Biomedical subjects

G Hasselgren

Publications and source records attributed to G Hasselgren.

At least 19 recordsLinked to original sources

PubMed2006

Inability of laser and rotary instrumentation to eliminate root canal infection.

BACKGROUND: The authors evaluated the antibacterial effectiveness of laser instrumentation and rotary instrumentation of anterior, single-rooted teeth infected with Enterococcus faecalis. METHODS: The authors divided 35 infected samples into five groups: Group A: inoculation, laser, 17 percent ethylene-diamine-tetra-acetate (EDTA), 2.5 percent sodium hypochlorite (NaOCl) (n=10); Group B: inoculation, laser, 17 percent EDTA, sterile saline (n = 10); Group C: inoculation, rotary, 17 percent EDTA, 2.5 percent NaOCl (n=10); Group D: inoculation, no instrumentation (positive control) (n=5); Group E: no inoculation, no instrumentation (negative control) (n=5). They sampled and incubated dentin shavings from each canal for bacterial growth. RESULTS: In Group A, eight tubes were positive for bacterial growth. In Group B, 10 tubes were positive for bacterial growth. In Group C, six tube were positive for bacterial growth. In Group D, all of the tubes were positive for bacterial growth. In Group E, no tubes showed bacterial growth. The Fisher exact test showed no significant differences among groups A, E and C. CONCLUSION: Neither the laser nor the rotary instrumentation was able to eliminate endodontic infection. CLINICAL IMPLICATIONS: Although lasers have been presented as high-tech tools for disinfecting root canals, the laser was ineffective in this study.

Chelating Agents↗

PubMed2005

A quantum biological hypothesis of human secondary dentinogenesis.

It is hypothesized that human coronal secondary dentin (SD) is a final classical mechanical (CM) response to a chain of prior quantum mechanical (QM) transductions of the information of initial CM occlusal loadings of enamel. Such CM energy is transduced into QM quanta (as protons) that are translocated centripetally via clustered water (CW), (as "proton wires"), that is structurally related to both enamel prism sheath and hydroxyapatite crystal hydration shells. These quanta pass into odontoblastic cell processes (OP), lying within dentinal tubules (DT). OP's contain abundant parallel arrays of cylindrical microtubules (MT). These are the sites of two further CW-related QM events: (i) proton translocation associated with conformal changes of MT tubulin protein dimers; and (ii) coherent energetic oscillations within the CW filling the MT's hollow cores. Finally, these quanta pass into the odontoblastic soma, where QM wave function collapse transduces this information into a final CM state that initiates the processes of SD formation. A critical portion of this hypothesis may be experimentally tested.

Dentin, Secondary↗

PubMed2002

Pathologic interactions in pulpal and periodontal tissues.

Both endodontic and periodontal disease are caused by a mixed anaerobic infection. The pathways for the spread of bacteria between pulpal and periodontal tissues have been discussed with controversy. This article is an attempt to provide a rational approach to the perio-endo/endo-perio question based on a review of the relevant literature. In the light of evidence, clinical concepts for the diagnosis and treatment of lesions involving both periodontal and pulpal tissues are discussed.

Bacteria, Anaerobic↗

PubMed2001

One week of treatment with esomeprazole-based triple therapy eradicates Helicobacter pylori and heals patients with duodenal ulcer disease.

BACKGROUND: Proton pump inhibitor (PPI) monotherapy is commonly continued for 3 weeks after Helicobacter pylori eradication with PPI-based triple therapy regimens to ensure duodenal ulcer (DU) healing. This randomized, double-blind, multicentre study evaluated whether only 1 week of triple therapy with the new PPI esomeprazole was sufficient to ensure high rates of ulcer healing and H. pylori eradication. METHODS: A total of 446 H. pylori-positive patients with active DU received twice daily treatment with esomeprazole 20 mg (n = 222) or omeprazole 20 mg (n = 224) in combination with amoxicillin 1 g and clarithromycin 500 mg for 1 week (EAC and OAC, respectively). Patients in the OAC group then received 3 weeks' monotherapy with omeprazole 20 mg once daily; those treated with EAC received placebo. Ulcer healing was assessed by endoscopy on completion of therapy and H. pylori status was assessed by (13)C-urea breath testing and histology 4-6 weeks later. RESULTS: Ulcer healing rates (95% CI) for intention-to-treat and per-protocol populations were: EAC + placebo 91% (87-95%) and 94% (90-97%); OAC + omeprazole 92% (88-95%) and 96% (92-98%). Corresponding H. pylori eradication rates were: EAC + placebo 86% (81-90%) and 89% (84-93%); OAC + omeprazole 88% (83-92%) and 90% (85-93%). Both eradication regimens were well tolerated, and patient compliance was high. CONCLUSIONS: A 1-week regimen of esomeprazole-based triple therapy is sufficient for DU healing and H. pylori eradication in patients with DU disease.

Amoxicillin↗

PubMed2001

Pharmacokinetic study of esomeprazole in the elderly.

OBJECTIVE: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of patients with acid-related diseases. The aim of this study was to examine the pharmacokinetics and tolerability of esomeprazole in the elderly, relative to middle-aged patients with gastro-oesophageal reflux disease (GORD). DESIGN: Nonblinded single-centre pharmacokinetic study with historical control group. PATIENTS AND PARTICIPANTS: 14 healthy elderly volunteers [mean age 74 (range 71 to 80) years]. METHODS: Participants received treatment with esomeprazole 40 mg once daily for 5 days, with 24-hour blood sampling on days 1 and 5. The total area under the plasma concentration-time curve (AUCinfinity), maximum plasma drug concentration (Cmax), terminal elimination half-life (t(1/2z)) and time to Cmax (tmax) were determined for the parent drug and its hydroxy and sulphone metabolites. AUCinfinity and Cmax data were compared with those in an historical group of 36 middle-aged patients [mean age 45 (range 29 to 58) years] with GORD, treated with an identical dosage of esomeprazole for 5 days. RESULTS: A total of 13 volunteers completed the study. On day 5, the mean plasma AUCinfinity of esomeprazole was 16.0 micromol x h/L, Cmax was 5.6 micromol/L, tmax was 1.5 hours and t(1/2z) was 1.7 hours. The AUCinfinity and Cmax values for the parent drug were 2- and 1.5-fold higher on day 5 compared with day 1. AUCinfinity and Cmax values for the sulphone metabolite increased to a slightly greater extent, and values for the hydroxy metabolite were unchanged. Ratios of the AUCinfinity and Cmax values between elderly volunteers and patients with GORD were 1.25 [95% confidence interval (CI) 0.94, 1.67] and 1.18 (0.91, 1.52), respectively. Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS: The AUCinfinity and Cmax values in the elderly were not significantly different from those obtained in a group of middle-aged patients. The difference for AUCinfinity was 25% (95% CI -6% to +67%). Esomeprazole has a wide therapeutic window and our results do not indicate that dosage adjustment should be necessary in the elderly.

Administration, Oral↗

PubMed2001

Pharmacokinetic studies with esomeprazole, the (S)-isomer of omeprazole.

This article reviews the pharmacokinetics of esomeprazole, the (S)-isomer of the proton pump inhibitor (PPI) omeprazole. Esomeprazole is the first single isomer PPI developed for the treatment of patients with acid-related diseases. In vitro experiments in human liver microsomes demonstrated that the formation of the hydroxy and 5-O-desmethyl metabolites of esomeprazole is via cytochrome P450 (CYP) 2C19, whereas that of the sulphone metabolite is via CYP3A4. The formation rate of the hydroxy metabolite from esomeprazole is lower than for (R)-omeprazole, but that of the 2 other metabolites is higher, demonstrating stereoselective metabolism. The sum of the intrinsic clearances of all 3 metabo- lites for esomeprazole was one-third of that for (R)-omeprazole, suggesting lower clearance of esomeprazole in vivo. In vivo investigations demonstrated that esomeprazole is chirally stable after administration. Esomeprazole is 97% bound to plasma proteins. In normal (extensive) metabolisers with regard to CYP2C19, esomeprazole is metabolised more slowly than omeprazole, resulting in a higher area under the concentration-time curve (AUC) after administration of the same dose. This is more pronounced after repeated administration rather than after a single dose. In poor metabolisers, the AUC is lower for esomeprazole than for omeprazole, contributing to less overall interindividual variability for esomeprazole than for omeprazole. In general, esomeprazole and omeprazole are subject to the same metabolic transformations. Almost complete recoveries were reported and the ratio between urinary and faecal excretion is about 4:1 for both compounds. The dose-dependent increase in AUC of esomeprazole with repeated administration results from a combination of decreased first-pass elimination and decreased systemic clearance. Patients with gastro-oesophageal reflux disease exhibit a pharmacokinetic pattern similar to that in healthy individuals, whereas elderly individuals exhibited a slightly lower metabolism rate. Patients with a severe deficit in their liver function had a lower rate of metabolism, as would be expected, whereas those with mild to moderate liver disease did not exhibit any alteration in the pharmacokinetics. The pharmacokinetics of esomeprazole in individuals with impaired renal function is unlikely to differ from that in healthy individuals. A slight sex difference in the pharmacokinetics of esomeprazole was demonstrated in that the AUC and peak plasma drug concentration were slightly, but not statistically significantly, higher in females than in males.

Animals↗

PubMed2001

Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole.

Esomeprazole, the (S)-isomer of omeprazole, is the first proton pump inhibitor (PPI) developed as a single isomer for the treatment of patients with acid related diseases. Because of the extensive use of PPIs, the documentation of the potential for drug interactions with esomeprazole is of great importance. Altered absorption or metabolism are 2 of the major mechanisms for drug-drug interactions. Since intragastric pH will increase with esomeprazole treatment, it can be hypothesised that the absorption of drugs with pH-sensitive absorption (e.g. digoxin and ketoconazole) may be affected. Esomeprazole does not seem to have any potential to interact with drugs that are metabolised by cytochrome P450 (CYP) 1 A2, 2A6, 2C9, 2D6 or 2E1. In drug interaction studies with diazepam, phenytoin and (R)-warfarin, it was shown that esomeprazole has the potential to interact with CYP2C19. The slightly altered metabolism of cisapride was also suggested to be the result of inhibition of a minor metabolic pathway for cisapride mediated by CYP2C19. Esomeprazole did not interact with the CYP3A4 substrates clarithromycin (2 studies) or quinidine. Since the slightly increased area under the concentration-time curve (AUC) of cisapride could be explained as an inhibition of CYP2C19, the data on these 3 CYP3A4 substrates indicate that esomeprazole does not have the potential to inhibit this enzyme. The minor effects reported for diazepam, phenytoin, (R)-warfarin, and cisapride are unlikely to be of clinical relevance. Clarithromycin interacts with the metabolism of esomeprazole resulting in a doubling of the AUC of esomeprazole. The increased plasma concentrations of esomeprazole are unlikely to have any safety implications. It can be concluded that the potential for drug-drug interactions with esomeprazole is low, and similar to that reported for omeprazole.

Anti-Ulcer Agents↗

PubMed2000

Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid-related diseases. METHODS: In this double-blind crossover study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic variables were measured. RESULTS: Thirty-six patients aged 29-58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS: Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.

Adult↗

PubMed2000

One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease.

BACKGROUND: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases. METHODS: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication. RESULTS: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy. CONCLUSIONS: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.

Adult↗

PubMed2000

Retreatment decisions--a comparison between general practitioners and endodontic postgraduates.

One of the most subjective areas with regard to interexaminer variations is the dental radiograph. The variations in radiographic interpretation lead to differences in treatment planning decisions. This study compared the endodontic retreatment planning decisions for endodontically treated teeth between 12 general practitioners and 12 endodontic postgraduate students. Utilizing dental radiographs of completed cases, both groups were asked to make treatment choices based on two hypothetical ages of a case: 1 or 3 yr postoperatively. General practitioners chose to initiate treatment at an earlier date and also chose more extensive treatment modalities. The age of the root filling was looked on as more important in treatment planning by the endodontics postgraduates.

Apicoectomy↗

PubMed2000

Overall mortality among patients surviving an episode of peptic ulcer bleeding.

STUDY OBJECTIVE: The authors investigated whether patients who have survived an acute episode of peptic ulcer bleeding (PUB) have an excess long term all cause mortality compared with the general population free of PUB. DESIGN: Follow up study of previously identified cohort of patients with a PUB episode and a general population cohort. SETTING: The source population included all people aged 30 to 89 years, registered with general practitioners in the United Kingdom. PATIENTS: All patients alive one month after the PUB episode constituted the cohort of PUB patients (n = 978). A control group of 5000 people was randomly sampled from the source population. The same eligibility criteria as for patients with PUB were applied to the control series. Also, controls had to be free of PUB before start date. MAIN RESULTS: Relative risk of mortality among PUB patients was 2.1, 95% CI: 1.7, 2.6) compared with the general population. This increased mortality risk occurred mainly in the patients less than 60 years old. No difference was observed between men and women. The excess mortality was not only circumscribed to deaths attributable to recurrent gastrointestinal bleed, but also cardiovascular, cancer and other causes. CONCLUSIONS: People who have survived an acute episode of PUB have a reduced long term survival compared with the general population. This reduction was stronger among middle age patients than in the elderly.

Adult↗

PubMed1998

Host mediators in endodontic exudates. I. Indicators of inflammation and humoral immunity.

Exudate is often found in the root canal when entering the chamber and canal of teeth with periapical lesions. The aim of this study was to determine possible relationships between clinical or radiographic findings and the concentrations of different host mediators in endodontic exudates. Thirty-two nonvital teeth with periapical symptoms were included in the study. A Clinical Periapical Index was developed to quantify clinical findings. Endodontic exudates were collected with methylcellulose filter paper strips every 3 min, after opening of the pulp chamber. The concentrations of the lysosomal acid glycohydrolase beta-glucuronidase, IgG, IgA, IgM, and interleukin-1 beta in the endodontic exudates were analyzed. The results demonstrated that exudates collected from teeth with suppuration (cloudy exudates), and teeth with higher periapical index scores (Orstavik et al., 1986) contained higher concentrations of beta-glucuronidase and interleukin-1 beta. Furthermore, when the periapical index indicated severe involvement, higher IgG was observed in the first samples. The exudates from patients who presented with a sinus tract or swelling contained higher concentrations of IgM, compared with the patients with only periapical sensitivity. Data showed that endodontic exudates from patient with endodontic lesions can be analyzed for host mediators, and differences in the mediators were seen with different clinical and radiographic symptoms.

Adolescent↗

PubMed1998

Host mediators in endodontic exudates. II. Changes in concentration with sequential sampling.

Exudate is often found in the root canal of teeth requiring endodontic therapy. The aim of this study was to evaluate the relationship of sequential changes of different host mediators in endodontic exudates to clinical and radiographic findings. Thirty-two nonvital teeth with periapical symptoms were evaluated. Exudates were collected with filter paper strips every 3 min after opening of the pulp chamber. The concentrations of beta-glucuronidase, IgG, IgA, IgM, and interleukin-1 beta in the exudates were analyzed. In general, the concentration of the mediators in exudates from less involved lesions did not change over time. The exception was an increase in the IgM concentration when patients presented with percussion or palpation sensitivity. In contrast, in the more involved lesions, the concentrations of IgA and IgM increased as sampling progressed. The concentrations of beta-glucuronidase and interleukin-1 beta decreased over time in the more involved lesions. These data suggest that the amount of proinflammatory mediators in the canal and periapical lesion is limited. Furthermore, IgM seemed to be a marker for the severity of periapical lesions. This may relate to vascular permeability that allows passage of this larger molecule into the extravascular environment.

Exudates and Transudates↗

PubMed1998

Short and long term course of elderly patients with peptic ulcer bleeding--analysis of factors influencing fatal outcome.

OBJECTIVE: To study long and short term survival in patients aged 60 years or over admitted with a peptic ulcer bleeding and find out which factors influence outcome. DESIGN: Cohort study with matched controls. SETTING: Two emergency hospitals, Sweden PATIENTS: 676 of the 687 patients aged 60 years or over admitted to the two emergency hospitals serving Gothenburg, Sweden during 1989-1993 who fulfilled the diagnostic criteria and whose case notes were available for study. MAIN OUTCOME MEASURES: Seven year survival rates and odds ratios for risk factors based on multiple logistic regression analyses. RESULTS: 37 patients died and the timing was evenly distributed within the first 30 days of admission with a cumulated case-fatality rate of 5.5% at day 30. Mortality was increased among the patients compared with the control group during the subsequent years. Factors that influenced day 30 mortality were age and Forrest class. CONCLUSION: Mortality is increased among patients with peptic ulcer bleeding even long after the event. Old age and signs of recent haemorrhage increase the risk.

Age Factors↗

PubMed1998

Comparison of mortality from peptic ulcer bleed between patients with or without peptic ulcer antecedents.

We studied mortality related to peptic ulcer bleed in a well defined cohort of patients in the month after the episode of peptic ulcer bleed. Our objective was to assess the contribution of peptic ulcer antecedents and other predictive factors on the risk of dying. The study cohort comprised 1,020 patients hospitalized for an episode of peptic ulcer bleed between January 1991 and March 1994 and identified in the General Practice Research Database in the United Kingdom. Six hundred twenty-three patients had no prior episode of peptic ulcer disease, and 384 had peptic ulcer antecedents; for 13 patients, information was not available. Forty-five patients died (mortality rate = 4.4 per 100 person-months; 95% confidence interval = 3.3-5.9) within 1 month of the peptic ulcer bleed. Patients with no peptic ulcer antecedent faced a greater risk of dying than patients with antecedents (relative risk = 3.0; 95% confidence interval = 1.2-7.1). Elderly patients, those undergoing surgery, and current users of acid-suppressing drugs or nonsteroidal antiinflammatory drugs all had an increased mortality risk. Patients presenting with their first-ever episode of peptic ulcer bleed have a higher case fatality rate than those with previous episodes of peptic ulcer.

Adult↗

PubMed1998

Optimization of acid suppression for patients with peptic ulcer bleeding: an intragastric pH-metry study with omeprazole.

OBJECTIVE: To study whether an intravenous infusion dose of omeprazole (80 mg + 8 mg/h) during 24 h can be subsequently reduced with maintained effect. Second, to study the effect of oral omeprazole 20 mg given once or twice daily up to day 10, after cessation of a 3-day intravenous infusion (80 mg + 8 mg/h). DESIGN: Prospective, randomized, partly blinded study. METHODS: Twelve Helicobacter pylori(+) patients and 12 H. pylori(-) subjects were included. In part I the patients received omeprazole, 80 mg + 8 mg/h, during 24 h followed by 8, 4 or 2 mg/h. In part II the subjects received 80 mg + 8 mg/h during 3 days followed by 20 mg omeprazole orally, once or twice daily until day 10. Intragastric pH was measured. RESULTS: All H. pylori(+) patients showed a rapid increase of intragastric pH with a mean intragastric pH of 6.7 during the second half of the first day. After the subsequent dose reduction, the mean pH decreased to 6.1-6.2. Patients continuing on 8 mg/h showed the best results. Likewise, all H. pylori(-) subjects showed a rapid and sustained reduction of intragastric acidity during the infusion. Subsequent dose reduction to 20 mg once daily led to a stable fraction of time with pH > 3 of 72%. CONCLUSIONS: Omeprazole given as a continuous infusion of 80 mg + 8 mg/h for 72 h followed by omeprazole 20 mg once daily raised the intragastric pH to and above levels alleged to allow haemostasis in patients with peptic ulcer bleeding and subsequent healing of the ulcer.

Adult↗

PubMed1998

Risk factors for rebleeding and fatal outcome in elderly patients with acute peptic ulcer bleeding.

OBJECTIVE: Mortality after peptic ulcer bleeding (PUB) is high in elderly patients despite therapeutic advances. Little is known about what actually determines rebleeding and mortality. The objective of this study was to investigate which factors may have an independent influence upon rebleeding and mortality in patients with PUB. DESIGN: Prospective cohort study. PARTICIPANTS: Patients, above 60 years of age, hospitalized due to an endoscopically verified acute PUB were included in the study (n = 508). INTERVENTIONS: The occurrence of rebleeding within 3 days and mortality within 30 days was registered for all patients. A predefined set of variables with a potential to influence rebleeding and mortality was analysed in a multiple logistic regression model. MAIN OUTCOME MEASURES: Odds ratios (with confidence intervals) for all predefined variables with respect to influence upon rebleeding and mortality, respectively. RESULTS: The risk of rebleeding was significantly increased with greater age and if the patient was suffering from shock, while omeprazole infusion, acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drug (NSAID) intake before admission and gastric ulcer localization were associated with a lower risk. Mortality was significantly increased with greater age, heart disease and blood pressure < 100 mmHg at admission. Previous ulcer history and the presence of a Forrest class IIa ulcer significantly reduced this risk. CONCLUSIONS: Elderly patients in shock admitted due to their first peptic ulcer bleeding run the greatest risk of an unfavourable outcome.

Acute Disease↗

PubMed1997

Effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers. Randomized double-blind placebo-controlled multicentre study.

BACKGROUND: Haemostasis is highly pH-dependent and severely impaired at low pH. However, there is no clear evidence that acid-suppressing drugs have beneficial effects in peptic ulcer haemorrhage. Endoscopic haemostatic treatment provides important reduction in morbidity and may be more efficient when a neutral intragastric pH is maintained. METHODS: We conducted a double-blind, placebo-controlled multicentre study of intravenous infusion of omeprazole (80 mg as bolus, followed by 8 mg/h) or placebo for 72 h. All patients received 20 mg omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer haemorrhage, endoscoped within 12 h after admission, and with a history or signs of circulatory failure and spurting bleeding, oozing bleeding, visible vessel, or clot, were included. Endoscopic intervention was aimed at when spurting bleeding, oozing bleeding, or a visible vessel was observed. The primary efficacy measure was the worst ranking on an overall outcome scale (5 = death, 4 = surgery, 3 = additional endoscopic treatment, 2 = more than 3 units of blood, and 1 = no more than 3 units of blood transfused). Base-line prognostic factors of treatment success by day 3 and of other binary outcomes were considered in a logistic regression model. RESULTS: Two hundred and seventy-four patients were randomly assigned to omeprazole (134 patients) or placebo (140 patients). The number of patients included in the 'intention-to-treat' analysis was 130 in the omeprazole group and 135 in the placebo group. The primary variable, the overall outcome at 72 h, showed a difference (P = 0.004) between the two treatments in favour of omeprazole. Treatment success by 72 h defined as no death, no operation, or no additional endoscopic treatment was 91.0% in the omeprazole group and 79.7% in the placebo group (therapeutic gain, 11.3 percentage units; 95% confidence interval, 2.3 to 20.4 percentage units). Significant differences in favour of omeprazole were also found for secondary variables such as number of blood transfusions, duration and degree of bleeding, and the need for surgery and additional endoscopic treatments on day 3 and day 21. However, the numbers of deaths by day 3, 21, or 35 were very similar. CONCLUSIONS: We found a beneficial effect of intravenous omeprazole in severe ulcer haemorrhage, with a reduction in the number of operations, in endoscopic treatments, and in the duration and severity of bleeding.

Aged↗