Effect of Helicobacter pylori eradication on the treatment of gastro-oesophageal reflux disease

The important issue of whether Heliobacter pylori eradication leads to increased reflux has been the subject of many apparently contradictory publications, but when we asked two leading authorities to give us their views, there turned out to be considerable consensus, as you can read below.     

Helicobacter pylori eradication does not exacerbate gastro-oesophageal reflux disease

The reciprocal influence of Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD), if both conditions occur concomitantly, has been an issue of debate for many years. The critical question is whether eradication of H pylori has a more beneficial, harmful, or simply no effect on the course of GORD.     

Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial

BACKGROUND: Pyoderma gangrenosum (PG) is a chronic ulcerating skin condition that often occurs in association with inflammatory bowel disease. There have been a number of reports of PG responding to infliximab, a monoclonal antibody against tumour necrosis factor alpha. AIM: In the first randomised placebo controlled trial of any drug for the treatment of PG, we have studied the role of infliximab in this disorder. SUBJECTS: Patients 18 years of age or older with a clinical diagnosis of PG were invited to take part. METHODS: Patients were randomised to receive an infusion of infliximab at 5 mg/kg or placebo at week 0. Patients were then assessed at week 2 and non-responders were offered open labelled infliximab. The primary end point was clinical improvement at week 2, with secondary end points being remission and improvement at week 6. RESULTS: Thirty patients were entered into the study. After randomisation, 13 patients received infliximab and 17 patients received placebo. At week 2, significantly more patients in the infliximab group had improved (46% (6/13)) compared with the placebo group (6% (1/17); p = 0.025). Overall, 29 patients received infliximab with 69% (20/29) demonstrating a beneficial clinical response. Remission rate at week 6 was 21% (6/29). There was no response in 31% (9/29) of patients. CONCLUSIONS: This study has demonstrated that infliximab at a dose of 5 mg/kg is superior to placebo in the treatment of PG. Open label treatment with infliximab also produced promising results. Infliximab treatment should be considered in patients with PG.     

A double blind randomised placebo controlled trial of hexopal in primary Raynaud's disease

Summary The peripheral vasospastic symptoms associated with Raynaud's disease continue to be an unsolved clinical problem. Hexopal (Hexanicotinate inositol) has shown promise in uncontrolled studies and its use in patients with Raynaud's disease may reduce such vasospasm. This study examines the effects of 4 g/day of Hexopal or placebo, during cold weather, in 23 patients with primary Raynaud's disease. The Hexopal group felt subjectively better and had demonstrably shorter and fewer attacks of vasospasm during the trial period. Serum biochemistry and rheology was not significantly different between the two groups. Although the mechanism of action remains unclear Hexopal is safe and is effective in reducing the vasospasm of primary Raynaud's disease during the winter months.

     

Budesonide treatment of collagenous colitis: a randomised,double blind,placebo controlled trial with morphometric analysis

BACKGROUND: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. AIMS: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. PATIENTS: Twenty patients with collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day and/or stool weight >200 g/day). METHODS: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. RESULTS: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. CONCLUSIONS: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.     

Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer? A randomised double blind placebo controlled study.

BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM: To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS: A randomised, double blind placebo controlled trial was performed to study the efficacy of an antibiotic only regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg clarithromycin, each given four times daily for two weeks, in the healing of duodenal ulcer as assessed by endoscopy. Symptoms were controlled with acetaminophen and antacids. RESULTS: Of 100 consecutive patients with endoscopically established duodenal ulcer, 97 with positive rapid urease test on antral biopsy specimens were admitted into the study and 81 completed the trial. Of these, 40 were randomised to receive antibiotics and 41 to receive placebo. Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI) 84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95% CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between the two treatment groups were significant at p < 0.001 at each time point and by life table analysis. Clearance of H pylori as assessed by urease test on antral biopsy specimens at four weeks and eradication of the organism as determined by 13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs 76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication, was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001 and < 0.003 respectively) in whom these processes failed. Stepwise discriminant analysis on 32 clinical, personal, and endoscopic characteristics as well as H pylori clearance and eradication identified H pylori clearance as the most discriminative variable for the healing of duodenal ulcer at four weeks, followed by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an antibiotic only regimen was effective for the healing of duodenal ulcer, and clearance as well as eradication of H pylori contributed significantly to the healing. The results constituted the strongest evidence to date that H pylori infection was aetiologically related to duodenal ulceration, and support the concept of treating duodenal ulcer associated with H pylori as an infection and relieving its symptoms with acid reducing agents such as antacids.     

Photodynamic therapy for dysplastic Barrett's oesophagus: a prospective, double blind, randomised, placebo controlled trial

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a treatment in which cell damage is achieved by the action of light on a photosensitizing agent. We have assessed the potential use of PDT in the ablation of Barrett's oesophagus. METHODS: Thirty six patients with dysplastic Barrett's oesophagus receiving acid suppression medication with omeprazole were randomised to receive oral 5-aminolaevulinic acid (ALA) 30 mg/kg or placebo, followed four hours later by laser endoscopy. Follow up endoscopy was performed at one, six, 12, and 24 months. RESULTS: Of 18 patients in the ALA group, a response was seen in 16 (median decrease in area in the treated region 30%; range 0-60%). In the placebo group, a decrease in area of 10% was observed in two patients with no change in 16 (median 0%; range 0-10%; treatment v placebo, p<0.001). No dysplasia was seen in the columnar epithelium within the treatment area of any patient in the PDT group. However, in the placebo group, persistent low grade dysplasia was found in 12 patients (p<0.001). There were no short or long term major side effects. The effects of treatment were maintained for up to 24 months. CONCLUSIONS: This is the first randomised controlled trial of PDT for Barrett's oesophagus. It demonstrates that ALA induced PDT can provide safe and effective ablation of low grade dysplastic epithelium.     

Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial

BACKGROUND: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. DESIGN AND SETTING: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. Patients and INTERVENTIONS: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. OUTCOME MEASURES: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. RESULTS: At 3 months, the percentage of patients who had reduced drug use by > or =50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. CONCLUSIONS: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.     

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

OBJECTIVE: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. METHODS: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. RESULTS: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: -2.2 cm (95% CI, -2.6 to -1.7) and -2.0 cm (-2.5 to -1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: -2.1 (-2.6 to -1.6) and -1.6 (-2.2 to -1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). CONCLUSIONS: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability.     

Helicobacter pylori and gastro-oesophageal reflux disease: a cross-sectional epidemiological study

BACKGROUND: H. pylori infection is accompanied by a lower prevalence of reflux disease. There is still an ongoing debate as to whether H. pylori actually protects against the development of reflux oesophagitis or is merely an epiphenomenon. A cross-sectional study was performed to study the relation of H. pylori with reflux oesophagitis, hiatus hernia and Barrett's oesophagus. MATERIAL AND METHODS: Consecutive patients undergoing upper gastrointestinal endoscopy in a period of ten years were studied. Included were patients with active reflux oesophagitis and/or hiatus hernia and/or Barrett's oesophagus. As a reference group, patients without macroscopic abnormalities were included. H. pylori was detected applying routine diagnostic modalities. RESULTS: In the ten years 11,691 consecutive patients were studied. Reflux oesophagitis was seen in 1535 patients, 307 patients had Barrett's oesophagus and a hiatus hernia was present in 2116 patients. The reference group consisted of 5341 patients. H. pylori was significantly less often detected in patients with reflux oesophagitis or Barrett's oesophagus compared with the reference group, 20 vs 29% (p<0.001). Also presence of H. pylori was significantly lower in patients with hiatus hernia 20 vs 29% (p<0.0001). CONCLUSION: The present study confirms, in a very large group of patients studied in one single centre, the findings of earlier papers. Patients without H. pylori gastritis suffer more often from reflux disease. There is a relation between H. pylori and reflux disease. However, the consequence of this relation will not be the same in every patient.     

Helicobacter pylori eradication and gastroesophageal reflux disease: a Meta-analysis

<正>Objective To systematically evaluate whether eradication of Helicobacter pylori(H.pylori)is associated with the development of endoscopic gastroesophageal reflux disease(GERD)and reflux symptoms.Methods Pub Med,CENTRAL,Embase,CNKI and Wanfang Database from April 1978 to April 2015 were retrieved to collect the randomized controled trials(RCTs)comparing the incidence of reflux symptoms or reflux esophagitis in     

Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial

BACKGROUND: Variceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the combination of somatostatin and nitrates has an additive effect in decreasing portal pressure. AIM: To compare the therapeutic efficacy of either intravenous infusion of somatostatin plus oral isosorbide 5-mononitrate or somatostatin alone in gastro-oesophageal variceal bleeding associated with liver cirrhosis. METHODS: A unicentre, double blind, placebo controlled, clinical trial was conducted. Sixty patients bleeding from oesophageal or gastric varices were randomised to receive intravenous infusion of somatostatin (250 microg/hour) plus oral isosorbide 5-mononitrate (40 mg/12 hours) (group I) or somatostatin infusion plus placebo (group II) for 72 hours. RESULTS: The two groups of patients had similar clinical, endoscopic, and haematological characteristics. Control of bleeding was achieved in 18 out of 30 patients (60%) in group I and 26 out of 30 patients (87%) in group II (p<0.05). There was no significant difference in mean transfusion requirements between the two groups: 2.6 (2.2) v 1.8 (1.6) respectively; means (SD). Mortality and side effects were similar in the two groups, but development of ascites was higher in group I (30%) than in group II (7%) (p<0.05). CONCLUSION: In cirrhotic patients with acute gastro-oesophageal variceal bleeding, addition of isosorbide 5-mononitrate to somatostatin does not improve therapeutic efficacy, induces more adverse effects, and should not be used.     

Limited effect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial

OBJECTIVE—To assess the efficacy and safety of sulphasalazine in reactive arthritis.
METHODS—Double blind placebo controlled trial of six months duration comparing sulphasalazine 2-3 g per day (n = 37) with matching placebo (n = 42) in adults with active reactive arthritis (age 19-57 years, median 34). Treatment response was evaluated once a month by changes in erythrocyte sedimentation rate (ESR), pain, peripheral arthritis, tender iliosacral joints, entesopathy, extra-articular manifestations, and working ability.
RESULTS—15 patients in the sulphasalazine group and eight in the placebo group withdrew from the study prematurely. Adverse events, primarily gastrointestinal, were the main reason for withdrawal in the actively treated group. Intention-to-treat analyses showed significant improvements over time in both groups in ESR, pain, and number of swollen joints (P < 0.01). Number of days on sick leave decreased significantly in the sulphasalazine group only (P < 0.01). No significant differences between the two groups were present after six months. Among the patients completing the trial according to protocol, persistent complete remission had occurred within two months in five (23%) of the actively treated, but in no placebo treated patients (P = 0.013).
CONCLUSIONS—Sulphasalazine seemed to improve only the very short term outcome of reactive arthritis. The possible beneficial effect of the drug should also be weighed against the risk of adverse events. Although these were mainly mild, almost 25% of the patients in the actively treated group gave up treatment for this reason.

     

Primary prevention of diclofenac associated ulcers and dyspepsia by omeprazole or triple therapy in Helicobacter pylori positive patients: a randomised,double blind,placebo controlled,clinical trial

BACKGROUND: There is much controversy as to whether or not treatment of Helicobacter pylori reduces the occurrence of peptic ulcers during therapy with a non-steroidal anti-inflammatory drug (NSAID). AIM: To assess the efficacy of triple therapy or omeprazole on the occurrence of diclofenac associated ulcers in H pylori positive patients. METHODS: This was a randomised, double blind, placebo controlled, multicentre trial in H pylori positive patients requiring NSAID therapy who had no past or current peptic ulcer. They received diclofenac 50 mg twice daily for five weeks in combination with one of the four randomly assigned treatments: anti-H pylori treatment for one week (omeprazole 20 mg+clarithromycin 500 mg+amoxicillin 1 g, all twice daily) followed by placebo for four weeks (OAC-P); anti-H pylori treatment for one week followed by antisecretory treatment with omeprazole 20 mg once daily for four weeks (OAC-O); omeprazole 20 mg once daily for five weeks (O-O); or placebo for five weeks (P-P). Patients were endoscoped before and after treatment. RESULTS: Data from 660 patients were included in an intention to treat analysis. The occurrence of peptic ulcers in the four treatment groups during the study period was: 1.2% for OAC-P, 1.2% for OAC-O, 0% for O-O, and 5.8% for P-P (p<0.05 between placebo and all active treatment groups). Patients who received active treatment developed therapy requiring dyspeptic symptoms less frequently than those who received placebo (p<0.05 between placebo and all active treatment groups). CONCLUSIONS: In H pylori infected patients, all three active therapies reduced the occurrence of NSAID associated peptic ulcer and dyspeptic symptoms requiring therapy.     

Effect of captopril on functional mitral regurgitation in dilated heart failure: a randomised double blind placebo controlled trial.

OBJECTIVE--To determine the efficacy and dose requirements of captopril to reduce functional mitral regurgitation in patients with dilated heart failure. DESIGN--A randomised double blind placebo controlled parallel arm trial. Incremental daily doses of 25 mg, 50 mg and 100 mg captopril used for a four week period each for a total of 12 weeks preceded by a two week placebo washout. Twenty eight ambulatory patients (mean age 72) New York Heart Association (NYHA) class II or III with apparently controlled ischaemic dilated heart failure (ejection fraction 29% (0.04%)) on digoxin, diuretics, and nitrates were randomised. All had at least grade 2/4 functional mitral regurgitation (> 5 cm2 regurgitant area on colour flow Doppler). RESULTS--Twenty three patients completed the study (13 on placebo and 10 on captopril). Significant improvements were confined to the captopril group. Compared with placebo the following improvements were noted in the captopril treated group: mitral regurgitant area decreased from a threshold at 50 mg/day (p < 0.05, mean (95% confidence interval (95% CI)) 3.1 (0.2 to 6.0) cm2), with a further decrease at 100 mg/day (p < 0.01, mean (95% CI) 5.3 (3.1 to 7.5) cm2). Significant improvements in all the other measurements were noted only after 100 mg/day. Stroke volume increased (p < 0.01, mean (95% CI) 11, (1.4 to 21) ml), systemic vascular resistance decreased (p < 0.05, mean (95% CI) 414 (35 to 793) dyn s cm5), left atrial area decreased (p < 0.05, mean (95% CI) 4.3 (0.03 to 8.6) cm2), and deceleration time increased (p < 0.01, mean (95% CI) 52 ms (7 to 98) ms). Left ventricular diameter decreased marginally (p = 0.06, mean (95% CI) 4 (-0.05 to 9 mm). Duke activity index score increased (p < 0.001, median (95% CI) 6.8 (4.5 to 12) points). Heart rate, mean arterial blood pressure, serum creatinine, and serum potassium did not change with either placebo or captopril. No patient was withdrawn directly due to the side effects of captopril. In an open phase nine placebo patients given captopril in rapid increments reaching 100 mg/day in the fourth week showed similar improvements. CONCLUSION--Captopril is efficacious in reducing functional mitral regurgitation in dilated heart failure. Patients require and must tolerate high doses (50-100 mg/day) for additive effects over supervised conventional treatment to occur.     

Amiodarone prophylaxis for tachycardias after coronary artery surgery: a randomised, double blind, placebo controlled trial.

BACKGROUND--Arrhythmias are a common cause of morbidity after cardiac surgery. This study assessed the efficacy of prophylactic amiodarone in reducing the incidence of atrial fibrillation or flutter and ventricular arrhythmias after coronary artery surgery. METHODS--A double blind, randomised, placebo controlled trial. 60 patients received a 24 hour intravenous infusion of amiodarone (15 mg/kg started after removal of the aortic cross clamp) followed by 200 mg orally three times daily for 5 days, and 60 patients received placebo. RESULTS--6 patients (10%) in the amiodarone group and 14 (23%) in the placebo group needed treatment for arrhythmias (95% confidence interval (95% CI) for the difference between groups was 0 to 26%, p = 0.05). The incidence of supraventricular tachycardia detected clinically and requiring treatment was lower in the amiodarone group (8% amiodarone v 20% placebo, 95% CI 0 to 24%, p = 0.07). The incidence detected by 24 hour Holter monitoring was similar (17% amiodarone v 20% placebo). Untreated arrhythmias in the amiodarone group were either clinically benign and undetected (n = 3) or the ventricular response rate was slow (n = 2). Age > 60 years was a positive risk factor for the development of supraventricular tachycardia in the amiodarone group but not in the placebo group. Fewer patients had episodes of ventricular tachycardia or fibrillation recorded on Holter monitoring in the amiodarone group (15% amiodarone v 33% placebo, 95% CI 3 to 33%, p = 0.02). Bradycardia (78% amiodarone v 48% placebo, 95% CI 14% to 46%, p < 0.005) and pauses (7% amiodarone v 0% placebo) occurred in more amiodarone treated patients. Bradycardia warranted discontinuation of treatment in one patient treated with amiodarone. CONCLUSIONS--The incidence of clinically significant tachycardia was reduced by amiodarone. The ventricular response rate was slowed in supraventricular tachycardia, but the induction of bradycardia may preclude the routine use of amiodarone for prophylaxis.