Incidence, causative factors and mortality rates of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in northern Italy: data from the REACT registry.

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. We assessed incidence, drug exposure and mortality, analysing data obtained from the Lombardy Registry of Severe Cutaneous Reactions (REACT). METHODS: Data were collected from hospitals in the Italian Lombardy region (9,502,272 people). A trained monitor was sent to the reporting hospital to collect data on drug exposure and clinical features. The algorithm for drug causality for epidermal necrolysis algorithm was applied to assess drug causality. Defined Daily Dose (DDD) was used to express drug consumption. RESULTS: From April 2009 to November 2014, 17 cases of TEN and 59 cases of SJS were collected. The overall incidence rate was 1.40 cases (95%CI, 1.12-1.76) per million people per year. A total of 15 cases died during hospitalization with a mortality rate of 16.9% for SJS and 29.4% for TEN. Overall, 55.4% of cases had a probable or very probable relation with drug exposure. In a total of five patients (6.6%), no causative drug for the reaction was identifiable. Allopurinol contributed to the highest number of cases (23 cases), while the highest incidence based on more than one case reported was observed for cotrimoxazole and lamotrigine, with 5.37 cases (95%CI, 2.09-13.80) and 3.54 (95%CI, 1.21-10.42) per 10 million DDD/year, respectively. CONCLUSIONS: We confirmed that SJS and TEN are rare adverse cutaneous reactions. As expected, mortality was influenced by the degree of skin detachment. The profile of drugs associated with the reactions was in agreement with data from other surveillance systems.

[Surveillance of severe cutaneous drug reactions: experience REACT-Lombardia]. / Sorveglianza di reazioni gravi cutanee da farmaco: l'esperienza REACT-Lombardia.

Adverse drug reactions affecting the skin have particular relevance as they may cause significant mortality and a possible modification of the benefit/risk profile of the concerned drug. The following entities are of special importance: Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug rash with eosinophilia and systemic symptoms (DRESS). On the above mentioned reactions we focused our surveillance programme in the Lombardy region, the REACT-Lombardia project. The REACT registry involved 22 hospital-based dermatological centres, collecting, from April 2009 up to March 2014, a total of 72 cases of SJS-TEN, 17 cases of AGEP and 9 cases of DRESS. Allopurinol was the drug associated with the largest number of cases of SJS/TEN (21 cases) followed by paracetamol (8 cases), levofloxacine (6 cases) and carbamazepine (4 cases). The risk for specific drug exposures was estimated by employing drug utilization data expressed as Defined Daily Doses (DDD). Mortality rate from SJS-TEN was 21%. Together with the registry, a "hub and spoke" clinical network for the management of severe cutaneous reactions was established with the Burn Unit of Niguarda Ca' Granda Hospital as the reference center for the most critical patients.

Statin-associated psychiatric adverse events: a case/non-case evaluation of an Italian database of spontaneous adverse drug reaction reporting.

BACKGROUND: The inhibitors of HMG-CoA reductase ('statins') are widely prescribed hypolipidaemic drugs, which have been evaluated in several clinical trials involving hundreds of thousands of patients. From a safety perspective, both clinical trials and post-marketing surveillance have demonstrated that statins are generally well tolerated, with rare serious adverse drug reactions (ADRs) that affect mainly muscle, liver and kidney. However, recent interest has been focused on a potential risk of psychiatric ADRs associated with statins, including memory loss, depression, suicidality, aggression and antisocial behaviour. Special attention is currently being paid to the potential for statin-induced sleep disorders. OBJECTIVE: To investigate the hypothesis that statins may be associated with psychiatric adverse events using quantitative and qualitative signal analysis. METHODS: The Interregional Group of Pharmacovigilance database holds reports of suspected ADRs submitted since 1988 from eight Italian regions. In the present analysis, only reports ranked at least 'possible', according to WHO causality assessment criteria, were considered. Association between statins and psychiatric events was assessed by the case/non-case methodology, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. Cases were defined as patients with at least one reported ADR combined with the system organ class (SOC) 'psychiatric disorders'. The non-cases comprised all patients who did not experience an ADR related to the SOC 'psychiatric disorders'. Index reports comprised all ADR reports involving at least one statin, while all ADR reports not involving statins as suspected drugs were used as controls. RESULTS: According to selection criteria, 35,314 reports were included in the analysis. A total of 71 psychiatric preferred terms combined with statins were identified in 60 reports. Among them, 14 reports (23.3%) noted a positive rechallenge. Both the unadjusted (0.8; 95% CI 0.6, 1.1) and adjusted ROR (0.7; 95% CI 0.6, 1.0) suggested a lower rate of reports of psychiatric events for statins as a whole class compared with all other drugs, although the difference was not significant. The five most frequently reported psychiatric events combined with statins were insomnia, somnolence, agitation, confusion and hallucination. Only insomnia was reported with higher frequency for statins compared with all other drugs (ROR = 3.3; 95% CI 1.9, 5.7), while confusion was reported with a lower frequency (ROR = 0.4; 95% CI 0.1, 0.9). Amongst statins available in Italy, only simvastatin (ROR = 0.5; 95% CI 0.2, 0.9) showed a significantly lower rate of reports of psychiatric events compared with all other drugs together. CONCLUSION: A relatively small number of possible statin-associated psychiatric ADRs have been found in our database. No significant risks for a higher overall reporting of psychiatric ADRs associated with statins were identified in comparison with all other drugs combined. However, statin-associated insomnia resulted in a significant ROR that requires further investigation.

Adequacy of treatment for patients with schizophrenia spectrum disorders and affective disorders in Lombardy, Italy.

OBJECTIVE: This study assessed whether patients being treated for schizophrenia spectrum and affective disorders in Lombardy receive adequate treatment and sought predictors of adequate treatment. METHODS: Patients were aged ≥ 18, were residents of Italy's Lombardy region, and were treated in 2007 for schizophrenia spectrum and affective disorders (N = 44,462). The patients were assessed as part of a retrospective analysis of pharmaceutical and mental health services databases. Adequacy of 12-month treatment from the first psychiatric contact in 2007 was assessed at the patient level. A hierarchical log-binomial regression model was fitted to estimate relative risk and 95% confidence intervals for association between patients, characteristics of the departments of mental health (DMH), and receipt of minimally adequate treatment. RESULTS: About half the patients with serious mental disorders did not receive adequate care; 45.5% of patients with depressive disorders, 55.7% of those with bipolar disorders, and 49.3% of those with schizophrenia spectrum disorders received minimally adequate treatment. Diagnosis of a schizophrenia spectrum disorder or bipolar disorder and male gender predicted adequate treatment, whereas employment and high comorbidity predicted inadequate treatment. Patients who received mental health services in the past year were significantly more likely to receive adequate treatment compared with those who had received services in the past five years or new patients. CONCLUSIONS: Minimally adequate treatment is a useful indicator to monitor quality of care in Italy's regional mental health system. These data should be used at regional and local levels to implement clinical audits, to create benchmark measures, and to define new quality-improvement projects to meet specific DMH needs.