An optimized clarithromycin-free 14-day triple therapy for Helicobacter pylori eradication achieves high cure rates in Uruguay / El tratamiento triple, optimizado y sin claritromicina durante 14 días consigue altas tasas de curación de Helicobacter pylori en Uruguay

Background: Strong acid inhibition increases cure rates with triple therapy and 14-day are more effective than 7-day treatments. The combination of amoxicillin plus metronidazole at full doses has been shown to overcome metronidazole resistance and to achieve good eradication rates even in patients harboring resistant strains. No previous studies have been reported in Latin-America with this optimized triple-therapy scheme. Aims: The aim of the present study was to assess the eradication rate and tolerance of a new first-line treatment regimen associating strong acid inhibition, amoxicillin and metronidazole. Methods: Patients from the Clínica de Gastroenterología of the Hospital de Clínicas (Montevideo, Uruguay) were included. Hp status was mainly assessed by at least one of the following: histologyor urea breath test (UBT). A 14-day treatment was prescribed comprising esomeprazole 40mg twice a day plus amoxicillin 1g and metronidazole 500mg, both three times a day. H. pylori cure was assessed by UBT. Results: Forty-one patients were enrolled. Mean age was 53.3±13 years and 17.1% of patients were male. Main indications for treatment were: functional dyspepsia (27.5%), gastritis (45%), gastric or duodenal erosions (20%), gastric ulcer (5%) and intestinal metaplasia (2.5%). H. pylori eradication was achieved in 33 of the 37 patients who returned for follow-up. Eradication rates were 80.5% (95% CI: 68.4-92.6) by intention-to-treat (ITT) analysis and 89.2% (95% CI; 79.2-99.2) per protocol (PP). No major side effects were reported; 26 patients (65.8%) complained of mild side effects (nausea, diarrhea and headache). Conclusions: Cure rates of this triple therapy including esomeprazole, amoxicillin and metronidazole were 81% per ITT and the treatment was well tolerated. These optimal results with a simple clarithromycin-free triple therapy are better than described for standard triple therapy but there is still room for improvement to reach the desired target of 90% per ITT (AU)

Antecedentes: La inhibición ácida potente aumenta las tasas de curación de la triple terapia, y 14 días de tratamiento son más efectivos que 7 días. La combinación de amoxicilina y metronidazol a dosis completas ha demostrado que supera la resistencia al metronidazol y que consigue buenas tasas de erradicación, incluso en pacientes que poseen cepas resistentes. No se han reportado estudios con este tratamiento triple optimizado en Latinoamérica. Objetivos: El objetivo del presente estudio es valorar las tasas de erradicación y la tolerancia de un nuevo tratamiento de primera línea que asocia inhibición ácida potente, amoxicilina y metronidazol. Métodos: Pacientes provenientes de la Clínica de Gastroenterología del Hospital de Clínicas (Montevideo, Uruguay) se incluyeron en el estudio. La infección por Helicobacter pylori fue demostrada por, al menos, una de las siguientes: histología o test del aliento. Se prescribió un tratamiento de 14 días con esomeprazol 40mg 2 veces al día junto a amoxicilina 1g y metronidazol 500mg ambos 3 veces al día. La curación de Helicobacter pylori fue confirmada por el test del aliento. Resultados: Se incluyeron 41 pacientes. La edad media fue de 53,3±13 años y el 17,1% de los pacientes eran hombres. La principal indicación para el tratamiento fue: dispepsia funcional (27,5%); gastritis (45%), erosiones gástricas o duodenales (20%), úlcera gástrica (5%) y metaplasia intestinal (2,5%). La erradicación de Helicobacter pylori se consiguió en 33 de los 37 pacientes que regresaron para el test de control. Las tasas de erradicación fueron del 80,5% (IC 95%: 68,4-92,6) por intención de tratar y del 89,2% (IC 95%: 79,2-99,2) por protocolo. No se reportaron efectos secundarios graves. Veintiséis pacientes (65,8%) presentaron efectos secundarios leves (náuseas, diarrea y cefalea). Conclusiones: Las tasas de erradicación de esta triple terapia que incluye esomeprazol, amoxicilina y metronidazol fueron del 81% por intención de tratar y el tratamiento fue bien tolerado. Estos resultados óptimos con un tratamiento triple sencillo, sin claritromicina, son mejores que los descritos para el tratamiento triple estándar, pero todavía existe espacio de mejora para alcanzar el objetivo deseado del 90% por intención de tratar (AU)

An optimized clarithromycin-free 14-day triple therapy for Helicobacter pylori eradication achieves high cure rates in Uruguay.

BACKGROUND: Strong acid inhibition increases cure rates with triple therapy and 14-day are more effective than 7-day treatments. The combination of amoxicillin plus metronidazole at full doses has been shown to overcome metronidazole resistance and to achieve good eradication rates even in patients harboring resistant strains. No previous studies have been reported in Latin-America with this optimized triple-therapy scheme. AIMS: The aim of the present study was to assess the eradication rate and tolerance of a new first-line treatment regimen associating strong acid inhibition, amoxicillin and metronidazole. METHODS: Patients from the Clínica de Gastroenterología of the Hospital de Clínicas (Montevideo, Uruguay) were included. Hp status was mainly assessed by at least one of the following: histologyor urea breath test (UBT). A 14-day treatment was prescribed comprising esomeprazole 40mg twice a day plus amoxicillin 1g and metronidazole 500mg, both three times a day. H. pylori cure was assessed by UBT. RESULTS: Forty-one patients were enrolled. Mean age was 53.3±13 years and 17.1% of patients were male. Main indications for treatment were: functional dyspepsia (27.5%), gastritis (45%), gastric or duodenal erosions (20%), gastric ulcer (5%) and intestinal metaplasia (2.5%). H. pylori eradication was achieved in 33 of the 37 patients who returned for follow-up. Eradication rates were 80.5% (95% CI: 68.4-92.6) by intention-to-treat (ITT) analysis and 89.2% (95% CI; 79.2-99.2) per protocol (PP). No major side effects were reported; 26 patients (65.8%) complained of mild side effects (nausea, diarrhea and headache). CONCLUSIONS: Cure rates of this triple therapy including esomeprazole, amoxicillin and metronidazole were 81% per ITT and the treatment was well tolerated. These optimal results with a simple clarithromycin-free triple therapy are better than described for standard triple therapy but there is still room for improvement to reach the desired target of 90% per ITT.

Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment.

BACKGROUND: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies. OBJECTIVES: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis. METHODS: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates. RESULTS: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies. CONCLUSIONS: PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.

[Evolution of the response to the first-line therapy for Helicobacter pylori infection in Uruguay]. / Evolución de la respuesta al tratamiento de primera línea de la infección por Helicobacter pylori en Uruguay.

INTRODUCTION: The eradication rate of the Helicobacter pylori (H pylori) infection using standard triple therapy has dropped globally in recent years, primarily due to the occurrence of antibiotic resistance. METHODS: Several therapy regimens were assessed in 823 patients treated the first time for H pylori infection in Uruguay, during the 1997 to 2011 period, divided into five-year groups. All patients underwent 13C isotope-urea breath testing, between the 8th and 24th weeks after therapy. The standard triple plan (amoxicillin, clarithromycin and proton pump inhibitors) was the most commonly used (86.8%). RESULTS: The overall eradication rate was 66.6% (548 patients). With the standard triple plan, the reported eradication rates were 75% for the first 5-year term and 70.1% for the second 5-year term. The difference between these two periods was not statistically significant (P = 0.201). However, in the last term the eradication rate further declined to 62.4%, with a statistically significant difference (P = 0.014). No significant correlations were found between the response to therapy in this population and either the use of alcohol and/or yerba mate or the smoking habits. CONCLUSIONS: In Uruguay, the eradication rate of H pylori infection has dropped in the last five years and is below the internationally accepted levels. This feature demands searching for more effective alternative therapies, adapting the management to the national reality based on local antibiotic resistance patterns and drug availability.

Evolución de la respuesta al tratamiento de primera línea de la infección por Helicobacter pylori en Uruguay / [Evolution of the response to the first-line therapy for Helicobacter pylori infection in Uruguay].

INTRODUCTION: The eradication rate of the Helicobacter pylori (H pylori) infection using standard triple therapy has dropped globally in recent years, primarily due to the occurrence of antibiotic resistance. METHODS: Several therapy regimens were assessed in 823 patients treated the first time for H pylori infection in Uruguay, during the 1997 to 2011 period, divided into five-year groups. All patients underwent 13C isotope-urea breath testing, between the 8th and 24th weeks after therapy. The standard triple plan (amoxicillin, clarithromycin and proton pump inhibitors) was the most commonly used (86.8

(548 patients). With the standard triple plan, the reported eradication rates were 75

for the first 5-year term and 70.1

for the second 5-year term. The difference between these two periods was not statistically significant (P = 0.201). However, in the last term the eradication rate further declined to 62.4

, with a statistically significant difference (P = 0.014). No significant correlations were found between the response to therapy in this population and either the use of alcohol and/or yerba mate or the smoking habits. CONCLUSIONS: In Uruguay, the eradication rate of H pylori infection has dropped in the last five years and is below the internationally accepted levels. This feature demands searching for more effective alternative therapies, adapting the management to the national reality based on local antibiotic resistance patterns and drug availability.

Evolución de la respuesta al tratamiento de primera línea de la infección por Helicobacter pylori en Uruguay. / [Evolution of the response to the first-line therapy for Helicobacter pylori infection in Uruguay].

INTRODUCTION: The eradication rate of the Helicobacter pylori (H pylori) infection using standard triple therapy has dropped globally in recent years, primarily due to the occurrence of antibiotic resistance. METHODS: Several therapy regimens were assessed in 823 patients treated the first time for H pylori infection in Uruguay, during the 1997 to 2011 period, divided into five-year groups. All patients underwent 13C isotope-urea breath testing, between the 8th and 24th weeks after therapy. The standard triple plan (amoxicillin, clarithromycin and proton pump inhibitors) was the most commonly used (86.8

). RESULTS: The overall eradication rate was 66.6

(548 patients). With the standard triple plan, the reported eradication rates were 75

for the first 5-year term and 70.1

for the second 5-year term. The difference between these two periods was not statistically significant (P = 0.201). However, in the last term the eradication rate further declined to 62.4

, with a statistically significant difference (P = 0.014). No significant correlations were found between the response to therapy in this population and either the use of alcohol and/or yerba mate or the smoking habits. CONCLUSIONS: In Uruguay, the eradication rate of H pylori infection has dropped in the last five years and is below the internationally accepted levels. This feature demands searching for more effective alternative therapies, adapting the management to the national reality based on local antibiotic resistance patterns and drug availability.

Prevalencia de la enfermedad por reflujo gastroesofágico en Uruguay / Prevalence of gastroesophageal reflux disease in Uruguay

Antecedente La enfermedad por reflujo gastroesofágico (ERGE) es una condición frecuente, con grandes diferencias geográficas en todo el mundo. Uruguay carece de datos epidemiológicos sobre esta enfermedad. Objetivo Estimar la prevalencia de la ERGE en 2 poblaciones adultas de Uruguay, urbana y hospitalaria, mediante el Gastroesophageal reflux disease Questionnaire (GerdQ) e interrogatorio de síntomas típicos. Material y método Se realizó un estudio descriptivo de corte transversal mediante el uso de 2 métodos diagnósticos administrados a 2 niveles: urbano y hospitalario. Uno de ellos fue el cuestionario GerdQ, estandarizado, de respuesta estructurada y el otro consistió en evaluar síntomas característicos de ERGE. Se incluyeron 1.141 personas procedentes de población urbana, con edad promedio de 52 (± 18 años) y 163 pacientes de una policlínica de gastroenterología, con edad promedio de 53 años (± 16 años).Resultados La prevalencia de ERGE en Uruguay utilizando el cuestionario GerdQ fue 4,69%, (IC 95% 2,92-6,46%), mientras que al considerar solo los síntomas típicos ascendió a 14,14% (IC 95% 12,57-15,71). En la muestra hospitalaria la prevalencia fue de 11,66% (IC 95% 6,42-16,89%) y 20,25% (IC 95% 14,01-26,48), respectivamente. Conclusión La prevalencia obtenida en la población urbana de Uruguay con el cuestionario GerdQ en la población sintomática (hospitalaria) fue más del doble respecto de la población general, 11,66 y 4,69%, respectivamente. La evaluación de síntomas, pirosis y/o regurgitación conduce sistemáticamente a un resultado de mayor prevalencia. El consenso en la definición de la ERGE y la herramienta utilizada son claves para interpretar y comparar los estudios epidemiológicos (AU)

Background Gastroesophageal reflux disease (GERD) is a common condition, with wide geographical differences worldwide. There are no epidemiological data on this disease for Uruguay. Objective To estimate the prevalence of GERD in two adult populations in Uruguay (urban and hospital) through the Gastroesophageal reflux disease Questionnaire (GerdQ) questionnaire and evaluation of typical symptoms. Material and method A descriptive, cross-sectional study was carried out through the use of two diagnostic methods administered in two settings: an urban and a hospital setting. The first method consisted of administration of the standardized GerdQ structured questionnaire and the other consisted of evaluating the typical symptoms of GERD. A total of 1141 persons from the urban population, with a mean age of 52 years (± 18 years), and 163 persons from a gastroenterology polyclinic, with a mean age of 53 years (± 16 years), were included. Results The prevalence of GERD in Uruguay was 4.69%, (95% CI 2.92-6.46%) when the GerdQ questionnaire was used, but increased to 14.14% (95% CI 12.57-15.71) when only typical symptoms were considered. In the hospital sample, the prevalence was 11.66% (95% CI 6.42-16.89%) and 20.25% (95% CI 14.01-26.48), respectively. Conclusion The prevalence obtained in the urban population of Uruguay with the GerdQ questionnaire in the symptomatic (hospital) population was more than double that in the general population, 11.66% and 4.69%, respectively. Evaluation of symptoms, pyrosis and/or regurgitation systematically yields a higher prevalence. Consensus on the definition of GERD and on the instrument used for its diagnosis are essential to interpret and compare epidemiological studies (AU)

[Prevalence of gastroesophageal reflux disease in Uruguay]. / Prevalencia de la enfermedad por reflujo gastroesofágico en Uruguay.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition, with wide geographical differences worldwide. There are no epidemiological data on this disease for Uruguay. OBJECTIVE: To estimate the prevalence of GERD in two adult populations in Uruguay (urban and hospital) through the Gastroesophageal reflux disease Questionnaire (GerdQ) questionnaire and evaluation of typical symptoms. MATERIAL AND METHOD: A descriptive, cross-sectional study was carried out through the use of two diagnostic methods administered in two settings: an urban and a hospital setting. The first method consisted of administration of the standardized GerdQ structured questionnaire and the other consisted of evaluating the typical symptoms of GERD. A total of 1141 persons from the urban population, with a mean age of 52 years (± 18 years), and 163 persons from a gastroenterology polyclinic, with a mean age of 53 years (± 16 years), were included. RESULTS: The prevalence of GERD in Uruguay was 4.69%, (95% CI 2.92-6.46%) when the GerdQ questionnaire was used, but increased to 14.14% (95% CI 12.57-15.71) when only typical symptoms were considered. In the hospital sample, the prevalence was 11.66% (95% CI 6.42-16.89%) and 20.25% (95% CI 14.01-26.48), respectively. CONCLUSION: The prevalence obtained in the urban population of Uruguay with the GerdQ questionnaire in the symptomatic (hospital) population was more than double that in the general population, 11.66% and 4.69%, respectively. Evaluation of symptoms, pyrosis and/or regurgitation systematically yields a higher prevalence. Consensus on the definition of GERD and on the instrument used for its diagnosis are essential to interpret and compare epidemiological studies.

Hepatotoxicidad, un problema global con especificidades locales: hacia la creación de una Red Hispano Latinoamericana de Hepatotoxicidad / Hepatotoxicity, a global problem with local features: toward the creation of a Pan-American Hepatotoxicity Network

El daño hepático tóxico inducido por fármacos (DILI) es una de las afecciones hepáticas más compleja debido a su capacidad de presentarse como cualquier otra enfermedad hepática aguda o crónica, potencial gravedad, y la ausencia de biomarcadores específicos para establecer la certeza diagnóstica que se sustenta en su sospecha y exclusión de causas alternativas. La incapacidad del proceso de desarrollo de los medicamentos de cribar completamente las moléculas hepatotóxicas e identificar a los sujetos susceptibles continúa haciendo imprescindible la farmacovigilancia poscomercialización. Los registros de hepatotoxicidad se convierten en un instrumento idóneo para la recogida sistemática, según criterios consensuados y con continuidad de datos bien definidos. Se describen sumariamente las aportaciones del Registro Español de Hepatotoxicidad, y de otros registros internacionales, y se invoca la oportunidad de incorporar a Latinoamérica en las iniciativas en marcha lo que promoverá la investigación y la comprensión de los complejos mecanismos involucrados en esta reacción adversa (AU)

Drug-induced liver damage is one of the most complex liver diseases due to its similar presentation to other acute or chronic liver processes, its potential severity and the absence of specific biomarkers to confirm diagnosis, which is based on clinical suspicion and exclusion of alternative causes. Because the drug development process fails to completely screen out hepatotoxic molecules and identify susceptible individuals, postmarketing pharmacovigilance remains essential. Hepatotoxicity registries are the ideal instrument for systematic and continual data collection, using preestablished criteria based on consensus. The present article briefly describes the contributions of the Spanish Hepatotoxicity Registry and those of other international registries. Hopefully, Latin American registries will be incorporated into existing initiatives, which will stimulate research and improve understanding of the complex mechanisms involved in this adverse reaction (AU)

[Hepatotoxicity, a global problem with local features: toward the creation of a Pan-American Hepatotoxicity Network]. / Hepatotoxicidad, un problema global con especificidades locales: hacia la creación de una Red Hispano Latinoamericana de Hepatotoxicidad.

Drug-induced liver damage is one of the most complex liver diseases due to its similar presentation to other acute or chronic liver processes, its potential severity and the absence of specific biomarkers to confirm diagnosis, which is based on clinical suspicion and exclusion of alternative causes. Because the drug development process fails to completely screen out hepatotoxic molecules and identify susceptible individuals, postmarketing pharmacovigilance remains essential. Hepatotoxicity registries are the ideal instrument for systematic and continual data collection, using preestablished criteria based on consensus. The present article briefly describes the contributions of the Spanish Hepatotoxicity Registry and those of other international registries. Hopefully, Latin American registries will be incorporated into existing initiatives, which will stimulate research and improve understanding of the complex mechanisms involved in this adverse reaction.

Clebopride: double-blind comparative evaluation with metoclopramide in dyspepsia

Sessenta e três pacientes com sintomas devido a dispepsia foram tratados durante oito semanas com cleboprida (30 pacientes) e com metoclopramida (33 pacientes). Ambas as drogas proporcionaram resultados satisfatórios e foram bem toleradas. Todavia, a cleboprida apresenta vantagens já que sua dose eficaz diária é 20 vezes mais baixa que a da metoclopramida