PPI Use Research Articles

Long Term Follow up of Patients Treated with Stretta

Purpose: Assess long term durability of Stretta procedure for GERD based on intent to cure criteria. Methods: Telephone and in person interviews were done on 56 of 61 patients who underwent Stretta procedure for GERD from 53 to 60 months previously. The only parameter used to judge long term effectiveness was the use of PPIs, as our intent was to resolve GERD symptoms. Quality of life assessments were not evaluated. Results: Of the 56 patients (92%) available for follow up only 9 (16%) were not using PPI. None of these patients have had post Stretta complaints requiring further evalutions of the esophagus or stomach. Of the 47 patients using PPI, 39 (83%) had 3, 6 and/or 12 month follow up questionnaires that indicated improvement in GERD symptoms, but later needed to resume PPI use. Time to resumption of PPI use in the nonresponders ranged from 0 to 23 months (median 14.6 months). Five patients (10%) developed symptoms of gastroparesis confirmed by nuclear imaging studies. Six patients (13%) required esophageal dilations for dysphagia. One patient in this group had a fundoplication after Stretta. No predictors of a favorable result could be identified based on pre Stretta evaluations with endoscopy, esophageal motility testing or 24 hr pH testing, but the highest DeMeester score in the favorable outcome group was 47.4. Conclusion: The Stretta procedure does not provide durable long term relief for GERD. If the intent of use of the Stretta procedure is to cure GERD symptoms and avoid use of PPIs, only a small percentage of patients can be expected to benefit. A substantial percent of nonresponders require further treatment for dysphagia and gastroparesis

GERD – Maintenance Therapy with PPI v/s “Pre-Emptive Use of PPI”

GERD – Maintenance Therapy with PPI v/s “Pre-Emptive Use of PPI”

Endoscopic Full-Thickness Plication with Two Serially Placed Implants Improves Esophagitis, GERD Symptoms and Reduces PPI Use and Esophageal Acid Exposure

Purpose: Recently, several endoluminal procedures for the treatment of GERD have been introduced. However, most of these techniques have been abandoned due to either lack of long-term efficacy or serious side effects. In a recently published prospective randomized, sham-controlled trial, the Plicator™ (NDO Surgical, Inc.) proved effective at controlling reflux symptoms and reducing medication use and esophageal acid exposure. Methods: In all studies to date, a single Plicator implant was placed to form a full thickness plication of the anterior gastric cardia. However, in several cases the narrowing of the GE-junction remained incomplete with this technique. Therefore, we evaluated the safety and effectiveness of placing two Plicator implants within 1 cm of the anterior GE-junction for the treatment of GERD. Results: 37 patients underwent endoscopic full-thickness plication using two serially placed Plicator implants. At 6 months post-treatment, the proportion of patients achieving >50% improvement in GERD-HRQL score was 68%. Complete PPI cessation was achieved in 59% of patients. In pH studies conducted at 6-months (N = 29), median percent time pH < 4 decreased 36%, with 28% of patients experiencing pH normalization. Erosive Reflux Disease (ERD) was diagnosed in 21 patients before endoscopic full-thickness plication. 16 patients had NERD before endoscopic full-thickness plication. Six months after endoscopic full-thickness plication the number of subjects with ERD was 15 and the number of subjects without esophagitis was 22. There were no serious adverse events observed. Minor adverse events included abdominal pain (73%), sore throat (54%), and chest pain (57%). All adverse events resolved spontaneously without intervention. Conclusion: In this study, endoscopic full-thickness plication using two serially placed Plicator implants was both safe and effective in reducing esophagitis, GERD symptoms, GERD medication use, and esophageal acid exposure. When compared to previous studies using a Plicator single implant technique, the Plicator multiple-implant technique demonstrates a similar safety profile and superior efficacy.

PPI use is associated with an increased risk of community-acquired pneumonia

PPI use is associated with an increased risk of community-acquired pneumonia

Intravenous Versus High-Dose Oral Proton Pump Inhibitor Therapy After Endoscopic Hemostasis of High-Risk Lesions in Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding

Intravenous proton pump inhibitors (IV PPIs) decrease rebleeding following endoscopic hemostasis of bleeding peptic ulcers. Oral PPIs may be equally efficacious and may significantly reduce health care costs. This study aimed to compare outcomes in patients receiving oral versus IV PPI therapy following endoscopic hemostasis in patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB). We performed a retrospective review of all patients who received PPI therapy following endoscopic hemostasis for ANVUGIB. The primary outcome was the adverse gastrointestinal event rate. One hundred sixty-two patients met the entry criteria (72 oral PPIs, 90 IV PPIs). The difference in the rate of adverse gastrointestinal events between the two groups was 1% (P = 0.85). Postendoscopic IV PPI use was associated with an odds ratio of 1.01 for developing an adverse outcome versus oral PPIs (95% CI: 0.44-2.33). We conclude that oral PPIs are probably equivalent to IV PPIs for preventing rebleeding in ANVUGIB patients.

Proton‐pump inhibitor failure/resistance: Proposed mechanisms and therapeutic algorithm

AbstractProton‐pump inhibitor (PPI) failure has become more prevalent with the increasing use of PPI as the first‐line agent in the treatment of gastroesophageal reflux disease (GERD). The underlying mechanisms are diverse and may overlap. The commonly available investigations are limited in their capacity in identifying the underlying cause for PPI failure. Multichannel intraluminal impedance with 24‐h pH sensors may be useful to identify non‐acid or duodenogastroesophageal reflux in selected cases. The management strategy for PPI failure is largely empirical. Patients who have symptomatic failure on normal dose of PPI shall try double dose PPI. Failing that, empirical treatment with transient lower esophageal sphincter relaxation reducers or pain modulators can be tried. Better understanding of the pathophysiology and mechanisms for PPI failure will help to improve the management of this rising problem.

Helicobacter pylori Infection (HP) Is Not Associated with Iron Deficiency in the Adult Population

Purpose: About 27% of the US population and 50% of the world population is infected with HP. Uncontrolled case series and epidemiologic studies based on sero-prevalence rates suggest an association between HP infection and iron store depletion. The aim of this study was to investigate the association between HP and iron deficiency with/without anemia in an adult population with negative endoscopic findings. Methods: This was a retrospective review of patients undergoing upper gastrointestinal endoscopy at the Syracuse VA medical center from Jan 2000 to Feb 2003. CLO test and gastric biopsy results were noted in 600 consecutive patients. HP infection was defined by a positive CLO test and/or positive biopsy result. Patient demographics, medication use and alcohol consumption, laboratory data, and endoscopic findings were recorded. Patients with an identifiable cause of iron deficiency at EGD (179), colonoscopy (48) or both (16); celiac disease (3), and bowel surgery (1) were excluded. An additional 14 patients with repeat EGD and HP testing were omitted. Statistical Analysis: Iron deficiency anemia was defined as hemoglobin (Hb) <11.5 in females and Hb <12.5 in males, ferritin<30 and transferrin saturation <29%. Patient characteristics, laboratory data, and prevalence of iron deficiency anemia was compared in groups with and without HP by student t-test, chi-square and Fisher exact test. Results: 339 patients (68 HP positive and 271 HP negative) were included in the final analyses. The HP negative group had significantly more Caucasians and higher use of PPI (Table 1). Hb, serum ferritin level and prevalence of iron deficiency anemia in both groups was similar (Table 2).Table 1: Patient characteristics in groups with and without HPTable 2: Comparison of laboratory dataConclusions: In adults with negative endoscopic findings, H. pylori infection is not associated with iron deficiency.

Clostridium difficile

Purpose: Recent studies have reported both an increased frequency and severity of C.difficile colitis. To better understand infection risk factors, we are prospectively collecting data on consecutive patients with a positive ELISA assay for Clostridium difficile toxin A and/or B at our institution from November 2005 – June 2006. Methods: Collected data included demographics, recent antibiotics, admission diagnosis, chemotherapy, hospital location, hospital procedures, laboratory data, intubation, PPI use, exposure to hospitalized sources, and laboratory data. Results: We identified 65 patients (7 were outpatients) with C. difficile toxin who agreed to participate. 34 men and 31 women had a mean age of 62.5. 13 patients declined to participate (4 inpatients, 9 outpatients). The antibiotics commonly used included: IV vancomycin 31%, fluoroquinilones 27%, piperacillin/tazobactam 15%. Multiple antibiotics were used in 35%. 37% of patients had a previous hospitalization. 14/65 (22%) patients did not receive antibiotics. Of these 14, 11 had a previous hospitalization without antibiotics, 2 had no risk factors, and 1 visited his wife in a nursing home. 28 patients were using PPIs, 24 patients had renal failure, and 7 patients were intubated. 4 patients died, all from septic complications and 3 of these patients were treated with metronidazole. Of the 61 with C. diificile toxin that resolved, 55 were treated with metronidazole. Conclusions: Our data confirms that there is a strong association of C. difficile with antibiotics, particularly fluoroquinolones and IV vancomycin. In addition to recent antibiotic use, inquiries about recent hospital admision should be included in the case history of a patient evaluated for diarrhea. We also confirm the recent report by the CDC of C. difficile infection in patients at low risk in the community.

One-Year Follow-Up After a Randomized, Sham-Controlled Trial of Endoscopic Gastroplication for the Treatment of Gastroesophageal Reflux Disease (GERD)

One-Year Follow-Up After a Randomized, Sham-Controlled Trial of Endoscopic Gastroplication for the Treatment of Gastroesophageal Reflux Disease (GERD) Matthijs P. Schwartz, Hiske Wellink, Melvin Samsom, Andre J. Smout Previously, we have shown in a randomized, sham-controlled trial that endoscopic gastroplication (EndoCinch suturing system) reduced PPI use and GERD symptoms, and improved quality of life (QoL) after 3 months. Esophageal acid exposure was not significantly reduced compared with sham. The open-label, oneyear results are now presented. Methods: 60 Patients with daily symptoms of GERD and abnormal 24-hr esophageal pH-metry were randomly assigned to either three endoscopic gastroplications (n Z 20), a sham procedure (n Z 20) or observation (n Z 20). Excluded were patients with a hiatal hernia O3 cm or grade C/D esophagitis. At 3 months, after unblinding, 30 patients (sham, n Z 19 and observation, n Z 11) chose to cross over to active treatment. Patients without sufficient symptom relief were offered retreatment at least 3 months after first treatment. Thirty-two patients (23M/9F; mean age 45 years) completed the 12-month follow up and were analyzed. Pre-procedure and post-procedure assessments included PPI use (mean % from baseline dose), GERD symptoms and QoL at 3, 6, 9, and 12 months. Symptoms and QoL were scored 1 week off medications. Esophageal manometry and 24-hr esophageal pH monitoring were repeated at 3 months. Results: Ten of the 32 patients (31%) were retreated after a median follow-up of 4.0 (range 3-7) months with a mean of 1.3 extra plications. At 3, 6, 9 and 12 months, PPI use was reduced to 33%, 37%, 38% and 41% from baseline (P ! 0.0001 for all), respectively. 23 Patients (72%) improved upon intervention (defined as a R50% reduction in PPI use at 12 months). GERD symptoms heartburn and regurgitation improved up to 12 months follow-up (Table). Three of six SF-20 QoL subscales improved: physical function (P Z 0.02), general health (P ! 0.01) and pain perception (P ! 0.001). Esophageal acid exposure (% pH ! 4) decreased from 9.1% to 7.2% at 3 months (n Z 20), but this was not statistically significant (P Z 0.10). Manometry outcomes did not change after treatment. One serious adverse event occurred: a mucosal tear requiring short clinical observation. Conclusions: After one year, endoscopic gastroplication reduces PPI use, improves GERD symptoms and quality of life in a majority of patients, although the reduction in esophageal acid exposure is small and a considerable number of patients require retreatment. Table. Effect of treatment on GERD symptoms

Endoscopic Injection of Durasphere for the Treatment of GERD - Long Term Human Pilot Study

Background: Endoscopic treatment of gastroesophageal reflux (GERD) remains suboptimal. The ideal endoscopic therapy for GERD should be safe, efficacious, durable, and easy to perform with minimal discomfort. The aim of this study was to demonstrate the feasibility, safety, and antireflux efficacy of submucosal augmentation, at or just below the squamocolumnar junction, with a biocompatible, nonmigratory, nonabsorbable pyrolytic carbon-coated bead suspension (Durasphere®. Methods: Ten GERD patients (mean age 40), with heartburn symptoms responsive to PPI use were enrolled. Clinical assessment included: endoscopy, esophageal manometry, Bravo pH monitoring, heartburn diary, and GERD-HRQL severity scoring at baseline, 3, 6, and 12 months. The procedure was performed in an outpatient endoscopy clinic using conscious sedation. Durasphere® was injected into the submucosal space, using a sclerotherapy catheter in two sets of 1-2 cc four quadrant injections, at and just below the squamocolumnar junction. The mean initial injection volume of Durasphere was 8.6 (4.7-13.9) mls. 3 patients who experienced incomplete symptom relief were reinjected. Outcome measures included PPI use, change in GERD-HRQL symptom scores, change in Bravo pH scores, and adverse events. Results: 12 month data is pending. At 6 months, 80% of patients had reduced their PPI dose by ≥50% compared to baseline, and 70% eliminated PPI use entirely (p < .001). The mean GERD-HRQL symptom score was 26.9 at baseline (off PPI) and 9.1 at follow-up - a 66% reduction (p < .002). Bravo pH results were available on eight patients. The mean percent total time with pH ≤ 4 for these patients was 14.2 at baseline and 9.9 following injection, a 30% reduction (p < .066). Symptomatic reflux episodes improved from an average of 46.7 at baseline to 6.6 episodes at follow-up - a reduction of 86% (p < .011). 3 of 8 patients normalized their DeMeester score. There were no serious adverse events. Transient (<12 hours) mild epigastric discomfort was reported by 60% of the patients but did not require analgesia. There was no dysphagia, and all patients resumed a regular diet within a few hours of the procedure. The technique was rated as “simple” by the endoscopist. Conclusions: Endoscopic injection of Durasphere into the submucosal space, at the GE junction, is a feasible, new method for the treatment of GERD. This preliminary clinical study has shown that Durasphere is technically simple, has excellent short-term efficacy and can be safely performed in an outpatient endoscopy clinic. Further study of this technique, evaluating a larger number of patients in the setting of a 1 year controlled trial is warranted.

Non-Cardiac Chest Pain (NCCP): Is It Really Non-Cardiac?

Introduction: Pts admitted for observation to the coronary care unit have chest pain that warrants investigation. Despite the scarcity of published data documenting the etiology of such symptoms, the esophagus is guilty by default if coronary angiography is reported as negative. We reasoned that the origin of NCCP should eventually make itself known: the characteristics and survival should be similar to a GERD group, if esophageal, or a Coronary Artery Disease group, if cardiac. Purpose: To determine whether the characteristics and long-term outcomes of Pts with NCCP are similar to those of Pts with GERD or Coronary Artery Disease. Methods: All Pts with NCCP from 1984 to 1996 who were referred for EGD by cardiology service after coronary angiography was interpreted as negative for cardiac-induced chest pain were included. Pts with GERD were referred for EGD for one of the usual symptoms of acid reflux. The baseline for all patients occurred in the pre-PPI era. Thus, the endoscopic findings reflected the natural state of the mucosa. Pts were followed in their usual outpt medical clinics. The VA DHCP computer system provided access to mortality data as well as details of all prescriptions filled since 1985. The 2 groups of pts were compared with regard to age, ethnic, smoking, and use of alcohol, ASA/NSAID's and PPI's. The prevalence of erosive esophagitis at baseline and any follow up EGDs, presence of hiatal hernia and hernia size were examined as factors related to GERD. Enrollment in cardiology clinic, use of cardiac meds and a diagnosis of CAD in the medical record were considered factors related to CAD. Results: During the study period, 1218 pts with GERD and 161 with NCCP underwent EGD. The mean follow-up period ranged from 1-22 years (mean 9.8 years). The groups were similar in age, gender, smoking and alcohol habits, but significantly greater proportion of Blacks were in the NCCP group vs the GERD group (17% Vs 11%: X2 = 4; P = 0.03). In every parameter, NCCP pts had significantly less evidence of the GERD factors (X2 = 140, P < 0.0001) and significantly more evidence of the cardiac factors (X2 = 426, P < 0.0001) (figure). The amount and duration of PPI therapy was significantly less in the NCCP group (31.0 months Vs 43.9 months: Diff = 12.9; CI = 8.2-17.6). There was no difference in survival curves for both groups. Conclusion: Pts referred for NCCP and for GERD are different with respect to factors related to GERD and CAD. This difference strongly suggests a non-GERD-related cause of the NCCP. This difference strongly suggests that cardiac factors contribute to NCCP.

Inappropriate Use of Intravenous Pantoprazole: Extent of the Problem and Successful Solutions

Indications for intravenous proton pump inhibitors (IV PPI) include upper gastrointestinal bleeding (UGIB) from peptic ulcer disease with high-risk stigmata and patients receiving nothing by mouth (NPO). The objectives were to assess the extent of errors in indications for IV PPI use and to determine whether multidisciplinary interventions could improve IV PPI use and costs. Part 1: Patients prescribed IV PPI during a period of 4 months were divided into 2 settings, UGIB or non-UGIB. The setting-specific appropriateness of the IV PPI indication and dosing regimen was determined. Part 2: Patients prescribed IV PPI before and after multidisciplinary interventions (educating physicians, a computerized dose template, pharmacists altering IV PPI orders in non-UGIB patients who were not NPO, and recommending a GI consult when a continuous infusion was ordered) were studied. Incidence of prescribing errors, IV PPI costs, and potential confounders were compared. Part 1: Only 50% of UGIB (n = 145) patients received IV PPI for an appropriate indication. Both indication and dosing regimen were appropriate in 21%. In the non-UGIB group (n = 95), 33% were truly NPO; 51% had a correct dosing frequency. Part 2: The postintervention (n = 105) group (vs the preintervention group, n = 113) showed a significant absolute reduction in the degree of inappropriate indication in the UGIB (26%; 95% confidence interval [CI], 10%-42%; P < .0001) and in the non-UGIB (41%; 95% CI, 24%-58%; P < .0001) subgroups. However, a greater improvement in underspending than overspending meant that overall costs were unchanged. IV PPI was frequently prescribed inappropriately and incorrectly; simple maneuvers resulted in reductions in errors.

Comparing 2 Revolutions

Purpose: H. pylori eradication has revolutionized the management of peptic ulcer disease. A second major revolution occurred when COX-2 selective inhibitors were introduced in 1999 with a GI safety advantage. We assessed the impact of COX-2 selective inhibitor use by examining trends of hospitalizations due to complicated gastric (GU) and duodenal ulcers (DU) over a period of 11 years and relating them to the total prescriptions of NSAIDs, H. pylori eradication, and PPI use. Methods: The Nationwide Inpatient Sample (NIS) is a stratified random sample of US community hospitals with information on all inpatient care regardless of insurance status. We studied all inpatient hospitalizations in NIS from 1990 to 2001 with a primary diagnosis of complicated GU, DU, or peptic ulcer disease (PUD) with hemorrhage, perforation, and/or obstruction, and analyzed them as a proportion of total NSAID prescriptions (data from IMS) during the same time. Results: From 1990–2001 there were 423,558,416 hospitalizations in 3.2 billion person-years of observation. Of these, 1,865,687 hospitalizations (0.44% of total) were for a primary diagnosis of a complicated GU, DU, or PUD (58.4 per 100,000 US population). During this time, there were 982.2 million NSAID prescriptions in the US. Annual NSAID prescriptions increased from 67.6 million (1990) to 112.8 million (2001), with the largest increase from 1998 (79.2 million) to 2001 (112.8 million). PPI prescriptions rose from 3.9 million in 1992 to 73.6 million in 2001. Complicated GU, DU, or PUD hospitalizations declined from 163,173 in 1990 to 139,597 in 2001. The rate of GU, DU or PUD hospitalizations per 100,000 NSAID prescriptions declined by almost 50%, from 241.5 in 1990 to 123.8 in 2001 (P < 0.0001). While such hospitalizations declined steadily from 1992 (perhaps reflecting PPI use), there were 2 periods of additional sharp declines: the first (10.8%, 1995) following the NIH consensus conference recommending H. pylori eradication, and the second (22.4%, 1999) after the introduction of COX-2 selective inhibitors. Conclusions: These data strongly suggest that the introduction of H. pylori eradication therapy, increasing use of PPIs and the introduction of COX-2 selective inhibitors account for the trend toward fewer hospitalizations for complicated ulcer disease in the US. The impact of COX-2 selective agents on ulcer hospitalizations and mortality is twice as much as that of H. pylori eradication.

Long-Term Follow Up of Endoluminal Anti-Reflux Procedures for GERD: Single-Center Experience with 3 Procedures

During the last few years, a number of endoscopic anti-reflux procedures (EARP), aiming at per-endoscopic improvement of the barrier function at the lower esophageal sphincter (LES), have emerged. Techniques include creation of plications (Endocinch® or ESD®), injection of inert material (Enteryx®) or delivery of radiofrequency-energy (Stretta®), and several studies reported short-term efficacy. The aim of this study was to evaluate the long-term efficacy of EARP on symptoms, anti-secretory drug use and pH monitoring in a single center. Methods: All GERD patients who underwent EARP at our center before 2004 were prospectively followed using endoscopy, pH monitoring, and questionnaires for heartburn and PPI use. All data are given as mean±SD and were analyzed by paired Student's t test. Results: Seventy-one patients underwent a Endocinch® or ESD® (n = 36), Enteryx® injection (n = 7) or a Stretta® procedure (n = 28). After a mean follow up of 2.5 ± 0.8 years, reflux scores had significantly improved in the Endocinch®/ESD® and Stretta® groups (table), but none of the procedures led to an important decrease of acid exposure. PPI use was stopped in only 14 to 32% and reduced in 14 to 22%. Long-term complications were loss of sutures in the Endocinch® group (2.0 ± 0.4 to 1.5 ± 0.8 after one year, p< 0.05) and oesophageal stenosis requiring repeated dilations (n = 10) in one Enteryx® patient. Fourteen patients (20%) were referred for anti-reflux surgery. Conclusion: In spite of significant symptom improvement, long-term evaluation after EARP in this single-center experience showed ongoing PPI use in the majority of patients and lack of normalisation on pH monitoring. Additional studies are needed to determine which patients, if any, may respond to these procedures.

Efficacy of Enteryx® in Post Fundoplication Patients

Objectives: This study was aimed to assess the efficacy of endoscopic implantation of nonresorbable biocompatible polymer (Enteryx®) in post fundoplication patients with recurrent/continued GERD. Methods: Physicians with experience using Enteryx were questioned about use in fundoplication patients. 19 GERD patients who had prior fundoplications were identified who underwent endoscopic Enteryx implantation. Most patients had refractory symptom while on high dose PPI therapy. Follow up HRQL symptoms and PPI used evaluations were performed at minimum 4 weeks later. Results: 19 patients had undergone a mean of 1.5 fundoplications/patient (range 1-3). Mean 24-hour pH total reflux time ≤4 was 27.4% pre treatment. Patients underwent a mean of 1.2 Enteryx implant sessions and received a mean of 6.9 ml Enteryx/session. All implantations were performed in standard fashion without apparent difficulty from the fundoplication wrap. Mean follow up time was 15 weeks (range 4-52). Of patients followed more than 4 weeks, 10/15 (66%) patients reduced dosage of PPI ≥ 50%. Heartburn and regurgitation HRQL scores mean were 19 and 9 before treatment on medication and were 14 and 6 post treatment at latest follow up on the same or reduced medication respectively. Overall 16/18 patients who answered the questionnaire reported “improved status.” Further treatment sessions are planned for several of these patients. Summary: Enteryx implantation is technically achievable in fundoplication patients without apparent difficulty. In this difficult to manage refractory symptom, postoperative group, partial improvement in PPI use and symptoms was seen. Conclusions: Enteryx is an available alternative therapy for treatment of GERD patients with continued symptoms after fundoplication. Longer-term follow up and prospective randomized controlled studies are awaited in this difficult patient management group.

Programme to control PPI use saves $US20 million

Programme to control PPI use saves $US20 million

Programme to control PPI use saves $US20 million

Programme to control PPI use saves $US20 million

The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting. Analysis of randomly selected patients endoscoped for nonvariceal upper gastrointestinal bleeding at 18 community and tertiary care institutions between 1999 and 2002. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression models identified predictors of outcomes. One thousand eight-hundred and sixty-nine patients were included (66 +/- 17 yr, 38% female, 2.5 +/- 1.6 comorbid conditions, hemoglobin, 96 +/- 27 g/L, 54% received a mean of 2.9 +/- 1.7 units of blood). Endoscopy was performed within 24 h in 76%, with ulcers (55%) most commonly noted. High-risk endoscopic stigmata and endoscopic therapy were reported in 37%. Rebleeding, surgery, and mortality rates were 14.1%, 6.5%, and 5.4%, respectively. Decreased rebleeding was significantly and independently associated with PPI use (85% of patients, mean daily dose 56 +/- 53 mg) in all patients regardless of endoscopic stigmata, (odds ratio (OR):0.53, 95% confidence interval, 95% CI:0.37-0.77) and endoscopic hemostasis in patients with high-risk stigmata (OR:0.39, 95% CI:0.25-0.61). PPI use (OR:0.18, 95% CI:0.04-0.80) and endoscopic therapy (OR:0.31, 95% CI:0.11-0.91) were also each independently associated with decreased mortality in patients with high-risk stigmata. These results appear to confirm the protective role of endoscopic therapy in patients with high-risk stigmata, and suggest that acute use of PPIs may be associated with a reduction of rebleeding in all patients, and lower mortality in patients with high-risk stigmata. Independent prospective validation of these observational findings is now required.

Use of intravenous proton pump inhibitors in community practice: an explanation for the shortage?

Since 2001, one intravenous proton pump inhibitor (pantoprazole) has been available in the United States. A drug shortage bulletin was issued for this agent in 2003. To evaluate the patterns of use of intravenous proton pump inhibitors (IV PPIs) in routine clinical practice. Prospective evaluation of IV PPI use in two community-based teaching hospitals. A computerized pharmacy ordering system was used to identify all patients for whom an IV PPI was ordered. Trained investigators obtained clinical data from patient records and these data were mapped to establish clinical criteria for the use of IV PPIs. Intravenous PPIs were prescribed in 238 patients over a 30-day period and a total of 1,631 doses were prescribed. Primary care providers prescribed 46% of prescriptions. Fifty-six percent of patients who received IV PPIs had no acceptable indication for their use. Of the 126 (81%) patients who were started on PPIs for the first time during their hospital stay, 102 were discharged on a PPI. Intravenous PPIs are widely used for poor indications, which may contribute to the shortage of these agents.

Reply

Sirs, We appreciate the opportunity to discuss the important issue of research support by industry and to highlight the features of our guideline development that make it of highest methodological quality, regardless of the source of support. We also found it ironic that Dr Graham suggested that industry support indicates that we were ‘willing, trusting, and possibly naïve’ tools of the study's sponsor. Review of Dr Graham's publications in the past 2 years reveals four articles assessing medications1-3 or a diagnostic test4 for which support was provided by the manufacturer of the product. Most articles published as guidelines, even those of the US national GI organizations, are not properly developed guidelines, but rather reviews by an author or authors who then make recommendations based on the results of their review. However, a guideline is far different from a systematic review.5 A panel representing all appropriate groups, including experts and front-line clinicians, rather than just a single subspecialty should be convened. Panels should not be so small as to fail to provide adequate opinions but not so large as to be unwieldy; six to 15 members has been recommended. The panel considers the available evidence and decides on its implications, making value judgments about possible outcomes – considering not only clinical outcomes but adverse events, cost, patient preferences, quality of life and practicality. Then, the panel synthesizes their opinions based on the available evidence to develop practice recommendations. This is the step of greatest weakness in most guidelines because there is no defined or objective process for this step in place for most guideline development panels. As mentioned in our Methods we went to great lengths to select a diverse panel of appropriate size, including a balanced composition of experts and primary care physicians, academics and community practice, and geographic sites. Recommendations for gastroenterologists and rheumatologists were obtained from the respective national organizations. Dr Graham suggests that we failed to include misoprostol in our assessment as a result of the sponsorship by a PPI company. We strongly considered inclusion of misoprostol in our clinical scenarios, and the sponsor had no input on our exclusion of this agent. Rather, our prior studies6, 7 had revealed that misoprostol is rarely used in the USA (misoprostol and sucralfate usage combined represents only 3–6% of all GI co-therapy with NSAIDs). This may well be due to the need for more frequent dosing and the significant increase in diarrhoea and days with abdominal pain with misoprostol, documented in Dr Graham's study.3 The guideline panel did not believe it necessary or practical to assess clinical scenarios employing a drug that is not used by the US physicians. Furthermore, the efficacy of PPIs in NSAID users has not only been documented in endoscopic studies, as suggested by Dr Graham. Large randomized trials from Hong Kong have documented significant reduction in complicated ulcers with PPI use.8, 9 Finally, perhaps the greatest strength of our guideline development relative to most other similar endeavours is our use of the Rand /UCLA Appropriateness Methodology. Guideline panels commonly review evidence and then develop recommendations via an undefined ‘black box’ process. In contrast, our methodology provides a transparent, objective, quantifiable, and validated method for a panel to develop guideline recommendations. Thus, we believe this guideline was developed using methodology superior to the guidelines sponsored by the ‘unbiased’ US National GI Organizations and that our process and article would have been the same regardless of the sponsor.