Borislav D Dimitrov

Validation of the CHADS2 clinical prediction rule to predict ischaemic stroke. A systematic review and meta-analysis.

Claire Keogh et al. — Sun, 08 Apr 2012 07:51:50 PDT

The CHADS2 predicts annual risk of ischaemic stroke in non-valvular atrial fibrillation. This systematic review and meta-analysis aims to determine the predictive value of CHADS2. The literature was systematically searched from 2001 to October 2010. Data was pooled and analysed using discrimination and calibration statistical measures, using a random effects model. Eight data sets (n = 2815) were included. The diagnostic accuracy suggested a cut-point of ≥ 1 has higher sensitivity (92%) than specificity (12%) and a cut-point of ≥ 4 has higher specificity (96%) than sensitivity (33%). Lower summary estimates were observed for cut-points ≥ 2 (sensitivity 79%, specificity 42%) and ≥ 3 (specificity 77%, sensitivity 50%). There was insufficient data to analyse cut-points ≥ 5 or ≥ 6. Moderate pooled c statistic values were identified for the classic (0.63, 95% CI 0.52-0.75) and revised (0.60, 95% CI 0.43-0.72) view of stratification of the CHADS2. Calibration analysis indicated no significant difference between the predicted and observed strokes across the three risk strata for the classic or revised view. All results were associated with high heterogeneity, and conclusions should be made cautiously. In conclusion, the pooled c statistic and calibration analysis suggests minimal clinical utility of both the classic and revised view of the CHADS2 in predicting ischaemic stroke across all risk strata. Due to high heterogeneity across studies and low event rates across all risk strata, the results should be interpreted cautiously. Further validation of CHADS2 should perhaps be undertaken, given the methodological differences between many of the available validation studies and the original CHADS2 derivation study.

Towards Knowledge Sharing and Patient Privacy in a Clinical Decision Support System

Liang Xiao et al. — Tue, 27 Mar 2012 08:05:06 PDT

Patient records and their disease and treatment history can be scattered among healthcare providers. Sharing the knowledge effectively and, at the same time, respecting patient privacy is crucial in providing safe and accurate clinical decision support systems (CDSSs). In this paper we reflect upon our experience in the HealthAgents project wherein a prototype system was developed and a novel approach employed that supports data transfer and decision making in human brain tumour diagnosis. Here we examine the capability of the Lightweight Coordination Calculus (LCC), a process calculus-based language, in combining together distributed healthcare services and meeting security challenges in pervasive settings. The result is that various clinical specialisms, being captured in representational abstractions and making contribution to patient diagnosis and management, retain their autonomy. However, at the same time, the behaviour of specialists in sharing clinical knowledge about their patients and providing clinical support is constrained by policies and rules in respect of their own clinical duties and responsibilities. Being introduced into the programme of the HRB Centre for Primary Care Research, this novel approach has the potential to help the provision of optimal solutions in data linkage and sharing across the Primary and Secondary Care interface. As added value, its application also advances the process of integrating clinical prediction rules and implementing CDSSs in practice and, ultimately, the improvement of quality of care.

A Concept for a Long-term Scalable Primary Care Model

Soha Maad et al. — Tue, 27 Mar 2012 08:05:04 PDT

This paper presents a concept for development of a unified bioengineering framework that consolidates efforts in extending the geographical boundaries and outreach of primary care in Ireland and ensure its long-term scalability. This framework encompasses infrastructures, devices, systems, techniques, materials, engineering practices and socio-technical set-ups for improved access, safety and quality of care at national and global levels. In particular, we address the development of special purpose solutions, technologies and devices for healthcare from a bioengineering perspective, within the wider biotechnology agenda in Ireland.

The prevalence of alpha-1 antitrypsin deficiency in Ireland.

Tomas P. Carroll et al. — Tue, 27 Mar 2012 08:05:02 PDT

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients.

METHODS: We present data from the first 3,000 individuals screened following ATS/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping.

RESULTS: The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes.

CONCLUSION: Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

Prognostic value of the ABCD2 clinical prediction rule: a systematic review and meta-analysis

Rose Galvin et al. — Tue, 27 Mar 2012 08:05:01 PDT

Purpose: The ABCD2 clinical prediction rule (CPR) is designed to predict early risk of stroke after transient ischaemic attack (TIA). The purpose of this systematic review with meta-analysis is to determine the predictive value of the ABCD2 at 7 and 90 days across three strata of risk. Methods: A systematic literature search was conducted to identify studies that validated the ABCD2. The derived rule was used as a predictive model and applied to subsequent validation studies. Comparisons were made between observed and predicted number of strokes stratified by risk group, low (0-3 points), moderate (4-5 points) and high (6-7 points). Pooled results are presented as risk ratios (RRs) with 95% confidence intervals, in terms of over-prediction (RR>1) or under-prediction (RR<1) of stroke at 7 and 90 days. Results: We include 16 validation studies. Fourteen studies report 7 day stroke risk (n=6282, 388 strokes). The ABCD2 rule correctly predicts occurrence of stroke at 7 days across all three risk strata: low, (RR 0.86, 95%CI(0.47-1.58), I2=16%); moderate, (RR 0.99, 95%CI(0.67-1.47), I2=68%); high, (RR 0.84, 95%CI(0.6-1.19), I2=46%). Eleven studies report 90 day stroke risk (n=6304). There is a non-significant trend towards over prediction of stroke in all risk categories at 90 days. There are 426 strokes observed in contrast to a predicted 626 strokes. As the trichotomised ABCD2 score increases, the risk of stroke increases (p<0.01). There is no evidence of publication bias in these studies (p>0.05). Conclusion: The ABCD2 is a useful CPR, particularly in relation to 7 day risk of stroke.

Primary health care models and suitability for provision of e-services: an overview.

Borislav D. Dimitrov et al. — Tue, 27 Mar 2012 08:04:59 PDT

We present an overview of the most frequently distributed types of primary health care (PHC) models of delivery across different countries and cultural environments. We summarise and describe most important definitions, principles of classification, attributes, necessary conditions (e.g., patient-management systems, electronic health records, ICT platforms) and organisation and key performance indicators (KPI) for functioning of the primary health care systems. We review and explore the suitability of different PHC models for provision of electronic (e-)services.

Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis.

Penka A A. Atanassova et al. — Tue, 27 Mar 2012 08:04:58 PDT

Quantitative data on melatonin in stroke patients are scarce. A gender- and age-matched cross-sectional case-control study in 33 patients with ischaemic stroke was performed and associations between nocturnal melatonin and other factors (e.g. cortisol) were evaluated. Clinical and laboratory (e.g. melatonin and cortisol) measurements (03.00 h and 08.00 h) with statistical techniques [e.g. multifactorial regressions, receiver operating characteristic (ROC) curve and curvilinear estimations] were used. We identified mean value and 95% confidence interval (CI) (69.70 pg/ml; 95% CI = 53.86-85.54) for control levels of nocturnal melatonin in healthy subjects. The patients with stroke had lower melatonin (48.1 +/- 35.9 pg/ml) and higher cortisol (297.3 +/- 157.8 nmol/l) at 03.00 h (P < 0.05) but not at 08.00 h (P > 0.05). Stroke was the strongest factor of disturbed nocturnal cortisol (P < 0.001), whereas decreased melatonin depended on stroke (P = 0.010) and gender (P = 0.018). At the same time, vice versa, only nocturnal measures were associated with an increased probability of the presence of stroke (accuracy > 75%, Pmodel < 0.001). Thus, a hypothesis that a decrease of melatonin with 1.0 pg/ml might be associated with > 2% increase in the probability of the presence of stroke [adjusted odds ratio (OR) = 1.020; 95% CI = 1.002-1.037] was also suggested. The ROC curve (0.67, P = 0.0119) and optimisation techniques indicated that a novel best cut-off < 51.5 pg/ml for decreased nocturnal melatonin in the view of the presence of stroke (OR = 3.12, P = 0.0463) might exist. The classification performance of such a cut-off might be confirmed by existing nocturnal melatonin and cortisol differences between the sub-groups; potential differences in diurnal melatonin were also suggested. In conclusion, a novel melatonin cut-off of 51.5 pg/ml may be associated with the presence of ischaemic stroke. As a single marker (84% sensitivity, 74% specificity), it is hypothesised that modelling performance was independent of age, gender and cortisol. These new results, including the suggested hypothesis, might be further tested in follow-up (cohort), longitudinal studies and be applied to explore melatonin disturbances as targets in high-risk pre-stroke and post-stroke patients.

Digital content preservation across domain verticals

Soha Maad et al. — Tue, 27 Mar 2012 08:04:56 PDT

The authors present a novel approach to develop scalable systems and services for preserving digital content generated from various application domains. The aim is to deliver an integrative scalable approach for digital content preservation across domain verticals. This would involve consolidating approaches for modeling document workflow, preserving the integrity of heterogeneous data, and developing robust and scalable tools for digital preservation ensuring interoperability across domains verticals. The authors consider various application domains including: healthcare, public, business and finance, media and performing art, and education. The authors focus on specific case studies of digital content preservation across the considered domain verticals. The authors describe an integrative framework for digital content preservation across domain verticals. This framework is developed at four levels and attempts to abstract and integrate the digital content workflow across domain verticals. The authors suggest a test bed to validate our integrative approach for digital content preservation. This integrates the digital content preservation activity along the value chain of domain verticals.

Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs.

Leonie GM Giesen et al. — Tue, 27 Mar 2012 08:04:54 PDT

Background: Acute urinary tract infections (UTI) are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (102 or 103 or 105 CFU/ml). We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making. Methods: Searches were performed through PubMed (1966 to April 2010), EMBASE (1973 to April 2010), Cochrane library (1973 to April 2010), Google scholar and reference checking.Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 102 CFU/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model.Results Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 102 CFU/ml; 55.4% at ≥ 103 CFU/ml and 44.8% at ≥ 102 CFU/ml ≥ 105 CFU/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 102 CFU/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41), frequency (+LR 1.10 95% CI 1.04-1.16), hematuria (+LR 1.72 95%CI 1.30-2.27), nocturia (+LR 1.30 95% CI 1.08-1.56) and urgency (+LR 1.22 95% CI 1.11-1.34) all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83) decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of UTI to 75.8% at ≥ 102 CFU/ml and 67.4% at ≥ 103 CFU/ml. Probability of UTI increases to 93.3% and 90.1% at ≥ 102 CFU/ml and ≥ 103 CFU/ml respectively when presence of hematuria is combined with a positive dipstick result for nitrites. Subgroup analysis shows improved diagnostic accuracy using lower reference standards ≥ 102 CFU/ml and ≥ 103 CFU/ml. Conclusions: Individual symptoms and signs have a modest ability to raise the pretest-risk of UTI. Diagnostic accuracy improves considerably when combined with dipstick tests particularly tests for nitrites.

Developing an electronic health record (EHR) for methadone treatment recording and decision support.

Liang Xiao et al. — Tue, 27 Mar 2012 08:04:53 PDT

BACKGROUND: In this paper, we give an overview of methadone treatment in Ireland and outline the rationale for designing an electronic health record (EHR) with extensibility, interoperability and decision support functionality. Incorporating several international standards, a conceptual model applying a problem orientated approach in a hierarchical structure has been proposed for building the EHR.

METHODS: A set of archetypes has been designed in line with the current best practice and clinical guidelines which guide the information-gathering process. A web-based data entry system has been implemented, incorporating elements of the paper-based prescription form, while at the same time facilitating the decision support function.

RESULTS: The use of archetypes was found to capture the ever changing requirements in the healthcare domain and externalises them in constrained data structures. The solution is extensible enabling the EHR to cover medicine management in general as per the programme of the HRB Centre for Primary Care Research.

CONCLUSIONS: The data collected via this Irish system can be aggregated into a larger dataset, if necessary, for analysis and evidence-gathering, since we adopted the openEHR standard. It will be later extended to include the functionalities of prescribing drugs other than methadone along with the research agenda at the HRB Centre for Primary Care Research in Ireland.

Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score.

Jolien Aalbers et al. — Tue, 27 Mar 2012 08:04:51 PDT

BACKGROUND: Stratifying patients with a sore throat into the probability of having an underlying bacterial or viral cause may be helpful in targeting antibiotic treatment. We sought to assess the diagnostic accuracy of signs and symptoms and validate a clinical prediction rule (CPR), the Centor score, for predicting group A β-haemolytic streptococcal (GABHS) pharyngitis in adults (> 14 years of age) presenting with sore throat symptoms.

METHODS: A systematic literature search was performed up to July 2010. Studies that assessed the diagnostic accuracy of signs and symptoms and/or validated the Centor score were included. For the analysis of the diagnostic accuracy of signs and symptoms and the Centor score, studies were combined using a bivariate random effects model, while for the calibration analysis of the Centor score, a random effects model was used.

RESULTS: A total of 21 studies incorporating 4,839 patients were included in the meta-analysis on diagnostic accuracy of signs and symptoms. The results were heterogeneous and suggest that individual signs and symptoms generate only small shifts in post-test probability (range positive likelihood ratio (+LR) 1.45-2.33, -LR 0.54-0.72). As a decision rule for considering antibiotic prescribing (score ≥ 3), the Centor score has reasonable specificity (0.82, 95% CI 0.72 to 0.88) and a post-test probability of 12% to 40% based on a prior prevalence of 5% to 20%. Pooled calibration shows no significant difference between the numbers of patients predicted and observed to have GABHS pharyngitis across strata of Centor score (0-1 risk ratio (RR) 0.72, 95% CI 0.49 to 1.06; 2-3 RR 0.93, 95% CI 0.73 to 1.17; 4 RR 1.14, 95% CI 0.95 to 1.37).

CONCLUSIONS: Individual signs and symptoms are not powerful enough to discriminate GABHS pharyngitis from other types of sore throat. The Centor score is a well calibrated CPR for estimating the probability of GABHS pharyngitis. The Centor score can enhance appropriate prescribing of antibiotics, but should be used with caution in low prevalence settings of GABHS pharyngitis such as primary care.

The Alvarado score for predicting acute appendicitis: a systematic review.

Robert Ohle et al. — Tue, 27 Mar 2012 08:04:49 PDT

BACKGROUND:

The Alvarado score can be used to stratify patients with symptoms of suspected appendicitis; the validity of the score in certain patient groups and at different cut points is still unclear. The aim of this study was to assess the discrimination (diagnostic accuracy) and calibration performance of the Alvarado score.

METHODS:

A systematic search of validation studies in Medline, Embase, DARE and The Cochrane library was performed up to April 2011. We assessed the diagnostic accuracy of the score at the two cut-off points: score of 5 (1 to 4 vs. 5 to 10) and score of 7 (1 to 6 vs. 7 to 10). Calibration was analysed across low (1 to 4), intermediate (5 to 6) and high (7 to 10) risk strata. The analysis focused on three sub-groups: men, women and children.

RESULTS:

Forty-two studies were included in the review. In terms of diagnostic accuracy, the cut-point of 5 was good at 'ruling out' admission for appendicitis (sensitivity 99% overall, 96% men, 99% woman, 99% children). At the cut-point of 7, recommended for 'ruling in' appendicitis and progression to surgery, the score performed poorly in each subgroup (specificity overall 81%, men 57%, woman 73%, children 76%). The Alvarado score is well calibrated in men across all risk strata (low RR 1.06, 95% CI 0.87 to 1.28; intermediate 1.09, 0.86 to 1.37 and high 1.02, 0.97 to 1.08). The score over-predicts the probability of appendicitis in children in the intermediate and high risk groups and in women across all risk strata.

CONCLUSIONS:

The Alvarado score is a useful diagnostic 'rule out' score at a cut point of 5 for all patient groups. The score is well calibrated in men, inconsistent in children and over-predicts the probability of appendicitis in women across all strata of risk.