The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns.

BACKGROUND: In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. METHODS: We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. RESULTS: Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. CONCLUSIONS: The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.

Adherence to routine use of pharmacological prophylaxis of heterotopic ossification after total hip arthroplasty: results from an Italian multicenter, prospective, observational survey.

BACKGROUND: In spite of the proven efficacy of pharmacological prophylaxis of heterotopic ossification following total hip arthroplasty, its routine use is still debated, and no data are available regarding the adherence to its administration in clinical practice. MATERIALS AND METHODS: In this prospective, observational, multicenter study, 480 consecutive patients operated on for primary total hip arthroplasty during the year 2009 were followed radiographically for 12 months after surgery in order to assess the incidence of periprosthetic heterotopic ossification. Surgeons were free to choose whether to administer pharmacological prophylaxis, and were asked to keep a record of the duration of the prophylaxis (if used) or the reasons for not using it. To facilitate the statistical analysis, all of the participating centers agreed to use only one drug (celecoxib) that had already proven to be effective. RESULTS: 368 patients were administered celecoxib and 112 patients did not receive any prophylaxis. Reported reasons for not administering celecoxib prophylaxis were the surgeon's opinion that prophylaxis was not needed on a routine basis (84/112 patients, 75%), previous history of gastrointestinal bleeding (17.8%), and concomitant cardiorenal pathologies (7.1%). The overall incidence of heterotopic ossification in the celecoxib-treated patients was 23% (no cases of Brooker grade 3 or 4 ossifications), compared to 55% in the untreated patients (Brooker grade 3 and 4: 8.9%). Multivariate analysis showed that celecoxib prophylaxis was the single most important variable when predicting the occurrence of heterotopic ossification. CONCLUSIONS: This study confirms the efficacy and tolerability of celecoxib for the prophylaxis of heterotopic ossification after total hip arthroplasty, and shows how the surgeon's belief that routine prevention is not required still plays an important role in the determination of this complication, together with the fear of possible unwanted side effects.

Do coxibs reduce prescription of gastroprotective agents? Results of a record linkage study.

BACKGROUND: Coxibs are claimed to be cost-effective drugs and reduced prescription of gastroprotective agents is assumed to be one of their major benefits. Real life prescription of these drugs may be substantially different than that considered in pharmacoeconomic analyses or claimed by drug companies, yet. Our objective was to evaluate whether coxibs were associated with reduced prescription of gastro-protective agents (GPAs, specifically proton pump inhibitors, H2 blockers and misoprostol) compared to non selective NSAIDs. METHODS: A record-linkage study was performed using 2001 outpatient prescription data from the province of Modena (about 632,000 inhabitants, in Northern Italy). Logistic regression was used to calculate the odds ratio of GPA prescription for coxib and non-selective NSAID adult users (> 14 years). Three categories of users were further investigated: "acute", "chronic and "incident or new". Main outcome measures were same-day co-prescription and 30 days prescription of GPAs in coxibs and non selective NSAIDs users. To limit selection bias, data were adjusted for age, sex, DDD of coxibs and non selective NSAIDs received during 2001, DDD of GPAs and (for non-incident users) DDD of NSAIDs received during the previous 4 years RESULTS: Same day co-prescription rates were similar considering the overall population and "acute" users. Chronic coxibs users instead showed higher co-prescription rates than chronic NSAIDs users (OR = 1.2, p < 0.05). GPA prescription within thirty days was also higher among all subgroups of coxibs users (OR ranging from 1.6 to 2.0, p < 0.001). CONCLUSION: Assumptions made in pharmacoeconomic analyses on coxibs (lower GPA prescription associated with coxibs use) may be overly optimistic. Claims made through cost-effectiveness data should be carefully interpreted, and mechanisms for attributing drug prices revised accordingly.