rapidly and objectively obtaining patient views on the effects and side-effects of treatment with antidepressants. The method entails a systematized search of many URLs (Uniform Resource Locators, or Web page addresses), using keywords and phrases to extract the named drug and symptom that are reliably relevant to the medication being taken by the individual reporting the experience online. Unwanted medical conditions (e.g., cancer) are excluded., Results: Three successive searches of thousands of Web pages revealed a cumulative total of 835 "mentions" of patient experience on duloxetine, 756 for venlafaxine, 637 for citalopram, 636 for sertraline, 559 for paroxetine, 457 for fluoxetine, 318 for desvenlafaxine, 289 for fluvoxamine, and 210 for mirtazapine, in association with various symptoms. A comparison of the associated symptoms for each of the antidepressants found that the prevalence of the combined factor of fatigue, drowsiness, tiredness or lethargy ranged from 6.4±0.8% down to 2.9±0.15% of the mentions, where the S.E. was derived from three repeats of the Web-based analysis. The prevalence of dizziness or vertigo ranged from 7.6±0.8% down to 1.9±0.3% of the mentions., Conclusions: Given the increasing number of patient narratives about drug experiences on open-access Web forums, this rapid novel method will have increasing utility in post-marketing surveillance and in comparing the effects of psychiatric medications., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2010. Published by Elsevier Ltd.)

Background: Systematic reviews are recognized as the most effective means of summarizing research evidence. However, they are limited by the time and effort required to keep them up to date. Wikis present a unique opportunity to facilitate collaboration among many authors. The purpose of this study was to examine the use of a wiki as an online collaborative tool for the updating of a type of systematic review known as a scoping review., Methods: An existing peer-reviewed scoping review on asynchronous telehealth was previously published on an open, publicly available wiki. Log file analysis, user questionnaires and content analysis were used to collect descriptive and evaluative data on the use of the site from 9 June 2009 to 10 April 2010. Blog postings from referring sites were also analyzed., Results: During the 10-month study period, there were a total of 1222 visits to the site, 3996 page views and 875 unique visitors from around the globe. Five unique visitors (0.6% of the total number of visitors) submitted a total of 6 contributions to the site: 3 contributions were made to the article itself, and 3 to the discussion pages. None of the contributions enhanced the evidence base of the scoping review. The commentary about the project in the blogosphere was positive, tempered with some skepticism., Interpretations: Despite the fact that wikis provide an easy-to-use, free and powerful means to edit information, fewer than 1% of visitors contributed content to the wiki. These results may be a function of limited interest in the topic area, the review methodology itself, lack of familiarity with the wiki, and the incentive structure of academic publishing. Controversial and timely topics in addition to incentives and organizational support for Web 2.0 impact metrics might motivate greater participation in online collaborative efforts to keep scientific knowledge up to date.

The exclusive distribution of 5-HT6 receptors in the brain regions associated with learning and memory makes it an ideal target for cognitive disorders. A novel series of 5-piperazinyl methyl-N 1-aryl sulfonyl indoles were designed and synthesized as 5-HT6R ligands. Most of the synthesized compounds are potent when tested by in vitro radioligand binding assay. The lead compound from the series does not have the CYP liabilities and is active in an animal model of cognition.

Background: Asynchronous telehealth captures clinically important digital samples (e.g., still images, video, audio, text files) and relevant data in one location and subsequently transmits these files for interpretation at a remote site by health professionals without requiring the simultaneous presence of the patient involved and his or her health care provider. Its utility in the health care system, however, still remains poorly defined. We conducted this scoping review to determine the impact of asynchronous telehealth on health outcomes, process of care, access to health services, and health resources., Methods: A search was performed up to December 2006 of MEDLINE, CINAHL, HealthSTAR, the Database of Abstracts of Reviews of Effectiveness, and The Cochrane Library. Studies were included if they contained original data on the use of asynchronous telehealth and were published in English in a peer-reviewed journal. Two independent reviewers screened all articles and extracted data, reaching consensus on the articles and data identified. Data were extracted on general study characteristics, clinical domain, technology, setting, category of outcome, and results. Study quality (internal validity) was assessed using the Jadad scale for randomized controlled trials and the Downs and Black index for non-randomized studies. Summary data were categorized by medical specialty and presented qualitatively., Results: The scoping review included 52 original studies from 238 citations identified; of these 52, almost half focused on the use of telehealth in dermatology. Included studies were characterized by diverse designs, interventions, and outcomes. Only 16 studies were judged to be of high quality. Most studies showed beneficial effects in terms of diagnostic accuracy, wait times, referral management, and satisfaction with services. Evidence on the impact of asynchronous telehealth on resource use in dermatology suggests a reduction in the number of, or avoidance of, in-person visits. Reports from other clinical domains also described the avoidance of unnecessary transfer of patients., Conclusions: A significant portion of the asynchronous telehealth literature involves its use in dermatology. Although the quality of many original studies remains poor, at least within dermatology, there is consistent evidence suggesting that asynchronous telehealth could lead to shorter wait times, fewer unnecessary referrals, high levels of patient and provider satisfaction, and equivalent (or better) diagnostic accuracy when compared with face-to-face consultations. With the exception of a few studies in pediatric asthma, the impact of this intervention on individual health outcomes remains unknown.

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.