Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study

Background Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Costs and outcomes of treatments for excessive alcohol consumption : making policy decisions with the available data

Aim: To determine which treatments for risky or dependent alcohol consumption provide the best health outcomes for a given expenditure. Methods: Economic evaluation expressing results in cost per unit outcome, from the perspective of the Australian healthcare system. Interventions considered include briefinterventions; psychosocial interventions (motivational approaches, cognitive-behaviouralapproaches and self-guided materials); and pharmacotherapies (acamprosate and naltrexone). Treatment outcomes and standard treatment costs were measured forselected studies, and costs per unit outcome were calculated. Findings: Twenty-nine studies were selected for the analysis. As treatment outcomeswere not consistently expressed in a single unit across interventions, two outcomes were used in the analysis: percentage change in alcohol consumption and percentage change inthe proportion of abstinent days. Brief interventions provided the best cost per unit outcome, followed by psychosocial interventions, then pharmacotherapies. Conclusions: By using two treatment outcomes instead of one we demonstrated that some treatments for alcohol dependence provide better value for money, but as a result wewere unable to complete a formal health economic evaluation. Consistent measurementof alcohol consumption outcomes in research studies would facilitate similar economic evaluations in the future. This work illustrates the difficulties of using research studies with non-comparable outcomes to inform policy on the cost-effectiveness of different treatments

A protocol for a discrete choice experiment: Understanding patient medicine preferences for managing chronic non-cancer pain

Introduction: High rates of chronic non-cancer pain (CNCP), concerns about adverse effects including dependence among those prescribed potent pain medicines, the recent evidence supporting active rather than passive management strategies and a lack of funding for holistic programme have resulted in challenges around decision making for treatment among clinicians and their patients. Discrete choice experiments (DCEs) are one way of assessing and valuing treatment preferences. Here, we outline a protocol for a study that assesses patient preferences for CNCP treatment. Methods and analysis: A final list of attributes (and their levels) for the DCE was generated using a detailed iterative process. This included a literature review, a focus group and individual interviews with those with CNCP and clinicians who treat people with CNCP. From this process a list of attributes was obtained. Following a review by study investigators including pain and addiction specialists, pharmacists and epidemiologists, the final list of attributes was selected (number of medications, risk of addiction, side effects, pain interference, activity goals, source of information on pain, provider of pain care and out-of-pocket costs). Specialised software was used to construct an experimental design for the survey. The survey will be administered to two groups of participants, those from a longitudinal cohort of patients receiving opioids for CNCP and a convenience sample of patients recruited through Australia\u27s leading pain advocacy body (Painaustralia) and their social media and website. The data from the two participant groups will be initially analysed separately, as their demographic and clinical characteristics may differ substantially (in terms of age, duration of pain and current treatment modality). Mixed logit and latent class analysis will be used to explore heterogeneity of responses. Ethics and dissemination: Ethics approval was obtained from the University of New South Wales Sydney Human Ethics committee HC16511 (for the focus group discussions, the one-on-one interviews and online survey) and HC16916 (for the cohort). A lay summary will be made available on the National Drug and Alcohol Research Centre website and Painaustralia\u27s website. Peer review papers will be submitted, and it is expected the results will be presented at relevant pain management conferences nationally and internationally. These results will also be used to improve understanding of treatment goals between clinicians and those with CNCP

Individual-level simulation model for cost benefit analysis in healthcare

Illicit drug use creates significant burden at societal, family and personal levels. Every year substantial resources are allocated for treatment and the consequences of illicit drug use in Australia and around the world. Heroin is one of the major forms of illicit drugs. Several independent heroin treatment strategies or interventions exist and state-of-the art research demonstrates their efficacy and relative costeffectiveness. However, assessing total potential gains and burden from providing all treatment interventions or varying the mix of heroin treatments has never been attempted. This paper proposed an individual-level simulation model (ISM) which addresses net social benefit over a lifetime that can accommodate the complexity of individuals going in and out of multiple treatments and their corresponding costs and benefits arising from different treatments during the life-course of heroin users in the context of New South Wales (NSW) Australia. This model is intended to serve as an effective tool for economic evaluation and policy making in the illicit drug area in Australia. The validity of the model has been assessed by comparing short term outcomes or examining the status of participants at a various points of time predicted from the model with other data sets that were not used to parameterise the model. Initial model results have been also presented to highlight different types of scenario analysis that can be conducted in future

Building a microsimulation model of heroin use careers in Australia

Illicit heroin use is a worldwide problem, with significant health and social costs. Treatment is known to be effective in changing heroin use habits, but it often needs to be provided over a lifetime, with people cycling in and out of treatment. It is therefore important to capture a long-term perspective on heroin use careers. The aim of this project was to build a lifetime microsimulation model of heroin using careers. This paper describes the conceptual logic of the model, the input parameters and the verification and validation results. A microsimulation model was chosen as the most appropriate simulation platform with 9 states, and 111,400 individuals (aged between 18 and 60) each with gender, HIV (human immunodeficiency virus) and HCV (hepatitis C) status, and treatment history. Probabilities associated with crime commission and individually calculated lengths of stay in each state were determined from multiple datasets. The model included costs associated with treatment provision, healthcare services, criminal activity, life years lost, and family benefit of treatment. The final model represented 42 years of a heroin use career for a cohort based on Australian (New South Wales) data. Individuals cycle into and out of heroin using states (including abstinence), as well as treatment and prison states. We were able to build a stable, tractable model and verified all parameters. Validation against external data sources revealed high validity. While there are limitations associated with any model, the heroin career model now has the potential to be used for simulations of alternate policy scenarios

Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study

Background Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain