A validation of the National Early Warning Score to predict outcome in patients with COPD exacerbation.

BACKGROUND: The National Early Warning Score (NEWS), proposed as a standardised track and trigger system, may perform less well in acute exacerbation of COPD (AECOPD). This study externally validated NEWS and modifications (Chronic Respiratory Early Warning Score (CREWS) and Salford-NEWS) in AECOPD. METHODS: An observational cohort study (2012-2014, two UK acute medical units (AMUs)), compared AECOPD (2361 admissions, 942 individuals, International Statistical Classification of Diseases and Related Health Problems-10 J40-J44 codes) with AMU patients (37 109 admissions, 20 415 individuals). OUTCOME: In-hospital mortality prediction was done by admission NEWS, CREWS and Salford-NEWS assessed by discrimination (area under receiver operating characteristic curves (AUROCs)) and calibration (plots and Hosmer-Lemeshow (H-L) goodness-of-fit). RESULTS: Median admission NEWS in AECOPD was 4 (IQR 2-6) versus 1 (0-3) in AMUs (p≤0.001), despite mortality of 4.5% in both. AECOPD AUROCs were NEWS 0.74 (95% CI 0.66 to 0.82), CREWS 0.72 (0.63 to 0.80) and Salford-NEWS 0.62 (0.53 to 0.70). AMU NEWS AUROC was 0.77 (0.75 to 0.78). At threshold NEWS=5 for AECOPD (44% of admissions), positive predictive value (PPV) of death was 8% (5 to 11) and negative predictive value (NPV) was 98% (97 to 99) versus AMU patients PPV of 17% (16 to 19) and NPV of 97% (97 to 97). For NEWS in AECOPD H-L p value=0.202. CONCLUSION: This first validation of the NEWS in AECOPD found modest discrimination to predict mortality. Lower specificity of NEWS in patients with AECOPD versus other AMU patients reflects acute and chronic respiratory physiological disturbance (including hypoxia), with resultant low PPV at NEWS=5. CREWS and Salford-NEWS, adjusting for chronic hypoxia, increased the specificity and PPV but there was no gain in discrimination.

Assessing the growth of preterm infants using detailed anthropometry.

AIM: Preterm infants display altered body composition compared to term infants, and weight gain is a crude indicator body composition. Childhood mid-upper arm circumference (MUAC) is a measure of nutritional status. This study investigates MUAC and mid-thigh circumference (MTC) to monitor growth in preterm infants. METHODS: Preterm infants (<30-week gestation) were recruited. MUAC, MTC, weight, length and head circumference (HC) were measured at recruitment and weekly intervals until discharge. Descriptive, correlation and regression analyses were used. RESULTS: Ninety-three infants were recruited. Median measurement duration was eight weeks (1-19). Median gestational age was 27 weeks (23-29). Analysis by curve estimation displayed a mean increase of 2.58 mm/week (left MUAC) (p ≤ 0.0001), 2.56 mm/week (right MUAC) (p ≤ 0.0001), 4.16 mm/week (left MTC) (p ≤ 0.0001), 4.20 mm/week (right MTC) (p ≤ 0.0001). Coefficients of determination (R2 ) were calculated using a growth regression model for MUAC and MTC (0.866-0.917); measures were comparable to growth modelling of weight (0.913), length (0.945) and HC (0.928). High concordance between left and right MUAC and MTC generated a Pearson's correlation coefficient of 0.999 (MUAC) (p ≤ 0.001) and 0.994 (MTC) (p ≤ 0.001). CONCLUSION: Data demonstrate the potential utility of MUAC and MTC as additional measures of growth in preterm infants that are reproducible over time. There is potential to gain insights to improve lean-mass accretion in preterm infants.

PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia.

Symptoms of primary ciliary dyskinesia (PCD) are nonspecific and guidance on whom to refer for testing is limited. Diagnostic tests for PCD are highly specialised, requiring expensive equipment and experienced PCD scientists. This study aims to develop a practical clinical diagnostic tool to identify patients requiring testing.Patients consecutively referred for testing were studied. Information readily obtained from patient history was correlated with diagnostic outcome. Using logistic regression, the predictive performance of the best model was tested by receiver operating characteristic curve analyses. The model was simplified into a practical tool (PICADAR) and externally validated in a second diagnostic centre.Of 641 referrals with a definitive diagnostic outcome, 75 (12%) were positive. PICADAR applies to patients with persistent wet cough and has seven predictive parameters: full-term gestation, neonatal chest symptoms, neonatal intensive care admittance, chronic rhinitis, ear symptoms, situs inversus and congenital cardiac defect. Sensitivity and specificity of the tool were 0.90 and 0.75 for a cut-off score of 5 points. Area under the curve for the internally and externally validated tool was 0.91 and 0.87, respectively.PICADAR represents a simple diagnostic clinical prediction rule with good accuracy and validity, ready for testing in respiratory centres referring to PCD centres.

Left and Right Parasternal Sensing for the S-ICD in Adult Congenital Heart Disease Patients and Normal Controls.

BACKGROUND: This study investigated the impact of a right parasternal sensing electrode position on the R- and T-wave amplitudes and the R:T ratio in three subcutaneous implantable cardioverter defibrillator (S-ICD) vectors in patients with adult congenital heart disease (ACHD) and normal controls. METHODS: Conventional left parasternal sensing electrode position and right parasternal sensing electrode positions were used to collect 10-second electrograms, recorded through an 80-electrode body surface mapping technology (Prime ECG™ system, Heartscape Technologies Inc., now Verathon, Columbia, MD, USA). Recordings were made in the supine, prone, left lateral, right lateral, sitting, and standing positions in using both the standard electrode vector position and the right parasternal positions. RESULTS: Forty patients were recruited and 37 patients were used for analysis. Twenty-seven (73%) had complex ACHD; 10 patients had normal hearts and acted as controls. A total of 3,708 data points were analyzed. There were no significant differences in the R:T ratio when measured in ACHD patients in the right compared to the left parasternal lead position. In contrast, there were important differences in the magnitude of the R:T ratio when measured in control patients in the right compared to the left parasternal lead position; in the primary vector, the R:T ratio was greater in right than left by 2.99 (P = 0.0002; 95% confidence interval [CI]: 1.48-4.50) and in the secondary vector, the R:T ratio was smaller in the right than in the left by 0.77 (P = 0.004; 95% CI: -1.58-0.05). CONCLUSION: In selected patients, a right parasternal lead position may provide a useful alternative sensing configuration for the S-ICD.

An external validation study of a clinical prediction rule for medical patients with suspected bacteraemia.

OBJECTIVE: The objective of this study was to externally validate a clinical prediction rule (CPR)-the 'Shapiro criteria'-to predict bacteraemia in an acute medical unit (AMU). METHODS: Prospectively collected data, retrospectively evaluated over 11 months in an AMU in the UK. From 4810 admissions, 635 patients (13%) had blood cultures (BCs) performed. The 100 cases of true bacteraemia were compared with a randomly selected sample of 100 control cases where BCs were sterile. RESULTS: To predict bacteraemia (at a cut-off score of two points), the Shapiro criteria had a sensitivity of 97% (95% CIs 91% to 99%), specificity 37% (28% to 47%), positive likelihood ratio 1.54 (1.3 to 1.8) and a negative likelihood ratio of 0.08 (0.03 to 0.25). The area under the receiver operating curve was 0.80 (0.74 to 0.86), and the Hosmer-Lemeshow p value was 0.45. CONCLUSIONS: A cut-off score of two points on the Shapiro criteria had high sensitivity to predict bacteraemia in a study of acute general medical admissions. Application of the rule in patients being considered for a BC could identify those at low risk of bacteraemia. Though the model demonstrated good discrimination, the lengthy number of variables (13) and difficulty automating the CPR may limit its use.

Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms.

BACKGROUND: Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear. OBJECTIVE: We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients. METHODS: Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed. RESULTS: Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13-secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine-high) and nonatopic forms. CONCLUSION: The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.

Early neurological and cognitive impairments in subclinical cerebrovascular disease.

BACKGROUND: The subclinical cerebrovascular disease (SCVD) is an important public health problem with demonstrated prognostic significance for stroke, future cognitive decline, and progression to dementia. The earliest possible detection of the silent presence of SCVD in adults at age at risk with normal functioning is very important for both clinical doctors and scientists. MATERIALS AND METHODS: Seventy-seven adult volunteers, recruited during the years 2005-2007, with mean age 58.7 (standard deviation 5.9) years, were assessed by four subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB)-Eclipse cognitive assessment system. We used a questionnaire survey for the presence of cerebrovascular risk factors (CVRFs) such as arterial hypertension, smoking and dyslipidemia, among others, as well as instrumental (Doppler examination) and neurological magnetic resonance imaging (MRI) procedures. Descriptive statistics, comparison (t-test, Chi-square) and univariate methods were used as followed by multifactor logistic regression and receiver operating characteristics analyses. RESULTS: The risk factor questionnaire revealed nonspecific symptoms in 44 (67.7%) of the subjects. In 42 (64.6%) of all 65 subjects, we found at least one of the conventional CVRFs. Abnormal findings from the extra- and trans-cranial Doppler examination were established in 38 (58.5%) of all studied volunteers. Thirty-four subjects had brain MRI (52.3%), and abnormal findings were found in 12 (35.3%) of them. Two of the four subtests of CANTAB tool appeared to be potentially promising predictors of the outcome, as found at the univariate analysis (spatial working memory 1 [SWM1] total errors; intra-extra dimensional set 1 [IED1] total errors [adjusted]; IED2 total trials [adjusted]). We established that the best accuracy of 82.5% was achieved by a multifactor interaction logistic regression model, with the role CVRF and combined CANTAB predictor "IED total ratio (errors/trials) × SWM1 total errors" (P = 0.006). CONCLUSIONS: Our results have contributed to the hypothesis that it is possible to identify, by noninvasive methods, subjects at age at risk who have mild degree of cognitive impairment and to establish the significant relationship of this impairment with existing CVRFs, nonspecific symptoms and subclinical abnormal brain Doppler/MRI findings. We created a combined neuropsychological predictor that was able to clearly distinguish between the presence and absence of abnormal Doppler/MRI findings. This pilot prognostic model showed a relatively high accuracy of >80%; therefore, the predictors may serve as biomarkers for SCVD in subjects at age at risk (51-65 years).

Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis.

BACKGROUND: Women with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in disease severity. METHODS: We evaluated the effects of estradiol and its metabolite estriol on P. aeruginosa in vitro and in vivo and determined the effect of estradiol on disease exacerbations in women with cystic fibrosis. RESULTS: Estradiol and estriol induced alginate production in P. aeruginosa strain 01 and in clinical isolates obtained from patients with and those without cystic fibrosis. After prolonged exposure to estradiol, P. aeruginosa adopted early mucoid morphology, whereas short-term exposure inhibited bacterial catalase activity and increased levels of hydrogen peroxide, which is potentially damaging to DNA. Consequently, a frameshift mutation was identified in mucA, a key regulator of alginate biosynthesis in P. aeruginosa. In vivo levels of estradiol correlated with infective exacerbations in women with cystic fibrosis, with the majority occurring during the follicular phase (P<0.05). A review of the Cystic Fibrosis Registry of Ireland revealed that the use of oral contraceptives was associated with a decreased need for antibiotics. Predominantly nonmucoid P. aeruginosa was isolated from sputum during exacerbations in the luteal phase (low estradiol). Increased proportions of mucoid bacteria were isolated during exacerbations occurring in the follicular phase (high estradiol), with a variable P. aeruginosa phenotype evident in vivo during the course of the menstrual cycle corresponding to fluctuating estradiol levels. CONCLUSIONS: Estradiol and estriol induced mucoid conversion of P. aeruginosa in women with cystic fibrosis through a mutation of mucA in vitro and were associated with selectivity for mucoid isolation, increased exacerbations, and mucoid conversion in vivo. (Funded by the Molecular Medicine Ireland Clinician-Scientist Fellowship Programme.).

Multimorbidity and the inequalities of global ageing: a cross-sectional study of 28 countries using the World Health Surveys.

BACKGROUND: Multimorbidity defined as the "the coexistence of two or more chronic diseases" in one individual, is increasing in prevalence globally. The aim of this study is to compare the prevalence of multimorbidity across low and middle-income countries (LMICs), and to investigate patterns by age and education, as a proxy for socio-economic status (SES). METHODS: Chronic disease data from 28 countries of the World Health Survey (2003) were extracted and inter-country socio-economic differences were examined by gross domestic product (GDP). Regression analyses were applied to examine associations of education with multimorbidity by region adjusted for age and sex distributions. RESULTS: The mean world standardized multimorbidity prevalence for LMICs was 7.8 % (95 % CI, 7.79 % - 7.83 %). In all countries, multimorbidity increased significantly with age. A positive but non-linear relationship was found between country GDP and multimorbidity prevalence. Trend analyses of multimorbidity by education suggest that there are intergenerational differences, with a more inverse education gradient for younger adults compared to older adults. Higher education was significantly associated with a decreased risk of multimorbidity in the all-region analyses. CONCLUSIONS: Multimorbidity is a global phenomenon, not just affecting older adults in HICs. Policy makers worldwide need to address these health inequalities, and support the complex service needs of a growing multimorbid population.

Developing an international register of clinical prediction rules for use in primary care: a descriptive analysis.

PURPOSE: We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. METHODS: To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. RESULTS: Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study), resulting in 989 individual studies. In all, 434 unique rules had gone through derivation; however, only 54.8% had been validated and merely 2.8% had undergone analysis of their impact on either the process or outcome of clinical care. The rules most commonly pertained to cardiovascular disease, respiratory, and musculoskeletal conditions. They had most often been studied in the primary care or emergency department settings. CONCLUSIONS: Many clinical prediction rules have been derived, but only about half have been validated and few have been assessed for clinical impact. This lack of thorough evaluation for many rules makes it difficult to retrieve and identify those that are ready for use at the point of patient care. We plan to develop an international web-based register of clinical prediction rules and computer-based clinical decision support systems.

The importance of submalleolar deformity in determining leg length discrepancy.

BACKGROUND AND PURPOSE: The association of leg length discrepancy (LLD) with a number of clinical disorders has made its determination a significant part of the physical examination. We believe that submalleolar causes of LLD may be under-acknowledged. The most common clinical method used to measure LLD is by tape from the anterior superior iliac spine (ASIS) to medial malleolus which disregards the potential for LLD arising from asymmetry in the foot distal to the tibiotalar joint. METHODS: The present pilot study involves a group of 5 volunteers (experimental group) and a group of 3 patients with flexible flat feet (clinical study). The differences in tibial tubercle height from the ground between full pronation and full supination were measured using the CODA MPX 30(®) system (Charnwood Dynamics Limited, Leicestershire, England). Correlations of the patterns within each group were produced. RESULTS: A significant relationship with leg lengths was found in the experimental group when they induced maximum pronation (R-squared = 0.62, p = 0.007) while an inverse relationship occurred with supination, although marginally significant (R-squared = 0.37, p = 0.064). CONCLUSIONS: We have demonstrated that significant leg length discrepancy can occur in patients who do not have obvious deformity when non weight bearing. We recommend using the blocks method routinely. Appropriately measuring LLD is of vital importance to properly diagnosing and treating patients with unequal leg lengths or related symptoms.

Comparison of serum Dkk1 (Dickkopf-1) and bone mineral density in patients on bisphosphonate treatment vs no treatment.

Complex pathways affect bone metabolism at the cellular level, and a balance between osteoblast and osteoclast activity is critical to bone remodeling. One of the major pathways affecting bone metabolism is Wnt/ß-catenin signaling, and its disturbances lead to a wide range of bone abnormalities. An important antagonist of this pathway is Dickkopf-1 (Dkk1). Higher Dkk1 levels have been associated with increased bone loss due to inhibition of Wnt pathway. Currently, bisphosphonates are the most commonly used agents to treat primary osteoporotic patients. This study demonstrates the effect of bisphosphonates on Dkk1 levels and its correlation with bone mineral density (BMD). Eighty patients with low BMD were recruited and divided into 2 groups of 40 each (bisphosphonate treatment group and control group). The mean Dkk1 level in the treatment group was significantly reduced to 2358.18 vs 3749.80 pg/mL in the control group (p<0.001). Pearson correlation coefficient showed negative correlation between Dkk1 and BMD at lumbar spine (r=-0.55) and femoral neck in the control group; however, no such correlation was found in the treatment group (r=-0.05). Hence, bisphosphonate therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in such patients.

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

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.

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.

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 ß-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 prevalence of alpha-1 antitrypsin deficiency in Ireland.

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.

OBJECTIVE: The purpose of this systematic review with meta-analysis is to determine the predictive value of the ABCD ²at 7 and 90 days across three strata of risk. Background. The risk of stroke after transient ischaemic attack (TIA) is significant. The ABCD ²clinical prediction rule is designed to predict early risk of stroke after TIA. A number of independent validation studies have been conducted since the rule was derived. 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 (CIs), 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%] and 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 trichotomized 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.

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

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

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 (10(2) or 10(3) or 10(5) 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 ≥ 10(2) 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 ≥ 10(2) CFU/ml; 55.4% at ≥ 10(3) CFU/ml and 44.8% at ≥ 10(2) CFU/ml ≥ 10(5) CFU/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 10(2) 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 ≥ 10(2) CFU/ml and 67.4% at ≥ 10(3) CFU/ml. Probability of UTI increases to 93.3% and 90.1% at ≥ 10(2) CFU/ml and ≥ 10(3) 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 ≥ 10(2) CFU/ml and ≥ 10(3) 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.