Prevalence of potentially inappropriate medications in older adults in Argentina using Beers criteria and the IFAsPIAM List.

Background Medications in which the risk of adverse events exceeds the expectations of clinical benefits are called potentially inappropriate medications (PIMs). To identify the use of PIMs in elderly patients, the most commonly used tool are the Beers criteria, developed for the population of the United States. Recently, a consensus panel of Argentine experts developed the first Latin American tool, called the IFAsPIAM List. Objective The present study aimed to identify PIM prescriptions in elderly outpatients, to estimate the prevalence of PIMs, and to evaluate their possible relation with polypharmacy and gender and age of the patients. Also, we aimed to compare the results obtained by using the Beers criteria and the IFAsPIAM List. Setting Ten community pharmacies of Rosario, Santa Fe, Argentina. Methods A cross-sectional observational study was conducted between February and September 2015. Data were acquired from 56,952 prescriptions prescribed to 2231 patients aged 65 years old or older. To detect the use of PIMs, we used two tools: the Beers criteria and the IFAsPIAM List. Main outcome measure The prevalence of PIM use according to the Beers criteria and the IFAsPIAM List. Results The monthly average of medications dispensed per patient was 4.35 ± 2.18 and 42.27% of the patients presented major polypharmacy. The prevalence of PIMs was 72.75% according to the Beers criteria and 71.13% according to the IFAsPIAM List (Kappa coefficient k = 0.72), and was significantly higher in patients with major polypharmacy, older than 75 years old, and females. The most frequent PIMs prescribed were anxiolytics, analgesics and antipsychotics. Conclusions The IFAsPIAM List is an effective tool to evaluate the prescription of PIMs in the elderly. The results showed a high prevalence of PIMs with a multicausal origin and directly associated with polypharmacy. As clarified by the authors of the IFAsPIAM List, the criteria specified in the list do not substitute the clinical evaluation of each patient.

Ingredientes Farmacéuticos Activos Potencialmente Inapropiados en Adultos Mayores: Lista IFAsPIAM: Panel de Consenso Argentino.

OBJECTIVES: To perform a list agreed by Argentinean experts and adapted to the local context containing potentially inappropriate (PI) medications in old people (OP) usingthe Delphi consensus technique optimized for this subject. METHODS: A preliminary list of potentially inappropriate medications (PIM) was drawn up based on foreign PIM lists and a selective search in the scientific literature. The iterative Delphi process was used to submit the active pharmaceutical ingredients (APIs) of the preliminary PIM list to the panel of Argentinean experts. The analysis of theanswers to determine the arrival to the consensus was carried out applying three criteria specially defined for this purpose. RESULTS: After two Delphi rounds, it was not reached agreement about 12 APIs. The List of explicit criteria for PIAPIs for use in OP (IFAsPIAM List) was finally constituted by 128 APIs corresponding to 9 groups of the ATC classification system to which they were organized. In addition to each API, information justifying the unfavorable benefit/risk profile and therapeutic alternatives or recommendations/precautions was recorded. The group with the most PI APIs was N (NervousSystem) (60; 47%) followed by groups C (Cardiovascular) and M (Musculoskeletal). CONCLUSION: This study presents the first Latin American list of PIM in OP developed using an expert consensus technique. The IFAs PIAM List would contribute to the rational use of drugs in elderly population, constituting a valuable tool in Argentinean public health.

[Criteria for defining consensus achievement in Delphi studies that assess potentially inappropriate medications in the elderly].

BACKGROUND: The statistical analysis of survey responses based on a categorical Likert scale, as those used in the Delphi technique, has been questioned because the methodology used is based on numerical data analysis. AIM: To develop criteria for defining the consensus achievement in Delphi studies conducted for the assessment of potentially inappropriate medications (PIM) in the elderly. METHODS: It was constructed an index (Yq) which takes into account the agreement by pairs of evaluators, whose calculus equation is based on combinatorial analysis. Yq was applied in a pilot study with Delphi methodology for assessing the safety of 12 drugs through a Likert scale with five response categories. RESULTS: On the basis of analyzing the distance (d) in between each pair of categories from the scale, it was determined the associated weighting, w=1-d, to be applied in the calculus of Yq: proportion of agreements weighted. There were defined three criteria that need to be satisfied to obtained the consensus in each item (drug) of Delphi questionnaire : a) Number of evaluators ≥60% of the panel members, b)Yq≥0,800; c) frequency of the statistical mode ≥60%. On regards to the analysis, 8/12 drugs were evaluated as potentially inappropriate for elderly adults while the remaining 4 should be revalued in successive rounds due to not obtaining consensus. CONCLUSION: The index takes into account the real distances between the Likert scale categories and the developed criteria constitute a simple tool for the analysis of the Delphi questionnaires made for the valuation of PIM on older adults.

[Cardiac adverse effects of domperidone in adult patients: a systematic review]. / Efectos adversos cardíacos de la domperidona en pacientes adultos: revisión sistemática.

BACKGROUND: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. AIM: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. MATERIAL AND METHODS: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. RESULTS: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. CONCLUSIONS: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.

Efectos adversos cardíacos de la domperidona en pacientes adultos: revisión sistemática / Cardiac adverse effects of domperidone in adult patients: a systematic review

Background: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. Aim: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Material and Methods: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Results: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Conclusions: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.

[Proarrhythmic effects of domperidone in infants: a systematic review]. / Revisión Sistemática de la evidencia de efectos proarrítmicos de domperidona en infantes.

AIMS: To assess the association of the use of domperidone in infants with QTc interval prolongation and proarrhythmic events. METHODS: A systematic search of the scientific literature was conducted without any date or language restriction. The electronic database MEDLINE and the sources LILACS, ScIELO and Cochrane library were consulted. RESULTS: From the twelve identified studies, eight were excluded because they did not meet the inclusion criteria. One case report and three pilot studies were selected. Rocha et al (2005) reported the case of an infant (age 3 months) with QTc interval = 463 ms after being treated during one month with 1.8 mg/kg/day of oral domperidone. Djeddi et al (2008) administered an average dose of 1.3 mg/kg/day to 31 neonates; QTc interval prolongation > 30 ms was observed in nine neonates. Hegar et al (2009) studied 10 infants (mean age 5.6 months) who received 0.8 mg/ kg/day of oral domperidone; QTc interval prolongation was not observed. Günlemez et al (2010) enrolled 40 premature infants who were administered 1 mg/kg/day of oral domperidone; the QTc interval increased to above 450 ms in two infants. CONCLUSIONS: Although evidence that orally administrated domperidone in infants produces prolongation of QTc interval was found, further studies are needed in order to quantify the risk associated with the drug in that population. We suggest that heath professionals should conduct ECGs to infants treated with domperidone and inform the pharmacovigilance system the occurrence of any case of adverse event.

Objetivo: Determinar si existe evidencia de prolongación del intervalo QTc y efectos proarrítmicos asociados al uso de domperidona oral en infantes. Método: Se realizó una revisión sistemática de la literatura científica consultando la base de datos electrónica MEDLINE y las fuentes LILACS, ScIELO y Biblioteca Cochrane a través de la Biblioteca Virtual de Salud, sin límite de fecha ni de idioma. Resultados: De los estudios identificados se excluyeron ocho por no cumplir con los criterios de inclusión, quedando seleccionados un reporte de caso y tres estudios pilotos. Rocha et al (2005) reportan el caso de un niño de 3 meses con intervalo QTc=463 mseg tras un mes de tratamiento con 1,8 mg/kg/día de domperidona oral. Djeddi et al (2008) administraron una dosis promedio de 1,3 mg/kg/día a 31 neonatos, observando prolongación del intervalo QTc>30 mseg en nueve. Hegar et al (2009) estudiaron a 10 niños con edad media de 5,6 meses tratados con 0,8 mg/kg/día y no observaron prolongación del intervalo QTc. Gunlemez et al (2010) incluyeron en su estudio a 40 infantes prematuros a quienes administraron 1 mg/kg/día de domperidona oral, en dos de ellos el intervalo QTc aumentó por encima de 450 mseg. Conclusiones: Aunque se encontró evidencia de prolongación del intervalo QTc en infantes tratados con domperidona oral, se necesitan más estudios para cuantificar el riesgo asociado a la droga en esta población. Se sugiere a los profesionales de la salud realizar un monitoreo electrocardiográfico de los infantes tratados con domperidona e informar al sistema de farmacovigilancia los casos de ocurrencia de eventos adversos.

Revisión Sistemática de la evidencia de efectos proarrítmicos de domperidona en infantes / Proarrhythmic effects of domperidone in infants: a systematic review

Objetivo: Determinar si existe evidencia de prolongación del intervalo QTc y efectos proarrítmicos asociados al uso de domperidonaoral en infantes. Método: Se realizó una revisión sistemática de la literatura científica consultando la base de datos electrónica MEDLINEy las fuentes LILACS, ScIELO y Biblioteca Cochrane a través de la Biblioteca Virtual de Salud, sin límite de fecha ni de idioma. Resultados: De los estudios identificados se excluyeron ocho por no cumplir con los criterios de inclusión, quedando seleccionados un reporte de caso y tres estudios pilotos. Rocha etal (2005) reportan el caso de un niño de 3 meses con intervalo QTc=463 mseg tras un mes de tratamiento con 1,8 mg/kg/díade domperidona oral. Djeddi et al (2008) administraron unadosis promedio de 1,3 mg/kg/día a 31 neonatos, observando prolongación del intervalo QTc>30 mseg en nueve. Hegar et al (2009) estudiaron a 10 niños con edad media de 5,6 meses tratados con 0,8 mg/kg/día y no observaron prolongación del intervalo QTc. Gunlemez et al (2010) incluyeron en su estudio a 40 infantes prematuros a quienes administraron 1 mg/kg/día de domperidona oral, en dos de ellos el intervalo QTc aumentó por encima de 450 mseg. Conclusiones: Aunque se encontró evidencia de prolongación del intervalo QTc en infantes tratados con domperidona oral, se necesitan más estudios para cuantificar el riesgo asociado a la droga en esta población. Se sugiere a los profesionales de la salud realizar un monitoreo electrocardiográfico de los infantes tratados con domperidona e informar al sistema de farmacovigilancia los casos de ocurrencia de eventos adversos

Aims: To assess the association of the use of domperidone in infants with QTc interval prolongation and proarrhythmic events. Methods: A systematic search of the scientific literature was conducted without any date or language restriction. The electronic database MEDLINE and the sources LILACS, ScIELO and Cochrane library were consulted. Results: From the twelve identified studies, eight were excluded because they did not meet the inclusion criteria. One case report and three pilot studies were selected. Rocha et al (2005) reported the case of an infant (age 3 months) with QTc interval = 463ms after being treated during one month with 1.8 mg/kg/day of oral domperidone. Djeddi et al (2008) administered an average dose of 1.3 mg/kg/day to 31 neonates; QTc interval prolongation > 30 ms was observed in nine neonates. Hegar et al (2009) studied 10 infants (mean age 5.6 months) who received 0.8 mg/ kg/day of oral domperidone; QTc interval prolongation was not observed. Günlemez et al (2010) enrolled 40 premature infants who were administered 1 mg/kg/day of oral domperidone; the QTc interval increased to above 450 ms in two infants. Conclusions: Although evidence that orally administrated domperidone in infants produces prolongation of QTc interval was found, further studies are needed in order to quantify the risk associated with the drug in that population. We suggest that heath professionals should conduct ECGs to infants treated with domperidone and inform the pharmacovigilance system the occurrence of any case of adverse event

Molecular characterization of methicillin-resistant coagulase-negative staphylococci from a neonatal intensive care unit.

OBJECTIVE: To evaluate clonal dissemination of methicillin-resistant coagulase-negative staphylococci (CNS). SETTING: Neonatal intensive care unit of a 180-bed, university-affiliated general hospital. PATIENTS: Neonates admitted to the neonatal intensive care unit between March 1999 and October 2000, from whom CNS were isolated as a unique pathogen. Patients from other wards from whom epidemiologically unrelated staphylococci strains were obtained served as control-patients. METHODS: Conventional methods were used for phenotypic characterization of CNS. Methicillin resistance was determined by mecA polymerase chain reaction (PCR) amplification. Genotypic characterization was done by random amplification of DNA with degenerated primers (RAPD) and repetitive element sequence-based PCR (rep-PCR). RESULTS: Forty methicillin-resistant CNS isolates obtained from neonates were characterized as Staphylococcus epidermidis (33), S. hominis (5), S. warneri (1), and S. auricularis (1). Both RAPD and rep-PCR indicated the presence of 4 different clones among the 33 S. epidermidis isolates. In turn, the 4 randomly selected, epidemiologically unrelated methicillin-resistant CNS strains obtained from control-patients showed 3 new profiles by RAPD and 2 by rep-PCR, which differed from the corresponding patterns mentioned earlier. Persistence of S. hominis in a neonate could be assessed by both genotypic techniques. CONCLUSIONS: The molecular characterization of the methicillin-resistant CNS studied indicated dissemination of one particular methicillin-resistant CNS clone among the neonates in the ward studied. Although RAPD showed a superior power to discriminate among methicillin-resistant CNS isolates, both RAPD and rep-PCR detected intraspecific and interspecific genomic diversity.

Importancia de la relación huésped-parásito en estafilococos coagulasa negativa aislados de neonatos / Clinical importance of understanding the bacterium-host interaction in coagulase-negative staphylococci isolated from neonates

OBJETIVOS. Los neonatos constituyen una población de alto riesgo para infecciones por estafilococos coagulasa negativa (ECN). Para comprender mejor dichos procesos se enfocó su estudio desde el punto de vista de la relación huésped-parásito. Para ello se propuso establecer si hay concordancia entre el resultado esperado de dicha relación dada por el índice de riesgo de los neonatos y el índice de virulencia de los microorganismos y la calificación de cepa colonizante o infectante, que surge del diagnóstico médico realizado en base a criterios clínicos. MÉTODOS. Se estudiaron 24 neonatos en los cuales se realizó un seguimiento epidemiológico estableciendo como factores de riesgo para infecciones por estos microorganismos: presencia de catéteres, sondas vesicales, cirugía previa, ingreso de más de 72 horas en el hospital, tratamiento prolongado con antibióticos y condiciones de inmunosupresión. En las cepas de ECN recuperadas de los materiales clínicos se determinaron los siguientes factores de patogenicidad: sinergismo de hemólisis, producción de polisacárido extracelular (slime), adherencia a catéter de teflon e hidrofobicidad. RESULTADOS. Hubo coincidencia entre el diagnóstico clínico y el resultado esperado de la relación húesped-parásito en 21 pacientes (87,5 por ciento). En 8 de estos pacientes no se produjo infección a pesar de presentar las cepas 3 de 4 factores de virulencia, ya que los pacientes no presentaban suficientes factores de riesgo. CONCLUSIONES. El estudio de la microbiología solamente en términos de identificación y tratamiento de los organismos causantes de enfermedad distorsiona el contexto biológico. Es necesario comprender la relación huésped-parásito para un enfoque adecuado del estudio de los procesos infecciosos (AU)