This review examines evidence for the effectiveness of cannabinoids in chronic noncancer pain (CNCP) and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL, and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 randomised controlled trials (RCTs) and 57 observational studies. Forty-eight studies examined neuropathic pain, 7 studies examined fibromyalgia, 1 rheumatoid arthritis, and 48 other CNCP (13 multiple sclerosis-related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, pooled event rates (PERs) for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo); significant effect for cannabinoids was found; number needed to treat to benefit was 24 (95% confidence interval [CI] 15-61); for 50% reduction in pain, PERs were 18.2% vs 14.4%; no significant difference was observed. Pooled change in pain intensity (standardised mean difference: -0.14, 95% CI -0.20 to -0.08) was equivalent to a 3 mm reduction on a 100 mm visual analogue scale greater than placebo groups. In RCTs, PERs for all-cause adverse events were 81.2% vs 66.2%; number needed to treat to harm: 6 (95% CI 5-8). There were no significant impacts on physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP.

Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED of morphine alone. In addition, the ED for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.

Aim: Develop a measure of frailty for older acute inpatients to be performed by non-geriatricians. Method: The Reported Edmonton Frail Scale (REFS) was adapted from the Edmonton Frail Scale for use with Australian acute inpatients. With acute patients aged over 70 years admitted to an Australian teaching hospital, we validated REFS against the Geriatrician's Clinical Impression of Frailty (GCIF), measures of cognition, comorbidity and function, and assessed inter-rater reliability.Results: REFS was moderately correlated with GCIF (n = 105, R = 0.61, P < 0.01), Mini-Mental State Examination impairment (n = 61, R = 0.49, P < 0.001), Charlson Comorbidity Index (n = 59, R = 0.51, P < 0.001) and Katz Daily Living Scale (n = 59, R = 0.51, P < 0.001). Inter-rater reliability of REFS administered by two researchers without medical training was excellent (kappa = 0.84, n = 31). Conclusion: In this cohort of older acute inpatients, REFS is a valid, reliable test of frailty, and may be a valuable research tool to assess the impact of frailty on prognosis and response to therapy.Key words: acute care, acute illness, aged, frailty, geriatric medicine. IntroductionFrailty may affect the safety and efficacy of therapy and may be a key prognostic marker in the care of acute geriatric medicine inpatients. To test this hypothesis, a reliable, valid measure of frailty in acute inpatients is required.The core feature of frailty is increased vulnerability to stressors because of impairments in multiple inter-related systems that lead to decline in homeostatic reserve and resiliency, although the definition of frailty remains contentious [1]. Many tools for the identification of frailty, such as the phenotype model developed by Fried and colleagues [2], rely on objective measures of physical function. Purser and colleagues [3] recently described the utility of several performance-based measures and of two composite scores to identify frailty in a group of older adult inpatients with significant cardiovascular disease. However, in an acute care hospital population, performance-based measures may provide more information about the severity and type of acute illness than about the underlying frailty of a patient. The estimation of frailty just prior to acute illness in inpatients may inform decisions on management and prognosis. Self-reported function has been shown to be a good estimate of objective measures of physical function [4].Large prospective studies on the role of frailty in the prognosis of acute illness will be facilitated by the use of a frailty measure that can be performed by non-geriatrician researchers. The Edmonton Frail Scale, which is administered by a research assistant without medical training, has been validated against the Geriatricians' Clinical Impression of Frailty (GCIF) in a Canadian population referred for comprehensive geriatric assessment [5]. Interestingly, the inpatients (40% of the study population) scored significantly higher on the Edmonton Frail Scale than outpatients. While this may represent the c...