Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

The management of menopausal sequelae in patients with breast cancer.

The use of chemotherapy and tamoxifen for young women with breast cancer results in premature menopause in a significant number of patients. Early menopause has serious vasomotor, psychological, genitourinary, cardiac and skeletal effects. Psychopharmacological and herbal preparations are widely used for the treatment of vasomotor symptoms. The incidence of psychological and depressive illness following the menopause in women with breast cancer is significantly higher than seen with the natural menopause. Targeting this population of patients for early diagnosis and psychiatric intervention is recommended. Local vaginal moisturising or oestrogen cream would help to alleviate some of the urogenital symptoms. Patients whose treatment included Anthracycline chemotherapy or radiation to the heart and those with a history of heart disease, should be monitored closely for latecardiac complications. Early menopause is the major risk factor for the development of osteoporosis. Weight bearing exercise, bisphosphonate or calcitonin therapy are all useful in treating osteoporosis. Should a woman with a history of breast cancer be given hormone replacement therapy is one of the most controversial issues in the oncology field. There are no published prospective randomised studies on the subject. The available data suggests an increase of 5% of breast cancer related events when hormone replacement therapy is given to women with breast cancer. However, in certain situations, this could be given after a detailed explanation and documentation. The patient and physician should balance the severity of symptoms against the increased breast cancer related events and the final decision should be left to the patient.

Comparison of analgesic effects of khat (Catha edulis Forsk) extract, D-amphetamine and ibuprofen in mice.

We have compared the analgesic properties of khat (Catha edulis Forsk) extract, amphetamine and ibuprofen in mice. After intragastric administration of the drugs analgesia was measured relative to water-injected controls using the hot-plate, the tail-flick, and abdominal-constriction tests. At the highest doses examined (amphetamine 1.8 mg kg(-1), ibuprofen 90 mg kg(-1), khat extract 1800 mg kg(-1)), all three substances produced analgesia, but the order of efficacy varied with the test. Khat and ibuprofen were significantly different from the control in the hot-plate assay at three or more time points post-injection. In the tail-flick test, khat and amphetamine were efficacious; ibuprofen means were somewhat lower but still significantly different from control. Higher doses of the drugs decreased the number of responses in the acetic acid-induced abdominal-constriction assay. We conclude that khat, like amphetamine and ibuprofen, can relieve pain. Differences in assay results may reflect differences in modes and sites of action, as well as in the type of pain generated by the chemical and thermal stimuli for nociception.

Antifertility activity of Ricinus communis seed in female guinea pigs.

OBJECTIVE: To investigate the anti-fertility effect of Ricinus communis seed extract. DESIGN: Laboratory-based experiment. SETTING: Laboratory of the Department of Pharmacology, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia in 1996. RESULTS: The seed extract was found to possess anti-implantation and abortifacient effects. It was also observed that the seed extract prolonged the oestrus cycle of guinea pigs. The dioestrus phase was significantly prolonged as well. After stopping administering the extract, however, the normal dioestrus phase and oestrus cycle started to resume. The seed extract also reduced the weight of the uterus without affecting that of the ovaries significantly. CONCLUSION: Ricinus communis possesses an anti-fertility effect in female guinea pigs, which might be extrapolated in human beings. These findings might support the accredited claim of its traditional use to avoid unwanted pregnancies. Further studies, however, should be pursued.