Background:
The use of opioids has increased dramatically, especially in Spain; between 2008 and 2015 the use of opioids increased an 83.5%. These medications have many adverse effects and there are few head to head studies with other non-opioid pain killers.
Hypothesis: The use of opioids is frequent in our populationa. Opioids have more adverse effects than other non-opioid pain killers.
Objectives: 1. To describe the drug utilization (sociodemographic, type, dosage, indications, persistence) of opioids (tramadol, codeine, morphine, fentanyle) (WP1) among subjects of at least 18 years old. 2.To assess the incidence of the adverse effects of the different opioids and compared with other non-opioid pain killers (oral NSAID, cox2 inhibitors, paracetamol, metamizole). To study the association between the long term use of opioids and paracetamol. All results will be stratified by indication and age.
Methods: A population based cohort study. The WP2 will encompass 3 cohorts: 1. incident opioid users, 2. incident non-anti-inflammatory drugs and 3. incident anti-inflammatory drug users. Data will be gathered from the SIDIAP database. Source population: All those registered at least 1 year in SIDIAP database during the study period. Study period: 01/01/2007-31/12/2016. Study population: all incident users of study drugs durgin the study period aged 18 and over. Inclusion: at least 2 consecutive dispensations of the study drugs during the study period. For the WP2 (in addition of the above): No use of index drugs in the previous year, no surgery in the 30 days before starting their first dispensation. No exclusions. Follow-up: from the lastest of 1. Start of study period or 1 year of valid data, until the earliest of: end of enrolment in database (moving out or death) or date of last data capturing. For the WP2: patients will be followed from the date of second drug dispensation which follows the latest of 1. start of study period or 1 year of valid data, until the earliest of 1.end of enrolment in the database, date of last data capturing or event of interest. Variables: Exposures: WP1: the main drugs of interest will be the opioids and the non-opioid pain killers will be the active comparators for the WP2. The exposure will be categorized in past, recent, current. Patients switching treatment will be censored at the date of switching. Concomitant use of drugs will be assessed and considered for secondary analysis. Outcomes: WP1: age, sex, BMI, Charlson Comorbidity Index (CCI), eFi frailty index, pfeiffer and minimental score, EQ5D, type and dosage of opioid used, type of prescriber, comorbidity for which the opioid was prescribed. In order to define periods of continious use of drugs, any 2 dispensations of the same drug will be concatenated if the gap is <90 days. A carry-over period of 30 days will be added after last prescription to account for lack of compliance and carryover effects. Compliance will be measured as medication possesion ratio. WP2: Cardiac arrhythmia, delirium/confusion, fractures (hip, pelvis, wrist, humerus), falls, sleep disorders (sleep apnea, somnolence), constipation, opioid dependence and abuse, all cause mortality. Potential confounders (in the year before index date): age, sex, BMI, sociodemographic status, medical conditions, CCI, bone fractures, major surgeries, drugs (hypnotics, benzodiacepines, aspirin, SSRI or anticonvulsant), number of different ATC prescribed, number of GP visit, hospital admisions, falls, traffic accidents. Statistical analysis: Kaplan Meier for drug persistence, Drug safety: Propensity score will be calculated using confounders. Cox regression will be used to estimate event risk according to drug use.