CACS, CCTA and mCAD-LT score in the pre-transplant assessment of coronary artery disease and the prediction of post-transplant cardiovascular events.

BACKGROUND: The optimal cardiovascular assessment of liver transplant (LT) candidates is unclear. We aimed to evaluate the performance of CT-based coronary tests (coronary artery calcium score [CACS] and coronary CT angiography [CCTA]) and a modification of the CAD-LT score (mCAD-LT, excluding family history of CAD) to diagnose significant coronary artery disease (CAD) before LT and predict the incidence of post-LT cardiovascular events (CVE). METHODS: We retrospectively analysed a single-centre cohort of LT candidates who underwent non-invasive tests; invasive coronary angiography (ICA) was performed depending on the results of non-invasive tests. mCAD-LT was calculated in all patients. RESULTS: Six-hundred-and-thirty-four LT candidates were assessed and 351 of them underwent LT. CACS, CCTA and ICA were performed in 245, 123 and 120 LT candidates, respectively. Significant CAD was found in 30% of patients undergoing ICA. The AUROCs of mCAD-LT (.722) and CCTA (.654) were significantly higher than that of CACS (.502) to predict the presence of significant CAD. Specificity of the tests ranged between 31% for CCTA and 53% for CACS. Among patients who underwent LT, CACS ≥ 400 and mCAD-LT were independently associated with the incidence of CVE; in patients who underwent CCTA before LT, significant CAD at CCTA also predicted post-LT CVE. CONCLUSION: In this cohort, mCAD-LT score and CT-based tests detect the presence of significant CAD in LT candidates, although they tend to overestimate it. Both mCAD-LT score and CT-based tests classify LT recipients according to their risk of post-LT CVE and can be used to improve post-LT risk mitigation.

Nuclear Magnetic Resonance-Based Lipidomics in the Assessment of Cardiometabolic Risk in Type 1 Diabetes: An Exploratory Analysis.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in type 1 diabetes (T1D). However, there is a need for daily practice tools for identifying those more prone to suffer from these events. We aimed to assess the relationships between nuclear magnetic resonance (1H NMR)-based lipidomic analysis and several CVD risk variables (including preclinical carotid atherosclerosis) in individuals with T1D at high risk. METHODS: We included patients with T1D without CVD, with at least one of the following: age ≥ 40 years, diabetic kidney disease, or ≥ 10 years of evolution with another risk factor. The presence of plaque (intima-media thickness > 1.5 mm) was determined by standardized ultrasonography protocol. Lipidomic analysis was performed by 1H NMR. Bivariate and multivariate-adjusted differences in 1H NMR lipidomics were evaluated. RESULTS: We included n = 131 participants (49.6% female, age 46.4 ± 10.3 years, diabetes duration 27.0 ± 9.5 years, 47.3% on statins). Carotid plaques were present in 28.2% of the individuals (n = 12, with ≥ 3 plaques). Glucose (HbA1c), anthropometric (body mass index and waist circumference), and insulin resistance-related (fatty liver index and estimated glucose disposal rate) variables were those most associated with 1H NMR-derived lipidomic analysis (p < 0.01 for all). Regarding preclinical atherosclerosis, sphingomyelin was independently associated with carotid plaque presence (for 0.1 mmol/L increase, OR 0.50 [0.28-0.86]; p = 0.013), even after adjusting for age, sex, hypertension, statin use, mean 5-year HbA1c and diabetes duration. Furthermore, linoleic acid and ω-6 fatty acids remained independently associated with higher plaque burden (≥ 3 plaques) in multivariate models (0.17 [0.03-0.93] and 0.27 [0.07-0.97], respectively; p < 0.05 for both). CONCLUSION: In our preliminary study of individuals with T1D at high risk, several 1H NMR-derived lipidomic parameters were independently associated with preclinical atherosclerosis. Specifically, ω-6 fatty acids and linoleic acid seem promising for identifying those with higher plaque burden.

Radiomics-Based Assessment of OCT Angiography Images for Diabetic Retinopathy Diagnosis.

Purpose: To evaluate the diagnostic accuracy of machine learning (ML) techniques applied to radiomic features extracted from OCT and OCT angiography (OCTA) images for diabetes mellitus (DM), diabetic retinopathy (DR), and referable DR (R-DR) diagnosis. Design: Cross-sectional analysis of a retinal image dataset from a previous prospective OCTA study (ClinicalTrials.govNCT03422965). Participants: Patients with type 1 DM and controls included in the progenitor study. Methods: Radiomic features were extracted from fundus retinographies, OCT, and OCTA images in each study eye. Logistic regression, linear discriminant analysis, support vector classifier (SVC)-linear, SVC-radial basis function, and random forest models were created to evaluate their diagnostic accuracy for DM, DR, and R-DR diagnosis in all image types. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) mean and standard deviation for each ML model and each individual and combined image types. Results: A dataset of 726 eyes (439 individuals) were included. For DM diagnosis, the greatest AUC was observed for OCT (0.82, 0.03). For DR detection, the greatest AUC was observed for OCTA (0.77, 0.03), especially in the 3 × 3 mm superficial capillary plexus OCTA scan (0.76, 0.04). For R-DR diagnosis, the greatest AUC was observed for OCTA (0.87, 0.12) and the deep capillary plexus OCTA scan (0.86, 0.08). The addition of clinical variables (age, sex, etc.) improved most models AUC for DM, DR and R-DR diagnosis. The performance of the models was similar in unilateral and bilateral eyes image datasets. Conclusions: Radiomics extracted from OCT and OCTA images allow identification of patients with DM, DR, and R-DR using standard ML classifiers. OCT was the best test for DM diagnosis, OCTA for DR and R-DR diagnosis and the addition of clinical variables improved most models. This pioneer study demonstrates that radiomics-based ML techniques applied to OCT and OCTA images may be an option for DR screening in patients with type 1 DM. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Landscape character assessment with GIS using map-based indicators and photographs in the relationship between landscape and roads.

Planning and monitoring of landscapes cannot be reduced to its outstanding features, but must take into account all its characteristics. In this context, the relationship of landscape with roads is of particular importance, because roads alter the territory's environmental resources but also constitute a resource through which the individual comes into contact with the landscape. The aim of this work is to design a methodology to evaluate both the character and the scenic quality of the landscape as viewed from motorways and to provide measures to assess whether the motorway conveys the character of the landscape of which it forms part. The main contribution of this research consists of assessing landscape character through a novel series of map-based indicators and combining the findings with a photo-based method of assessing visual landscape quality. The method has been applied to a case study around a motorway in Madrid Region (Spain). Landscape character values regarding coherence, complexity, naturalness, visual scale, disturbance, historicity, and ephemera are obtained using Geographic Information Systems. Additionally, the landscape quality results derived using photographs allow the incorporation of the user's perception at a local scale.

Modifications of the homeostasis model assessment of insulin resistance index with age.

The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, and an oral glucose tolerance test in subjects without diabetes. In the Di@bet.es study overall, an increase occurred in blood glucose until the age of 50, after which it remained stable (data adjusted for gender, body mass index, abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p < 0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra study, the HOMA-IR was significantly lower after 6-year follow-up in the whole study population. Subjects with a HOMA-IR level higher than the 75th percentile at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2-3.9; p = 0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not increase HOMA-IR levels, changes that might be related to higher rates of obesity and AGR in older subjects. The HOMA-IR was associated with an increased risk of developing type 2 diabetes 6 years later.

[Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis]. / Etanercept y otras terapias biológicas en artritis reumatoide. Un análisis de costo-efectividad.

OBJECTIVE: to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. METHODS: a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). RESULTS: the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. CONCLUSIONS: we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

Objetivo: analizar la relación costo-efectividad del etanercept en comparación con otras terapias biológicas para tratar la artritis reumatoide moderada o severa en pacientes con falla previa a fármacos antirreumáticos modificadores de la enfermedad. Métodos: se empleó un modelo farmacoeconómico basado en el análisis de decisiones para valorar la evolución clínica con etanercept, infliximab, adalimumab o tocilizumab para tratar artritis reumatoide moderada o severa. Los parámetros de efectividad fueron las tasas de mejoría igual o superior a 20 % (ACR 20) y de mejoría igual o superior a 70 % (ACR 70). Resultados: etanercept tuvo la mayor efectividad terapéutica: en 79.7 % de los pacientes se observó una ACR 20 y en 31.4 %, una ACR 70. También tuvo el menor costo asociado ($149 629.1 por paciente) y fue más costo-efectiva ($187 740.4 por éxito clínico para obtener ACR 20 y $476 525.8 por éxito clínico para obtener ACR 70) que las demás terapias biológicas. Conclusiones: el etanercept fue el fármaco más efectivo y menos costoso, por lo que resulta la opción terapéutica más eficiente, desde el punto de vista de la relación costo-efectividad media y en términos incrementales para el tratamiento de la artritis reumatoide.

Análisis del costo y la efectividad de los esquemas de administración de factores de coagulación para el manejo de niños con hemofilia A en México / Cost-effectiveness analysis of prophylaxis vs. ''on demand'' approach in the management in children with hemophilia A in Mexico

Introducción. La hemofilia A es causada por la deficiencia del factor VIII. El tratamiento consiste principalmente en aumentar la concentración del FVIII en la sangre utilizando productos de remplazo. El objetivo de este trabajo fue estimar los beneficios clínicos y económicos del manejo profiláctico con factor VIII en niños con hemofilia A en México. Métodos. Se realizó la evaluación económica del manejo profiláctico (PROF) y del tratamiento sobre demanda (SD). Las estrategias comparadas fueron el manejo profiláctico -consistente en FVIII recombinante 25 UI/kg cada tercer día- vs. tratamiento sobre demanda -consistente en FVIII derivado de plasma 40 UI/kg. Se reportó el número de sangrados evitados (SE). Se empleó una tasa de descuento del 5%. Los resultados se expresaron en pesos mexicanos. Resultados. El costo de incremental de PROF respecto a SD fue de $7,727,554 pesos. El manejo con PROF ofrece una reducción de 112 SE frente al manejo de SD (162.9 vs. 50.7). El costo por SE fue de $68,876 pesos. Conclusiones. Un abordaje con PROF mejora la calidad de vida respecto al manejo SD y reduce el número de hemorragias que enfrentan los niños con hemofilia A. PROF es una alternativa costo-efectiva (RCEI $68,876 pesos) para reducir sangrados de acuerdo con la disponibilidad de pago establecida por las autoridades de salud en México.

Background. Hemophilia A is due to a deficiency of factor VIII. Treatment consists primarily of increasing the concentration of FVIII in the blood using replacement products. The aim of this study was to estimate the clinical and economic benefits of prophylactic management with factor VIII in children with hemophilia A in Mexico. We undertook this study to estimate the clinical and economic benefits of prophylactic management (PROF) with factor VIII (FVIII) in children with severe hemophilia in Mexico. Methods. We carried out an economic evaluation of PROF vs. treatment on demand (OD). The strategies compared were management with PROF consisting of recombinant FVIII (rFVIII) 25 IU kg every other day vs. OD management consisting of plasma-derived FVIII (pdFVIII) 40 IU kg. A Markov model was performed with a time horizon of 16 years in patients with severe hemophilia for 2 years, reporting the number of events of bleeding averted (BA). We used a discount rate of 5%. The results are expressed in Mexican pesos (2012). Results. The incremental cost of PROF regarding SD was $7,727,554 pesos. PROF management provides a reduction of 112 BA vs. OD management (162.9 vs. 50.7). Cost per BA was $68,876 pesos. Conclusions. Management with PROF reduces the number of bleeding events facing children with hemophilia A compared to OD management. PROF is a cost-effective alternative to reduce bleeding ($68,876 pesos per BA) according to the willingness to pay established by health authorities in Mexico.

[Economic analysis of parecoxib in the management of postsurgical pain in gynecology]. / Análisis económico de parecoxib en el tratamiento del dolor postoperatorio en ginecología.

BACKGROUND: Poorly managed postoperative pain has a negative impact in healing patients and costs of care. METHODS: A model to estimate economic and health consequences of parecoxib 40 mg and morphine 12 mg regarding ketorolac 30 mg, on the management of postoperative pain in gynecologic laparotomy surgery from the perspective of the Mexican Social Security Institute (IMSS) was developed. A systematic review to identify the proportion of patients that rated their analgesic treatment as "excellent" or "good" in the Patient Global Evaluation of Study Medication, 12 hours after administration of the analgesic (responders), was performed. The patients who rated "fair" or "poor" their treatment were administered additional 4 mg of morphine. Costs in the model correspond to the acquisition costs of analgesics in which the institution would incur. RESULTS: The proportion and cost per responder were: morphine: 14.44% and $192.79, ketorolac: 32.44% and $34.82, parecoxib: 35.51% and $121.25.Treatment with morphine was more expensive and less effective than both, ketorolac and parecoxib, while the cost per additional percent point of responders with parecoxib (compared to ketorolac) was $28.15. For the management of postoperative pain, ketorolac and parecoxib are more effective and less expensive than morphine, additionally parecoxib would be an alternative for patients with contraindication to ketorolac use. CONCLUSION: The management of postoperative pain with parecoxib is more effective and, in the context of IMSS, less expensive than morphine, also constitutes an alternative with a reasonable incremental cost compared to ketorolac.

[Economic analysis of dalteparin use in knee surgery at Instituto Mexicano del Seguro Social]. / Análisis económico de dalteparina en la indicacióncirugía de rodilla en el Instituto Mexicano del Seguro Social.

BACKGROUND: Knee surgery is a risk factor for thromboembolic disease. Prophylaxis reduces the risk of this condition. METHODS: Economic and health consequences of drugs preventing and treating thromboembolic disease in patients undergoing knee surgery from the institutional perspective (time horizon: 1 year) were estimated. The measures of effectiveness were: reduction in the number of cases (per 1,000 patients) of deep vein thrombosis, pulmonary embolism, hospital admissions and deaths. Transition probabilities were estimated by meta-analysis. The alternatives were: warfarin (reference), dalteparin, enoxaparin, nadroparin, unfractionated heparin + warfarin, and non-prophylaxis. Data on resources use and costs corresponds to the Instituto Mexicano del Seguro Social (IMSS). Acceptability curves were constructed. RESULTS: No prophylaxis implied three times higher cost ($18,835.10 versus $5,967.10) and less effectiveness in comparison with warfarin. The incremental cost-effectiveness ratios for enoxaparin were $3, $13, $17 and $3 per each additional case of deep vein thrombosis, pulmonary embolism, death and hospital admission avoided. Results of nadroparin and unfractionated heparin were inferior to warfarin (59.1% and 72.9% more costly and less effective in three measures of effectiveness, respectively). Dalteparin showed higher health outcomes and lower cost compared with warfarin (-20.6%). Dalteparin had a higher probability of being cost-effective than enoxaparin. DISCUSSION: thromboprophylaxis is a clinically and economically favorable alternative. The identification of a pharmacoeconomic profile of alternatives to perform it becomes relevant given the increasing pressure on institutional budgets. CONCLUSIONS: Dalteparin would be a cost-saving alternative in thromboprophylaxis of patients undergoing knee surgery at IMSS.

Costo Efectividad del Tratamiento de Tumores Neuroendócrinos Pancreáticos Avanzados no Operables con Sunitinib en México.

OBJECTIVES: Sunitinib had showed a substantial clinical benefit in patients with non-resectable pancreatic Neuroendocrine Tumors (NET). The objective of this study was to estimate the cost-effectiveness of sunitinib in the treatment of non-resectable pancreatic NET, from the perspective of the Social Security Mexican Institute (IMSS). METHODS: A Markov model (2-week cycles) was used to estimate the health and economic consequences of sunitinib 37.5mg/day+best supportive care (BSC) regarding placebo+BSC (ten-years horizon, discount rate: 5%). Effectiveness measures were: overall survival (OS), progression-free survival (PFS) and quality adjusted life years (QALY). Resource utilization (BSC, adverse events management, medical follow-up) was estimated through a survey with Mexican oncologists (n=10). Unit costs of medication and medical resources were obtained from institutional sources. Sensitivity analyses were performed and acceptability curves were constructed. RESULTS: Sunitinib+BSC gained 0.49 years (PFS), 1.18 years (OS) and 0.70 QALY against placebo+BSC. Sunitinib+BSC increased medical direct costs (2011 US$) per patient in $20,854, which was driven by acquisition costs of sunitinib and medical follow up before progression. ICER's were $42,157, $17,662 and $29,808 per progression-free year, life-year and QALY gained, respectively, which remained robust through±25% changes in main parameters. At willingness to pay higher than $40,000, $22,400 and $37,600 sunitinib+BSC becomes the most cost-effective alternative in regards to PFS, OS and QALYs, respectively. CONCLUSION: At IMSS, sunitinib+BSC would provide substantial clinical benefits to patients suffering unresectable pancreatic NET, although the latter would increase medical costs of treatment and clinical follow up.

Cost Utility of Sirolimus versus Tacrolimus for the Primary Prevention of Graft Rejection in Renal Transplant Recipients in Mexico.

OBJECTIVE: Therapies for end-stage renal disease improve quality of life, and survival. In Mexico, clinicians often must choose between different therapies without the availability of comparative outcomes evaluation. The present study evaluates the comparative cost-utility of sirolimus (SIR) versus tacrolimus (TAC) for the primary prevention of graft rejection in renal transplant recipients in Mexico. METHODS: We used modeling techniques to estimate the cost-effectiveness of SIR versus TAC to prevent graft rejection in patients with end-stage renal disease in the Mexican setting. The model estimates the cost of quality-adjusted life-year (QALY) per patient. We applied a 20-year horizon (1-year Markov cycles). Cost-effectiveness was expressed in terms of cost per QALY. All costs are presented in 2011 US dollars. Probabilistic sensitivity analyses were conducted. RESULTS: The total cost for the SIR treatment arm over the 20-year duration of the model is estimated to be $136,778. This compares with $142,624 for the TAC treatment arm, resulting in an incremental cost of SIR compared with that of TAC of-$5,846. Over 20 years, SIR was estimated to have 8.18 QALYs compared with 7.33 QALYs for TAC. The resulting incremental utility of SIR compared with that of TAC is 0.84 QALY gained. SIR is estimated to be both less costly and more effective than TAC, indicating that it is the dominant strategy. Notably, results suggest that SIR has a 78% probability of being dominant over the TAC strategy and a 100% probability of having an incremental cost-effectiveness ratio at or below $10,064 (1 GDP) per QALY. CONCLUSIONS: These analyses suggest that in the Mexican setting, the use of SIR in place of TAC for the prevention of graft rejection in this population is likely to be cost saving.

[Economic evaluation of an infant immunization program in Mexico, based on 13-valent pneumococcal conjugated vaccines]. / Evaluación económica de un programa de inmunización infantil en México basado en la vacuna neumocócica conjugada 13-valente.

OBJECTIVES: Vaccination is an effective intervention for reduce child morbidity and mortality associated to pneumococcus. The availability of new anti-pneumococcal vaccines makes it necessary to evaluate its potential impact on public health and costs related to their implementation. The aim of this study was to estimate the cost-effectiveness and cost-utility of immunization strategies based on pneumococcal conjugated vaccines (PCV's) currently available in Mexico from a third payer perspective. MATERIAL AND METHODS: A decision tree model was developed to assess both, economic and health impact, of anti-pneumococcal vaccination in children <2 years (lifetime time horizon, discount rate: 5% annual). Comparators were: no-vaccination (reference) and strategies based on 7, 10 and 13-valent PCV's. Effectiveness measures were: child deaths avoided, life-years gained (LYG) and quality adjusted life years (QALY's) gained. Effectiveness, utility, local epidemiology and cost of treating pneumococcal diseases were extracted from published sources. Univariate sensitivity analysis were performed. RESULTS: Immunization dominates no-vaccination: strategy based on 13-valent vaccine prevented 16.205 deaths, gained 331.230 LY's and 332.006 QALY's and saved US$1.307/child vaccinated. Strategies based on 7 and 10-valent PCV's prevented 13.806 and 5.589 deaths, gained 282.193 and 114.251 LY's, 282.969 and 114.972 QALY's and saved US$1.084 and US$731/child vaccinated, respectively. These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. CONCLUSIONS: In Mexico, immunization strategies based on 7, 10 and 13-valent PCV's would be cost-saving interventions, however, health outcomes and savings of the strategy based on 13-valent vaccine are greater than those estimated for 7 and 10-valent PCV's.

Evaluation of accessibility and use of new communication technologies in patients with type 1 diabetes mellitus.

BACKGROUND: The role of patients in the management and control of type 1 diabetes mellitus, a chronic disease, is well established. The advent of new communication technologies is expected to improve patients' access to health information. However, little is known about the extent to which patients with type 1 diabetes mellitus use the Internet to retrieve medical information and about the impact, if any, this retrieval has on their health status. OBJECTIVE: To evaluate the accessibility and use of new communication technologies in a population of patients with type 1 diabetes mellitus. METHODS: Patients with type 1 diabetes mellitus attending the Diabetes Clinic of the Hospital de Sabadell, Sabadell, Spain, in a 6-month period were asked to answer a structured questionnaire about education level, Internet accessibility, use of health-related Web sites, and mobile-phone ownership and use. RESULTS: Of 302 patients with type 1 diabetes mellitus attending the Diabetes Clinic on a regular basis, 244 (115 men, 129 women) were interviewed (response rate 80.8%). Personal computers were owned by 58.2% of patients. Fifty-nine percent had access to the Internet, 39.3% had access to the Internet at home; however, only 36.5% were regular Internet users. Internet users were younger, more frequently men, and of higher education level. Among Internet users only 49.4% had ever accessed a health-related Web site. Internet users who had ever accessed a health-related Web site had a higher level of education, presented severe hypoglycemia more frequently, and were more likely to have access to the Internet at home. No differences were found in metabolic control between Internet users and nonusers or between Internet users who had ever accessed a health-related Web site and Internet users who had never accessed a health-related Web site. Of the 76.6% of the patients that owned a mobile phone, 96% used it more than once a week. CONCLUSIONS: The impact of new communication technologies might be jeopardized by the low rate of access and utilization of the Internet for health-related purposes. Because of their high rate of ownership and use, mobile phones show promise as a tool in health care communication technologies.