Comparative Analysis of Clinical Practice Guidelines for the Pharmacological Treatment of Type 2 Diabetes Mellitus in Latin America.

PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) is one of the leading causes of death and disability in the world. The majority of diabetes deaths (> 80%) occur in low- and middle-income countries, which are predominant in Latin America. Therefore, the purpose of this article is to compare the clinical practice guideline (CPG) for the pharmacological management of T2DM in Latin America (LA) with international reference guidelines. RECENT FINDINGS: Several LA countries have recently developed CPGs. However, the quality of these guidelines is unknown according to the AGREE II tool and taking as reference three CPGs of international impact: American Diabetes Association (ADA), European Diabetes Association (EASD), and Latin American Diabetes Association (ALAD). Ten CPGs were selected for analysis. The ADA scored > 80% on the AGREE II domains and was selected as the main comparator. Eighty percent of LA CPGs were developed before 2018. Only one was not recommended (all domains < 60%). The CPGs in LA have good quality but are outdated. They have significant gaps compared to the reference. There is a need for improvement, as proposing updates every three years to maintain the best available clinical evidence in all guidelines.

Premezclados como alternativa para el uso seguro de medicamentos intravenosos en escenarios de atención en salud / Premixed products, an alternative for safe intravenous medications use in health care settings / As pré-misturas como alternativa para o uso seguro de drogas intravenosas em ambientes de saúde

RESUMEN Objetivo: presentar el panorama de errores de medicación, los recursos asociados a la preparación de medicamentos intravenosos y el uso de premezclados en la aten ción en salud. Metodología: se realizaron búsquedas en diferentes bases de datos, sin límite de fecha o tipo de estudio. Adicionalmente se realizó un análisis para estimar los costos, validando con expertos los recursos en central de mezclas. Resultados: los errores de medicación son un error médico común a nivel global. Los datos disponi bles son heterogéneos, pero sugieren que los errores de medicación pueden ser una causa considerable de morbilidad y mortalidad en ciertas poblaciones y contextos, con intervenciones adicionales, estancias hospitalarias prolongadas, mayores costos de atención y reducción en la probabilidad de que el tratamiento sea oportuno y eficaz. En medicinas intravenosas resultan escenarios de mayor gravedad y mayor nivel de costos. Los costos laborales anuales para una central de mezclas en Colombia se estiman entre 281,5 y 422,3 millones de pesos. La estandarización, como parte de los fármacos premezclados proporciona menor riesgo de contaminación, menor posibilidad de error en la preparación, menor incidencia de complicaciones rela cionadas con la terapia, disminución del desperdicio, mejora en la oportunidad de dispensación, optimización en el trabajo de los equipos de farmacia y reducción de costos asociados con este proceso. Conclusiones: el uso de premezclados, como parte de un programa de reducción de errores de medicación, puede mejorar los indicadores de calidad en administración de medicamentos y garantizar un uso más seguro de la terapia intravenosa.

SUMMARY Objective: To present an overview of medication preparation and administration errors, the resources implied in the preparation of intravenous medications, and the use of premixed drugs in healthcare settings. Methodology: We performed a litera ture review without limits by date or type of study. Additionally, analysis and vali dation by pharmaceutical experts were carried out to estimate the use of resources and related costs. Results: The available heterogeneous data suggest that medication errors are a significant cause of morbidity and mortality in specific populations and settings. Error medications cause additional interventions, prolonged hospitalization, higher costs of care, and a reduction in the treatment probability of success. Errors involving intravenously administered drugs have more severe consequences and generate higher costs. Annual labor costs for centralized medication mixing in Colombia are estimated between $281.5 and $422.3 million. Premixed drugs decrease the risk of contamination, the possibility of error in the preparation, and the incidence of complications related to therapy. Also, its use is related to the reduc tion of waste, improvement in the timing of dispensing, optimizing the pharmacy team, and reducing costs associated with this process. Conclusions: The use of premixes as part of a program to reduce medication errors can improve the quality indicators in drug administration and guarantee a safer use of intravenous therapy.

RESUMO Objetivo: apresentar o panorama dos erros de medicação, os recursos associados ao preparo de medicamentos intravenosos e o uso de pré-misturas na assistência à saúde. Metodologia: as buscas foram realizadas em diferentes bases de dados, sem limite de data ou tipo de estudo. Além disso, foi realizada uma análise para estimar os custos, validando com especialistas os recursos no centro de mistura. Resultados: erros de medicação são um erro médico comum globalmente. Os dados disponíveis são heterogêneos, mas sugerem que os erros de medicação podem ser uma causa significativa de morbidade e mortalidade em certas populações e contextos, com intervenções adicionais, internações hospitalares mais longas, custos mais altos de atendimento e probabilidade reduzida de que o tratamento seja oportuno e eficaz. Nos medicamentos intravenosos, resultam cenários de maior gravidade e maior nível de custos. Os custos anuais de mão de obra para uma usina de mistura na Colômbia são estimados entre 281,5 e 422,3 milhões de pesos. A padronização, como parte dos medicamentos pré-misturados, proporciona menor risco de contaminação, menor possibilidade de erro no preparo, menor incidência de complicações relacionadas à terapêutica, redução de desperdícios, melhoria na oportunidade de dispensação, otimização no trabalho das equipes. da farmácia e redução dos custos associados a este processo. Conclusões: o uso de pré-misturas, como parte de um programa de redução de erros de medicação, pode melhorar os indicadores de qualidade na admi nistração de medicamentos e garantir um uso mais seguro da terapia intravenosa.

Characterization of new psychoactive substances by integrating benchtop NMR to multi-technique databases.

New psychoactive substances (NPS) have become a serious threat for public health due to their ability to be sold in the street or on internet. NPS are either derived from commercial drugs which are misused (recreational rather than medical use) or whose structure is slightly modified. To regulate NPS, it is essential to accurately characterize them, either to recognize molecules that were previously identified or to quickly elucidate the structure of unknown ones. Most approaches rely on the determination of the exact mass obtained by high-resolution mass spectrometry requiring expensive equipment. This motivated us to develop a workflow in which the elucidation is assisted with databases and does not need the exact mass. This workflow combines 1D and 2D NMR measurements performed on a benchtop spectrometer with IR spectroscopy, for creating a multi-technique database to characterize pure and mixed NPS. The experimental database was created with 57 entries mostly coming from seizures, mainly cathinones, cannabinoids, amphetamines, arylcyclohexylamines, and fentanyl. A blind validation of the workflow was carried out on a set of six unknown seizures. In the first three cases, AF, AB-FUBINACA, and a mixture of 2C-I and 2C-E could be straightforwardly identified with the help of their reference spectra in the database. The two next samples were elucidated for the first time with the help of the database to reveal NEK and MPHP substances. Finally, a precise quantification of each characterized NPS was obtained in order to track NPS trafficking networks.

Human-induced ecological cascades: Extinction, restoration, and rewilding in the Galápagos highlands.

Oceanic islands support unique biotas but often lack ecological redundancy, so that the removal of a species can have a large effect on the ecosystem. The larger islands of the Galápagos Archipelago once had one or two species of giant tortoise that were the dominant herbivore. Using paleoecological techniques, we investigate the ecological cascade on highland ecosystems that resulted from whalers removing many thousands of tortoises from the lowlands. We hypothesize that the seasonal migration of a now-extinct tortoise species to the highlands was curtailed by decreased intraspecific competition. We find the trajectory of plant community dynamics changed within a decade of the first whaling vessels visiting the islands. Novel communities established, with a previously uncommon shrub, Miconia, replacing other shrubs of the genera Alternanthera and Acalypha. It was, however, the introduction of cattle and horses that caused the local extirpation of plant species, with the most extreme impacts being evident after c. 1930. This modified ecology is considered the natural state of the islands and has shaped subsequent conservation policy and practice. Restoration of El Junco Crater should emphasize exclusion of livestock, rewilding with tortoises, and expanding the ongoing plantings of Miconia to also include Acalypha and Alternanthera.

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy / Predictores de eventos clínicos en una cohorte de pacientes con enfermedad de Fabry en tratamiento sustitutivo enzimático

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. Study design: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120). Results: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. (AU)

El objetivo de este estudio es realizar un mapa del tratamiento actual de la enfermedad de Fabry en España, analizando el efecto de diferentes factores en el desarrollo de eventos clínicos a largo plazo. Diseño del estudio: Análisis observacional retrospectivo multicéntrico. Criterios de inclusión: pacientes diagnosticados y tratados de enfermedad de Fabry. Se recogieron datos generales en relación con el diagnóstico, síntomas y tipo mutación, tipo de tratamiento recibido, evolución renal y cardiológica. Durante un tiempo de seguimiento de 60 meses (24-120), se recogió el primer evento clínico tras el inicio de tratamiento sustitutivo enzimático definido como mortalidad, evento renal, cardiológico o neurológico. Resultados: Se incluyeron 69 pacientes (42 H, 27 M) con una edad media de 44,6±13,7 años. A los cinco años de tratamiento, el FGe y la hipertrofia ventricular izquierda se mantuvieron estables, y la albuminuria tiende a disminuir, siendo este descenso más significativo en el grupo de pacientes tratados con beta-galactosidasa (de 242 a 128mg/g (p=0,05). Veintiún pacientes sufrieron un evento clínico (30%): seis renales, dos neurológicos y 13 cardiológicos (incluidas tres muertes). Los pacientes con ERC (FGe<60) antes del inicio de tratamiento tuvieron más eventos (log-rank 12.423, p=0,001), manteniéndose la predicción si excluíamos los eventos renales (log-rank 4.086 (p=0,043) en hombres y mujeres. La peor función renal al inicio del tratamiento aumentó entre tres y siete veces el riesgo de eventos clínicos en diferentes modelos de Cox ajustados. Conclusiones: La función renal al inicio de tratamiento sustitutivo enzimático es la principal predictora de desarrollo de eventos clínicos a largo plazo, tanto en hombres como mujeres. El inicio de tratamiento sustitutivo enzimático precoz antes del desarrollo de ERC mejoraría el pronóstico. (AU)

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Oximetry and neonatal examination for the detection of critical congenital heart disease: a systematic review and meta-analysis.

Background: Undiagnosed congenital heart disease in the prenatal stage can occur in approximately 5 to 15 out of 1000 live births; more than a quarter of these will have critical congenital heart disease (CCHD). Late postnatal diagnosis is associated with a worse prognosis during childhood, and there is evidence that a standardized measurement of oxygen saturation in the newborn by cutaneous oximetry is an optimal method for the detection of CCHD. We conducted a systematic review of the literature and meta-analysis comparing the operational characteristics of oximetry and physical examination for the detection of CCHD. Methods: A systematic review of the literature was conducted on the following databases including published studies between 2002 and 2017, with no language restrictions: Pubmed, Science Direct, Ovid, Scopus and EBSCO, with the following keywords: oximetry screening, critical congenital heart disease, newborn OR oximetry screening heart defects, congenital, specificity, sensitivity, physical examination. Results: A total of 419 articles were found, from which 69 were selected based on their titles and abstracts. After quality assessment, five articles were chosen for extraction of data according to inclusion criteria; data were analyzed on a sample of 404,735 newborns in the five included studies. The following values were found, corresponding to the operational characteristics of oximetry in combination with the physical examination: sensitivity: 0.92 (CI 95%, 0.87-0.95), specificity: 0.98 (CI 95%, 0.89-1.00), for physical examination alone sensitivity: 0.53 (CI 95%, 0.28-0.78) and specificity: 0.99 (CI 95%, 0.97-1.00). Conclusions: Evidence found in different articles suggests that pulse oximetry in addition to neonatal physical examination presents optimal operative characteristics that make it an adequate screening test for detection of CCHD in newborns, above all this is essential in low and middle-income settings where technology medical support is not entirely available.

Cost-effectiveness analysis of newborn pulse oximetry screening to detect critical congenital heart disease in Colombia.

BACKGROUND: In many countries, economic assessments of the routine use of pulse oximetry in the detection of Critical Congenital Heart Disease (CCHD) at birth has not yet been carried out. CCHDs necessarily require medical intervention within the first months of life. This assessment is a priority in low and medium resource countries. The purpose of this study was to assess the cost-effectiveness (CE) relation of pulse oximetry in the detection of cases of CCHD in Colombia. METHODS: A full economic assessment of the cost-effectiveness type was conducted from the perspective of society. A decision tree was constructed to establish a comparison between newborn physical examination plus pulse oximetry, versus physical examination alone, in the diagnosis of CCHDs. The sensitivity and specificity of pulse oximetry were estimated from a systematic review of the literature; to assess resource use, micro-costing analyses and surveys were conducted. The time horizon of the economic evaluation was the first week after birth and until the first year of life. The incremental cost-effectiveness ratio (ICER) was determined and, to control for uncertainty, deterministic and probabilistic sensitivity analysis were made, including the adoption of different scenarios of budgetary impact. All costs are expressed in US dollars from 2017, using the average exchange rate for 2017 [$2,951.15 COP for 1 dollar]. RESULTS: The costs of pulse oximetry screening plus physical examination were $102; $7 higher than physical examination alone. The effectiveness of pulse oximetry plus the physical examination was 0.93; that is, 0.07 more than the physical examination on its own. The ICER was $100 for pulse oximetry screening; that is, if one wishes to increase 1% the probability of a correct CCHD diagnosis, this amount would have to be invested. A willingness to pay of $26.292 USD (direct medical cost) per probability of a correct CCHD diagnosis was assumed. CONCLUSIONS: At current rates and from the perspective of society, newborn pulse oximetry screening at 24 h in addition to physical examination, and considering a time horizon of 1 week, is a cost-effective strategy in the early diagnosis of CCHDs in Colombia.Trial registration "retrospectively registered".

Colonoscopia y endocarditis: una relación comprometida / Colonoscopy and endocarditis: a compromised relationship

No disponible

«Las otras¼ bradicardias / Those "other" bradycardias

La bradicardia es un hallazgo frecuente en el contexto de pacientes hospitalizados. Algunas veces se detecta de manera incidental y se minimizan sus implicaciones clínicas. No obstante, en ocasiones se asocia con la presencia de síntomas o compromiso hemodinámico en los pacientes que ameritan una intervención adicional. La etiología de la bradicardia no siempre es fácil de determinar y no es extraño que se inicien múltiples estudios con el fin de aclarar el porqué de la situación. Los clínicos estamos familiarizados con el efecto farmacológico y los efectos adversos de variados medicamentos que usamos cotidianamente. A pesar de esto, existen múltiples medicamentos con potencial para desarrollar la bradicardia como respuesta a una propiedad farmacológica menos conocida o en relación con efectos adversos infrecuentes, pero sin duda significativos. El objetivo de la presente revisión es repasar las propiedades farmacológicas y el impacto clínico de algunas sustancias que se han relacionado con la bradicardia, más allá de los que todos conocemos, con el fin de orientar las intervenciones a realizar en los pacientes con causas farmacológicas y reversibles de la bradicardia.

Bradycardia is a common finding in the context of hospitalized patients. Sometimes it is incidentally detected and its clinical implications are minimized. But sometimes it is associated with the presence of symptoms or hemodynamic compromise in patients who warrant further intervention. The etiology of the bradycardia is not always easy to determine and it is not surprising that many studies are initiated in order to clarify the reason for the situation. Clinicians are familiar with the pharmacological and adverse effects of various drugs we use every day. Despite this, there are many drugs with potential to develop bradycardia in response to a less known pharmacological properties or effects related to rare but certainly significant effects. The aim of this review is to explain the pharmacological properties and clinical impact of some substances that have been associated with bradycardia, beyond which we all know, in order to target interventions to be performed in patients with pharmacological and reversible causes of bradycardia.

Impacts of climate variability and human colonization on the vegetation of the Galápagos Islands.

A high-resolution (2-9 year sampling interval) fossil pollen record from the Galápagos Islands, which spans the last 2690 years, reveals considerable ecosystem stability. Vegetation changes associated with independently derived histories of El Niño Southern Oscillation variability provided evidence of shifts in the relative abundance of individual species rather than immigration or extinction. Droughts associated with the Medieval Climate Anomaly induced rapid ecological change that was followed by a reversion to the previous state. The paleoecological data suggested nonneutral responses to climatic forcing in this ecosystem prior to the period of human influence. Human impacts on the islands are evident in the record. A marked decline in long-term codominants of the pollen record, Alternanthera and Acalypha, produced a flora without modern analogue before 1930. Intensified animal husbandry after ca. 1930 may have induced the local extinction of Acalypha and Alternanthera. Reductions in populations of grazing animals in the 1970s and 1980s did not result in the return of the native flora, but in invasions by exotic species. After ca. 1970 the trajectory of habitat change accelerated, continuously moving the ecosystem away from the observed range of variability in the previous 2690 years toward a novel ecosystem. The last 40 years of the record also suggest unprecedented transport of lowland pollen to the uplands, consistent with intensified convection and warmer wet seasons.

Consideraciones prácticas para el uso de los nuevos anticoagulantes orales / Practical considerations for the use of new oral anticoagulants

A pesar de la eficacia comprobada acerca del uso de warfarina como terapia anticoagulante, las múltiples interacciones, el estrecho margen terapéutico y la necesidad de monitorización seriada han planteado el escenario para el desarrollo de nuevos medicamentos como dabigatran, rivaroxaban y apixaban que ofrecen nuevas alternativas para el tratamiento del paciente anticoagulado. El conocimiento de las características farmacológicas y farmacocinéticas así como el contexto específico en el cual pueden usarse se convierten en una necesidad para los médicos que se enfrentan a este tipo de pacientes.

Despite the proven efficacy on the use of warfarin as anticoagulant therapy, the multiple interactions, narrow therapeutic index and the need for serial monitoring have raised the need for the development of new drugs such as dabigatran, rivaroxaban and apixaban, that offer new alternatives for treating the anticoagulated patient. Knowledge of the pharmacologic and pharmacokinetic characteristics and the specific context in which they can be used become a necessity for physicians faced with these patients.

Modelos de evaluación económica: su aplicación en las decisiones sanitarias / Economic evaluation models and their application in health decision making

Objetivo: Introducir los conceptos clave sobre modelos de evaluación económica en salud como herramientas de toma de decisiones, sector donde la asignación eficiente de recursos se da en ambientes de escasez e incertidumbre. Método: Se desarrolló un análisis simplificado de los principales conceptos empleados en la construcción de un modelo de evaluación económica en salud a partir de las principales referencias sobre toma de decisiones en salud de acuerdo con los portales de evaluación económica como CEA Tufts University, CRD de la Universidad de York, Medline y Pubmed. Desarrollo: Se definieron modelos en el contexto de evaluación económica en salud, necesarios en un sistema cambiante y de incertidumbre. Se analizaron los pasos para el desarrollo de un buen modelo y la estructuración de una evaluación crítica de éstos. Se finalizó con la discusión y conclusiones de la actualización de la información. Como anexo se incluye una lista de revisión para verificar la confiabilidad de los modelos que se van a realizar. Conclusión: Los modelos en evaluación económica aparecen como herramienta de toma de decisiones en salud; por esta razón, y como simplificadores de la realidad, deben ser transparentes y reproducibles de manera que todos los elementos considerados estén respaldados sistemáticamente con descripciones claras y puntuales...

Objective: To introduce the key concepts of economic evaluation models as tools in health decision-making, a sector where the efficient allocation of resources is done in an environment of scarcity and uncertainty. Method: We developed a simplified analysis of the main concepts used in the construction of a model of economic assessment in health from the main references on decision-making in health according to economic assessment portals such as CEA Tufts University, CRD at University of York, Medline, and Pubmed. Development: Models were defined in the context of economic assessment in health as needed in a system of ever-changing requirements and uncertainty. It discusses the steps for developing a good model and the structure for a critical evaluation of it, ending with a discussion and the conclusions of the updated information. Attached is a checklist for verifying the reliability of the models to be executed. Conclusion: Economic evaluation models develop as a tool for decision making in health; for this reason and as simplifications of reality, they must be transparent and reproducible so that all elements are considered systematically backed with clear and precise descriptions...