Introduction: Europe has seen a steady increase in the use of prescription opioids, especially in non-cancer indications. Epidemiological data on the patterns of use of opioids is required to optimize prescription. We aim to describe the patterns of opioid therapy initiation for non-cancer pain and characteristics of patients treated in a region with five million inhabitants in the period 2012 to 2018.Methods: Population-based retrospective cohort study of all adult patients initiating opioid therapy for non-cancer pain in the region of Valencia. We described patient characteristics at baseline and the characteristics of baseline and subsequent treatment initiation. We used multinominal regression models to identify individual factors associated with initiation.Results: A total of 957,080 patients initiated 1,509,488 opioid treatments (957,080 baseline initiations, 552,408 subsequent initiations). For baseline initiations, 738,749 were with tramadol (77.19%), 157,098 with codeine (16.41%) 58,436 (6.11%) with long-acting opioids, 1,518 (0.16%) with short-acting opioids and 1,279 (0.13%) with ultrafast drugs. When compared to tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and had more comorbidities, whereas initiators with codeine were more prone to be healthier and younger. Treatments lasting less than 7 days accounted for 41.82% of initiations, and 11.89% lasted more than 30 days. 19.55% of initiators with ultrafast fentanyl received more than 120 daily Morphine Milligram Equivalents (MME), and 16.12% of patients initiating with long-acting opioids were prescribed more than 90 daily MME (p < 0.001). Musculoskeletal indications accounted for 65.05% of opioid use. Overlap with benzodiazepines was observed in 24.73% of initiations, overlap with gabapentinoids was present in 11.04% of initiations with long-acting opioids and 28.39% of initiators with short-acting opioids used antipsychotics concomitantly. In subsequent initiations, 55.48% of treatments included three or more prescriptions (vs. 17.60% in baseline initiations) and risk of overlap was also increased.Conclusion: Opioids are initiated for a vast array of non-oncological indications, and, despite clinical guidelines, short-acting opioids are used marginally, and a significant number of patients is exposed to potentially high-risk patterns of initiation, such as treatments lasting more than 14 days, treatments surpassing 50 daily MMEs, initiating with long-acting opioids, or hazardous overlapping with other therapies.

Background Multi-state models are complex stochastic models which focus on pathways defined by the temporal and sequential occurrence of numerous events of interest. In particular, the so-called illness-death models are especially useful for studying probabilities associated to diseases whose occurrence competes with other possible diseases, health conditions or death. They can be seen as a generalization of the competing risks models, which are widely used to estimate disease-incidences among populations with a high risk of death, such as elderly or cancer patients. The main advantage of the aforementioned illness-death models is that they allow the treatment of scenarios with non-terminal competing events that may occur sequentially, which competing risks models fail to do. Methods We propose an illness-death model using Cox proportional hazards models with Weibull baseline hazard functions, and applied the model to a study of recurrent hip fracture. Data came from the PREV2FO cohort and included 34491 patients aged 65 years and older who were discharged alive after a hospitalization due to an osteoporotic hip fracture between 2008-2015. We used a Bayesian approach to approximate the posterior distribution of each parameter of the model, and thus cumulative incidences and transition probabilities. We also compared these results with a competing risks specification. Results Posterior transition probabilities showed higher probabilities of death for men and increasing with age. Women were more likely to refracture as well as less likely to die after it. Free-event time was shown to reduce the probability of death. Estimations from the illness-death and the competing risks models were identical for those common transitions although the illness-death model provided additional information from the transition from refracture to death. Conclusions We illustrated how multi-state models, in particular illness-death models, may be especially useful when dealing with survival scenarios which include multiple events, with competing diseases or when death is an unavoidable event to consider. Illness-death models via transition probabilities provide additional information of transitions from non-terminal health conditions to absorbing states such as death, what implies a deeper understanding of the real-world problem involved compared to competing risks models.

Osteoporotic hip fractures in older people may confer an increased risk of subsequent hip fractures and death. The aim of this study was to estimate the cumulative incidence of both recurrent hip fracture and death in the Valencia region. We followed a cohort of 34,491 patients aged ≥65 years who were discharged alive from Valencia Health System hospitals after an osteoporotic hip fracture between 2008 and 2015, until death or end of study (December 31, 2016). Two Bayesian illness-death models were applied to estimate the cumulative incidences of recurrent hip fracture and death by sex, age, and year of discharge. We estimated 1-year cumulative incidences of recurrent hip fracture at 2.5% in women and 2.3% in men, and 8.3% and 6.6%, respectively, at 5 years. Cumulative incidences of total death were 18.3% in women and 28.6% in men at 1 year, and 51.2% and 69.8% at 5 years. One-year probabilities of death after recurrent hip fracture were estimated at 26.8% and 43.8%, respectively, and at 57.3% and 79.2% at 5 years. Our analysis showed an increasing trend in the 1-year cumulative incidence of recurrent hip fracture from 2008 to 2015, but a decreasing trend in 1-year mortality. Male sex and age at discharge were associated with increased risk of death. Women showed higher incidence of subsequent hip fracture than men although they were at the same risk of recurrent hip fracture. Probabilities of death after recurrent hip fracture were higher than those observed in the general population.