Emili Gené

Triple vs. quadruple therapy for treating Helicobacter pylori infection: an updated meta‐analysis

Background: Triple therapy (proton pump inhibitor, clarithromycin and amoxicillin or an imidazole) is the first‐line treatment for Helicobacter pylori infection. However, the effectiveness of triple therapy is decreasing due to the increase in antibiotic resistance. Quadruple therapy (proton pump inhibitor, tetracycline, metronidazole and a bismuth salt) is a very effective regimen even in areas of high prevalence of antibiotic resistance, and may be an alternative first‐line treatment.

Helicobacter pylori eradication therapy vs. antisecretory non‐eradication therapy for the prevention of recurrent bleeding from peptic ulcer

Aim : To perform a meta‐analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. antisecretory non‐eradication therapy for the prevention of recurrent bleeding from peptic ulcer.

Has H. pylori prevalence in bleeding peptic ulcer been underestimated? A meta-regression.

OBJECTIVES:It has been suggested that prevalence of Helicobacter pylori (Hp) in peptic ulcer bleeding (PUB) is lower than that in non-complicated ulcers. As Hp infection is elusive in PUB, we hypothesized that this low prevalence could be related to an insufficiently intensive search for the bacteria. The aim of the study was to evaluate whether the prevalence of Hp in PUB depends on the diagnostic methods used in a given study.METHODS:A systematic review was performed of studies assessing the prevalence of Hp infection in patients with PUB. Data were extracted in duplicate. Univariate and multivariate random-effects meta-regression analyses were performed to determine the factors that explained the differences in Hp prevalence between studies.RESULTS:The review retrieved 71 articles, including 8,496 patients. The mean prevalence of Hp infection in PUB was 72%. The meta-regression analysis showed that the most significant variables associated with a high prevalence of Hp infection were the use of a diagnostic test delayed until at least 4 weeks after the PUB episode—odds ratio: 2.08, 95% confidence interval: 1.10–3.93, P=0.024—and a lower mean age of patients—odds ratio: 0.95 per additional year, 95% confidence interval: 0.92–0.99, P=0.008.CONCLUSIONS:Studies that performed a delayed test and those including younger patients found a higher prevalence of Hp, approaching that recorded in cases of non-bleeding ulcers. These results suggest that the low prevalence of Hp infection described in PUB may be related to the methodology of the studies and to patients’ characteristics, and that the true prevalence of Hp in PUB is still to be determined. Our data also support the recent recommendations of the International Consensus on Non-Variceal Upper Gastrointestinal Bleeding regarding the performance of a delayed diagnostic test when Hp tests carried out during the acute PUB episode are negative.Am J Gastroenterol advance online publication, 8 February 2011; doi:10.1038/ajg.2011.2

What is the optimal length of proton pump inhibitor-based triple therapies for H. pylori? A cost-effectiveness analysis

Triple therapy with a proton pump inhibitor, clarithromycin and amoxicillin is widely used for H. pylori infection. The appropriate length of treatment remains controversial.

Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX ™ tool in Spain.

BackgroundAge-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years.Methods/DesignTo assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations. Study population: Patients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors. Measurements: At baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site.DiscussionSince more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.

FRAX® tool, the WHO algorithm to predict osteoporotic fractures: the first analysis of its discriminative and predictive ability in the Spanish FRIDEX cohort.

BackgroundThe WHO has recently published the FRAX® tool to determine the absolute risk of osteoporotic fracture at 10 years. This tool has not yet been validated in Spain.Methods/designA prospective observational study was undertaken in women in the FRIDEX cohort (Barcelona) not receiving bone active drugs at baseline. Baseline measurements: known risk factors including those of FRAX® and a DXA. Follow up data on self-reported incident major fractures (hip, spine, humerus and wrist) and verified against patient records. The calculation of absolute risk of major fracture and hip fracture was by FRAX® website. This work follows the guidelines of the STROBE initiative for cohort studies. The discriminative capacity of FRAX® was analyzed by the Area Under Curve (AUC), Receiver Operating Characteristics (ROC) and the Hosmer-Lemeshow goodness-of-fit test. The predictive capacity was determined using the ratio of observed fractures/expected fractures by FRAX® (ObsFx/ExpFx).ResultsThe study subjects were 770 women from 40 to 90 years of age in the FRIDEX cohort. The mean age was 56.8 ± 8 years. The fractures were determined by structured telephone questionnaire and subsequent testing in medical records at 10 years. Sixty-five (8.4%) women presented major fractures (17 hip fractures). Women with fractures were older, had more previous fractures, more cases of rheumatoid arthritis and also more osteoporosis on the baseline DXA. The AUC ROC of FRAX® for major fracture without bone mineral density (BMD) was 0.693 (CI 95%; 0.622-0.763), with T-score of femoral neck (FN) 0.716 (CI 95%; 0.646-0.786), being 0.888 (CI 95%; 0.824-0.952) and 0.849 (CI 95%; 0.737-0.962), respectively for hip fracture. In the model with BMD alone was 0.661 (CI 95%; 0.583-0.739) and 0.779 (CI 95%; 0.631-0.929). In the model with age alone was 0.668 (CI 95%; 0.603-0.733) and 0.882 (CI 95%; 0.832-0.936). In both cases there are not significant differences against FRAX® model. The overall predictive value for major fracture by ObsFx/ExpFx ratio was 2.4 and 2.8 for hip fracture without BMD. With BMD was 2.2 and 2.3 respectively. Sensitivity of the four was always less than 50%. The Hosmer-Lemeshow test showed a good correlation only after calibration with ObsFx/ExpFx ratio.ConclusionsThe current version of FRAX® for Spanish women without BMD analzsed by the AUC ROC demonstrate a poor discriminative capacity to predict major fractures but a good discriminative capacity for hip fractures. Its predictive capacity does not adjust well because leading to underdiagnosis for both predictions major and hip fractures. Simple models based only on age or BMD alone similarly predicted that more complex FRAX® models.

Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency.

Objective Intravenous iron is widely used to treat iron deficiency in day-care units. Ferric carboxymaltose (FCM) allows administration of larger iron doses than iron sucrose (IS) in each infusion (1000 mg vs. 200 mg). As FCM reduces the number of infusions required but is more expensive, we performed a cost-minimization analysis to compare the cost impact of the two drugs. Materials and Methods The number of infusions and the iron dose of 111 consecutive patients who received intravenous iron at a gastrointestinal diseases day-care unit from 8/2007 to 7/2008 were retrospectively obtained. Costs of intravenous iron drugs were obtained from the Spanish regulatory agencies. The accounting department of the Hospital determined hospital direct and indirect costs for outpatient iron infusion. Non-hospital direct costs were calculated on the basis of patient interviews. In the pharmacoeconomic model, base case mean costs per patient were calculated for administering 1000 mg of iron per infusion using FCM or 200 mg using IS. Sensitivity analysis and Monte Carlo simulation were performed. Results Under baseline assumptions, the estimated cost of iron infusion per patient and year was €304 for IS and €274 for FCM, a difference of €30 in favour of FCM. Adding non-hospital direct costs to the model increased the difference to €67 (€354 for IS vs. €287 for FCM). A Monte Carlo simulation taking into account non-hospital direct costs favoured the use of FCM in 97% of simulations. Conclusion In this pharmacoeconomic analysis, FCM infusion reduced the costs of iron infusion at a gastrointestinal day-care unit.

Limited usefulness of a seven-day twice-a-day quadruple therapy

Objective To test the usefulness of a twice‐a‐day, simplified quadruple therapy to cure Helicobacter pylori infection. Design Helicobacter pylori‐positive ulcer patients were treated with omeprazole 20 mg twice a day (b.d.), amoxicillin 1 g b.d., tinidazole 500 mg b.d. and bismuth subcitrate 240 mg b.d. for 7 days in an experimental, noncomparative pilot study. Setting The gastroenterology unit of a county hospital. Participants Forty‐four consecutive patients with peptic ulcer disease and H. pylori infection. Measurements Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy. Results One patient was lost to follow‐up. Of the remaining 43, 37 were cured at the first control, giving an intention‐to‐treat cure rate of 84.1% (95% CI 69‐93%) and a per protocol cure rate of 86% (95% CI 71‐94%). Thirty‐three cured patients agreed to return for a six‐month breath test. All but one were cured (long‐term per protocol cure rate 82.1%; 95% CI 66‐92%). Conclusions This particular quadruple therapy is well tolerated and easy to comply with. However, cure rates did not reach 90%.

Modified seven‐day, quadruple therapy as a first line Helicobacter pylori treatment

Cure rates of 7‐day triple therapy seem to be decreasing. Quadruple therapies may be an alternative, although their complex administration makes patient acceptance difficult.

Manejo de la infección por Helicobacter pylori en atención primaria en España

Resumen Introduccion Las indicaciones sobre cuando y como diagnosticar y tratar la enfermedad ulcerosa y la infeccion por Helicobacter pylori son razonablemente claras en la actualidad. El objetivo fue analizar el manejo de la infeccion por H. pylori y el acceso a las pruebas diagnosticas de la infeccion en atencion primaria. Material y metodos Estudio observacional, transversal, realizado mediante cuestionario anonimo administrado a medicos de atencion primaria de todo el territorio espanol.Las indicaciones y los tratamientos se analizaron evaluando su adecuacion a las recomendaciones de consenso sobre lainfeccion por H. pylori . Resultados Se recogieron 991 encuestas. El 87,7% de los medicos realizo uno o mas tratamientos erradicadores en el ultimo ano, el 79,9% en ulcera duodenal, el 75,3% en ulcera gastrica y el 18,3% en enfermedad por reflujo. El 74,7% indico una pauta de tratamiento erradicador cuya composicion fue correcta. El 29% la indico con una duracion superior a la recomendada (14 dias). El 67% no indico tratamiento erradicador en el paciente ulceroso bien controlado con antisecretores y continua el tratamiento antisecretor de mantenimiento. El 64,7% de los medicos tiene acceso a la endoscopia, el 67,4% al test del aliento, el 59,6% a la serologia y el 11,9% a la prueba de deteccion de antigeno de H. pylori en heces. Se detectaron variaciones importantes entre las diversas comunidades autonomas en el acceso a las pruebas diagnosticas. Conclusiones El porcentaje de adecuacion a las recomendaciones es razonable. Sin embargo, se observa una notable variabilidad geografica e importantes restricciones en el acceso a pruebas diagnosticas, lo que dificulta la aplicacion de las recomendaciones.