Background Predicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models... Show moreBackground Predicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models is of great interest.Nowadays, there is a strong discussion in the medical field about machine learning (ML) and whether it has greater potential than traditional regression models when dealing with complex data. Criticism to ML is related to unsuitable performance measures and lack of interpretability which is important for clinicians. Methods In this paper, ML techniques such as random forests and neural networks are applied to large data of 62294 patients from the United States with 97 predictors selected on clinical/statistical grounds, over more than 600, to predict survival from transplantation. Of particular interest is also the identification of potential risk factors. A comparison is performed between 3 different Cox models (with all variables, backward selection and LASSO) and 3 machine learning techniques: a random survival forest and 2 partial logistic artificial neural networks (PLANNs). For PLANNs, novel extensions to their original specification are tested. Emphasis is given on the advantages and pitfalls of each method and on the interpretability of the ML techniques. Results Well-established predictive measures are employed from the survival field (C-index, Brier score and Integrated Brier Score) and the strongest prognostic factors are identified for each model. Clinical endpoint is overall graft-survival defined as the time between transplantation and the date of graft-failure or death. The random survival forest shows slightly better predictive performance than Cox models based on the C-index. Neural networks show better performance than both Cox models and random survival forest based on the Integrated Brier Score at 10 years. Conclusion In this work, it is shown that machine learning techniques can be a useful tool for both prediction and interpretation in the survival context. From the ML techniques examined here, PLANN with 1 hidden layer predicts survival probabilities the most accurately, being as calibrated as the Cox model with all variables. Show less
Najafabadi, A.H.Z.; Meer, P.B. van der; Boele, F.W.; Taphoorn, M.J.B.; Klein, M.; Peerdeman, S.M.; ... ; Dirven, L. 2020
Introduction Meningioma is a heterogeneous disease and patients may suffer from long-term tumor- and treatment-related sequelae. To help identify patients at risk for these late effects, we first... Show moreIntroduction Meningioma is a heterogeneous disease and patients may suffer from long-term tumor- and treatment-related sequelae. To help identify patients at risk for these late effects, we first assessed variables associated with impaired long-term health-related quality of life (HRQoL) and impaired neurocognitive function on group level (i.e. determinants). Next, prediction models were developed to predict the risk for long-term neurocognitive or HRQoL impairment on individual patient-level. Methods Secondary data analysis of a cross-sectional multicenter study with intracranial WHO grade I/II meningioma patients, in which HRQoL (Short-Form 36) and neurocognitive functioning (standardized test battery) were assessed. Multivariable regression models were used to assess determinants for these outcomes corrected for confounders, and to build prediction models, evaluated with C-statistics. Results Data from 190 patients were analyzed (median 9 years after intervention). Main determinants for poor HRQoL or impaired neurocognitive function were patients' sociodemographic characteristics, surgical complications, reoperation, radiotherapy, presence of edema, and a larger tumor diameter on last MRI. Prediction models with a moderate/good ability to discriminate between individual patients with and without impaired HRQoL (C-statistic 0.73, 95% CI 0.65 to 0.81) and neurocognitive function (C-statistic 0.78, 95%CI 0.70 to 0.85) were built. Not all predictors (e.g. tumor location) within these models were also determinants. Conclusions The identified determinants help clinicians to better understand long-term meningioma disease burden. Prediction models can help early identification of individual patients at risk for long-term neurocognitive or HRQoL impairment, facilitating tailored provision of information and allocation of scarce supportive care services to those most likely to benefit. Show less
Background: Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic... Show moreBackground: Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%integral T > 1-4xMIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment.Methods: This prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (integral T > MICECOFF and integral T > 4xMIC(ECOFF)) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes.Results: A total of 147 patients were included, of whom 63.3% achieved PDT of 100% integral T > MICECOFF and 36.7% achieved 100% integral T > 4xMIC(ECOFF). Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) >= 90 mL/min/1.73 m(2), and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100% integral T > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival.Conclusions Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients. Show less
Background: Peripheral arterial occlusive disease (PAOD) and chronic venous insufficiency (CVI) in organ transplant recipients (OTR) can lead to harmful outcomes. We made an inventory of cutaneous... Show moreBackground: Peripheral arterial occlusive disease (PAOD) and chronic venous insufficiency (CVI) in organ transplant recipients (OTR) can lead to harmful outcomes. We made an inventory of cutaneous manifestations of PAOD and CVI in OTR in relation with diabetes and other potential risk factors.Methods: A prospective study in a single center was performed. OTR (n = 112) were included at the outpatient clinic to investigate clinical signs of PAOD and CVI. The most commonly associated risk factors were determined.Results: PAOD had been diagnosed in 15.6% and CVI in 30.0% of the patients. Diabetes was the cause of organ failure in 9.8% of the patients. Type 1 diabetes had been diagnosed in 8.9% and type 2 diabetes in 21.4% (59.1% newonset diabetes alter transplantation). Type 1 diabetes showed an increased risk for PAOD and limb amputation with hazard ratios of 11.0 (95%CI 3.0-40.2) and 9.1 (95%CI 1.4-58.6). Type 2 diabetes showed no increased risk.Conclusions: Patients with a history of type 1 diabetes were at high risk for PAOD even years after a simultaneous pancreas kidney transplantation and they should remain under dose observation for PAOD even though they are supposedly "cured" from their diabetes to prevent a harmful outcome. (C) 2020 Elsevier Inc. All rights reserved. Show less
Esch, C.C.L. van der; Kloosterboer, S.M.; Ende, J. van der; Reichart, C.G.; Kouijzer, M.E.J.; Kroon, M.M.J. de; ... ; Dierckx, B. 2020
Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term... Show moreAntipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI)zscore, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMIzscore for a follow-up of < 15 weeks, 15-52 weeks or > 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMIzscore points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMIzscore increase per week beta = 0.02, 95% CI 0.01-0.03,p = 0.002). A higher baseline BMIzscore and the absence of stimulant use were associated with a higher BMIzscore during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMIzscore. Show less
Purpose Displaced distal radius fractures in children are common and often reduced if necessary and immobilized in cast. Still, fracture redisplacement frequently occurs. This can be prevented by... Show morePurpose Displaced distal radius fractures in children are common and often reduced if necessary and immobilized in cast. Still, fracture redisplacement frequently occurs. This can be prevented by fixation of fracture fragments with K-wires, but until now, there are no clear guidelines for treatment with primary K-wire fixation. This meta-analysis aimed to identify risk factors for redisplacement after reduction and cast immobilization of displaced distal radius fractures in children, and thereby determine which children will benefit most of primary additional K-wire fixation. Methods Eight databases were searched to identify studies and extract data on the incidence of and risk factors for redisplacement of distal radius fractures after initial reduction and cast immobilization in children. Results Twelve studies, including 1256 patients, showed that initial complete displacement (odds ratio [OR] 4.69, 95% confidence interval [CI] 2.98-7.39) and presence of a both-bone fracture (OR 1.95, 95% CI 1.34-2.85) were independent risk factors for redisplacement. Anatomical reduction reduced the redisplacement risk (OR 0.14, 95% CI 0.05-0.40). No significant influence on redisplacement risk could be established for female sex, experience level of the attending surgeon, Cast Index < 0.8, Three-Point Index < 0.8 and patient's age. Conclusions For children with a displaced distal radius fracture, the presence of a both-bone fracture, complete displacement of the distal radius and non-anatomical reduction are risk factors for redisplacement after reduction of their initially displaced distal radius fracture. Children with one or more of these risk factors probably benefit most of reduction combined with primary K-wire fixation. Show less
Background & Aims: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination... Show moreBackground & Aims: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF.Methods: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded.Results: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required >= 1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC).Conclusions: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge.Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. Show less
Berger, F.A.; Sijs, H. van der; Becker, M.L.; Gelder, T. van; Bemt, P.M.L.A. van den 2020
Background The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs... Show moreBackground The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice. Methods A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden's index were calculated. Results The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51-0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54-0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively. Conclusions A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs. Show less
The aim of this thesis is to identify emerging risk factors for VTE. To achieve this goal, we describe the supposedly causal role of statin and glucocorticoid use (i.e. two drugs that can influence... Show moreThe aim of this thesis is to identify emerging risk factors for VTE. To achieve this goal, we describe the supposedly causal role of statin and glucocorticoid use (i.e. two drugs that can influence inflammation) with changes in hemostasis and VTE risk. Systemic glucocorticoid use increases the relative risk of first VTE by more than three-fold and confers an 5% absolute risk of recurrent VTE per year. On the other hand, rosuvastatin use may reduce the risk of first VTE by 40%. Although the mechanisms behind this association are not fully elucidated, this thesis shows that rosuvastatin is capable of decreasing the thrombin generation potential by 10% in patients with a prior VTE. This thesis has shown that both statins and systemic glucocorticoids can affect the risk of VTE, improving the knowledge on the influence of these two commonly prescribed drugs on VTE pathophysiology. These findings have the potential to further refine the assessment of VTE risk since they highlight that the use of these drugs should be considered when evaluating the risk of VTE. Finally, this thesis provides insight into new therapeutic approaches since the results underscore that treatment strategies on VTE prevention in patients already taken statins, which may be sufficient for VTE prevention, are lacking. Treatment strategies to prevent glucocorticoid-associated VTE are also needed. Show less
Background: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%.Aims:... Show moreBackground: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%.Aims: This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis.Methods: A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores.Results: 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease.Conclusion: This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia postliver transplantation and younger age at time of liver transplantation. (C) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Show less
Objective: The objective of this study was to determine the clinical relevance of postcarotid endarterectomy hypertension (PEH) by investigating the effect of PEH on hospital length of stay (LOS)... Show moreObjective: The objective of this study was to determine the clinical relevance of postcarotid endarterectomy hypertension (PEH) by investigating the effect of PEH on hospital length of stay (LOS) and by investigating short-term and long-term complications of PEH. In addition, risk factors for PEH were determined.Methods: A single-center retrospective cohort study was performed. Demographic, preoperative, intraoperative, and postoperative outcomes of 192 patients undergoing carotid endarterectomy were evaluated. Outcomes were compared between patients with PEH and patients without PEH. PEH was defined as an acute systolic blood pressure (SBP) rise >170 mm Hg or persistent SBP >150 mm Hg on the ward and leading to the consultation of an internist. The overall survival and event-free survival were compared using a Kaplan-Meier analysis and a Cox regression analysis. A multivariate logistic regression analysis was performed to determine risk factors for PEH.Results: PEH developed in 44 of 192 patients (25%). Preoperative hypertension (SBP >150 mm Hg) was determined to be a risk factor for PEH (odds ratio, 3.3; 95% confidence interval [CI], 1.6-6.9). Hospital LOS was prolonged in patients with PEH compared with patients without PEH (median LOS of 5 days vs 3 days, respectively; P <.001). No difference in the occurrence of ischemic neurologic events or rebleeding during hospitalization was observed (P =.58 and P =.72, respectively). Cardiovascular and ischemic neurologic events during follow-up did not occur more often in patients with PEH than in patients without PEH (P =.46). There was no difference in mortality between the PEH and non-PEH groups (hazard ratio, 1.6; 95% CI, 0.6-4.3). The same applies to the event-free survival (hazard ratio, 0.77; 95% CI, 0.4-1.7). Combined event-free survival for stroke and myocardial infarction was 92% (95% CI, 87%-97%) at 2 years for patients without PEH and 86% (95% CI, 74%-98%) at 2 years for patients with PEH (P =.25). Event-free survival for mortality was 90% (95% CI, 85%-96%) at 2 years for patients without PEH and 94% (95% CI, 86%-100%) at 2 years for patients with PEH (P =.36).Conclusions: Patients with PEH had a significant increase in hospital LOS. However, adverse short-term and long-term events did not occur more often in patients with PEH. High preoperative SBP was identified as a risk factor for PEH; no other demographic and clinical variables were associated with PEH. Show less
Montfort, S.J.T. van; Slooter, A.J.C.; Kant, I.M.J.; Leur, R.R. van der; Spies, C.; Bresser, J. de; ... ; Dellen, E. van 2020
Delirium, the clinical expression of acute encephalopathy, is a common neuropsychiatric syndrome that is related to poor outcomes, such as long-term cognitive impairment. Disturbances of functional... Show moreDelirium, the clinical expression of acute encephalopathy, is a common neuropsychiatric syndrome that is related to poor outcomes, such as long-term cognitive impairment. Disturbances of functional brain networks are hypothesized to predispose for delirium. The aim of this study in non-delirious elderly individuals was to investigate whether predisposing risk factors for delirium are associated with fMRI network characteristics that have been observed during delirium. As predisposing risk factors, we studied age, alcohol misuse, cognitive impairment, depression, functional impairment, history of transient ischemic attack or stroke, and physical status. In this multicenter study, we included 554 subjects and analyzed resting-state fMRI data from 222 elderly subjects (63% male, age range: 65-85 year) after rigorous motion correction. Functional network characteristics were analyzed and based on the minimum spanning tree (MST). Global functional connectivity strength, network efficiency (MST diameter) and network integration (MST leaf fraction) were analyzed, as these measures were altered during delirium in previous studies. Linear regression analyses were used to investigate the relation between predisposing delirium risk factors and delirium-related fMRI characteristics, adjusted for confounding and multiple testing. Predisposing risk factors for delirium were not associated with delirium-related fMRI network characteristics. Older age within our elderly cohort was related to global functional connectivity strength (beta = 0.182, p < 0.05), but in the opposite direction than hypothesized. Delirium-related functional network impairments can therefore not be considered as the common mechanism for predisposition for delirium. Show less
Timmis, A.; Townsend, N.; Gale, C.P.; Torbica, A.; Lettino, M.; Petersen, S.E.; ... ; European Heart Agcy 2020
Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular... Show moreAims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets.Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index >= 30 kg/m(2)) and diabetes has increased two- to three-fold during the last 30years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5-23.1%] vs. 15.7% (IQR 14.5-21.1%)}, diabetes [7.7% (IQR 7.1-10.1%) vs. 5.6% (IQR 4.8-7.0%)], and among males smoking [43.8% (IQR 37.4-48.0%) vs. 26.0% (IQR 20.9-31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0-10.8) vs. 16.7% (IQR 13.9-19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655-8115)] compared with high-income [2235 (IQR 1896-3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures.Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest. Show less
