Training in data definitions improves quality of intensive care data

BACKGROUND: Our aim was to assess the contribution of training in data definitions and data extraction guidelines to improving quality of data for use in intensive care scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II in the Dutch National Intensive Care Evaluation (NICE) registry. METHODS: Before and after attending a central training programme, a training group of 31 intensive care physicians from Dutch hospitals who were newly participating in the NICE registry extracted data from three sample patient records. The 5-hour training programme provided participants with guidelines for data extraction and strict data definitions. A control group of 10 intensive care physicians, who were trained according the to train-the-trainer principle at least 6 months before the study, extracted the data twice, without specific training in between. RESULTS: In the training group the mean percentage of accurate data increased significantly after training for all NICE variables (+7%, 95% confidence interval 5%–10%), for APACHE II variables (+6%, 95% confidence interval 4%–9%) and for SAPS II variables (+4%, 95% confidence interval 1%–6%). The percentage data error due to nonadherence to data definitions decreased by 3.5% after training. Deviations from 'gold standard' SAPS II scores and predicted mortalities decreased significantly after training. Data accuracy in the control group did not change between the two data extractions and was equal to post-training data accuracy in the training group. CONCLUSION: Training in data definitions and data extraction guidelines is an effective way to improve quality of intensive care scoring data

Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy

BACKGROUND: Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (arvcrisk.com). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise. METHODS: We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models. RESULTS: We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7-9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase 18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53-2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71-0.84) and showed no significant improvement (Akaike information criterion change, <2). CONCLUSIONS: Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification

Exercise does not influence development of phenotype in PLN p.(Arg14del) cardiomyopathy

BACKGROUND: Endurance and frequent exercise are associated with earlier onset of arrhythmogenic right ventricular cardiomyopathy (ARVC) and ventricular arrhythmias (VA) in desmosomal gene variant carriers. Individuals with the pathogenic c.40_42del; p.(Arg14del) variant in the PLN gene are frequently diagnosed with ARVC or dilated cardiomyopathy (DCM). The aim of this study was to evaluate the effect of exercise in PLN p.(Arg14del) carriers. METHODS: In total, 207 adult PLN p.(Arg14del) carriers (39.1% male; mean age 53 ± 15 years) were interviewed on their regular physical activity since the age of 10 years. The association of exercise with diagnosis of ARVC, DCM, sustained VA and hospitalisation for heart failure (HF) was studied. RESULTS: Individuals participated in regular physical activities with a median of 1661 metabolic equivalent of task (MET) hours per year (31.9 MET-hours per week) until clinical presentation. The 50% most and least active individuals had a similar frequency of sustained VA (18.3% vs 18.4%; p = 0.974) and hospitalisation for HF (9.6% vs 8.7%; p = 0.827). There was no relationship between exercise and survival free from (incident) sustained VA (p = 0.65), hospitalisation for HF (p = 0.81), diagnosis of ARVC (p = 0.67) or DCM (p = 0.39) during follow-up. In multivariate analyses, exercise was not associated with sustained VA or HF hospitalisation during follow-up in this relatively not-active cohort. CONCLUSION: There was no association between the amount of exercise and the susceptibility to develop ARVC, DCM, VA or HF in PLN p.(Arg14del) carriers. This suggested unaffected PLN p.(Arg14del) carriers can safely perform mild-moderate exercise, in contrast to desmosomal variant carriers and ARVC patients

Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium

In relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy

Predicting arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis

While many studies evaluate predictors of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC), a systematic review consolidating this evidence is currently lacking. Therefore, we searched MEDLINE and Embase for studies analyzing predictors of ventricular arrhythmias (sustained ventricular tachycardia/fibrillation (VT/VF), appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death) in patients with definite ARVC, patients with borderline ARVC, and ARVC-associated mutation carriers. In the case of multiple publications on the same cohort, the study with the largest population was included. This yielded 45 studies with a median cohort size of 70 patients (interquartile range 60 patients) and a median follow-up of 5.0 years (interquartile range 3.3 - 6.7 years). The average proportion of arrhythmic events observed was 10.6%/y in patients with definite ARVC, 10.0%/y in patients with borderline ARVC, and 3.7%/y with mutation carriers. Predictors of ventricular arrhythmias were population dependent: consistently predictive risk factors in patients with definite ARVC were male sex, syncope, T-wave inversion in lead >V3, right ventricular dysfunction, and prior (non)sustained VT/VF; in patients with borderline ARVC, 2 additional predictors—inducibility during electrophysiology study and strenuous exercise—were identified; and with mutation carriers, all aforementioned predictors as well as ventricular ectopy, multiple ARVC-related pathogenic mutations, left ventricular dysfunction, and palpitations/presyncope determined arrhythmic risk. Most evidence originated from small observational cohort studies, with a moderate quality of evidence. In conclusion, the average risk of ventricular arrhythmia ranged from 3.7 to 10.6%/y depending on the population with ARVC. Male sex, syncope, T-wave inversion in lead >V3, right ventricular dysfunction, and prior (non)sustained VT/VF consistently predict ventricular arrhythmias in all populations with ARVC

Correct Dosing of Artemether-Lumefantrine for Management of Uncomplicated Malaria in Rural Tanzania: Do facility and Patient Characteristics Matter?

Use of artemisinin-based combination therapy (ACT), such as artemether-lumefantrine (AL), requires a strict dosing schedule that follows the drugs' pharmacokinetic properties. The quality of malaria case management was assessed in two areas in rural Tanzania, to ascertain patient characteristics and facility-specific factors that influence correct dosing of AL for management of uncomplicated malaria. Exit interviews were conducted with patients attending health facilities for initial illness consultation. Information about health workers' training and supervision visits was collected. Health facilities were inventoried for capacity and availability of medical products related to care of malaria patients. The outcome was correct dosing of AL based on age and weight. Logistic regression was used to assess health facility factors and patient characteristics associated with correct dosing of AL by age and weight. A total of 1,531 patients were interviewed, but 60 pregnant women were excluded from the analysis. Only 503 (34.2%) patients who received AL were assessed for correct dosing. Most patients who received AL (85.3%) were seen in public health facilities, 75.7% in a dispensary and 91.1% in a facility that had AL in stock on the survey day. Overall, 92.1% (463) of AL prescriptions were correct by age or weight; but 85.7% of patients received correct dosing by weight alone and 78.5% received correct dosing by age alone. In multivariate analysis, patients in the middle dosing bands in terms of age or weight, had statistically significant lower odds of correct AL dosing (p < 0.05) compared to those in the lowest age or weight group. Other factors such as health worker supervision and training on ACT did not improve the odds of correct AL dosing. Although malaria treatment guidelines indicate AL dosing can be prescribed based on age or weight of the patient, findings from this study show that patients within the middle age and weight dosing bands were least likely to receive a correct dose by either measure. Clinicians should be made aware of AL dosing errors for patients aged three to 12 years and advised to use weight-based prescriptions whenever possible

Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation. METHODS AND RESULTS: We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%). CONCLUSION: The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals

Costs and cost-effectiveness of malaria control interventions - a systematic review

<p>Abstract</p> <p>Background</p> <p>The control and elimination of malaria requires expanded coverage of and access to effective malaria control interventions such as insecticide-treated nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment (IPT), diagnostic testing and appropriate treatment. Decisions on how to scale up the coverage of these interventions need to be based on evidence of programme effectiveness, equity and cost-effectiveness.</p> <p>Methods</p> <p>A systematic review of the published literature on the costs and cost-effectiveness of malaria interventions was undertaken. All costs and cost-effectiveness ratios were inflated to 2009 USD to allow comparison of the costs and benefits of several different interventions through various delivery channels, across different geographical regions and from varying costing perspectives.</p> <p>Results</p> <p>Fifty-five studies of the costs and forty three studies of the cost-effectiveness of malaria interventions were identified, 78% of which were undertaken in sub-Saharan Africa, 18% in Asia and 4% in South America. The median financial cost of protecting one person for one year was $2.20 (range$0.88-$9.54) for ITNs,$6.70 (range $2.22-$12.85) for IRS, $0.60 (range$0.48-$1.08) for IPT in infants,$4.03 (range $1.25-$11.80) for IPT in children, and $2.06 (range$0.47-$3.36) for IPT in pregnant women. The median financial cost of diagnosing a case of malaria was$4.32 (range $0.34-$9.34). The median financial cost of treating an episode of uncomplicated malaria was $5.84 (range$2.36-$23.65) and the median financial cost of treating an episode of severe malaria was$30.26 (range $15.64-$137.87). Economies of scale were observed in the implementation of ITNs, IRS and IPT, with lower unit costs reported in studies with larger numbers of beneficiaries. From a provider perspective, the median incremental cost effectiveness ratio per disability adjusted life year averted was $27 (range$8.15-$110) for ITNs,$143 (range $135-$150) for IRS, and $24 (range$1.08-$44.24) for IPT.</p> <p>Conclusions</p> <p>A transparent evidence base on the costs and cost-effectiveness of malaria control interventions is provided to inform rational resource allocation by donors and domestic health budgets and the selection of optimal packages of interventions by malaria control programmes.</p

A multi-tier adaptive grid algorithm for the evolutionary multi-objective optimisation of complex problems

The multi-tier Covariance Matrix Adaptation Pareto Archived Evolution Strategy (m-CMA-PAES) is an evolutionary multi-objective optimisation (EMO) algorithm for real-valued optimisation problems. It combines a non-elitist adaptive grid based selection scheme with the efficient strategy parameter adaptation of the elitist Covariance Matrix Adaptation Evolution Strategy (CMA-ES). In the original CMA-PAES, a solution is selected as a parent for the next population using an elitist adaptive grid archiving (AGA) scheme derived from the Pareto Archived Evolution Strategy (PAES). In contrast, a multi-tiered AGA scheme to populate the archive using an adaptive grid for each level of non-dominated solutions in the considered candidate population is proposed. The new selection scheme improves the performance of the CMA-PAES as shown using benchmark functions from the ZDT, CEC09, and DTLZ test suite in a comparison against the (μ+λ) μ λ Multi-Objective Covariance Matrix Adaptation Evolution Strategy (MO-CMA-ES). In comparison with MO-CMA-ES, the experimental results show that the proposed algorithm offers up to a 69 % performance increase according to the Inverse Generational Distance (IGD) metric

Understanding the role of growth factors in modulating stem cell tenogenesis

Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.Authors thank the Portuguese Foundation for Science and Technology (FCT) for the research project BIBS (PTDC/CVT/102972/2008) and for the post-doc fellowship grant: SFRH/BPD/86775/2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript