Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Helicobacter pylori eradication in dyspeptic primary care patients: a randomized controlled trial of a pharmacy intervention. Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets of clinical idiopathic parkinsonism to Helicobacter pylori eradication. A randomized, double-blind, placebo-controlled efficacy study. Does the eradication of Helicobacter pylori cure duodenal ulcer disease in communities with a high prevalence rate? Comparison with long-term acid suppression. Effect of the eradication of Helicobacter pylori on duodenal ulcer healing and ulcer relapse: randomized controlled study in Japan. Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease. Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection. Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study. Management of Helicobacter pylori eradication--the influence of structured counselling and follow-up.
To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations.
                In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment.
                Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics.
                These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics. To determine the effectiveness of structured adherence counseling by pharmacists on the eradication of Helicobacter pylori when using a standard drug treatment regimen.
                Randomized controlled clinical trial.
                Nonprofit group-practice health maintenance organization (HMO).
                HMO primary care providers referred 1,393 adult dyspeptic patients for carbon 14 urea breath testing (UBT).
                Those whose tests were positive for H pylori (23.3%) were provided a standard antibiotic regimen and randomly assigned to receive either usual-care counseling from a pharmacist or a longer adherence counseling session and a follow-up phone call from the pharmacist during drug treatment. All subjects were given the same 7-day course of omeprazole, bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (OBMT). Dyspepsia symptoms were recorded at baseline and following therapy.
                The main outcome was eradication of H pylori as measured by UBT at 3-month follow-up. Secondary outcomes were patient satisfaction and dyspepsia symptoms at 3-month follow-up.
                Of the 333 participants randomly assigned to treatment, 90.7% completed the 3-month follow-up UBT and questionnaires. Overall eradication rate with the OBMT regimen was 80.5% with no significant difference in eradication rates between the 2 groups (P=0.98). Conclusions In this study, additional counseling by pharmacists did not affect self-reported adherence to the treatment regimen, eradication rates, or dyspepsia symptoms but did increase patient satisfaction. Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized.
                Proof-of-principle that infection contributes to idiopathic parkinsonism.
                Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism. Intervention was 1 week's triple eradication therapy/placebos. Routine deblinding at 1 year (those still infected received open-active), with follow-up to 5 years post-eradication. Primary outcome was mean stride length at free-walking speed, sample size 56 for a difference, active vs. placebo, of 3/4 (between-subject standard deviation). Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was stopped at 31, because of marked deterioration with eradication failure. Interim analysis was made in the 20 who had reached deblinding, seven of whom were receiving antiparkinsonian medication (long-t(1/2), evenly spaced) which remained unchanged.
                Improvement in stride-length, on active (n = 9) vs. placebo (11), exceeded size of effect on which the sample size was calculated when analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six weekly assessments, including (p = .02) and excluding (p = .05) those on antiparkinsonian medication. Active eradication (blind or open) failed in 4/20, in whom B-lymphocyte count was lower. Their mean time course was: for stride-length, -243 (95% CI -427, -60) vs. 45 (-10, 100) mm/year in the remainder (p = .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58 (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of stance-walk videos (worst-best per individual identical with 0-100 mm), -64 vs. -3 mm from anterior and -50 vs. 11 lateral (p = .004 and .02).
                Interim analysis points to a direct or surrogate (not necessarily unique) role of a particular infection in the pathogenesis of parkinsonism. With eradication failure, bolus release of antigen from killed bacteria could aggravate an effect of ongoing infection. The long-term effect of Helicobacter pylori eradication on the natural history of duodenal ulcer has been investigated and compared with long-term acid suppression treatment in an endemic community for infection. Seventy-three patients with endoscopically verified H. pylori positive active duodenal ulcer disease were included in this prospective study. Patients were divided into two groups. Group A patients (n = 39) were given an omeprazole-based triple eradication regimen, while group B patients (n = 34) were given omeprazole alone followed by long-term famotidine 20 mg daily as maintenance treatment. A control endoscopy was performed at the third month of treatment. The bacterium was eradicated in 32 (82%) of group A patients. All patients were followed up for two years and an endoscopy performed at the end of each year. H. pylori recurred in 13 patients and the reinfection rate was 44.8% over two years. Duodenal ulcer recurred in seven of these patients at two years (24.1%). There was a close association between H. pylori reinfection and ulcer relapse. Group B patients remained H. pylori positive during the study and the ulcer recurred in five of these patients (6.6%) despite continuous famotidine treatment. There was no statistically significant difference in ulcer relapse rate between the groups. These results suggested that H. pylori eradication is not an absolute solution for duodenal ulcer disease in high endemic regions and continuous maintenance treatment with H2-receptor antagonists is still an alternative approach in some chronic recurrent cases. To investigate the effect of the eradication of Helicobacter pylori on the healing and relapse of duodenal ulcers. 50 patients with active duodenal ulcer and H. pylori infection were randomly allocated to two treatment groups. One group (cimetidine group) received cimetidine 400 mg twice daily for 6 weeks and the other group (double-therapy group) received 300 mg amoxicillin granules and 250 mg metronidazole thrice daily for 2 weeks, in addition to the same regimen of cimetidine as the cimetidine group. Forty-two patients completed the study. After confirmation of ulcer scar, all patients were followed up for 6 months while receiving treatment with teprenone, an agent that does not affect acid secretion or the eradication of H. pylori. The healing rates at 6 weeks were 90% in the cimetidine group and 95.5% in the double-therapy group. H. pylori eradication occurred in 0% of the cimetidine group and in 73.7% of the double-therapy group (P = 0.004). The cumulative relapse rates in the two groups at 6 months were 64.3% and 11.1%, respectively (P = 0.0007). In the double-therapy group, the cumulative relapse rate at 6 months in the patients in whom H. pylori persisted was 50% (2/4); the rate was 0% (0/14) in the patients in whom H. pylori had been eradicated (P = 0.005). Histological gastritis significantly improved compared with the baseline in the double-therapy group, but no such improvement was seen in the cimetidine group. White scarring was found in 7.1% of the cimetidine group and in 83.3% of the double-therapy group after 6 months (P < 0.0001). The eradication of H. pylori markedly decreased the relapse rate in duodenal ulcer patients, and it significantly improved both the grade of gastritis and the quality of the ulcer scar. The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome.
                To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy.
                Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years.
                Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred.
                Eradication of H. pylori infection changes the natural course of peptic ulcer. To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration.
                Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued.
                Teaching and district general hospitals between 1991 and 1994.
                107 patients with benign gastric ulcer associated with H pylori.
                Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test).
                172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001).
                Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use. Long-term levodopa treatment in Parkinson's disease is typically associated with "motor side effects" consisting in dyskinesias and/or fluctuations in motility referred to as the on-off phenomena. The main objective of this prospective, randomized, multi-centre study was to determine to what extent the development of such complications could be prevented by partial substitution of levodopa monotherapy (L-DOPA/benserazide) by bromocriptine in patients with early symptoms of the disease. The basic trial population included 674 newly diagnosed Parkinsonian patients that were randomly allocated to monotherapy with levodopa or a combination therapy based upon a nearly 40% replacement of levodopa by bromocriptine. The two target regimens had to be consistently maintained for 42 months. Parkinsonian symptoms were assessed by means of the Webster rating scale, the Hoehn and Yahr scale, and the Zung Self-Rating Depression scale. Motor side effects and adverse events were recorded at each regular clinic visit. Neurological symptoms improved and stabilized in a similar manner during treatment with both regimens throughout the study period. Motor side effects were observed in more patients on levodopa alone than on combination therapy (28.8 vs 20%; p = 0.008). According to Kaplan-Meier estimates the cumulative probability of experiencing motor side effects was 0.43 on monotherapy, compared to 0.28 on combination therapy, which was equal to a one third reduction of risk (p = 0.025). In regard to motor side effects, the degree of substitution of levodopa proved relevant: patients with > 50% substitution by bromocriptine exhibited half the risk observed in those with < 30% (p = 0.045). The overall burden of motor side effects, as reflected by a sum score based upon the relevance, the severity and the extent of motor dysfunction, was also significantly less on combination therapy (p = 0.046). In conclusion, partial substitution of levodopa by bromocriptine (> 30%) as first-line treatment of Parkinson's disease proves active in the prophylaxis of levodopa associated motor side effects. Early combination therapy therefore extends the period of optimal disease control. Helicobacter pylori (H. pylori) eradication rate varies according to the treatment regimen used and other factors, e.g. antimicrobial resistance and patient compliance. The aim of the present study was to evaluate the influence of patient counselling and follow-up on H. pylori eradication rates and to document the effectiveness of a 1 week eradication regimen consisting of lansoprazole (30 mg once daily), amoxicillin (1 g twice daily) and clarithromycin (500 mg twice daily).
                Seventy-six dyspeptic patients, who at endoscopy were found to have gastritis, duodenitis or ulceration, and a positive H. pylori urease test, were recruited. Patients were randomly assigned to an intervention group (n = 38) or a control group (n = 38). Intervention patients received their medicines via the hospital pharmacy and were counselled (and followed up) by a hospital pharmacist. Control patients were given a standard advice sheet and referred to their GP who prescribed the same therapy.
                Intervention patients exhibited a statistically significant improvement in the H. pylori eradication rate (94.7% vs 73.7%; P = 0.02) and compliance (92.1% vs 23.7; P < 0.001). Of the 64 H. pylori eradicated patients, 62 were able to eliminate their antisecretory medication compared with only 12 of the H. pylori persistent patients (P < 0.001). A pharmacoeconomic evaluation indicated that counselling and follow-up reduced the direct costs of eradication by approximately 30 UK pounds per patient.
                Structured patient counselling and follow-up can have a significant effect on H. pylori eradication rates and should be a routine part of therapy.
There is currently a lack of evidence on the effects of screening and treating H pylori in patients with Parkinson's disease. There is limited evidence to suggest that H Pylori eradication improves the absorption of levodopa and improves motor symptoms. Results from an ongoing trial will inform the evidence base and will be incorporated in an update of this review. There is a need for well-conducted randomised controlled trials with standard outcome measures for motor symptoms and incorporating the costs of screening and treatment.