Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain ). They found a paucity of placebo‐controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate‐certainty to low‐certainty evidence). Nonsteroidal anti‐inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate‐to‐severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

To identify and quantify risk factors for incident knee osteoarthritis (KOA) across the lifespan. This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio (HR), or risk ratio (RR) and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to determine the certainty of evidence. Population attributable fractions (PAFs) were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets. We identified 132 studies evaluating >150 risk factors. Higher body mass index (BMI), previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 1.56 (1.25, 1.95), 3.02 (1.93, 4.71), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors including occupational physical activity also contribute to radiographic or symptomatic KOA. Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA. PROSPERO ID: CRD42023391187 FUNDING: Sydney Musculoskeletal Health, Faculty of Medicine and Health, The University of Sydney.

Identifying potentially inappropriate medicines (PIMs) leading to adverse drug events may reduce the risk of morbidity and mortality in older people.