Quadruple, sequential, and concomitant first-line therapies for H. pylori eradication: a prospective, randomized study.

BACKGROUND: Current Italian guidelines recommend 10-day bismuth-based or bismuth-free (sequential and concomitant) regimens for first-line H. pylori eradication. However, comparison among these regimens is lacking in our country. AIM: To perform a 'head-to-head' comparison among these three therapies as first-line treatment for H. pylori eradication in clinical practice. METHODS: This was a prospective, open-label randomized study enrolling consecutive patients diagnosed with H. pylori infection never previously treated. Patients were randomized to receive one of the following 10-day therapies: (a) Bismuth-based therapy: esomeprazole 20mg b.i.d and Pylera 3 tablets q.i.d; (b) Concomitant therapy: esomeprazole 20mg plus amoxicyllin 1,000mg, clarithromycin 500mg and tinidazole 500mg (all b.i.d.), and (c) Sequential therapy: esomeprazole 20mg plus amoxicyllin 1,000mg for 5days followed by esomeprazole 20mg plus clarithromycin 500mg and tinidazole 500mg for 5days (all b.i.d). H. pylori eradication was assessed by using UBT 4-6 weeks after the end of therapy. RESULTS: Overall, 187 patients were enrolled. The eradication rates achieved with Pylera, concomitant and sequential were 85.2%, 95.2%, and 93.6%, respectively, at intention to treat, and 94.5%, 96.7%, and 95.1% at per protocol analyses, without a statistically significant difference. The incidence of severe side-effects was higher with the bismuth-based therapy than with the two bismuth-free regimens (9.8% vs 1.6%; p=0.046). CONCLUSIONS: Bismuth-based and bismuth-free therapies are equally effective for first-line H. pylori eradication. However, bismuth therapy was more frequently interrupted for side-effects than bismuth-free therapies.

The efficacy, safety and cost-effectiveness of hydrotalcite versus esomeprazole in on-demand therapy of NERD: A multicenter, randomized, open-label study in China.

OBJECTIVE: The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole, a proton pump inhibitor, in on-demand therapy for non-erosive reflux disease (NERD). METHODS: This was a multicenter, randomized, open-label clinical trial with initial and on-demand therapy. Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy. The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points. The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points. RESULTS: In total, 398 patients were recruited in the initial therapy group, among whom 253 were included in on-demand therapy, with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group. 14 (11.0%) patients in the hydrotalcite group and six (4.8%) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control (P = 0.065). Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole (per person/day) was 35.3% in the on-demand therapy. Similar number of patients achieved symptom relief in both groups. CONCLUSION: Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action.

Constipation in older patients: effects on quality of life.

Constipation, often related to diet, physical immobility, concurrent illness or multiple medication use, is common in older people. Despite potential for serious complications, constipation may often be overlooked. Management of constipation is a critical part of the care of older patients with chronic conditions. Risk assessment and appropriate nursing interventions and/or medication should mean that constipation can be minimized, preventing additional medication burden and reducing the risk of non-adherence. The relationship between quality of life and constipation has been assessed in numerous studies, showing that patients with constipation generally have an impaired quality of life compared with the general population, although studies in older patients are limited. In long-term survivors of colorectal or anal carcinoma, constipation is one of the factors that has the most negative impact on quality of life. Strategies for prevention and minimization of constipation have the potential to substantially improve quality of life for older people.

Assessing overmedication: biology, philosophy and common sense.

Overmedication is nowadays a serious problem in health care due to influences from the pharmaceutical industry and agencies responsible for regulation. The situation has indeed become appalling in psychiatry, where both theories and treatments have deteriorated under the impact of the industry. The overmedication problem is associated with biased biology in medicine. Adequate biological approaches would indicate that drug therapies must yield to diet therapies, particularly treatments involving omega-3 fatty acids, in many cases. To the extent that philosophy of science adapts to mainstream medicine in analyses of the current situation, it may reinforce the existing bias. To redress imbalances in health care, we ultimately have to rely on common sense.

Review article: over-the-counter drugs and the gastrointestinal tract.

An increasing number of drugs are becoming available over-the-counter, empowering patients to treat them- selves. Although drugs presently available over-the-counter are generally safe, there are issues of safety and possible delays in diagnosis of serious conditions. Therefore it is vital that patients are made aware of the indications and limitations of over-the-counter drugs through improved communication and education. Pharmacists and drug companies will have an increasingly important role in giving information and advice to patients. This review looks at the present and future of over-the-counter medication, highlighting the safety aspects.

Current guidelines on stress ulcer prophylaxis.

Acute uppergastrointestinal bleeding in intensive care unit (ICU) patients may occur due to peptic ulcer disease, adverse drug effects, gastric tube lesions, acute renal failure, liver failure or stress-induced gastric mucosal lesions. Gastric acid hypersecretion can be observed in patients with head trauma or neurosurgical procedures. Gastric mucosal ischaemia due to hypotension and shock is the most important risk factor for stress ulcer bleeding. Preventive strategies aim to reduce gastric acidity (histamine H2 receptor antagonists, antacids), strengthen mucosal defensive mechanisms (sucralfate, antacids, pirenzepine) and normalise gastric mucosal microcirculation (sucralfate, pirenzepine). However, the most important prophylactic measure is an optimised resuscitation and ICU regime aiming to improve oxygenation and microcirculation. All drugs approved for stress ulcer prophylaxis in Europe (H2 antagonists, antacids, pirenzepine, sucralfate) have been shown to be effective in prospective controlled randomised trials. However, due to insufficient clinical data, prostaglandins and omeprazole cannot be recommended for this use. Stress ulcer prophylaxis is indicated only in patients at risk, and not in every ICU patient. The selection of drugs today depends not only on efficacy but also on possible adverse effects and on costs. In this regard, the most cost-effective drug is sucralfate. The clinical relevance of nosocomial pneumonia due to gastric bacterial overgrowth has decreased during the past decade due to several changes in the management of critically ill patients.

Prophylaxis of upper gastrointestinal tract bleeding in mechanically ventilated patients. A randomized study comparing the efficacy of sucralfate, cimetidine, and antacids.

Sixty-two mechanically ventilated patients were randomized into three study groups to compare the efficacy of sucralfate vs cimetidine and antacid regimens for the prevention of upper gastrointestinal tract bleeding. Only five study patients (8%) developed bright-red blood per nasogastric tube; four patients received the antacid regimen and one received cimetidine. None of the patients receiving sucralfate developed acute upper gastrointestinal tract bleeding. Bleeding was not severe enough in any patient to require endoscopy or surgery. There were no significant differences in the three groups when several major risk factors for gastrointestinal tract bleeding were analyzed, including sepsis, hypotension, steroid use, adult respiratory distress syndrome, gastric pH of 4 or less, previous peptic ulcer disease, peritonitis, and jaundice. A significantly higher incidence of acute renal failure was noted in the antacid-treated group when compared with the cimetidine and sucralfate groups. We find preliminary evidence that sucralfate is as efficacious as and more cost-effective than either cimetidine or antacids for prophylaxis of stress-related gastrointestinal tract bleeding in the critically ill ventilator-dependent patient.

Drug-antacid interactions: assessment of clinical importance.

Antacids and adsorbents are commonly used preparations that are generally considered to be pharmacologically inert and free from adverse effects. They may, however, interact with a diverse range of primary drugs and the sequelae can be disadvantageous to the efficacy of the primary medication. Many such reports in the literature are based on animal experiments, or on single-dose studies in healthy subjects. Some reports are anecdotal and are unconfirmed; others are based solely on in vitro evidence. Potentially important interactions have been suggested for a relatively small group of drugs: tetracyclines, phenytoin, digoxin, chloroquine, cimetidine, quinidine, nonsteroidal antiinflammatory drugs, and beta-blocking agents. The evidence for these has been critically evaluated, as well as for antacid-anticoagulant and antacid-nitrofurantoin interactions that have been wrongly emphasized in the literature. The majority of literature reports on interactions with antacids have been overemphasized; only ferrous sulfate-, isoniazid-, and tetracycline-antacid interactions fall into a category I importance (scale I-III of descending importance). This category is for those interactions with good evidence of actual or potential importance in patients or in relevant studies on normal subjects.

Prophylaxis of stress ulcers: antacid titration vs. histamine2-receptor blockade.

The near universal occurrence of stress ulcers in critically ill patients emphasizes the need for early and effective prophylaxis. Intraluminal gastric acidity, ischemic insult to the bowel, and the presence of stress factors are the major precipitants of stress ulcers. The use of H2-receptor antagonists vs. antacid titration for stress ulcer prophylaxis is reviewed. The goals of preventive therapy are to eliminate the stress factors and to maintain intragastric pH greater than 5. Hourly gastric pH monitoring and antacid titration are the mainstay of stress ulcer prophylaxis, with high potency antacids being the preferred agents. H2-receptor antagonists may serve as adjuncts in patients requiring large doses of antacids or having acid-base abnormalities from high gastric output states.

Controlled clinical assessment of the efficacy and tolerance of triletide versus antacids in patients with gastric and duodenal ulcers.

A study was carried out in 30 out-patients with endoscopically confirmed active, benign gastric or duodenal ulceration to assess the comparative effectiveness and tolerance of treatment with triletide, a new synthetic tripeptide with anti-ulcer properties, with that of conventional antacids. Patients were allocated at random to receive treatment with either 1.6 g aluminium hydroxide and 1.6 g magnesium hydroxide per day or the antacids plus 1.5 g triletide per day over a period of 8 weeks. Heartburn and epigastric pain, monitored every other week, were significantly relieved by both treatments, but to a significantly greater extent (70% vs 20% on average, p less than 0.01) and significantly faster (p less than 0.01) in the presence of triletide. Endoscopic control showed that the patients who had triletide experienced complete healing in a significantly greater proportion (73% vs 27%, p less than 0.02) than those who had antacids only. The efficacy of treatments was the same, regardless of the actual ulcer location. Routine haematology and haematochemistry findings were unaffected by either treatment, and subjective possible side-reactions were limited to constipation (9 complaints overall) which is a well-known side-effect of antacid treatment. It would appear, therefore, that triletide is at least as well tolerated as antacids, while promoting the healing of peptic ulcers in a significantly greater proportion of patients and easing symptoms significantly faster and to a greater extent than antacids alone, regardless of the ulcer location.

Medical versus surgical therapy for duodenal ulcer: making the right choices.

Significant advances have recently been made in the medical and surgical treatment of duodenal ulcer. Safe and more effective or better utilized drugs have emerged concurrently with improvements in surgical therapy. Identifying the proper candidates for each treatment modality has become a challenging task, although fortunately it has also implied a firm step forward in our struggle to conquer duodenal ulcer disease.

Peptic ulcer: antacids or cimetidine?

Controlled studies indicate that both high-dose antacids and cimetidine can be highly effective. Thus, the choice must rest on other considerations--acceptability, compliance, side effects, and cost. The problem of recurrence is addressed.