Kevin Harris

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)

Audit-based education lowers systolic blood pressure in chronic kidney disease: the Quality Improvement in CKD (QICKD) trial results

Strict control of systolic blood pressure is known to slow progression of chronic kidney disease (CKD). Here we compared audit-based education (ABE) to guidelines and prompts or usual practice in lowering systolic blood pressure in people with CKD. This 2-year cluster randomized trial included 93 volunteer general practices randomized into three arms with 30 ABE practices, 32 with guidelines and prompts, and 31 usual practices. An intervention effect on the primary outcome, systolic blood pressure, was calculated using a multilevel model to predict changes after the intervention. The prevalence of CKD was 7.29% (41,183 of 565,016 patients) with all cardiovascular comorbidities more common in those with CKD. Our models showed that the systolic blood pressure was significantly lowered by 2.41u2009mmu2009Hg (CI 0.59–4.29u2009mmu2009Hg), in the ABE practices with an odds ratio of achieving at least a 5u2009mmu2009Hg reduction in systolic blood pressure of 1.24 (CI 1.05–1.45). Practices exposed to guidelines and prompts produced no significant change compared to usual practice. Male gender, ABE, ischemic heart disease, and congestive heart failure were independently associated with a greater lowering of systolic blood pressure but the converse applied to hypertension and age over 75 years. There were no reports of harm. Thus, individuals receiving ABE are more likely to achieve a lower blood pressure than those receiving only usual practice. The findings should be interpreted with caution due to the wide confidence intervals.

Quality-improvement strategies for the management of hypertension in chronic kidney disease in primary care: a systematic review.

BACKGROUNDnChronic kidney disease (CKD) is a relatively recently recognised condition. People with CKD are much more likely to suffer from cardiovascular events than progress to established renal failure. Controlling systolic blood pressure should slow the progression of disease and reduce mortality and morbidity. However, no systematic review has been conducted to explore the effectiveness of quality-improvement interventions to lower blood pressure in people with CKD.nnnAIMnTo assess the effectiveness of quality-improvement interventions to reduce systolic blood pressure in people with CKD in primary care, in order to reduce cardiovascular risk and slow the progression of renal disease.nnnMETHODnPapers were identified from the trial data bases of the Cochrane Effective Practice and Organisation of Care Group (EPOC) and Cochrane renal groups. In a three-round process, at least two investigators read the papers independently. Studies were initially excluded based on their abstracts, if these were not relevant to primary care. Next, full papers were read, and again excluded on relevance. Quantitative and, where this was not possible, qualitative analyses of the findings were performed.nnnRESULTSnThe selected studies were usually carried out on high-risk populations including ethnic minorities. The interventions were most often led by nurses or pharmacists. Three randomised trials showed a combined effect of a reduction in systolic blood pressure of 10.50 mmHg (95% confidence interval [CI] = 5.34 to 18.41 mmHg). One non-randomised study showed a reduction in systolic blood pressure of 9.30 mmHg (95% CI = 3.01 to 15.58 mmHg).nnnCONCLUSIONnQuality-improvement interventions can be effective in lowing blood pressure, and potentially in reducing cardiovascular risk and slowing progression in CKD. Trials are needed in low-risk populations to see if the same improvements can be achieved.

Association of anaemia in primary care patients with chronic kidney disease: cross sectional study of quality improvement in chronic kidney disease (QICKD) trial data

BackgroundAnaemia is a known risk factor for cardiovascular disease and treating anaemia in chronic kidney disease (CKD) may improve outcomes. However, little is known about the scope to improve primary care management of anaemia in CKD.MethodsAn observational study (Nu2009=u20091,099,292) with a nationally representative sample using anonymised routine primary care data from 127 Quality Improvement in CKD trial practices (ISRCTN5631023731). We explored variables associated with anaemia in CKD: eGFR, haemoglobin (Hb), mean corpuscular volume (MCV), iron status, cardiovascular comorbidities, and use of therapy which associated with gastrointestinal bleeding, oral iron and deprivation score. We developed a linear regression model to identify variables amenable to improved primary care management.ResultsThe prevalence of Stage 3–5 CKD was 6.76%. Hb was lower in CKD (13.2 g/dl) than without (13.7 g/dl). 22.2% of people with CKD had World Health Organization defined anaemia; 8.6% had Hbu2009≤u200911 g/dl; 3% Hbu2009≤u200910 g/dl; and 1% Hbu2009≤u20099 g/dl. Normocytic anaemia was present in 80.5% with Hbu2009≤u200911; 72.7% with Hbu2009≤u200910 g/dl; and 67.6% with Hbu2009≤u20099 g/dl; microcytic anaemia in 13.4% with Hbu2009≤u200911 g/dl; 20.8% with Hbu2009≤u200910 g/dl; and 24.9% where Hbu2009≤u20099 g/dl. 82.7% of people with microcytic and 58.8% with normocytic anaemia (Hbu2009≤u200911 g/dl) had a low ferritin (<100ug/mL). Hypertension (67.2% vs. 54%) and diabetes (30.7% vs. 15.4%) were more prevalent in CKD and anaemia; 61% had been prescribed aspirin; 73% non-steroidal anti-inflammatory drugs (NSAIDs); 14.1% warfarin 12.4% clopidogrel; and 53.1% aspirin and NSAID. 56.3% of people with CKD and anaemia had been prescribed oral iron. The main limitations of the study are that routine data are inevitably incomplete and definitions of anaemia have not been standardised.ConclusionsMedication review is needed in people with CKD and anaemia prior to considering erythropoietin or parenteral iron. Iron stores may be depleted in over >60% of people with normocytic anaemia. Prescribing oral iron has not corrected anaemia.

Confidence and quality in managing CKD compared with other cardiovascular diseases and diabetes mellitus: a linked study of questionnaire and routine primary care data

BackgroundMuch of chronic disease is managed in primary care and chronic kidney disease (CKD) is a recent addition. We are conducting a cluster randomised study of quality improvement interventions in CKD (QICKD) - Clinical Trials Registration: ISRCTN56023731. CKD registers have a lower than expected prevalence and an initial focus group study suggested variable levels of confidence in managing CKD.Our objective is to compare practitioner confidence and achievement of quality indicators for CKD with hypertension and diabetes.MethodWe validated a new questionnaire to test confidence. We compared confidence with achievement of pay-for-performance indicators (P4P) and implementation of evidence-based guidance. We achieved a 74% (148/201) response rate.Results87% (n = 128) of respondents are confident in managing hypertension (HT) compared with 59% (n = 87) in managing HT in CKD (HT+CKD); and with 61% (n = 90) in HT, CKD and diabetes (CKD+HT+DM).85.2% (P4P) and 62.5% (National targets) of patients with hypertension are at target; in patients with HT and CKD 65.1% and 53.3%; in patients with HT, CKD and DM 67.8% and 29.6%.Confidence in managing proteinuria in CKD is low (42%, n = 62). 87% of respondents knew BP treatment thresholds in CKD, but only 53% when proteinuria is factored in. Male GPs, younger (< 35 yrs), and older (> 54 yrs) clinicians are more confident than females and 35 to 54 year olds in managing CKD.84% of patients with hypertension treated with angiotensin modulating drugs achieve achieved P4P targets compared to 67% of patients with CKD.ConclusionsPractitioners are less likely to achieve management targets where their confidence is low.

The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease - prospective longitudinal study in a multiethnic population

BackgroundUncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations.Methods/designIohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components:1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30xa0mg/mmol) will comprise 20-30% of the study cohort.2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3) A biological variability study to establish reference change values for reference and test measures.4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline.DiscussionThe eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice.Trial registrationISRCTN42955626.

Association of chronic kidney disease (CKD) and failure to monitor renal function with adverse outcomes in people with diabetes: a primary care cohort study

BackgroundChronic kidney disease (CKD) is a known risk factor for cardiovascular events and all-cause mortality. We investigate the relationship between CKD stage, proteinuria, hypertension and these adverse outcomes in the people with diabetes. We also study the outcomes of people who did not have monitoring of renal function.MethodsA cohort of people with type 1 and 2 diabetes (Nu2009=u200935,502) from the Quality Improvement in Chronic Kidney Disease (QICKD) cluster randomised trial was followed up over 2.5xa0years. A composite of all-cause mortality, cardiovascular events, and end stage renal failure comprised the outcome measure. A multilevel logistic regression model was used to determine correlates with this outcome. Known cardiovascular and renal risk factors were adjusted for.ResultsProteinuria and reduced estimated glomerular filtration rate (eGFR) were independently associated with adverse outcomes in people with diabetes. People with an eGFR <60xa0ml/min, proteinuria, and hypertension have the greatest odds ratio (OR) of adverse outcome; 1.58 (95% CI 1.36-1.83). Renal function was not monitored in 4460 (12.6%) people. Unmonitored renal function was associated with adverse events; OR 1.35 (95% CI 1.13-1.63) in people with hypertension and OR 1.32 (95% CI 1.07-1.64) in those without.ConclusionsProteinuria, eGFRu2009<u200960xa0ml/min, and failure to monitor renal function are associated with cardiovascular and renal events and mortality in people with diabetes.

Trends and transient change in end-digit preference in blood pressure recording: studies of sequential and longitudinal collected primary care data.

Background:u2002 End‐digit preference (EDP) is a known cause of inaccurate BP recording. Distortion has been reported around pay‐for‐performance (P4P) indicators.

Effect of angiotensin type 2 receptor over-expression on the rat mesangial cell fibrotic phenotype: effect of gender

Background and aim: The protective role of angiotensin type 2 receptors (AT2-Rs) is still controversial. As AT2-Rs are minimally expressed in adult tissues the aim of the current study was to over-express AT2-Rs in rat mesangial cells in order to ascertain their potential role in modulating renal scarring. Methods: Male and female mesangial cells were transiently transfected with AT2-R or control vector then ‘injured’ with macrophage-conditioned medium (MCM). Culture supernatants and extracted RNA were analysed for evidence of an anti-fibrotic phenotype. Results: Supernatant fibronectin levels in female mesangial cells treated with MCM were reduced in AT2-R transfected cells (p < 0.001) compared to controls. AT2-R transfected male cells showed a trend towards lower constitutive fibronectin levels. There was no effect of AT2-R transfection on TGF-β or TNF-α secretion; however, IL-1β levels were reduced in male cells treated with MCM. RT-PCR demonstrated that constitutive kallikrein mRNA levels were suppressed in both male and female AT2-R transfected cells. Bradykinin receptors (BkB2-R and BkB1-R) were unaffected in female cells although the BkB1-R was upregulated in male cells treated with MCM. Conclusion: This data provides a case for AT2 receptors playing a protective role in rat mesangial cells independent of the effects of blood pressure control.