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London, United Kingdom
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De Silva D.,Evidence Center | Geromi M.,Evidence Center | Panesar S.S.,University of Edinburgh | Muraro A.,University of Padua | And 14 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts. Methods Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized. Results Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration. Conclusions Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Nherera L.,National Collaborating Center for Primary Care | Nherera L.,National Collaborating Center for Womens and Childrens Health | Calvert N.W.,National Collaborating Center for Primary Care | Demott K.,National Collaborating Center for Primary Care | And 4 more authors.
Current Medical Research and Opinion | Year: 2010

To estimate, using probabilistic decision-analytic modelling techniques, the cost effectiveness of treating familial hypercholesterolaemia (FH) patients with high-intensity statins compared to treatment with low-intensity statins. For the purpose of this economic analysis, and based on their known differences, statins were categorised as high intensity if they produce greater LDL-cholesterol reductions than simvastatin 40mg (e.g., simvastatin 80mg and appropriate doses of atorvastatin and rosuvastatin or combination of statins+ezetimibe). A lifetime Markov model was developed to estimate the incremental cost per quality adjusted life year (QALY) of treating a hypothetical cohort of 1000 FH patients aged between 20 and 70 years. Baseline coronary heart disease risks reported in the NICE TA 94 on statins, and age-adjusted risk of cardiovascular disease reported in the FH population, were used to populate the model. A meta-analysis estimate of the reduction in cardiovascular events from using high-intensity compared with low-intensity statins was obtained from published trials. Results were interpreted using a cost-effectiveness threshold of £20 000/QALY. Fewer cardiovascular events and deaths were predicted to occur in the group treated with higher-intensity statins, and the incremental cost-effectiveness ratio (ICER) was estimated at £11 103/QALY. The ICER remained below the £20 000 threshold for 20-39-year-olds and 40-59-year-olds, but rose above this threshold in individuals aged over 60 years. One-way sensitivity analysis showed that results were most sensitive to variation in treatment effect on mortality and the cost of high-intensity statins. Modelling demonstrates that high-intensity statins are cost-effective for the treatment of younger FH patients. If, as is likely, the relative price of high-intensity statins fall in the future as they come off patent, then their cost effectiveness will improve further. © 2010 Informa UK Ltd.


Uhlig K.,Tufts University | Leff B.,Johns Hopkins University | Kent D.,Institute for Clinical Research and Health Policy Studies | Brunnhuber K.,Evidence Center | And 11 more authors.
Journal of General Internal Medicine | Year: 2014

Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement. © Society of General Internal Medicine 2014.


De Silva D.,Evidence Center | Geromi M.,Evidence Center | Halken S.,University of Southern Denmark | Host A.,University of Southern Denmark | And 18 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults. Methods: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized. Results Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults. Conclusions: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Nherera L.,Assessment Technology Group | Marks D.,London School of Hygiene and Tropical Medicine | Minhas R.,Evidence Center | Thorogood M.,University of Warwick | Humphries S.E.,University College London
Heart | Year: 2011

Objective: To estimate the probabilistic cost-effectiveness of cascade screening methods in familial hypercholesterolaemia (FH) from the UK NHS perspective. Design: Economic evaluation (cost utility analysis) comparing four cascade screening strategies for FH: Using low-density lipoprotein (LDL) cholesterol measurements to diagnose affected relatives (cholesterol method); cascading only in patients with a causative mutation identified and using DNA tests to diagnose relatives (DNA method); DNA testing combined with LDL-cholesterol testing in families with no mutation identified, only in patients with clinically defined 'definite' FH (DNA+DFH method); DNA testing combined with LDL-cholesterol testing in no-mutation families of both 'definite' and 'probable' FH patients (DNA+DFH+PFH). A probabilistic model was constructed to estimate the treatment benefit from statins, with all diagnosed individuals receiving high-intensity statin treatment. Population: A cohort of 1000 people suspected of having FH aged 50 years for index cases and 30 years for relatives, followed for a lifetime. Main outcomes: Costs, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER). Results: The DNA+DFH+PFH method was the most cost-effective cascade screening strategy. The ICER was estimated at £3666/QALY. Using this strategy, of the tested relatives 30.6% will be true positives, 6.3% false positives, 61.9% true negatives and 1.1% false negatives. Probabilistic sensitivity analysis showed that this approach is 100% cost-effective using the conventional benchmark for cost-effective treatments in the NHS of between £20 000 and £30 000 per QALY gained. Conclusion: Cascade testing of relatives of patients with DFH and PFH is cost-effective when using a combination of DNA testing for known family mutations and LDL-cholesterol levels in the remaining families. The approach is more cost-effective than current primary prevention screening strategies.


Hunter R.F.,Queen's University of Belfast | De Silva D.,Evidence Center | Reynolds V.,Intelligent Health Ltd | Bird W.,Intelligent Health Ltd | Fox K.R.,University of Bristol
BMC Research Notes | Year: 2015

Background: Active travel to school can be an important contributor to the total physical activity of children but levels have declined and more novel approaches are required to stimulate this as an habitual behaviour. The aim of this mixed methods study was to investigate the feasibility of an international walk to school competition supported by novel swipecard technology to increase children's walking to/from school. Methods: Children aged 9-13 years old participated in an international walk to school competition to win points for themselves, their school and their country over a 4-week period. Walks to and 1from school were recorded using swipecard technology and a bespoke website. For each point earned by participants, 1 pence (£0.01) was donated to the charity of the school's choice. The primary outcome was number of walks to/from school objectively recorded using the swipecard tracking system over the intervention period. Other measures included attitudes towards walking collected at baseline and week 4 (post-intervention). A qualitative sub-study involving focus groups with children, parents and teachers provided further insight. Results: A total of 3817 children (mean age 11.5 ± SD 0.7) from 12 schools in three cities (London and Reading, England and Vancouver, Canada) took part in the intervention, representing a 95% intervention participation rate. Results show a gradual decline in the average number of children walking to and from school over the 4-week period (week 1 mean 29% ± SD2.5; week 2 mean 18% ± SD3.6; week 3 mean 14% ± SD4.0; week 4 mean 12% ± SD1.1). Post intervention, 97% of children felt that walking to school helped them stay healthy, feel happy (81%) and stay alert in class (76%). These results are supported by qualitative findings from children, parents and teachers. Key areas for improvement include the need to incorporate strategies for maintenance of behaviour change into the intervention and also to adopt novel methods of data collection to increase follow-up rates. Conclusions: This mixed methods study suggests that an international walk to school competition using innovative technology can be feasibly implemented and offers a novel way of engaging schools and motivating children to walk to school. © 2015 Hunter et al.; licensee BioMed Central.


Panesar S.S.,Baylor College of Medicine | Desilva D.,Evidence Center | Carson-Stevens A.,University of Cardiff | Cresswell K.M.,University of Edinburgh | And 8 more authors.
BMJ Quality and Safety | Year: 2016

Importance Improving patient safety is at the forefront of policy and practice. While considerable progress has been made in understanding the frequency, causes and consequences of error in hospitals, less is known about the safety of primary care. Objective We investigated how often patient safety incidents occur in primary care and how often these were associated with patient harm. Evidence review We searched 18 databases and contacted international experts to identify published and unpublished studies available between 1 January 1980 and 31 July 2014. Patient safety incidents of any type were eligible. Eligible studies were critically appraised using validated instruments and data were descriptively and narratively synthesised. Findings Nine systematic reviews and 100 primary studies were included. Studies reported between <1 and 24 patient safety incidents per 100 consultations. The median from population-based record review studies was 2-3 incidents for every 100 consultations/records reviewed. It was estimated that around 4% of these incidents may be associated with severe harm, defined as significantly impacting on a patient's well-being, including long-term physical or psychological issues or death (range <1% to 44% of incidents). Incidents relating to diagnosis and prescribing were most likely to result in severe harm. Conclusions and relevance Millions of people throughout the world use primary care services on any given day. This review suggests that safety incidents are relatively common, but most do not result in serious harm that reaches the patient. Diagnostic and prescribing incidents are the most likely to result in avoidable harm. Systematic review registration This systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42012002304).


Sharma V.,Royal Infirmary | Sharma V.,University of Aberdeen | Sharma V.,Evidence Center | Davey J.G.N.,Royal Infirmary | And 2 more authors.
Histopathology | Year: 2013

Aims: Cancer datasets drive report quality, but require more work to inform compliant reports. The aim of this study was to correlate the number of words with measures of quality, to examine the impact of the drive for improved quality on the workload of histopathology reporting over time. Methods and results: We examined the first 10 reports of colon, breast, renal, lung and ovarian carcinoma, melanoma resection, nodal lymphoma appendicitis and seborrhoeic keratosis (SK) issued in 1991, 2001 and 2011. Correlations were analysed using Pearson's partial correlation coefficients. Word count increased significantly over time for most specimen types examined. Word count almost always correlated with units of information, indicating that the word count was a good measure of the amount of information contained within the reports; this correlation was preserved following correction for the effect of time. A good correlation with compliance with cancer datasets was also observed, but was weakened or lost following correction for the increase in word count and units of information that occurred between time points. Conclusions: These data indicate that word count could potentially be used as a measure of information content if its integrity and usefulness are continuously validated. Further prospective studies are required to assess and validate this approach. © 2013 John Wiley and Sons Ltd.


Gauld R.,University of Otago | Burgers J.,Guideline | Dobrow M.,University of Toronto | Luxford K.,Clinical Excellence Commission | And 3 more authors.
International Journal of Clinical Practice | Year: 2012

Healthcare system performance improvement is on the policy agenda of governments, healthcare funders and providers across the high-income world. Given this, we sought to assess the extent to which policy makers in our respective countries were promoting policy areas known to be associated with healthcare system improvement, namely quality improvement, information technology and primary care. This article reports our findings. © 2012 Blackwell Publishing Ltd.


PubMed | Child Health Epidemiology Unit, Trinity College Dublin, Dublin City University, University of California at Berkeley and 4 more.
Type: | Journal: BMC medical genetics | Year: 2015

Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.Replication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.Of the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.We report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis.

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