Getting in early: primary skin cancer prevention at 55 German kindergartens.

BACKGROUND: Skin neoplasms are the most frequent types of neoplasms in white populations, and their incidence is increasing. Epidemiological studies have shown that the major environmental aetiological factor for their development is sunlight exposure. Sun protection programmes are urgently needed to raise awareness of the health hazards of ultraviolet radiation. In 2010 the 'SunPass' project was implemented at 55 kindergartens in Germany. This is the first nationwide environmental education programme for sun safety designed to teach children in kindergartens and their caregivers how to protect themselves from overexposure to the sun. OBJECTIVES: An interventional lecture, site inspections and a certification were part of the programme. Effects of these interventions were studied. METHODS: The gain in knowledge and changed sun-behavioural attributes were quantified by questionnaires administered before and after the 'SunPass' interventions. RESULTS: The total number of children was 5424. Sun-protection behaviour after the intervention improved significantly (P < 0·001). Among parents, 22·2% reported one to five sunburns of their child since birth. There was a significant increase in hat use by children in kindergartens (P = 0·029), as well as some significantly improved shade practices. There was a significantly increased demand for protective clothing for children (P < 0·001). The change in sunscreen use in kindergartens was not significant. CONCLUSIONS: Although some aims of the 'SunPass' project were not fulfilled, such as the precise knowledge of skin types and a change of sunscreen use, the study had some positive outcomes in increasing the awareness of skin cancer and its prevention possibilities. The findings of the present study suggest that relatively brief interventions in kindergartens lead to improved sun protection of children. The whole investigation reaching over 5400 children and their parents underlines the importance of learning appropriate sun-protective behaviour in early childhood in order to decrease the risk for skin cancer.

Efficacy and safety of formoterol delivered through the Novolizer, a novel dry powder inhaler (DPI) compared with a standard DPI in patients with moderate to severe asthma.

BACKGROUND & OBJECTIVE: Because of environmental concerns CFC-containing pressurised metered dose inhalers (pMDI) had to be replaced by dry powder inhalers (DPI). The Novolizer, a novel DPI has previously been shown to be as effective as the Turbuhaler in delivering budesonide. The objective of this study was to show non-inferiority of inhaled formoterol therapy delivered through the Novolizer compared to formoterol delivered through the Aerolizer in patients suffering from moderate to severe asthma. METHODS: In this double-blind, double-dummy, multicentre study 392 patients were randomised and received a dose of 12 microg formoterol twice daily for 4 weeks either through the Aerolizer or the Novolizer. FEV1 after 4 weeks of treatment was the primary variable. Secondary variables were FVC, PEF, consumption of short-acting; 2 adrenoceptor agonists, asthma symptoms, tolerability and safety. RESULTS: After 4 weeks of treatment, the mean trough FEV1 (95% CI) was 2.34 L (2.24-2.45) for the Novolizer and 2.31 L (2.21-2.41) for the Aerolizer. Non-inferiority was proven (p<0.0001, pre-defined; of 0.25 L). All secondary variables (incl. PEF) confirmed these findings. Treatment with both devices was safe and well tolerated. CONCLUSION: Inhalation of 12 microg formoterol twice daily via Novolizer was shown to be equally therapeutically effective compared to the inhalation via Aerolizer in the treatment of moderate to severe persistent asthma. Treatment via both inhalers was safe and well tolerated.

Effect of loteprednol etabonate nasal spray suspension on seasonal allergic rhinitis assessed by allergen challenge in an environmental exposure unit.

BACKGROUND: Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR). METHODS: In this single-center, double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 microg LE nasal spray, or placebo for 14 days. The patients underwent three 4-h allergen challenges with grass pollen in an environmental exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV(1) were measured every hour during allergen challenges. RESULTS: After 14 days of treatment, patients who received 400 microg LE had significantly lower total nasal symptom scores compared with those receiving placebo (P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo (P < 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated. CONCLUSIONS: Loteprednol 400 microg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.

Possibilities in improvement of glucocorticoid treatments in asthma with special reference to loteprednol etabonate.

Allergic conditions contribute significantly to the burden of chronic disease in the industrialized world. The increasing prevalence has lead research into the discovery and development of various new therapeutic strategies. Despite considerable efforts of the pharmaceutical industry, the leukotriene antagonists were the only new class of asthma treatments to be licensed in the past 30 years. Topical glucocorticoids (GCs) are the most potent and effective therapy for treating allergic diseases. However, their use is limited by diverse undesired effects. Changes in pharmacokinetic parameters of GCs may be an interesting and promising approach to improve efficacy and safety of inhaled GCs. Loteprednol etabonate has been developed on the basis of the retrometabolic drug design. In animal studies, it has been demonstrated to have long-lasting anti-allergic (anti-asthmatic) effects without influencing the hypothalamic-pituitary axis (HPA). This soft steroid is now in phase III of the clinical development. Recently, loteprednol has been proven to be effective in the management of allergic rhinitis (400 microg once daily). No suppression of HPA was observed at clinically effective and higher doses. In conclusion, loteprednol as the first representative of soft steroids elicits marked anti-inflammatory effects, but has no impact on endocrine responses. It may represent a promising new therapy in the treatment of allergic rhinitis and asthma.

Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis.

OBJECTIVE AND SETTING: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study. RESEARCH DESIGN: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion. Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period. Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale. RESULTS: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >/=3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p = 0.005; sodium cromoglycate p = 0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion. CONCLUSION: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.

Topical azelastine in perennial allergic conjunctivitis.

OBJECTIVE: Azelastine is a selective H(1)-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC). The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo. RESEARCH DESIGN AND METHODS: A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment. RESULTS: Azelastine significantly improved itching and conjunctival redness compared to placebo (p < 0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9 +/- 1.1 and with levocabastine by 1.5 +/- 1.2 compared to placebo (0.6 +/- 1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction. CONCLUSIONS: Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H(1)-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.

[Concepts of anthropological medicine]. / Konzepte der anthropologischen Medizin.

Medical anthropology is the teaching of the ill human being, of being ill; anthropological medicine is the realization of this teaching in practice. This concept was first developed and assessed in the "Gestaltkreis" and in the Pathosophy (44), in Medicine in Motion (39), and in the Bipersonality (10). The four most important concepts are represented, which have their origin and aim in anthropological medicine: anthropological medicine, Balint-work, family-oriented medicine, and salutogenesis. These concepts are exemplified in the Aachen psychosomatic liaison model, the Aachen Balint cooperation model, and the Aachen model of psychosomatic care. We wish to portray the meaning of these resources for the medicine of the future, since they have proven to be effective, cost-saving, and easy to be handled. In the latter part of our presentation, we will document this point with a pilot study conducted in Israel and in our own clinic in Aachen.

Comparison of azelastine eye drops with levocabastine eye drops in the treatment of seasonal allergic conjunctivitis.

A randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients' diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastine-treated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.

Comparative efficacy of azelastine nasal spray and terfenadine in seasonal and perennial rhinitis.

The efficacy and tolerability of intranasal azelastine (0.14 mg/nostril twice daily) and oral terfenadine (60 mg twice daily) were compared under double-blind conditions in two 6-week, multicenter, parallel-group studies, including 167 patients suffering from seasonal and 52 patients suffering from perennial allergic rhinitis. In both studies, patients were symptomatic on entry and showed significant improvement on both treatments within the first 8 d of therapy, showing little further improvement with continued treatment. Symptoms most pronounced on entry--nasal itching, rhinorrhea, sneezing, and nasal obstruction--responded best to treatment (response rates 80-90%). Objective signs such as mucosal swelling and conjunctivitis improved in a manner parallel to symptoms. In perennial rhinitis, azelastine showed a trend to a superior relief of rhinorrhea and nasal obstruction, whereas terfenadine showed a trend toward better control of sneezing and nasal itchiness. No clinically relevant or statistically significant differences between treatments could be identified. The incidence of adverse effects of possible causal relationship to therapy was low. The most frequent effects in azelastine-treated patients were related to application site disorders, e.g., nasal irritation. Results indicate that with the dose used azelastine nasal spray is an effective treatment for both seasonal and perennial allergic rhinitis.

Efficacy and tolerability of azelastine nasal spray in patients with allergic rhinitis compared to placebo and budesonide.

The efficacy and safety of a new antiallergic drug, intranasal azelastine (CAS 58581-89-8), in the treatment of seasonal allergic rhinitis was investigated in a 16 patient double-blind comparison with placebo and another 36 patient open comparison with budesonide (CAS 51333-22-3). Efficacy was assessed in terms of 13 signs and symptoms of allergic rhinitis and tolerability on the basis of spontaneously reported adverse events. In the first study, compared to placebo a one week's treatment with azelastine resulted in substantial relief of sneezing (p = 0.009), nasal itching (p = 0.009), swelling of the nasal mucosa (p = 0.067) and rhinorrhoea (p = 0.262) in patients having the above symptoms at baseline of at least moderate to severe intensity. According to the judgement of the supervising physician, 7/8 azelastine-treated patients but none receiving placebo responded well to therapy (p = 0.001). In the second study a two weeks' treatment with intranasal azelastine was found not to differ significantly from budesonide 67% of patients showed improvement in principal signs of rhinitis after one week's therapy irrespective of treatment. Nasal symptoms, including nasal obstruction, were most markedly improved by both treatments. Azelastine, but not budesonide, also relieved ocular symptoms associated with rhinitis. Adverse events did not occur more frequently under azelastine than under placebo treatment and were often of uncertain relationship to treatment.

Investigation of long-term efficacy and tolerability of azelastine nasal spray in the treatment of perennial allergic rhinitis.

The long-term efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.d.) was investigated in patients suffering from perennial allergic rhinitis. 185 patients entered an initial 6 months' study; 35 of them continued in a follow-up for a further 30 to 60 weeks' treatment. Azelastine both attenuated the severity and reduced the incidence of rhinitis symptoms, with the highest rate of improvement during the first month with some additional improvement during the following months. The most marked effects were on those symptoms which were initially most severe: nasal obstruction, mucosal swelling, rhinorrhoea, sneezing and nasal itching. Signs of rhinitis identified by rhinoscopic examination improved in parallel to symptoms. 84.1% of patients reported 'good' or 'very good' efficacy as did 94.3% during the follow-up. Approximately 96% of patients rated the tolerability of treatment as 'very good' or 'good'. The incidence of adverse events of possibly causal relationship to azelastine treatment was low during the first 6 months. The most frequent events were the experience of application site reactions (e.g. burning) and bitter or unpleasant taste, specific to azelastine. No unwanted effects were reported by patients continuing treatment. In addition, results of nasal biopsies indicate that with the dose used azelastine nasal spray is a safe drug for long-term treatment of perennial allergic rhinitis.

Intranasal treatment of perennial allergic rhinitis. Comparison of azelastine nasal spray and budesonide nasal aerosol.

The efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.d.) and budesonide (CAS 51333-22-3) nasal aerosol (0.05 mg/nostril b.i.d.) were compared in a 6-week, multicentre, parallel group study of 193 patients suffering from perennial allergic rhinitis. Total rhinitis symptoms complex (TSC) scores derived from 10 rhinitis symptoms improved during treatment by a mean of 11.4 +/- 6.8 with azelastine and 10.8 +/- 6.4 with budesonide. Response rates, defined as a decrease in TSC of at least 50% at the end of therapy, was 79% with azelastine and 73% with budesonide. There were no significant differences between the treatment groups with respect to either target variable. Objective measurements of nasal flow rate showed a return to normal values during the 6-week therapy. Signs of rhinitis identified by rhinoscopic examination improved in parallel to symptoms. Both medications were well tolerated. The incidence of adverse events of possibly causal relationship to therapy was low. The most frequent event in azelastine treated patients was the experience of an "unpleasant" taste or smell. Occasional epistaxis occurred in both treatment groups but more frequently with budesonide. Results indicate that with the dose used azelastine nasal spray is an effective treatment for perennial allergic rhinitis comparable to that of budesonide nasal aerosol.

Effects of (22S,23S)-Homobrassinolide and Related Compounds on Membrane Potential and Transport of Egeria Leaf Cells.

(22S,23S)-Homobrassinolide was tested for its effect on the electric cell potential, proton extrusion, ferricyanide reduction, and amino acid and sucrose uptake of leaves of Egeria densa Planchon. In the light, (22S,23S)-homobrassinolide and its derivative, 2alpha-3alpha-dihydroxy-5alpha-stigmast-22-en-6-one, were similar to each other and similar to fusicoccin in causing hyperpolarization and proton extrusion, whereas stigmasterol was less effective. In darkness, the three sterols showed comparable effects. (22S,23S)-Homobrassinolide slightly stimulated ferricyanide reduction and promoted uptake of sucrose and alpha-aminoisobutyric acid. The results are compatible with a stimulation of an electrogenic proton pump mechanism at the plasmalemma by (22S,23S)-homobrassinolide.