The status of proton pump inhibitor use: a prescription survey of 45 hospitals in China.

BACKGROUND: proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. OBJECTIVE: to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. MATERIALS AND METHODS: PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. RESULTS: in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. CONCLUSION: this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs.

Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects.

Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (~)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.

Possible drug-drug interaction between high-dose esomeprazole and phenprocoumon.

PURPOSE: It is established that omeprazole increases (R)+ warfarin levels with around 10 %. Whether (es)omeprazole also increase the plasma levels of acenocoumarol or phenprocoumon is still uncertain. We analyzed whether addition of (es)omeprazole to acenocoumarol or phenprocoumon increases the international normalized ratio (INR) levels and the risk of overanticoagulation. METHODS: We analyzed all hospital admissions in four teaching hospitals. Patients who used coumarins and pantoprazole or (es)omeprazole simultaneously for at least four consecutive days were included in the study. We analyzed the highest INR level and whether patients had an INR level above six. We compared patients using omeprazole or esomeprazole with patients using pantoprazole, because for pantoprazole, no interaction has been reported. RESULTS: We analyzed 5747 admissions with 4540 patients using one of the drug combinations. For acenocoumarol (4578 admissions), no significant differences were found between users of esomeprazole, omeprazole, and pantoprazole. For phenprocoumon (1169 admissions), the highest INR measured was significantly higher in users of esomeprazole than in users of pantoprazole (4.7 versus 4.3; p = 0.035). No significant difference was found with omeprazole versus pantoprazole (4.3 versus 4.3; p = 0.66). A non-significant association was found between the esomeprazole dose and the highest INR level (p = 0.055). The risk of an INR above six did not differ significantly between esomeprazole and pantoprazole (27.7 % versus 22.9 %; p = 0.34). CONCLUSIONS: The use of esomeprazole simultaneously with phenprocoumon during hospital admissions might increase the anticoagulant effect. The clinical relevance seems to be limited, because no statistically significant increased risk of overanticoagulation was found.

[Proton Pump Inhibitor and High-dose Methotrexate: Two Cases Reports]. / Inhibiteurs de pompe à proton et méthotrexate haute dose : à propos de deux cas.

Methotrexate (MTX) is a cytotoxic agent prescribed at high dose in treatment of malignancy. Association of MTX to proton pump inhibitor (PPI) is not recommended if doses are more than 20 mg per weeks and only to take into account for smaller doses. Review relate some cases of delayed elimination of methotrexate in patients taking PPI, which increase risk of toxic event. However, currently there is no status quo on interaction between PPI and MTX according to available data. We report two clinical cases illustrating one more time a toxic event to MTX in presence of PPI. In absence of risk/benefit ratio set correctly, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk.

Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress.

BACKGROUND: The incidence of upper gastrointestinal bleeding from stress ulcers has decreased within the last 30 years. Improvements in intensive care medicine including advanced equipment for artificial ventilation, better sedoanalgesic therapies, and the use of stress ulcer prophylaxis are credited for the decline. OBJECTIVES: To determine the effectiveness of proton pump inhibitors (PPIs) on gastric pH in patients exposed to a defined severe stress situation during a specified time period. METHODS: Prospective open study in a tertiary community hospital. A high dose (80 mg bolus followed by 8 mg/h) of either pantoprazol or omeprazol was infused in 17 patients with opiate dependence who were undergoing ultra-rapid opiate withdrawal by barbiturate anesthesia. MEAN OUTCOME MEASURE: Gastric pH. RESULTS: Gastric pH did not change significantly in the majority of patients (mean pH 1.2 ± 0.9 immediately before, 1.5 ± 1.6 at 60 min after, and 1.3 ± 1.5 at 120 min after PPI infusion began). Gastric pH increased temporarily in two of the nine patients receiving omeprazol. In two of the eight patients, pantoprazol led to a late but sustained increase in gastric pH (pH 3.9 and 6.0 at 120 min post infusion). CONCLUSION: High doses of PPIs are ineffective in elevating gastric pH in patients exposed to severe stress such as ultra-rapid opiate detoxification. Therefore, adequate sedoanalgesia might be the main factor responsible for preventing stress-related bleeding in critically ill patients.

Effect of Perilla frutescens fixed oil on experimental esophagitis in albino Wistar rats.

The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats (n = 6), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, n - 3) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis.

The pharmacokinetics of ilaprazole for gastro-esophageal reflux treatment.

INTRODUCTION: Approximately 20% of the Western population is affected by gastro-esophageal reflux disease (GERD). To date, proton pump inhibitors (PPIs) represent the mainstay of GERD medical treatment. However, despite their undoubted benefit, about 40% of GERD patients display an inadequate response to these drugs. Recently, a new PPI, ilaprazole , at oral doses of 10 mg has shown higher suppression of gastric acid secretion, more prolonged plasma half-life, and similar safety compared to 20 mg omeprazole. AREAS COVERED: This review provides an update on the following points: pharmacokinetic profile and metabolism of ilaprazole in relation to its pharmacodynamic properties; comparative data on the pharmacokinetics and pharmacodynamics of ilaprazole with currently available PPIs; and implications for studies on the therapeutic efficacy of ilaprazole in GERD. EXPERT OPINION: Different studies show that ilaprazole, a benzimidazole derivative, has an extended plasma half-life in comparison with all other approved PPIs. In addition, ilaprazole metabolism is not significantly influenced by CYP2C19, compared to the available PPIs. Furthermore, the pharmacological characteristics of ilaprazole confer theoretical advantages that are expected to translate into an improved acid control, particularly at night time. However, studies comparing the clinical pharmacokinetics and pharmacodynamics of ilaprazole with those of second-generation PPIs are insufficient. Moreover, further investigations assessing the efficacy of ilaprazole in the management of GERD are required. In healthy volunteers, as well as in patients with gastric or duodenal ulcers, ilaprazole has not shown clinically relevant changes in hematology and biochemistry testing, nor significant treatment-related adverse symptoms.

Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection.

BACKGROUND: The decreasing efficacy of H. pylori eradication treatments over time makes the search for better regimens and adjuvant medications a priority. AIM: To conduct a meta-analysis of studies comparing rabeprazole or esomeprazole with other proton pump inhibitors (PPI) or with each other in H. pylori eradication treatment. SELECTION OF STUDIES: Randomised clinical trials comparing esomeprazole or rabeprazole with first-generation PPIs (omeprazole-lansoprazole-pantoprazole) or with each other. RESULTS: The meta-analysis (35 studies, 5998 patients) showed higher eradication rates for esomeprazole than for first-generation PPIs: 82.3% vs. 77.6%; OR = 1.32(1.01-1.73); NNT = 21. Rabeprazole also showed better results than first-generation PPIs: 80.5% vs. 76.2%; OR = 1.21(1.02-1.42); NNT = 23. PPI dosage sub-analysis: only esomeprazole 40 mg b.d. improved results [83.5% esomeprazole vs. 72.4% first generation; OR = 2.27(1.07-4.82); NNT = 9]. Whereas rabeprazole 10 and 20 mg b.d. maintained results, esomeprazole 20 mg b.d. obtained lower efficacy. Esomeprazole vs. rabeprazole sub-analysis (five studies): no significant differences were found: 78.7% vs. 76.7%; OR = 0.90(0.70-1.17). CYP2C19 sub-analysis: Genotype did not significantly affect eradication either in first [OR = 1.76(0.99-3.12)] or new generation [OR = 1.19(0.73-1.95)] PPIs. However, sub-analysis considering only extensive metaboliser patients showed higher eradication with new-generation PPIs [OR = 1.37(1.02-1.84)]. CONCLUSIONS: Esomeprazole and rabeprazole show better overall H. pylori eradication rates than first-generation PPIs. This clinical benefit is more pronounced in esomeprazole 40 mg b.d. regimens. In CYP2C19 extensive metabolisers, new-generation PPIs are more effective than first-generation PPIs for H. pylori eradication. However, a general recommendation of using new-generation PPIs in all scenarios remains unclear.

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction.

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the ¹³C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy.

BACKGROUND: High dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy. METHODS: Patients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month. RESULTS: From April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50) in the intravenous group and 4% (2/50) in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01). CONCLUSION: Patients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed. TRIAL REGISTRATION: NCT01123031.

Multiple-antibiotic-resistant Helicobacter pylori infection eradicated with a tailor-made quadruple therapy.

In 2008, a 44-year-old woman with mild epigastralgia diagnosed as having Helicobacter pylori-positive chronic gastritis without peptic ulcer underwent eradication therapy with lansoprazole (LPZ), amoxicillin (AMPC) and clarithromycin (CAM) for 7 days, but it failed, so treatment with rabeprazole, AMPC, and metronidazole (MNZ) for another 7 days was given, but it also failed. She was then prescribed a modified, 14-day sequential therapy of LPZ and AMPC with an increased dose of CAM followed by MNZ supplement, but the infection was still not eradicated. The H. pylori was cultured and examined for antibiotic susceptibility with the agar dilution method and was found to be resistant to CAM, MNZ, and levofloxacin, and non-sensitive to AMPC, namely multiple-antibiotic-resistant, although sensitive to minocycline. The CYP2C19 genotype of the patient was an extensive metabolizer (G681A: G/A, G636A: G/G). In 2010, she gave informed consent for a 14-day, tailor-made, modified classical (or modified high-dose PPI + AMPC) quadruple therapy comprising 30 mg LPZ, 500 mg AMPC and 500 mg bismuth subnitrate, qid, and 100 mg minocycline, bid. Two months later, her urea breath test was negative. Histology and bacterial culture were still negative 1 year after the therapy. She did not have any adverse events during or after the novel therapy, nor did she feel any further epigastralgia.

In vitro release profile of anti-ulcer drug rabeprazole from biocompatible psyllium-PVA hydrogels.

The present article discusses the synthesis, characterization and haemocompatibility behaviour of the psyllium-PVA hydrogels prepared by chemical method in the presence of N,N'-methylenebisacrylamide. These hydrogels have been characterized by Fourier Transform infrared spectroscopy, thermo gravimetric analysis, swelling and drug release studies. The release of model drug rabeprazole sodium from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism. Psyllium itself acts as anti-ulcer agent and release of rabeprazole from the drug loaded hydrogels may enhance the curing potential of the drug delivery device. The haemocompatibility was evaluated by studying the blood interactions with hydrogels with reference to thrombogenicity and haemolytic potential. Thrombogenicity results indicate that hydrogels are non-thrombogenic as the weight of clot formed and thrombus percentage for hydrogels was less than the positive control. The haemolytic index has been observed <5%. These observations indicate that these hydrogels are haemo-compatible and hence could be used for oral administration of antiulcer drugs.

Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan.

BACKGROUND: To seek a promising therapeutic regimen for proton pump inhibitor (PPI)-refractory patients with gastroesophageal reflux disease (GERD) after the standard PPI treatment, we compared the efficacies of rikkunshito (a Japanese traditional medication) combined with rabeprazole (RPZ) and a double dose of RPZ in a prospective randomized multicenter trial in Japanese PPI-refractory GERD patients. METHODS: One hundred and four patients with GERD symptoms remaining after 4-week treatment with RPZ (10 mg/day) were randomly assigned to 4 weeks of either combination therapy [rikkunshito (7.5 g/day) with a standard dose of RPZ (10 mg/day)] or a double dose of RPZ (20 mg/day). The primary endpoint was the improvement rate, calculated based on the frequency scale for the symptoms of GERD (FSSG) before and after treatment. Subgroup analysis was also performed with respect to each subject's background factors such as reflux esophagitis (RE)/non-erosive GERD (NERD), age, gender, and body mass index (BMI). RESULTS: Four-week treatment with rikkunshito combined with RPZ significantly decreased the FSSG score from 17.6 ± 6.5 to 12.0 ± 6.9, similar to the decrease seen on treatment with a double dose of RPZ. Regarding the therapeutic improvement rate, there were also significant effects in both groups. However, in the subgroup analysis based on RE/NERD, the improvement rate of male NERD patients in the rikkunshito group was significantly greater than that of such patients in the other group (P < 0.05). In the rikkunshito group, the treatment was more effective in NERD patients with a low BMI than in those with a high BMI (P < 0.05). CONCLUSION: Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients.

Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett's oesophagus for 1 year.

BACKGROUND: Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus. AIM: To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. METHODS: Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL. RESULTS: In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). CONCLUSIONS: Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole.

Moxifloxacin-tetracycline-lansoprazole triple therapy for first-line treatment of Helicobacter pylori infection: a prospective study.

AIM: To document the efficacy and tolerability of 14-day moxifloxacine-tetracycline-lansoprazole (MTL) regimens for Helicobacter pylori (Hp) eradication as a first-line therapy. METHOD: Fifty-six Hp-positive patients were enrolled. Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and Hp infection was diagnosed through histologic examination of antral and body bioptic samples. Primary end point of this study was to evaluate the eradication rate of 14-day MTL regimen therapies. Hp eradication was assessed using the 13C urea breath test performed. All patients were asked to fill in a validated questionnaire to report therapy-related side effects. Each symptom was graded from absent or present. RESULTS: Fifty-six patients (29 men and 27 women) were enrolled. The studied therapeutic regimens were completed by 96.4% patients. Two dropouts occurred in the MTL group because of side effects. The eradication rate in MTL regimens was 55.4%. The overall prevalence of side effects was high in the MTL group. CONCLUSION: The MTL regimen failed to achieve the recommended eradication rates and had higher adverse effect rate. Hence, MTL regimen does not seem to be a suitable choice as a first-line Hp eradication therapy.

Kefir improves the efficacy and tolerability of triple therapy in eradicating Helicobacter pylori.

Preliminary evidence has suggested that probiotics may improve eradication rates in patients infected with Helicobacter pylori treated by triple therapy. This study examined the effect of combining triple therapy with kefir, a fermented milk drink containing probiotics. A randomized, double-blind study was carried out on 82 consecutive patients with symptoms of dyspepsia and H. pylori infection confirmed by the urea breath test. Patients were given a two times a day, 14-day course of lansoprazole (30 mg), amoxicillin (1,000 mg), and clarithromycin (500 mg) with either 250 mL of kefir twice daily (triple therapy + kefir, n = 46) or 250 mL of milk containing placebo (triple therapy + placebo, n = 36). Side effects were determined using a standard questionnaire form at 15 days after beginning treatment. Patients returned for urea breath tests 45 days after beginning treatment. Significantly more triple therapy + kefir patients achieved eradication (36 of 46 [78.2%]) compared with triple therapy + placebo patients (18 of 36 [50.0%]) (P = .026, χ(2) test). Side effects were significantly less frequent and less severe in triple therapy + kefir patients than in triple therapy + placebo patients. We conclude that a 14-day regimen of triple therapy with kefir is more effective in achieving H. pylori eradication than is triple therapy alone.

The effects of three alternative treatment strategies after 8 weeks of proton pump inhibitor therapy for GERD in children.

OBJECTIVES: The purpose of this 24-week treatment study was to evaluate the effects of three treatment strategies after 8 weeks of lansoprazole therapy for gastroesophageal reflux disease in children. DESIGN: Open-labelled, uncontrolled, prospective study. SETTING: Samsung Medical Center, Seoul, Korea. METHODS: 37 erosive reflux disease (ERD) and 20 non-erosive reflux disease (NERD) patients were divided into three groups by symptom assessment at 8 weeks: (1) observation without treatment in the 'symptoms-resolved' group, (2) 'on-demand' treatment for an additional 16 weeks in the 'symptoms-attenuated' group and (3) continuous treatment in the 'symptoms-persistent' group. RESULTS: For ERD, six (100%) out of six patients in the 'symptoms-resolved' group remained improved at weeks 16 and 24. Sixteen (72.7%) out of 22 patients in the 'symptoms-attenuated' group had improvement of symptoms at 16 weeks, and 18 (81.8%) patients at 24 weeks. Six (66.7%) out of nine patients in the 'symptoms-persistent' group remained improved at weeks 16 and 24. For NERD, seven (100%) out of seven patients in the 'symptoms-resolved' group remained improved at weeks 16 and 24. Eight (80.0%) out of 10 patients in the 'symptoms-attenuated' group remained improved at week 16, and 10 (100.0%) patients at week 24. None out of three patients in the 'symptoms-persistent' group remained improved at weeks 16 and 24. CONCLUSIONS: The selection of each alternative for long-term management according to the results of the assessment of symptoms at week 8 was useful and well tolerated. 'On-demand' therapy was equally effective. The 16-week therapy had the same efficacy as the 24-week therapy with regard to long-term lansoprazole treatment.

A purging procedure for pantoprazole and 4-lumen catheters to prevent IV drug incompatibilities.

OBJECTIVE OF THE STUDY: The purpose of this prospective intervention study was to assess the number of patients with Y-site incompatibilities before and after implementation of quality improvement measures to prevent incompatibilities consisting of a focused instruction for pantoprazole as a drug frequently involved in incompatible drug pairs and of a recommendation to use 4-lumen instead of 3-lumen catheters to increase the number of available central infusion lines. SETTING: Cardiovascular intensive care unit where several standard operating procedures (SOPs) dealing with compatibility were already in place. METHOD: In a prospective intervention study, patients' IV medication was assessed for potential incompatibilities using a database containing compatibility information on approximately 60,000 drug pairs. In a first period, routine administration was monitored in 53 consecutive patients (control group). Then, quality improvement measures were implemented recommending a purging procedure before and after bolus administration of pantoprazole as a drug frequently causing incompatibilities in this setting. Additionally, the use of 4-lumen instead of 3-lumen catheters was suggested whenever considered useful by the responsible physicians. The monitoring was repeated during a second period in another 58 patients consecutively admitted to the same unit (intervention group). MAIN OUTCOME MEASURE: Overall number of patients with at least one incompatible drug pair and number of patients receiving incompatible pantoprazole combinations. RESULTS: The number of patients receiving incompatible pantoprazole combinations decreased from 15 of the 15 patients receiving pantoprazole (100.0%) in controls to 9/16 (56.2%) in the intervention group (P < 0.01). The overall number of patients with incompatibilities was not influenced by the intervention with 36/58 (62.1%) compared to controls with 38/53 (71.7%, P = 0.28). The fraction of central lines contributed by four lumen central catheters was larger due to the intervention (80/168 lines, 47.6%) compared to controls (16/184, 8.7%, P < 0.001). Only sporadically there were incompatible combinations of drugs governed by the already existing SOPs. CONCLUSION: In an intensive care setting with good SOP adherence, purging before and after administration decreased the respective incompatibility rate whereas the use of 4-lumen instead of 3- lumen catheters had not the expected benefit on separating drug pairs.

Effect of the mucolytic erdosteine on the success rate of PPI-based first-line triple therapy for Helicobacter pylori eradication: a prospective, double-blind, randomized, placebo-controlled study.

OBJECTIVE: Because Helicobacter pylori creates a well-sheltered microenvironment within the gastric mucus layer, it has been speculated that the disruption of this space by a mucolytic agent may enhance the eradication rate. The aim of the present study was to investigate the effect of erdosteine, a strong mucolytic agent, on the effectiveness of PPI-based, first-line triple therapy in the eradication of H. pylori. MATERIAL AND METHODS: Initially, 196 patients were enrolled to the study. Of these, 79 H. pylori-positive patients were randomized to the erdosteine group (triple therapy consisting of pantoprazole, amoxicillin and clarithromycin plus erdosteine; n = 40) or the placebo group (triple therapy plus placebo; n = 39) for 14 days. Endoscopic biopsies and (13)C-urea breath tests were performed at entry and at 4-6 weeks after the completion of the treatment. Additionally, rapid urease tests were performed at entry. RESULTS: The eradication of H. pylori was achieved in 30 (75%) of the 40 patients in the erdosteine group and in 20 (51.3%) of the 39 patients in the placebo group, according to the ITT analysis (p = 0.028). When the PP analysis was performed as well, H. pylori eradication was achieved in 30 (78.9%) of the 38 patients in the erdosteine group and in 20 (52.6%) of the 38 patients in the placebo group (p = 0.016). CONCLUSIONS: Erdosteine is an efficient adjuvant therapy that could be used in conjunction with first-line triple therapy in the treatment of H. pylori.

Ten-day sequential therapy of Helicobacter pylori infection in Thailand.

OBJECTIVES: Antimicrobial resistance has decreased eradication rates of Helicobacter pylori worldwide. The objective of this study was to determine whether a sequential therapy regimen is effective in eradicating H. pylori in adults with nonulcer dyspepsia or peptic ulcer disease in Thailand. METHODS: A total of 115 patients with dyspepsia or peptic ulcer were enrolled in the study. (14)C-urea breath test, upper endoscopy, rapid urease test, bacterial culture, and antibiotic resistance assessment were conducted during the course of the treatment. In all, 115 patients underwent a 10-day sequential regimen, which consisted of lansoprazole (30 mg) plus amoxicillin (1 g) twice a day for 5 days, then lansoprazole (30 mg) with metronidazole (500 mg) twice a day, and clarithromycin (1,000 mg) once a day for another 5 consecutive days. Successful eradication was evaluated by negative urea breath test at least 4 weeks after stopping treatment. RESULTS: Successful eradication was achieved in 106 of 115 patients (95%). All patients completed the treatment, without any dropouts. Mild adverse effects included headache and palpitations. The prevalence rate of clarithromycin-resistant H. pylori was found to be 6.1%. CONCLUSIONS: The 10-day sequential treatment for H. pylori is well tolerated and provides a high eradication rate. This regimen can overcome the emergence of antibiotic resistance and may have a role as a first-line treatment for H. pylori infection in Thailand.