Rethinking the laryngopharyngeal reflux treatment algorithm: Evaluating an alternate empiric dosing regimen and considering up-front, pH-impedance, and manometry testing to minimize cost in treating suspect laryngopharyngeal reflux disease.

OBJECTIVES/HYPOTHESIS: Empiric proton pump inhibitor (PPI) trials for laryngopharyngeal reflux (LPR) are common. A majority of the patients respond to acid suppression. This work intends to evaluate once-daily, 40 mg omeprazole and once-nightly, 300 mg ranitidine (QD/QHS) dosing as an alternative regimen, and use this study's cohort to evaluate empiric regimens prescribed for LPR as compared to up-front testing with pH impedance multichannel intraluminal impedance (MII) with dual pH probes and high-resolution manometry (HRM) for potential cost minimization. STUDY DESIGN: Retrospective cohort review and cost minimization study. METHODS: A chart review identified patients diagnosed with LPR. All subjects were treated sequentially and outcomes recorded. Initial QD/QHS dosing increased after 3 months to BID if no improvement and ultimately prescribed MII and HRM if they failed BID dosing. Decision tree diagrams were constructed to determine costs of two empiric regimens and up-front MII and HRM. RESULTS: Ninety-seven subjects met the criteria. Responders and nonresponders to empiric therapy were identified. Seventy-two subjects (74%) responded. Forty-eight (67% of responders and 49% of all) improved with QD/QHS dosing. Forty-nine (51%) subjects escalated to BID dosing. Twenty-four subjects (33% of responders and 25% of all) improved on BID therapy. Twenty-five subjects (26%) did not respond to acid suppression. Average weighted cost was $1,897.00 per patient for up-front testing, $3,033.00 for initial BID, and $3,366.00 for initial QD/QHS. CONCLUSIONS: An alternate QD/QHS regimen improved the majority who presented with presumed LPR. Cost estimates demonstrate that the QD/QHS regimen was more expensive than the initial BID high-dose PPI for 6 months. Overall per-patient cost appears less with up-front MII and HRM. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:S1-S13, 2017.

Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.

Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were significantly superior to the pre-treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7-MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon-induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K-27 is a promising alternative to pyridostigmine.

Assessment of the use of clopidogrel associated with gastroprotective medications in outpatients.

OBJECTIVES: Check the progress of hospitalization and death of the patients that use clopidogrel associated with omeprazole and the patients that do not. METHODS: A retrospective cohort was conducted between January 2007 and November 2009 to evaluate patients that were using clopidogrel in association or not with omeprazole. RESULTS: The study included 2823 patients. Of these patients, 36% were female and 64% were male, the mean age was 63 years. Regarding the association of drugs for gastric protection, omeprazole was prescribed to 45%, ranitidine for 9%, while 46% of patients were not receiving gastroprotective medication. As for the analysis by groups, 35.5% of the omeprazole group was hospitalized after starting treatment with clopidogrel, compared with 25.7% in the group without omeprazole. In evaluating the deaths among patients using clopidogrel in the study period, we found the occurrence of 36 deaths, 22 in the omeprazole group and 14 in the other group. CONCLUSIONS: In our study, we did not evaluate the clinical status of the patients and the rates of reinfarction. And, as our study data showed, there are not any statistically differences between the groups that used clopidogrel associated with omeprazole, with ranitidine or that did not use any gastroprotective medication.

Effect of gastric emptying and entero-hepatic circulation on bioequivalence assessment of ranitidine.

The aim of study was to compare the bioavailability of ranitidine obtained from either Ranitidine (300 mg tablet; LPH® S.C. LaborMed Pharma S.A. Romania: the test formulation) and Zantac® (300 mg tablet; GlaxoSmithKline, Austria: the reference formulation). Twelve, Romanian, healthy volunteers were enrolled in the study. An open-label, two-period, crossover, randomized design was used. Plasma levels of ranitidine were determined using the validated, high-pressure liquid chromatography (HPLC) method. The physiologically motivated time-delayed model was used for the data evaluation and a paired Student's t-test and Schuirmann's two one-sided tests were carried out to compare parameters. Nonmodeling parameters (AUC(t), AUC, C(max), T(max)) were tested by the paired Student's t-test and the 90 confidence intervals of the geometric mean ratios were determined by Schuirmann's tests. Paired Student's t-test showed no significant differences between nonmodeling and modeling parameters. The results of the Schuirmann's tests however indicated significant statistical differences with reference to AUC(t), AUC, C(max), T(max) and other modeling parameters, especially MT(c) and τ(c). Schuirmann's tests revealed significant bioequivalence between ranitidine formulations using the modeling parameters MRT and n. The presented model can be useful as an additional tool to assess drug bioequivalence, by screening for disruptive parameters.

Omission of day 2 of antiemetic medications is a cost saving strategy for improving chemotherapy-induced nausea and vomiting control: results of a randomized phase III trial.

OBJECTIVES: Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we showed that delayed chemotherapy-induced nausea and vomiting control could be potentially improved by skipping the administration of a 5-hydroxytryptamine 3 (5-HT3) antagonist on day 2. We report here a trial confirming our previous findings. MATERIALS AND METHODS: A phase III randomized placebo-controlled trial was conducted in which patients received intravenously ondansetron 16 mg, dexamethasone 20 mg, and ranitidine 50 mg before highly/moderately emetogenic chemotherapy (day 1). Starting on day 2, all patients received metoclopramide 10 mg per oral every 8 hours (days 2, 3, and 4), dexamethasone 8 mg daily (days 2 and 3), and ranitidine 150 mg every 12 hours (days 2 and 3). Patients were randomized to receive either granisetron 0.5 mg per oral (days 2 and 3) (group A) or placebo instead of granisetron on day 2 and granisetron 0.5 mg on days 3 and 4 (group B). RESULTS: Seventy-three patients were enrolled. Groups were similar regarding clinical characteristics, despite better control during the acute phase of chemotherapy-induced nausea and vomiting in group A (P = 0.04). Complete delayed protection from nausea and vomiting (DCPNV) from day 2 to 5 was similar in both groups (30% vs. 32%; P = 0.5). Analyzing DCPNV by logistic regression multivariate analyses, acute complete protection from nausea and vomiting (P = 0.001) and study group (P = 0.06) were independently associated with DCPNV. Selecting patients who achieved acute complete protection from nausea and vomiting, we observed that group B had a superior DCPNV (85% vs. 50%, P = 0.02). CONCLUSION: DCPNV can be improved just by skipping day 2 of 5-HT3-antagonists. Future studies should compare this inexpensive strategy with NK1-antagonists or second generation 5-HT3-antagonists.

Six-month management of patients following treatment for gastroesophageal reflux disease symptoms -- a Norwegian randomized, prospective study comparing the costs and effectiveness of esomeprazole and ranitidine treatment strategies in a general medical practitioners setting.

This study assesses the difference in direct medical costs between on-demand treatment with esomeprazole 20 mg, continuous treatment with esomeprazole 20 mg once-daily and continuous treatment with ranitidine 150 mg twice-daily to prevent symptomatic relapse in patients with gastroesophageal reflux disease over 26 weeks. Two hundred eighty-one GP clinics in Norway enrolled 2156 patients to an open, randomized, parallel group, Norwegian society perspective study during 2000-2001. The total direct medical costs of each strategy were 171.9 Euros for on-demand esomeprazole (n = 634), 221.6 Euros for ranitidine (n = 610) and 248.8 Euros for continuous esomeprazole (n = 658). The total costs for on-demand and continuous esomeprazole treatment and ranitidine treatment were 221.5, 286.5 and 295.8 Euros, respectively. The highest proportion of costs was because of the study medication cost in each strategy. The on-demand and continuous treatment strategies with esomeprazole were found to be cost-effective, compared with ranitidine.

Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients.

BACKGROUND: Many hospitalized patients continue to receive intravenous medications longer than necessary. Earlier conversion from the intravenous to the oral route could increase patient safety and comfort, reduce costs, and facilitate earlier discharge from the hospital without compromising clinical care. We examined the effect of a computer-based intervention to prompt physicians to switch appropriate patients from intravenous to oral medications. METHODS: This study was performed at Brigham and Women's Hospital, an academic tertiary care hospital at which all medications are ordered online. We targeted 5 medications with equal oral and intravenous bioavailability: fluconazole, levofloxacin, metronidazole, ranitidine, and amiodarone. We used the hospital's computerized order entry system to prompt physicians to convert appropriate intravenous medications to the oral route. We measured the total use of the targeted medications via each route in the 4 months before and after the implementation of the intervention. We also measured the rate at which physicians responded to the intervention when prompted. RESULTS: The average intravenous defined daily dose declined by 11.1% (P =.002) from the preintervention to the postintervention period, while the average oral defined daily dose increased by 3.7% (P =.002). Length of stay, case-mix index, and total drug use at the hospital increased during the study period. The average total monthly use of the intravenous preparation of all of the targeted medications declined in the 4 months after the intervention began, compared with the 4 months before. In 35.6% of 1045 orders for which a prompt was generated, the physician either made a conversion from the intravenous to the oral version or canceled the order altogether. CONCLUSIONS: Computer-generated reminders can produce a substantial reduction in excessive use of targeted intravenous medications. As online prescribing becomes more common, this approach can be used to reduce excess use of intravenous medications, with potential benefits in patient comfort, safety, and cost.

Quality of life and cost-effectiveness of combined therapy for reflux esophagitis.

OBJECTIVE: To evaluate clinical, Quality of Life (QoL) and medical cost outcomes in patients with symptomatic reflux esophagitis (RE) receiving different "triple combination therapy". METHODS: A multicenter medical effectiveness trial conducted in 10 hospitals of 5 regions in Zhejiang Province. 248 patient-volunteers were assigned to 8 weeks of "triple combination therapy" with Lansoprazole plus Cisapride and Sucralfate or Ranitidine plus Cisapride and Sucralfate. Main outcomes assessment included symptoms scale scores, RE severity, QoL at baseline and 8 weeks. Medical cost data were collected with cost analysis questionnaire. RESULTS: (1) More Lansoprazole group patients noted RE symptoms resolution than Ranitidine group (92.3% vs 78.4%, P<0.01). There was no striking difference between two groups in RE healing rate (90.8% vs 82.9%, P>0.05). (2) RE significantly impaired QoL of patients (P<0.001). Compared with Ranitidine group, QoL in Lansoprazole group had significant improvement (rate of "good" QoL 64.5% vs 45.6%, P<0.01). (3) There was close correlation between symptomic effectiveness and QoL rating scale in both the Lansoprazole and Ranitidine group (P<0.01, r=0.235 and 0.353 respectively). There were no statistical difference of medical cost between the two groups (P>0.05). CONCLUSION: RE significantly impaired QoL of patients. "Triple combination therapies" can significantly improve RE symptoms and QoL. Lansoprazole combination therapy was more cost-effective than Ranitidine combination group.

Helicobacter pylori eradication in patients on long-term H2 receptor antagonists. Economic and symptomatic benefits. A large prospective study in primary care.

BACKGROUND: A large proportion of patients in primary care are still being maintained on long-term acid suppression, without any attempts to identify Helicobacter pylori status and to treat those that test positive. OBJECTIVES: To assess the prevalence and economic and symptomatic benefits of H. pylori eradication in patients maintained on long-term H2 receptor antagonists (H2RA) in primary care. PATIENTS AND METHODS: Patients on long-term (i.e. 6 months or longer) H2RA were identified from the computerised records of six practices in north England. Helicobacter pylori status was identified using serology and H. pylori positive patients were then offered standard 7-day proton pump based triple therapy, followed by a urea breath test (UBT) to confirm H. pylori eradication. Those who had a positive UBT were offered a second line course of H. pylori eradication therapy. Follow up period was 1 year. The main outcome measures were improvement in dyspepsia symptom scores, amount of H2RA being consumed, and economic benefits after H. pylori eradication. RESULTS: One thousand and seven patients (1.5%) were identified on long-term H2RA, of whom 471 (46%) ultimately had their H. pylori serology assessed. Sixty-three (297) percent of the patients tested had a positive serology for H. pylori, the majority of whom (58%, 172) had prior evidence of peptic ulcer disease. The mean duration of therapy and mean time since endoscopy/barium studies was significantly longer in patients with peptic ulcer disease compared to their counterparts with nonulcer dyspepsia and gastro-oesophageal reflux disease, p =.0002 and.0001, respectively. After successful H. pylori eradication (which was possible in 84% of the patients), at the end of the 1-year study period, on an intention to treat basis 62% of the patients could either stop or significantly reduce dosage of their H2RA. There was also significant reduction in the mean dose of H2RA being consumed and severity of symptoms at the end of the study period (p <.00001). CONCLUSION: Almost two-thirds of patients on long-term H2RA in primary care will have a positive serology for H. pylori; the majority of these will have peptic ulcer disease. In over 60% of cases H. pylori eradication led to significant improvement in symptom scores and reduction in dosage of H2RA being consumed. Cessation or reduction in long-term H2RA prescribing is cost effective.

A systematic comparison of triple therapies for treatment of Helicobacter pylori infection with proton pump inhibitor/ ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole.

BACKGROUND: Triple therapies with proton pump inhibitor/ranitidine bismuth citrate (RBC), clarithromycin (C) and either amoxicillin (A) or a nitroimidazole (I) are widely accepted as treatment for Helicobacter pylori infection. However, it is not clear which of these antibiotic combinations should be preferred. AIM: To evaluate whether there is a difference in efficacy between triple therapies with proton pump inhibitor/RBC, clarithromycin and either amoxicillin or a nitroimidazole. METHODS: The literature was examined for randomized trials comparing proton pump inhibitor/RBC-C-A and proton pump inhibitor/RBC-C-I. Studies were grouped according to the type of acid inhibitor used (proton pump inhibitor or RBC) and differences between pooled cure rates were calculated. RESULTS: Forty-seven studies were identified: seven using RBC, 39 using proton pump inhibitor, one using both. RBC-C-I was somewhat superior to RBC-C-A, although this difference only reached statistical significance in intention-to-treat analysis. Overall, proton pump inhibitor-C-I and proton pump inhibitor-C-A were equally effective, but in nitroimidazole-susceptible strains, proton pump inhibitor-C-I performed better, in nitroimidazole-resistant strains, proton pump inhibitor-C-A performed better. No serious side-effects were reported and pooled drop-out rates were equal. CONCLUSIONS: In general, proton pump inhibitor-C-I and proton pump inhibitor-C-A are equally effective and therefore other factors such as local prevalence of resistant strains, cost of therapy and options for second-line treatment should determine which regimen should be preferred. When using RBC, the RBC-C-I combination is somewhat superior to RBC-C-A.

The economic impact of the diagnosis of dysplasia in Barrett's esophagus.

OBJECTIVE: Cost-effective strategies for identifying patients with Barrett's esophagus who are most likely to develop cancer have not been developed. Surveillance endoscopy is currently used, and we hypothesized that more frequent surveillance intervals would identify patients with "transient positive" diagnoses of dysplasia--dysplasia found on one examination but not on subsequent ones. Our aim was to explore the potential economic impact of transient positive diagnoses of dysplasia on alternative surveillance strategies over a 10-yr period. METHODS: Data were derived from a 2-yr randomized, prospective study comparing omeprazole to ranitidine in 95 patients with Barrett's esophagus. A transient positive diagnosis of dysplasia was defined as a patient who was diagnosed with dysplasia during the study period but whose 24-month biopsies revealed no dysplasia. We calculated the number of transient positive diagnoses of dysplasia and modeled the potential economic impact of a diagnosis of dysplasia over a 10-yr period. RESULTS: Thirty patients (31%) had at least one reading of dysplasia during the study period. Nineteen patients (20%) had a transient positive diagnosis of dysplasia. During the study period, no cancers were found. A surveillance strategy of every other year and every 6 months for dysplasia would result in 1072 endoscopies over a 10-yr period at a discounted cost of $1,587,184. A total of 61% of endoscopies would be because of transient positive diagnoses of dysplasia. A strategy of yearly surveillance and every 6 months for dysplasia would result in 1404 endoscopies at a discounted cost of $2,096,733, of which 28% would result from transient positive diagnoses of dysplasia. The discounted incremental costs of more frequent surveillance in this cohort of patients over 10 yr is $509,549. CONCLUSIONS: Based on current practice strategies, transient positive diagnoses of dysplasia account for 28-61% of endoscopies in Barrett's surveillance programs. This analysis suggests that the endoscopy workload and costs associated with surveillance could be substantially reduced if patients with transient positive diagnoses of dysplasia reverted to usual surveillance after two negative examinations.

Cost effectiveness of rabeprazole versus generic ranitidine for symptom resolution in patients with erosive esophagitis.

OBJECTIVE: To compare the cost effectiveness of rabeprazole (RAB) and ranitidine (RAN) in acute and maintenance therapy for erosive esophagitis using symptom response, rather than endoscopic healing, as the clinical outcome. STUDY DESIGN: Decision analysis was used to model the cost effectiveness of competing therapies based on the results of clinical trials of RAB versus RAN and estimates from the medical literature. METHODS: The model's base case scenario compared brand-name RAB (estimated average wholesale price) with generic RAN (25% of the average wholesale price of brand-name RAN). Medical costs for hospitalizations, procedures, and office visits reflected 1998 Medicare payments. The 1-year maintenance model accounted for drug-class switching and symptomatic, rather than endoscopic, recurrences. Effectiveness was reported as the percentage of patients in whom a symptomatic recurrence was prevented. The cost per symptomatic recurrence prevented was reported as an average and an incremental cost-effectiveness ratio. RESULTS: The per-patient cost of RAB therapy was higher than that of RAN therapy ($2020 vs $1917); RAB therapy, however, was more effective than RAN therapy in preventing symptomatic recurrences (74% vs 41%). The average cost-effectiveness ratio was lower for RAB therapy than for RAN therapy ($2748 per symptomatic recurrence prevented vs $4719 per symptomatic recurrence prevented). The cost of preventing one additional symptomatic recurrence with RAB rather than RAN was $313 (incremental cost-effectiveness ratio). Sensitivity analysis conducted on key clinical and cost variables supported the robustness of the decision model. CONCLUSION: This analysis demonstrates that management of esophagitis with RAB is more effective, and may be more cost effective, than management with generic RAN, despite RAB's higher per-unit cost.

The use of intravenous H2-receptor antagonists in a tertiary care hospital.

OBJECTIVE: The rationale for the widespread use of intravenous H2 receptor antagonists(IVH2 RA) in hospitalized patients is not clear. We therefore examined prescribing patterns and, using strict criteria, determined whether use was appropriate. Cost of administration and potential savings were also determined. METHODS: Data were obtained prospectively on 100 consecutive patients prescribed intravenous ranitidine and retrospectively on patients admitted with gastrointestinal (GI) bleeding. RESULTS: For the prospective study, various indications for prescribing intravenous ranitidine were given, including postoperative patients and patients treated with steroids. Using criteria from published literature 80% of the use was considered inappropriate. Nearly 40% of the doses were given while the patient was tolerating oral intake. Creatinine clearance was impaired in 26% of patients, though only one had dosage reduction. Estimated annual cost of intravenous ranitidine was $317,000. The retrospective study of 86 consecutive patients admitted with GI bleeding revealed that all patients received intravenous ranitidine on admission, none of which was considered appropriate. The final diagnoses were peptic ulcer (49), colonic process (11), esophagitis (seven), gastric erosions (five), esophageal varices (five), Mallory-Weiss tears (four), duodenitis (two), no diagnosis (three), and jejunal ulcer (one). CONCLUSIONS: Inappropriate use of intravenous ranitidine is common. This includes inappropriate indication, dosage, and duration of use. Large financial benefits could have been obtained if close attention was given to prescribing patterns.

Cost effectiveness of omeprazole and ranitidine in intermittent treatment of symptomatic gastro-oesophageal reflux disease.

OBJECTIVE: This 1-year study compared the cost effectiveness of omeprazole and ranitidine when used as initial therapy in an intermittent treatment strategy for the management of patients with symptomatic gastro-oesophageal reflux disease with or without erosive oesophagitis. DESIGN AND SETTING: A prospective health economic analysis was conducted alongside an international multicentre randomised, double-blind clinical study. The economic analysis was performed from a societal perspective. PATIENTS: A total of 704 patients in the UK, the Republic of Ireland, Germany, France, Italy and Spain were randomised to 1 of the 3 treatment groups. INTERVENTIONS: Patients were randomised to receive either omeprazole 20 mg once daily, omeprazole 10 mg once daily or ranitidine 150 mg twice daily. Initial treatment failure resulted in dose titration and drug switching from ranitidine to omeprazole, and subsequently open maintenance treatment. MAIN OUTCOME MEASURES AND RESULTS: The estimated mean direct medical costs (medication and number of visits and endoscopies) were found to be lower for both dosages of omeprazole than for ranitidine in all countries except Germany. However, none of the differences were statistically significant. The differences between omeprazole 10 mg and omeprazole 20 mg were small and nonsignificant. With regard to numbers of symptom-free days, both omeprazole 20 mg and omeprazole 10 mg were found to be more effective than ranitidine. However, none of the differences were statistically significant. CONCLUSIONS: Following a pragmatic interpretation, incorporating intermediate short term results, the results in this study give no support to the notion that a step-up approach, either as dose titration from omeprazole 10 mg to omeprazole 20 mg or as drug switching from ranitidine to omeprazole, will result in cost savings and thereby be cost effective.

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

[Triple ranitidine therapy in Helicobacter pylori infection. Recommendation for effective, safe and cost effective combination for Helicobacter pylori eradication]. / Tripel-Ran-Therapie bei der Helicobacter-pylori-Infektion. Vorschlag für eine effektive, sichere und preiswerte Kombination zur H.p.-Eradikation.

Peptic ulcer disease induced by infection with Helicobacter pylori can be cured by eradicating the organism. In the meantime, such eradication therapy has moved beyond the experimental stage and can now be applied in the doctor's office, effectively, safely and inexpensively. A seven to twelve day course of treatment comprising a gastric acid inhibitor (20 mg omeprazole twice daily is no more effective than 300 mg ranitidine daily), 500 mg metronidazole twice daily, and 1 g amoxicillin twice daily results in an eradication rate of about 90%. That is, repeat treatment is needed in only one in ten patients. The cost of eradication therapy, however, varies considerably: the treatment recommended by the "initiative in support of the new form of ulcer treatment" costs DM 512.27, while equally effective treatment using generics costs only about one-fifth of this amount. In this way, a troublesome illness that for thousands of years has received only symptomatic treatment and whose sequelae cause high costs can now be treated causally with a high success rate and also a favourable cost-benefit ratio.

[Evaluation of intravenous ranitidine and omeprazole effect on the 24-hour gastric ph-metry in duodenal ulcer hemorrhage]. / Valoración de ranitidina y omeprazol intravenosos por pH-metría gástrica de 24 horas en hemorragia digestiva por úlcera duodenal.

BACKGROUND: The pharmacotherapy of bleeding peptic ulcer is directed to improve the environment of the bleeding point by keeping the gastric pH above the proteolytic range for pepsin. OBJECTIVE: To evaluate the best pharmacological approach to inhibit gastric acid secretion with current antisecretory drugs in patients with bleeding duodenal ulcers. METHODS: Forty-seven patients with bleeding duodenal ulcers were randomized to receive I.V.: I) Omeprazole: an initial bolus of 80 mg + perfusion of 3.3 mg/h; II) Omeprazole: an initial bolus of 80 mg + 40 mg/12 h; III) Omeprazole: 40 mg/8 h; IV) Ranitidine: perfusion of 12.5 mg/h; V) Ranitidine: 50 mg/4 h. Gastric acidity was measured and recorded by 24 h gastric pH monitoring. RESULTS: All types of treatment with omeprazole were superior to either continuous perfusion or intermittent bolus of ranitidine in increasing the pH for 24 h and reducing the % of time the gastric pH was below 4 and 6, and the number of time the gastric pH was below 4 for more than 5 min. There were no statistical differences between the different regimens of omeprazole, but continuous perfusion of ranitidine was superior to intermittent ranitidine bolus. CONCLUSIONS: Parenteral omeprazole is better than parenteral ranitidine in keeping the intragastric pH above the proteolytic range for pepsin in patients with bleeding duodenal ulcers.

[Comparison of the cost-efficacy ratio of omeprazole and ranitidine in the treatment of reflux esophagitis]. / Comparaison des rapports coût-efficacité du traitement de l'oesophagite par reflux par oméprazole et ranitidine.

OBJECTIVE: The objective of this study was to compare the cost of achieving a unit of clinical success for treatment of reflux oesophagitis with either ranitidine or omeprazole. METHODS: After randomisation 430 patients with reflux oesophagitis (grade 2 or 3) were assigned to receive omeprazole 20 mg or ranitidine 150 b.i.d. for 8 weeks. Patients were given diary cards to assess their symptoms every day, and record every two weeks a life satisfaction index. Patients were seen after 4 and 8 weeks for symptoms assessment and repeat endoscopy at 8 weeks. The perspective of the analysis was that of the payer. The costs of medical care were based in French drug costs currently advertised, payment for physician and actual mean payment for upper GI endoscopy. RESULTS: The healing rates at 8 weeks in the omeprazole group and the ranitidine group were 93 and 67.5% respectively. After 8 weeks of treatment, life satisfaction was good in 81 and 53.6% and the relief of pain was 86,6 and 69,5% respectively. For each effectiveness criteria, omeprazole was more cost effective than ranitidine: cost per healed patient (2,338 F vs 2,744 F), cost per asymptomatic patient (2,510 F vs 2,964 F), cost per patient with a good or very good life satisfaction index (2,687 F vs 3,456 F). This advantage remained independent of the oesophagitis initial severity. The sensitivity analysis showed that the results were unsensitive to the variations of the efficacy variables in their confidence interval. CONCLUSIONS: This cost-effectiveness analysis suggests that in the treatment of reflux oesophagitis, the strategy with the more effective treatment is more cost-effective.

Adjusting dosage intervals of intermittent intravenous ranitidine according to creatinine clearance: a cost-minimization analysis.

To provide effective ranitidine therapy at the lowest possible cost to institutions and patients, the main study objectives were to develop a dosage intervention strategy for intermittent intravenous ranitidine and to document the resultant cost savings through cost-minimization analysis. During a 6-week baseline phase, a pharmacy resident prospectively monitored all patients in the intensive care unit receiving intravenous ranitidine and evaluated appropriateness of dose according to creatinine clearance. Staff pharmacists collected identical data during the 6-week intervention phase but also made recommendations for dosage interval adjustment. In patients with creatinine clearance rates less than 50 mL per minute, the mean number of doses per patient treatment-day was reduced from 2.33 +/- 0.81 during baseline phase to 1.56 +/- 0.70 during intervention phase (P < 0.001). The hospital cost per patient treatment-day was decreased by 33%, from $5.29 +/- 1.83 to $3.54 +/- 1.59 (P < 0.001). Thus a program of prospective monitoring and verbal interventions by pharmacists effectively reduced the number of inappropriate ranitidine doses and hospital cost.

Long-term consequences with regard to clinical outcome and cost-effectiveness of episodic treatment with omeprazole or ranitidine for healing of duodenal ulcer.

The clinical outcome and cost-effectiveness of episodic treatment of duodenal ulcer with omeprazole and ranitidine were evaluated over a 5-year period. The analysis was based on data from published clinical trials comparing healing rates obtained with omeprazole and with ranitidine, as well as on data from the literature on ulcer recurrence and other clinical events. Patients with an active duodenal ulcer were treated until healed or for a maximum of 24 weeks. Maintenance therapy was instituted in patients with ulcers that were very slow to heal and in patients with frequent relapses after cessation of treatment. Patients who experienced frequent relapses while receiving maintenance therapy, and those whose ulcer had not healed after 24 weeks of continuous treatment, were defined as candidates for surgery. A statistical model was set up and a random number generator used to generate a sequence of clinical events, month by month, over a 5-year period for each patient in a large cohort. Episodic treatment with omeprazole was shown to be more effective in avoiding maintenance treatment and surgery when compared with episodic treatment with ranitidine. Patients who received episodic treatment with omeprazole also spent more time in remission from disease. Using current Swedish cost data, it was found that episodic treatment with omeprazole was more cost-effective than episodic treatment with ranitidine.