Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials

BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.     

A Cost Minimization Analysis of Ready-to-Administer Prefilled Sterilized Syringes in a Dutch Hospital

PurposePreparation errors occur frequently during conventional preparation of parenteral medication in the clinical environment, causing patient harm and costs for the national health care system. The use of ready-to-administer prefilled sterilized syringes (PFSSs) produced by the hospital pharmacy can reduce preparation errors and the risk of bacteremia from contamination of the intravenous medication. The aim of this research is to compare the total costs of the conventional preparation method (CPM) with the PFSS method.MethodsIn this cost-minimization analysis, costs related to the preparation of the medication, bacteremia from contamination, adverse drug events as a result of preparation medication errors, and wastage of syringes were taken into account. Annual costs in a general Dutch hospital were consistently calculated. Three scenarios were analyzed: (1) all preparations as CPM (864,246 administrations per year), (2) all preparations as PFSSs, and (3) 50% as PFSSs and 50% as CPM. Deterministic and probabilistic sensitivity analyses were performed.FindingsThe first scenario found higher annual costs at €14.0 million (US$16.0 million) compared with the second scenario (€4.1 million, US$4.7 million). The most realistic situation (third scenario) found savings of €4.9 million (US$5.6 million) compared with the first scenario. Sensitivity analyses revealed that cost savings of PFSSs were strongly influenced by decreased risk of medication errors and contamination of intravenous medication. Extrapolating these results nationwide indicated potential savings of >€300 million (US$342 million) if only PFSSs were used.ImplicationsThe use of PFSSs prepared in the hospital pharmacy yielded cost savings compared with the CPM on the ward in the Dutch hospital.     

Are COX‐2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?

Rationale In developed countries, cyclooxygenase 2 (COX‐2) inhibitors were shown to be less costly than the combination of non‐steroidal anti‐inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) in treatment of patients with high risk of serious gastrointestinal (GI) adverse effects. It is questionable if such results apply to developing countries where health service costs are lower and there is high discrepancy between generic and patent protected drug prices. We analysed the direct cost of treatment with generic NSAIDs in combination with PPIs versus branded COX‐2 inhibitors in patients with high risk of serious GI adverse effects from the perspective of the public health service in Serbia. Methods Total cost of treatment of serious GI complications and the use of NSAID+PPI versus COX‐2 inhibitors were calculated. A model for estimation of cost of treatment of NSAID+PPI versus COX‐2 inhibitors which included the probability of developing serious GI adverse effects was developed. Results Total cost of treatment of serious GI adverse effects resulted in an average of $814/patient. Considering the relative risk of such adverse effects for patients with four or more risk factors, the least costly treatment over 6 months was the use of celecoxib ($487). Compared with diclofenac+omeprazole, cost savings were estimated at $59 and $22 per patient with celecoxib and etoricoxib, respectively. Conclusion Cost savings may be achieved by using COX‐2 inhibitors in patients at high risk of GI adverse effects even in countries with moderate health care service expenditures. Such possibility requires further investigation.     

The proton-pump inhibitors: similarities and differences

OBJECTIVE: This paper examines the clinical pharmacology of the proton-pump inhibitors (PPIs) and briefly reviews some comparative studies of these agents. BACKGROUND: PPIs have emerged as the treatment of choice for acid-related diseases, including gastroesophageal reflux disease (GERD) and peptic ulcer disease. Although these drugs-omeprazole, lansoprazole, pantoprazole, and rabeprazole-share a common structure (all are substituted benzimidazoles) and mode of action (inhibition of H+,K+-adenosine triphosphatase [ATPase]), each differs somewhat in its clinical pharmacology. RESULTS: In comparative clinical trials found in MEDLINE, PPIs administered once daily produced endoscopic evidence of healing in >90% of patients with duodenal ulcer after 4 weeks of treatment, in >90% of those with gastric ulcer after 6 weeks of treatment, and in >90% of those with ulcerative or erosive GERD after 8 weeks of treatment. Maintenance therapy with daily doses of a PPI has been shown to be an effective means of preventing GERD relapse. PPIs also inhibit the growth of Helicobacter pylori, now recognized as an important factor in peptic ulcer disease, and, when administered in combination with antibiotics, provide the best treatment for eradication of the bacterium. Rabeprazole has a more rapid onset of H+,K+-ATPase inhibition than the other PPIs and, compared with omeprazole, a greater effect on intragastric pH after the first dose. Omeprazole and lansoprazole have a greater potential for drug-drug interactions than do pantoprazole and rabeprazole. CONCLUSION: Although the individual PPIs have similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen.     

Net health plan savings from reference pricing for angiotensin-converting enzyme inhibitors in elderly British Columbia residents

BACKGROUND: Reference drug pricing (RP) is a cost-sharing strategy commonly used to control drug expenditures. Under RP, a benefit plan fully reimburses medications that are equally or less expensive than the reference price, and requires patients to pay the extra cost of therapeutically equivalent but higher priced drugs. Critics argued that drug plan savings are offset by administrative costs and increased spending on other health services. OBJECTIVE: We evaluated net healthcare savings in beneficiaries >or=65 years from the perspective of the British Columbia provincial health insurance system after it applied RP to angiotensin-converting enzyme (ACE) inhibitors in 1997. METHODS: We estimated savings in new users of antihypertensives after the start of RP plus associated administrative costs and savings from reductions in retail drug prices. Findings were integrated with earlier results on the consequences of RP on expenditures for drugs, physicians, and hospitalizations among all seniors who used ACE inhibitors before the introduction of RP. RESULTS: During the first year after the implementation of RP, savings for continuous users were CAN dollars 6.0 million. Savings for new users were dollars 0.2 million. Approximately five sixths thereof were achieved by utilization changes and one sixth by cost shifting to patients. There were no savings through drug price changes. Administering RP cost dollars 0.42 million. Overall net savings were estimated to be dollars 5.8 million during the first year after the start of RP. The magnitude of these savings is equal to 6% of all cardiovascular drug expenditures in seniors. After 10 years, approximately 50% of savings will be achieved by new users. CONCLUSION: We observed substantial net savings from RP for ACE inhibitors for the provincial health insurance system in British Columbia, although there were generous exemptions from the policy. In other jurisdictions, savings could be higher if drug prices decline after the start of reference pricing.     

Health and economic impact of posttransfusion hepatitis B and cost-effectiveness analysis of expanded HBV testing protocols of blood donors: a study focused on the European Union

BACKGROUND: Residual risk of posttransfusion hepatitis B (PT-HB) may be reduced through implementation of HBV NAT or the new, enhanced-sensitivity HBsAg assays in routine donor testing. However, there are some doubts about the cost-effectiveness of these new safety measures, because hepatitis B acquired in adulthood is not regarded as a severe disease in western countries. STUDY DESIGN AND METHODS: A computer model was designed to estimate the health outcomes and associated costs of patients with PT-HB. Results from this model and estimations of the residual risk of HBV transmission, the risk reduction yielded by the new assays, and their cost were used to calculate the cost-effectiveness of including the new HBsAg assays or single-sample HBV NAT in the routine screening of blood donors. RESULTS: The model predicts that 0.97 percent of patients with PT-HB die of liver disease (54% of them due to fulminant hepatitis). The mean loss of life expectancy was 0.178 years per patient, and the present value of the lifetime costs of treating PT-HB was 4160 euros per patient. Single-donor HBV NAT or the new HBsAg assays would increase the life expectancy of blood recipients by 16 (95% CI, 8-40) or 14 (95% CI, 7-28) years, respectively, per every 10 million donations tested. The projected cost per life-year gained was 0.79 (95% CI, 0.15-1.85) million euros for the enhanced-sensitivity HBsAg assays and 5.8 (95% CI, 1.9-13.1) million euros for single-donation HBV NAT, both compared with current HBsAg assays. If single-donation HBV NAT is compared with the new HBsAg assays, its cost- effectiveness ratio increases to 53 (95% CI, 16-127) million euros. CONCLUSION: PT-HB has few health or economic repercussions. Single-donation HBV NAT would provide a small health benefit at a very high cost. Instead, in some circumstances, the cost-effectiveness of enhanced-sensitivity HBsAg assays would be within acceptable ranges for new public health interventions.     

Influence of antisecretory treatment with proton pump inhibitors on serum pepsinogen I levels

It has been reported in literature that serum pepsinogen levels rise during omeprazole and lansoprazole administration. However, the influence of pantoprazole and esomeprazole on serum pepsinogens levels is still to be assessed. The aim of this study was to evaluate the influence of proton pump inhibitor (PPI) therapy on pepsinogen I (PGI) levels. PGI and gastrin (G17) levels (EIA; Biohit, Helsinki, Finland) in 126 consecutive patients (M 57; F 69, mean age 53, range 15-91), with upper gastrointestinal symptoms at baseline condition and after 2 months of PPI treatment, were evaluated. Patients underwent a therapy schedule based on: omeprazole 20 mg b.i.d. (20 patients), pantoprazole 40 mg b.i.d. (27 patients), esomeprazole 40 mg b.i.d. (29 patients), lansoprazole 30 mg b.i.d. (21 patients) and rabeprazole 20 mg b.i.d. (26 patients) for 2 months. A significant increase in serum PGI (sPGI) levels was found after a 2-month treatment for all five different PPIs: omeprazole, pantoprazole, esomeprazole, lansoprazole and rabeprazole (P < 0.05). The effect of rabeprazole on sPGI was less pronounced as compared with other PPIs, whereas esomeprazole achieved superior sPGI levels, with no overall statistically significant difference among the five groups (P > 0.05). However, a comparison within a single group of PPIs showed a statistical significance when the esomeprazole group was compared with the rabeprazole group (P = 0.007). sPGI levels are significantly influenced by antisecretory therapy, rising under PPI treatment. Moreover, a statistically significant difference in sPGI levels between the rabeprazole and esomeprazole groups has been demonstrated.     

Cost-of-illness of neck pain in The Netherlands in 1996

The prevalence of neck pain in the general population ranges from 10 to 15%. The complaints can result in substantial medical consumption, absenteeism from work and disability. In this study we investigated the costs of neck pain in the Netherlands in 1996 to assess the financial burden to society. The study was based on prevalence data. Data sources included national registries, reports of research institutes and health care authorities. Direct health care costs were estimated for hospital care, general practice care and paramedical care. These costs were calculated using fees. Calculation of indirect costs (absenteeism and disability) was based on the Human Capital Method (HCM). As an alternative approach the Friction Cost Method (FCM) was used. The total cost of neck pain in The Netherlands in 1996 was estimated to be US $686 million. The share of these costs was about 1% of total health care expenditures and 0.1% of the Gross Domestic Product (GDP) in 1996. Direct costs were $160 million (23%). Paramedical care accounted for largest proportion of direct costs (84%). When applying the HCM for calculating indirect costs, these costs amounted to $527 million (77%). The total number of sick days related to neck pain were estimated to be 1.4 million with a total cost of $185.4 million in 1996. Disability for neck pain accounted for the largest proportion (50%) of the total costs related to neck pain in 1996 ($341). When applying the FCM for calculating the indirect costs, these costs were reduced to $96 million. The costs related to neck pain in 1996 in The Netherlands were substantial. Some caution should be taken in interpretation, as a number of assumptions had to be made in order to estimate the total costs. The cost structure shown in this study, with high indirect costs, has also been found in other studies. From an economical point of view it seems to be important to prevent patients from having to take sick leave and disability. One way in achieving this goal is to develop and investigate more effective treatments for acute neck pain, in order to prevent patients developing chronic pain and disability. Another option is to protect chronic patients from sick leave and disability by careful management. Thus, also in the area of direct medical costs, there may be room for cost savings by stimulating and improving cost-efficiency and cost-effectiveness of the (para)medical care. In order to deal with the lack of specific disease information, more detailed information of medical consumption, sick leave and disability is required for future cost analysis.     

Cost-benefit analysis of capecitabine versus 5-fluorouracil/leucovorin in the treatment of colorectal cancer in the Netherlands

BACKGROUND: Capecitabine is an oral prodrug of 5-fluorouracil and has been studied for the treatment of colorectal cancer. In 2 Phase III trials, capecitabine was at least as effective as 5-fluorouracil plus leucovorin and had a more favorable toxicity profile. OBJECTIVE: A cost-benefit analysis was used to assess the pharmacoeconomic profile of capecitabine compared with 5-fluorouracil/leucovorin, given according to the Mayo regimen, for colorectal cancer patients treated in the Netherlands. METHODS: The medical files of patients treated for colorectal cancer at a single center from 1999 to 2002 were examined to determine the numbers of outpatient visits for 5-fluorouracil/leucovorin administration, health care use and medication to manage adverse effects, and travel distance to and from the hospital. The costs of capecitabine treatment were simulated by assuming that the same patients were treated with capecitabine instead of 5-fluorouracil/leucovorin. Toxicity data for capecitabine were derived from 2 Phase III studies that compared capecitabine and 5-fluorouracil/leucovorin. RESULTS: The files of 65 patients were reviewed. Thirty-two patients received adjuvant treatment and 33 patients were treated palliatively for metastatic disease. The mean total costs of palliative treatment were Euro 4004 with capecitabine and Euro 5614 with 5-fluorouracil/leucovorin. These results were robust in sensitivity analyses. The cost savings were primarily related to the number of outpatient visits for capecitabine versus the number of day-care treatment days for 5-fluorouracil/leucovorin, despite the higher acquisition costs of capecitabine. CONCLUSIONS: Based on this analysis, treatment of colorectal cancer with oral capecitabine is cost saving in the Netherlands compared with 5-fluorouracil plus leucovorin administered according to the Mayo regimen. Baseline savings were estimated at Euro 1610 for palliative treatment and Euro 934 for adjuvant treatment.     

质子泵抑制剂导致的急性泛发性发疹性脓疱病:基于真实世界的药物警戒研究

  目的  探讨不同质子泵抑制剂(proton pump inhibitors, PPIs)与急性泛发性发疹性脓疱病(acute generalized exanthematous pustulosis, AGEP)的关联性及特点。  方法  检索2004年1月至2020年6月美国食品药品监督管理局不良事件报告系统(Food and Drug Administration's adverse events reporting system, FAERS)数据库中PPIs/AGEP相关报告,采用比例失衡测量法及贝叶斯法对不同PPIs导致的AGEP进行关联性分析,并比较其发病时间及预后。  结果  共检索到此期间PPIs导致的AGEP病例报告162例。应用的PPIs药物主要为奥美拉唑(33.95%,55/162),其次为埃索美拉唑(29.63%,48/162)、泮托拉唑(26.54%,43/162)。以泮托拉唑与AGEP的关联性最强,其次为奥美拉唑和兰索拉唑,埃索美拉唑与AGEP的关联性较弱。PPIs导致AGEP发病时间的中位数为6(2,12)d,60.00%~83.33%的患者于用药后10 d内发病(除雷贝拉唑外)。3例(1.86%)AGEP患者死亡,128例(79.50%)需住院治疗。以埃索美拉唑导致的AGEP患者住院比率最高(91.49%,43/47),其次为泮托拉唑(88.37%,38/43)、兰索拉唑(85.71%,12/44),奥美拉唑(61.82%,34/55)最低。  结论  基于对FAERS数据库的药物警戒研究,揭示不同PPIs导致AGEP的风险及特点,可为临床合理用药提供依据。     

Economic evaluation of a randomized trial comparing Helicobacter pylori test-and-treat and prompt endoscopy strategies for managing dyspepsia in a primary-care setting

BACKGROUND: In western European countries, most dyspeptic patients are initially managed by their general practitioners (GPs), who use a range of strategies to manage dyspepsia. We performed an economic analysis of a Helicobacter pylori test-and-treat strategy versus a prompt endoscopy approach in a primary care setting. METHODS: Data were used from the Strategy: Endoscopy versus Serology (SENSE) study, performed in The Netherlands from 1998 to 2001. Patients were randomized to a prompt endoscopy (n = 105) or test-and-treat (n = 118) group. Follow-up lasted 1 year. Adverse events were not recorded in the SENSE study. Health care costs were based on the total amount of dyspepsia-related drugs used, the number of dyspepsia-related GP visits, the number of diagnostic tests, and the number of dyspepsia-related referrals to specialists. The use of medical resources was calculated as standardized costs for 1999, recorded as euros. (On December 31, 1999, 1.00 Euro = 1.00 US dollar.) Quality of life was measured at inclusion and 1 year later, using the RAND-36 questionnaire. To calculate quality-adjusted life-years (QALYs), we transformed the individual scores of the RAND-36 into 1 overall score, the Health Utilities Index Mark 2, which introduced a limitation to the study. An incremental cost-effectiveness ratio (ICER) was calculated. The 95% confidence limits were calculated using a parametric bootstrap method with angular transformation. All cost data were analyzed from a third-party payer perspective. RESULTS: The total costs per patient were 511 Euros, with 0.037 QALY gained per patient, in the test-and-treat group, and 748 Euros, with 0.032 QALY gained per patient, in the endoscopy group (between groups, P < 0.001 and P = NS, respectively). The point estimate of the ICER indicated that the test-and-treat strategy yielded cost savings and QALYs gained. Parametric bootstrap confidence limits indicated cost savings per QALY gained in 75.7% of the bootstrap simulations. CONCLUSION: This analysis of data from the SENSE1026 study suggests that the H pylori test-and-treat strategy was more cost-effective than prompt endoscopy in the initial management of dyspepsia in general practice, from the perspective of a third-party payer.     

Cost analysis of plasma-exchange therapy for the treatment of Guillain-Barré syndrome

Objective: To undertake a cost analysis of therapeutic strategies with plasma exchange (PE) for the treatment of patients with Guillain-Barré syndrome. Design: A randomized clinical trial including 556 patients with Guillain-Barré syndrome. We demonstrated that in the group with mild disease (walking possible) two PEs were more effective than none in shortening the time to beginning motor recovery. In the groups with moderate disease (walking impossible) and or severe disease (mechanically ventilated patients) four sessions were more effective than two and no more effective than six in shortening the time to recovery of walking with assistance and for the recovery rate of full muscle strength within 1 year. Data on outcomes and costs was collected. Complete cost data were available on 546 from the 556 patients of the trial. Costs were estimated from the viewpoint of the healthcare system and computed over a 1-year period. Because the analysis of medical outcomes did not show any difference regarding mortality but only on intermediate short-term and long-term outcomes, we carried out a cost minimization analysis. Results: In two groups a dominant strategy appeared, with greater efficacy and lower costs in the two-PE arm for the mild group: 21,353 euros vs. 38,753 euros and in the four-PE arm in the moderate group: 59,480 euros vs. 80,737 euros. In the severe group four PEs were as efficient and somewhat less expensive than six: 57,621 vs. 61,056 euros. Conclusion: The treatment of Guillain-Barré syndrome by PE at the onset of disease appears to have medical justification. The least expensive strategies are either more or equally efficient as more expensive strategies. Received: 3 November 1999 Final revision received: 5 May 2000 Accepted: 9 May 2000     

Cost effects of restricting cost-effective therapy

This article examines the cost effects of a closed pharmaceutical formulary on Medicaid expenditures for peptic ulcer disease. Studies were performed before and after the imposition of a closed pharmaceutical formulary and indicated that total Medicaid costs for peptic ulcer treatment were 15.0% lower during the closed formulary than open formulary periods. The overall savings were due mainly to a sharp decline in the number of peptic ulcer patients served by Medicaid. The cost per patient-month of therapy increased by 9.4% between study periods. Pharmaceutical costs per patient-month declined by 78.9%, monthly physician payments increased by 3.1%, and monthly inpatient hospital costs increased by 23.6%. The small, short-term savings may be negated by increased expenditures in the near future when sicker patients, previously denied peptic ulcer drug treatment, may reenter the Medicaid system in need of expensive inhospital treatment.     

An economic assessment of losartan-based versus atenolol-based therapy in patients with hypertension and left-ventricular hypertrophy: results from the Losartan Intervention For Endpoint reduction (LIFE) study adapted to The Netherlands

BACKGROUND: The Losartan Intervention For Endpoint reduction (LIFE) study was a randomized, doubleblind trial that compared the effects of losartan-based treatment with those of atenolol-based treatment on cardiovascular disease (CVD)-related morbidity and mortality in 9193 patients with hypertension and left-ventricular hypertrophy (LVH). Compared with atenolol, losartan reduced the combined risk for CVD-related morbidity and mortality by 13% (P = 0.021), and reduced the risk for stroke by 25% (P = 0.001), with comparable blood pressure control in both trial arms. OBJECTIVE: The aim of this study was to analyze the cost-effectiveness of losartan compared with atenolol in the treatment of stroke from the Dutch health care perspective. METHODS: Utilization of losartan and atenolol within the trial period (mean, 4.8 years) and an estimation of direct medical costs of stroke for The Netherlands were combined with estimates of reduction in life expectancy through stroke. Medication costs and stroke incidence during 5.5 years of patient follow-up were estimated separately, adjusted for the baseline degree of LVH and Framingham risk score. To estimate lifetime stroke costs, the cumulative incidence of stroke was multiplied by the lifetime direct medical costs attributable to stroke. All costs are in 2006 Dutch prices and discounted following the former (4% costs and effects) and new Dutch guideline (4% costs, 1.5% effects) for conducting pharmacoeconomic analyses. RESULTS: With 4% discounting, prevention of stroke was associated with a gain of 3.7 life-years. As a consequence, losartan treatment was associated with 0.059 life-year gained (LYG) per patient treated with losartan. Losartan reduced stroke-related costs by 1,076 Euros (US $1,349) per patient. After inclusion of study medication cost, net cost per patient was 51 Euros ($64) higher for losartan than atenolol. The net cost per LYG was 864 Euros ($1083), which is below the Dutch pharmacoeconomic threshold of 20,000 Euros/LYG (~$25,000/LYG) for accepting interventions. The corresponding probability of a cost-effectiveness ratio below this Dutch threshold was 0.95. Discounting money and health following the new Dutch guideline resulted in an even more favorable cost-effectiveness for losartan. CONCLUSIONS: Results from the present analysis suggest that, in The Netherlands, treatment with losartan compared with atenolol may well be a cost-effective intervention based on the reduced risk for stroke observed in the LIFE trial.     

Combination drug therapy for gastroesophageal reflux disease

OBJECTIVE: To evaluate the role of combination therapy with proton-pump inhibitors (PPIs) and histamine(2) receptor antagonists in gastroesophageal reflux disease (GERD). DATA SOURCES: Clinical literature identified through MEDLINE (January 1966-August 2001). Key search terms included gastroesophageal reflux, benzimidazoles; omeprazole; lansoprazole; pantoprazole; rabeprazole; receptor antagonists, histamine(2); therapy, combination drug; therapy, combined modality; and combinations, drug. DATA SYNTHESIS: Approximately 80-90% of patients show healing of reflux esophagitis after 8 weeks of once-daily PPI therapy. Patients taking PPI therapy twice daily still have nocturnal acid breakthrough (periods of gastric pH <4 lasting for > or =60 min during the night) as much as 70% of the time. The clinical application of this finding has not been shown. One trial has shown that omeprazole in the morning plus ranitidine at bedtime is not as effective as omeprazole twice daily given before the morning and evening meals at controlling nocturnal acid breakthrough. Further, 1 small trial in healthy subjects without GERD showed that the addition of a 1-time dose of ranitidine at bedtime to a twice-daily regimen of omeprazole may decrease the occurrence of nocturnal acid breakthrough. However, the clinical significance of this finding is not clear. CONCLUSIONS: No studies in patients with GERD demonstrate that the addition of histamine(2) receptor antagonists to twice-daily PPI therapy provides any further benefit above that derived from PPIs alone. The parameter used to measure the efficacy of combination regimens for GERD thus far--nocturnal acid breakthrough--has not been proven to correlate with improvement of GERD symptoms in any controlled or prospective clinical trials. Further investigation is needed to determine optimal therapy in patients refractory to standard doses of PPIs.     

A cost analysis of enterally administered lorazepam in the pediatric intensive care unit

OBJECTIVE: To determine the cost savings of replacing intravenous midazolam with enterally administered lorazepam in mechanically ventilated children who require long-term continuous sedation. DESIGN: Retrospective review of patients treated according to a preestablished pediatric intensive care unit (ICU) sedation protocol. SETTING: Twenty-six-bed pediatric ICU in a tertiary care children's hospital. PATIENTS: The records of 30 mechanically ventilated children were analyzed. The median age was 1.5 yrs and the median weight was 8.0 kg. Patients required continuous sedation for a total of 16 days (median). INTERVENTIONS: According to our pediatric ICU sedation protocol, midazolam infusion was continued until the hourly midazolam requirement was stable for at least 24 hrs. Thereafter, patients with a nasojejunal tube who were likely to require a minimum of three additional days of continuous sedation were transitioned from intravenous midazolam to enterally administered lorazepam. The goal in transitioning therapy was to titrate the lorazepam dose and reduce midazolam administration while maintaining an unchanged level of sedation. MEASUREMENTS AND MAIN RESULTS: The rate of midazolam administration was significantly (p<.05) reduced beginning on day 1 of lorazepam treatment. Midazolam was successfully discontinued in 24 (80%) patients in 3 days (median), and adequate and appropriate sedation was maintained with lorazepam monotherapy. Six patients in whom midazolam could not be discontinued experienced a 52% reduction in the rate of midazolam administration as a result of adding lorazepam. Total projected midazolam utilization was defined as the sum of midazolam administration before initiating lorazepam and the projected midazolam requirement after initiating lorazepam. Projected midazolam cost was calculated as the product of total projected midazolam utilization and midazolam acquisition cost. Actual expenditures for both midazolam and lorazepam were subtracted from the projected midazolam cost to calculate the estimated cost savings. Overall, midazolam utilization (in milligrams) was reduced by 46.7+/-27.6% (median 52). Total projected midazolam cost for the 30 patients was $90,771. The actual cost of midazolam and lorazepam combined was $47,867, resulting in a cost savings of $42,904. CONCLUSIONS: Transitioning from intravenous midazolam to enterally administered lorazepam in critically ill children who require long-term sedation results in significant cost savings. The oral formulation of lorazepam was convenient to use, inexpensive, and effective in maintaining a continuous and appropriate level of sedation once midazolam was discontinued.