The multinational birth cohort of EuroPrevall: background, aims and methods.

BACKGROUND/AIM: The true prevalence and risk factors of food allergies in children are not known because estimates were based predominantly on subjective assessments and skin or serum tests of allergic sensitization to food. The diagnostic gold standard, a double-blind placebo-controlled food provocation test, was not performed consistently to confirm suspected allergic reactions in previous population studies in children. This protocol describes the specific aims and diagnostic protocol of a birth cohort study examining prevalence patterns and influential factors of confirmed food allergies in European children from different regions. METHODS: Within the collaborative translational research project EuroPrevall, we started a multi-center birth cohort study, recruiting a total of over 12 000 newborns in nine countries across Europe in 2005-2009. In addition to three telephone interviews during the first 30 months, parents were asked to immediately inform the centers about possible allergic reactions to food at any time during the follow-up period. RESULTS: All children with suspected food allergy symptoms were clinically evaluated including double-blind placebo-controlled food challenge tests. We assessed sensitization to different food allergens by measurements of specific serum immunoglobulin E and skin prick tests, collect blood, saliva or buccal swabs for genetic tests, breast milk for measurement of food proteins/cytokines, and evaluate quality-of-life and economic burden of families with food allergic children. CONCLUSIONS: This birth cohort provides unique data on prevalence, risk factors, quality-of-life, and costs of food allergies in Europe, leading to the development of more informed and integrated preventative and treatment strategies for children with food allergies.

Maternal smoking increases risk of allergic sensitization and wheezing only in children with allergic predisposition: longitudinal analysis from birth to 10 years.

BACKGROUND: The role of passive smoking for allergies and asthma in children above the age of 3 years remains unclear and possible interactive effects with parental allergies have not been formally evaluated in long-term studies. To examine the interaction of passive smoking and an allergic predisposition regarding allergic sensitization, allergic airway symptoms and respiratory infections during the first 10 years of life. METHODS: In a prospective multicenter birth cohort study with 1314 recruited children in Germany, we assessed serum immunoglobulin E against common allergens at seven time points, and parental smoking and respiratory symptoms annually by using questionnaires. Longitudinal analyses were performed using generalized estimating equation models (stratified by parental allergy status). RESULTS: During the first 10 years, 18% of the children were exposed to regular maternal smoking since pregnancy, 43% to irregular maternal or only paternal smoking. Among children with two allergic parents, a mother who smoked regularly significantly increased the odds for allergic sensitization (adjusted OR 4.8, 95% CI 1.3-18.2) and wheezing (adjusted OR 5.7, 95% CI 1.7-19.0) in her child compared with children who were never exposed. For those with only one allergic parent, the odds were doubled and also statistically significant, whereas in children without allergic parents maternal smoking had no effects. There was no association of maternal smoking with allergic rhinitis or respiratory infections. CONCLUSIONS: Our results suggest that regular maternal smoking is a strong risk factor for allergic sensitization and asthma symptoms during the first 10 years of life, but only in children with allergic parents.

Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment of atopic dermatitis in infancy.

BACKGROUND: Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis. METHODS: Infants aged 3-12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15-40) without current antiinflammatory treatment were randomized to receive LGG (5 x 10(9) colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL). RESULTS: Fifty-four infants (LGG group, mean +/- SD SCORAD index 24.6 +/- 8.8) and 48 infants (placebo group, SCORAD index 23.6 +/- 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 +/- 12.4 vs 20.6 +/- 9.9), 8 weeks (22.5 +/- 14.6 vs 17.9 +/- 13.1), and 12 weeks (19.6 +/- 15.4 vs 15.1 +/- 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 +/- 45.0 g vs 3.5 +/- 29.8 g), increase in mean logarithmic total serum IgE (0.17 +/- 0.30 kU/l vs 0.26 +/- 0.45 kU/l), and newly developed allergic sensitization against hen's egg or cow's milk (18.8%vs 10.0%). CONCLUSION: This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy.

European birth cohort studies on asthma and atopic diseases: II. Comparison of outcomes and exposures--a GA2LEN initiative.

BACKGROUND: The Global Allergy and Asthma European Network (GA2LEN) is a consortium of 26 leading European research centres committed to establish a European research area of excellence in the field of allergy and asthma. AIM: One of the GA2LEN work packages was designed to identify and compare the existing European birth cohort studies on asthma and atopic diseases. The present review compares their subjective and objective outcomes as well as exposure variables. METHODS: A common database was established to assess study characteristics of observational birth cohort studies designed to examine asthma and atopic diseases. Data were collected by visiting most of the participating research teams and interviewing all relevant study personnel. For each study, the type of objective/subjective outcome parameters and potentially influential factors were recorded precisely for every time point during follow-up. RESULTS: Eighteen birth cohort studies on asthma and atopic diseases were identified in eight European countries. Thirteen studies collected data on specific immunoglobulin E (IgE) to various inhalant and food allergens, whereas 12 performed skin prick tests (many at several time points during follow up). Several studies measured lung function, but across the cohorts no comparable standard procedures were used. For subjective evaluation of asthma and allergic rhinitis most studies applied the ISAAC questionnaire (sometimes modified), whereas the assessment of eczema was rather heterogeneous across the studies. CONCLUSION: This GA2LEN initiative established a unique common database of 18 European birth cohorts on asthma and atopic diseases. For selected cohorts, it seems that pooling data and performing common analyses may be possible to examine associations between certain exposure variables (e.g. pet ownership, tobacco smoke exposure and day-care) and selected outcome measures for atopy, asthma or allergic rhinitis (e.g. sensitization assessed by IgE or skin prick tests, doctor's diagnosis of asthma, parental perception regarding asthma/wheezing or hay fever symptoms).

Histological effects of esomeprazole therapy on the squamous epithelium of the distal oesophagus.

BACKGROUND: Proton pump inhibitor therapy has been reported to reduce proliferative changes of the oesophagus significantly in gastro-oesophageal reflux disease (GERD). AIM: To assess the histological effects of esomeprazole treatment on the oesophagus. METHODS: Data were derived from a subgroup of patients participating in the proGERD study, who had either erosive reflux disease (n = 720) or non-erosive reflux disease (n = 35) and who had biopsy data from two sites [(i) 2 cm above the z-line and (ii) at the z-line], obtained at baseline and following treatment with esomeprazole. Proliferative changes of the squamous epithelium were assessed histologically by measuring thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness. RESULTS: In erosive reflux disease patients, the thickness of the basal cell layer and length of the papillae pretreatment were associated with the severity of oesophagitis (P < 0.05), at both biopsy sites. After esomeprazole treatment, baseline thickness and length of papillae were significantly reduced (P < 0.05) at both biopsy sites in non-erosive reflux disease and erosive reflux disease patients (particularly those with Los Angeles grades C and D). CONCLUSION: This demonstrates a strong correlation between severity of GERD and histological parameters. Esomeprazole therapy resulted in clear reversal of proliferative changes observed prior to treatment in the squamous epithelium at both biopsy locations.

Long-term clinical course of extra-oesophageal manifestations in patients with gastro-oesophageal reflux disease. A prospective follow-up analysis based on the ProGERD study.

BACKGROUND: Gastro-oesophageal reflux disease can be associated with extra-oesophageal reflux disease such as chronic cough or laryngeal symptoms. The aim of this study was to analyse the clinical course of extra-oesophageal reflux disease in a large population with gastro-oesophageal reflux disease and extra-oesophageal reflux disease under routine clinical care. METHODS: ProGERD is a prospective multicentre cohort study of 6215 outpatients with gastro-oesophageal reflux disease. At baseline all patients underwent endoscopies and were interviewed for extra-oesophageal reflux disease. Initial standardised treatment was esomeprazole for up to 8 weeks. After 2 years of follow-up, reflux symptoms and the prevalence of extra-oesophageal reflux disease were assessed. A multivariate analysis was performed with resolved versus persistent symptoms for chronic cough and laryngeal symptoms as dependent predictors. Independent variables were gender, age, body mass index (BMI), alcohol consumption, cigarette smoking, gastro-oesophageal reflux disease classification, history of gastro-oesophageal reflux disease in the family, duration of gastro-oesophageal reflux disease and proton pump inhibitors medication. RESULTS: Four thousand four hundred and four patients (71%) were available for analysis at 2 years, including 570 and 454 patients who had chronic cough and laryngeal disorders at baseline, respectively. In 63% and 74% of the patients, chronic cough and laryngeal disorders had resolved. Patients with persistent respiratory symptoms in year 2 had significantly more reflux symptoms. Further clinically relevant associations were smoking and non-steroidal anti-inflammatory drugs use. According to the multivariate analysis, classification of gastro-oesophageal reflux disease, proton pump inhibitors medication or duration of gastro-oesophageal reflux disease were not associated with the resolution of cough or laryngeal symptoms. CONCLUSION: In most patients with gastro-oesophageal reflux disease and extra-oesophageal reflux disease, respiratory symptoms resolve during long-term routine care. A high reflux symptom load was associated with the persistence of respiratory disorders.

European birth cohort studies on asthma and atopic diseases: I. Comparison of study designs -- a GALEN initiative.

BACKGROUND: The reasons for the rise in asthma and allergies remain unclear. To identify risk or protective factors, it is essential to carry out longitudinal epidemiological studies, preferably birth cohort studies. In Europe, several birth cohort studies on asthma and atopic diseases have been initiated over the last two decades. AIM: One of the work packages within the Global Allergy and Asthma European Network (GA(2)LEN) project was designed to identify and compare European birth cohorts on asthma and atopic diseases. The present review (part I) describes their objectives, study settings, recruitment process and follow-up rates. A subsequent review (part II) will compare outcome and exposure parameters. METHODS: For each birth cohort, we collected detailed information regarding recruitment process, study setting, baseline data (pregnancy, birth, parents/siblings) as well as follow-up rates, outcome and exposure parameters at each time point. RESULTS: We identified and assessed 18 European birth cohorts on asthma, allergic rhinitis and eczema. Six of these studies also focused on food allergies. The birth cohorts were mostly initiated in the 1990s with predominantly urban/metropolitan settings. Many studies were able to maintain high follow-up rates, even after five or more years. CONCLUSIONS: Due to the unique cooperation within the GA(2)LEN project a common database was established containing study characteristics of European birth cohorts on asthma and atopic diseases. This can be used as a basis for evaluating the possibility to pool data and perform meta-analyses, as well as to recommend criteria for conducting future birth cohorts.

Cost-of-disease analysis in patients with gastro-oesophageal reflux disease and Barrett's mucosa.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common and frequently chronic condition that causes considerable costs. AIM: To estimate the economic burden caused by patients with erosive and non-erosive reflux disease, and Barrett's oesophagus. METHODS: The Progression of Gastro-oesophageal Reflux Disease study includes a total of 6,215 patients. At baseline, patients were categorized as non-erosive reflux disease, erosive reflux disease, or Barrett's oesophagus according to endoscopic findings alone or as confirmed by histology. Direct and indirect disease-related costs were calculated based on 5,273 patients with complete information in the second year of the study. RESULTS: A total of 73% of the Progression of Gastro-oesophageal Reflux Disease patients had taken GERD medication, 61% had visited a doctor, and 2% had been hospitalized because of GERD during the previous 12 months. Of all employed persons, 6% reported days off work because of GERD. This health resource utilization caused direct costs of 342+/-864 (mean+/-s.d.) and indirect costs of 40+/-473 per patient and year. Total costs for patients with Barrett's oesophagus or erosive reflux disease were higher than those for patients with non-erosive reflux disease. CONCLUSION: Patients with GERD frequently need long-term medication and doctor care. The disorder is associated with a considerable health economic burden to society.

Utility of the ratio of food-specific IgE/total IgE in predicting symptomatic food allergy in children.

BACKGROUND: Double-blind, placebo-controlled food challenges are time-consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value. OBJECTIVE: To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy. METHODS: We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)-curves were performed; predicted probabilities and predictive decision points were calculated. RESULTS: A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat. CONCLUSION: In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice.

Validation of the Reflux Disease Questionnaire for a German population.

OBJECTIVE: We describe the validation of a German-language version of the Reflux Disease Questionnaire in what is the first validation study of this patient questionnaire for a non-English speaking population. Gastro-oesophageal reflux disease is one of the most common diseases in primary care and has a significant negative impact on patients' quality of life. There is no gold standard for diagnosing gastro-oesophageal reflux disease, however, so the valid assessment of symptoms is especially important. DESIGN AND METHODS: A total of 5689 patients (92%) completed the questionnaire both before treatment and after 2 weeks. The results were tested for validity and reliability. Predictive validity was tested in a pilot study of 100 patients. Convergent validity was examined using the Quality of Life in Reflux and Dyspepsia Questionnaire for the assessment of disease-specific quality of life and the McMaster Overall Treatment Evaluation for the assessment of therapeutic success. RESULTS: Principal component analysis suggested a three-factor solution with the subscores heartburn, regurgitation, and dyspepsia. The internal consistencies of the subscores were between 0.84 and 0.86. Item difficulty ranged from 0.33 to 0.53, and corrected item-total correlation from 0.66 to 0.72. Effect sizes were between 0.8 and 1.0. CONCLUSION: The German version of the questionnaire has good psychometric properties and is responsive to changes in health. Thus, we conclude that the German Reflux Disease Questionnaire is suitable for the assessment of heartburn, regurgitation, and treatment response, both in primary care settings and clinical studies.

What parameters are relevant for the histological diagnosis of gastroesophageal reflux disease without Barrett's mucosa?

BACKGROUND/AIMS: There are still ongoing controversies as to which histological parameters allow the diagnosis of gastroesophageal reflux disease (GERD). The aim of the present analysis was to relate histological changes of the esophageal squamous epithelium to different severities of GERD. METHODS: Data were obtained from patients participating in the ProGERD study, who had either erosive reflux disease (ERD, n = 3,245) or non-erosive reflux disease (NERD, n = 2,970). 1,475 patients fulfilled our requirement of having complete biopsy data from two sites (2 cm above the z-line and at the z-line). Changes in the squamous epithelium were assessed by measuring the thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness and counting interepithelial inflammatory cells. RESULTS: The most useful parameters for histological assessment of GERD (given as means, 2 cm above the z-line and at the z-line, respectively) were elongation of the papillae: NERD 40.7 and 48.9%; ERD 46.1 and 54.9% and basal cell hyperplasia: NERD 12.7 and 17.9%; ERD 15.7 and 23.0%. The occurrence of intraepithelial lymphocytic infiltrates, however, is dependent on the severity of GERD, and they are more common than neutrophilic and eosinophilic granulocytes. CONCLUSION: This study shows that both NERD and ERD can be diagnosed histologically if biopsies are obtained from the distal esophagus or from the z-line. Intraepithelial inflammatory cells are rare and show a high specificity, but very low sensitivity.

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children.

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone. CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.

Risk factors of gastroesophageal reflux disease: methodology and first epidemiological results of the ProGERD study.

OBJECTIVE: We describe the design and report the first results of the Progression of Gastroesophageal Reflux Disease (ProGERD) study, to our knowledge the largest prospective study of GERD patients. STUDY DESIGN AND SETTING: Patients were recruited at 1,253 centers in Germany, Austria, and Switzerland. Following an assessment of medical history, all patients were endoscoped and received esomeprazole for 2 to 8 weeks before entering the 5-year observational phase. RESULTS: A total of 6,215 patients (53% male, age 54+/-14) were included. Of these patients, 46% reported at least daily symptoms, 15% were unable to work at least once during the prior year, and 71% had visited a physician due to reflux symptoms. Barrett's esophagus (BE) was found in 11% of our GERD patients. In polychotomous regression analysis, the main factors related to the occurrence of the three GERD subgroups (nonerosive, erosive disease, and BE) were age, gender, duration of GERD, body mass index (BMI), smoking, and previous PPI use. Factors associated with longer disease duration were increasing age, male gender, BMI, increasing symptom severity, presence of erosive GERD or BE, positive family history, and smoking. CONCLUSION: The findings indicate that GERD is a great burden for patients, and has significant socioeconomic implications. The long-term follow-up period with further endoscopic and histologic evaluations, will help further our understanding of the natural course of the disease.

Change in quality of life in the year following cardiac rehabilitation.

The aim of the present study was to assess change in health-related quality of life (HRQoL) after cardiac rehabilitation in the usual care setting, and to determine predictors for change. In the Post Infarction Care Study, 2441 patients were consecutively included at admission to 18 inpatient cardiac rehabilitation centres following coronary events. HRQoL was assessed with the SF-36 questionnaire at baseline as well as 6 and 12 months after discharge. HRQoL improved significantly in patients after coronary artery bypass grafting (CABG) but not in patients after myocardial infarction. Significant baseline predictors for change of the SF-36 physical component summary (PCS) score were the exercise ECG result at admission (0.59 absolute change/10-watt increase; 95% CI: 0.39, 0.79), an income > or = 1750 euros (1.64; 95% CI: 0.35, 2.93), baseline PCS score (-0.63; 95% CI: -0.69, -0.57), and CABG as indication for admission (3.65; 95% CI: 2.27, 5.04). Significant predictors for change of the mental component summary (MCS) score were age (1.28/10-year increase; 95% CI: 0.62, 1.94), East Germany as area of residence (2.62; 95% CI: 1.32, 3.91), baseline MCS score (-0.58; 95% CI: -0.63, -0.52), and CABG as indication for admission (1.68; 95% CI: 0.36, 3.01). The identification of predictors of HRQoL in the present study may aid in the further development and evaluation of cardiac rehabilitation programmes.

ErbB-1 expression in experimental model of inflammatory bowel disease in rats.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) belong to inflammatory bowel disease (IBD). The etiology of IBD is still unknown. Therapy remains empiric or is used for the relief of specific symptoms. The erbB-1 oncogene coding epidermal growth factor receptor (EGFR) is typed as a prognostic marker in several benign and malignant tissues. The aim of our study was to examine the erbB-1 expression in experimental surgically performed model of IBD in rats and to find out if there is any correlation between severity of the intestinal inflammation and altered level of erbB-1 expression. After inducing an experimental colitis samples were taken from different parts of the intestine in all studied groups of rats for histopathology. ErbB-1 mRNA expression was estimated by RT-PCR. PCR products were separated on a 1.5% TBE-agarose gel and visualized with ethidium bromide. The integrated optical density (IOD) of electrophoretically separated amplification products was measured using a video densitometer and Gel-Pro 3.0 software. Nonparametrical statistical test has been used throughout in analyzing the results. Relative erbB-1 expression was determined by comparing to cyclophiline expression. RESULTS: Microscopic changes were similar to those observed in IBD. ErbB-1 expression was significantly higher in inflamed tissues of the bowel ( P = 0.04 for the transverse colon and P = 0.027 for the cecum). Significantly higher erbB-1 expression in inflamed tissues of the bowel suggests that EGFR overexpression may play a role in the pathogenesis of IBD. Overexpression of erbB-1 correlates with the severity of inflammation in bowel tissues.

Quality of life in relation to symptoms in patients with gastro-oesophageal reflux disease-- an analysis based on the ProGERD initiative.

AIMS: To determine the impact of gastro-oesophageal reflux disease (GERD) on the quality of life, to assess changes in the quality of life during treatment with esomeprazole and to define factors that can predict these changes. METHODS: Patients with GERD (n=6215) were included in a prospective cohort study (ProGERD). All patients underwent endoscopy and received esomeprazole. At baseline and after 2 weeks of treatment, symptoms and quality of life were assessed. Factors that influenced changes in the quality of life were determined by multiple regression analyses. RESULTS: At baseline, the quality of life in GERD patients was lower than that in the general population, and was similar to that in patients after acute coronary events. No differences in symptoms or quality of life were observed between the subgroups of patients with non-erosive GERD, erosive GERD and Barrett's oesophagus. After treatment with esomeprazole, the symptoms and quality of life were improved in all subscales within 2 weeks (P<0.001). The mean score of the disease-specific quality of life instrument (Quality of Life in Reflux and Dyspepsia Patients) increased from 4.6 to 6.2 points, representing a highly relevant clinical improvement. The generic quality of life (SF-36) reached levels similar to those in the general population, but, again, no difference was found between the three different subgroups of GERD patients. The main factors associated with an improvement in the quality of life after treatment were symptom relief, severe erosive reflux disease, absence of extra-oesophageal disorders, avoidance of non-steroidal anti-inflammatory drug intake and positive Helicobacter pylori status. CONCLUSIONS: GERD causes a significant impairment in the quality of life that can be attenuated or normalized within a time period as short as 2 weeks by treatment with esomeprazole. These findings were similar across the whole GERD patient spectrum.

Prevalence of extra-oesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD Study.

BACKGROUND AND AIMS: Gastro-oesophageal reflux disease (GERD) can be associated with a variety of extra-oesophageal disorders (EED) such as chronic cough, asthma, laryngeal disorder or chest pain. The aim of the study was to estimate and compare the prevalence of EED in a population with symptomatic GERD presenting as either erosive reflux disease (ERD) or non-erosive reflux disease (NERD). METHODS: Baseline data were collected from a prospective, multicentre, open cohort study (ProGERD) in which patients will be followed for 5 years after initial treatment with esomeprazole. Within the framework of this trial, all patients underwent gastroscopy and filled out a questionnaire designed to assess EED. The influence of potential prognostic factors on the prevalence of EED was analysed by multivariate (stepwise logistic regression) analysis. RESULTS: 6215 patients (3303 male, 2912 female; mean age 54 years) presenting with heartburn were included. EED was detected in 32.8% of all patients. The proportion was significantly higher (P = 0.0002) in ERD patients (34.9%) than in NERD patients (30.5%). As judged from the multivariate analysis, female gender, age, oesophagitis of LA grade C/D, duration of GERD disease greater than 1 years and smoking were significantly associated with EED. ERD patients with oesophagitis of LA grade A or B did not have a significantly higher risk of EED than patients with NERD. CONCLUSIONS: Patients with GERD have a high probability of experiencing EED, which may be associated with a number of prognostic factors such as duration and severity of GERD. Extra-oesophageal disorders are slightly, but statistically, more prevalent in ERD than in NERD patients.

A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer.

AIM: To compare the effectiveness of Helicobacter pylori eradication in curing peptic ulcer disease in trials involving both gastric ulcer and duodenal ulcer. METHODS: Twenty-four relevant randomized controlled trials and randomized comparative trials met the predefined selection criteria. Only proton pump inhibitor-based eradication trials were considered for the evaluation of eradication efficacy and ulcer healing. For the determination of relapse rates, all trials independent of the eradication therapy regimen were considered. RESULTS: Data from 2102 patients were analysed comparing gastric ulcer with duodenal ulcer. No statistical differences between gastric ulcer and duodenal ulcer patients were found with regard to eradication rates (summarized odds ratio, 1.23; 95% confidence interval, 0.98-1.55) or ulcer relapse rates, whether in successfully H. pylori eradicated patients (summarized odds ratio, 0.69; 95% confidence interval, 0.26-1.84) or unsuccessfully H. pylori eradicated patients (summarized odds ratio, 1.48; 95% confidence interval, 0.85-2.56). Owing to heterogeneity, healing rates were not comparable. CONCLUSIONS: The eradication of H. pylori infection cures both gastric and duodenal ulcer, and the cure rates are similar. This suggests that H. pylori is the key factor in peptic ulcer disease independent of the ulcer site.

Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensitization, and atopic manifestation in longitudinally followed early Bacille Calmette-Guérin-vaccinated and nonvaccinated children.

BACKGROUND: Bacille Calmette-Guérin (BCG) is a strong T helper 1 incentive and, thus, may contribute to a decreased risk of T helper 2-dependent atopic disease. OBJECTIVE: To investigate the natural course of specific immunoglobulin E (IgE) responses and atopic disease in BCG-vaccinated and nonvaccinated children. PARTICIPANTS: Seven hundred seventy-four children from a prospectively followed birth cohort. OUTCOME MEASURES: Physical examination and case history were performed at 3, 6, 12, 18, 24, 36, 48, 60, 72, and 84 months of age. Total and specific serum IgE levels to 9 common inhalant and food allergens were determined (CAP; Pharmacia, Freiburg, Germany) at 12, 24, 36, 60, 72, and 84 months of age. Purified protein derivative (PPD) skin testing was performed at 84 months. RESULTS: Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life, whereas no such trend was found after the second birthday or for allergic rhinitis. The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time. No statistically significant differences were found for total IgE levels (median). Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life. The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of >/=5 mm and those with a smaller diameter. CONCLUSION: These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy. In addition, PPD skin test reactivity was not impaired in atopic individuals.

Cardiac risk factors, medication, and recurrent clinical events after acute coronary disease; a prospective cohort study.

AIMS: Systematic data are sparse on clinical outcome after acute coronary disease followed by cardiac rehabilitation therapy. Therefore, our objective was to determine the long-term development of cardiac risk factors, recurrent clinical events, and cardiac medication in patients undergoing routine in hospital cardiac rehabilitation therapy. METHODS AND RESULTS: In the prospective PIN Study (Post Infarct Care), 2441 consecutive patients (78% men, 60+/-10 years, 22% women, 65+/-10 years) were enrolled in 18 inpatient rehabilitation centres in Germany following myocardial infarction (56%), coronary artery bypass graft (38%) or percutaneous transluminal coronary angioplasty (6%). Cardiac risk factors, pre-specified clinical end-points, and the prescription of cardiac medication were prospectively documented on admission to and at discharge from rehabilitation therapy, and 3, 6 and 12 months later by obtaining information with standardized questionnaires from the patients and their physicians. The cardiac risk factors improved initially during cardiac rehabilitation therapy, but deteriorated within the following 12 months: 39% patients smoked at the beginning vs 5% at the end of in hospital rehabilitation vs 10% at 12 months follow-up (P<0.001). The respective numbers for patients with blood pressure >140 and/or 90 mmHg were 24 vs 8 vs 25% (P<0.01) and with plasma cholesterol >200 mg. dl(-1)57 vs 29 vs 51% (P<0.01). A total of 886 patients experienced one or more recurrent clinical events during the first year, 69% of those within the initial 6 months. At 12 months follow-up, 77% of patients received aspirin, 70% beta-blockers, 62% lipid lowering medication, and 53% angiotensin converting enzyme inhibitors. CONCLUSION: The present results indicate that the benefit of cardiac rehabilitation therapy following acute coronary events is only partially maintained during the following year. Continuous strategies of medical care need to be developed to improve the long-term outcome in coronary patients.