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1.  Reporting standards for studies of diagnostic test accuracy in dementia 
Neurology  2014;83(4):364-373.
To provide guidance on standards for reporting studies of diagnostic test accuracy for dementia disorders.
An international consensus process on reporting standards in dementia and cognitive impairment (STARDdem) was established, focusing on studies presenting data from which sensitivity and specificity were reported or could be derived. A working group led the initiative through 4 rounds of consensus work, using a modified Delphi process and culminating in a face-to-face consensus meeting in October 2012. The aim of this process was to agree on how best to supplement the generic standards of the STARD statement to enhance their utility and encourage their use in dementia research.
More than 200 comments were received during the wider consultation rounds. The areas at most risk of inadequate reporting were identified and a set of dementia-specific recommendations to supplement the STARD guidance were developed, including better reporting of patient selection, the reference standard used, avoidance of circularity, and reporting of test-retest reliability.
STARDdem is an implementation of the STARD statement in which the original checklist is elaborated and supplemented with guidance pertinent to studies of cognitive disorders. Its adoption is expected to increase transparency, enable more effective evaluation of diagnostic tests in Alzheimer disease and dementia, contribute to greater adherence to methodologic standards, and advance the development of Alzheimer biomarkers.
PMCID: PMC4115600  PMID: 24944261
2.  Risk of uterine cancer in symptomatic women in primary care: case–control study using electronic records 
The British Journal of General Practice  2013;63(614):e643-e648.
Uterine cancer is the fourth most common cancer in women in the UK, with approximately 7700 new diagnoses and 1700 deaths annually.
To identify and quantify features of uterine cancer in primary care.
Design and setting
Case–control study using electronic primary care records in primary care in the UK.
Putative features of uterine cancer were identified in the year before diagnosis, and odds ratios (ORs) calculated using conditional logistic regression. Positive predictive values (PPVs) were calculated for women who consulted.
A total of 2732 women aged ≥40 years with uterine cancer between 2000 and 2009, and 9537 age-, sex- and practice-matched controls were selected from the General Practice Research Database. The median age at diagnosis was 67 years. Nine features were significantly associated with uterine cancer: postmenopausal bleeding (OR = 160; 95% confidence interval [CI] = 100 to 240), excessive vaginal bleeding (OR = 22; 95% CI = 12 to 42), irregular menstruation (OR = 42; 95% CI = 27 to −63), vaginal discharge (OR = 14; 95% CI = 10 to 21), haematuria (OR = 8.7; 95% CI = 5.0 to 15), abdominal pain (OR = 2.0; 95% CI = 1.4 to 2.8), low haemoglobin (OR = 2.1; 95% CI = 1.5 to 2.9), raised platelets (OR = 1.5; 95% CI = 1.0 to 2.3), and raised glucose (OR = 1.4; 95% CI = 1.1 to 1.8); all P<0.01, other than raised platelets, P = 0.05 and raised glucose, P = 0.02. In the year before diagnosis, 1725 (63%) cases had a record of abnormal vaginal bleeding compared to 135 (1%) controls. The PPV of uterine cancer with postmenopausal bleeding was 4%, and was higher in women with multiple or repeated symptoms.
This study confirms the importance of several features, particularly postmenopausal bleeding, for uterine cancer. Haematuria is an important risk marker. The results of this study may inform GPs in the selection of women for investigation and should assist the NICE in their update of GP referral guidance.
PMCID: PMC3750804  PMID: 23998845
diagnosis; general practice; primary health care; uterine neoplasms
3.  Neuropsychological tests for the diagnosis of Alzheimer’s disease dementia and other dementias: a generic protocol for cross-sectional and delayed-verification studies 
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the cross-sectional diagnostic accuracy of [index test] at various thresholds for ADD and other dementias [target condition] in [target population].ORTo determine the accuracy of [index test] at various thresholds for diagnosing ADD and other dementias [target condition] in [target population] after a follow-up period (delayed-verification studies).To investigate the heterogeneity of test accuracy in the included studies.To highlight the quality and quantity of research evidence available on the effectiveness of the index test in the target population.To identify gaps in the evidence and determine where further research is required.
PMCID: PMC4147664  PMID: 25177209
4.  Development of an economic evaluation of diagnostic strategies: the case of monogenic diabetes 
BMJ Open  2013;3(5):e002905.
To describe the development process for defining an appropriate model structure for the economic evaluation of test–treatment strategies for patients with monogenic diabetes (caused by mutations in the GCK, HNF1A or HNF4A genes).
Experts were consulted to identify and define realistic test–treatment strategies and care pathways. A systematic assessment of published diabetes models was undertaken to inform the model structure.
National Health Service in England and Wales.
Experts in monogenic diabetes whose collective expertise spans the length of the patient care pathway.
Primary and secondary outcomes
A defined model structure, including the test–treatment strategies, and the selection of a published diabetes model appropriate for the economic evaluation of strategies to identify patients with monogenic diabetes.
Five monogenic diabetes test–treatment strategies were defined: no testing of any kind, referral for genetic testing based on clinical features as noted by clinicians, referral for genetic testing based on the results of a clinical prediction model, referral for genetic testing based on the results of biochemical and immunological tests, referral for genetic testing for all patients with a diagnosis of diabetes under the age of 30 years. The systematic assessment of diabetes models identified the IMS CORE Diabetes Model (IMS CDM) as a good candidate for modelling the long-term outcomes and costs of the test–treatment strategies for monogenic diabetes. The short-term test–treatment events will be modelled using a decision tree which will feed into the IMS CDM.
Defining a model structure for any economic evaluation requires decisions to be made. Expert consultation and the explicit use of critical appraisal can inform these decisions. Although arbitrary choices have still been made, decision modelling allows investigation into such choices and the impact of assumptions that have to be made due to a lack of data.
PMCID: PMC3657677  PMID: 23793674
Diabetes & Endocrinology; Genetics; Health Economics
5.  A cross-country comparison of intensive care physicians’ beliefs about their transfusion behaviour: A qualitative study using the theoretical domains framework 
Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians’ transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study.
Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians’ responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared.
Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients’ clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients’ clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients’ relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that guideline is important for other professionals), and Motivation and goals (opposing beliefs about the importance of restrictive transfusion and compatibility with other goals), were also identified in this study. Similar to the UK study, the Theory of Planned Behaviour, Social Cognitive Theory, Operant Learning Theory, Action Planning, and Knowledge-Attitude-Behaviour model were identified as potentially relevant theories and models for further study. Personal project analysis was added to the Canadian study to explore the Motivation and goals domain in further detail.
A wide range of beliefs was identified by the Canadian ICU physicians as likely to influence their transfusion behaviour. We were able to demonstrate similar though not identical results in a cross-country comparison. Designing targeted behaviour-change interventions based on unique beliefs identified by physicians from two countries are more likely to encourage restrictive transfusion in ICU physicians in respective countries. This needs to be tested in future prospective clinical trials.
PMCID: PMC3527303  PMID: 22999460
6.  Stem Cell Donation –What advice can be given to the donor? 
British journal of haematology  2009;147(1):71-76.
Haemopoietic stem cell transplantation (HSCT) is widely used to treat patients with a range of haematological and non-haematological disorders. Both bone marrow and peripheral blood stem cell collection are associated with morbidity and, very rarely, mortality. We investigated the information that exists to adequately inform donors about the relative merits of each procedure. We carried out a systematic review analysing data from 6 prospective randomised controlled trials of related donors and discuss here the merits and drawbacks of this approach. Registry data mostly describes patient outcome but stem cell donor registries collect and report information on unrelated donors which could easily be extended to related donors. Further well-designed, randomised studies are required.
PMCID: PMC3409390  PMID: 19681886
Stem Cell donation; peripheral blood; bone marrow; granulocyte; colony-stimulating factor; stem cell donor registries
7.  The acute management of trauma hemorrhage: a systematic review of randomized controlled trials 
Critical Care  2011;15(2):R92.
Worldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality.
Comprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials,, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database.
A total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid.
Despite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.
PMCID: PMC3219356  PMID: 21392371
8.  Using theories of behaviour to understand transfusion prescribing in three clinical contexts in two countries: Development work for an implementation trial 
Blood transfusion is an essential part of healthcare and can improve patient outcomes. However, like most therapies, it is also associated with significant clinical risks. In addition, there is some evidence of overuse. Understanding the potential barriers and enablers to reduced prescribing of blood products will facilitate the selection of intervention components likely to be effective, thereby reducing the number of costly trials evaluating different implementation strategies. Using a theoretical basis to understand behaviours targeted for change will contribute to a 'basic science' relating to determinants of professional behaviour and how these inform the selection of techniques for changing behaviour. However, it is not clear which theories of behaviour are relevant to clinicians' transfusing behaviour. The aim of this study is to use a theoretical domains framework to identify relevant theories, and to use these theories to identify factors that predict the decision to transfuse.
The study involves two steps: interview study and questionnaire study. Using a previously identified framework, we will conduct semi-structured interviews with clinicians to elicit their views about which factors are associated with waiting and further monitoring the patient rather than transfusing red blood cells. Interviews will cover the following theoretical domains: knowledge; skills; social/professional role and identity; beliefs about capabilities; beliefs about consequences; motivation and goals; memory, attention, and decision processes; environmental context and resources; social influences; emotion; behavioural regulation; nature of the behaviour. The interviews will take place independently in Canada and the UK and involve two groups of physicians in each country (UK: adult and neonatal intensive care physicians; Canada: intensive care physicians and orthopaedic surgeons). We will: analyse interview transcript content to select relevant theoretical domains; use consensus processes to map these domains on to theories of behaviour; develop questionnaires based on these theories; and mail them to each group of physicians in the two countries. From our previous work, it is likely that the theories will include: theory of planned behaviour, social cognitive theory and the evidence-based strategy, implementation intention. The questionnaire data will measure predictor variables (theoretical constructs) and outcome variables (intention and clinical decision), and will be analysed using multiple regression analysis. We aim to achieve 150 respondents in each of the four groups for each postal survey.
PMCID: PMC2777847  PMID: 19852832
9.  The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials 
Conduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders.
There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals.
The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems.
Standard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006.
Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies.
57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes.
Parenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.
PMCID: PMC2660289  PMID: 19261188
10.  Assessing the diagnostic test accuracy of natriuretic peptides and ECG in the diagnosis of left ventricular systolic dysfunction: a systematic review and meta-analysis 
In 2003 the National Institute of Clinical Excellence published guidelines recommending the use of brain natriuretic peptide (BNP) and the electrocardiogram (ECG) as part of the diagnostic work up of individuals with heart failure. However, the guideline did not address whether one test was superior to the other or whether performing both tests was superior to performing single tests.
To investigate the relative test accuracy of the ECG, BNP, N terminal-pro brain natriuretic peptide (NT-proBNP) and combinations of two or more tests in the diagnosis of left ventricular systolic dysfunction (LVSD) in the primary care setting.
Design of study
Cohort studies making within-subject comparisons of intervention diagnostic test(s) with reference standard results.
Standard systematic review methodology was followed.
Thirty-two primary studies met the review inclusion criteria. Studies were of variable quality and highly clinically heterogeneous, therefore restricting the use of meta-analysis. Within these limitations BNP, NT-proBNP and the ECG all had similar test sensitivity (>80% in the majority of studies). Specificity of the three tests was not as good. Three studies directly comparing BNP and the ECG found no difference in sensitivity and limited support for improved specificity of BNP. Two studies found no difference in sensitivity and limited evidence for an improvement in specificity for the combination of the ECG and BNP compared to single tests.
On the basis of existing evidence, the ECG, BNP and NT-proBNP are useful in excluding a diagnosis of LVSD (good sensitivity). However, use of abnormal test results to select individuals for echocardiography may overwhelm services. There is currently no evidence to justify the use of one test over another or the use of tests in combination. The additional cost of BNP is not self-evidently justified by improved test accuracy. Further research is needed to directly compare the diagnostic performance of these tests in homogeneous, representative primary care populations.
PMCID: PMC1821403  PMID: 16438815
diagnostic tests; electrocardiography; natriuretic peptides; review; systematic
11.  Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy 
BMJ : British Medical Journal  2002;324(7340):757.
To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy.
Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment.
Patients with any stage of HIV infection who had not received antiretroviral therapy.
Main outcome measures
Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers).
Search strategy
Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001.
54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality.
Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.
What is already known on this topicTriple combination antiretroviral therapy is accepted by clinicians and patients as the usual treatment for HIV and has evolved through an incremental strategy in the numbers of drugs combinedGuidance on treatment, however, has predominantly been based on early reports of researchThere are no published analyses that assess the effectiveness of the increasing numbers of drugs used in combinationWhat this study addsThe results of this systematic review support the use of triple therapy but there is inadequate evidence for quadruple or higher combinationsHeterogeneity in the effect estimates seems to result from variable effectiveness of different drug combinations, trial duration, and problems with study quality
PMCID: PMC100314  PMID: 11923157
14.  Systematic review of near patient test evaluations in primary care 
BMJ : British Medical Journal  1999;319(7213):824-827.
To identify and qualitatively synthesise the findings from all studies that have examined the performance and effect of near patient tests in the primary care setting.
Systematic review of published and unpublished research 1986-99.
Main outcome measures
Test performance characteristics, measures of effect on clinical practice or patient outcome.
101 relevant publications were identified. The general quality of these papers was low, and consequently only 32 papers were assessed in detail. Although these papers gave some indication of the value of near patient testing in areas such as anticoagulation monitoring and group A β haemolytic streptococcus testing, the research raised many more questions than it answered. Almost no reports were found of unbiased assessment of the effect of near patient tests in primary care on patient outcomes, organisational outcomes, or cost.
Available research provides little evidence to guide the expansion of use of near patient testing in primary care. Further research is needed in areas of clinical practice where near patient tests might be most beneficial.
Key messages Near patient testing is a rapidly evolving technology with potential to improve the quality of diagnosis and management in primary care The performance of most tests has not been adequately evaluated in primary care No robust studies of the effectiveness of near patient tests in improving patient outcomes have been conducted High quality evaluations of the performance and effectiveness of near patient tests in defined clinical situations are needed before further expansion
PMCID: PMC314212  PMID: 10496828

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