To develop and assess the validity of the Referee Training Activity Questionnaire (RTAQ), a systematic process was employed: 1) item generation; 2) assessments of content and face validity; and 3) ...assessments of criterion validity. In stage 1, items were generated following semi-structured interviews with an expert panel (n = 8). Following content analyses, the RTAQ was developed and comprised 3 primary sections (12 sub-sections) assessing: 1) attributes perceived to underpin soccer officiating performance; 2) general training information; and 3) specific training practices. In stage 2, the preliminary RTAQ was assessed for content and face validity by a sample of experts (n = 6). Based upon the content validity index (CVI), content validity was confirmed for 8 sub-sections (CVI ≥ 0.78) with 5 sub-sections being deemed invalid (CVI < 0.78). Various amendments were carried out in accordance with participant feedback. In stage 3, the RTAQ was completed by a cohort of officials (n = 25) who subsequently recorded a detailed training diary. Negligible mean biases, wide 95% LOA, and significant Pearson correlations were observed between the RTAQ and training diaries for most training activities, suggesting the RTAQ holds promise as a useful and effective alternative of acquiring insight into the training practices of soccer officials.
leucine-rich repeat structure Bella, J; Hindle, K. L; McEwan, P. A ...
Cellular and molecular life sciences : CMLS,
08/2008, Letnik:
65, Številka:
15
Journal Article
Recenzirano
The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of ...two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.
Aims
Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment‐related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study ...assessed the health economic value of maintained reductions in HbA1c, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.
Methods
The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life‐years and quality‐adjusted life‐years (QALYs) for individuals with Type 1 diabetes at different baseline HbA1c, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per‐person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.
Results
Modelled subjects with an HbA1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per‐person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per‐person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per‐person net monetary benefit, and up to £197 for the avoidance of one non‐severe hypoglyceamic event.
Conclusions
Maintained reductions in HbA1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.
What's new?
This study demonstrated the burden of inadequate Type 1 diabetes management, and quantified the value of reducing HbA1c, weight and hypoglycaemia frequency among the UK Type 1 diabetes population.
Significant cost savings, quality‐adjusted life‐year gains and net monetary benefit were predicted in those who achieve HbA1c targets recommended in national guidelines; nevertheless, any incremental improvement in glycaemic management substantially reduced the burden of Type 1 diabetes mellitus on individuals and healthcare systems.
Given the influence of weight and hypoglycaemia on health economic outcomes, these factors should also be key considerations when assessing the value of Type 1 diabetes technologies.
Background. The UK National Health Service (NHS) will fund renal services using Payment by Results (PbR), from 2009. Central to the success of PbR will be the creation of tariffs that reflect the ...true cost of medical services. We have therefore estimated the cost of different dialysis modalities in the Cardiff and Vale NHS Trust and six other hospitals in the UK. Methods. We used semi-structured interviews with nephrologists, head nurses and business managers to identify the steps involved in delivering the different dialysis modalities. We assigned costs to these using published figures or suppliers’ published price lists. The study used mixed costing methods. Dialysis costs were estimated by a combination of microcosting and a top-down approach. Where we did not have access to detailed accounts, we applied values for Cardiff. Results. The most efficient modalities were automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD), the mean annual costs of which were £21 655 and £15 570, respectively. Hospital-based haemodialysis (HD) cost £35 023 per annum and satellite-unit-based HD cost £32 669. The cost of home-based HD was £20 764 per year (based on data from only one unit). The main cost drivers for PD were the costs of solutions and management of anaemia. For HD they were costs of disposables, nursing, the overheads associated with running the unit and management of anaemia. Conclusions. Renal tariffs for PbR need to reflect the true cost of dialysis provision if choices about modalities are not to be influenced by erroneous estimates of cost. Knowledge of the true costs of modalities will also maximize the number of established renal failure patients treated by dialysis within the limited funds available from the NHS.
Type 2 diabetes mellitus (T2DM) is a chronic, progressive condition where the primary treatment goal is to maintain control of glycated haemoglobin (HbA1c). In order for healthcare decision makers to ...ensure patients receive the highest standard of care within the available budget, the clinical benefits of each treatment option must be balanced against the economic consequences. The aim of this study was to assess the cost-effectiveness of dapagliflozin, the first-in-class sodium-glucose co-transporter 2 (SGLT2) inhibitor, compared with a dipeptidyl peptidase-4 inhibitor (DPP-4i), when added to metformin for the treatment of patients with T2DM inadequately controlled on metformin alone.
The previously published and validated Cardiff diabetes model was used as the basis for this economic evaluation, with treatment effect parameters sourced from a systematic review and network meta-analysis. Costs, derived from a UK healthcare system perspective, and quality-adjusted life years (QALYs), were used to present the final outcome as an incremental cost-effectiveness ratio (ICER) over a lifetime horizon. Univariate and probabilistic sensitivity analyses (PSA) were carried out to assess uncertainty in the model results.
Compared with DPP-4i, dapagliflozin was associated with a mean incremental benefit of 0.032 QALYs (95% confidence interval CI: -0.022, 0.140) and with an incremental cost of £216 (95% CI: £-258, £795). This resulted in an ICER point estimate of £6,761 per QALY gained. Sensitivity analysis determined incremental costs to be insensitive to variation in most parameters, with only the treatment effect on weight having a notable impact on the incremental QALYs; however, there were no scenarios which raised the ICER above £15,000 per QALY. The PSA estimated that dapagliflozin had an 85% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained.
Dapagliflozin in combination with metformin was shown to be a cost-effective treatment option from a UK healthcare system perspective for patients with T2DM who are inadequately controlled on metformin alone.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Economic evaluations of new diabetes therapies rely heavily upon the UK Prospective Diabetes Study (UKPDS) equations for prediction of cardiovascular events; however, concerns persist ...regarding their relevance to current clinical practice and appropriate use in populations other than newly diagnosed patients. This study refits the UKPDS 68 event equations, using contemporary data describing low- and intermediate-risk patients.
Research Design and Methods
Anonymized patient data describing demographics, risk factors and incidence of cardiovascular and microvascular events were extracted from The Health Improvement Network (THIN) database over the 10-year period from 1 January 2000 to 31 December 2009. Following multiple imputation of missing values, accelerated failure-time Weibull regression equations were refitted to produce new coefficients for each risk group. Discriminatory performance was assessed and compared with both UKPDS 68 and UKPDS 82 risk equations, and the implication of coefficient choice within an economic evaluation was assessed using the Cardiff type 2 diabetes model.
Results
When applied to patient-level data, the three sets of coefficients (UKPDS, THIN low-risk and intermediate-risk) lead to fairly consistent predictions of the 5-year risk of events. Exceptions include lower predicted rates of myocardial infarction and higher rates of ischaemic heart disease, congestive heart failure and end-stage renal disease with both sets of revised THIN coefficients compared with UKPDS. Over a modelled lifetime, the coefficients derived from the low-risk data predict fewer total cardiovascular events compared with UKPDS, while those from the intermediate-risk data predict a greater number. The areas under the receiver–operating characteristic curves demonstrated a marginal improvement in the discriminatory performance of the refitted equations. The incremental cost-effectiveness ratio associated with dapagliflozin versus sulphonylurea in addition to metformin changed from £7,708 to £7,519 and £6,906 per QALY gained, using the THIN intermediate- and low-risk coefficients, respectively.
Conclusion
The results suggest that while the UKPDS equations perform best in newly diagnosed patients, they may overpredict the lifetime risk in this group and underpredict it in patients with more advanced diabetes. Implementation of the revised coefficients will result in different absolute numbers of predicted diabetes-related events; however, they are not expected to significantly affect the conclusions of economic modelling.
Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment-related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed ...the health economic value of maintained reductions in HbA
, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.
The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life-years and quality-adjusted life-years (QALYs) for individuals with Type 1 diabetes at different baseline HbA
, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per-person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.
Modelled subjects with an HbA
of 86 mmol/mol (10.0%) were associated with discounted lifetime per-person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA
of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA
of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per-person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per-person net monetary benefit, and up to £197 for the avoidance of one non-severe hypoglyceamic event.
Maintained reductions in HbA
significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.
Objective: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0–3.0 and to explore the ...relation between achieved INR control and clinical outcomes. Design: Record linkage study of routine activity records and INR measurements. Setting: Cardiff and the Vale of Glamorgan, South Wales, UK. Participants: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements. Main outcome measures: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring. Results: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range. Conclusions: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.
POCKETT R.D., CASTELLANO D., MCEWAN P., OGLESBY A., BARBER B.L. & CHUNG K. (2010) European Journal of Cancer Care19, 755–760 The hospital burden of disease associated with bone metastases and ...skeletal‐related events in patients with breast cancer, lung cancer, or prostate cancer in Spain
Metastatic bone disease (MBD) is the most common cause of cancer pain and of serious skeletal‐related events (SREs) reducing quality of life. Management of MBD involves a multimodal approach aimed at delaying the first SRE and reducing subsequent SREs. The objective of the study was to characterise the hospital burden of disease associated with MBD and SREs following breast, lung and prostate cancer in Spain. Patients admitted into a participating hospital, between 1 January 2003 and 31 December 2003, with one of the required cancers were identified and selected for inclusion into the study. The index admission to hospital, incidence of patients admitted and hospital length of stay were analysed. There were 28 162 patients identified with breast, lung and prostate cancer. The 3 year incidence rates of hospital admission due to MBD were 95 per 1000 for breast cancer, 156 per 1000 for lung cancer and 163 per 1000 for prostate cancer. For patients admitted following an SRE, the incidence rates were 211 per 1000 for breast cancer, 260 per 1000 for lung cancer and 150 per 1000 for prostate cancer. This study has shown that cancer patients consume progressively more hospital resources as MBD and subsequent SREs develop.
Aims
To assess the cost‐effectiveness of dapagliflozin, a sodium–glucose co‐transporter–2 (SGLT–2) inhibitor, compared with a sulfonylurea, when added to metformin for treatment of UK people with ...Type 2 diabetes mellitus inadequately controlled on metformin alone.
Methods
Clinical inputs sourced from a head‐to‐head randomized controlled trial (RCT) informed the Cardiff diabetes decision model. Risk equations developed from the United Kingdom Prospective Diabetes Study (UKPDS) were used in conjunction with the clinical inputs to predict disease progression and the incidence of micro‐ and macrovascular complications over a lifetime horizon. Cost and utility data were generated to present the incremental cost‐effectiveness ratio (ICER) for both treatment arms, and sensitivity and scenario analyses were conducted to assess the impact of uncertainty on the final model results.
Results
The dapagliflozin treatment arm was associated with a mean incremental benefit of 0.467 quality‐adjusted life years (QALYs) 95% confidence interval (CI): 0.420; 0.665, with an incremental cost of £1246 (95% CI: £613; £1637). This resulted in an ICER point estimate of £2671 per QALY gained. Incremental costs were shown to be insensitive to parameter variation, with only treatment‐related weight change having a significant impact on the incremental QALYs. Probabilistic sensitivity analysis determined that dapagliflozin had a 100% probability of being cost‐effective at a willingness‐to‐pay threshold of £20 000 per QALY.
Conclusions
Dapagliflozin in combination with metformin was shown to be a cost‐effective treatment option compared with sulfonylurea from a UK healthcare perspective for people with Type 2 diabetes mellitus who are inadequately controlled on metformin monotherapy.
What's new?
Dapagliflozin is a selective sodium–glucose co–transporter–2 (SGLT‐2) inhibitor licensed in the European Union (EU) for use in people with Type 2 diabetes mellitus when diet and exercise plus metformin fail to achieve glycaemic control.
Sulfonylureas are commonly prescribed as second‐line agents and therefore are relevant comparators for dapagliflozin.
This is the first health economic model to assess the cost‐effectiveness of dapagliflozin versus sulfonylureas as an add‐on to metformin in the treatment of Type 2 diabetes mellitus.
Dapagliflozin in combination with metformin was shown to be a cost‐effective treatment option compared with sulfonylurea added on to metformin from a United Kingdom (UK) healthcare perspective.
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