Hospitalizations for gastrointestinal and cardiovascular events in the CADEUS cohort of traditional or Coxib NSAID users.

AIMS: To assess hospital admission rates for gastrointestinal (GI) or cardiovascular (CV) events in real-life use of nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: CADEUS is a real-life population-based cohort study of 23 535 coxib (celecoxib or rofecoxib) and 22 919 traditional NSAID (tNSAID) users. Each hospitalization reported between index day (NSAID delivery) and questionnaire submission (median = 75 days) was explored using hospital discharge summaries. An expert committee validated blindly serious GI and CV events according to predefined criteria. RESULTS: Coxib users were older and had more GI history than tNSAID users. There were 21 hospitalizations for GI events, 12 in the coxib cohort and nine in the tNSAID cohort (respectively one and three upper GI haemorrhages and no ulcer perforations). Rates of GI events were 0.39 per 1000 patients [95% confidence interval (CI) 0.18, 0.75] for tNSAID users and 0.51 per 1000 patients (95% CI 0.26, 0.89) for coxib users. There were 21 hospitalizations for CV events, 13 in the coxib cohort and eight in the tNSAID cohort. None was fatal. Rates of CV events were, respectively, 0.59 (95% CI 0.24, 1.22), 0.51 (95% CI 0.19, 1.11) and 0.35 (95% CI 0.15, 0.69) per 1000 patients for celecoxib, rofecoxib and tNSAIDs. GI or CV event rates were not different between products even for patients >60 years old. CONCLUSIONS: Hospitalization rates for GI bleeding were 10-20 times lower than expected from published randomized clinical trials, probably because of differences in drug usage and concomitant gastroprotection. CV event rates conformed to those expected from general population data. These results emphasize the necessity of developing population healthcare databases to explore such low event rates.

Impact of prescriber nonresponse on patient representativeness.

BACKGROUND: In pharmacoepidemiology studies where patients are selected by prescribers, there is concern that the patients of responding prescribers are not necessarily an unbiased sample of all patients. However, this usually cannot be explored. In the CADEUS study, patients and prescribers were independently contacted so that data are available for patients irrespective of whether their prescriber responded or not. Our objective was to compare the characteristics of patients whose prescriber did or did not respond. METHODS: The CADEUS study included patients treated with COX-2 inhibitors (celecoxib, rofecoxib) or traditional NSAIDs from September 2003 to August 2004. Redeemed prescriptions were randomly sampled on a monthly basis within the database of the French national healthcare insurance system for salaried persons during 1 year. Patients and prescribers were questioned independently. Data from patients and from the database were used to compare patients whose prescriber responded and those whose prescriber did not. RESULTS: Of 45,217 patients, 26,618 had prescriber data. Patients whose prescriber responded were similar to patients whose prescriber did not respond for the main study outcomes: age (56.8 +/- 16.3 years vs. 56.1 +/- 16.3 years), sex (66.0% female vs. 64.8%), cardiovascular disease history (52.2% vs. 52.0%), gastrointestinal disease history (39.5% vs. 39.4%), concomitant prescription of gastroprotective agents (22.4% vs. 23.7%), and NSAID indication, prescription type, use, and duration. CONCLUSIONS: We found no evidence for a difference between patients whose prescriber responded and patients whose prescriber did not participate in the study.

Estimation of the prevalence and incidence of chronic pancreatitis and its complications.

UNLABELLED: Incidence and prevalence of chronic pancreatitis (CP) are poorly known and prospective nationwide epidemiologic estimation has never been performed. AIMS: To estimate prospectively national incidence and prevalence of patients attending gastroenterologists for CP in France. PATIENTS AND METHODS: Study was proposed to all of the French gastroenterologists (N=3215) of whom 753 accepted to participate (24% private, 40% hospital and 36% both). Were included all patients suffering from proved or suspected CP, from 04-2003 to 07-2003. Certain diagnostic criteria were pancreatic calcifications, ductal or histological abnormalities. For all of non-responder gastroenterologists, a tracking system was used (mail or by phone). RESULTS: A total of 456 gastroenterologists returned at least 1 case on 1748 patients. Median patient age was 51 years; sex-ratio was 5.07. Median duration between the first CP sign and the inclusion was 41 months. CP cause was alcoholism (84%), hereditary (1%), cystic fibrosis (1%), idiopathic (9%), other (6%). CP diagnosis was certain in 77%: calcifications (85%), ductal abnormalities (57%), and histology (8%). CP symptoms were: chronic abdominal pain (53%), acute pancreatitis episodes (67%), pseudocysts (40%), bi-liary tract compression (21%), diabetes mellitus (32%), pancreatic exocrine insufficiency (36%). Maximal annual incidence was 4,646 (crude annual incidence: 7.7 per 100,000; 12.9 in male; 2.6 in female) and prevalence was 15,832 cases (crude prevalence: 26.4 per 100,000; 43.8 in male; 9.0 in female). CONCLUSION: New CP patients attending gastroenterologists are about 5,000 a year. CP prevalence is about 16,000 patients (in France: 60,400,000 inhabitants). Frequency of main complications is close to hospital series, confirming that results issued from these centers are not or a few biased.

Impact of irritable bowel syndrome (IBS) on health-related quality of life (HRQOL).

AIMS: To assess the impact of irritable bowel syndrome (IBS) on patient-reported health-related quality of life (HRQOL). METHODS: Two HRQOL instruments were administered by telephone interviews to a sample of 253 IBS French patients recruited from the general population. IBS was diagnosed according to the Manning, Rome I and Rome II criteria. Patients with organic diseases were excluded from the study. A generic instrument, the Short Form 36 (SF-36), and an IBS disease-specific instrument, the IBSQOL, were used. RESULTS: Patients with IBS had statistically significant (P<0.05) lower scores for all SF-36 QOL domains compared with the general French population. Women (N=192) reported significantly (P<0.05) poorer HRQOL on both the SF-36 and the IBSQOL scores than men (N=61) for all domains except energy on the SF36 and the sleep on the IBSQOL. HRQOL deteriorated with time since onset of IBS symptoms for some domains such as diet. For both instruments, a positive correlation was observed between low scores and intensity of pain and discomfort. IBS patients with a predominance of diarrhea (N=72) exhibited significantly greater impairment of HRQOL in the emotional domain than IBS persons with constipation predominance (N=65) (P

Validation of the short-form REFLUX-QUAL (RQS), a gastro-esophageal reflux disease (GERD) specific quality of life questionnaire.

INTRODUCTION: Being an easy-to-use (eight items) quality of life questionnaire specific to GERD, the Reflux-Qual Short form (RQS) was developed for use in everyday practice. The purpose of this study was to assess the psychometric properties of the RQS. METHODS AND MATERIALS: The reliability of the RQS was measured by the Cronbach's alpha coefficient and its clinical validity by comparing the RQS score for increasing clinical severity groups. The RQS discriminative power was compared with that of the SF12. Sensitivity to change over time was measured by calculating effect-sizes. RESULTS: The reliability and validity of the questionnaire were assessed on a sample of 1195 patients. Its psychometric properties were very satisfactory: Cronbach alpha = 0.84; RQS score significantly reduced for the worst-affected patients; the discriminative power was up to 5 times higher when compared with the SF-12. Sensitivity to change over time, evaluated with 362 patients, showed highly significant differences between groups with different levels of clinical progression (P = 0.0001). CONCLUSION: The RQS is a quality of life measurement instrument specific to GERD which is short, reliable, valid, and sensitive to within and between-subject differences.

Remission of protein-losing enteropathy after nodal lymphoma treatment in a patient with primary intestinal lymphangiectasia.

Primary intestinal lymphangiectasia (PIL), so-called Waldmann's disease, is an uncommon condition, characterized by dilated intestinal submucosal and subserosal lymphatics of the gastrointestinal tract. Protein-losing enteropathy is the most common manifestation of this supposed congenital disease. Since the initial description in 1961, 11 cases of lymphoma have been reported suggesting that PIL predisposes to lymphoma. Here, we report the first case of primary nodal location lymphoma during PIL with recovery of the protein-losing enteropathy after its treatment by radiochemotherapy.

Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study.

OBJECTIVE: To evaluate the main changes in characteristics, practices and outcome between 1996 and 2000 in patients admitted for an acute upper gastrointestinal haemorrhage (AUGIH). PATIENTS AND METHODS: All consecutive patients (n=1165) admitted for an AUGIH in four French administrative areas were entered into two separate 6-month studies conducted in 1996 (n=712) and 2000 (n=453). Epidemiological and biological characteristics, endoscopic haemostatic procedures and outcomes were compared. RESULTS: Patient characteristics remained unchanged between the two studies; the two main bleeding lesions were peptic ulcer and oesophagogastric varices (30.2 versus 31.1% and 22.5 versus 20.3%). The use of non-steroidal anti-inflammatory drugs or aspirin was more frequent in 2000 (26.5 versus 32.6%; P<0.03). Proton pump inhibitor preventative therapy was administered in less than 15% of patients with a high risk of peptic ulcer bleeding in each period. In patients admitted for varices bleeding, the use of endoscopic haemostatic ligation increased (17.1 versus 40%; P<0.001), with a concomitant decrease in endoscopic sclerotic therapy (76.1 versus 37.5%; P<0.001). We observed a significant decrease in AUGIH mortality in the whole group (11.7 versus 7.2%; P=0.03), and particularly in the subgroup of cirrhotic patients (19.5 versus 11.1%; P=0.05) whatever the source of their bleeding. CONCLUSION: Our time-trend evaluation of changes in AUGIH characteristics revealed that peptic ulcer and varices were still the two most frequent bleeding lesions. In patients with varices bleeding, endoscopic ligation became the routine standard treatment instead of varices sclerosis. The mortality rate decreased significantly over the 5-year study period in the whole group and particularly in the subgroup of cirrhotic patients.

Epidemiological and phylogenetic evidence for patient-to-patient hepatitis C virus transmission during sclerotherapy of varicose veins.

The aim of this study was to provide evidence for patient-to-patient nosocomial hepatitis C virus (HCV) transmission during sclerotherapy of varicose veins. Forty-three patients who had evidence of current infection by genotype 2 HCV have had sclerotherapy by the same physician. Based on this observation, a detailed epidemiological questionnaire on risk factors for HCV in genotype 2 infected patients was conducted. Seventeen sequences in the hypervariable region 1 (HVR1) of the HCV genome obtained from 17 HCV RNA positive patients with a past history of sclerotherapy, were compared with 17 sequences derived from genotype 2 patients with no past history of sclerotherapy, and with 25 sequences sampled from GenBank. Two hundred seven genotype 2 HCV infected patients were included. The main risk factors for HCV infection were transfusion (n = 76), drug use (n = 6), and sclerotherapy of varicose veins (n = 62 including 43 (20.8%) by the same physician), other or unknown (n = 76). These sclerotherapy sessions were carried out in the 1980s for many years. Five of these 43 patients had jaundice within a few weeks after a sclerotherapy session. Sequence analysis of HVR1 from 17 patients who had sclerotherapy by the same physician revealed that they were all infected with HCV genotype 2c. The phylogenetic tree indicated clustering of the patients with a past history of sclerotherapy. The method by which infection was likely to have been transmitted was probably the use of a single vial for multiple patients. This study provides strong evidence that sclerotherapy of varicose veins is a risk factor for HCV infection.

Predictors of response to infliximab in luminal Crohn's disease.

AIMS: To identify predictive factors of response to infliximab in luminal Crohn's disease (CD). PATIENTS AND METHODS: All consecutive patients with luminal CD treated with infliximab between October 1999 and March 2003 in Bordeaux's referral centers were included. All had at least 3 months follow-up post infliximab infusion and no prior treatment with infliximab. Response rates were determined 2 and 8 weeks after infusion according to Crohn's Disease Activity Index (CDAI) (remission=CDAI<150 and response=CDAI decrease more than 100). RESULTS: Among 44 patients (33 female; mean age 35 +/- 14 yr.), 39 (88%) had a clinical response 2 weeks after infusion (79% in remission). At week 8, the rate of response was 61.4% and exclusive colonic involvement predicted sustained response to treatment (P=0.03). The probability of remission at 56 weeks was 21.4%. Multivariate analysis demonstrated that the only factor associated with response duration was initiating immunosuppressive (IS) therapy in women (RR=3.61 95%CI[1.25-10.41], P=0.017). CONCLUSION: Exclusive colonic involvement is the only predictive factor of sustained response to infliximab in luminal CD. At the time of infliximab infusion, initiation or modification of IS therapy may favor sustained response, at least in women.

Acute upper gastrointestinal bleeding in patients with liver cirrhosis and in noncirrhotic patients: epidemiology and predictive factors of mortality in a prospective multicenter population-based study.

GOALS: To assess epidemiologic features and predictive factors of mortality of acute upper gastrointestinal bleeding (UGIB). STUDY: During a 6-month period, a prospective population-based study including all the UGIB occurring in a geographic area of 3 million people was conducted. Data from cirrhotic patients were compared with those of noncirrhotic patients. RESULTS: A total of 2,133 UGIB were recorded, 21.9% in cirrhotic patients (n = 468). Endoscopic hemostasis was performed in 46.5% and 8.3% in cirrhotic and noncirrhotic patients, respectively (P < 0.001). Mortality during hospitalization was 23.5% in cirrhotic patients and 11.2% in noncirrhotic patients (P < 0.001). Six independent predictive factors of mortality were observed in both patient groups: a prothrombin level less than 40%, an UGIB occurring in inpatients, a concomitant digestive carcinoma, a hematemesis revealing the UGIB, a recent use of steroid drugs, and age over 60 years. Four other predictive factors of mortality were also identified in noncirrhotic patients. CONCLUSIONS: Although epidemiologic features, clinical course, management, and prognosis of UGIB were quite different in cirrhotic and noncirrhotic patients, the majority of predictive factors of mortality were the same in both patient groups. These data underline the major role of debilitated status and hepatic failure in the prognosis of UGIB in cirrhotic patients.

Should a liver biopsy be done in patients with subclinical chronically elevated transaminases?

In 10% of the patients with chronic abnormal alanine aminotransferase (ALT) levels no cause is found. The prognosis of this liver disease, the increased risk of liver fibrosis regardless of the types of histological lesions and the need for a liver biopsy are unknown. Nearly 50% of these cases are explained by non-alcoholic steatohepatitis (NASH). The aim of this study was to evaluate, in patients with accidentally detected chronically elevated ALT levels, the prevalence of fibrosis and NASH, and the clinical and biological factors associated with each entity. Retrospectively, 67 patients (mean age, 46.6 +/- 12.1 years; 45 males) were included. All patients had a liver biopsy and were hepatitis B virus, hepatitis C virus, human immunodeficiency virus seronegative without alcohol, drug, autoimmune or genetically induced liver disease, with ALT > N (the upper limit of normal). NASH was evaluated according to necroinflammatory lesions and fibrosis. Fibrosis was evaluated according to the METAVIR score. Statistical analyses were performed using Student's t test, the Mann-Whitney rank-sum test and the chi-square test. Fibrosis scores were: F0, 37.3%; F1, 32.8%; F2, 26.9%; F3, 1.5%; and F4, 1.5%. NASH was absent in 59.7% and present in 40.3%. Significant differences were observed between F < 2 and F > or = 2 fibrosis patients for aspartate aminotransferase (AST) and ALT and between patients with NASH or without for body mass index. Overall, the risk of F > or = 2 fibrosis was increased in patients with AST > N, ALT > 2N or AST > N and ALT > 2N. The prevalence of F > or = 2 fibrosis and NASH in patients with unexplained chronic abnormal ALT are 30% and 40%, respectively. Since the risk of F > or = 2 fibrosis is significantly increased in patients with AST > N and/or ALT > 2N, liver biopsy should be performed only in patients with AST > N or ALT > 2N.

Validation of the French version of the Fecal Incontinence Quality-of-Life (FIQL) scale.

INTRODUCTION: The aim of this multicenter study was to validate the French version of the fecal incontinence quality-of-life scale (FIQL scale) developed in the Unites States of America. PATIENTS AND METHODS: The FIQL scale has 29 items in four scales: lifestyle, coping/behavior, depression/self-perception and embarrassment. Each item is scored from 1 to 4, with poorest quality-of-life scored 1. An average is calculated for each scale. After linguistic validation of the questionnaire, the French version of the FIQL scale was tested twice, at day 0 and day 7, by 100 patients with fecal incontinence (FI). Construction validity, internal reliability, clinical validity and reproducibility were analysed. RESULTS: Analysis of convergent validity of the French version of the FIQL scale showed very good correlation between items and the corresponding scale for lifestyle (0.50-0.79) and depression/self-perception (0.44-0.74), good correlation for coping/behavior (0.31-0.70) and weak correlation for embarrassment (0.30-0.40). Valid discrimination was observed for 24 of the 29 items. Internal reliability was good for each scale (alpha Cronbach between 0.78 and 0.92). Scores determined with the FIQL scale were significantly correlated with Wexner FI scores, demonstrating the clinical validity of the instrument. Reproducibility, evaluated in patients whose FI was unchanged between day 0 and day 7, was good with intraclass correlation coefficients ranging from 0.80 (embarrassment) to 0.93 (lifestyle). CONCLUSIONS: The linguistic and psychometric evaluation demonstrated the validity of the French version of the FIQL scale. This standardized instrument is now available for clinical use in France for quality-of-life assessment in patients with FI.

Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic criteria.

OBJECTIVES: The main objectives of this study were to assess whether the use of different definitions of irritable bowel syndrome (IBS) could influence measurements of its prevalence and characterize the patient population fulfilling these different diagnostic criteria. METHOD: A telephone survey was carried out by contacting 8,221 subjects aged >or=18 Years representative of the French population. A "screening" questionnaire based on three algorithms of IBS classification (Manning, with or without a notion of a minimal duration of symptoms, Rome I and Rome II) was used by specialised inquirers. RESULTS: Twenty three percent of the subjects interviewed stated that they had suffered from abdominal pain during the previous 12 Months. The prevalence of IBS considerably varied, depending on the diagnostic criteria used: 12% based on Manning criteria without reference to the duration of symptoms; 2.5% if the notion of duration of symptoms was added to the Manning criteria, and 2.1% and 1.1% based on the Rome I and Rome II criteria, respectively (the latter including the same notion of duration). In total, 212 subjects (2.6%) met at least one of the criteria including a minimal duration of symptoms, with a predominance for women (sex-ratio close to 2). CONCLUSION: The prevalence of IBS is strongly dependent on the classification algorithm employed. The requirement of a minimum duration of symptoms eliminates IBS in a large number of subjects complaining of abdominal disorders. Once these methodological variations were taken into account, the prevalence of IBS in France was found to be comparable to that published in international literature.

[Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature]. / Maladie coeliaque et maladies auto-immunes ou maladies systémiques.

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.

Isolated idiopathic chronic pancreatitis associated with a compound heterozygosity for two mutations of the CFTR gene.

We report the case of a patient suffering from idiopathic chronic pancreatitis (ICP) and compound heterozygous for mutations G542X and S1235R of the cystic fibrosis transmembrane regulator (CFTR) gene. The patient had normal sweat test and no other clinical sign usually linked with a typical or moderate pathology (bronchiectasis, nasal polyposis, congenital absence of the vas deferens) of the CFTR gene. G542X is a severe mutation, which is usually found in classical cystic fibrosis when associated with other severe mutations. S1235R is a quite rare abnormality recently reported as being potentially pathogenic when combined in trans with a second CF mutation. Our case is quite similar to the only other six patients in the literature in whom only the pancreas is affected and who bear a rare mutation with moderate effect. The history and the clinical features of our patient indicate an unambiguous isolated ICP in which the presence of the S1235R mutation--in trans with regard to G542X--is likely responsible for the ICP phenotype. This case could throw light on some of the as yet poorly known abnormalities of the CFTR gene in the ICP phenotype.