ABSTRACT: 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 (1-4 vs. 5-10) and score of 7 (1-6 vs. 7-10). Calibration was analysed across low (1-4), intermediate (5-6) and high (7-10) 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 0.87-1.28; intermediate 1.09, 0.86-1.37 and high 1.02, 0.97-1.08). 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.

BACKGROUND: Screening for methicillin-resistant Staphylocccus aureus (MRSA) is advocated as part of control measures, but screening all patients on admission to hospital may not be cost-effective. OBJECTIVE: Our objective was to evaluate the additional yield of screening all patients on admission compared with only patients with risk factors and to assess cost aspects. METHODS: A prospective, nonrandomized observational study of screening nonrisk patients ≤72 hours of admission compared with only screening patients with risk factors over 3 years in a tertiary referral hospital was conducted. We also assessed the costs of screening both groups. RESULTS: A total of 48 of 892 (5%) patients was MRSA positive; 28 of 314 (9%) during year 1, 12 of 257 (5%) during year 2, and 8 of 321 (2%) during year 3. There were significantly fewer MRSA-positive patients among nonrisk compared with MRSA-risk patients: 4 of 340 (1%) versus 44 of 552 (8%), P ≤ .0001, respectively. However, screening nonrisk patients increased the number of screening samples by 62% with a proportionate increase in the costs of screening. A backward stepwise logistic regression model identified age > 70 years, diagnosis of chronic pulmonary disease, previous MRSA infection, and admission to hospital during the previous 18 months as the most important independent predictors to discriminate between MRSA-positive and MRSA-negative patients on admission (94.3% accuracy, P <.001). CONCLUSION: Screening patients without risk factors increased the number of screenings and costs but resulted in few additional cases being detected. In a hospital where MRSA is endemic, targeted screening of at-risk patients on admission remains the most efficient strategy for the early identification of MRSA-positive patients.

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.

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.

This study aims to identify periods of elevated risk of drug-related mortality during methadone maintenance treatment (MMT) in primary care using a cohort of 3,162 Scottish drug users between January 1993 and February 2004. Deaths occurring during treatment or within 3 days after last methadone prescription expired were considered as cases "on treatment." Fatalities occurring 4 days or more after leaving treatment were cases "off treatment." Sixty-four drug-related deaths were identified. The greatest risk of drug-related death was in the first 2 weeks of treatment (adjusted hazard ratio 2.60, 95% confidence interval 1.03-6.56). Risk of drug-related death was lower after the first 30 days following treatment cessation, relative to the first 30 days off treatment. History of psychiatric admission was associated with increased risk of drug-related death in treatment. Increasing numbers of treatment episodes and urine testing were protective. History of psychiatric admission, increasing numbers of urine tests, and coprescriptions of benzodiazepines increased the risk of mortality out of treatment. The risk of drug-related mortality in MMT is elevated during periods of treatment transition, specifically treatment initiation and the first 30 days following treatment dropout or discharge.

Surgical patients are at particular risk of healthcare-associated infection (HCAI) due to the presence of a surgical site leading to surgical site infection (SSI), and because of the need for intravascular access resulting in catheter-related bloodstream infection (CRBSI). A two-year initiative commenced with an initial audit of surgical practice; this was used to inform the development of a targeted educational initiative by surgeons specifically for surgical trainees. Parameters assessed during the initial audit and a further audit after the educational initiative were related to intra- and postoperative aspects of the prevention of SSIs, as well as care of peripheral venous catheters (PVCs) in surgical patients. The proportion of prophylactic antibiotics administered prior to incision across 360 operations increased from 30.0% to 59.1%(P<0.001). Surgical site dressings were observed in 234 patients, and a significant decrease was found in the percentage of dressings that were tampered with during the initial 48h after surgery (16.5% vs 6.2%, P=0.030). In total, 574 PVCs were assessed over the two-year period. Improvements were found in the proportion of unnecessary PVCs in situ (37.9% vs 24.4%, P<0.001), PVCs in situ for >72h (10.6% vs 3.1%, P<0.001) and PVCs covered with clean and intact dressings (87.3% vs 97.6%, P<0.001). Significant improvements in surgical practice were established for the prevention of SSI and CRBSI through a focused educational programme developed by and for surgeons. Potentially, other specific measures may also be warranted to achieve further improvements in infection prevention in surgical practice.

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. 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. 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). 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.

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.