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.

The impact of eHealth on the quality and safety of health care: a systematic overview.

BACKGROUND: There is considerable international interest in exploiting the potential of digital solutions to enhance the quality and safety of health care. Implementations of transformative eHealth technologies are underway globally, often at very considerable cost. In order to assess the impact of eHealth solutions on the quality and safety of health care, and to inform policy decisions on eHealth deployments, we undertook a systematic review of systematic reviews assessing the effectiveness and consequences of various eHealth technologies on the quality and safety of care. METHODS AND FINDINGS: We developed novel search strategies, conceptual maps of health care quality, safety, and eHealth interventions, and then systematically identified, scrutinised, and synthesised the systematic review literature. Major biomedical databases were searched to identify systematic reviews published between 1997 and 2010. Related theoretical, methodological, and technical material was also reviewed. We identified 53 systematic reviews that focused on assessing the impact of eHealth interventions on the quality and/or safety of health care and 55 supplementary systematic reviews providing relevant supportive information. This systematic review literature was found to be generally of substandard quality with regards to methodology, reporting, and utility. We thematically categorised eHealth technologies into three main areas: (1) storing, managing, and transmission of data; (2) clinical decision support; and (3) facilitating care from a distance. We found that despite support from policymakers, there was relatively little empirical evidence to substantiate many of the claims made in relation to these technologies. Whether the success of those relatively few solutions identified to improve quality and safety would continue if these were deployed beyond the contexts in which they were originally developed, has yet to be established. Importantly, best practice guidelines in effective development and deployment strategies are lacking. CONCLUSIONS: There is a large gap between the postulated and empirically demonstrated benefits of eHealth technologies. In addition, there is a lack of robust research on the risks of implementing these technologies and their cost-effectiveness has yet to be demonstrated, despite being frequently promoted by policymakers and "techno-enthusiasts" as if this was a given. In the light of the paucity of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, it is vital that future eHealth technologies are evaluated against a comprehensive set of measures, ideally throughout all stages of the technology's life cycle. Such evaluation should be characterised by careful attention to socio-technical factors to maximise the likelihood of successful implementation and adoption.

Computer-assisted history-taking systems (CAHTS) in health care: benefits, risks and potential for further development.

BACKGROUND: A computer-assisted history-taking system (CAHTS) is a tool that aids clinicians in gathering data from patients to inform a diagnosis or treatment plan. Despite the many possible applications and even though CAHTS have been available for nearly three decades, these remain underused in routine clinical practice. OBJECTIVE: Through an interpretative review of the literature, we provide an overview of the field of CAHTS, which also offers an understanding of the impact of these systems on policy, practice and research. METHODS: We conducted a search and critique of the literature on CAHTS. Using a comprehensive set of terms, we searched: MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, The Cochrane Central Register of Controlled Trials, The Cochrane Methodology Register, Health Technology Assessment Database and the NHS Economic Evaluation Database over a ten-year period (January 1997 to May 2007) to identify systematic reviews, technical reports and health technology assessments, and randomised controlled trials. RESULTS: The systematic review of the literature suggests that CAHTS can save professionals' time, improve delivery of care to those with special needs and also facilitate the collection of information, especially potentially sensitive information (e.g. sexual history, alcohol consumption). The use of CAHTS also has disadvantages that impede the process of history taking and may pose risks to patients. CAHTS are inherently limited when detecting non-verbal communication, may pose irrelevant questions and frustrate the users with technical problems. Our review suggests that barriers such as a preference for pen-and-paper methods and concerns about data loss and security still exist and affect the adoption of CAHTS. In terms of policy and practice, CAHTS make input of data from disparate sites possible, which facilitates work from disparate sites and the collection of data for nationwide screening programmes such as the vascular risk assessment programme for people aged 40-74, now starting in England. CONCLUSIONS: Our review shows that for CAHTS to be adopted in mainstream health care, important changes should take place in how we conceive, plan and conduct primary and secondary research on the topic so that we provide the framework for a comprehensive evaluation that will lead to an evidence base to inform policy and practice.

An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation.

OBJECTIVES: This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses. DESIGN AND SETTING: Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions. PARTICIPANTS: Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients' PCPs and cancer treatment specialists (CTSs) are surveyed, and 'data rules' are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases. MAIN OUTCOMES: Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types. CONCLUSION: An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children: a matched case-control study.

BACKGROUND: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. AIMS: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. METHODS: We conducted an age- and sex-matched case-control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. RESULTS: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08-1.20; adjusted OR=1.11, 95% CI, 1.03-1.19) and girls (OR=1.37, 95% CI, 1.26-1.50; adjusted OR=1.38, 95% CI, 1.23-1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96-1.60; boys: OR=1.09, 95% CI, 0.99-1.19). CONCLUSIONS: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation.

Predicting language change between 3 and 5 years and its implications for early identification.

BACKGROUND AND OBJECTIVE: Early language delays across the preschool period have important implications for children, parents, and services raising the significance of early identification. Screening tests are an appealing solution but have proved problematic. A combined risk model would seem promising but has yet to be tested. The goal of this study was to examine the factors that predict language change in a nationally representative sample of children between 3 and 5 years when most children are identified as being in need of services. METHODS: By using data from children (n = 13,016) in the Millennium Cohort Study (a national UK birth cohort), linear regression was used to predict 5-year performance from 3-year test performance data coupled with sociodemographic and within-child factors and indicators of parental concern. Patterns of change were identified and logistic regression was used to predict the difference between children for whom profiles change and those for whom they do not. RESULTS: The final model (predicting 32% of the variance) included maternal education, pattern construction, behavior, language concerns, and 3-year vocabulary. Four change patterns were identified: one consistently low (n = 201), one consistently high (n = 12,066), a group that is resilient (n = 572), and one with a declining profile (n = 177). The models accurately predicted 71% of the declining group and 99% of the resilient group. Maternal education (odds ratio: 0.49) and behavior (odds ratio: 0.9) were significant predictors for the former and maternal education (odds ratio: 0.6) and pattern construction (odds ratio: 1.03) the latter. CONCLUSIONS: Early identification of delayed language remains problematic but, once identified, there are key indicators that predict which children are likely to be more or less at risk across time. The implications are discussed in terms of policy and practice.

Prevalence of allergic disorders among primary school-aged children in Madinah, Saudi Arabia: two-stage cross-sectional survey.

BACKGROUND: There are limited data on the epidemiology of allergic disorders in Saudi Arabia. Such data are needed for, amongst other things, helping to plan service provision at a time when there is considerable investment taking place in national healthcare development. We sought to estimate the prevalence of atopic eczema, allergic rhinitis and asthma in primary school children in Madinah, Saudi Arabia. METHODS AND FINDINGS: We conducted a two-stage cross-sectional survey of schoolchildren in Madinah. Children were recruited from 38 randomly selected schools. Questionnaires were sent to the parents of all 6,139 6-8 year old children in these schools. These parental-completed questionnaires incorporated questions from the International Study of Asthma and Allergies in Childhood (ISAAC), which had previously been validated for use in Arab populations. We undertook descriptive analyses, using the Generalized Estimating Equation (GEE) to calculate 95% confidence intervals. The overall response rate was 85.9% (n = 5,188), 84.6% for girls and 86.2% for boys, respectively. Overall, parents reported symptoms suggestive of a history of eczema in 10.3% (95%CI 9.4, 11.4), rhinitis in 24.2% (95%CI 22.3, 26.2) and asthma in 23.6% (95%CI 21.3, 26.0) of children. Overall, 41.7% (95%CI 39.1, 44.4) of children had symptoms suggestive of at least one allergic disorder, with a substantial minority manifesting symptoms indicative of co-morbid allergic disease. Comparison of these symptom-based prevalence estimates with reports of clinician-diagnosed disease suggested that the majority of children with eczema and asthma had been diagnosed, but only a minority (17.4%) of children had been diagnosed with rhinitis. International comparisons indicated that children in Madinah have amongst the highest prevalence of allergic problems in the world. CONCLUSIONS: Symptoms indicative of allergic disease are very common in primary school-aged children in Madinah, Saudi Arabia, with figures comparable to the highest risk regions in the world.

Avoiding inappropriate invitations to cancer screening programmes: the role of primary care.

OBJECTIVES: To examine current procedures for cancer screening invitation list (SIL) checking in primary care, and to make recommendations for the future use of these procedures. SETTING: Cancer screening departments/units and associated general practices across England. METHODS: 1) An analysis of the outputs of screening programme SIL checking, and accompanying practice questionnaire, for cancers of the cervix (9 screening centres, 36 general practices), breast (6 centres, 76 practices) and bowel (pilot hub, 7 practices)--supplemented by an audit of calls to screening centres to identify inappropriate invitations; 2) a national postal questionnaire survey sent to all 80 breast screening departments across England and 320 associated general practices; 3) telephone interviews with 13 NHS screening staff to obtain detailed perspectives about SIL checking procedures. RESULTS: SIL checking in primary care is undertaken by a variety of clinical and non-clinical staff. It plays a useful role in cervical screening with tangible evidence of refinements to the SIL and support from both primary care and screening centre staff. Conversely, its role in breast and bowel screening is not supported by the results of this study. Overall, there is no significant evidence of adverse effects from inappropriate invitations. CONCLUSIONS: SIL checking in primary care for cervical cancer should continue, but its use in breast and bowel cancer screening is not supported by our results. New ways of undertaking the SIL checking process to make it more accurate and less burdensome should be examined.

Reduced lung function in patients with abdominal aortic aneurysm is associated with activation of inflammation and hemostasis, not smoking or cardiovascular disease.

OBJECTIVE: Abdominal aortic aneurysms often coexist with reduced lung function and chronic obstructive pulmonary disease (COPD). These conditions are each associated with cigarette smoking, cardiovascular disease, and evidence of increased inflammatory and hemostatic activity. The aim of this study was to determine if these factors accounted for the link between aneurysms and pulmonary disease. METHODS: The design was a case-control study comparing patients with an asymptomatic abdominal aortic aneurysm with population-based controls without an aneurysm. Aneurysms were diagnosed by ultrasound scan, and pulmonary function was measured by respiratory questionnaire and spirometry. Activation of inflammation and hemostasis was measured by assay of plasma interleukin-6 (IL-6), fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA) antigen, fibrin D-dimer, and plasmin antiplasmin complexes. RESULTS: Cases with an abdominal aortic aneurysm (n = 89) had more COPD and worse expiratory lung function as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) than controls (n = 98) (FEV1, 1.9 vs 2.2 L, P < .01; FEV1/FVC, 0.67 vs 0.75, P < .001) and did not differ in restrictive function (FVC, 2.9 vs 3.0 L, P = .33). Cases also had higher levels of lifetime cigarette smoking (30 vs 24 pack-years, P < 0.01), cardiovascular disease (35% vs 18%, P = .01), plasma fibrinogen (3.5 vs 3.1 g/L, P = .02), IL-6 (2.8 vs 1.8, pg/mL, P < .001), plasmin antiplasmin complexes (596 vs 384 microg/L, P = .01), and D-dimer (442 vs 93 ng/mL, P < .001). On multiple logistic regression analysis of lung function and COPD on the risk of aneurysm, both cigarette smoking and cardiovascular disease had little effect on the relationships. For the markers of activated inflammation and hemostasis, plasmin antiplasmin complexes and D-dimer had the most important confounding effect on the odds ratios. All markers combined had a substantial effect: odds ratio of aneurysm for a one standard deviation decrease in FEV1 fell from 2.3 (95% confidence interval [CI], 1.5 to 3.5) (P < .01) to 1.3 (95% CI, 0.55 to 2.4) (P > or = .05). CONCLUSION: The association between reduced respiratory function and abdominal aortic aneurysm was not accounted for by cigarette smoking or cardiovascular disease. We hypothesize that activation of inflammation and hemostasis in response to injury may be an important explanation of the association between aneurysm formation and reduced respiratory function. Further studies are required to test this hypothesis.