Incidence of pneumococcal infections among children under 15 years in southern Catalonia throughout the heptavalent conjugate vaccine era, 2002-2009.

PURPOSE: Updating epidemiological studies to document current incidences of pneumococcal diseases are greatly needed in the current era of new pneumococcal conjugate vaccines (PCVs). The aim of this study is to analyze the incidence and distribution of different serotypes causing pneumococcal infections among the pediatric population in southern Catalonia, Spain, throughout the 2002-2009 PCV7 eras. METHODS: A population-based surveillance study was conducted among children aged ≤ 14 years in the region of Tarragona (Catalonia, Spain) during the period 2002-2009. All cases of pneumococcal infections (invasive and non-invasive cases) were included in the study. Incidence rates (per 100,000 population-year) and prevalence of infections caused by serotypes included in different PCV formulations were calculated for the 2002-2005 and 2006-2009 periods. RESULTS: Globally, across the total 2002-2009 period, the incidence of pneumococcal infections was 48.2 per 100,000 children-year (22.4 and 25.8 for invasive and non-invasive infections, respectively). Between 2002-2005 and 2006-2009, the incidence rates largely decreased among children aged <2 years (from 171 to 111 per 100,000 children-year; p = 0.059), but they did not substantially vary among children aged 2-14 years. The percentages of cases caused by serotypes included in PCV7 (60.0 vs. 16.7 %; p < 0.001), PCV10 (75.0 vs. 47.4 %; p = 0.028), and PCV13 (85.0 vs. 70.5 %; p = 0.190) decreased in both periods. CONCLUSION: In this study, which was conducted in a setting with intermediate PCV7 uptakes, a considerable protective direct effect of vaccination occurred among young infants, but an indirect protective effect did not emerge in the rest of the pediatric population. Despite new PCVs with higher serotype coverage, an important proportion of pneumococcal infections is still not covered by these vaccines.

Efficacy and tolerability of ebastine 10 mg plus pseudoephedrine 120 mg in the symptomatic relief of the common cold.

Background: The objective of this multicenter, parallel, double-blind, placebo-controlled clinical trial was to determine the efficacy and tolerability of the combination of ebastine 10 mg plus pseudoephedrine 120 mg once daily after 3 days of treatment in the symptomatic relief of patients with a common cold. Methods: The principal variable studied was the evaluation of overall efficacy and secondary variables were improvement of the patient, evolution of symptoms, disposition of the patient to take the medication again, and variation in nasal peak flow. Results: The percentage of subjects showing a good or excellent treatment efficacy was significantly higher in the group treated with ebastine plus pseudoephedrine (75.8%) than in the group treated with placebo (57.6%; p<0.001). Statistically significant differences were also found in favor of ebastine plus pseudoephedrine when comparing the changes in the sum of scores for nasal and ocular symptoms (p<0.006) or total symptoms (p<0.0016). The tolerability of the active treatment studied was good; that is, no significant differences were found between ebastine 10 mg plus pseudoephedrine 120 mg and placebo. Most adverse events described were slight or moderate in intensity, and no serious adverse events were reported. Conclusions: The combination of ebastine 10 mg immediate release and pseudoephedrine 120 mg sustained release was found effective in the symptomatic treatment of patients suffering from a common cold and as safe as placebo.

A study comparing the inhibitory effects of single and repeated oral doses of ebastine and fexofenadine against histamine-induced skin reactivity.

OBJECTIVE: The aim of this double-blind, randomized, crossover, placebo-controlled clinical trial was to compare the inhibition of the histamine-induced skin reaction induced by ebastine 20 mg with respect to that induced by fexofenadine 120 mg or placebo. METHODS: Eighteen volunteers (10 males, 8 females) received the three treatments once daily for 5 days, with a mean 7-day washout period between treatments. Intradermal tests, using 0.05 ml from a solution containing 100 microg/ml of histamine, were performed at baseline and at 1, 1.5, 2, 3, 10 and 24 h after a single dose and repeated 5-day dose, and in addition after 34, 48, 58 and 72 h after repeated 5-day dose. RESULTS: After 24 h of acute administration, ebastine 20 mg was significantly more effective than fexofenadine 120 mg in reducing the wheal and flare induced by histamine challenge (p<0.001). Although fexofenadine 120 mg had the shortest onset of action (1.5 vs. 3 h in ebastine 20 mg), the duration of its antihistamine effect was the shortest (24 vs. 58 h in ebastine 20 mg) and wheal reduction after 24 h was not significantly different from placebo. The overall effect after single and repeated 5-day dose, expressed as the AUC of reduction of wheal and flare area (%/h), showed the following order of magnitude: ebastine 20 mg>fexofenadine 120 mg>placebo. No significant differences in the incidence of adverse events were found between the three treatments. CONCLUSIONS: The present results clearly show a superior and long-acting effect of ebastine 20 mg compared with fexofenadine 120 mg on the skin response to histamine 24 h after dosing.

Inhibition of the histamine wheal by ebastine compared with cetirizine, fexofenadine and loratadine at steady state.

The objective of this double-blind, randomized, placebo-controlled, 5-way crossover study was to compare the pharmacodynamic effects of the H1 antihistamine ebastine (10 mg once daily, E10) with those of cetirizine (10 mg once daily, C10), loratadine (10 mg once daily, L10), fexofenadine (60 mg, twice daily, F60 x 2) and placebo (P) after 6 days of treatment in healthy volunteers. The pharmacodynamic variable was the mean percent reduction from baseline (pretreatment) of the wheal area induced by intradermal histamine 0.1% on the morning after 6 days' treatment. A secondary variable was the concentration of histamine required to produce a wheal of area 150 mm2. E10 reduced wheal size more than did P (p < 0.001) or F60 x 2 (p < 0.019). No significant differences were found among E10, C10 and L10. After E10, a significantly greater concentration of histamine was needed to induce a wheal of 150 mm2 than after P (p < 0.001), L10 (p < 0.001) or F60 x 2 (p < 0.001). No significant differences were found between E10 and C10. In conclusion, this study shows that, at the end of the conventional dosing interval, ebastine 10 mg and cetirizine 10 mg once daily in repeated doses suppressed the histamine wheal more effectively than did loratadine 10 mg once daily or fexofenadine 60 mg twice daily.

Tolerability and efficacy of almotriptan in the long-term treatment of migraine.

BACKGROUND: Almotriptan is a highly specific 5-HT(1B/1D) receptor agonist, which acts selectively on blood vessels of the brain. Short-term studies have demonstrated that almotriptan provides rapid, effective and reliable relief of migraine attacks, while offering excellent tolerability. PURPOSE: To assess the long-term tolerability and efficacy of oral almotriptan 12.5 mg administered for every migraine attack over a 1-year period. METHODS: A total of 762 patients treated 13,751 attacks (1-97 per patient); 61.5% of attacks were treated with one 12.5-mg dose, while for 38.5% of attacks, patients took a second dose within 24 h. RESULTS: Three hundred and ninety-one patients (51.3%) experienced a total of 1,617 adverse events (AEs). The majority (88.6%) of AEs were of mild-to-moderate intensity, and only 28.8% of AEs were considered to be related to the study drug. Only 2 patients experienced serious AEs possibly related to almotriptan, syncope and chest pain; both recovered without any sequelae. Patients reported at least 1 AE in 11% of attacks treated. The incidence of AEs decreased during the study. Only 6 (0.8%) study withdrawals were due to AEs considered to be related to almotriptan. Tolerability was not compromised in patients taking 2 doses of almotriptan or in those using migraine prophylactics. Patient age or sex did not influence the incidence of AEs. There was no evidence of tachyphylaxis in those patients completing the study. Pain relief at 2 h after the initial dose was achieved in 84.2% of moderate/severe attacks. Patients were pain free at 2 h after dose in 58.2% of all attacks. Older patients (> 40 years) tended to respond better than younger ones (< 40 years). Efficacy was not modified by use of migraine prophylactics or hormonal contraceptives. Efficacy measurements were consistent on treating repeated moderate/severe migraine attacks. CONCLUSION: This large, open study indicates that the new, specific 5-HT(1B/1D) agonist almotriptan, at a dose of 12.5 mg, is a well tolerated and effective treatment for migraine pain when used over a period of up to 1 year.

Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study.

In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.

Comparative clinical studies with ebastine: efficacy and tolerability.

Ebastine is a nonsedating and selective histamine H1 receptor antagonist without anticholinergic or sedative effects at therapeutic doses. It has shown a rapid onset and long duration of action, and doses of 10 and 20mg once daily are effective in relieving the nasal and non-nasal symptoms of seasonal and perennial allergic rhinitis (SAR and PAR, respectively). In 3 randomised double-blind, multicentre clinical trials in patients with SAR, ebastine 10 and 20mg once daily for 2 to 3 weeks significantly reduced symptoms (nasal discharge, stuffiness, sneezing, itchy nose, itchy/watery eyes) when compared with placebo. Similarly, in patients with PAR, two 3-week studies demonstrated that ebastine 10mg twice daily and 20mg once daily significantly relieved the symptoms of PAR, as measured by the Perennial Index. Ebastine was well tolerated in these studies and had no effect on the QTc interval.

A scintigraphic study to evaluate the deposition patterns of a novel anti-asthma drug inhaled from the Cyclohaler dry powder inhaler.

A scintigraphic study was performed, in 10 healthy volunteers, to determine the deposition patterns of a novel anti-asthma drug, LAS 31025, inhaled from a dry powder inhaler, the Cyclohaler. In addition, plasma concentrations of drug following inhalation were determined to investigate their relationship to the deposition patterns. Increasing doses of LAS 31025 were inhaled by the volunteers on four separate study days; 2.25, 4.5, 9.0 and 18.0 mg. The average lung deposition values corresponding to these dose levels were 19.1, 20.9, 19.5 and 17.5%, respectively. Deposition patterns within the lungs were similar on each of the four study days, with slightly more of the dose deposited in the central and intermediate regions compared to the peripheral lung region. The scintigraphic data were supported by the pharmacokinetic measurements as there was an increase in the maximum plasma concentration and area under the concentration-time curve corresponding to the increased doses of LAS 31025 on successive study days.

[Renal digital angiography in the study of hypertensive patients]. / La angiografía digital renal en el estudio de pacientes hipertensos.

50 patients, 31 male and 19 female with mean age of 45.1 +/- 9.4 years afflicted with blood hypertension (BH) were studied. RDA was performed on all of them as part of the etiological study. The variables evaluated were: systolic blood pressure (SBP), diastolic blood pressure (DBP), therapy index (TI), evolution time of its BH and type of BH (refractory BH, severe BH, mild-moderate BH). The organ affliction was also evaluated (renal function, ECG, presence of cardiomyopathy, vascular disease, and retinopathy. RDA alteration appeared in 16 cases, 1 (10%) in refractory BH group, 8 (28.6%) in severe BH group, and 7 (58.3%) in mild-moderate BH group. A shorter BH evolution period having been observed in patients with altered RDA than in those with normal RDA (3.49 +/- 3.96 years vs 6.93 +/- 4.68 years p = 0.01). We conclude that only this variable is a feature for suspicion of renovascular BH, without an apparent difference between the results of RDA and those of I.V. urography, obtained during the diagnosis screening. The significant differences observed between the mild-moderate BH and the other groups suggests that the clinical suspicion, and not the severity of the BH, is the point which should determine the patients to be renovascularly explored.

[Effect of muscle relaxation in hypertensive patients]. / Efecto de la relajación muscular en pacientes hipertensos.

The efficacy of muscle relaxation in the treatment of hypertension has been described by several authors. Our experience with this type of technique is analyzed in this report. The clinical histories of 38 individuals who have taken part in the relaxation program since the end of 1984 (relaxation group: RG) with at least 6 months of follow up, have been reviewed. For each RG patient, two sex, age, and initial diastolic blood pressure (DBP) matched controls were found, obtaining thus a control group (CG) consisting of 70 hypertensive patients who were not participating in any relaxation program. The final efficacy of the program was evaluated recording the systolic blood pressure (SBP), the DBP, and heart rate (HR) 6 and 12 months after the initiation of the program also considering the drop outs and the need of drugs (evaluated with a therapeutic index: TI). There were no differences in the initial parameters between the two groups except for the TI (uncontrollable variable) which was higher in the RG. The final values in the RG showed a slightly lower blood pressure (RG = 135.2/86.9 mm Hg; CG = 139.4/90.4 mm Hg, p = 0.082 for the DBP) as well as a lower number of drop outs (RG = 18.4%); CG = 32.9%, p less than 0.1). 10 patients in the RG while none in the CG were medically discharged. (p = 0.000). The only significant difference found was the increase in TI in the CG (p = 0.000), while the increase observed in the RG was not statistically significant.