Analgesic use in a Norwegian general population: Change over time and high-risk use - The Tromsø Study

Published version, also available at http://dx.doi.org/10.1186/s40360-015-0016-yBackground: Increased use of analgesics in the population is a cause for concern in terms of drug safety. There is a paucity of population-based studies monitoring the change in use over time of both non-prescription (OTC) analgesics and prescription (Rx) analgesics. Although much is known about the risks associated with analgesic use, we are lacking knowledge on high-risk use at a population level. The purpose of this study was to estimate the prevalence of non-prescription and prescription analgesic use, change over time and the prevalence in the presence of potential contraindications and drug interactions in a general population. Methods: A repeated cross-sectional study with data from participants (30–89 years) of the Tromsø Study in 2001–02 (Tromsø 5; N = 8039) and in 2007–08 (Tromsø 6; N = 12,981). Participants reported use of OTC and Rx analgesics and regular use of all drugs in the preceding four weeks. Change over the time period was analyzed with generalized estimating equations. The prevalence of regular analgesic use in persons with or without a clinically significant contraindication or drug interaction was determined in the Tromsø 6 population, and differences were tested with logistic regression. Results: Analgesic use increased from 54 to 60 % in women (OR = 1.24, 95 % CI 1.15–1.32) and from 29 to 37 % in men (OR = 1.39, 95 % CI 1.27–1.52) in the time period; the increase was due to sporadic use of OTC analgesics. There was substantial regular use of analgesics in several of the contraindication categories examined; the prevalence of non-steroidal anti-inflammatory drugs was more than eight per cent among persons with chronic kidney disease, gastrointestinal ulcers, or high primary cardiovascular risk. About four per cent of the study population demonstrated at least one potential drug interaction with an analgesic drug. Conclusions: The use of analgesics increased in the time period due to an increase in the use of OTC analgesics. Analgesic exposure in the presence of contraindications or drug interactions may put patients at risk. Public and prescriber awareness about clinically relevant contraindications and drug interactions with analgesics need to be increased

Rapid responses Topic collections Primary care Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials

Abstract Objective To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with osteoarthritis of the knee. Design Systematic review and meta-analysis of randomised placebo controlled trials. Studies reviewed 23 trials including 10 845 patients, median age of 62.5 years. 7807 patients received adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average duration of symptoms was 8.2 years. Main outcome measure Change in overall intensity of pain. Results Methodological quality of trials was acceptable, but 13 trials excluded patients before randomisation if they did not respond to NSAIDs. One trial provided long term data for pain that showed no significant effect of NSAIDs compared with placebo at one to four years. The pooled difference for pain on visual analogue scale in all included trials was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31). Conclusion NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended

Post mortem tissue distribution of quetiapine in forensic autopsies

The antipsychotic drug quetiapine is widely used, and increasingly prescribed off-label. Furthermore, quetiapine use has been linked to increased mortality rates, most likely due to a range of cardiovascular and metabolic adverse effects. This makes quetiapine a relevant substance in forensic toxicology casework. Quetiapine is believed to undergo significant post mortem redistribution. Herein, we present tissue distribution and concentration levels of quetiapine in post mortem whole blood, brain tissue, skeletal muscle, and liver tissue in a series of 14 quetiapine-implicated forensic autopsy cases along with the quetiapine concentrations determined in femoral whole blood in conjunction with the autopsies. Quantification was performed using liquid-liquid extraction and a validated UPLC-MSMS method. Six deaths were attributed to intoxication with quetiapine in combination with other substances; there were no quetiapine monointoxications. In eight cases, death was attributed to other causes than drug toxicity. In a majority of the cases, liver tissue contained the highest quetiapine concentrations, while whole blood levels were the lowest. Central (heart) blood concentrations were generally higher than peripheral (femoral) blood levels. Quetiapine concentrations in femoral blood correlated most strongly with concentrations in skeletal muscle. Otherwise, there was no consistent hierarchy of quetiapine tissue concentrations, and the tissue distribution showed no clear relationship with the length of the post mortem interval

Sikkerhet ved bruk av langtidsvirkende β₂-agonister ved astma

BAKGRUNN Bruk av β-agonister til inhalasjon har siden introduksjonen for mer enn 50 år siden blitt assosiert med økt dødelighet. På 2000-tallet har bekymringene vært spesielt knyttet til langtidsvirkende β2-selektive agonister. Formålet med denne gjennomgangen var å kartlegge dokumentasjonen for en eventuelt økt risiko for død og alvorlige hendelser ved bruk av disse midlene. KUNNSKAPSGRUNNLAG Etter søk i PubMed selekterte vi ti studier som oppfylte forhåndsdefinerte inklusjonskriterier. RESULTATER De ti inkluderte studiene omfattet 66 664 pasienter. Det ble observert 16 astmarelaterte dødsfall i grupper eksponert for langtidsvirkende β2-selektive agonister (totalt 33 043 pasienter) og fire i kontrollgruppene (totalt 33 621 pasienter). Mesteparten av dødsfallene er registrert i én enkelt, stor og pragmatisk studie. FORTOLKNING Bruk av langtidsvirkende β2-selektive agonister er assosiert med en liten økning i dødelighet. Det er usikkert om samtidig bruk av inhalasjonssteroider fullt ut opphever denne effekten