Long-term treatment of patients with gastro-oesophageal reflux disease in routine care - results from the ProGERD study.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common condition frequently requiring long-term pharmacological treatment. AIM: To describe the long-term pattern of GERD medication use in GERD patients receiving routine care. METHODS: Patients were recruited as part of the ongoing ProGERD study, a 10-year-cohort study including 6215 patients at baseline. GERD medication and symptoms were assessed with patient questionnaires. During follow-up, medical treatment was prescribed by participating primary care physicians. Associations between patient characteristics and medication were analysed by logistic regression. RESULTS: The percentage of patients who reported using any GERD medication remained constant from year 1 to year 4 (74%, 74%, 73% and 71%). Of patients who reported using GERD medication, the majority were taking proton pump inhibitors (PPI) (79%, 84%, 85%, and 87%). Continuous PPI intake was the predominant prescription pattern (53%, 49%, 56% and 56%), followed by on-demand treatment (26%, 35%, 29% and 29%). Continuous PPI intake was strongly associated with the presence of erosive GERD. CONCLUSION: Three-quarters of the GERD population in our study reported long-term treatment with a PPI. Continuous PPI intake was the predominant treatment pattern, and the proportion of patients taking a PPI on a continuous basis remained constant over time.

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.

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.

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.

Extraesophageal manifestations in gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common condition that affects about 20-30% of the adult population, presenting with a broad spectrum of symptoms and varying degrees of severity and frequency. Other manifestations are being increasingly recognized: the so-called ''extraesophageal'' manifestations, such as laryngitis, hoarseness, chronic cough, asthma, or non-cardiac chest pain. Epidemiological studies consistently demonstrate significant associations between pulmonary manifestations and GERD. Up to 50% of patients with an endoscopically proven esophagitis suffer from symptoms other than heartburn or acid regurgitation. However, the published estimates of extraesophageal disorders in patients with GERD vary widely, which may be a result of referral bias. The most effective initial approach in suspected reflux-related extraesophageal symptoms is empiric proton pump inhibitor (PPI) therapy. However, studies demonstrated that the advantage of long-term PPI treatment over placebo could have been overestimated.

A comparison of omeprazole, lansoprazole and pantoprazole in the maintenance treatment of severe reflux oesophagitis.

BACKGROUND: Proton pump inhibitors are effective for the healing of oesophagitis. Standard doses of omeprazole, lansoprazole or pantoprazole are sufficient for healing in mild to moderate cases of oesophagitis. AIM: To compare the efficacy of double the standard doses of omeprazole, lansoprazole or pantoprazole for maintenance treatment of severe oesophagitis complicated by a stricture. METHODS: Thirty-six patients with reflux oesophagitis and stricture confirmed by endoscopy were included in a prospective study comparing three maintenance therapies. In all cases weekly dilatation of the stenosis was performed and patients were treated with omeprazole 20 mg b.d. until healing of oesophagitis and dysphagia relief were achieved. Thirty participants responded to therapy and were then randomly assigned to 4 weeks of maintenance treatment with omeprazole (20 mg b.d.; n = 10), lansoprazole (30 mg b.d.; n = 10) or pantoprazole (40 mg b.d.; n = 10). Subsequently, endoscopies were performed-the endoscopists were blinded to the therapy assignment. The endpoints were defined as the absence of oesophagitis, oesophageal stricture and complaints. RESULTS: After 4 weeks of treatment, the number of patients remaining in remission (no oesophagitis or stricture and no symptoms) was nine out of 10 (90%) in the omeprazole group, two out of 10 (20%) in the lansoprazole group (P < 0.01) and three out of 10 (30%) in the pantoprazole group (P < 0.01). CONCLUSIONS: In our study omeprazole was superior to either lansoprazole or pantoprazole in the maintenance treatment of complicated gastro-oesophageal reflux disease.

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.

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.

Drug-induced oesophageal disorders: pathogenesis, incidence, prevention and management.

Drug-induced injury of the oesophagus is a common cause of oesophageal complaints. 'Pill-induced' oesophagitis is associated with the ingestion of certain drugs and accounts for many cases of erosive oesophagitis. To date, more than 70 drugs have been reported to induce oesophageal disorders. Antibacterials such as doxycycline, tetracycline and clindamycin are the offending agents in more than 50% of cases. Other commonly prescribed drugs that cause oesophageal injury include aspirin (acetylsalicylic acid), potassium chloride, ferrous sulfate, quinidine, alprenolol and various steroidal and nonsteroidal anti-inflammatory agents. However, many physicians and even more patients are not aware of this problem. Capsules or tablets are commonly delayed in their passage through the oesophagus. Highly caustic coatings, direct medication injury and poor oesophageal clearance of pills can lead to acute inflammation. Oesophageal damage occurs when the caustic contents of a drug remain in the oesophagus long enough to produce mucosal lesions. Taking medications at bedtime or without fluids is a common cause of oesophagitis. The possibility of drug-related damage should be suspected in all cases of oesophagitis, chest pain and dysphagia. History and gastrointestinal endoscopy will confirm the diagnosis. Treatment is supportive, although acid reduction is used frequently as an adjunct. This review reflects the current state of knowledge in this field.

Omeprazole-amoxycillin therapy for eradication of Helicobacter pylori in duodenal ulcer bleeding: preliminary results of a pilot study.

Thirty-five patients with duodenal ulcer bleeding and Helicobacter pylori-colonization were assigned to receive 2 x 20 mg omeprazole and 3 x 750 mg amoxycillin daily for 2 weeks. Eradication was defined as no evidence of H. pylori infection by urease test and by histology 4 weeks after completion of therapy. Two patients were lost to follow up. All ulcers healed completely (100% ulcer healing rate). Twenty-nine out of the 33 patients were H. pylori-negative (87.9% eradication rate). Three patients complained of typical side effects of amoxycillin (9.1% side effect rate). The patients were prospectively followed for 12 months. After ulcer healing, no maintenance therapy was given. One of the 29 patients in whom H. pylori eradication had been successful suffered a second ulcer hemorrhage with H. pylori reinfection (3.4% relapse rate of ulcer bleeding), and this was managed endoscopically. Recurrent ulcer hemorrhage occurred in 2 out of 4 H. pylori-resistant patients. At the end of the follow-up period, of the patients in whom H. pylori eradication had been initially successful, only the patient with re-bleeding remained reinfected. The 4 H. pylori-resistant patients showed persistent H. pylori colonization. In conclusion, omeprazole plus amoxycillin is a safe and effective treatment for eradicating H. pylori; this treatment reduces the relapse rate of duodenal ulcer bleeding.

Effect of omeprazole on the course of associated esophagitis and laryngitis.

Esophagitis has increasingly been implicated as a cause of chronic laryngitis and there is some evidence that gastro-esophageal reflux disease (GERD) is more common in patients with laryngitis. The aim of this study was to evaluate whether patients with esophagitis and laryngitis responded to treatment with omeprazole. Of 74 consecutive patients with endoscopically proven GERD, 21 had laryngitis. These 21 patients with associated esophagitis and chronic laryngitis were treated for 4 weeks with omeprazole 40 mg per day. After 2 weeks of treatment and at the conclusion of the study, 2 weeks later, esophagoscopy and laryngoscopy were performed and the patients responded to a questionnaire on their symptoms. The follow-up period was 1 year. Twenty-one of the 74 patients (28.4%) had esophagitis (grade I, n = 12; grade II, n = 9) and associated laryngitis (grade I, n = 14; grade II, n = 7). The severity of the esophagitis accorded with the severity of the laryngitis. After 2 weeks' treatment with omeprazole, both the esophageal and the laryngeal symptoms had improved in all 21 patients. Endoscopically, the healing rates were 62% for esophagitis and 33.3% for laryngitis. At the end of the study period, at 4 weeks, all patients were symptom-free and the esophagitis and laryngitis had healed completely. No patient suffered from drug-induced side effects. Patients with associated laryngitis and esophagitis should be given adequate anti-reflux therapy. Both the laryngeal and esophageal symptoms improved with the omeprazole treatment, suggesting that reflux was the underlying etiology.

Significantly lower prevalence of Helicobacter pylori in uremic patients than in patients with normal renal function.

The objective of the study was to evaluate the prevalence of Helicobacter pylori in patients with different degrees of renal function. Two hundred and twenty consecutive patients requiring gastroscopy for upper intestinal symptoms were enrolled in the study: group I (normal renal function, n = 127), group II (chronic renal failure, creatinine clearance > 5 < 90 ml/min, n = 59), and group III (hemodialysis therapy, n = 34). On endoscopy, biopsy specimens were taken for analysis of H. pylori infection by urease test and histology. The prevalence of H. pylori in patients with renal dysfunction proved to be significantly lower than that in patients with normal renal function (22.6% vs 37%, P < 0.05). The incidence of ulcer disease in patients with normal renal function was higher than that in uremic patients (14.2% vs 10.8%, not significant). These findings indicate that uremic patients seem to be partly protected against H. pylori infection.

Videoendoscopic analysis of nasal steroid distribution.

Topical corticosteroids are one of the main pillars in the treatment of nasal polyps. The exact topography of their intranasal deposition has not yet been adequately visualised. The intranasal distribution of a 1% sodium fluorescein solution applied with original Pulmicort Topinasal (budesonide) metered pump bottles was analysed by videoendoscopy. The study group included eight healthy subjects and ten patients who had undergone endonasal sinus surgery. Videoendoscopy was performed in the study group within the first minute after application of the fluorescein solution. Additionally the deposition pattern of Pulmicort Topinasal was analyzed using a nasal model. The examination showed that the majority of the substance is deposited on the anterior portion of the nasal septum and the head of the inferior turbinate. Only a small fraction actually reaches the middle meatus. The distribution is improved by application during the decongested phase of the nasal cycle, after use of vasoconstricting nasal drops and maintaining a spraying angle of 45 degrees upwards. The development of new delivery techniques and systems could improve the efficacy of intranasally administered corticosteroids and reduce the complication rate.

Computer-assisted documentation and analysis of wound healing of the nasal and oesophageal mucosa.

Our aim was to analyse the dynamics of healing processes in the nose and oesophagus by videoendoscopic examination and reconstruction of the natural dynamics and continuity of a process using modern computer technology and so-called morphing software. Thirteen patients were followed-up for six months after sinus surgery and three weeks after oesophagitis. Four overlapping and meshing phases of wound healing following sinus surgery with significant interindividual differences. Topical budesonide shortened the duration of wound healing phases. Healing of oesophagitis occurred approximately symmetrically from the wound edges to the centre with constant velocity. Computer-assisted morphing enables dynamic analysing of mucosal processes under the following preconditions: Availability of a valid imaging method for documentation and measurement with the generation of congruent images. The process under analysis must run without sudden leaps and there must be adequate choice of timing of single measurement procedures.

Nasopharyngeal endoscopy adds to reliability of clinical diagnosis of infectious mononucleosis.

Frequently, the clinical picture in the oropharynx alone does not lend itself to a reliable differentiation between acute pharyngotonsillitis in infectious mononucleosis and a streptococcal inflammation. Such a differentiation, however, is essential for the indication of antibiotic therapy. Therefore, it was the aim of the present study to investigate whether or not endoscopic verification of larger-than-normal lymphatic tissue with fibrinous membranes in the nasopharynx would enhance the reliability of diagnosis. Fifty hospitalized patients exhibiting the clinical picture of acute pharyngotonsillitis were examined for the following parameters: nasopharyngeal endoscopy, determination of glutamine-oxaloacetic transaminase (GOT), glutamine-pyruvic transaminase (GPT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leucocytes and haemogram, antibodies to viral capsid antigen (VCA)-IgM, Epstein-Barr virus nuclear antigen (EBNA), and cytomegalovirus (CMV). In 24 patients with acute tonsillitis/peritonsillar abscess, and in 26 patients with infectious mononucleosis, the total leucocyte count in the blood and the blood/erythrocyte sedimentation rate were comparable. Atypical lymphocytes or absolute lymphocytosis were not seen in acute tonsillitis, but were found in 88.5 per cent of patients with infectious mononucleosis. Elevated transaminase levels were noted in 77 (GOT) and 88.5 per cent (GPT) of patients with infectious mononucleosis, and in acute tonsillitis in 4.2 (GOT) and 12.5 per cent (GPT) of patients. The CRP was higher than normal in 91.7 per cent of patients with acute tonsillitis, and in 57.7 of patients with infectious mononucleosis. In none of the patients with acute tonsillitis was lymphatic tissue with fibrinous membranes seen in the nasopharyngeal cavity. In contrast, nasopharyngeal endoscopy in infectious mononucleosis was positive in 24 out of 26 patients. Hence, the sensitivity was 92.3 per cent, the specificity 100 per cent, and the prediction value for a positive test turned out to be 1. Endoscopy of the nasopharngeal cavity employed as a simple and supplementary procedure adds to the reliability of diagnosis of infectious mononucleosis.

Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care--the ProGERD study.

BACKGROUND: The evolution of gastro-oesophageal reflux disease (GERD) under current management options remains uncertain. AIM: To examine whether, depending on the initial presentation, non-erosive (NERD) and erosive reflux disease (ERD) without Barrett's oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition. METHODS: Patients with the primary symptom of heartburn were included at baseline, and stratified into non-erosive (NERD) and erosive reflux disease (ERD), LA grades A-D (Los Angeles classification). After a 2- to 8-week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett's oesophagus after 5 years. RESULTS: A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5-year follow-up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett's oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett's oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett's oesophagus at 5 years. CONCLUSION: Most GERD patients remain stable or improve over a 5-year observation period under current routine clinical care.

[Spleen ruptures after screening colonoscopy]. / Milzruptur nach Vorsorgekoloskopie.

Splenic injury during colonoscopy is a rare but potentially life-threatening complication. The case of an 82-year-old male patient with a ruptured spleen after screening colonoscopy is reported. The predisposing risk factors for a laceration of the spleen during colonoscopy are discussed as well as the diagnostic and therapeutic approaches.