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1.  Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS) 
Background
Diabetes–related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).
There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.
Review questions;
1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?
2. Can the data from each study be adjusted for a consistent set of adjustment factors?
3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics?
Methods
MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.
We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using “study” as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable.
Discussion
This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines.
doi:10.1186/1471-2288-13-22
PMCID: PMC3599337  PMID: 23414550
2.  Behavioural change in relation to alcohol exposure in early pregnancy and impact on perinatal outcomes - a prospective cohort study 
Background
There has been limited research addressing whether behavioural change in relation to alcohol exposure in pregnancy results in better perinatal outcomes.
Methods
A cohort study of 6725 women who booked for antenatal care and delivered in a large urban teaching hospital in 2010–2011. A detailed history of alcohol consumption pre-pregnancy and during early pregnancy was recorded at the first antenatal visit with follow-up of the mother and infant until discharge following birth. Adverse perinatal outcomes were compared for ‘non-drinkers’, ‘ex-drinkers’ and ‘current drinkers’.
Results
Of the 6017 (90%) women who reported alcohol consumption prior to pregnancy 3325 (55%) engaged in binge drinking and 266 (4.4%) consumed more than 14 units on average per week. At the time of booking 5649 (94%) women were ex-drinkers and of the 368 women who continued to drink 338 (92%) had a low intake (0–5 units per week), 30 (8%) an excess intake (6-20+ units per week) and 93 (25%) reported at least one episode of binge drinking. Factors associated with continuing to drink in early pregnancy included older maternal age (30–39 years), (OR 1.6; 95% CI 1.3 to 1.8), Irish nationality (OR 3.1; 95% CI 2.2 to 4.3) and smoking (OR 2.6; 95% CI 1.9 to 3.5). Ex-drinkers had similar perinatal outcomes to non-drinkers. Compared to non-drinkers current drinking was associated with an increased risk of intrauterine growth restriction (IUGR) (13% versus 19%, crude OR 1.6; 95% CI 1.1 to 2.2, adjusted OR 1.2; 95% CI 0.8 to 1.8). The greatest risk of IUGR was among women who continued to both drink and smoke, (9% versus 32%, crude OR 4.8; 95% CI 3.3 to 7.0, adjusted OR 4.5; 95% CI 3.1 to 6.7).
Conclusions
Public Health campaigns need to emphasise the potential health gains of abstaining from both alcohol and smoking in pregnancy.
doi:10.1186/1471-2393-13-8
PMCID: PMC3549282  PMID: 23324650
Alcohol exposure; Prospective cohort study; Pregnancy; Perinatal outcomes
3.  Proton pump inhibitors: potential cost reductions by applying prescribing guidelines 
Background
There are concerns that proton pump inhibitors (PPI) are being over prescribed in both primary and secondary care. This study aims to establish potential cost savings in a community drug scheme for a one year period according to published clinical and cost-effective guidelines for PPI prescribing.
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.
doi:10.1186/1472-6963-12-408
PMCID: PMC3529111  PMID: 23163956
Proton pump inhibitors; Cost-effective; Guidelines; Generic
5.  Diagnostic accuracy of the STRATIFY clinical prediction rule for falls: A systematic review and meta-analysis 
BMC Family Practice  2012;13:76.
Background
The STRATIFY score is a clinical prediction rule (CPR) derived to assist clinicians to identify patients at risk of falling. The purpose of this systematic review and meta-analysis is to determine the overall diagnostic accuracy of the STRATIFY rule across a variety of clinical settings.
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.
doi:10.1186/1471-2296-13-76
PMCID: PMC3460792  PMID: 22870921
Falls assessment; STRATIFY; Sensitivity and specificity; Systematic review; Meta-analysis
6.  Authors' response 
doi:10.3399/bjgp11X572670
PMCID: PMC3103680
7.  Identifying suspected breast cancer: development and validation of a clinical prediction rule 
The British Journal of General Practice  2011;61(586):e205-e214.
Background
An evidence-based approach is needed to identify women with breast symptoms who are most likely to have breast cancer so that timely and appropriate referral can take place.
Aim
To report the development and validation of a clinical prediction rule for the diagnosis of breast cancer.
Design and setting
Cohort study with two prospective groups of women: those presenting to a symptomatic breast clinic (derivation cohort) and a separate cohort presenting to 11 general practices (validation cohort) in Tayside, Scotland.
Method
Regression analysis was used to derive a clinical prediction rule from presenting symptoms, personal and family history, and clinical findings. Validation consisted of estimating the number of breast cancers predicted to occur compared with the actual number of observed breast cancers across deciles of risk.
Results
In the derivation cohort of 802 patients, 59 (7%) were diagnosed with breast cancer. Independent clinical predictors for breast cancer were: increasing age by year (adjusted odds ratio [AOR] 1.10, 95% confidence interval [CI] = 1.07 to 1.13); presence of a discrete lump (AOR 15.20, 95% CI = 4.88 to 47.34); breast thickening (AOR 7.64, 95% CI = 2.23 to 26.11); lymphadenopathy (AOR 3.63, 95% CI = 1.33 to 9.92); and lump ≥2 cm (AOR 5.41, 95% CI = 2.36 to 12.38). All eight patients with skin tethering had breast cancer. The regression model had good predictive power, identifying all five breast cancers in the validation cohort of 97 patients in the top two deciles of risk.
Conclusion
The clinical prediction rule discriminates between patients at high risk of breast cancer from those at low risk, and can be implemented as an evidence-based recommendation to enhance appropriate referral from general practice to a symptomatic breast clinic. Ongoing validation in further populations is required.
doi:10.3399/bjgp11X572391
PMCID: PMC3080225  PMID: 21619744
breast cancer; diagnosis; primary care
8.  The Alvarado score for predicting acute appendicitis: a systematic review 
BMC Medicine  2011;9:139.
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.
doi:10.1186/1741-7015-9-139
PMCID: PMC3299622  PMID: 22204638
9.  Self-monitoring and other non-pharmacological interventions to improve the management of hypertension in primary care: a systematic review 
The British Journal of General Practice  2010;60(581):e476-e488.
Background
Patients with high blood pressure (hypertension) in the community frequently fail to meet treatment goals: a condition labelled as ‘uncontrolled’ hypertension. The optimal way to organise and deliver care to hypertensive patients has not been clearly identified.
Aim
To determine the effectiveness of interventions to improve control of blood pressure in patients with hypertension.
Design of study
Systematic review of randomised controlled trials.
Setting
Primary and ambulatory care.
Method
Interventions were categorised as following: self-monitoring; educational interventions directed to the patient; educational interventions directed to the health professional; health professional- (nurse or pharmacist) led care; organisational interventions that aimed to improve the delivery of care; and appointment reminder systems. Outcomes assessed were mean systolic and diastolic blood pressure, control of blood pressure and proportion of patients followed up at clinic.
Results
Seventy-two RCTs met the inclusion criteria. The trials showed a wide variety of methodological quality. Self-monitoring was associated with net reductions in systolic blood pressure (weighted mean difference [WMD] −2.5mmHg, 95%CI = −3.7 to −1.3 mmHg) and diastolic blood pressure (WMD −1.8mmHg, 95%CI = −2.4 to −1.2 mmHg). An organised system of regular review allied to vigorous antihypertensive drug therapy was shown to reduce blood pressure and all-cause mortality in a single large randomised controlled trial.
Conclusion
Antihypertensive drug therapy should be implemented by means of a vigorous stepped care approach when patients do not reach target blood pressure levels. Self-monitoring is a useful adjunct to care while reminder systems and nurse/pharmacist -led care require further evaluation.
doi:10.3399/bjgp10X544113
PMCID: PMC2991764  PMID: 21144192
hypertension; prevention and control; primary care; systematic review
10.  Framework for the impact analysis and implementation of Clinical Prediction Rules (CPRs) 
Clinical Prediction Rules (CPRs) are tools that quantify the contribution of symptoms, clinical signs and available diagnostic tests, and in doing so stratify patients according to the probability of having a target outcome or need for a specified treatment. Most focus on the derivation stage with only a minority progressing to validation and very few undergoing impact analysis. Impact analysis studies remain the most efficient way of assessing whether incorporating CPRs into a decision making process improves patient care. However there is a lack of clear methodology for the design of high quality impact analysis studies.
We have developed a sequential four-phased framework based on the literature and the collective experience of our international working group to help researchers identify and overcome the specific challenges in designing and conducting an impact analysis of a CPR.
There is a need to shift emphasis from deriving new CPRs to validating and implementing existing CPRs. The proposed framework provides a structured approach to this topical and complex area of research.
doi:10.1186/1472-6947-11-62
PMCID: PMC3216240  PMID: 21999201
11.  Validity of British Thoracic Society guidance (the CRB-65 rule) for predicting the severity of pneumonia in general practice: systematic review and meta-analysis 
The British Journal of General Practice  2010;60(579):e423-e433.
Background
The CRB-65 score is a clinical prediction rule that grades the severity of community-acquired pneumonia in terms of 30-day mortality.
Aim
The study sought to validate CRB-65 and assess its clinical value in community and hospital settings.
Design of study
Systematic review and meta-analysis of validation studies of CRB-65.
Method
Medline (1966 to June 2009), Embase (1988 to November 2008), British Nursing Index (BNI) and PsychINFO were searched, using a diagnostic accuracy search filter combined with subject-specific terms. The derived (index) rule was used as a predictive model and applied to all validation studies. Comparison was made between the observed and predicted number of deaths stratified by risk group (low, intermediate, and high) and setting of care (community or hospital). Pooled results are presented as risk ratios (RRs) in terms of over-prediction (RR>1) or under-prediction (RR<1) of 30-day mortality.
Results
Fourteen validation studies totalling 397 875 patients are included. CRB-65 performs well in hospitalised patients, particularly in those classified as intermediate (RR 0.91, 95% confidence interval [CI] = 0.71 to 1.17) or high risk (RR 1.01, 95% CI = 0.87 to 1.16). In community settings, CRB-65 over-predicts the probability of 30-day mortality across all strata of predicted risk, low (RR 9.41, 95% CI = 1.75 to 50.66), intermediate (RR 4.84, 95% CI = 2.61 to 8.69), and high (RR 1.58, 95% CI = 0.59 to 4.19).
Conclusion
CRB-65 performs well in stratifying severity of pneumonia and resultant 30-day mortality in hospital settings. In community settings, CRB-65 appears to over-predict the probability of 30-day mortality across all strata of predicted risk. Caution is needed when applying CRB-65 to patients in general practice.
doi:10.3399/bjgp10X532422
PMCID: PMC2944951  PMID: 20883616
general practice; meta-analysis; pneumonia; prognosis; severity of illness index
12.  Cardiovascular medication: improving adherence 
Clinical Evidence  2009;2009:0220.
Introduction
Adherence to medication is generally defined as the extent to which people take medications as prescribed by their healthcare providers. It can be assessed in many ways (e.g., by self-reporting, pill counting, direct observation, electronic monitoring, or by pharmacy records). This review reports effects of intervention on adherence to cardiovascular medications however adherence has been measured.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to improve adherence to long-term medication for cardiovascular disease in adults? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: patient health education; prescriber education; prompting mechanisms; reminder packaging (calendar [blister] packs; multi-dose pill boxes); and simplified dosing.
Key Points
Adherence to medication is generally defined as the extent to which people take medications as prescribed by their healthcare providers. It can be assessed in many ways (e.g., by self-reporting, pill counting, direct observation, electronic monitoring, or through pharmacy records). In this review, we have reported adherence to cardiovascular medications however it has been measured.
The RCTs we found used a variety of different interventions in different populations, measured adherence differently, and expressed and analysed results differently. The diversity and complexity of interventions employed in RCTs makes it difficult to separate out any individual components that might be of benefit.
We found evidence that simplified dosing regimens may increase adherence compared with more complex regimens. While simplifying the frequency of dosage may increase adherence, it is not known whether simplified regimens may increase adherence when someone is taking multiple drugs, as may be the case with cardiovascular medicines.In altering a drug regimen simply to increase adherence, any changes could potentially affect the effectiveness of the treatment, and could also potentially increase adverse effects.
Prompting mechanisms may also increase adherence to medication. Some prompting mechanisms may be simple and inexpensive (e.g., mailed reminders), while others (e.g., daily telephone calls, installing videophones) seem impracticable for use in routine practice.
Patient health education does not seem effective in increasing adherence. Adherence behaviour is complex. Traditional education methods may fail to address this.We found some evidence that a combination of strategies, for example, education plus prompting, may be more successful than a single educational strategy.
We found no evidence from one RCT that reminder packaging (a calendar blister pack) was effective, and found insufficient evidence on other types of reminder packaging such as multi-dose pill boxes.
We don't know whether prescriber education is effective, as we found no RCTs.
PMCID: PMC2907813
13.  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 
BMC Medicine  2011;9:67.
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.
doi:10.1186/1741-7015-9-67
PMCID: PMC3127779  PMID: 21631919
14.  Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure - retrospective cohort study in an urban obstetric population in Ireland 
Background
Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption.
Methods
A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (>20 units per week).
Results
Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (<32 weeks gestation) even after controlling for socio-demographic factors, adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups.
Conclusions
Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.
doi:10.1186/1471-2393-11-27
PMCID: PMC3080836  PMID: 21481224
15.  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.
doi:10.1186/1472-6947-11-5
PMCID: PMC3039554  PMID: 21284849
16.  Improving adherence to drugs for hypertension 
BMJ : British Medical Journal  2007;335(7628):1002-1003.
General practitioners who provide effective explanations of treatment achieve better results
doi:10.1136/bmj.39371.489398.80
PMCID: PMC2078650  PMID: 17991934
17.  Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs 
BMC Family Practice  2010;11:78.
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.
doi:10.1186/1471-2296-11-78
PMCID: PMC2987910  PMID: 20969801
18.  Effect of antibiotic prescribing strategies and an information leaflet on longer-term reconsultation for acute lower respiratory tract infection 
Background
Limited evidence suggests that delayed prescribing may influence future consultation behaviour.
Aim
To assess the effects of antibiotic prescribing strategy on reconsultation in the year following presentation with acute lower respiratory tract infection (LRTI).
Design of study
Balanced factorial randomised trial.
Setting
Primary care.
Method
Eight hundred and seven subjects, aged ≥3 years, had acute illness presenting with cough as the main symptom, plus at least one symptom or sign from sputum, chest pain, dyspnoea or wheeze. The subjects were randomised to one of three prescribing strategies (antibiotics, delayed antibiotic, no antibiotic) and a leaflet. Prior antibiotic use and reconsultation were assessed by medical record review.
Results
Patients who had been prescribed antibiotic for cough in the previous 2 years were much more likely to reconsult (incidence rate ratio [IRR] = 2.55, 95% confidence interval [CI] = 1.62 to 4.01) and use of a delayed prescription strategy is associated with reduced reconsultation in this group. In those with prior antibiotic exposure, there was a 34% reduction in consultation rate in the no antibiotic group (IRR = 0.66, 0.30 to 1.44, P = 0.295) and a 78% reduction for the delayed antibiotic group (IRR = 0.22, 0.10 to 0.49, P<0.001) when compared with those given immediate antibiotics. This effect was not observed in patients who had not been prescribed antibiotics in the previous 2 years; there was no reduction in consultations in the no antibiotic group (IRR = 1.23, 0.79 to 1.92, P = 0.358) or the delayed antibiotic group (1.19, 0.78 to 1.80, P = 0.426). There was an increase in consultation rate with an information leaflet (IRR = 1.27, 0.86 to 1.87, P = 0.229). Past attendance with cough, or past attendance with other respiratory illness and smoking, also predicted reconsultation with cough.
Conclusion
Delayed antibiotic prescribing for LRTI appears effective in modifying reconsultation behaviour, particularly in those with a prior history of antibiotic prescription for LRTI.
doi:10.3399/bjgp09X472601
PMCID: PMC2751917  PMID: 19843421
anti-bacterial agents; primary health care; referral and consultation; respiratory tract infections
19.  Tackling therapeutic inertia: role of treatment data in quality indicators  
BMJ : British Medical Journal  2007;335(7619):542-544.
Many patients with hypertension remain undertreated despite the apparent rosy picture given by doctors meeting current targets. Different measures are needed to overcome therapeutic inertia, argue Bruce Guthrie, Melanie Inkster, and Tom Fahey
doi:10.1136/bmj.39259.400069.AD
PMCID: PMC1976517  PMID: 17855323
20.  Construction and assumptions of models should be explicit 
BMJ : British Medical Journal  2007;334(7598):814.
doi:10.1136/bmj.39185.472743.3A
PMCID: PMC1853174  PMID: 17446585
21.  Authors' response 
doi:10.3399/bjgp09X395157
PMCID: PMC2629827
23.  Adherence to statin or aspirin or both in patients with established cardiovascular disease: exploring healthy behaviour vs. drug effects and 10-year follow-up of outcome 
Aims
To characterize adherence in patients with established cardiovascular disease taking statins and aspirin and to estimate the effects of adherence due to health behaviour, a lack of beneficial drug effect, or both on recurrence of cardiovascular disease or all-cause mortality over 10 years.
Methods
A population-based cohort study using a record-linkage database in Tayside, Scotland. Subjects with cardiovascular disease (n = 7657; 4185 aspirin-alone cohort, 671 statin-alone cohort and 2801 combination use cohort) were studied between 1993 and 2003. The effects of adherence on recurrence of cardiovascular disease or mortality were assessed using Poisson regression model.
Results
In subjects taking both aspirin and statins, those adherent to statins but not aspirin had a lower risk of recurrence [adjusted risk ratio (RR) 0.64; 95% confidence interval 0.49, 0.82], but those adherent to aspirin but not statins has no such effect (adjusted RR 0.91; 0.72, 1.15), suggesting that adherence behaviour alone was not responsible for the beneficial effect. Within the group adherent to aspirin, ≥80% adherence to statins was associated with reduced recurrence compared with those poorly adherent (adjusted RR 0.76; 0.62, 0.94), but no such effect of aspirin was seen in those adherent to statins. Similar results were found for all-cause mortality.
Conclusions
Poor health behaviour is not a sufficient explanation of adverse outcome in poorly adherent patients. Adverse outcome is more likely to be driven by foregone drug benefits.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Aspirin and statins are widely-used drugs in patients with cardiovascular disease.There is less information on healthy behaviour vs. drug effects.
WHAT THIS STUDY ADDS Long-term adherence to aspirin and statin treatments in patients with established cardiovascular disease has been investigated.Poor health behaviour is not a sufficient explanation of adverse outcome in poorly adherent patients.
doi:10.1111/j.1365-2125.2008.03212.x
PMCID: PMC2485263  PMID: 18492127
aspirin; cardiovascular recurrence; long-term adherence; statin
24.  Comparison of self-reported health & healthcare utilisation between asylum seekers and refugees: an observational study 
BMC Public Health  2009;9:214.
Background
Adult refugees and asylum seekers living in Western countries experience a high prevalence of mental health problems, especially post traumatic stress disorder (PTSD), depression and anxiety. This study compares and contrasts the prevalence of health problems, and potential risk factors as well as the utilisation of health services by asylum seekers and refugees in the Irish context.
Methods
Cross sectional study using validated self reported health status questionnaires of adult asylum seekers (n = 60) and refugees (n = 28) from 30 countries, living in Ireland. Outcome measures included: general health status (SF-36), presence of PTSD symptoms and anxiety/depression symptoms. Data on chronic conditions and pre or post migration stressors are also reported. The two groups are compared for utilisation of the health care system and the use of over the counter medications.
Results
Asylum seekers were significantly more likely than refugees to report symptoms of PTSD (OR 6.3, 95% CI: 2.2–17.9) and depression/anxiety (OR 5.8, 95% CI: 2.2–15.4), while no significant difference was found in self-reported general health. When adjusted by multivariable regression, the presence of more than one chronic disease (OR 4.0, 95%CI: 1.3–12.7; OR 3.4, 95% CI: 1.2–10.1), high levels of pre migration stressors (OR 3.6, 95% CI: 1.1–11.9; OR 3.3, 95% CI: 1.0–10.4) or post migration stressors (OR 17.3, 95% CI: 4.9–60.8; OR 3.9, 95% CI: 1.2–12.3) were independent predictors of self reported PTSD or depression/anxiety symptoms respectively, however, residence status was no longer significantly associated with PTSD or depression/anxiety. Residence status may act as a marker for other explanatory variables; our results show it has a strong relationship with post migration stressors (χ2 = 19.74, df = 1, P < 0.001).
In terms of health care utilisation, asylum seekers use GP services more often than refugees, while no significant difference was found between these groups for use of dentists, medication, hospitalisation or mental health services.
Conclusion
Asylum seekers have a higher level of self reported PTSD and depression/anxiety symptoms compared to refugees. However, residence status appears to act as a marker for post migration stressors. Compared to refugees, asylum seekers utilise GP services more often, but not mental health services.
doi:10.1186/1471-2458-9-214
PMCID: PMC2711949  PMID: 19566954
25.  Predicting the duration of symptoms in lower respiratory tract infection 
Background
Acute lower respiratory tract infection (LRTI) presenting in primary care has a long natural history. Antibiotic treatment makes little or no difference to the duration of cough. Limited information is currently available regarding predictors of illness duration.
Aim
To determine predictors of illness duration in acute LRTI in primary care.
Design of study
Secondary analysis of trial data to identify independent predictors of illness severity and duration.
Setting
Primary care.
Method
Eight-hundred and seven patients aged 3 years and over with acute illness (21 days or less) presenting with cough as the main symptom plus at least one symptom or sign from sputum, chest pain, dyspnoea, or wheeze were recruited to the study. Main outcomes were duration of symptoms (rated at least a slight problem) and more severe symptoms (rated at least moderately bad).
Results
The average duration of cough (rated at least a slight problem) was 11.7 days and was shorter among children (duration −1.72 days; 95% confidence interval [CI] = −3.02 to −0.41) or in individuals with a history of fever (−1.22 days; 95% CI = −0.18 to 2.27). The duration of cough was longer among those with restricted activities on the day they saw the doctor (+0.69 days for each point of a 7-point scale). The duration of more severe symptoms was longer in those with a longer duration of symptoms prior to consultation, with a more severe cough on the day of seeing the doctor, and restriction of activities on the day of seeing the doctor.
Conclusion
Illness duration may be predicted from a limited number of clinical symptoms and from prior history. These findings should be subjected to validation in a separate population. To minimise expectation about rapid resolution of illness, adults who have restricted activities could be advised that they are likely to experience symptoms for longer.
doi:10.3399/bjgp08X264045
PMCID: PMC2233957  PMID: 18307851
bronchitis; cough; prognosis; respiratory tract infections

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