METHODS/DESIGN: This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted.

DISCUSSION: This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges.

TRIAL REGISTRATION: Current controlled trials ISRCTN41694007.

METHODS: Retrospective population-based cohort study in the Republic of Ireland using the Health Services Executive (HSE) Primary Care Reimbursement Services (PCRS) pharmacy claims database. The HSE-PCRS scheme is means tested and provides free health care including medications to approximately 30% of the Irish population. Prescription items are WHO ATC coded and details of every drug dispensed and claimants' demographic data are available. Potential cost savings (net ingredient cost) were estimated according to UK NICE clinical guidelines for all HSE-PCRS claimants on PPI therapy for ≥3 consecutive months starting in 2007 with a one year follow up (n=167,747). Five scenarios were evaluated; (i) change to PPI initiation (cheapest brand); and after 3 months (ii) therapeutic switching (cheaper brand/generic equivalent); (iii) dose reduction (maintenance therapy); (iv) therapeutic switching and dose reduction and (v) therapeutic substitution (H2 antagonist).

RESULTS: Total net ingredient cost was €88,153,174 for claimants on PPI therapy during 2007. The estimated costing savings for each of the five scenarios in a one year period were: (i) €36,943,348 (42% reduction); (ii) €29,568,475 (34%); (iii) €21,289,322 (24%); (iv) €40,505,013 (46%); (v) €34,991,569 (40%).

CONCLUSION: There are opportunities for substantial cost savings in relation to PPI prescribing if implementation of clinical guidelines in terms of generic substitution and step-down therapy is implemented on a national basis.

METHODS/DESIGN: This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05.

DISCUSSION: This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting.

TRIAL REGISTRATION: Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20.

METHODS/DESIGN: This is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05.

DISCUSSION: This clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment. REGISTRATION: ISRCTN26944158 and EudraCT Number 2010-022001-18.

METHODS: A literature search was performed to identify all studies that validated the STRATIFY rule. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A STRATIFY score of ≥2 points was used to identify individuals at higher risk of falling. All included studies were combined using a bivariate random effects model to generate pooled sensitivity and specificity of STRATIFY at ≥2 points. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity.

RESULTS: Seventeen studies were included in our meta-analysis, incorporating 11,378 patients. At a score ≥2 points, the STRATIFY rule is more useful at ruling out falls in those classified as low risk, with a greater pooled sensitivity estimate (0.67, 95% CI 0.52-0.80) than specificity (0.57, 95% CI 0.45 - 0.69). The sensitivity analysis which examined the performance of the rule in different settings and subgroups also showed broadly comparable results, indicating that the STRATIFY rule performs in a similar manner across a variety of different 'at risk' patient groups in different clinical settings.

CONCLUSION: This systematic review shows that the diagnostic accuracy of the STRATIFY rule is limited and should not be used in isolation for identifying individuals at high risk of falls in clinical practice.

STUDY DESIGN AND SETTING: Thirty primary care journals were manually searched for CPRs. This was compared with electronic search filters using alternative methodologies: (1) textword searching; (2) proximity searching; (3) inclusion terms using specific phrases and truncation; (4) exclusion terms; and (5) combinations of methodologies.

RESULTS: We manually searched 6,344 articles, revealing 41 CPRs. Across the 45 search filters, sensitivities ranged from 12% to 98%, whereas specificities ranged from 43% to 100%. There was generally a trade-off between the sensitivity and specificity of each filter (i.e., the number of CPRs and total number of articles retrieved). Combining textword searching with the inclusion terms (using specific phrases) resulted in the highest sensitivity (98%) but lower specificity (59%) than other methods. The associated precision (2%) and accuracy (60%) were also low.

CONCLUSION: The novel use of combining textword searching with inclusion terms was considered the most appropriate for updating a register of primary care CPRs where sensitivity has to be optimized.

The cerebral venous sinus thrombosis is a challenging condition and it is most common than previously thought. CVST accounts for 0.5% to 1.0% of all strokes and usually affects young individuals. Important advances have been made in the understanding of the pathophysiology of this vascular disorder. The diagnosis of CVST is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often sub-acute or lingering onset. Patients with CVST commonly present with headache, although some develop a focal neurological deficit, decreased level of consciousness, seizures, or intracranial hypertension without focal neurological signs. Uncommonly, an insidious onset may create a diagnostic challenge. The main problem of this disorder is that it is very often unrecognised at initial presentation. In particular, a prothrombotic factor or a direct cause is identified in approximately 66% of the CVST patients (a list of most important causal and risk factors are listed in Table 1).

Cerebral venous thrombosis is more common in women than men, with a female to male ratio of 3:1 (cited in Ferro & Canhao, 2011). The imbalance may be due to the increased risk of CVST associated with pregnancy and puerperium and with oral contraceptives. The female predominance in CVST is found in young adults, but not in children or older adults.

METHODS: An audit of surgical practice in infection prevention was carried out in Beaumont Hospital from July to November 2009. An educational Web site was developed targeting deficiencies highlighted in the audit. Interactive clinical cases were constructed using PHP coding, an HTML-embedded language, and then linked to a MySQL relational database. PowerPoint tutorials were produced as online Flash audiovisual movies. An online repository of streaming videos demonstrating best practice was made available, and weekly podcasts were made available on the iTunes© store for free download. Usage of the e-learning program was assessed quantitatively over 6 weeks in May and June 2010 using the commercial company Hitslink.

RESULTS: During the 5-month audit, deficiencies in practice were highlighted, including the timing of surgical prophylaxis (33% noncompliance) and intravascular catheter care in surgical patients (38% noncompliance regarding necessity). Over the 6-week assessment of the educational material, the SurgInfection.com Web pages were accessed more than 8000 times; 77.9% of the visitors were from Ireland. The most commonly accessed modality was the repository with interactive clinical cases, accounting for 3463 (43%) of the Web site visits. The average user spent 57 minutes per visit, with 30% of them visiting the Web site multiple times.

DISCUSSION: Interactive virtual cases mirroring real-life clinical scenarios are likely to be successful as an e-learning modality. User-friendly interfaces and 24-hour accessibility will increases uptake by surgical trainees.

METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes.

RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status.

CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.

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.

METHODS: A systematic review of observational studies addressing miscarriage, congenital malformations and perinatal mortality among pregnant women with type 1 and type 2 diabetes was carried out. Literature searches were performed in MEDLINE, EMBASE, CINAHL and Cochrane Library. Observational studies with data on glycated haemoglobin (HbA1c) levels categorised into poor and optimal control (as defined by the study investigators) were selected. Relative risks and odds ratios were calculated for HbA1c and pregnancy outcomes. Adjusted relative risk estimates per 1-percent decrease in HbA1c were calculated for studies which contained information on mean and standard deviations of HbA1c.

RESULTS: The review identified thirteen studies which compared poor versus optimal glycaemic control in relation to maternal, fetal and neonatal outcomes. Twelve of these studies reported the outcome of congenital malformations and showed an increased risk with poor glycaemic control, pooled odds ratio 3.44 (95%CI, 2.30 to 5.15). For four of the twelve studies, it was also possible to calculate a relative risk reduction of congenital malformation for each 1-percent decrease in HbA1c, these varied from 0.39 to 0.59. The risk of miscarriage was reported in four studies and was associated with poor glycaemic control, pooled odds ratio 3.23 (95%CI, 1.64 to 6.36). Increased perinatal mortality was also associated with poor glycaemic control, pooled odds ratio 3.03 (95%CI, 1.87 to 4.92) from four studies.

CONCLUSION: This analysis quantifies the increase in adverse pregnancy outcomes in women with diabetes who have poor glycaemic control. Relating percentage risk reduction in HbA1c to relative risk of adverse pregnancy events may be useful in motivating women to achieve optimal control prior to conception.

METHODS: The Medical Research Council (MRC) framework for the development and evaluation of complex interventions for randomised control trials (RCT) was used as a theoretical guide to designing the intervention. The first three phases (Preclinical Phase, Phase 1, Phase 2) of this framework were examined in depth. The Preclinical Phase included a review of the literature relating to type 2 diabetes and peer support. In Phase 1 the theoretical background and qualitative data from 4 focus groups were combined to define the main components of the intervention. The preliminary intervention was conducted in Phase 2. This was a pilot study conducted in two general practices and amongst 24 patients and 4 peer supporters. Focus groups and semi structured interviews were conducted to collect additional qualitative data to inform the development of the intervention.

RESULTS: The four components of the intervention were identified from the Preclinical Phase and Phase 1. They are: 1. Peer supporters; 2. Peer supporter training; 3. Retention and support for peer supporters; 4. Peer support meetings. The preliminary intervention was implemented in the Phase 2. Findings from this phase allowed further modeling of the intervention, to produce the definitive intervention.

CONCLUSION: The MRC framework was instrumental in the development of a robust intervention of peer support of type 2 diabetes in primary care.

TRIAL REGISTRATION: Current Controlled Trials ISRCTN42541690.

METHODS: Design: Incidence and prevalence-based cost-of-illness study from the perspectives of the UK NHS and of parents and caregivers. Setting: 11 general practices in Bristol, UK. Subjects: 121 children without known asthma aged 3 to 59 months presenting for the first time with an acute (

RESULTS: Mean cost per episode to the NHS: pound27.43 (95% CI: pound24.38 - pound30.49). Mean cost per episode to parents and carers: pound14.77 ( pound4.90 - pound24.65). Annual cost to the NHS in the UK: at least pound31.5 m (95% CI: pound28.0 m - pound35.0 m).

CONCLUSION: The cost burden on the healthcare provider of acute cough in pre-school children is substantial; the majority of this cost arises from consultations with general practitioners. Parents experience some personal cost through travel and expenditure on over-the-counter preparations, and may suffer significantly if loss of earnings is experienced. There is scope for evaluating interventions designed to reduce this burden.

METHODS: Diagnostic accuracy systematic review, we searched Medline (1966 to March 2008), EMBASE (1988 to March 2008), Central, Cochrane and ZETOC using a diagnostic accuracy search filter. We included cross-sectional or cohort studies that assess the diagnostic utility of clinical history, symptoms, signs and diagnostic tests, against a reference standard of echocardiography. We calculated pooled positive and negative likelihood ratios and assessed heterogeneity using the I2 index.

RESULTS: 24 studies incorporating 10,710 patients were included. The median prevalence of LVSD was 29.9% (inter-quartile range 14% to 37%). No item from the clinical history or symptoms provided sufficient diagnostic information to "rule in" or "rule out" LVSD. Displaced apex beat shows a convincing diagnostic effect with a pooled positive likelihood ratio of 16.0 (8.2-30.9) but this finding occurs infrequently in patients. ECG was the most widely studied diagnostic test, the negative likelihood ratio ranging from 0.06 to 0.6. Natriuretic peptide results were strongly heterogeneous, with negative likelihood ratios ranging from 0.02 to 0.80.

CONCLUSION: Findings from the clinical history and examination are insufficient to "rule in" or "rule out" a diagnosis of LVSD in primary care settings. BNP and ECG measurement appear to have similar diagnostic utility and are most useful in "ruling out" LVSD with a normal test result when the probability of LVSD is in the intermediate range.