External validation and comparison of six cardiovascular risk prediction models in the Prospective Urban Rural Epidemiology (PURE)-Colombia study.

AIMS: To external validate the SCORE2, AHA/ACC Pooled Cohort Equation (PCE), Framingham Risk Score (FRS), Non-Laboratory INTERHEART Risk Score (NL-IHRS), Globorisk-LAC, and WHO prediction models and compare their discrimination and calibration capacity. METHODS: Validation in individuals aged 40-69 years with at least 10 years follow-up and without baseline use of statins or cardiovascular diseases from the Prospective Urban Rural Epidemiology prospective cohort study (PURE)-Colombia. For discrimination, the C-statistic, and Receiver Operating Characteristic curves with the integrated area under the curve (AUCi) were used and compared. For calibration, the smoothed time-to-event method was used, choosing a recalibration factor based on the integrated calibration index (ICI). In the NL-IHRS, linear regressions were used. RESULTS: In 3,802 participants (59.1% women), baseline risk ranged from 4.8% (SCORE2 women) to 55.7% (NL-IHRS). After a mean follow-up of 13.2 years, 234 events were reported (4.8 cases per 1000 person-years). The C-statistic ranged between 0.637 (0.601-0.672) in NL-IHRS and 0.767 (0.657-0.877) in AHA/ACC PCE. Discrimination was similar between AUCi. In women, higher overprediction was observed in the Globorisk-LAC (61%) and WHO (59%). In men, higher overprediction was observed in FRS (72%) and AHA/ACC PCE (71%). Overestimations were corrected after multiplying by a factor derived from the ICI. CONCLUSIONS: Six prediction models had a similar discrimination capacity, supporting their use after multiplying by a correction factor. If blood tests are unavailable, NL-IHRS is a reasonable option. Our results suggest that these models could be used in other countries of Latin America after correcting the overestimations with a multiplying factor.

Detecting people at high risk of cardiovascular disease and implementing preventive interventions in this population is a key strategy in primary prevention. Recently, new risk calculation tools have been developed, but before their application and routine use in populations different from those where it was developed, it's necessary to validate them. The recommendations for predicting cardiovascular risk in Colombia's guidelines are based on studies with noteworthy limitations. This study involving 3,802 healthy individuals in Colombia supports the recommendation of using these prediction models. The estimation result should be multiplied by a correction factor, because most of the prediction models overestimate cardiovascular risk. For example, the correction factors suggested in women for AHA/ACC PCE and SCORE2 are 0.54 and 0.75, respectively. In men, the correction factors suggested in AHA/ACC PCE and SCORE2 are 0.28 and 0.61, respectively. Therefore, the present study with a contemporary population provides additional evidence to update these recommendations in Colombia and perhaps in Latin America.

Sex Differences in Cardiovascular Disease Risk Factor Prevalence, Morbidity, and Mortality in Colombia: Findings from the Prospective Urban Rural Epidemiology (PURE) Study.

Background: Controversies exist on whether the presence of cardiovascular risk factors and their association with major cardiovascular events (MACE) is different between men and women. Most of the evidence comes from high-income countries, hindering extrapolation of sociocultural and demographic factors of other regions. Objective: To evaluate sex differences in the prevalence of cardiovascular risk factors and the incidence of MACE and diabetes in Colombian adults. Methods: We performed a survival analysis from women and men aged 35-70 belonging to the Prospective Urban Rural Epidemiology-Colombia prospective study. Incidence rates for MACE composite (myocardial infarction, stroke, heart failure, death) and each outcome and diabetes were calculated. Kaplan-Meier curves and log-rank tests were performed. The association between demographic, behavioral, and metabolic variables with MACE and diabetes were evaluated with Cox proportional hazards models. Results: 7,552 participants (50±9.7 years) were included; 64% were women. Women had higher hypertension prevalence, body mass index, levels of total cholesterol, LDL-c, and HDL-c but lower triglycerides levels. Women were more sedentary but fewer smokers or active alcohol consumers and had higher educational levels. After 12-year mean follow-up (SD 2.3), the incidence rate of MACE composite was higher in men [4.2 (3.6-4.9) vs. 3.2 (2.8-3.7) cases per 1000 person-years]. Diabetes had the greatest association with MACE (HR = 2.63 95%CI:1.85;3.76), followed by hypertension (HR = 1.75 95%CI:1.30;2.35), low relative grip strength (HR = 1.53 95%CI:1.15;2.02), smoking (HR = 1.47 95%CI: 1.11;1.93), low physical activity (HR = 1.42 95%CI: 1.03;1.96). When evaluating risk factors by sex, only an increased waist-to-hip ratio was more strongly associated with MACE in men (p-interaction <0.05). Conclusions: The composite MACE outcome was higher in men despite having a lower overall burden of risk factors. The risk factors contribution was similar, leading us to reconsider the need to carrying out differentiated cardiovascular risk prevention and management campaigns, at least in our region.

Waist circumference cut-off points to identify major cardiovascular events and incident diabetes in Latin America: findings from the prospective Urban rural epidemiology study Colombia.

Background: Abdominal obesity (AO) indirectly represents visceral adiposity and can be assessed by waist circumference (WC) measurement. In Latin America, cut-off points for the diagnosis of AO are based on Asian population data. We aim to establish the WC cut-off points to predict major cardiovascular events (MACE) and incident diabetes. Methods: We analyzed data from the cohort PURE study in Colombia. WC cut-off points were defined according to the maximum Youden index. Multivariate logistic regression was used to obtain associations between WC and MACE, diabetes, and cumulative incidence of outcomes visualized using Kaplan-Meier curves. Results: After a mean follow-up of 12 years, 6,580 individuals with a mean age of 50.7 ± 9.7 years were included; 64.2% were women, and 53.5% were from rural areas. The mean WC was 85.2 ± 11.6 cm and 88.3 ± 11.1 cm in women and men, respectively. There were 635 cases of the MACE composite plus incident diabetes (5.25 events per 1,000 person-years). Using a cut-off value of 88.85 cm in men (sensitivity = 0.565) and 85.65 cm in women (sensitivity = 0.558) resulted in the highest value for the prediction of the main outcome. These values were associated with a 1.76 and 1.41-fold increased risk of presenting the composite outcome in men and women, respectively. Conclusions: We defined WC cut-off points of 89 cm in men and 86 cm in women to identify the elevated risk of MACE and incident diabetes. Therefore, we suggest using these values in cardiovascular risk assessment in Latin America.

Handgrip Strength Is Associated with Specific Aspects of Vascular Function in Individuals with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a disorder associated with an increased risk for the development of diabetes mellitus and its complications. Lower isometric handgrip strength (HGS) is associated with an increased risk of cardiometabolic diseases. However, the association between HGS and arterial stiffness parameters, which are considered the predictors of morbidity and mortality in individuals with MetS, is not well defined. OBJECTIVE: To determine the association between HGS and HGS asymmetry on components of vascular function in adults with MetS. METHODS: We measured handgrip strength normalized to bodyweight (HGS/kg), HGS asymmetry, body composition, blood glucose, lipid profile, blood pressure, pulse wave velocity (PWV), reflection coefficient (RC), augmentation index @75 bpm (AIx@75) and peripheral vascular resistance (PVR) in 55 adults with a diagnosis of MetS between 25 and 54 years old. RESULTS: Mean age was 43.1 ± 7.0 years, 56.3% were females. HGS/kg was negatively correlated with AIx@75 (r = -0.440), p < 0.05, but these associations were not significant after adjusting for age and sex. However, when interaction effects between sex, HGS/kg and age were examined, we observed an inverse relationship between HGS/kg and AIx@75 in the older adults in the sample, whereas in the younger adults, a weak direct association was found. We also found a significant association between HGS asymmetry and PVR (beta = 30, 95% CI = 7.02; 54.2; p <0.012). CONCLUSIONS: Our findings suggest that in people with MetS, maintaining muscle strength may have an increasingly important role in older age in the attenuation of age-related increases in AIx@75-a marker of vascular stiffness-and that a higher HGS asymmetry could be associated with a greater vascular resistance.

Reductions in systolic blood pressure achieved by hypertensives with three isometric training sessions per week are maintained with a single session per week.

Isometric handgrip or (wall) squat exercise performed three times per week produces reductions in systolic blood pressure (SBP) in adults with hypertension. We aimed to compare these interventions and the potential to retain benefits with one exercise session per week. We compared blood pressure changes following handgrip and squat isometric training interventions with controls in a randomized controlled multicentre trial in 77 unmedicated hypertensive (SBP ≥ 130 mmHg) adults. Exercise sessions were performed in the workplace and consisted of four repetitions-three sessions per week for the first 12 weeks (phase 1), and one session per week for the subsequent 12 weeks (phase 2). Office blood pressure (BP) was measured at baseline, post-phase 1 and post-phase 2. Post-phase 1, mean reductions in SBP were significantly greater in handgrip (-11.2 mmHg, n = 28) and squat (-12.9 mmHg, n = 27) groups than in controls (-.4 mmHg; n = 22) but changes in DBP were not. There were no significant within-group changes during phase 2 but SBP was 3.8 mmHg lower in the wall squat than the handgrip group-a small magnitude but clinically important difference. While both interventions produced significant SBP reductions, the wall squat appears to be more effective in maintaining benefits with a minimal training dose. The low time investment to achieve and retain clinically significant SBP reductions-42 and 12 min, respectively-and minimal cost, particularly of the wall squat, make it a promising intervention for delivery in public health settings.

Insulin Resistance Markers to Detect Nonalcoholic Fatty Liver Disease in a Male Hispanic Population.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease and is closely associated with cardiometabolic disorders, being insulin resistance (IR) the common pathogenic mechanism. The triglycerides/glucose (TyG) index and triglycerides/HDL-c (TG/HDL) ratio are markers correlated with IR. We compared the capacity of these two indexes, alongside IR, to detect NAFLD. Methods: In a cross-sectional cohort study, we examined 263 active military personnel from the Colombian Air Force, aged between 29 and 54 years. Anthropometric measurements and biochemical determinations (glycemia, lipid profile, and insulin) were obtained, and ultrasound studies were performed to evaluate the presence of NAFLD. HOMA-IR index was calculated as (fasting insulin (µIU/mL) × fasting glucose (mmol/L)/22.5), the TyG index as Ln (triglycerides (mg/dL) × fasting glucose (mg/dL)/2), and the TG/HDL ratio as (triglycerides (mg/dL)/HDL-c (mg/dL)). Results: NAFLD ultrasound criteria were met in 70 individuals (26.6%). Subjects with NAFLD had significantly higher values of HOMA-IR (2.55 ± 1.36 vs. 1.51 ± 0.91), TyG (9.17 ± 0.53 vs. 8.7 ± 0.51), and TG/HDL (6.6 ± 4.54 vs. 3.52 ± 2.32) compared to those without NAFLD (p < 0.001). A TyG cutoff point of 8.92 showed an AUC of 0.731, while cutoff points of 3.83 for TG/HDL and 1.68 for HOMA-IR showed an AUC of 0.766 and 0.781, respectively. Conclusion: Our study shows that novel and lower-cost markers of IR are useful for detecting NALFD, with a performance comparable to the HOMA-IR index. These markers should be used as the first step when screening patients for NAFLD.

Ethnic Differences in the Prevalence of Hypertension in Colombia: Association With Education Level.

BACKGROUND: A higher prevalence of hypertension is reported among Afro-descendants compared with other ethnic groups in high-income countries; however, there is a paucity of information in low- and medium-income countries. METHODS: We evaluated 3,745 adults from 3 ethnic groups (552 White, 2,746 Mestizos, 447 Afro-descendants) enrolled in the prospective population-based cohort study (PURE)-Colombia. We assessed associations between anthropometric, socioeconomic, behavioral factors, and hypertension. RESULTS: The overall prevalence of hypertension was 39.2% and was higher in Afro-descendants (46.3%) than in Mestizos (37.6%) and Whites (41.5%), differences that were due to the higher prevalence in Afro-descendant women. Hypertension was associated with older age, increased body mass index, waist circumference and waist-to-hip ratio, independent of ethnicity. Low education was associated with hypertension in all ethnic groups, and particularly in Afro-descendants, for whom it was the factor with the strongest association with prevalence. Notably, 70% of Afro-descendants had a low level of education, compared with 52% of Whites-26% of Whites were university graduates while only 7% of Afro-descendants were. We did not find that education level alone had a mediator effect, suggesting that it is not a causal risk factor for hypertension but is an indicator of socioeconomic status, itself an important determinant of hypertension prevalence. CONCLUSIONS: We found that a higher prevalence of hypertension in Colombian Afro-descendants than other ethnic groups. This was principally associated with their lower mean educational level, an indicator of lower socioeconomic status.

Joint Estimation of Relative Risk for Dengue and Zika Infections, Colombia, 2015-2016.

We jointly estimated relative risk for dengue and Zika virus disease (Zika) in Colombia, establishing the spatial association between them at the department and city levels for October 2015-December 2016. Cases of dengue and Zika were allocated to the 87 municipalities of 1 department and the 293 census sections of 1 city in Colombia. We fitted 8 hierarchical Bayesian Poisson joint models of relative risk for dengue and Zika, including area- and disease-specific random effects accounting for several spatial patterns of disease risk (clustered or uncorrelated heterogeneity) within and between both diseases. Most of the dengue and Zika high-risk municipalities varied in their risk distribution; those for Zika were in the northern part of the department and dengue in the southern to northeastern parts. At city level, spatially clustered patterns of dengue high-risk census sections indicated Zika high-risk areas. This information can be used to inform public health decision making.

Two-level resolution of relative risk of dengue disease in a hyperendemic city of Colombia.

Risk maps of dengue disease offer to the public health officers a tool to model disease risk in space and time. We analyzed the geographical distribution of relative incidence risk of dengue disease in a high incidence city from Colombia, and its evolution in time during the period January 2009-December 2015, identifying regional effects at different levels of spatial aggregations. Cases of dengue disease were geocoded and spatially allocated to census sectors, and temporally aggregated by epidemiological periods. The census sectors are nested in administrative divisions defined as communes, configuring two levels of spatial aggregation for the dengue cases. Spatio-temporal models including census sector and commune-level spatially structured random effects were fitted to estimate dengue incidence relative risks using the integrated nested Laplace approximation (INLA) technique. The final selected model included two-level spatial random effects, a global structured temporal random effect, and a census sector-level interaction term. Risk maps by epidemiological period and risk profiles by census sector were generated from the modeling process, showing the transmission dynamics of the disease. All the census sectors in the city displayed high risk at some epidemiological period in the outbreak periods. Relative risk estimation of dengue disease using INLA offered a quick and powerful method for parameter estimation and inference.

Spatio-Temporal Modeling of Zika and Dengue Infections within Colombia.

The aim of this study is to estimate the parallel relative risk of Zika virus disease (ZVD) and dengue using spatio-temporal interaction effects models for one department and one city of Colombia during the 2015⁻2016 ZVD outbreak. We apply the integrated nested Laplace approximation (INLA) for parameter estimation, using the epidemiological week (EW) as a time measure. At the departmental level, the best model showed that the dengue or ZVD risk in one municipality was highly associated with risk in the same municipality during the preceding EWs, while at the city level, the final model selected established that the high risk of dengue or ZVD in one census sector was highly associated not only with its neighboring census sectors in the same EW, but also with its neighboring sectors in the preceding EW. The spatio-temporal models provided smoothed risk estimates, credible risk intervals, and estimation of the probability of high risk of dengue and ZVD by area and time period. We explore the intricacies of the modeling process and interpretation of the results, advocating for the use of spatio-temporal models of the relative risk of dengue and ZVD in order to generate highly valuable epidemiological information for public health decision making.

Relative risk estimation of dengue disease at small spatial scale.

BACKGROUND: Dengue is a high incidence arboviral disease in tropical countries around the world. Colombia is an endemic country due to the favourable environmental conditions for vector survival and spread. Dengue surveillance in Colombia is based in passive notification of cases, supporting monitoring, prediction, risk factor identification and intervention measures. Even though the surveillance network works adequately, disease mapping techniques currently developed and employed for many health problems are not widely applied. We select the Colombian city of Bucaramanga to apply Bayesian areal disease mapping models, testing the challenges and difficulties of the approach. METHODS: We estimated the relative risk of dengue disease by census section (a geographical unit composed approximately by 1-20 city blocks) for the period January 2008 to December 2015. We included the covariates normalized difference vegetation index (NDVI) and land surface temperature (LST), obtained by satellite images. We fitted Bayesian areal models at the complete period and annual aggregation time scales for 2008-2015, with fixed and space-varying coefficients for the covariates, using Markov Chain Monte Carlo simulations. In addition, we used Cohen's Kappa agreement measures to compare the risk from year to year, and from every year to the complete period aggregation. RESULTS: We found the NDVI providing more information than LST for estimating relative risk of dengue, although their effects were small. NDVI was directly associated to high relative risk of dengue. Risk maps of dengue were produced from the estimates obtained by the modeling process. The year to year risk agreement by census section was sligth to fair. CONCLUSION: The study provides an example of implementation of relative risk estimation using Bayesian models for disease mapping at small spatial scale with covariates. We relate satellite data to dengue disease, using an areal data approach, which is not commonly found in the literature. The main difficulty of the study was to find quality data for generating expected values as input for the models. We remark the importance of creating population registry at small spatial scale, which is not only relevant for the risk estimation of dengue but also important to the surveillance of all notifiable diseases.

Bayesian dynamic modeling of time series of dengue disease case counts.

The aim of this study is to model the association between weekly time series of dengue case counts and meteorological variables, in a high-incidence city of Colombia, applying Bayesian hierarchical dynamic generalized linear models over the period January 2008 to August 2015. Additionally, we evaluate the model's short-term performance for predicting dengue cases. The methodology shows dynamic Poisson log link models including constant or time-varying coefficients for the meteorological variables. Calendar effects were modeled using constant or first- or second-order random walk time-varying coefficients. The meteorological variables were modeled using constant coefficients and first-order random walk time-varying coefficients. We applied Markov Chain Monte Carlo simulations for parameter estimation, and deviance information criterion statistic (DIC) for model selection. We assessed the short-term predictive performance of the selected final model, at several time points within the study period using the mean absolute percentage error. The results showed the best model including first-order random walk time-varying coefficients for calendar trend and first-order random walk time-varying coefficients for the meteorological variables. Besides the computational challenges, interpreting the results implies a complete analysis of the time series of dengue with respect to the parameter estimates of the meteorological effects. We found small values of the mean absolute percentage errors at one or two weeks out-of-sample predictions for most prediction points, associated with low volatility periods in the dengue counts. We discuss the advantages and limitations of the dynamic Poisson models for studying the association between time series of dengue disease and meteorological variables. The key conclusion of the study is that dynamic Poisson models account for the dynamic nature of the variables involved in the modeling of time series of dengue disease, producing useful models for decision-making in public health.

Purified capsular polysaccharide of Neisseria meningitidis serogroup A as immune potentiator for antibody production.

The development of new immune potentiators for human vaccines is an important and expanding field of research. In the present study, the ability of the capsular polysaccharide from Neisseria meningitidis serogroup A (CPS-A), a mannose-containing carbohydrate, to enhance the antibody production against a co-administered model vaccine antigen, is examined. A protein-meningococcal serogroup C capsular polysaccharide (CPS-C) conjugate was selected as the model antigen for this study. After subcutaneous immunization of Balb/C mice, the conjugate mixed with CPS-A induced higher anti-CPS-C IgG and IgG(2a) antibody levels and higher anti-meningococcal serogroup C bactericidal titers than the conjugate alone or mixed with CPS-C. The immuno-stimulatory properties exhibited by CPS-A and the fact that vaccines based on purified CPS-A has been safely used during decades to fight the serogroup A meningococcal disease, support the proposal to use CPS-A as immune potentiator for human vaccination studies.

Reemplazo total de rodilla pososteotomias altas fallidas: dificultades tecnicas y resultados / Total knee replacement after failed high tibial osteotomy: technical diffculties and results

El reemplazo total de rodilla pososteotomia tibial alta es una cirugia que debe planificarse con cuidado en el preoperatorio. Esa planificacion permitira sobrellevar en forma satisfactoria las dificultades tecnicas que implican este tipo de revisiones (retraccion de las partes blandas, incisiones previas, deficiencias oseas, etc). Se compararon 2 grupos de pacientes. Grupo 1: 30 rodillas operadas con reemplazo total de rodilla pososteotomia tibial. Grupo 2: 30 rodillas intervenidas con reemplazo total de rodilla primaria. Ambos grupos fueron similares en deformidad angular (varo), edad, sexo y tipo de protesis (Insall-Burstein II). Todos fueron evaluados con el puntaje para rodilla de Hungerford. Seguimiento: en ambos grupos, de 3 a 10 años. Se evaluo en forma especial la funcionalidad de las rodillas comparando la amplitud de movimiento, el dolor y la deambulacion posoperatorias. Los resultados de los reemplazos pososteotomias resultaron similares a los de los reemplazos articulares primarios. (AU)

Reemplazo total de rodilla: estudio retrospectivo de 92 pacientes (105 rodillas) con conservación de la rótula (1988-1998) / Total knee replacement: retrospective study in 92 patients (105 knees) with patellar retention (1988-1998)

Introducción: Se presenta el estudio retrospectivo efectuado en nuestro servicio de cirugía de rodilla entre los años 1988 y 1998 al realizar los reemplazos articulares con la conservación de la rótula sin colocar componente protésico. Materiales y métodos: Durante ese período se operaron 167 pacientes (186 rodillas) con esta técnica. Se incluyeron en el trabajo 92 pacientes, 13 de ellos con artroplastias bilaterales. Sesenta y dos eran mujeres y 30 varones, 61 rodillas eran derechas y 44 rodillas, izquierdas. Los pacientes fueron evaluados con el puntaje de Hungerford para la función global de la rodilla y con la evaluación recomendada por Freeman para la rótula en forma específica. Las prótesis utilizadas fueron el modelo Insall-Burnstein II en 86 rodillas y el modelo AGC (Biomet) en las 19 restantes. En lo que respecta a la rótula, se la trató de la siguiente manera: remoción de los osteófitos marginales, regularización de la superficie rotuliana con sierra, descompresión del hueso subcondral rotuliano mediante perforaciones con mecha de 2 mm y desnervación. Resultados: Los resultados obtenidos han sido altamente satisfactorios en un seguimiento a largo plazo en lo que respecta al dolor en la cara anterior de la rodilla y la funcionalidad de la articulación, en especial, la femoropatelar. Conclusiones: Se ha demostrado que este procedimiento es una opción válida para tener en cuenta. Se enumeran las indicaciones absolutas y relativas del procedimiento

Reemplazo total de rodilla pososteotomias altas fallidas: dificultades tecnicas y resultados / Total knee replacement after failed high tibial osteotomy: technical diffculties and results

El reemplazo total de rodilla pososteotomia tibial alta es una cirugia que debe planificarse con cuidado en el preoperatorio. Esa planificacion permitira sobrellevar en forma satisfactoria las dificultades tecnicas que implican este tipo de revisiones (retraccion de las partes blandas, incisiones previas, deficiencias oseas, etc). Se compararon 2 grupos de pacientes. Grupo 1: 30 rodillas operadas con reemplazo total de rodilla pososteotomia tibial. Grupo 2: 30 rodillas intervenidas con reemplazo total de rodilla primaria. Ambos grupos fueron similares en deformidad angular (varo), edad, sexo y tipo de protesis (Insall-Burstein II). Todos fueron evaluados con el puntaje para rodilla de Hungerford. Seguimiento: en ambos grupos, de 3 a 10 años. Se evaluo en forma especial la funcionalidad de las rodillas comparando la amplitud de movimiento, el dolor y la deambulacion posoperatorias. Los resultados de los reemplazos pososteotomias resultaron similares a los de los reemplazos articulares primarios.