Efficacy of Calcipotriol-Betamethasone Ointment in Patients with Mild to Moderate Plaque Psoriasis: Subgroup Analyses.

BACKGROUND: Several factors have been shown to affect psoriasis pathogenesis, clinical presentation and treatment response. OBJECTIVES: The aim of this study was to investigate the potential relationship between patients' baseline characteristics and the efficacy of calcipotriol-betamethasone ointment in patients with mild to moderate plaque psoriasis and to evaluate whether the efficacy is consistent across subgroups. METHOD: Using data from the therapeutic equivalence study on patients with plaque psoriasis, post hoc analyses were performed to evaluate the impact of baseline demographic and disease characteristics, habits and comorbidities on the response to treatment with calcipotriol-betamethasone ointment. RESULTS: Body mass index (BMI) and obesity were each independently associated (univariate analysis, p < 0.05) with reduction in modified Psoriasis Area and Severity Index (mPASI) and PASI75 (≥75% improvement in mPASI from baseline). Increased body weight is more common in patients with late-onset psoriasis. There was a significant trend for lower response rates with increasing BMI (p = 0.007) and obesity (p = 0.003). The odds of achieving PASI75 is 2.3 times lower for obese compared to normal-weight subjects.If patients with obesity or hypertension were treated with calcipotriol-betamethasone, they were still more likely to achieve PASI75 after 4-week treatment compared to vehicle (p < 0.001). CONCLUSION: Increased BMI and obesity present risk factors for reduced treatment effectiveness. Importantly, the efficacy of calcipotriol-betamethasone ointment was consistent in all subgroups.

A Novel Simulation-Based Approach for Comparing the Population Against Average Bioequivalence Statistical Test for the Evaluation of Nasal Spray Products on Spray Pattern and Droplet Size Distribution Parameters.

The aim of this work is to evaluate average bioequivalence (ABE) and population bioequivalence (PBE) statistical approaches so as to identify which approach is most suitable for in vitro bioequivalence (IVBE) testing of nasal spray products. For droplet size distribution (DSD) and spray pattern (SP), in vitro data were collected using a well-established nasal spray on the market (Nasonex®, manufactured by Merck Sharp & Dohme Limited). Simulations were performed using in vitro data to comparatively investigate ABE and PBE tests. For highly variable parameters such as SP area, this study clearly demonstrates that the level of agreement between ABE and PBE test conclusions is much smaller as compared with that of DSD Dv(50), which was found to have moderate variability. PBE approach dictates equivalence for both means and variances, and was found to handle both SP and DSD parameters with similar passing rates compared to the passing rates from the ABE approach. However, pronounced asymmetric behavior of PBE empirical power curves for highly variable SP area was observed. A modified PBE statistical approach is proposed for DSD span and Dv(50) in vitro parameters, where acceptance criteria would be based on comparison of reference/branded product to itself as part of "pre-IVBE study" via innovative statistical bootstrap simulations. Due to inherent high variability of the SP area parameter driving pronounced asymmetric behavior of PBE power curves, and due to unclear in vivo relevance for SP area and ovality, authors propose that SP parameters be used as development and quality control tools rather than for demonstration of IVBE.

Differences in reporting Pearl Indices in the United States and Europe: Focus on a 91-day extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

BACKGROUND: Regulatory agencies in the United States (US) and Europe differ in requirements for defining pregnancies after the last dose of oral contraceptive, sometimes resulting in discrepant Pearl Indices (PIs) for the same product despite identical clinical data. This brief report highlights one such example, a 91-day extended-regimen combined oral contraceptive (COC). METHODS: The US- and European-based PI methodologies were compared for a 91-day extended-regimen COC consisting of 84 days of active levonorgestrel/EE 150 µg/30 µg tablets, followed by seven days of EE 10 µg tablets in place of placebo. CONCLUSIONS: At the times of approval of the 91-day extended-regimen COC in the US and Europe, the requirements for defining 'on-treatment' pregnancies differed (14-day vs. 2-day rule, respectively). This difference resulted in a higher PI in the US- vs. European-based calculation (1.34 and 0.76, respectively). The differences in the PI should not be interpreted as the extended-regimen COC being less effective in preventing pregnancy in the US compared with Europe.

Effects of traffic air pollution and hornbeam pollen on adult asthma hospitalizations in Zagreb.

BACKGROUND: Environmental factors play an important role in asthma morbidity, although the contribution of individual pollutants or pollens in exacerbating asthma is not completely elucidated. Despite the evidence of importance of the hornbeam pollen in inducing allergic sensitization, its role in provoking asthma exacerbation has not been evaluated. The aim of the present study was to investigate effects of traffic pollutants on adult asthma hospitalization adjusting for pollens including hornbeam. METHODS: During a 3-year period, health and environmental data were collected and analyzed. Daily asthma hospitalizations were regressed on pollutants and potential confounding variables using an autoregressive Poisson model. RESULTS: The risk of asthma hospitalization was associated significantly with the 95th to 99th percentile increase in levels of nitrogen dioxide (RR = 1.22; 95% CI: 1.05-1.40), carbon monoxide (RR = 1.25; 95% CI: 1.01-1.55) and hornbeam pollen (RR = 1.21; 95% CI: 1.11-1.30). The effect of nitrogen dioxide was delayed by 5 days. No statistically significant increase in the risk of asthma hospitalization was found for PM(10) particles. A comparison among the standardized regression coefficients and their respective p values indicates that the most important risk factor for asthma hospitalization is associated with hornbeam pollen levels. No statistically significant interactions between pollutants and pollens were detected. CONCLUSIONS: The current results suggest that traffic-related air pollution is associated with increased risk of adult asthma hospitalization. Nonetheless, the most significant risk for asthma hospitalization is associated with hornbeam pollen levels in the city of Zagreb.

Knowledge and use of folic acid in Croatian pregnant women--a need for health care education initiative.

Adequate periconceptional folic acid (FA) intake reduces the risk of neural tube defects. There are still no official FA supplementation guidelines, FA fortification policies or larger studies of awareness regarding FA or number of planned pregnancies in Croatia. This study assesses the knowledge and practice regarding FA supplementation and reports the trends in pregnancy planning in Croatia. A total of 569 pregnant women completed an anonymous questionnaire and about 72% of them were aware of the benefits of FA. Despite 75.53% of planned pregnancies, only 14.41% of all women took FA appropriately. Croatian women get information about FA from the media, health professionals and friends, but 63.77% got this information too late. The present study showed low percentage of appropriate FA intake despite high number of planned pregnancies in Croatia. It emphasizes the need for immediate and continuous public health education initiative about FA intake targeted to the women of childbearing age before their pregnancies have occurred.