A plant extract and its modified preparation in functional dyspepsia. Results of a double-blind placebo controlled comparative study

AIMS: To assess the efficacy and safety of the commercially available herbal preparation (Iberogast, STW-5*) containing extracts from bitter candy tuft, chamomile flower, peppermint leaves, caraway fruit, licorice root, lemon balm leaves, angelica root, celandine herbs, milk thistle fruit and its research preparation STW-5-S (without bitter candy tuft) in patients with functional dyspepsia. PATIENTS AND METHODS: After a standardized diagnostic work-up and at least 7 days free of medication, 60 patients, diagnosed with functional dyspepsia, were recruited in a multicenter trial and randomly assigned to one of 3 treatment groups (STW-5, STW-5-S or placebo). Each patient received the treatment for 4 weeks. The main outcome variables were the improvement of a gastrointestinal symptom score (GIS), a sumscore consisted of 10 dyspeptic symptoms rated on a Likert scale. Dyspeptic symptoms were assessed at baseline, 2 and 4 weeks after treatment. RESULTS: 60 patients completed the trial (mean age 46.8 years, range 25-70, female 38 patients). Compared with placebo-group both herbal preparations STW-5 and STW-5-S showed a clinically significant improvement of GIS after 2 and 4 weeks of treatment (p < 0.001). No statistically significant difference could be observed between the efficacy of STW-5 and STW-5 S (p > 0.05), but a solid improvement of gastrointestinal symptoms could be achieved earlier with STW-5 than with its research preparation STW-5-S without bitter candy tuft (p = 0.023). CONCLUSIONS: In patients with functional dyspepsia, the commercially available herbal preparation STW-5 and its modified dispense STW-5-S tested improved dyspeptic symptoms significantly better than placebo. The extract bitter candy tuft appeared to have an additive effect on dyspeptic symptoms.     

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan

BACKGROUND AND AIM: Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. METHODS: In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. RESULTS: Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). CONCLUSIONS: Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.     

Clinical Presentation and Personality Factors Are Predictors of the Response to Treatment in Patients with Functional Dyspepsia: A Randomized, Double-Blind Placebo-Controlled Crossover Study

The role of psychological factors or symptom pattern for the response to treatment in patients with unexplained (functional) dyspepsia is unknown. We hypothesized that patients with reflux- and ulcer-like symptoms would be more likely to respond to acid-lowering therapy, while psychological disturbances would be associated with a less favorable response to treatment. Seventy-eight patients with a diagnosis of functional dyspepsia were recruited and 75 completed the trial. Patients were treated for 4 weeks in a double-blind, placebo-controlled crossover trial starting in random order with either active drug (ranitidine, 150 mg b.d.) or placebo. Every 7 days, medication was switched from active drug to placebo, or vice versa. At entry, patient characteristics were assessed utilizing a semistructured standardized interview and standardized questionnaires, and weekly intensity of symptoms was assessed utilizing a visual analogue scale. Patients with a greater reduction of the symptom score during active treatment and an overall reduction of the global symptom score by more than 50% at the end of the study period were categorized as responders. Logistic regression analysis was utilized to assess the influence of symptom type and presence of psychological disturbances on the treatment response. During treatment the symptom score decreased significantly, from 32.1 +/- 1.44 (SD) to 21.3 +/- 1.9 at the end of the trial (P < 0.001). Twenty of 75 were responders. High scores for somatization (OR, 3.6; 95% Cl, 1.2-11.4), anxiety (OR, 3.3; 95% Cl, 0.9-11.8), and reflux-like symptoms (OR, 5.3; 95% Cl, 1.7-16.7) were associated with response to treatment, while dysmotility-like symptoms were associated with an unfavorable response (OR, 0.3; 95% Cl, 0.1-0.9). Symptom pattern and psychological disturbances are independent predictors of treatment response. Patients with reflux-like symptoms and greater psychological disturbances are more likely to respond to an acid-lowering compound.     

Dyspepsia on withdrawal of ranitidine in previously asymptomatic volunteers

OBJECTIVE: H2 receptor antagonist therapy has been shown to produce rebound acid hypersecretion. The clinical significance of this phenomenon is not known. We performed this study to determine whether withdrawal of H2 receptor antagonist therapy results in dyspepsia in previously asymptomatic volunteers. METHODS: Thirty-five Helicobacter pylori-positive asymptomatic volunteers were randomized in double-blind fashion to receive 2 months' treatment with either ranitidine 300 mg nocte or placebo. Dyspeptic symptoms were measured before starting treatment and over the course of 10 days after stopping treatment by means of a validated questionnaire. RESULTS: Thirty-one subjects completed the study; 17 were randomized to ranitidine. The pretreatment median aggregate dyspepsia score of the placebo group was 0 (0-4), as was that of the ranitidine group (0-8) (N.S.). During the 10 days after completion of ranitidine, the median aggregate dyspepsia score was 1.4 (0-30), compared with 0 (0-6.3) after placebo (p < 0.01). Of those given ranitidine, 59% experienced dyspepsia after treatment, compared with only 14% who took placebo. In the subgroup that developed dyspepsia after active therapy, the median duration of symptoms was 2 days, symptom severity being maximal on the second day after completion of the tablets. On the days when dyspepsia was experienced, the median daily dyspepsia score was 5 (range, 2-10), which was similar to that of a control group with active duodenal ulcer disease (5; range, 0-11). CONCLUSIONS: Withdrawal of a 2-month course of ranitidine 300 mg nocte results in the development of dyspeptic symptoms in a proportion of previously asymptomatic subjects. Patients receiving ranitidine should be warned about this rebound dyspepsia and advised not to immediately resume treatment, as rebound symptoms are likely to improve within a few days.     

Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.     

Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia

OBJECTIVES: The aim of this study was to compare the effect of a combination of lansoprazole, clarithromycin, and amoxicillin (LCA) versus placebo on the severity of symptoms in functional dyspepsia patients who were positive for Helicobacter pylori (H. pylori). METHODS: This was a double-blind, randomized, controlled clinical trial in adult patients with functional dyspepsia who were H. pylori positive. Patients were randomized to 7-day treatment with LCA or identical looking placebo. H. pylori status was confirmed by the urea breath test performed at baseline, at 6 wk, and at 6 and 12 months. The severity of eight upper GI symptoms was measured on a five-point Likert scale. The main outcomes were the change in average severity of the dyspepsia summary score of the eight symptoms and the proportion of patients who improved >/=4 points on the dyspepsia summary score. RESULTS: A total of 157 patients were included in the intention-to-treat analysis. LCA achieved cure of H. pylori infection in 82% of patients compared to 6% in the placebo group. The severity of dyspepsia symptoms improved over the 12-month study period, but for none of the outcome measures was there a significant difference between LCA and placebo. CONCLUSIONS: There was no difference in sustained improvement of dyspepsia symptoms when LCA was compared with placebo. An 82% cure rate of H. pylori infection was observed with LAC.     

Helicobacter pylori eradication and standardized 3-month omeprazole therapy in functional dyspepsia

OBJECTIVES: The role of Helicobacter pylori in functional dyspepsia remains unclear. This study evaluated the long term consequences for symptoms and quality of life in patients with H. pylori-positive functional dyspepsia after H. pylori eradication therapy with a standardized 3-month omeprazole treatment. METHODS: A total of 151 H. pylori-positive patients with functional dyspepsia were randomized to receive either eradication therapy or placebo-antibiotics. The initial medication was administered in a double-blinded fashion. In addition, to standardize acid suppression, every patient received omeprazole therapy for the first 3-month period. Dyspeptic symptoms were evaluated by a questionnaire every 3 months, and quality of life was measured by a validated RAND 36-item health survey 1.0 questionnaire at the beginning of the study and after 12 months of follow-up. As the main outcome measure, the scores of patients who had received H. pylori eradication therapy and omeprazole were compared with those who received placebo and omeprazole during the 12 months of follow-up. RESULTS: A total of 136 patients completed the 1-yr follow-up. In all, 77 patients received eradication therapy and 74 patients remained as controls. After 12 months, the mean reduction in the dyspepsia score was 28.8% in patients with H. pylori eradication therapy and 21.7% in the control group. The reduction of dyspepsia was significant (p < 0.0001) in both groups compared to baseline value, but no statistically significant differences in changes of dyspeptic symptoms or in quality of life were demonstrated between the H. pylori eradication therapy group and controls after 1 yr. In both patient groups, regurgitation (p < 0.001) and heartburn (p < 0.01) revealed relapse after cessation of 3-month omeprazole treatment. CONCLUSIONS: No clear differences in symptoms or in quality of life were found between patients treated with H. pylori eradication therapy and omeprazole compared with patients receiving placebo and omeprazole after 1 yr. Regardless of H. pylori status, omeprazole treatment reduced heartburn and regurgitation. The placebo effect on the symptoms of functional dyspepsia and on quality of life was marked.     

Long-term efficacy and safety of fluticasone propionate powder administered once or twice daily via inhaler to patients with moderate asthma

OBJECTIVE: To evaluate the efficacy and safety of fluticasone propionate administered as a once-daily or twice-daily regimen over a period of 1 year to patients with moderate asthma. DESIGN: Double-blind, randomized, parallel group, and placebo-controlled phase (12 weeks) and an open-label phase (54 weeks). SETTING: Multicenter study in an outpatient setting. PARTICIPANTS: Patients (n = 253; age, > or = 12 years) with a mean FEV(1) of 67% predicted normal were stratified according to baseline therapy of maintenance inhaled corticosteroids vs beta(2)-agonists alone. MEASUREMENTS AND INTERVENTIONS: Fluticasone propionate (250 microg bid or 500 microg qd) or placebo (bid) was administered via the Diskus multidose powder inhaler (Glaxo Wellcome; Research Triangle Park, NC) for 12 weeks. During open-label treatment, patients were re-randomized to once-daily or twice-daily fluticasone propionate. RESULTS: Compared to placebo, fluticasone propionate administered qd or bid significantly improved FEV(1) (p < 0.001), morning (p < 0.001) and evening peak expiratory flow (PEF; p < 0.001), asthma symptom scores (p < or = 0.001), and albuterol use (p 相似文献   

A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study

BACKGROUND: The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies. METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months. RESULTS: Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p < 0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine. CONCLUSION: Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.     

Impact of functional dyspepsia on quality of life and health care consumption after cessation of antisecretory treatment. A multicentre 3-month follow-up study.

BACKGROUND: The impact of response to treatment on subsequent symptoms, quality of life, health care consumption, and absence from work in functional dyspepsia is unknown. METHODS: Patients with functional dyspepsia from Denmark, France, Germany, The Netherlands, Hungary, and Poland (n = 567 (215 men), 18-80 years old) were followed up for 3 months after a 4-week treatment trial with omeprazole (20 mg or 10 mg) or placebo. The patients were blinded to the initial treatment. Dyspeptic symptoms and quality of life were assessed, and dyspepsia-related costs were calculated in terms of number of clinic visits, days on medication, and absence from work. RESULTS: Responders had fewer clinic visits than non-responders (1.5 versus 2.0 mean visits) and fewer days on medication (mean, 9 days versus 23 days) over the 3-month period (both, P < 0.001). The quality of life in responders was better at study entry and persisted over 3 months (all, P < 0.001). When analysed country by country, health care costs due to clinic visits and medications were significantly lower in responders in all countries (P < 0.05), except Denmark and The Netherlands. CONCLUSION: Symptom resolution in patients with functional dyspepsia has a positive impact on quality of life and reduces the subsequent costs over a 3-month period after cessation of initial treatment.     

Esomeprazole 40 mg once a day in patients with functional dyspepsia: the randomized, placebo-controlled "ENTER" trial

OBJECTIVE: The etiologies of functional dyspepsia (FD) are unclear, but in some studies, treatment with a proton pump inhibitor has been beneficial. The objective of this study was to evaluate the efficacy of esomeprazole 40 mg once a day compared to placebo in achieving symptom relief in primary care patients with FD. METHODS: This was a randomized, placebo-controlled trial in adult FD patients, who had at least moderate severity of symptoms, defined as a score of > or =4 on a 7-point Global Overall Symptom (GOS) scale. Patients were excluded if they had predominant symptoms of heartburn or regurgitation; after a normal baseline endoscopy, patients were randomized to esomeprazole 40 mg once daily or placebo for 8 wk. The primary outcome measure was symptom relief (GOS < or =2) at 8 wk. RESULTS: Of the 502 enrolled patients, 224 were randomized. The main reasons for exclusion were abnormal endoscopic findings, especially esophagitis. A significantly greater proportion of patients in the esomeprazole group achieved symptom relief at 4 but not at 8 wk compared to placebo: 4 wk esomeprazole 50.5% versus placebo 32.2%, p= 0.009; 8 wk esomeprazole 55.1% versus placebo 46.1%, p= 0.16. A similar relationship at 4 and 8 wk was seen for symptom resolution (GOS = 1) and improvement (DeltaGOS > or =2). CONCLUSION: For the primary outcome measure of symptom relief at 8 wk, there was no statistically significant difference between esomeprazole 40 mg once a day and placebo. However, at 4 wk, esomeprazole was significantly more effective than placebo for symptom relief. The difference in therapeutic gain between 4 and 8 wk was largely due to a higher placebo response rate at 8 wk.     

Helicobacter pylori eradication treatment does not benefit patients with nonulcer dyspepsia

OBJECTIVES: The aim of this study was to assess the still controversial role of treatment of Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter trial comparing the efficacy of 7 days of eradication treatment (lansoprazole 15 mg b.i.d., amoxicillin I g b.i.d., and clarithromycin 500 mg b.i.d.) with a control treatment (lansoprazole 15 mg b.i.d. and placebo) in H. pylori-infected patients with nonulcer dyspepsia. 13C breath tests were performed at baseline and during follow-up. We assessed patient symptoms, health status (based on the SF-12 questionnaire), patient satisfaction, drug consumption, health care consultation behavior, and absenteeism related to dyspepsia over a 1-yr period. RESULTS: A total of 74 patients randomized to eradication treatment and 70 patients randomized to placebo were compared. The rate of eradication of H. pylori infection was 75% in the active treatment group and 4% in the placebo group (p < 0.005). The symptom score improved to a similar extent in the group receiving active treatment (-4.0; 95% CI = -5.0 to -3.0) and placebo (-3.6; 95% CI = -4.5 to -2.7). Treatment response was not related to the severity or duration of initial symptoms or to the severity of gastritis on histology. Quality of life scores were comparable at 12 months. There was no significant difference in dyspepsia-related absenteeism or satisfaction with management of NUD. Patients receiving active treatment were more likely not to have had to use any dyspepsia treatment over the 12 months (60.8% vs 44.3%; p = 0.047). CONCLUSIONS: This study did not demonstrate any substantial benefit of curing H. pylori infection in patients with nonulcer dyspepsia. The study adds further evidence that H. pylori is not the main pathogenetic or therapeutic target in these patients.     

The symptomatic effect of 1-day treatment periods with cimetidine in dyspepsia. Combined results from randomized, controlled, single-subject trials

Before endoscopy a double-blind, randomized, controlled, single-subject trial comparing the symptomatic effect of 1-day treatment periods with cimetidine and placebo was conducted in patients with dyspepsia. Results from 339 patients were analysed. The trial lasted 12 days and consisted of 6 treatment days with 400 mg cimetidine three times daily and 6 days with placebo three times daily. The order of the treatments was randomized within six pairs, and a randomization test based on daily measures of global symptoms provided individual p values. Aggregation of the measures from all subjects showed that cimetidine alleviated the symptoms significantly better than placebo in peptic ulcer disease (PUD) (p less than 0.0001), oesophagitis (p less than 0.001), and non-ulcer dyspepsia (NUD) (p less than 0.0001). Twenty-seven per cent of the patients with PUD, 26% of those with oesophagitis, and 12% of the patients with NUD obtained individual p values of less than 0.10 and were defined as responders. The best predictors of the response to cimetidine in NUD were age above 40 years, heartburn or acid regurgitations being the worst symptom, and night pains relieved by food, milk, or antacids. In conclusion, the applied single-subject trial confirmed the overall symptomatic effect of cimetidine in dyspepsia and identified individual responders among patients with NUD with a clinically reasonable profile. The low proportion of responders among patients with PUD or oesophagitis suggests that the model has a low sensitivity for identification of individual responders and that the single-subject trial design in dyspepsia needs further refinement.     

Double blind,randomised, placebo controlled study of four weeks of lansoprazole for the treatment of functional dyspepsia in Chinese patients

BACKGROUND: The use of proton pump inhibitors for the treatment of functional dyspepsia is controversial and the role of Helicobacter pylori infection in functional dyspepsia is uncertain. AIM: To evaluate the efficacy of different doses of lansoprazole for the treatment of functional dyspepsia in Chinese patients. METHOD: Patients with a clinical diagnosis of functional dyspepsia according to the Rome II criteria and normal upper gastrointestinal endoscopy were recruited and randomised to receive: (1) lansoprazole 30 mg, (2) lansoprazole 15 mg, or (3) placebo, all given daily for four weeks. Dyspepsia symptom scores and quality of life (SF-36 score) were evaluated before and four weeks after treatment. RESULTS: A total of 453 patients were randomised. There was no difference in the proportion of patients with complete symptom relief in the lansoprazole 30 mg (23%) and lansoprazole 15 mg (23%) groups compared with the placebo group (30%). The proportion of H pylori positive patients with a complete response was similar with lansoprazole 30 mg (34%) and lansoprazole 15 mg (20%) versus placebo (22%). All symptom subgroups (ulcer-like, dysmotility-like, reflux-like, and unspecified dyspepsia) had similar proportions of patients with complete symptom relief after treatment. CONCLUSION: Proton pump inhibitor treatment is not superior to placebo for the management of functional dyspepsia in Chinese patients.     

STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study

BACKGROUND: Functional dyspepsia (FD) constitutes a complex picture with a variety of epigastric symptoms. No standard therapy is currently available for FD. OBJECTIVE: This multicenter, placebo-controlled, double-blind study evaluated the efficacy and tolerability of the herbal drug STW 5, mainly comprising a fresh plant extract from Iberis amara. METHODS: Patients with FD were included. Gastrointestinal endoscopy, H. pylori-status, and a 7-day run-in phase were required. A total of 315 patients were treated with 3 x 20 drops/day of either STW 5 or placebo. Symptom assessment: day 0, 2, 4, and 8 wk of treatment. The principal outcome criterion was the change in a validated Gastrointestinal Symptom Score (GIS). Symptom severity was rated using the Likert scale. RESULTS: A total of 315 patients remained in the safety population. Of them, 158 were treated with STW 5 and 157 with placebo. The intention-to-treat population comprised 308 patients. Dropout number was similar in both groups. GIS showed improvement during the treatment period. The STW 5 group improved 6.9+/-4.8 points up to day 56, placebo group by 5.9+/-4.3 (P<0.05). H. pylori did not influence the results. Drug tolerability and safety were similar in both groups. CONCLUSION: This placebo-controlled study with an 8-wk treatment period documents the efficacy of STW 5 in FD.     

Effects of anakinra monotherapy on joint damage in patients with rheumatoid arthritis. Extension of a 24-week randomized, placebo-controlled trial

OBJECTIVE: To determine the effects of treatment on the radiologic manifestations of joint damage in patients with rheumatoid arthritis (RA) who participated in a 24-week extension study of a randomized, placebo-controlled clinical trial of anakinra, a recombinant human interleukin 1 receptor antagonist. METHODS: The patients had entered a 24-week, randomized, double-blind, placebo-controlled study. Anakinra was self-administered by subcutaneous injection of 30, 75, or 150 mg/day. Upon completion of the placebo-controlled phase, the patients entering the extension study who had received placebo were randomized to one of the 3 treatment dosages for a further 24 weeks, and the patients who had been initially randomized to one of the 3 anakinra dosages continued to receive the same dosage. Radiographs of the hands were obtained at baseline and at 24 and 48 weeks. The radiographs were evaluated using a modified Sharp method. RESULTS: A total of 472 patients were recruited. The mean change in the total modified Sharp score of 178 patients who completed 48 weeks treatment, including all dosages, was significantly less than the change observed in 58 patients who received placebo for 24 weeks and anakinra for 24 weeks (p = 0.015). A significant reduction in the change of the total modified Sharp score was observed in the patients who received anakinra 75 and 150 mg/day. The total modified Sharp score was reduced significantly more during the second 24-week treatment period, compared to the first (p < 0.001). Significant reductions in the second 24-week period were observed following anakinra 75 mg/day (p = 0.006) and 150 mg/day (p = 0.008). CONCLUSION: Patients with RA who received anakinra for 48 weeks demonstrated significant slowing of radiographic joint damage. The treatment effect observed after the first 24-week period appeared to increase when anakinra was continued for 48 weeks.     

Impact of Functional Dyspepsia on Quality of Life and Health Care Consumption after Cessation of Antisecretory Treatment: A Multicentre 3-Month Follow-up Study

Background: The impact of response to treatment on subsequent symptoms, quality of life, health care consumption, and absence from work in functional dyspepsia is unknown. Methods: Patients with functional dyspepsia from Denmark, France, Germany, The Netherlands, Hungary, and Poland (n = 567 (215 men), 18-80 years old) were followed up for 3 months after a 4-week treatment trial with omeprazole (20 mg or 10 mg) or placebo. The patients were blinded to the initial treatment. Dyspeptic symptoms and quality of life were assessed, and dyspepsia-related costs were calculated in terms of number of clinic visits, days on medication, and absence from work. Results: Responders had fewer clinic visits than non-responders (1.5 versus 2.0 mean visits) and fewer days on medication (mean, 9 days versus 23 days) over the 3-month period (both, P &lt; 0.001). The quality of life in responders was better at study entry and persisted over 3 months (all, P &lt; 0.001). When analysed country by country, health care costs due to clinic visits and medications were significantly lower in responders in all countries (P &lt; 0.05), except Denmark and The Netherlands. Conclusion: Symptom resolution in patients with functional dyspepsia has a positive impact on quality of life and reduces the subsequent costs over a 3-month period after cessation of initial treatment.     

Cisapride treatment of patients with non-ulcer dyspepsia and erosive prepyloric changes. A double-blind, placebo-controlled trial.

One hundred and twenty consecutive outpatients with non-ulcer dyspepsia (NUD) and erosive prepyloric changes (EPC) were, after a 2-week placebo run-in period, randomly allocated to double-blind treatment with either 10-mg cisapride tablets or placebo three times daily for 4 weeks. The patients' global evaluation and total symptom score were significantly in favour of cisapride at 2 weeks (p less than 0.05). At 4 weeks the effect of cisapride was no longer significant (p = 0.22). Similarly, the investigators' global evaluation showed marked to moderate symptom improvement in 47% of the cisapride-treated patients as compared with 30% of the placebo-treated patients at 2 weeks. The 95% confidence interval of the difference (18%) was 0% to 35%. At 4 weeks the intergroup difference was only 10% (cisapride, 50% versus placebo 40%). Pain on awakening was the only symptom improved in favour of cisapride at 4 weeks. Thus, when patients with NUD and EPC are treated with cisapride, the therapeutic gain might vanish after the 2nd week of treatment.     

Effect of Amitryptiline on Symptoms, Sleep, and Visceral Perception in Patients With Functional Dyspepsia

Objective : Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders, yet the mechanism(s) of action of these drugs in these disorders is not known. In the current study, we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms, perceptual responses to gastric distension, and subjective and objective measures of sleep. Methods : Patients were randomized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo. There was a 3-wk washout phase, followed by a cross-over to the alternate treatment. Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period. Diaries of symptoms were maintained throughout. Results : Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo. Five of seven patients had evidence for altered perception of gastric balloon distension during placebo. However, the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension. Baseline sleep dysfunction in the form of reduced sleep efficiency, increased arousal, or abnormal amounts of REM sleep was found in all seven patients. Amitryptiline significantly reduced absolute and relative amounts of REM sleep, but had no effect on sleep parameters related to nonregenerative sleep. Conclusion : The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension, or to measures of arousal from sleep. An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect.     

Treatment of uninvestigated dyspepsia with cisapride for patients with negative Helicobacter pylori serologies

OBJECTIVE: The aim of this study was to compare symptoms for patients with uninvestigated dyspepsia and a negative Helicobacter pylori serology who were treated with cisapride or placebo. METHODS: Helicobacter pylori-seronegative patients with chronic dyspepsia were randomized to receive cisapride 10 mg t.i.d. or placebo t.i.d. for 30 days. Symptom scores were performed 1 month and 3 months after randomization. Outcomes measured were dyspepsia symptom scores and a treatment "success" variable defined as absence of symptoms or decrease in the most severe individual symptom by two grades. RESULTS: A total of 60 patients were randomized; 56 completed the 1-month follow-up and 40 completed the 3-month follow-up interview. The mean score for all patients at the time of entry was 11.0 and declined to 8.3 and 8.2 at 1 and 3 months, respectively, after randomization. At 1 month and 3 months after randomization, there was no significant difference in the number of patients meeting the "success" variable for patients receiving cisapride as compared to placebo. The mean decline in symptom severity scores was not significantly different for patients receiving placebo or cisapride at 1 month (mean, -2.8 vs -3.1; difference = 0.3, p = 0.74) or 3 months (-3.1 vs -2.6, difference = -0.5, p = 0.58) after randomization. CONCLUSIONS: No significant difference in the severity of dyspeptic symptoms was found for patients receiving cisapride as compared to placebo in the setting of uninvestigated dyspepsia and a negative Helicobacter pylori serology.