GRADE guidance 23: considering cost-effectiveness evidence in moving from evidence to health-related recommendations.

BACKGROUND: This is the 23rd in a series of articles describing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the certainty of evidence and strength of recommendations for systematic reviews, health technology assessments, and clinical guideline development. OBJECTIVES: We outline how resource utilization and cost-effectiveness analyses are integrated into health-related recommendations, using the GRADE Evidence to Decision (EtD) frameworks. STUDY DESIGN AND SETTING: Through iterative discussions and refinement, in-person, and online meetings, and through e-mail communication, we developed draft guidance to incorporate economic evidence in the formulation of health-related recommendations. We developed scenarios to operationalize the guidance. We presented a summary of the results to members of the GRADE Economic Evaluation Project Group. RESULTS: We describe how to estimate the cost of preventing (or achieving) an event to inform assessments of cost-effectiveness of alternative treatments, when there are no published economic evaluations. Evidence profiles and Summary of Findings tables based on systematic reviews of cost-effectiveness analyses can be created to provide top-level summaries of results and quality of multiple published economic evaluations. We also describe how this information could be integrated in GRADE's EtD frameworks to inform health-related recommendations. Three scenarios representing various levels of available cost-effectiveness evidence were used to illustrate the integration process. CONCLUSION: This GRADE guidance provides practical information for presenting cost-effectiveness data and its integration in the development of health-related recommendations, using the EtD frameworks.

Good or best practice statements: proposal for the operationalisation and implementation of GRADE guidance.

An evidence-based approach is considered the gold standard for health decision-making. Sometimes, a guideline panel might judge the certainty that the desirable effects of an intervention clearly outweigh its undesirable effects as high, but the body of supportive evidence is indirect. In such cases, the application of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach for grading the strength of recommendations is inappropriate. Instead, the GRADE Working Group has recommended developing ungraded best or good practice statement (GPS) and developed guidance under which circumsances they would be appropriate.Through an evaluation of COVID-1- related recommendations on the eCOVID Recommendation Map (COVID-19.recmap.org), we found that recommendations qualifying a GPS were widespread. However, guideline developers failed to label them as GPS or transparently report justifications for their development. We identified ways to improve and facilitate the operationalisation and implementation of the GRADE guidance for GPS.Herein, we propose a structured process for the development of GPSs that includes applying a sequential order for the GRADE guidance for developing GPS. This operationalisation considers relevant evidence-to-decision criteria when assessing the net consequences of implementing the statement, and reporting information supporting judgments for each criterion. We also propose a standardised table to facilitate the identification of GPS and reporting of their development. This operationalised guidance, if endorsed by guideline developers, may palliate some of the shortcomings identified. Our proposal may also inform future updates of the GRADE guidance for GPS.

A multistakeholder development process to prioritize and translate COVID-19 health recommendations for patients, caregivers and the public. A case study of the COVID-19 recommendation map.

BACKGROUND AND OBJECTIVES: To develop a digital communication tool to improve the implementation of up-to-date COVID-19 recommendations. Specifically, to improve patient, caregiver and public understanding of healthcare recommendations on prevention, diagnoses and treatment. METHODS: Multi-stakeholder engagement design. In conjunction with the COVID-19 Recommendations and Gateway to Contextualization RecMap, we co-developed a stakeholder prioritization, drafting and editing process to enhance guideline communication and understanding. RESULTS: This paper presents the multi-stakeholder development process with three distinct plain language recommendation formats: formal recommendation, good practice statement, and additional guidance. Our case study of COVID-19 plain language recommendations PLRs addresses both public health interventions (e.g., vaccination, face masks) and clinical interventions (e.g., home pulse oximetry). CONCLUSION: This paper presents a novel approach to engaging stakeholders in improving the communication and understanding of published guidelines during the COVID-19 pandemic.

Which actionable statements qualify as good practice statements In Covid-19 guidelines? A systematic appraisal.

OBJECTIVES: To evaluate the development and quality of actionable statements that qualify as good practice statements (GPS) reported in COVID-19 guidelines. DESIGN AND SETTING: Systematic review . We searched MEDLINE, MedSci, China National Knowledge Infrastructure (CNKI), databases of Grading of Recommendations Assessment, Development and Evaluation (GRADE) Guidelines, NICE, WHO and Guidelines International Network (GIN) from March 2020 to September 2021. We included original or adapted recommendations addressing any COVID-19 topic. MAIN OUTCOME MEASURES: We used GRADE Working Group criteria for assessing the appropriateness of issuing a GPS: (1) clear and actionable; (2) rationale necessitating the message for healthcare practice; (3) practicality of systematically searching for evidence; (4) likely net positive consequences from implementing the GPS and (5) clear link to the indirect evidence. We assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: 253 guidelines from 44 professional societies issued 3726 actionable statements. We classified 2375 (64%) as GPS; of which 27 (1%) were labelled as GPS by guideline developers. 5 (19%) were labelled as GPS by their authors but did not meet GPS criteria. Of the 2375 GPS, 85% were clear and actionable; 59% provided a rationale necessitating the message for healthcare practice, 24% reported the net positive consequences from implementing the GPS. Systematic collection of evidence was deemed impractical for 13% of the GPS, and 39% explained the chain of indirect evidence supporting GPS development. 173/2375 (7.3%) statements explicitly satisfied all five criteria. The guidelines' overall quality was poor regardless of the appropriateness of GPS development and labelling. CONCLUSIONS: Statements that qualify as GPS are common in COVID-19 guidelines but are characterised by unclear designation and development processes, and methodological weaknesses.

Design of an algorithm for the diagnostic approach of patients with joint pain.

BACKGROUND: Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. OBJECTIVE: To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. METHODS: Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point "joint pain" as a common symptom for the four diseases. RESULTS: Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. CONCLUSION: We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain. Key Points • We developed an algorithm with the participation of rheumatologists from 18 countries of Ibero-America, which gives a global vision of the clinical context of the patient with joint pain. • We integrated four rheumatic diseases into one tool with one common symptom: joint pain. It is a novel tool, as it is the first algorithm that will support the primary care physician in the consideration of four different rheumatic diseases. • It will improve the correct diagnosis and reduce the number of paraclinical tests requested by primary care physicians, in the management of patients with joint pain. This point was verified in a recently published study in the journal Rheumatology International (reference number 31).

El método Delphi en la investigación en reumatología: ¿lo estamos haciendo bien? / Delphi method in rheumatology research: Are we doing well?

RESUMEN Introducción: El método Delphi es una técnica que permite llegar al consenso en un grupo de expertos que opinan sobre un asunto específico. Se ha usado ampliamente en diferentes áreas del conocimiento, entre ellas las ciencias de la salud. La reumatología es una de las especialidades médicas que más ha empleado esta técnica de consenso. Objetivos: Realizar una revisión del proceso ideal que debe cumplir la aplicación del método Delphi. Describir el impacto actual del método Delphi en la investigación en salud y hacer una mirada crítica a su aplicación en la investigación en reumatología. Materiales y métodos: Se evaluó la frecuencia del uso del método Delphi en las publicaciones indexadas en MEDLINE como una aproximación a la medición de su empleo en ciencias de la salud. Se realizó una búsqueda de los artículos que reportan el uso del método Delphi como método de investigación en el área de reumatología. Resultados: Al realizar una búsqueda en Medline usando el término MeSH Delphi Technique se encontraron 4.574 artículos. Se incluyeron 148 artículos que aplicaron el método Delphi en investigación de reumatología. Se encontró que la aplicación del método no ha seguido los lineamientos definidos originalmente, ya sea tanto por no cumplir sus características definitorias u omitir alguna de sus fases, como por la falta de rigurosidad en el desarrollo de las mismas, hasta tal punto que solo una quinta parte de los artículos analizados cumplía las características definitorias del método, lo que puede poner en riesgo la validez de los resultados reportados por estas investigaciones. Conclusiones: El uso del método Delphi en investigación en salud es cada vez mayor, y la reumatología no es la excepción. La no estandarización y el apego a la metodología Delphi puede poner en riesgo la validez de los resultados que se obtienen de su uso en investigación. Los investigadores deben tener en cuenta los aspectos metodológicos básicos que definen el método Delphi para incluirlos en sus trabajos.

ABSTRACT Introduction: The Delphi method is a technique that allows consensus to be reached by a group of experts who have opinions on a specific issue. It has been widely used in different areas of knowledge, including health sciences. Rheumatology is one of the medical specialties that has used this consensus technique the most. Objectives: To conduct a review of the ideal process for application of the Delphi method. To describe the current impact of the Delphi method on health research, and take a critical look at its application in rheumatology research. Materials and methods: The frequency of use of the Delphi method in publications indexed in MEDLINE was evaluated, as an approximation to the measurement of its use in health sciences. A search was made of the articles that mentioned the use of the Delphi method as a research tool in rheumatology. Results: A total of 4,574 articles were found when searching Medline using the MeSH term "Delphi Technique". The analysis included 148 articles that applied the Delphi method in rheumatology research. It was found that the application of the method did not follow the guidelines originally defined. This was due to not meeting its defining characteristics, or omitting some of its phases. There was also lack of rigour in developing it, to the point that only a fifth of the articles analysed fulfilled the defining characteristics of the method. All these can put the validity of the results reported by these investigations at risk. Conclusions: Use of the Delphi method in health research is growing, and rheumatology is no exception. The lack of standardisation and adherence to the Delphi methodology may jeopardise the validity of the results obtained from its use in research. Researchers must take into account the basic methodological aspects that define the Delphi method, in order to include them in their work.

¿Is seropositivity in patients with rheumatoid arthritis treated with adalimumab a factor to develop anti-adalimumab antibodies? / ¿Es la seropositividad en pacientes con artritis reumatoide tratados con adalimumab un factor para desarrollar anticuerpos anti-adalimumab?

ABSTRACT Objective: To determine whether seropositivity in rheumatoid arthritis patients treated with adalimumab (ADL) is associated with the presence of anti-adalimumab (anti-ADL) antibodies. Materials and methods: A descriptive observational study that included patients diagnosed with rheumatoid arthritis according to ACR 1987 criteria, and who were on treatment with ADL as the first biological, for at least six months. All patients were evaluated for rheumatoid factor, anti-citrulline antibodies, erythrocyte sedimentation rate, C-reactive protein, clinimetric indices, and level of anti-ADL antibodies. Results: A total of 80 patients with a mean age of 56 years were evaluated, of whom 86% were women. The mean duration of the disease was 15 years, and the ADL exposure time was 52 months (median value). The seropositivity for rheumatoid factor tended to be higher in patients who developed anti-ADL antibodies compared to those who did not (90.5% vs. 66.1%). The magnitude of the association between rheumatoid factor and the presence of anti-ADL antibodies was shown to be strong and statistically significant (OR = 4.87, 95% CI; 1.03-23.03). Adjusted multivariate regression analyses showed a strong association (OR = 9.77, 95% CI; 1.74-54.79) between seropositivity and the presence of anti-ADL antibodies, which, given the low number of patients, lacks precision (95% CI very wide). Conclusions: Seropositive patients tend to have more anti-ADL antibodies. However, a larger sample size is required to obtain the necessary precision and greater certainty in these findings.

RESUMEN Objetivo: Determinar si la seropositividad en pacientes con artritis reumatoide tratados con adalimumab (ADL), se asocia a la presencia de anticuerpos anti-adalimumab (anti-ADL). Materiales y métodos: Es un estudio observacional descriptivo que incluyó pacientes con diagnóstico de artritis reumatoide según criterios ACR1987, que estaban en tratamiento con ADL como primer biológico, por al menos 6 meses. Todos los pacientes se evaluaron para factor reumatoide, anticuerpos anticitrulina, velocidad de sedimentación globular, proteína C reactiva, índices clinimétricos y nivel de anticuerpos anti-ADL. Resultados: Se evaluaron 80 pacientes con edad promedio de 56 arios, el 86% fueron mujeres, la duración promedio de la enfermedad fue de 15 años y el tiempo de exposición a ADL de 52 meses (valor mediano). La seropositividad para factor reumatoide tendió a ser mayor en los pacientes que desarrollaron anticuerpos anti-ADL en comparación con los que no (90,5% vs. 66,1%). La magnitud de la asociación entre factor reumatoide y la presencia de anticuerpos anti-ADL tendió a ser fuerte y estadísticamente significativa (OR = 4,87; IC 95%: 1,03-23,03). Los análisis ajustados de regresión multivariable mostraron una asociación fuerte (OR = 9,77; IC 95%: 1,74-54,79) entre la seropositividad y la presencia de anticuerpos anti-ADL, que dado el bajo número de pacientes carece de precisión (IC 95% muy amplios). Conclusiones: Los pacientes seropositivos tienden a presentar más anticuerpos anti-ADL; sin embargo, se requiere tener un mayor tamaño muestral para obtener la precisión necesaria y tener mayor certeza en estos hallazgos.

GRADE Guidelines: 19. Assessing the certainty of evidence in the importance of outcomes or values and preferences-Risk of bias and indirectness.

OBJECTIVES: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group defines patient values and preferences as the relative importance patients place on the main health outcomes. We provide GRADE guidance for assessing the risk of bias and indirectness domains for certainty of evidence about the relative importance of outcomes. STUDY DESIGN AND SETTING: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance and consulted GRADE members and other stakeholders for feedback. RESULTS: This is the first of two articles. A body of evidence addressing the importance of outcomes starts at "high certainty"; concerns with risk of bias, indirectness, inconsistency, imprecision, and publication bias lead to downgrading to moderate, low, or very low certainty. We propose subdomains of risk of bias as selection of the study population, missing data, the type of measurement instrument, and confounding; we have developed items for each subdomain. The population, intervention, comparison, and outcome elements associated with the evidence determine the degree of indirectness. CONCLUSION: This article provides guidance and examples for rating the risk of bias and indirectness for a body of evidence summarizing the importance of outcomes.

GRADE guidelines: 20. Assessing the certainty of evidence in the importance of outcomes or values and preferences-inconsistency, imprecision, and other domains.

OBJECTIVE: To provide Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidance for assessing inconsistency, imprecision, and other domains for the certainty of evidence about the relative importance of outcomes. STUDY DESIGN AND SETTING: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance, and consulted GRADE members and other stakeholders for feedback. RESULTS: We describe the rationale for considering the remaining GRADE domains when rating the certainty in a body of evidence for the relative importance of outcomes. As meta-analyses are not common in this context, inconsistency and imprecision assessments are challenging. Furthermore, confusion exists about inconsistency, imprecision, and true variability in the relative importance of outcomes. To clarify this issue, we suggest that the true variability is neither equivalent to inconsistency nor imprecision. Specifically, inconsistency arises from population, intervention, comparison and outcome and methodological elements that should be explored and, if possible, explained. The width of the confidence interval and sample size inform judgments about imprecision. We also provide suggestions on how to detect publication bias and discuss the domains to rate up the certainty. CONCLUSION: We provide guidance and examples for rating inconsistency, imprecision, and other domains for a body of evidence describing the relative importance of outcomes.

Using patient values and preferences to inform the importance of health outcomes in practice guideline development following the GRADE approach.

BACKGROUND: There are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development. METHODS: In 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives. RESULTS: We found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences. CONCLUSIONS: Currently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings.

The GRADE evidence-to-decision framework: a report of its testing and application in 15 international guideline panels.

BACKGROUND: Judgments underlying guideline recommendations are seldom recorded and presented in a systematic fashion. The GRADE Evidence-to-Decision Framework (EtD) offers a transparent way to record and report guideline developers' judgments. In this paper, we report the experiences with the EtD frameworks in 15 real guideline panels. METHODS: Following the guideline panel meetings, we asked methodologists participating in the panel to provide feedback regarding the EtD framework. They were instructed to consider their own experience and the feedback collected from the rest of the panel. Two investigators independently summarized the responses and jointly interpreted the data using pre-specified domains as coding system. We asked methodologists to review the results and provide further input to improve the structure of the EtDs iteratively. RESULTS: The EtD framework was well received, and the comments were generally positive. Methodologists felt that in a real guideline panel, the EtD framework helps structuring a complex process through relatively simple steps in an explicit and transparent way. However, some sections (e.g., "values and preferences" and "balance between benefits and harms") required further development and clarification that were considered in the current version of the EtD framework. CONCLUSIONS: The use of an EtD framework in guideline development offers a structured and explicit way to record and report the judgments and discussion of guideline panels during the formulation of recommendations. In addition, it facilitates the formulation of recommendations, assessment of their strength, and identifying gaps in research.

Economic Evaluation of Exercise-Based Cardiac Rehabilitation Programs for Chronic Heart Failure Patients in Colombia.

PURPOSE: Cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) has met with resistance from third-party payers in low- and middle-income countries because of lack of evidence regarding its cost-effectiveness. We aimed to provide information to help better inform this decision-making process. METHODS: Costs associated with a 12-week exercise-based rehabilitation program in Colombia for patients with CHF were estimated. We collected data on all medical resources used in ambulatory care and data on hospital costs incurred for treating patients with uncompensated CHF. A literature search to establish the hospitalization rates because of uncompensated CHF, death because of CHF, and potential decreases in these data because of the utilization of CR was conducted. We modeled incremental costs and effectiveness over a period of 5 years from the perspective of the third-party payer. RESULTS: All costs were converted from Colombian pesos to US dollars. For an exercise-based CR program of 12-week duration (36 sessions), costs ranged from US$265 to US$369 per patient. Monthly costs associated with ambulatory care of CHF averaged US$128 ± US$321 per patient, and hospitalization costs were US$3621 ± US$5 444 per event. Yearly hospitalization incidence rates with and without CR were 0.154 and 0.216, respectively. The incremental cost of CR would be US$998 per additional quality-adjusted life-year. Sensitivity analysis did not significantly change these results. CONCLUSIONS: Cardiac rehabilitation in patients with CHF in settings such as Colombia can be a cost-effective strategy, with minimal incremental costs and better quality of life, mainly because of decreased rates of hospitalization.

Evaluación económica para Colombia de las principales intervenciones farmacológicas como monoterapia para el tratamiento de la hipertensión arterial leve a moderada recién diagnosticada / Economic evaluation for Colombia of the main pharmacological interventions as monotherapy for the treatment of newly diagnosed mild to moderate hypertension

Objetivo: en el año 2012 se desarrolló para Colombia la guía de práctica clínica para manejo de la hipertensión arterial (HTA). Esta evaluación económica (EE) fue desarrollada para identificar la costo-efectividad de los diferentes tratamientos farmacológicos usados como monoterapia, y soportar las recomendaciones en la guía. Diseño: se simuló una cohorte de pacientes adultos, con diagnóstico de hipertensión arterial. La EE se basó en un modelo desarrollado para el National Institute for Clinical Excellence (NICE) del Reino Unido. Este modelo fue adaptado para Colombia en consumo de recursos y costos. La efectividad de las intervenciones y probabilidades de transición fueron actualizadas para 2012. Resultados: los resultados del análisis del caso de referencia (hombre y mujer de 65 años, 2% de riesgo anual de enfermedad CV, 1% de falla cardiaca, 1.1% de diabetes, 20 años de seguimiento), mostraron que los años de vida ajustados por calidad (QALY) obtenidos con la terapia de diuréticos, inhibidores de enzima convertidora/bloqueadores del receptor de angiotensina (ACEi/ARB) y calcioantagonistas fue 9.24, 9.24 y 9.26, respectivamente. Los costos favorecen a los diuréticos (COP $6 498 624), en comparación con ACEi/ARB o calcioantagonistas (COP $13 178 919, y COP $27 774 098), respectivamente. La terapia con betabloqueadores y la no intervención fueron dominadas. Conclusiones: la opción de tratamiento con diuréticos tipo tiazidas como mono-terapia inicial es la más costo-efectiva. La principal diferencia entre las alternativas está dada especialmente por las diferencias en el costo de los medicamentos, ya que la efectividad es similar entre los tratamientos con diuréticos y ACEi/ARB, y sólo discretamente mejor con calcio-antagonistas. (Acta Med Colomb 2015; 40: 279-287).

Objective: in 2012 the guide of clinical practice for management of arterial hypertension (AHT) was developed for Colombia. This economic evaluation (EE) was developed to identify the cost effectiveness of different pharmacological treatments used as monotherapy, and to support the recommendations in the guidelines. Design: a cohort of adult patients with a diagnosis of hypertension was simulated. The EE was based on a model developed for the National Institute for Clinical Excellence (NICE) in the UK. This model was adapted for Colombia in resource consumption and costs. The effectiveness of interventions and transition probabilities were updated for 2012. Results: the results of the analysis of the reference case (man and woman of 65.2% annual risk of cardiovascular disease, 1% of heart failure, 1.1% of diabetes, 20 years of follow-up) showed that quality-adjusted life year (QALY) obtained with diuretic therapy, converting enzyme inhibitors / angiotensin receptor blockers (ACEi / ARB) and calcium antagonists was 9.24, 9.24 and 9.26, respectively. Costs favor diuretics (COP $6 498 624) compared with ACEi / ARB or calcium antagonists (COP $ 13 178 919 and $ 27 774 098 COP), respectively. Therapy with beta-blockers and non-intervention were dominated. Conclusions: the choice of treatment with thiazide-type diuretics as initial monotherapy is the most cost-effective. The main difference between alternatives is given especially by differences in drug costs, since the effectiveness is similar between treatments with diuretics and ACEi / ARB, and only slightly better with calcium antagonists. (Acta Med Colomb 2015; 40: 279-287).

Costos ambulatorios y hospitalarios de la falla cardiaca en dos hospitales de Bogotá / Outpatient and inpatient costs of heart failure in two hospitals in Bogotá

Objetivo: realizar una aproximación a la determinación de costos directos de la falla cardiaca (FC) en el país, a través de la evaluación de costos asociados con el cuidado de pacientes atendidos en dos instituciones prestadoras de salud de Bogotá. Métodos: estudio de costos bajo la perspectiva del tercer pagador. La identificación de eventos generadores de costos en atención ambulatoria se realizó mediante revisión de historias clínicas de pacientes atendidos durante 2011 en la consulta externa especializada de una institución. Los costos de interconsultas y paraclínicos se determinaron según los valores del Acuerdo 256 de 2001, con adición de 30%. Los costos de la medicación se determinaron a partir del registro SISMED. La identificación de eventos generadores de costos en hospitalización se realizó mediante revisión de listados y facturas de pacientes atendidos entre 2009 y 2010 en dos instituciones. Los resultados se presentan resumidos por medidas de tendencia central y de dispersión, en pesos colombianos (COP) de 2011. Resultados: el costo mensual promedio del tratamiento ambulatorio de FC fue de 304.318 COP (D.E. 760.876), con una mediana de 45.280 COP (RIC 25.539 - 109.715); los medicamentos representaron la fuente principal de consumo de recursos (55,2%). El costo promedio de la hospitalización por descompensación de FC fue de 6.427.887 COP (D.E. 9.663.176); la estancia hospitalaria representó la mayor proporción del costo (29,1%). Conclusiones: los costos ambulatorios, y especialmente los hospitalarios, asociados con la FC en Colombia son sustanciales. La fuente principal de costos difiere dependiendo de si el manejo es hospitalario (estancia) o ambulatorio (medicamentos). (Acta Med Colomb 2013; 38: 208-212).

Objective: to make an approach to the determination of direct costs of heart failure (HF) in the country through the evaluation of costs associated with the care of patients seen in two health institutions in Bogota. Methods: low cost third-party payer perspective. Identification of cost generating events in ambulatory care was performed by review of medical records of patients seen during 2011 in the specialized outpatient clinic of an institution. Interconsultations and paraclinical costs were determined according to the 256 Agreement of 2001, with addition of 30%. Medication costs were determined from the SISMED register. Identification of events that generate costs in hospitalization was conducted by reviewing lists and bills of patients treated between 2009 and 2010 in two institutions. The results are presented summarized by measures of central tendency and dispersion, in Colombian pesos (COP) of 2011. Results: the average monthly cost for outpatient treatment of HF was 304,318 COP (D.E. 760 876), with a median of 45,280 COP (RIC 25,539-109,715); drugs represented the main source of resource consumption (55.2%). The average cost of hospitalization for decompensated HF was 6,427,887 COP (D.E. 9.663.176); hospital stay accounted for the largest proportion of the cost (29.1%). Conclusions: outpatient costs, and especially the inpatient ones associated with HF in Colombia are substantial. The main source of costs differs depending on whether the management is hospitable (stay) or outpatient (drugs). (Acta Med Colomb 2013; 38: 208-212).

Regional variation on rates of bronchopulmonary dysplasia and associated risk factors.

Background. An abnormally high incidence (44%) of bronchopulmonary dysplasia with variations in rates among cities was observed in Colombia among premature infants. Objective. To identify risk factors that could explain the observed high incidence and regional variations of bronchopulmonary dysplasia. Study Design. A case-control study was designed for testing the hypothesis that differences in the disease rates were not explained by differences in city-of-birth specific population characteristics or by differences in respiratory management practices in the first 7 days of life, among cities. Results. Multivariate analysis showed that premature rupture of membranes, exposure to mechanical ventilation after received nasal CPAP, no surfactant exposure, use of rescue surfactant (instead of early surfactant), PDA, sepsis and the median daily FIO(2), were associated with a higher risk of dysplasia. Significant differences between cases and controls were found among cities. Models exploring for associations between city of birth and dysplasia showed that being born in the highest altitude city (Bogotá) was associated with a higher risk of dysplasia (OR 1.82 95% CI 1.31-2.53). Conclusions. Bronchopulmonary dysplasia was manly explained by traditional risk factors. Findings suggest that altitude may play an important role in the development of this disease. Prenatal steroids did not appear to be protective at high altitude.

Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children.

BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. CLINICAL TRIAL REGISTRATION: NCT00487253.

[Reference values for respiratory parameters in the adult population of Bogotá, D.C., Colombia]. / Valores de referencia para parámetros de espirometría en la población adulta residente en Bogotá, D. C., Colombia.

INTRODUCTION: Reference values for pulmonary function parameters, generally applicable to most populations, have shown little validity in the correct interpretation of pulmonary function tests when applied to the adult population in Bogotá. OBJECTIVE: To identify which of four prediction models generated for use in populations of a similar ethnic background to that found in Colombia is the most accurate for use in adults in Bogotá. MATERIALS AND METHODS: 534 subjects (male and female) between 18 and 65 years of age were recruited from a pool of workers employed by three private Bogotá companies. All subjects had resided in Bogotá for at least five years before the initiation of the study. Smokers and those with altered pulmonary function were excluded. Pulmonary function parameters were measured by flow volume curve. The results were analyzed (specifically, the difference between predicted and observed values) and the limits were calculated using the Bland & Altman method. A maximum average prediction error of 5% was accepted as valid for the observed value of each parameter. RESULTS: The models shown to be valid were as follows: Crapo for forced vital capacity (FVC) in men; Pérez-Padilla for FVC in women and for the ratio forced expiratory volume in the first second (FEV1/FVC) in both sexes, and the Hankinson model for Mexican-Americans, for all parameters in both sexes. CONCLUSIONS: The Hankinson model proved to be the most accurate in predicting all spirometry parameters. However, its poor classification average (7%) is a limitation. In the future, new models with a better predictive accuracy will be required.