Pharmacological dependency in chronic treatment of gastroesophageal reflux disease: a randomized controlled clinical trial.

BACKGROUND: Despite evidence of the overuse of acid suppressive medication for gastroesophageal reflux disease (GERD), a transfer to noncontinuous therapy after long-term treatment proves difficult. AIM: To quantify the effect of blinded dosage reduction after long-term therapy on symptom control and quality of life while assessing pharmacological and placebo needs. METHODS: Primary care patients with a history of GERD and long-term treatment were randomized to daily placebo with pantoprazole rescue (n = 141) or daily pantoprazole with placebo rescue (n = 62) upon relief after 4 weeks pantoprazole 20 mg. The number of rescue tablets, symptom control and generic quality of life were analyzed. RESULTS: Measured from the daily placebo arm, 19% of the patients terminated treatment, 33% managed with 2-6 tablets/week, 38% needed a daily dosage and 10% needed more than a daily dosage in the long run. At these final dosages, symptom control and quality of life were dosage-independent and, furthermore, equal to values of patients on fixed daily pantoprazole. A temporal decrease in well-being was seen in 24% of the patients. CONCLUSION: A significant placebo response is apparent in long-term users of acid suppressive medication and pharmacological dependency is overestimated. Despite their history of long-term treatment, the majority of GERD patients can be switched from daily to on-demand treatment without impairing symptom control and quality of life.

Maintenance treatment for GERD: residual symptoms are associated with psychological distress.

AIM: The aim of this study was to explore determinants of residual reflux symptoms among patients with gastroesophageal reflux disease (GERD) despite maintenance treatment with acid suppressive medication (ASM). METHODS: Primary care GERD patients on chronic ASM were classified as symptom-free (55%) or symptomatic (45%) according to the impact of their residual reflux symptoms (QolRad). They were compared with respect to lifestyle (BMI, alcohol, smoking, physical exercise), compliance (daily ASM dosage), disease history, psychological factors (SCL-90) and quality of life (SF-36). RESULTS: None of the investigated lifestyle factors, nor dosage and disease history were related to residual symptoms. However, symptomatic patients differed from patients with relief on all psychological and quality of life dimensions. In a multiple logistic regression model somatization, hostility, mental health, body pain, as well as gender were independently associated with residual symptoms; the derived ROC curve had an AUC of 0.78. CONCLUSIONS: The majority of GERD patients is symptom-free on chronic ASM; they display a healthy psychological state and high quality of life. Residual symptoms however, are associated with psychological distress and lower quality of life. Recognition of this subgroup might hold the key to improving long-term management of gastroesophageal reflux.

Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common health problem, often presenting in primary care as well as in internal medicine and gastroenterology outpatient clinics. Therapeutic options are dominated by drug therapies but there is uncertainty about their effectiveness. OBJECTIVES: The primary objective of this review was to evaluate the efficacy of bulking agents, antispasmodic and antidepressant medication for the treatment of IBS. SEARCH STRATEGY: A computer assisted search of MEDLINE, EMBASE, PsychInfo and the Cochrane Library was performed for the years 1966-2001; local and national databases were searched in 10 European countries. SELECTION CRITERIA: Randomised trials comparing bulking agents, antispasmodic or antidepressant medications with a placebo, in IBS patients over 12 years of age. Only studies published as a full paper were included. No language criterion was applied. DATA COLLECTION AND ANALYSIS: The search identified 687 studies, 66 of which fulfilled all eligibility criteria. After removal of cross-over studies that did not report separately on the first phase, data from 40 studies remained for analysis. Relative risk (RR), risk difference (RD) and standardized mean difference (SMD) along with 95% confidence intervals were calculated for all subgroups. The number needed to treat (NNT) was also calculated where appropriate. MAIN RESULTS: Forty-one study reports from 40 studies, comprising 78 comparisons, were analysed. These included 11 reports on bulking agents, 6 on antidepressants, and 24 on spasmolytics.BULKING AGENTS: Three studies comprising 159 patients reported a dichotomous outcome for relief of abdominal pain. The pooled RR using a random effects model was 1.22 (95% CI 0.86 - 1.73). Three studies comprising 128 patients reported a continuous outcome for relief of abdominal pain. Using the random effects model, the SMD was 0.68 (95% CI -0.86 - 2.33). Nine studies comprising 482 patients reported a dichotomous outcome for global assessment of improvement. The pooled RR was 1.09 (95% CI 0.78 - 1.50). Five studies comprising 253 patients reported a dichotomous outcome for improvement of symptom score. The pooled RR using a random effects model was 0.93 (95% CI 0.56 - 1.54). Two studies comprising 70 patients reported a continuous outcome for improvement of symptom score; the SMD using a fixed effects model was -0.44 (95% CI -1.20 - 0.31). SPASMOLYTIC AGENTS: Eleven studies comprising 1260 patients reported a dichotomous outcome for relief of abdominal pain. The pooled RR using a random effects model was 1.34 (95% CI 1.13 - 1.59; RD=0.17, 95% CI 0.06 -0.28; NNT=6, 95% CI 4 - 15). Seven studies comprising 467 patients reported a continuous outcome for relief of abdominal pain. Using a fixed effects model the pooled SMD was -0.65 (95% CI -0.94 to -0.35). Sixteen studies comprising 1236 patients reported a dichotomous outcome for global assessment of improvement. The pooled RR using a random effects model was 1.42 (95% CI 1.17 - 1.72; RD=0.20, 95% CI 0.09 -0.30; NNT=5, 95% CI 3 - 11). One study comprising 34 patients reported a dichotomous variable for improvement of symptom score. The RR was 1.33 (95% CI 0.96 - 1.85). Three studies reported a continuous outcome for improvement of symptom score; two studies comprising 66 patients could be pooled. Using a fixed effects model, the SMD was -0.37 (95% CI -0.85 - 0.12). ANTIDEPRESSANTS: Two studies comprising 81 patients reported a dichotomous outcome for relief of abdominal pain. Using the random effects model, the pooled RR was 0.83 (95% CI 0.33 - 2.12). Two studies comprising 101 patients reported a continuous outcome for relief of abdominal pain. The SMD using a random effects model was -0.53 (95% CI -2.29 - 1.23). Four studies comprising 241 patients reported a dichotomous variable for global assessment of improvement. The pooled RR was 1.16 (95% CI 0.78 - 1.73). AUTHORS' CONCLUSIONS: The evidence for efficacy of drug therapies for IBS is weak. Although there is evidence of benefit for antispasmodic drugs for abdominal pain and global assessment of symptoms; it is unclear whether anti-spasmodic subgroups are individually effective. There is no clear evidence of benefit for antidepressants or bulking agents. The physician should be aware that global assessment is a construct containing various dimensions. For each individual, these will have a different weighting and treatment should be aimed at the most debilitating symptom. Stool problems are by definition part of the IBS symptom complex. Bulking agents may improve constipation and can be used empirically, but should be evaluated at an early stage for individual benefit. Future research should pay attention to study methodology and the use of valid outcome measures.

Helicobacter pylori treatment instead of maintenance therapy for peptic ulcer disease: the effectiveness of case-finding in general practice.

BACKGROUND: Maintenance therapy with acid-inhibiting medication is common in general practice. Since the eradication of Helicobacter pylori has become the treatment of choice for peptic ulcer disease, H. pylori treatment could replace maintenance therapy in patients with an ulcer history. AIM: To determine the effectiveness of a full peptic ulcer disease history case-finding strategy, together with subsequent H. pylori testing and treatment, in discontinuing maintenance therapy. METHOD: Patients were included from seven general practices, who had been using acid-inhibiting medication for more than 3 months in the period May 1996-May 1997. Patients with a history of proven peptic ulcer disease were tested, and treated with proton pump inhibitor-triple therapy if positive. Maintenance therapy was discontinued and restart within 12 months was monitored. RESULTS: Long-term acid suppression was used by 2.8% of the practice-populations. A peptic ulcer disease history was found in 18% of the patients, 73% of whom were offered the 'H. pylori test and treat' alternative. The majority responded: 92% of the H. pylori-infected patients were treated, 78% of whom successfully discontinued long-term medication. CONCLUSION: Implementing an 'H. pylori test and treat' strategy enabled one-third of the patients with a peptic ulcer disease history to stop maintenance therapy successfully. The strategy contributes to reduction of long-term drug use, but compliance needs improvement.

In-practice evaluation of whole-blood Helicobacter pylori test: its usefulness in detecting peptic ulcer disease.

BACKGROUND: Approximately 10% of patients presenting with dyspepsia to the general practitioner have peptic ulcers; the large majority of which are related to infection with Helicobactor pylori. Office-based tests for H. pylori detection are generally validated and evaluated in selected patient groups. AIM: To evaluate the clinical effectiveness of a whole-blood serology test for infection with Helicobacter pylori in detecting peptic ulcer disease (PUD) in daily general practice. METHOD: A descriptive study of 171 primary care dyspepsia patients selected for open-access endoscopy in primary care and aged between 18 and 75 years, in 92 general practices in central, southern, and eastern parts of the Netherlands. H. pylori status was assessed using the BM-test Helicobacter pylori, which is identical to the Helisal test. Dyspepsia severity score was measured using a validated symptom score. Symptom characteristics and probability of relevant disease were assessed by the general practitioner. Endoscopy was carried out in local hospitals. Diagnostic outcome of both endoscopy and H. pylori reference test was supplied by local specialists. The BM-test was evaluated against endoscopic results. RESULTS: A high number (61.8%) of false-negative BM-tests resulted in a low sensitivity (95% confidence interval [CI] = 48-75%) for detection of H. pylori infection. Only 12 out of 32 patients with PUD had a positive BM-test, resulting in a positive likelihood ratio (LR) for PUD of 1.41 and a negative LR of 0.85. CONCLUSIONS: This study confirms the relatively poor performance of the BM-test in daily general practice, and shows the limited diagnostic value of H. pylori office-tests for detecting PUD in primary care. The discriminative value of the test result is too small to support either a 'test-and-endoscope' of a 'test-and-treat' strategy in general practice.

Participation and successful patient recruitment in primary care.

OBJECTIVE: The demand for family physicians (FPs) to participate in research is growing. The delicate balance between research participation and the daily practice routine might explain the often-disappointing number of patients recruited. We analyzed practice and physician characteristics associated with successful patient recruitment. STUDY DESIGN: We used a survey to conduct this study. POPULATION: There was a total of 165 FPs who participated in a combined randomized clinical trial/cohort study on drug treatment of dyspepsia in the Netherlands. OUTCOMES MEASURED: We surveyed FPs about personal and practice characteristics and their motivation for participation in the project. These data were then related to the number of patients recruited. Univariate associations were calculated; relevant factors were entered into a logistic model that predicted patient recruitment. RESULTS: Data on 128 FPs could be analyzed (80% response rate); these FPs recruited 793 patients in the cohort study (mean = 6.3 per FP) and 527 in the clinical trial (mean = 4.2 per FP). The main reasons for participation were the research topic (59%) and the participation of an academic research group in the study (63%). Many FPs felt that participation was a professional obligation (39%); the financial incentive played a minor role (15%). The number of recruited patients was only independently associated with the participation of an academic research group. CONCLUSIONS: Successful patient recruitment in primary care research is determined more by motivation driven by the research group than by financial incentives, the research topic, or research experience.

How useful is paracetamol absorption as a marker of gastric emptying? A systematic literature study.

Functional dyspepsia is a common disorder in primary care and gastroenterology units; however, the pathophysiology is poorly understood. Delayed gastric emptying is present in nearly 40% of patients. We evaluated the validity of the paracetamol absorption test in comparison with scintigraphy for gastric emptying assessment. Studies comparing scintigraphy with paracetamol absorption were selected through a structured Medline search. A correlation coefficient between scintigraphy and paracetamol absorption over 0.6 was considered good, between 0.45 and 0.6 intermediate, and below 0.45 poor. Feasibility was assessed by studying the administration of paracetamol, frequency of blood sampling, duration of the test period, and parameters used in the analysis. Thirteen studies were identified, eight (127 subjects) found a good correlation between scintigraphy and paracetamol absorption, two studies (28 subjects) found a moderate correlation, and three (25 subjects) found no correlation. Parameters used were area under the curve (N = 9), fixed-time concentrations (N = 6), concentration-max (N = 4) and time-to-concentration-max (N = 5). Repetitive blood samples ranged from 6 to 20 samples. The durations were 1.5-8 h. In conclusion, the paracetamol absorption technique generally correlates well to scintigraphy of liquid phase gastric emptying. The execution and outcome parameters however need further standardization to optimize its' value for clinical use and research purposes.

A phenotypic male with true hermaphroditism and a 46,XX/46,XY/47,XXY karyotype.

A phenotypic boy presenting with gynaecomastia showed a mixed karyotype of 46,XX/46,XY/47,XXY. The left gonad was normally descended into the scrotum, but proved to be an ovary without any testicular structures. After left gonadectomy, plasma androgen and estrogen levels showed that the right gonad only contained testicular tissue. Seven patients with this form of triple mosaicism have been described but the clinical features are strikingly different among the described cases.

Dyspepsia management in primary care in The Netherlands: to what extent is Helicobacter pylori diagnosis and treatment incorporated? Results from a survey among general practitioners in The Netherlands.

BACKGROUND: Many guidelines on the management of Helicobacter pylori (HP)-related dyspepsia have been launched over the past decade. The suggested policies in these guidelines are often more consensus- than evidence-based (test-and-treat policy, test and endoscope), which may cause confusion among primary-care physicians. AIM: To determine the current management of HP-related dyspepsia by Dutch general practitioners (GPs). METHODS: A random sample of 5% of all Dutch GPs (n = 355) were sent a questionnaire on the diagnosis and treatment of HP infections in dyspepsia management. RESULTS: The response rate was 66.2% (n = 235). Almost 80% of the responding GPs stated they had conducted HP testing (via endoscopy or serology) during the previous 12 months. In the same time period, more than 94% had actually prescribed a HP eradication therapy. A total of 70% of the GPs stated that they used endoscopy to test for HP infection, 54% used serology (ELISA); whole-blood tests and carbon urea breath tests were not used. Patients with a history of peptic ulcer disease, those on chronic acid-suppressive drugs and patients with recurrent ulcer-like complaints were most frequently tested for HP infection. CONCLUSIONS: Given the frequency of consultations for dyspepsia in primary care in the Netherlands (150 new dyspeptic patients per average practice per year), and the reported average number of HP tests performed (1-5 per GP per year), HP diagnosis plays a modest role in the management of dyspepsia in Dutch general practices. Neither the 'test-and-treat' policy recommended in the Maastricht guidelines, nor its advice regarding the choice of diagnostic tests (carbon urea breath test or serology), is being followed. The majority of GPs uses endoscopy for the detection of HP infection.

Dyspepsia in primary care: acid suppression as effective as prokinetic therapy. A randomized clinical trial.

BACKGROUND: While dyspeptic patients in primary care often receive empirical treatment with antisecretory drugs, a substantial number suffer from motility disturbances which may be associated with their complaints. We aimed to compare the effectiveness of treatment with antisecretory treatment with a prokinetic agent in uninvestigated dyspepsia. METHODS: 563 patients presenting dyspeptic complaints to the general practitioner with a low likelihood of organic (ulcer, reflux or malignant) disease, i.e. absence of alarm symptoms or a history of peptic ulcer disease or gastro-oesophageal reflux disease were included. They entered a randomized, double-blind trial of 4 weeks of ranitidine 150 mg bid compared with 4 weeks of cisapride 10 mg bid, with 3 months follow-up. Treatment failure was defined as no response to treatment or a relapse of symptoms within the follow-up period. Also studied were the effect on dyspepsia severity, response to treatment after 4 weeks, and time to relapse. RESULTS: For all randomized patients, the incidence of overall treatment success after 3 months follow-up with antisecretory treatment was 107/271 (39.5%) and with a prokinetic agent 122/282 (43.3%); the risk difference was 3.8% (95% CI -4.4% to 12.0%); the difference in symptom severity score after 4 weeks of treatment was 0.3; 95% CI -0.4% to 1.0%. For patients responding to 4 weeks of treatment, relapse-free time was 86 days in the prokinetic group and 79 days in the acid suppression group (P = 0.005). CONCLUSIONS: Antisecretory and prokinetic therapies are equally effective in primary care patients with uninvestigated dyspeptic complaints, though relapse rates are lower in patients treated with prokinetic treatment.

What makes the dyspeptic patient feel ill? A cross sectional survey of functional health status, Helicobacter pylori infection, and psychological distress in dyspeptic patients in general practice.

BACKGROUND: Dyspepsia is prevalent in about 30% of the general population in Europe, but only 25% of people with complaints consult their general practitioner. AIMS: To study the relation between the severity of dyspeptic complaints and the health status of patients presenting to the general practitioner; and the relation with patient characteristics, Helicobacter pylori infection, and psychological distress. METHODS: A cross sectional, general practice based survey of 360 unselected primary care dyspeptic patients from 92 general practices in The Netherlands was conducted. Symptom severity was measured using a validated symptom score, H pylori using a whole blood test, and psychological distress using the GHQ-12 test. Functional health status was assessed using the COOP/Wonca charts. RESULTS: Symptoms lasting more than three months and presence of relevant psychological distress were both associated with higher levels of dyspepsia. H pylori infection, frequency of symptoms, and age had no influence on dyspepsia severity. Severity of dyspepsia and psychological distress, but not H pylori infection or duration of symptoms, affected health status univariately. Dyspepsia correlated with general health, daily activities, and social activities. In logistic modelling, health status was far better predicted by psychological distress than by dyspepsia severity. CONCLUSION: The relation between dyspeptic symptom severity and health status is limited. H pylori infection relates neither to functional health status, nor to intensity of dyspepsia. Psychological distress is a major determinant of impaired health of dyspeptic patients in general practice and may be the clue to improvement of health status in many dyspeptic patients.

Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysis.

Functional dyspepsia is a common disorder with a diverse pathophysiological background, but the role of motility disorders in functional dyspepsia remains unclear. We aimed to quantify the relationship between disturbed gastric emptying and functional dyspepsia, using a meta-analytic approach. Through a structured literature search of Medline and Embase from 1983 to 1996, we selected all studies in which scintigraphic solid-phase gastric emptying was measured in both functional dyspeptic patients and controls. Seventeen studies involving 868 dyspeptic patients and 397 controls were pooled. Gastric emptying in patients with functional dyspepsia was 1.46 (1.23-1.69) times slower than controls; the proportion of patients with abnormally slow emptying was either 37% (34-40%, simple numeric pooling) or 39% (29-49%, weighted pooling). We conclude that gastric emptying of solids in patients with functional dyspepsia is 1.5 times slower than in healthy controls and that a significant delay of emptying is present in almost 40% of patients with functional dyspepsia.