Rajnikant Mehta

A real-time electronic alert to improve detection of acute kidney injury in a large teaching hospital

BACKGROUND Acute kidney injury (AKI) is a common and serious problem in hospitalized patients. Early detection is critical for optimal management but in practice is currently inadequate. To improve outcomes in AKI, development of early detection tools is essential. METHODS We developed an automated real-time electronic alert system employing algorithms which combined internationally recognized criteria for AKI [Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN)]. All adult patients admitted to Nottingham University Hospitals were included. Where a patients serum creatinine increased sufficiently to define AKI, an electronic alert was issued, with referral to an intranet-based AKI guideline. Incidence of AKI Stages 1-3, in-hospital mortality, length of stay and distribution between specialties is reported. RESULTS Between May 2011 and April 2013, 59,921 alerts resulted from 22,754 admission episodes, associated with 15,550 different patients. Overall incidence of AKI for inpatients was 10.7%. Highest AKI stage reached was: Stage 1 in 7.2%, Stage 2 in 2.2% and Stage 3 in 1.3%. In-hospital mortality for all AKI stages was 18.5% and increased with AKI stage (12.5, 28.4, 35.7% for Stages 1, 2 and 3 AKI, respectively). Median length of stay was 9 days for all AKI. CONCLUSIONS This is the first fully automated real time AKI e-alert system, using AKIN and RIFLE criteria, to be introduced to a large National Health Service hospital. It has provided one of the biggest single-centre AKI datasets in the UK revealing mortality rates which increase with AKI stage. It is likely to have improved detection and management of AKI. The methodology is transferable to other acute hospitals.

The prevalence and nature of prescribing and monitoring errors in English general practice: a retrospective case note review

BACKGROUND Relatively little is known about prescribing errors in general practice, or the factors associated with error. AIM To determine the prevalence and nature of prescribing and monitoring errors in general practices in England. DESIGN AND SETTING Retrospective case-note review of unique medication items prescribed over a 12-month period to a 2% random sample of patients. Fifteen general practices across three primary care trusts in England. METHOD A total of 6048 unique prescription items prescribed over the previous 12 months for 1777 patients were examined. The data were analysed by mixed effects logistic regression. The main outcome measures were prevalence of prescribing and monitoring errors, and severity of errors, using validated definitions. RESULTS Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all prescription items (95% confidence interval [CI] = 4.4% to 5.5%). The vast majority of errors were of mild to moderate severity, with 0.2% (11/6048) of items having a severe error. After adjusting for covariates, patient-related factors associated with an increased risk of prescribing and/or monitoring errors were: age <15 years (odds ratio [OR] = 1.87, 95% CI = 1.19 to 2.94, P = 0.006) or >64 years (OR = 1.68, 95% CI = 1.04 to 2.73, P = 0.035), and higher numbers of unique medication items prescribed (OR = 1.16, 95% CI = 1.12 to 1.19, P<0.001). CONCLUSION Prescribing and monitoring errors are common in English general practice, although severe errors are unusual. Many factors increase the risk of error. Having identified the most common and important errors, and the factors associated with these, strategies to prevent future errors should be developed, based on the study findings.

Echocardiography‐based score to predict outcome after renal transplantation

Background: Given the high cardiac mortality of renal transplant recipients, identification of high-risk patients is important to offer appropriate treatment before transplantation. Aim: To determine patients with high mortality after renal transplantation despite selection according to current criteria. Methods: Preoperative parameters were collected from 203 renal transplant recipients over a follow-up time of 3.6 (1.9) years. The primary end point was all-cause mortality. Results: 22 deaths (11%) and 12 cardiac failures (6%) were observed. Non-survivors were older (p⩽0.001), had larger left ventricular end-systolic diameter (LVSD) (p⩽0.001) and end-diastolic diameter (p = 0.002), and lower ejection fraction (p⩽0.001). Left ventricular mass index (p = 0.001), maximal wall thickness (p = 0.006) and the proportion with mitral annular calcification (p = 0.001) were significantly higher in the non-survivors. The risk factors for ischaemic heart disease and exercise test data were not significantly different between the two groups. Four independent predictors of mortality after renal transplantation were identified: age ⩾50 years (p = 0.002), LVESD ⩾3.5 cm (p = 0.002), maximal wall thickness ⩾1.4 cm (p = 0.014) and mitral annular calcification (p = 0.036). The 5-year survival estimates for 0, 1, 2 and 3 prognostic factors were 96%, 86%, 69% and 38%, respectively. No patient had four prognostic factors. In patients ⩾50 years, the 5-year survival estimates for 0, 1 and 2 additional prognostic factors were 73%, 45% and 18%, respectively. Conclusion: In addition to selection according to current guidelines, age and three conventional echocardiography parameters may further improve risk stratification before renal transplantation.

Supporting adherence for people starting a new medication for a long-term condition through community pharmacies: a pragmatic randomised controlled trial of the New Medicine Service

Objective To examine the effectiveness of the New Medicine Service (NMS), a national community pharmacy service to support medicines-taking in people starting a new medicine for a long-term condition, compared with normal practice. Methods Pragmatic patient-level parallel randomised controlled trial, in 46 community pharmacies in England. Patients 1:1 block randomisation stratified by drug/disease group within each pharmacy. 504 participants (NMS: 251) aged 14 years and over, identified in the pharmacy on presentation of a prescription for asthma/chronic obstructive pulmonary disease, hypertension, type 2 diabetes or an anticoagulant/antiplatelet agent. NMS intervention: One consultation 7–14 days after presentation of prescription followed by another 14–21 days thereafter to identify problems with treatment and provide support if needed. Controls received normal practice. Adherence, defined as missing no doses without the advice of a medical professional in the previous 7 days, was assessed through patient self-report at 10 weeks. Intention-to-treat analysis was employed, with outcome adjusted for recruiting pharmacy, NMS disease category, age, sex and medication count. Cost to the National Health Service (NHS) was collected. Results At 10 weeks, 53 patients had withdrawn and 443 (85%) patients were contacted successfully by telephone. In the unadjusted analysis of 378 patients still taking the initial medicine, 61% (95% CI 54% to 67%) and 71% (95% CI 64% to 77%) patients were adherent in the normal practice and NMS arms, respectively (p=0.04 for difference). In the adjusted intention-to-treat analysis, the OR for increased adherence was 1.67 (95% CI 1.06 to 2.62; p=0.027) in favour of the NMS arm. There was a general trend to reduced NHS costs, albeit, statistically non-significant, for the NMS intervention: saving £21 (95% CI −£59 to £100, p=0.128) per patient. Conclusions The NMS significantly increased the proportion of patients adhering to their new medicine by about 10%, compared with normal practice. Trial registration numbers ClinicalTrials.gov trial reference number NCT01635361 (http://clinicaltrials.gov/ct2/show/NCT01635361). Current Controlled trials: trial reference number ISRCTN 23560818 (http://www.controlled-trials.com/ISRCTN23560818/; DOI 10.1186/ISRCTN23560818). UK Clinical Research Network (UKCRN) study 12494 (http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12494).

Risk factors associated with cerebrovascular recurrence in symptomatic carotid disease: a comparative study of carotid plaque morphology, microemboli assessment and the European Carotid Surgery Trial risk model.

Background The European Carotid Surgery Trial (ECST) risk model is a validated tool for predicting cerebrovascular risk in patients with symptomatic carotid disease. Carotid plaque hemorrhage as detected by MRI (MRIPH) and microembolic signals (MES) detected by transcranial Doppler (TCD) are 2 emerging modalities in assessing instability of the carotid plaque. The aim of this study was to assess the strength of association of MES and MRIPH with cerebrovascular recurrence in patients with symptomatic carotid artery disease in comparison with the ECST risk prediction model. Methods and Results One hundred and thirty‐four prospectively recruited patients (mean [SD]: age 72 [9.8] years, 33% female) with symptomatic severe (50% to 99%) carotid stenosis underwent preoperative TCD, MRI of the carotid arteries to assess MES, PH, and the ECST risk model. Patients were followed up until carotid endarterectomy, recurrent cerebral event, death, or study end. Event‐free survival analysis was done using backward conditional Cox regression analysis. Of the 123 patients who had both TCD and MRI, 82 (66.7%) demonstrated PH and 46 (37.4%) had MES. 37 (30.1%) cerebrovascular events (21 transient ischemic attacks, 6 amaurosis fugax, and 10 strokes) were observed. Both carotid PH (HR=8.68; 95% CI 2.66 to 28.40, P<0.001) as well as MES (HR=3.28; 95% CI 1.68 to 6.42, P=0.001) were associated with cerebrovascular event recurrence. Combining MES and MRIPH improved the strength of association (HR=0.74, 95% CI 0.65 to 0.83; P<0.001). The ECST risk model was not associated with recurrence (HR=0.86; 95% CI 0.45 to 1.65; P=0.65). Conclusions The presence of carotid plaque hemorrhage is better associated with recurrent cerebrovascular events in patients with symptomatic severe carotid stenosis than the presence of microembolic signals; combining MES and MRIPH, further improves the association while the ECST risk score was insignificant.

The effect of the electronic transmission of prescriptions on dispensing errors and prescription enhancements made in English community pharmacies: a naturalistic stepped wedge study

Objectives To compare prevalence and types of dispensing errors and pharmacists’ labelling enhancements, for prescriptions transmitted electronically versus paper prescriptions. Design Naturalistic stepped wedge study. Setting 15 English community pharmacies. Intervention Electronic transmission of prescriptions between prescriber and pharmacy. Main outcome measures Prevalence of labelling errors, content errors and labelling enhancements (beneficial additions to the instructions), as identified by researchers visiting each pharmacy. Results Overall, we identified labelling errors in 5.4% of 16 357 dispensed items, and content errors in 1.4%; enhancements were made for 13.6%. Pharmacists also edited the label for a further 21.9% of electronically transmitted items. Electronically transmitted prescriptions had a higher prevalence of labelling errors (7.4% of 3733 items) than other prescriptions (4.8% of 12 624); OR 1.46 (95% CI 1.21 to 1.76). There was no difference for content errors or enhancements. The increase in labelling errors was mainly accounted for by errors (mainly at one pharmacy) involving omission of the indication, where specified by the prescriber, from the label. A sensitivity analysis in which these cases (n=158) were not considered errors revealed no remaining difference between prescription types. Conclusions We identified a higher prevalence of labelling errors for items transmitted electronically, but this was predominantly accounted for by local practice in a single pharmacy, independent of prescription type. Community pharmacists made labelling enhancements to about one in seven dispensed items, whether electronically transmitted or not. Community pharmacists, prescribers, professional bodies and software providers should work together to agree how items should be dispensed and labelled to best reap the benefits of electronically transmitted prescriptions. Community pharmacists need to ensure their computer systems are promptly updated to help reduce errors.

The diagnostic and prognostic value of tissue Doppler imaging during dobutamine stress echocardiography in end-stage renal disease.

ObjectiveTo determine whether a quantitative measurement of peak systolic velocity (PSV) during dobutamine stress echocardiography (DSE) detects severe coronary artery disease (CAD) and predicts mortality in patients with end-stage renal disease. MethodsOne hundred and forty renal transplant candidates had DSE and coronary angiography. DSE analysis was performed using conventional visual wall motion assessment, longitudinal PSV, and combining the two modalities. Failure of PSV to rise by more than 50% predicted an ischemic response. Significant CAD was defined as luminal stenosis greater than 70%. ResultsThe number of positive DSE studies according to conventional, PSV, and combined criteria was 41 (30%), 42 (31%), and 46 (34%) respectively. Forty patients (29%) had significant CAD at angiography. The sensitivity, specificity, positive and negative predictive values for conventional DSE analysis were 84, 91, 86, and 90% respectively. The same values for PSV analysis were 86, 92, 86, and 91%, respectively. The same values for the combination of visual and PSV analysis were 88, 94, 87, and 92% respectively. The differences between the three methods were not statistically significant. Sensitivity for single-vessel CAD (P=0.05) and circumflex artery disease (P=0.05) diagnosis was higher with PSV compared with conventional DSE analysis. Failure of PSV to rise by more than 50% during DSE was associated with significantly increased mortality (P=0.001). ConclusionA quantitative interpretation of DSE, based on the percentage rise of PSV during stress, accurately detects CAD and predicts prognosis in end-stage renal disease.

Important differences in the durability of glycaemic response among second-line treatment options when added to metformin in type 2 diabetes: a retrospective cohort study

Abstract Importance There is limited information about the durability of glycaemic control when different oral glucose-lowering therapies (GLTs) are used as add-on treatments to metformin (MET) in patients with type 2 diabetes mellitus (T2DM). Objective To compare time to treatment failure between different classes of oral GLT when used as second line (add-on) treatments to MET monotherapy at HbA1c ≥ 7.5%. Design, setting and participants A retrospective cohort study on 20,070 patients who were newly treated with a sulphonylurea (SU), dipeptidyl-peptidase-4 (DPP-4) inhibitor or thiazolidinedione (TZD) following MET therapy failure (2007–2014). Patients’ data was sourced from UK General Practices via The Health Improvement Network (THIN) database. The risk of dual therapy failure was compared between three treatment groups: MET + SU (reference group, n = 15,508), MET + DPP-4 inhibitor (n = 3,080) and MET + TZD (n = 1,482). Follow-up was until treatment substitution or intensification with a 3rd GLT, or for up to 5 years (totalling 46,430 person-years). Propensity score weighting and Cox proportional hazard regression analyses were employed. Main outcomes and measures Risk of dual therapy failure was compared between treatment groups while adjusting for baseline covariates. Results Unadjusted survival analysis showed the incidence of dual therapy failure at 1 year was 15% with SU, 23% with DPP-4 inhibitor and 8% with TZD. Corresponding failure rates at 2 years were 26, 38 and 12%, respectively. Adjusted multivariate models showed that, compared to the SU group, adding a DPP-4 inhibitor was associated with an increased risk of treatment failure (adjusted hazard ratio, aHR, 1.58; 95% CI: 1.48–1.68), while adding a TZD was associated with a reduced hazard (aHR, 0.45; 95% CI: 0.41–0.50). Baseline parameters associated with an increased hazard of intensification included HbA1c, diabetes duration, gender, smoking status and the use of statins. Conclusions and relevance In routine clinical practice, adding a DPP-4 inhibitor to MET is associated with an increased, earlier requirement for treatment intensification compared to adding an SU or TZD. Adding a TZD to MET resulted in the most durable glycaemic response. Key messages The Agency for Healthcare Research and Quality has suggested that the durability of glycaemic response after treatment intensification is best investigated using well-designed long-term observational studies. In routine clinical practice, among patients with T2DM receiving a second line glucose lowering treatment as add-on to MET, the addition of a Thiazolidinediones is associated with the most durable glycaemic response, followed by a Sulfonylurea and then a DPP-4 inhibitor. Factors associated with earlier dual therapy failure included concomitant use of statin therapy, being female, a smoker, those with longer diabetes duration and higher baseline HbA1c levels. The addition of a Thiazolidinediones was associated with significant weight gain (1.8 kg, p < 0.001), while add-on DPP-4 inhibitor produced a significant weight reduction (−1.8 kg, p < 0.001). A very small reduction in body weight was observed with the SU (−0.2 kg, p < 0.001).

Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes

Objectives To analyse time to cardiovascular events and mortality in patients with type 2 diabetes (T2D) who received treatment intensification with insulin or a glucagon-like peptide-1 (GLP-1ar) analogue following dual therapy failure with metformin (MET) and sulphonylurea (SU). Methods A retrospective cohort study was conducted in 2003 patients who were newly treated with a GLP-1ar or insulin following dual therapy (MET+SU) failure between 2006 and 2014. Data were sourced from The Health Improvement Network database. Risks of major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke and all-cause mortality) were compared between MET+SU+insulin (N=1584) versus MET+SU+GLP-1ar (N=419). Follow-up was for 5 years (6614 person-years). Propensity score matching analysis and Cox proportional hazard models were employed. Results Mean age was 52.8±14.1 years. Overall, the number of MACE was 231 vs 11 for patients who added insulin versus GLP-1ar, respectively (44.5 vs 7.7 per 1000-person-years adjusted HR (aHR): 0.27; 95% CI 0.14 to 0.53; p<0.0001). Insulin was associated with significant increase in weight compared with GLP-1ar (1.78 vs −3.93 kg; p<0.0001) but haemoglobin A1c reduction was similar between both treatment groups (−1.29 vs −0.98; p=0.156). In a subgroup analysis of obese patients (body mass index >30 kg/m2) there were 84 vs 11 composite outcomes (38.6 vs 8.1 per 1000 person-years; aHR: 0.31; 95% CI 0.16 to 0.61; p=0.001) in the insulin and GLP-1ar groups, respectively. Conclusions In this cohort of obese people with T2DM, intensification of dual oral therapy by adding GLP-1ar analogue is associated with a lower MACE outcome in routine clinical practice, compared with adding insulin therapy as the third glucose-lowering agent.

Understanding the epidemiology of avoidable significant harm in primary care: protocol for a retrospective cross-sectional study

Introduction Most patient safety research has focused on specialist-care settings where there is an appreciation of the frequency and causes of medical errors, and the resulting burden of adverse events. There have, however, been few large-scale robust studies that have investigated the extent and severity of avoidable harm in primary care. To address this, we will conduct a 12-month retrospective cross-sectional study involving case note review of primary care patients. Methods and analysis We will conduct electronic searches of general practice (GP) clinical computer systems to identify patients with avoidable significant harm. Up to 16 general practices from 3 areas of England (East Midlands, London and the North West) will be recruited based on practice size, to obtain a sample of around 100 000 patients. Our investigations will include an ‘enhanced sample’ of patients with the highest risk of avoidable significant harm. We will estimate the incidence of avoidable significant harm and express this as ‘per 100 000 patients per year’. Univariate and multivariate analysis will be conducted to identify the factors associated with avoidable significant harm. Ethics/Dissemination The decision regarding participation by general practices in the study is entirely voluntary; the consent to participate may be withdrawn at any time. We will not seek individual patient consent for the retrospective case note review, but if patients respond to publicity about the project and say they do not wish their records to be included, we will follow these instructions. We will produce a report for the Department of Healths Policy Research Programme and several high-quality peer-reviewed publications in scientific journals. The study has been granted a favourable opinion by the East Midlands Nottingham 2 Research Ethics Committee (reference 15/EM/0411) and Confidentiality Advisory Group approval for access to medical records without consent under section 251 of the NHS Act 2006 (reference 15/CAG/0182).