Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project.

PURPOSE: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. METHODS: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. RESULTS: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2). CONCLUSIONS: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

How to early recognize mood disorders in primary care: A nationwide, population-based, cohort study.

BACKGROUND: Mood disorders are managed predominantly in primary care. However, general practitioners' (GPs) ability to detect and diagnose patients with mood disorders is still considered unsatisfactory. The aim of the present study was to identify predictors for the early recognition of depressive disorder (DD) and bipolar disorder (BD) in general practice. METHODS: A cohort of 1,144,622 patients (605,285 women, 539,337 men) was investigated, using the Health Search IMS Health Longitudinal Patient Database. Predictors of DD or BD were identified at baseline encompassing somatization-related features, lifestyle variables, medical and psychiatric comorbidities. Patients were followed up as long as the following events occurred: diagnoses of DD or BD, death, end of the registration with the GP, end of the study period. RESULTS: We found an incidence rate of DD or BD of 53.61 and 1.5 per 10,000 person-years, respectively. For both the conditions, the incidence rate grew with age. Most of the lifestyle variables and medical comorbidities increased the risk of mood disorders. The strongest effect was found for migraine/headache (HR [95% CI]=1.32 [1.26-1.38]), fatigue (1.32 [1.25-1.39]) irritable bowel syndrome (1.15 [1.08-1.23]), and pelvic inflammation disease (1.28 [1.18-1.38]). CONCLUSIONS: Several predictors, in particular somatic symptoms, could be interpreted as an early sign of a mood disorder, and represent a valid indication for the GPs diagnostic process of mental disorders.

Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study.

UNLABELLED: Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy. INTRODUCTION: A signal of cardiac valve disorders with use of bisphosphonates was identified in the literature and EudraVigilance database, which contains reports of suspected adverse drug reactions from worldwide sources. The aim of this study was to evaluate the association using population-based healthcare data. METHODS: This was a case-control study among users of bisphosphonates and other drugs for osteoporosis in six healthcare databases covering over 30 million individuals in Italy, Netherlands and the UK from 1996 to 2012. Prescriptions/dispensations were used to assess drug exposure. Newly diagnosed cases of cardiac valvulopathy were identified via disease codes/free-text search. Controls were matched to each case by age, sex, database and index date. Adjusted odds ratios (ORs) were estimated using conditional logistic regression for the pooled data and meta-analysis of individual database risk estimates. RESULTS: A small but statistically significant association was found between exposure to bisphosphonates as a class and risk of valvulopathy. Overall risk was 18 % higher (95 % CI 12-23 %) in those currently exposed to any bisphosphonate (mainly alendronate and risedronate) vs. those not exposed within the previous year. Risk of valve regurgitation was 14 % higher (95 % CI 7-22 %). Decreased valvulopathy risk was observed with longer cumulative duration of bisphosphonate use, compared to use of less than 6 months. Meta-analyses of database-specific estimates confirmed results from pooled analyses. CONCLUSIONS: The observed increased risks of cardiac valvulopathy with bisphosphonate use, although statistically significant, were quite small and unlikely to be clinically significant. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy and to investigate possible mechanisms for the association.

Allopurinol adherence among patients with gout: an Italian general practice database study.

AIMS: Allopurinol is used as long-term therapy to reduce the occurrence of gout flares. This study estimated the impact of patient adherence to allopurinol on hyperuricaemia (serum uric acid levels, sUA > 6 mg/dl) and the identification of non-adherence predictors. METHODS: The Italian Health Search-CSD Longitudinal Patient Database was accessed to identify outpatients aged ≥ 18 years with gout and prescribed with allopurinol during the years 2002-2011. Patients with a proportion of days covered ≥ 80% were considered adherent to allopurinol. Data on sUA levels over the first year of therapy were categorised in three time-windows (30-89; 90-149; 150-365 days). Logistic regressions were used to estimate the association between adherence and hyperuricaemia, as well as non-adherence predictors. RESULTS: A total of 3727 patients were included. In the interval 0-29 days, the proportion of patients adherent to allopurinol was 45.9%, while up to 89, 149 and 365 days the percentages were 16.7%, 10.0% and 3.2%, respectively. The proportions of hyperuricaemic patients for each time-window were 43.1%, 42.4%, 32.6% and 59.0%, 64.0%, 66.4% among adherent and non-adherent patients, respectively. In the multivariable analysis, adherence was associated with a significant lower risk of hyperuricaemia. The adjusted ORs were 0.49 (95% CI: 0.33-0.73), 0.40 (95% CI: 0.24-0.67) and 0.23 (95% CI: 0.15-0.34) for the first, second and third time-window, respectively. Patients with hypertension (adjusted OR = 0.64, 95% CI: 0.42-0.99) and history of gout flares (adjusted OR = 0.55, 95% CI: 0.32-0.95) were significantly adherent to allopurinol. CONCLUSIONS: Adherence monitoring in patients with gout is pivotal to ensure the effectiveness of therapy. To gain a better patient adherence, the communication between physicians and patients should be improved.

Use and treatment modalities for SSRI and SNRI antidepressants in Italy during the period 2003-2009.

OBJECTIVES: This drug utilization study aims to evaluate the incidence and prevalence of prescribed antidepressants (SSRIs or SNRIs) and to describe treatment modalities in Italy during the period 2003-2009. METHODS: This retrospective analysis on the prescription and treatment modalities of SSRIs or SNRIs is based on an Italian general practice database, which includes data on about 1,000,000 patients. Eligible patients should have age≥18 years, and ≥1 year of clinical history. Prevalence, incidence of use and adherence were calculated for SSRIs and SNRIs and for the individual agents. RESULTS: The prevalence of SSRI use increased from 7.5% (2003) to 13.1% (2009) while the prevalence of SNRI use increased from 0.8% to 2.5%. The most evident increase was reported for escitalopram (+2.78%). The number of new antidepressant users (incidence rate) showed a modest decrease for SSRIs (-0.3%) and a slight increase for SNRIs (+0.9%). A higher percentage of continuers was reported for SSRIs versus SNRIs (15.1% vs 13.0%). Escitalopram was associated with the highest percentage of continuers and with the highest number of days of uninterrupted treatment. Overall, over 10% of antidepressant users switched their first choice during one year of follow-up. Escitalopram was associated with the highest frequency of 'high' adherers (28.5%). CONCLUSIONS: SSRIs may be regarded as the elective treatment for depression. Of the SSRIs, escitalopram seems to be associated with the highest number of days of uninterrupted treatment, the lowest proportion of switchers and the highest adherence. This consideration might have practical relevance when comparing escitalopram to other SSRIs and to venlafaxine and duloxetine.

Occurrence of Lily mottle virus on Lilium in Italy.

Lily mottle virus (LMoV), a member of the genus Potyvirus, is one of the main viruses infecting lily. Symptoms on lily differ according to the susceptibility and sensitivity of different cultivars and hybrids. They range from leaf mottle or mosaic, vein clearing, chlorotic and yellow streaking, leaf curling, and necrotic spots, to milder forms of leaf symptoms. Plants may even be symptomless at some stages of growth. A varietal collection of Lilium from the early 1990s is held in Pistoia Province (Tuscany, Italy) and is composed of Asian hybrids obtained from intraspecific breeding of commercial cultivars. During a survey conducted from May to June 2010, several plants showing vein clearing, leaf mottle, leaf mosaic, and reddish brownish necrotic spots were observed. Leaf samples from 60 symptomatic or symptomless lily plants, belonging to 20 cultivars, were collected and tested for the presence of LMoV. Samples were assayed by double-antibody sandwich (DAS)-ELISA and eight of them, belonging to four different cultivars, tested positive. Total RNA was extracted from 2 g of leaf tissue of every collected sample according to the protocol described earlier (3) and cDNA synthesis was performed with an iScript cDNA Synthesis Kit (Bio-Rad, Hercules, CA). Samples were tested by reverse transcription (RT)-PCR and real-time PCR assays using primers LMoV1 (5'-GCAAATGAGACACTCAATGCTG-3') and LMoV2 (5'-CGTGCGTGAAGTAACTTCATAG-3') designed to amplify 651 bp of the coat protein (CP) gene of LMoV (1). Results obtained with RT-PCR and real-time PCR exactly matched those achieved with ELISA assay, and the eight positive samples showed amplicons of the expected size. PCR products from five infected samples were directly sequenced from both directions and submitted in GenBank (Accessions Nos. JQ655106 to JQ655110). Our isolates share more than 99% nucleotide identity among each other. Comparison with other LMoV-CP gene sequences present in GenBank showed nucleotide identities ranging from 93 to 94% with LMoV isolates from South Korea (GenBank Accession Nos. GQ150683 to GQ150686), China (GenBank Accession Nos. EU348826, AJ748256, AJ564636, and AJ564637), Australia (GenBank Accession No. JN127341), and Japan (GenBank Accession No. AB570195). To our knowledge, this is the first report of LMoV on Lilium in Italy where this virus was already reported to infect escarole (2). Considering the economic importance of Lilium production as a flowering plant in Pistoia Province, and in several other areas of Italy, the report of LMoV present on lilies suggests the use of healthy propagation material and the adoption of preventive measures to avoid its diffusion. References: (1) J.-H. Lim et al. Korean J. Microbiol. 45:251, 2009. (2) V. Lisa et al. Plant Dis. 86:329, 2002. (3) D. J. MacKenzie et al. Plant Dis. 81:222, 1997.

[Interrelationship between oral contraceptives and some parameters of the coagulative-fibrinolytic function (author's transl)].

PIP: The effect of 2 oral contraceptives (OCs) (0.05 mg ethinyl estradiol + 0.250 mg norgestrel; 0.03 mg ethinyl estradiol + 0.125 mg norgestrel) on some parameters of the coagulative-fibrinolytic function was studied in a group of young women 19-26 years of age. To this end, blood samples were taken before OC use and during the 2nd month of suspension after 3, 6, 12, 18, 24, 30, 36, 42, and 48 months of treatment. The parameters examined were: fibrinogen, plasminogen, antithrombin 3, chi 2 macroglobulin, and FDP. The most significant data (presented in tabular form) were: the gradual reduction of antithrombin 3 until the 36th month of treatment, the diminution of chi 2 macroglobulin, the progressive increase of FDP, and the stability of fibrinogen and plasminogen during the period of observation. (author's)^ieng

[Oestroprogestogen interference on some haematochemical parameters: glycaemia, lipid metabolism and hepatic functionality (author's transl)].

PIP: The collateral effects of 2 oral contraceptives (OCs) (0.05 mg ethinyl estradiol + 0.250 mg norgestrel; 0.03 mg ethinyl estradiol + 0.125 mg norgestrel) were studied in a group of young women ages 19-26. These effects were investigated by evaluating some hemato-chemical parameters such as glycemia; lipid metabolism (triglycerides, cholesterol, and total lipids); and hepatic functionality (SGOT, SGPT, serum bilirubin, alkaline phosphatase). Blood samples were taken before OC use and then during the 2nd month of suspension after 3, 6, 12, 18, 24, 30, 36, 42, and 48 months of treatment. This research, carried out over a period of 4 years found no significant variations which would necessitate cessation of treatment. (author's)^ieng