Jonathan Belsey

A method of identifying and correcting miscoding, misclassification and misdiagnosis in diabetes: a pilot and validation study of routinely collected data

Diabet. Med. 27, 203–209 (2010)

Meta-analysis: efficacy of small bowel preparation for small bowel video capsule endoscopy.

Abstract Objective: It is unclear whether small bowel visibility in video capsule endoscopy (VCE) is enhanced by the use of bowel preparation in addition to pre-procedural fasting. The objective of this study was to clarify this issue by means of a systematic review of the literature and meta-analysis. Methods: Randomised controlled trials comparing the use of laxative bowel preparation with fasting alone were identified using a literature search. Categorical measures of treatment efficacy were extracted from qualifying studies and pooled using random-effects meta-analyses. Primary analysis compared any bowel preparation with fasting alone; subsidiary analyses assessed diagnostic yield and results for each regimen. Results: Eight studies were identified, using either polyethylene glycol (PEG) or sodium phosphate (NaP) based regimens. No qualifying studies were identified using other laxatives. Study quality was sufficiently high to warrant meta-analysis. Use of any form of bowel preparation yielded significantly better visibility than fasting alone (OR = 2.31; 95% CI = 1.46–3.63; p < 0.0001). Similar results were seen for diagnostic yield (OR = 1.88; 95% CI = 1.24–2.84; p = 0.023). When sub-analysed according to the treatment used, PEG-based regimens showed benefit (OR = 3.11; 95% CI = 1.96–4.94; p < 0.0001), while NaP-based regimens yielded no significant difference from fasting alone (OR = 1.32; 95% CI = 0.59–2.96; p < 0.0001). Limitations: The study did not consider results from retrospective studies, nor those which did not give a categorical measure of efficacy. The impact of prokinetic and other adjunctive treatments was not considered. The results are only relevant to the most commonly used video capsule, as data for newer alternative devices have not yet been published. Conclusion: Based on the results of this analysis, the use of bowel preparation alongside fasting is recommended for VCE. PEG-based regimens offer a clear advantage in these patients, while the currently available evidence base does not support the use of NaP. For VCE, lower volume PEG appears to be as efficacious as higher volumes traditionally used for colonoscopy preparation.

Consensus guidelines for the use of bowel preparation prior to colonic diagnostic procedures: colonoscopy and small bowel video capsule endoscopy

Abstract Background: Adequate bowel preparation prior to colonic diagnostic procedures is essential to ensure adequate visualisation. Scope: This consensus aims to provide guidance as to the appropriate use of bowel preparation for a range of defined clinical circumstances. A consensus group from across Europe was convened and met to discuss appropriate bowel preparation. The use of polyethylene glycol (PEG), sodium picosulphate and sodium phosphate (NaP), together with other agents, prokinetics and simethicone, in colonoscopy and small bowel video capsule endoscopy were considered. A systematic review of the literature was carried out and additional unpublished data was obtained from the members of the consensus group where required. Recommendations were graded according to the level of evidence. Findings: PEG-based regimens are recommended first line for both procedures, since their use is supported by good efficacy and safety data. Sodium-picosulphate-based regimens are recommended second line as their cleansing efficacy appears less than PEG-based regimens. NaP is not recommended for bowel cleansing due to the potential for renal damage and other adverse events. However, the use of NaP is acceptable in patients in whom PEG or sodium picosulphate is ineffective or not tolerated. NaP should not be used in patients with chronic kidney disease, pre-existing electrolyte disturbances, congestive heart failure, cirrhosis or a history of hypertension. The timing of the dose, dietary restrictions, use in special patient groups and recording of the quality of bowel preparation are also considered for patients undergoing colonoscopy. During the development of the guidelines the European Society of Gastrointestinal Endoscopy (ESGE) issued guidance on bowel preparation for colonoscopy. The ESGE guidelines and these consensus guidelines share many recommendations; differences between the guidelines are reviewed. Conclusion: The use of bowel preparation should be tailored to the individual patient and their specific clinical circumstances.

Validation of the Harefield Cleansing Scale: a tool for the evaluation of bowel cleansing quality in both research and clinical practice

BACKGROUND Variations in bowel cleansing quality before colonoscopy can cause confounding of results within clinical trials and inappropriate treatment decisions in clinical practice. A new tool-the Harefield Cleaning Scale-has been developed, which addresses the limitations of existing scales. OBJECTIVE Validation exercise for the new cleansing scale. DESIGN Retrospective validation study. SETTING Various colonoscopy units in France. PATIENTS Patients who had a total of 337 colonoscopies recorded. INTERVENTION Video-recorded colonoscopy. MAIN OUTCOME MEASUREMENTS Comparisons of 2 scoring systems to assess direct correlation, interrater reliability, internal consistency, and test-retest reliability, based on assessment of video recordings from 337 colonoscopies. RESULTS Correlation analysis for expert scores by using the 2 scales yielded a Spearman correlation coefficient of 0.833. Similarly, the comparison of the segmental sum score revealed a Spearman correlation coefficient of -0.778. Cross-tabulation for successful colon cleansing was 92.88% versus unsuccessful colon cleansing in 7.12%. Reliability assessment indicated an acceptable internal consistency with a Cronbach alpha coefficient of 0.81. Test-retest reliability demonstrated an overall agreement of 0.639 (kappa statistic). Receiver operating characteristic analysis versus Aronchick Scale scores yielded an area under the curve of 0.945, with sensitivity of 99% and specificity of 83% at the optimum score cut-off point. LIMITATIONS Test-retest reliability was assessed by using a different patient population to the other measures. There were insufficient patient numbers to assess performance by using adenoma detection rate. CONCLUSION This validation analysis has demonstrated that the Harefield Cleansing Scale is a robust, reliable, and consistent tool that has the potential to improve the effective standardization of bowel preparation assessment in both clinical and research practice.

Cost effectiveness of oral triptan therapy: a trans-national comparison based on a meta-analysis of randomised controlled trials

Objective: The objective of this study was to appraise the relative cost effectiveness of oral triptan therapy in the management of acute migraine, comparing the results obtained using drug cost data from six different countries, USA, UK, Canada, Germany, Italy and The Netherlands. Method: A meta-analysis of randomised placebo controlled trials of single dose oral triptans was carried out in order to calculate aggregate Numbers Needed to Treat (NNT) for each triptan and dose. Cost effectiveness ratios were then derived for each treatment by applying mean drug acquisition costs for each country to these NNTs. Using a graphical plot for each country, incremental cost effectiveness comparisons were then made versus sumatriptan 100mg, the most commonly used oral triptan. Results: When analysed in terms of 2-h pain free outcomes, rizatriptan 10mg and eletriptan 40 and 80 mg were the most effective oral triptans. Rizatriptan 10mg has the most advantageous absolute cost effectiveness ratio in all six countries studied, although levels of statistical significance compared to other agents varied from one country to another. When compared to sumatriptan 100mg, rizatriptan 10mg and eletriptan 40 mg are most consistently the cost effective treatment choices, both being cost dominant in five out of six countries studied. Conclusions: There are systematic differences in triptan efficacy that have an impact on treatment choice. Differences in pricing structure between countries mean that hierarchies of cost effectiveness will vary. Country-specific data should therefore be examined before defining treatment strategies.

Disparities in testing for renal function in UK primary care: cross-sectional study.

BACKGROUND In the UK, explicit quality standards for chronic disease management, including for diabetes and chronic kidney disease (CKD), are set out National Service Frameworks and pay-for-performance indicators. These conditions are common with a prevalence of 4% and 5.4%, respectively. CKD is largely asymptomatic, detected following renal function testing and important because associated with increased mortality and morbidity, especially in people with diabetes and proteinuria. OBJECTIVES To investigate who has their renal function tested and any association with age, sex, ethnicity and diabetes. METHOD A cross-sectional survey in a primary care research network in south-west London (n = 220 721). The following data were extracted from routine data: age, gender, ethnicity, latest serum creatinine, diagnosis of diabetes and recording of proteinuria. We used logistic regression to explore any association in testing for CKD. RESULTS People (82.1%) with diabetes had renal function and proteinuria tested; the proportion was much smaller (<0.5%) in those without. Women were more likely to have a creatinine test than men (28% versus 24%, P < 0.05), but this association was modified by age, ethnicity and presence of diabetes. People >75 years and with diabetes were most likely to have been tested. Black [adjusted odds ratio (AOR) 2.1, 95% confidence interval (CI) 2.0-2.2] and south Asian (AOR 1.65, 95% CI 1.56-1.75) patients were more likely to be tested than whites. Those where ethnicity was not stated were the only group not tested more than whites. CONCLUSIONS Quality improvement initiatives and equity audits, which include CKD should take account of disparities in renal function testing.

Addressing the health technology assessment of biosimilar pharmaceuticals

Abstract The growing number of biosimilars presents challenges to regulatory and health technology assessment (HTA) systems. This paper illustrates these challenges by focusing on biosimilars used in the oncological setting. In particular, discordances between data required by regulatory and HTA authorities potentially deprive patients of effective treatments and hinder optimal resource allocation. Regulatory and HTA authorities need to harmonize requirements to foster the development and widespread use of biosimilars, which potentially release considerable resources. The authors believe that often-inappropriate methodology creates a very real chance that HTA authorities will reject some biosimilars. This would effectively extend patent protection and, in the absence of competitor pressure from biosimilars, result in prices remaining unnecessarily high. The authors propose that HTA organizations should accept pharmacokinetic and pharmacodynamic equivalence between the brand and the biosimilar as a proxy of biological comparability. HTA organizations should then adopt, in the absence of compelling reasons otherwise, cost-minimization analysis (CMA) as the basis of the cost-effectiveness deliberations. In the absence of adequate studies demonstrating equivalent efficacy, a prerequisite of CMA, HTA organizations should require threshold analysis. Once approved, biosimilar manufacturers and regulators should maintain rigorous pharmacovigilance to exclude immunoreactivity or other rare adverse events. Furthermore, cancer centres and trusts should regularly audit and publish the impact of biosimilars on clinical outcomes and resource use. When appropriate, regulatory and HTA authorities should demand revised cost-effectiveness analyses from biosimilar manufacturers. This approach would hone the accuracy of the cost-effectiveness analyses, protect patients and allow health services rapid access to low cost treatments.

Abnormal lipids in high-risk patients achieving cholesterol targets: a cross-sectional study of routinely collected UK general practice data

ABSTRACT Background and objectives: Lipid management in UK general practice targets the achievement of total cholesterol (TC) targets in high-risk individuals. Statins alone have a modest effect on non-LDL-C components of the lipid profile, leaving these patients at significant residual cardiovascular (CV) risk. Improving risk further would require the addition of non-statin therapies. This analysis explores what proportion of the UK population with cardiovascular disease (CVD) and TC levels at or below target may still be at risk because of residual dyslipidaemia. Methods: CV risk profiles were extracted from a research database of 602 222 patients from 98 UK general practices. Patients were categorised according to their prior CV history and use of statins. Mean values and proportions achieving treatment targets were assessed for TC, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and triglycerides (TG). Results: In all, 48 499 patients with pre-existing CVD or diabetes were identified. 73% of statin-treated patients and 63% of untreated patients had a TC ≤ 5 mmol/L. 28.6% of patients treated to a TC target had LDL-C > 3 mmol/L. Amongst those with both TC and LDL-C treated to target, 22.5% had low HDL-C and 37.2% had high triglyceride (TG). Within this group, more women than men had abnormal HDL-C (25.4 vs. 20.7% p < 0.0001). Patients with diabetes were more likely than non-diabetics to have abnormalities of both HDL-C (28.9 vs. 16.4% p < 0.0001) and triglyceride (44.9 vs. 29.5% p < 0.0001) despite normal TC and LDL-C. Conclusions: Around 60% of high-risk patients have residual dyslipidaemias despite achieving the Quality and Outcomes Framework (QOF) TC target. New patterns of treatment are required in order to extend lipid management beyond simple total cholesterol lowering.

Switch strategies in the management of hypertension: a cost minimisation analysis of angiotensin receptor blocker based regimen.

ABSTRACT Background and objective: Budgetary pressures within health care systems have led many health care providers to consider the switching of patients on long term antihypertensive medication to agents with the lowest acquisition price. The long term success of this strategy hinges on price differentials remaining stable, an assumption that may not be valid in drug classes where patent expiry times vary. The treatment of hypertension using angiotensin receptor blockers (ARBs) represents just such a case. The present study, therefore, modelled the 5-year cost consequences of treatment based on losartan, candesartan, valsartan and irbesartan, based on expected patent expiry dates. Methods: A Markov model was constructed, applying dose-specific blood-pressure lowering and costs to a cohort of uncontrolled mild–moderate hypertensive patients and assessing the anticipated cost of treatment over a 5 year period. A probabilistic approach was adopted to account for between-patient and between-treatment differences. Results: For both undiscounted and discounted models, a losartan-based regimen represents the least costly option of the four agents tested. Median (IQR) discounted expenditure per patient for each agent was: losartan: £506 (£441–£650), candesartan: £610 (£542–£766), valsartan: £809 (£796–£1078), irbesartan £696 (£694–£934). Conclusion: Switching hypertensive patients taking ARBs to the agent with the lowest current acquisition cost may yield only transient budgetary savings. Once patent expiry is taken into account, this model suggests that maintaining or switching patients to losartan would yield considerably greater savings over 5 years.

Reducing coronary risk by raising HDL-cholesterol: risk modelling the addition of nicotinic acid to existing therapy

ABSTRACT Background and objectives: Reduction in total cholesterol (TC) and LDL-cholesterol (LDL-C) forms one of the principal objectives of most cardiovascular secondary prevention strategies. Many patients being treated with statins, however, have significant residual dyslipidaemia, with many having suboptimal HDL-cholesterol (HDL-C) levels. The addition of nicotinic acid to a statin has been shown to improve this profile, although clinical outcome evidence is currently lacking. This study set out to model the impact of nicotinic acid therapy on cardiovascular risk in these patients, based on Framingham risk assessments on a cohort of patients drawn from UK general practitioner records. Methods: Cardiovascular risk profiles were extracted from a research database of 602 222 patients from 98 UK general practices. 23 262 statin-treated patients with established cardiovascular disease or diabetes were identified and their 4-year Framingham risk was estimated. Patients who had either TC or HDL-C outside the desirable range then had their lipid profile adjusted in accordance with the likely performance of nicotinic acid, and the Framingham risk was then re-assessed. Results: Baseline 4-year coronary risk in the group as a whole was 11.5% (95%CI: 11.4–11.6). After adjustment of the lipid profile, this was reduced to 9.7% (95%CI: 9.6–9.8), a reduction in risk of 15.9% (95%CI: 15.1–16.6). When modelling was limited to those with diabetes or an abnormal treated lipid profile, the magnitude of change was increased to 23–29% depending on sex and subgroup. Conclusions: Risk factor modelling suggests that raising HDL-C levels using nicotinic acid in statin-treated patients is likely to yield significant incremental clinical benefits. The results of clinical trials currently under way are awaited with interest.