Long-term Prevention Studies Research Articles

Therapeutic Options for the Prevention of Type 2 Diabetes Mellitus in the Metabolic Syndrome

The increasing prevalence of metabolic syndrome has created an impetus to prevent complications such as diabetes. There are no defined treatments for metabolic syndrome apart from addressing each of its components such as obesity, hypertension, dyslipidemia, and hyperglycemia. To evaluate diabetes-prevention strategies, we performed a Medline search and identified evidence suggesting that lifestyle intervention and certain medications can prevent diabetes. In addition, there are several agents on the horizon that seem promising. The mechanism responsible for diabetes prevention relates to improved insulin resistance as a result of weight loss or other processes. Lifestyle interventions and medications such as metformin are effective and safe in long-term prevention studies. However, the safety and efficacy of newer agents need clarification.

Assessing Cancer Prevention Studies—A Matter of Time

Assessing Cancer Prevention Studies—A Matter of Time

Traitements curatif et préventif des ulcères gastro-duodénaux induits par les AINS

The use of treatments to heal or to prevent nonsteroidal anti-inflammatory drugs (NSAIDs) associated gastroduodenal lesions is based on replacement of mucosal prostaglandin deficiency or inhibition of acid secretion. Four-week acid suppression by proton pump inhibitors (PPI) with 7-day eradication triple therapy in Helicobacter pylori positive patients is effective in healing gastric and duodenal ulcer upon discontinuation of NSAIDs. In the event NSAIDs must be continued, PPIs (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) are more effective than H2-blockers and cytoprotective agents (sucralfate, misoprostol) to heal mucosal lesions. In long-term prevention studies, omeprazole 20 mg, lansoprazole 15 mg, and pantoprazole 20 mg significantly reduce gastric and duodenal ulcer rates. Misoprostol 800 microg is as effective as PPIs for preventing symptomatic and complicated gastric ulcers, but less effective to prevent duodenal ulcer, with a high rate of adverse effects such as diarrhea. Helicobacter pylori eradication in infected patients decrease the risk of NSAIDs-associated lesions but is less effective than concomitant antisecretory treatment. Current data from comparative studies of PPIs vs ranitidine or misoprostol are in favor of the PPIs as well tolerated and effective drugs in the prophylaxis of NSAIDs-related gastroduodenal lesions in high-risk patients.

Prophylaxis and treatment of non-steroidal anti-inflammatory drug-induced upper gastrointestinal side-effects

The use of specific agents to heal mucosal lesions or to prevent non-steroidal anti-inflammatory drug toxicity, has focused upon two approaches: replacement of prostaglandin deficiency and inhibition of acid secretion. Acid suppression with traditional ulcer healing doses of H 2-blockers is effective in healing gastric and duodenal ulcers upon dis-continuation of the offending drug. In the event the non-steroidal anti-inflammatory drug must be continued, the use of H 2-blockers is associated with a decrease in the healing rate. In long-term prevention studies, H 2-blockers significantly reduce duodenal ulcer rates, but are ineffective in reducing gastric ulceration. More potent acid inhibition with a double-dose of H2_blockers (famotidine 80 mg daily, ranitidine 600 mg daily) may reduce the risk of gastric and duodenal ulcers. Marked acid suppression with proton pump inhibitors (omeprazole 20–40 mg, lansoprazole 30 mg daily) also appears to be very effective in healing gastric and duodenal ulcers in patients continuing the offending drug as well. An analysis of pooled data from comparative studies on omeprazole vs ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of the proton pump inhibitor, ranging from 10 to 40%. In long-term prevention studies, omeprazole (20 mg daily) and pantoprazole (40 mg daily) have also been shown to reduce the risk of gastric and duodenal ulcers and non-steroidal anti-inflammatory drug-related dyspepsia. Current data from recent comparative studies of omeprazole (20 mg daily) vs ranitidine (150 mg daily) and misoprostol (200,μg daily) showed that, after 6 months' follow-up, the proton pump inhibitor was significantly superior to control drugs in reducing the risk both of gastric and duodenal ulcer. Misoprostol (at doses ranging from 400 μg to 800 μg/day is an effective form of therapy for preventing non-steroidal anti-inflammatory drug-induced gastroduodenal lesions. However, high-dose misoprostol only, seems adequate for the prevention of ulcer complications, mainly in high-risk non-steroidal anti-inflammatory drug users. Thus, available data are undoubtedly in favour of the proton pump inhibitors as well tolerated and effective drugs in the prophylaxis and treatment of non-steroidal anti-inflammatory drug-related mucosal lesions in the gastrointestinal tract.

Prevention studies with pentoxifylline: new clinical projects.

Pentoxifylline (PTX) is a methylxanthine derivative whose diverse mechanisms of action are now extensively documented. It may play a role in various diseases via a pharmacologic modification of cytokine dysregulation. Despite many encouraging results in animal models, it has not yet been demonstrated that PTX could have beneficial effects in other diseases than intermittent claudication. We selected three clinical conditions that may benefit from PTX and are trying to clarify its potential for use in these disorders. The use of allogeneic bone marrow transplantation is limited by its toxicity, although this form of therapy is able to cure many hematologic malignancies. We are performing a placebo-controlled trial to evaluate the ability of PTX to decrease transplant-related toxicity. In severe chronic respiratory insufficiency, a study is ongoing to compare the number of infectious exacerbations under PTX or placebo. Finally, we have planned a long-term prevention study in patients with peripheral arterial disease. We present here the rationale and design of these trials.