Machine Learning Methods in Health Economics and Outcomes Research-The PALISADE Checklist: A Good Practices Report of an ISPOR Task Force.

Advances in machine learning (ML) and artificial intelligence offer tremendous potential benefits to patients. Predictive analytics using ML are already widely used in healthcare operations and care delivery, but how can ML be used for health economics and outcomes research (HEOR)? To answer this question, ISPOR established an emerging good practices task force for the application of ML in HEOR. The task force identified 5 methodological areas where ML could enhance HEOR: (1) cohort selection, identifying samples with greater specificity with respect to inclusion criteria; (2) identification of independent predictors and covariates of health outcomes; (3) predictive analytics of health outcomes, including those that are high cost or life threatening; (4) causal inference through methods, such as targeted maximum likelihood estimation or double-debiased estimation-helping to produce reliable evidence more quickly; and (5) application of ML to the development of economic models to reduce structural, parameter, and sampling uncertainty in cost-effectiveness analysis. Overall, ML facilitates HEOR through the meaningful and efficient analysis of big data. Nevertheless, a lack of transparency on how ML methods deliver solutions to feature selection and predictive analytics, especially in unsupervised circumstances, increases risk to providers and other decision makers in using ML results. To examine whether ML offers a useful and transparent solution to healthcare analytics, the task force developed the PALISADE Checklist. It is a guide for balancing the many potential applications of ML with the need for transparency in methods development and findings.

Natural Language Processing for Automated Classification of Qualitative Data From Interviews of Patients With Cancer.

OBJECTIVES: This study sought to explore the use of novel natural language processing (NLP) methods for classifying unstructured, qualitative textual data from interviews of patients with cancer to identify patient-reported symptoms and impacts on quality of life. METHODS: We tested the ability of 4 NLP models to accurately classify text from interview transcripts as "symptom," "quality of life impact," and "other." Interview data sets from patients with hepatocellular carcinoma (HCC) (n = 25), biliary tract cancer (BTC) (n = 23), and gastric cancer (n = 24) were used. Models were cross-validated with transcript subsets designated for training, validation, and testing. Multiclass classification performance of the 4 models was evaluated at paragraph and sentence level using the HCC testing data set and analyzed by the one-versus-rest technique quantified by the receiver operating characteristic area under the curve (ROC AUC) score. RESULTS: NLP models accurately classified multiclass text from patient interviews. The Bidirectional Encoder Representations from Transformers model generally outperformed all other models at paragraph and sentence level. The highest predictive performance of the Bidirectional Encoder Representations from Transformers model was observed using the HCC data set to train and BTC data set to test (mean ROC AUC, 0.940 [SD 0.028]), with similarly high predictive performance using balanced and imbalanced training data sets from BTC and gastric cancer populations. CONCLUSIONS: NLP models were accurate in predicting multiclass classification of text from interviews of patients with cancer, with most surpassing 0.9 ROC AUC at paragraph level. NLP may be a useful tool for scaling up processing of patient interviews in clinical studies and, thus, could serve to facilitate patient input into drug development and improving patient care.

Systematic literature review of trials assessing recommended systemic treatments in hepatocellular carcinoma.

AIM: To identify and evaluate the similarity of all trials assessing recommended treatments for advanced hepatocellular carcinoma. MATERIALS & METHODS: Single arm and randomized trials from any phase and published any time up to February 2021 were systematically searched. RESULTS: From 5677 records reviewed, 50 trials were included in the review, and 24 for assessed for similarity. In the first-line (1L) setting, several trials assessing sorafenib were noted for enrolling patients with more severe disease and/or performance status than other 1L trials; trials within the second-line (2L) setting were generally similar. Median survival was <2 years in all trial arms. CONCLUSIONS: Trials assessing recommended treatments are largely similar and appropriate for quantitative comparisons of several efficacy and safety outcomes.

Effect of biomolecules derived from human platelet-rich plasma on the ex vivo expansion of human adipose-derived mesenchymal stem cells for clinical applications.

Mesenchymal stem cells are a tool in cell therapies but demand a large cell number per treatment, for that, suitable culture media is required which contains fetal bovine serum (FBS). However, for cell-based therapy applications, the use of FBS is problematic. Several alternatives to FBS have been explored, including human derivatives from platelet-rich plasma (hD-PRP). Although various studies have evaluated the impact of hD-PRP on MSC proliferation and differentiation, few of them have assessed their influence on processes, such as metabolism and gene expression. Here, we cultured human adipose-derived MSCs (hAD-MSCs) in media supplemented with either 10% hD-PRP (hD-PRP-SM) or 10% FBS (FBS-SM) in order to characterize them and evaluate the effect of hD-PRP on cell metabolism, gene expression of associated regenerative factors, as well as chromosome stability during cell expansion. We found that hAD-MSCs cultured in hD-PRP-SM have a greater cell elongation but express similar surface markers; in addition, hD-PRP-SM promoted a significant osteogenic differentiation in the absence of differentiation medium and increased the growth rate, maintaining chromosomal stability. In terms of cell metabolic profile, hAD-MSC behavior did not reveal any differences between both culture conditions. Conversely, significant differences in collagen I and angiopoietin 2 expression were observed between both conditions. The present results suggest that hD-PRP may influence hAD-MSC behavior.

Limitations and Challenges of Conducting Budget Impact Analyses in Rare Diseases: A Case Study of Alpha-1 Antitrypsin Deficiency.

OBJECTIVES: There are challenges in conducting a budget impact analysis (BIA) for rare disorders. Through this case study, we present some challenges and limitations of a BIA of managing patients affected with alpha-1 antitrypsin deficiency (AATD). We explored a conceptual basis and barriers for health services researchers interested in quantifying budget impacts of rare disease management program (DMP). METHODS: We developed a static budget impact cost calculator model in Microsoft Excel, obtaining the clinical impact of a DMP from the literature and translating it into costs using OLDW. Cost inputs and resource use was obtained from 2010 to 2015 claims data using the OLDW. Insurers' payments were calculated and categorized into the following cost buckets: physician visits, emergency room visits, inpatients stays, augmentation therapy, other prescription drugs costs, and other costs. RESULTS: Data were based on 6832 patients with alpha-1 antitrypsin deficiency identified among over 21 million OLDW enrollees observed between January 1, 2010, and December 31, 2015. The introduction of a DMP was estimated to decrease costs of the management of patients with alpha-1 antitrypsin deficiency by $13.5 million over 5 years. The savings attributed to the program over the 5-year time horizon are due to 2555 exacerbations, 5180 emergency room visits, 9342 specialist visits, and 105 358 general practitioner visits avoided. CONCLUSIONS: A comprehensive DMP for a rare condition might provide cost savings to a health plan. BIAs for rare disease may be more informative if they focus on DMPs rather than on individual drugs.

Tratamiento de malformaciones y tumores vasculares, en un centro de referencia en Bogotá / Treatment of vascular malformations and tumors in a reference center in Bogotá

Introducción. Las malformaciones vasculares son anomalías que están presentes desde el nacimiento, no desaparecen y pueden crecer a lo largo de la vida. Se ha demostrado en estudios retrospectivos que la terminología para clasificar las anomalías vasculares es inexacta en un 69 % de casos, por lo que se hace un diagnostico inadecuado y en un 53 % de casos se brinda al paciente y su familia una información incorrecta del tratamiento y el curso clínico. Métodos. Estudio prospectivo longitudinal, realizado entre 2016 y 2019, donde se incluyeron pacientes con anomalías vasculares, que consultaron a nuestra institución, fueron valorados por el servicio de cirugía vascular, se hizo un plan diagnóstico y manejo integral, vía endovascular, quirúrgica o mixta, de acuerdo con cada caso. Resultados. La malformación más común fue la de tipo venoso, en el 40,3 % de los casos. Se realizó manejo endovascular en el 93,1 % de casos de malformaciones vasculares y quirúrgico en el 6,9 %. La mejoría de los síntomas que motivaron la consulta fue del 100 % para los tumores vasculares y del 70,8 % para las malformaciones. Sin embargo, los resultados son heterogéneos. Discusión. Es necesario realizar un adecuado diagnóstico de las anomalías vasculares, para alcanzar un trata-miento eficaz, con mejoría de los síntomas

Introduction. Vascular malformations are abnormalities that are present from birth, do not disappear and can grow throughout life. It has been shown in retrospective studies that the terminology to classify vascular anomalies is inaccurate in 69% of cases, an inappropriate diagnosis is made and in 53% of cases the patient and their family are given incorrect information on the treatment and the clinical course.Methods. Longitudinal prospective study conducted between 2016 and 2019. Patients with vascular anomalies and consulted to our institution were included. They were evaluated by the vascular surgery service, and a comprehensive diagnosis and management plan was made, including endovascular, surgical or mixed, according to each case. Results. The most common malformation was the venous type in 40.3% of the cases. Endovascular management was performed in 93.1% of cases and surgery in 6.9%. The improvement in the symptoms that led to the con-sultation was 100% for vascular tumors and 70.8% for malformations. However, the results are heterogeneous.Conclusions. It is necessary to obtain an adequate diagnosis of vascular anomalies, to achieve an effective treatment, with improvement of the symptoms

A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

BACKGROUND: Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. OBJECTIVE: To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. METHODS: Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. RESULTS: Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. CONCLUSIONS: This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. DISCLOSURES: Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.

Impact of formulary restrictions on medication intensification in diabetes treatment.

OBJECTIVES: To explore formulary restrictions on noninsulin antihyperglycemic drugs (NIADs) in Medicare Part D plans and to estimate the impact of formulary restrictions on use of NIADs among low-income subsidy (LIS) recipient enrollees with type 2 diabetes (T2D) undergoing treatment intensification. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort of 2919 LIS enrollees with T2D receiving metformin monotherapy during the first quarter of 2012 who intensified treatment later in the year was tracked to assess selection of and days' supply with sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and other NIADs. We tested whether being enrolled in a Part D plan with significant formulary restrictions on sole-source brand name NIADs reduced the likelihood of receiving such agents and, if so, what the impact was on days of therapy with the second agent. A 2-part regression model was estimated with explanatory variables for plan-level restrictions and individual covariates. RESULTS: We found that 63% of study subjects initiated a sulfonylurea, 25% a DPP-4 inhibitor, and 12% another NIAD. Greater restrictions on DPP-4 inhibitors as a class were associated with small reductions in initiation of DPP-4 inhibitors and a concomitant increase in use of sulfonylureas, but neither effect was statistically significant. For individual DPP-4 inhibitors, step therapy requirements on sitagliptin and formulary exclusion of saxagliptin resulted in significant reductions in uptake of the specific drugs but had no significant impact on total days' supply of antihyperglycemic therapy. CONCLUSIONS: Part D formulary restrictions on sole-source brand name NIADs had little impact on patterns of treatment intensification for T2D among LIS recipients enrolled in Medicare Part D plans in 2012.

Solving the negative impact of congestion in the postanesthesia care unit: a cost of opportunity analysis.

BACKGROUND: Congestion in the postanesthesia care unit (PACU) leads to the formation of waiting queues for patients being transferred after surgery, negatively affecting hospital resources. As patients recover in the operating room, incoming surgeries are delayed. The purpose of this study was to establish the impact of this phenomenon in multiple settings. METHODS: An operational mathematical study based on the queuing theory was performed. Average queue length, average queue waiting time, and daily queue waiting time were evaluated. Calculations were based on the mean patient daily flow, PACU length of stay, occupation, and current number of beds. Data was prospectively collected during a period of 2 months, and the entry and exit time was recorded for each patient taken to the PACU. Data was imputed in a computational model made with MS Excel. To account for data uncertainty, deterministic and probabilistic sensitivity analyses for all dependent variables were performed. RESULTS: With a mean patient daily flow of 40.3 and an average PACU length of stay of 4 hours, average total lost surgical opportunity time was estimated at 2.36 hours (95% CI: 0.36-4.74 hours). Cost of opportunity was calculated at $1592 per lost hour. Sensitivity analysis showed that an increase of two beds is required to solve the queue formation. CONCLUSIONS: When congestion has a negative impact on cost of opportunity in the surgical setting, queuing analysis grants definitive actions to solve the problem, improving quality of service and resource utilization.

Examining psychotropic medication use among youth in the U.S. by race/ethnicity and psychological impairment.

OBJECTIVE: Clinical practice guidelines underscore the need for careful evaluation of the risk-benefit ratio of psychotropic medications treating mental health disorders among youth. While it is well known that racial/ethnic disparities exist in psychotropic medication use, little is known about whether these differences are driven by over-prescribing among white youth, under-prescribing among minority youth, or both. To build evidence in this area, this study examined racial/ethnic differences in the prescription of psychotropic medications among youth with and without psychological impairment. METHODS: Secondary data on two-year medication use from the 2004-2011 Medical Expenditure Panel Surveys were analyzed. We capitalized on two-year panel data, creating variables that allow for differential sequencing of psychological impairment and medication prescription (e.g., impairment in year 1 or year 2, and a psychotropic medication fill in year 2). Statistical differences were determined using unadjusted rate comparisons and logistic regression models, after adjustment for socio-contextual and health status characteristics. RESULTS: Compared to Black and Latino youth with psychological impairment, White youth were more likely to be prescribed psychotropic medications when impaired. Among youth never having psychological impairment, White youth were also more likely to be prescribed medications compared to their racial/ethnic minority counterparts. CONCLUSIONS: Differences in rates of medication use among youth with and without impairment suggest poor medication targeting across racial/ethnic groups. These results, combined with recent psychotropic medication risk warnings and concerns over increases in psychotropic medication use among youth, suggest that a continued emphasis on accurate targeting of prescribing patterns is needed across racial/ethnic groups.

Framework for enhancing clinical practice guidelines through continuous patient engagement.

BACKGROUND: Patient engagement in clinical practice guideline (CPG) development is recommended by multiple institutions and instruments measuring guideline quality. Approaches to engaging patients, however, vary between oversight organizations, quality tools and guideline developers. OBJECTIVE: We propose a ten-step framework outlining steps and options for patient engagement in guideline development with the goal of highlighting steps for patient engagement and methods by which this can be achieved. DISCUSSION: This framework provides a model for continuous patient engagement in CPGs by outlining ten steps of guideline development occurring at the levels of the developer/committee and the individual guideline project. At the developer level, patients can assist in topic nomination (step 1), topic prioritization (step 2) and guideline development group selection (step 3). Within specific guideline projects, patients' opinions may be incorporated when framing the question (step 4), creating an analytic framework and research plan (step 5), conducting the systematic review and conclusion formation (step 6), development of recommendations (step 7) and dissemination and implementation (step 8). At the end of process, patients can again be engaged at the developer level by helping determine when guidelines need updating (step 9) and evaluating the developer's approach to patient engagement (step 10). CONCLUSIONS: Patient engagement at each CPG development step has different purposes, mechanisms, advantages and disadvantages, and implications for resource utilization. This framework can serve as a resource for guideline developers desiring to increase patient engagement and reference for researchers investigating engagement methodology at different steps of the CPG lifecycle.

Cost-effectiveness of kidney transplantation compared with chronic dialysis in end-stage renal disease.

To estimate the costs and effectiveness measured in quality-adjusted life years (QALY) of kidney transplantation compared with dialysis in adults suffering from end-stage renal disease from the perspective of the Colombian healthcare system, we designed a Markov model with monthly cycles over a five-year time horizon and eight transitional states, including death as an absorbing state. Transition probabilities were obtained from international registries, costs from different local sources [case studies, official tariffs (ISS 2001 + 35%) for procedures and SISMED for medications]. Data were validated by an expert panel and we performed univariate, multivariate and probabilistic sensitivity analyses. Effectiveness indicators were months of life gained, months of dialysis averted and deaths prevented. The annual discount rate was 3% and the cost-utility threshold (willingness to pay) was three times gross domestic product (GDP) = USD 20,000 per QALY. The costs were adopted in US dollars (USD) using the 2012 average exchange rate (1 USD = COP$ 1798). The discounted average total cost for five years was USD 76,718 for transplantation and USD 76,891 for dialysis, with utilities 2.98 and 2.10 QALY, respectively. Additionally, renal transplantation represented 6.9 months gained, 35 months in dialysis averted per patient and one death averted for each of the five patients transplanted in five years. We conclude that renal transplantation improves the overall survival rates and quality of life and is a cost-saving alternative compared with dialysis.

Implicaciones y costo-efectividad del alta temprana del binomio madre-hijo después de un parto normal / Implications and cost-effectiveness of early discharge of the mother-child pair after normal parturition

Introducción: Se revisó la literatura internacional sobre alta temprana (24-48 horas) y su relación con complicaciones, para elaborar un modelo de costo-efectividad en recién nacidos, por parto vaginal a término no complicado, comparándola con ultratemprana (<24 horas) que incluya un programa de control posnatal organizado que permita evaluar a la madre y al bebe a las 48- 72 horas. Materiales y métodos: Se diseñó un árbol de decisión para un hospital que preste servicio de obstetricia, desde la perspectiva del sistema de salud colombiano. El horizonte de tiempo fue el periodo neonatal (primer mes de vida extrauterina). La efectividad fue medida en los siguientes desenlaces: reconsultas evitadas y hospitalizaciones evitadas. Resultados: Se estima que cada año nacen 336.000 niños por partos vaginales a término. Cada día de reducción de estancia hospitalaria implicaría 29 mil millones de pesos de ahorro para el sistema de salud colombiano. Comparada con el alta temprana ($88.015) el alta ultratemprana cuesta más ($93.129) y se asocia con una mayor tasa de hospitalización (55 incrementales por cada 1000) y de reconsultas (320 adicionales por cada 1000). Conclusión: Un alta ultratemprana se justifi caría solo si se cumpliera con una detallada lista de chequeo para garantizar que el ahorro para el sistema no se traduzca en mayores complicaciones para la madre y el niño.

Introduction: We reviewed international literature on early discharge (24-48 hours), and its relationship with complications, to develop a cost-effectiveness model in normal uncomplicated vaginally delivered newborns, compared with "ultra-early" discharge (<24 hours) which includes an organized postnatal program to assess the mother and the baby at 48-72 hours. Materials and Methods: A decision tree model was designed for a hospital providing obstetrical service, from the perspective of the Colombian health system. The time horizon was the neonatal period (fi rst month after birth). Effectiveness was measured in the following outcomes: reconsultations avoided and hospitalizations avoided. Results: It is estimated that each year 336.000 children are born at term vaginal deliveries. Each day reduction in hospital means 29 billion pesos in savings for the health system in Colombia. Compared with early discharge ($ 88.015), "ultra-early" discharge costs more ($ 93.129) and is associated with a higher rate of hospitalizations (55 more per 1000) and reconsultations (320 more per 1.000). Conclusion: "ultra-early" discharge could be justifi ed only if the hospital complies with a detailed checklist to ensure that the savings to the system do not result in major complications for mother or child.

Análisis de costos de atención de infarto cerebral agudo con o sin fibrilación auricular / Cost analysis of acute stroke care with or without atrial fibrillation

Objetivo. Estimar los costos totales y los componentes del costo de la atención hospitalaria en una serie de pacientes con infarto cerebral agudo (ICA) de gran vaso tratados en el Hospital Universitario San Ignacio, comparando aquellos con y sin fibrilación auricular (FA). Materiales y métodos. Se recogió una muestra secuencial de pacientes mayores de 50 años entre diciembre de 2010 y marzo de 2013. Para un análisis separado, se realizó un pareamiento por edad y NIHSS de ingreso en proporción 1:1 de pacientes con y sin FA. A todos los pacientes se les registró: edad, sexo, NIHSS de ingreso y egreso, Rankin modificado, y puntaje de CHAD2S2 VASC. En cada paciente se cuantificó el uso de recursos intrahospitalarios así como el costo total de la atención durante el evento agudo, calculado en pesos colombianos. Resultados. Se recogió información de 166 pacientes (125 sin y 41 con FA). El costo total promedio de la atención fue de $8.635.419 (DE $12.929.905). Este valor fue de $10.341.065 (DE $15.130.716) para los pacientes con FA y $8.056.718 (DE $12.114.840) para los pacientes sin FA. Conclusiones. A pesar de un costo de tratamiento mayor en pacientes con FA, que son de mayor edad y tienen infartos cerebrales más severos, la diferencia no fue estadísticamente significativa cuando se ajustó por edad y por severidad del compromiso neurológico.

Objective. To estimate the total costs and resource use of hospital care in a series of patients with large vessel ischemic stroke treated at the Hospital Universitario San Ignacio. Material and methods. Prospective convenience sample of all patients 50 years of age or older admitted between December 2010 and March 2013 diagnosed with ischemic stroke. Patients with and without atrial fibrillation (AF) were compared. The following variables were measured: age, sex, admission and discharge NIHSS, modified Rankin, and CHA2DS2 VASC score. We also quantified inpatient resource use and total cost of care during the acute event. Results. We analyzed 166 patients, 125 without non-valvular AF and 41 with non-valvular AF. For a separate analysis, we matched patients with and without AF (37 per group) by age and initial NIHSS, in a 1:1 ratio. The average total cost of care in Colombian pesos (as of February 2012, 1 US$= COP$1,805) for all stroke patients was $8,635,419 (SD $12,929,905). This value was $10,341,065 (SD $15,130,716) for patients with AF and $8,056,718 (SD $12,114,840) for patients without AF. Conclusions. Despite higher treatment cost in patients with AF, these are older and severe strokes. The difference is reduced and does not reach statistical significance, when adjusted for age and stroke severity.

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease".

Economic Evaluation of Four Drug Administration Systems in Intensive Care Units in Colombia.

INTRODUCTION: Intensive care units (ICUs) are the most frequent setting for serious medical errors, which not only have serious health consequences but also an economic impact. In this article, using a theoretical model, we evaluate four medication administration systems: conventional preparation by nursing staff, MINIBAG Plus delivery system, compounding center preparation, and premix drugs. METHODS: We designed a decision tree model from a third-party payer perspective, and the time horizon of the acute event. Local costs, in Colombian pesos (US $1 = 1784 COP$), were obtained from tariff manuals, medication costs from Sismed information system, and clinical variables from the published literature, and uncertainty was dealt with by an expert panel. The drug used for the model was dopamine. RESULTS: Average costs for each dopamine dose delivered were $46,995 for premix, $47,625 for compounding center, $101,934 for MINIBAG Plus, and $108,870 for drug prepared in the ICU. The variability of these results is higher for compounding center than for premix, and even higher for MINIBAG Plus and nurse delivery. CONCLUSIONS: The use of premix drugs can be a cost-saving strategy, which decreases medical errors in drug administration in the ICU, particularly if it is part of an integral error reduction program.

Estudio MULATA: muestra latinoamericana de pacientes con tensión arterial elevada / MULATA study: Latin American sample of high blood pressure patients

Introducción: Por prevalencia y trascendencia como factor de riesgo para enfermedad cardiovascular, la hipertensión arterial es una de las enfermedades de mayor importancia en la práctica médica. Este trabajo describe las características clínicas y sociodemográficas de una muestra de pacientes hipertensos con al menos un factor de riesgo cardiovascular adicional, en Argentina, Colombia y Venezuela. Metodología: Es un estudio de corte transversal, con recolección prospectiva de la información en una muestra por conveniencia de pacientes con hipertensión arterial que consultaron a los médicos participantes en cada uno de los tres países. Resultados: Se detectaron diferencias estadísticamente significativas en la distribución de los factores de riesgo cardiovascular (obesidad central, hipertensión arterial no controlada, tabaquismo y dislipidemia) entre las poblaciones de Colombia, Venezuela y Argentina. La población participante estuvo compuesta en su mayoría por mujeres (53,7%), la edad promedio fue de 59,3 +/- DE 13,6 años; 29% de los participantes en el estudio tenían cifras tensionales controladas en el momento de la evaluación. El manejo con dos medicamentos fue el más frecuente en la población total (40,6%) así como en los subgrupos, argentino (47,1%) y colombiano (46,4%), mientras que en la población venezolana el manejo más común fue monoterapia (45%). Los bloqueadores del sistema renina angiotensina II fueron los más utilizados en los tres países. Discusión: Los factores de riesgo cardiovascular susceptibles de ser modificados tienen diferencias geográficas que justifican cambios en su manejo. La hipertensión requiere no solamente manejo farmacológico, sino la intervención sobre estos factores.

Introduction: Due to its high prevalence and its importance as a risk factor for stroke, heart disease, and renal failure, hypertension is one of the most important diseases in common medical practice. The aim of this study was to describe the clinical and demographic characteristics of a sample of hypertensive patients, with at least one additional cardiovascular risk factor, in Argentina, Colombia and Venezuela. Methods: We performed a cross sectional study, with prospective data collection from a convenience sample of patients. Results: we found statistically significant differences in the distribution of cardiovascular risk factors (obesity, non-controlled hypertension, smoking and dyslipidemia) in the population of the different countries. There were slightly more women in our sample (53.7%), the average age was 59.3 (SD 13.6) years. In 29% of the patients hypertension was controlled. The most common practice in the whole sample was the use of two different drugs (40.6%). This was true both in Colombia (46.4%) and in Argentina (47.1%), while in Venezuela the use of monotherapy was more common (45%). Angiotensin II receptor antagonists are the most commonly used drug family in the three countries, either alone or in combination with other therapies. Discussion: Our population shows a poor control of blood pressure. Our patients need a more strict pharmacological therapy together with a strategy to identify and reduce all modifiable cardiovascular risk factors.

Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections in children. It results in about 3.4 million hospitalisations annually in children under five. Palivizumab is an anti-RSV monoclonal antibody, administered intramuscularly at a dose of 15 mg/kg once every 30 days. The efficacy and safety of palivizumab has been evaluated in multicentre, randomised controlled trials (RCTs) and a large number of economic evaluations (EEs) have tested its cost-effectiveness. OBJECTIVES: To assess the effectiveness and safety of palivizumab prophylaxis compared with placebo, or another type of prophylaxis, in reducing the risk of complications (hospitalisation due to RSV infection) in high-risk infants and children. To assess the cost-effectiveness (or cost-utility) of palivizumab prophylaxis compared with no prophylaxis in infants and children in different risk groups. SEARCH METHODS: We searched CENTRAL 2012, Issue 7, MEDLINE (1996 to July week 4, 2012), EMBASE (1996 to August 2012), CINAHL (1996 to August 2012) and LILACS (1996 to August 2012) for studies of effectiveness and safety. We searched the NHS Economic Evaluations Database (NHS EED 2012, Issue 4), Health Economics Evaluations Database (HEED, 9 August 2012) and Paediatric Economic Database Evaluations (PEDE, 1980 to 2009), MEDLINE (1996 to July week 4, 2012) and EMBASE (1996 to August 2012) for economic evaluations. SELECTION CRITERIA: We included RCTs comparing palivizumab prophylaxis with a placebo, no prophylaxis or another type of prophylaxis in preventing serious lower respiratory tract disease caused by RSV in paediatric patients at high risk. We included cost-effectiveness analyses and cost-utility analyses comparing palivizumab prophylaxis with no prophylaxis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias for the included studies and extracted data for both the RCTs and EEs. We calculated risk ratios (RRs) and their associated 95% confidence intervals (CIs) for dichotomous outcomes and for adverse events (AEs). We provided a narrative summary of results for continuous outcomes, due to missing data on standard deviations. We performed fixed-effect meta-analyses for the estimation of pooled effects whenever there was no indication of heterogeneity between included RCTs. We summarised the results reported in included EEs, such as incremental costs, incremental effectiveness, and incremental cost-effectiveness and/or cost-utility ratios (ICERs), and we calculated ICER present values in 2011 Euros for all studies. MAIN RESULTS: Of the seven available RCTs, three compared palivizumab with a placebo in a total of 2831 patients, and four compared palivizumab with motavizumab in a total of 8265 patients. All RCTs were sponsored by the drug manufacturing company. The overall quality of RCTs was good, but for most of the outcomes assessed only data from two studies contributed to the analysis. Palivizumab prophylaxis was associated with a statistically significant reduction in RSV hospitalisations (RR 0.49, 95% CI 0.37 to 0.64) when compared to placebo. When compared to motavizumab, palivizumab recipients showed a non-significant increase in the risk of RSV hospitalisations (RR 1.36, 95% CI 0.97 to 1.90). In both cases, the proportion of children with any AE or any AE related to the study drug was similar between the two groups.In terms of economic evidence, we included 34 studies that reported cost-effectiveness and/or cost-utility data for palivizumab prophylaxis compared with no prophylaxis, in high-risk children with different underlying medical conditions. The overall quality of EEs was good, but the variations in modelling approaches were considerable across the studies, leading to big differences in cost-effectiveness results. The cost-effectiveness of palivizumab prophylaxis depends on the consumption of resources taken into account by the study authors; and on the cost-effectiveness threshold set by the healthcare sector in each country. AUTHORS' CONCLUSIONS: There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease or those born preterm.Results from economic evaluations of palivizumab prophylaxis are inconsistent, implying that economic findings must be interpreted with caution. ICER values varied considerably across studies, from highly cost-effective to not cost-effective. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.

Hyperproteic hypocaloric enteral nutrition in the critically ill patient: A randomized controlled clinical trial.

INTRODUCTION: Our aim was to evaluate the impact of hyperproteic hypocaloric enteral feeding on clinical outcomes in critically ill patients, particularly on severity of organic failure measured with the Sequential Organ Failure Assessment (SOFA). MATERIALS AND METHODS: In a double blind clinical trial, 80 critically ill adult patients were randomized to hyperproteic hypocaloric or to isocaloric enteral nutrition; all patients completed follow-up of at least 4 days. Prescribed caloric intake was: Hyperproteic hypocaloric enteral nutrition (15 kcal/kg with 1.7 g/kg of protein) or isocaloric enteral nutrition (25 kcal/kg with 20% of the calories as protein). The main outcome was the differences in delta SOFA at 48 h. Secondary outcomes were intensive care unit (ICU) length of stay, days on ventilator, hyperglycemic events, and insulin requirements. RESULTS: There were no differences in SOFA score at baseline (7.5 (standard deviation (SD) 2.9) vs 6.7 (SD 2.5) P = 0.17). The total amount of calories delivered was similarly low in both groups (12 kcal/kg in intervention group vs 14 kcal/kg in controls), but proteic delivery was significantly different (1.4 vs 0.76 g/kg, respectively P ≤ 0.0001). The intervention group showed an improvement in SOFA score at 48 h (delta SOFA 1.7 (SD 1.9) vs 0.7 (SD 2.8) P = 0.04) and less hyperglycemic episodes per day (1.0 (SD 1.3) vs 1.7 (SD 2.5) P = 0.017). DISCUSSION: Enteral hyperproteic hypocaloric nutrition therapy could be associated with a decrease in multiple organ failure measured with SOFA score. We also found decreased hyperglycemia and a trend towards less mechanical ventilation days and ICU length of stay.

Burden of pneumococcal infection in adults in Colombia.

INTRODUCTION: The burden of Streptococcus pneumoniae infections is highest in children. Estimates in adult population are uncommon. We determined the burden of disease associated with pneumococcus in adults in Colombia in year 2008. METHODOLOGY: Using different data sources (official mortality records, medical databases, published literature and local epidemiological data) we estimated prevalence, incidence, mortality and disability due to bacterial pneumonia, bacterial meningitis and bacteremia of any cause for year 2008, and the fraction of these that can be attributed to S. pneumoniae. RESULTS: A total of 63,463 DALYs are lost due to S. pneumoniae in Colombians age 15 or over. Most of this burden (51,848 DALYs, 81.7%) is due to pneumonia, followed by meningitis (9241 DALYs, 14.6%). The three conditions, overall, represent 2.03 DALYs per 1000 Colombians in that age range. CONCLUSIONS: Despite the lower incidence of pneumococcal disease in adults, as compared with children, its burden is still significant, comparable to that of schizophrenia or epilepsy. This study may provide a benchmark for future preventive interventions.