Kevin McLaughlin

Acute interstitial nephritis due to omeprazole.

Omeprazole is a proton pump inhibitor that is used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Thus far, 17 cases of acute interstitial nephritis (AIN) secondary to omeprazole have been described. Another case of AIN is described in a 36-yr-old woman presenting with nausea, vomiting, weight loss, and a rising serum creatinine concentration. Omeprazole therapy had ceased 2 wk before admission. AIN was diagnosed by renal biopsy and corticosteroid therapy was initiated. After 4 wk of therapy the serum creatinine concentration had normalized. Among the reported cases in the literature, AIN was diagnosed after an average of 2.7 months of therapy with 20–40 mg of omeprazole daily. Recurrence was universal on rechallenge. Common symptoms included fatigue, fever, anorexia, and nausea. The classic triad of fever, rash, and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, pyuria, eosinophilia, and anemia. Management consisted of withdrawal of omeprazole and corticosteroid therapy in some patients. All but one patient recovered normal renal function. Corticosteroid therapy was well tolerated and may have been beneficial.

The Role of Genetic Polymorphisms of Angiotensin-Converting Enzyme in the Progression of Renal Diseases

The renin-angiotensin system is likely to be important in the progression of renal diseases because of its effect on tissue hemodynamics and glomerular cell function. Recent evidence from small studies has suggested a possible role for the genetic determinants of angiotensin converting enzyme activity in the rate of progression of renal failure. We studied the effect of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene on the rate of renal function deterioration in 822 patients with a variety of renal diseases. We found that the slope of the reciprocal serum creatinine-versus-time plot was steeper in patients homozygous for the deletion allele (DD) compared with those homozygous for the insertion allele (II) (P = .015). When patients with similar renal function at presentation (creatinine < 200 mumol/L) were compared, II homozygotes had significantly improved renal survival (P = .039). Separate analyses of patients with glomerular diseases and tubulointerstitial diseases demonstrated an effect of this genotype in glomerular diseases only. These data provide further evidence of the possible role of the angiotensin-converting enzyme gene in the rate of progression of renal failure, although further studies are required to evaluate the role of this and other proposed candidate genes in renal diseases.

Renal artery stenosis

Renal artery stenosis is becoming increasingly common because of atherosclerosis in an ageing population. Patients usually present with hypertension and varying degrees of renal impairment, although silent renal artery stenosis may be present in many patients with vascular disease. Despite improvements in diagnostic and interventional techniques, controversy remains over whether, when, and how to revascularise the kidneys of patients with renal artery stenosis. #### Charac teristics of renal artery stenosis ##### Fibromuscular dysplasia ##### Atherosclerosis The pathophysiology of unilateral renal artery stenosis provides a clear example of how hypertension develops. Narrowing of the renal artery, due to atherosclerosis or, rarely, fibromuscular dysplasia, leads to reduced renal perfusion. The consequent activation of the renin-angiotensin system causes hypertension (mediated by angiotensin II), hypokalaemia, and hyponatraemia (which are features of secondary hyperaldosteronism). Although these features may be reversed by correcting the stenosis, a classic presentation is uncommon, and hypertension is rarely cured in patients with atheromatous renal artery stenosis. In addition, it is now known that renal artery stenosis is underdiagnosed and may present as a spectrum of disease from secondary hypertension to end stage renal failure, reflecting variation in the underlying disease process. Thus, the presence of overt, or coincidental, renal artery stenosis usually reflects widespread vascular disease, with the associated implications for cardiovascular risk and patient survival. Atheromatous lesions may affect different sized vessels within the kidney, and multiple lesions may exist. The site limits the potential for revascularisation; only lesions within the large vessels are amenable. The commonest site, at the ostium of the renal artery, is more effectively treated by stenting. Ulcerated atheromatous plaques may also generate cholesterol microemboli (particularly after vascular intervention) #### Prevalence of atheromatous renal artery stenosis

Original ResearchThe Emotional and Cognitive Impact of Unexpected Simulated Patient Death: A Randomized Controlled Trial

BACKGROUND Observational studies suggest that emotions experienced during simulation training may affect cognitive load and learning outcomes. The objective of this study was to manipulate emotions during simulation training and assess the impact on cognitive load and learning. METHODS In this prospective randomized trial, 116 final-year medical students received training in a simulated scenario of a 70-year-old woman presenting with reduced consciousness due to aminosalicylic acid ingestion. Training groups were randomly allocated to one of two endings for the scenario: The patient was transferred to another service, or she experienced a cardiorespiratory arrest and died. Participants rated their emotions and cognitive load after training. Three months later, we evaluated their performance on a simulation Objective Structured Clinical Examination station of a 60-year-old man presenting with reduced consciousness due to ethylene glycol ingestion. RESULTS Emotions tended to be more negative for students in training groups where the simulated patient died. These students also reported a higher cognitive load (mean ± SD, 7.63 ± 0.97 vs 7.25 ± 0.84; P = .03; d = 0.42) and were less likely to be rated as competent to diagnose and manage a patient with reduced consciousness due to toxin ingestion (OR, 0.37; 95% CI, 0.14-0.95; P = 0.04) 3 months later. CONCLUSIONS Students exposed to unexpected simulated patient death reported increased cognitive load and had poorer learning outcomes. Educators need to expose learners to negative experiences; therefore, further studies are needed on how best to use negative emotional experiences during simulation training.

Cardiovascular complications of renal disease

Advances in the technology and delivery of renal replacement therapy (dialysis and transplantation) have revolutionised the outcome of patients with progressive renal disease. However, the paradox of this success has been to uncover a greatly increased risk of cardiovascular disease (CVD), up to 20 times that of the normal population, a pattern similar to that seen in diabetes following the discovery of insulin. However, the magnitude of the problem is greater in renal disease and there is less agreement on the mechanisms or evidence on which to base interventional strategies. The importance of CVD in this population is reflected by recent publications1-3 and a report from a specific task force of the US National Kidney Foundation. The recognition that large scale outcome studies are required has resulted in the initiation of several studies that will report over the next few years. This review is a personal view in which we will cover the background to CVD at different stages in the natural history of progressive renal disease, current treatments, unresolved problems, and ongoing studies To appreciate the problems and management of CVD in progressive renal disease it is necessary to consider the key differences between patients with renal disease and other patient groups. The first is the course of renal disease (fig 1). Patients with progressive renal disease suffer a period of deteriorating renal function, over months to many years (depending on the underlying disease) and leading ultimately to end stage renal disease (ESRD) in a proportion of patients. Most patients with ESRD (around 100 per million population per annum) currently enter renal replacement therapy programmes involving either peritoneal dialysis or haemodialysis. Thereafter, approximately one third will be considered for renal transplantation and, over a period of years, the majority of these will proceed to have a successful cadaveric …

Twelve tips for blueprinting

Background: Content validity is a requirement of every evaluation and is achieved when the evaluation content is congruent with the learning objectives and the learning experiences. Congruence between these three pillars of education can be facilitated by blueprinting. Aims: Here we describe an efficient process for creating a blueprint and explain how to use this tool to guide all aspects of course creation and evaluation. Conclusions: A well constructed blueprint is a valuable tool for medical educators. In addition to validating evaluation content, a blueprint can also be used to guide selection of curricular content and learning experiences.

A Cluster Randomized Trial of an Enhanced eGFR Prompt in Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Despite reporting estimated GFR (eGFR), use of evidence-based interventions in CKD remains suboptimal. This study sought to determine the effect of an enhanced eGFR laboratory prompt containing specific management recommendations, compared with standard eGFR reporting in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cluster randomized trial of a standard or enhanced eGFR laboratory prompt was performed in 93 primary care practices in Alberta, Canada. Although all adult patients with CKD (eGFR <60 ml/min per 1.73 m(2)) were included, medication data were only available for elderly patients (aged ≥66 years). The primary outcome, the proportion of patients with diabetes or proteinuria receiving an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), was assessed in elderly CKD patients. RESULTS There were 5444 elderly CKD patients with diabetes or proteinuria who were eligible for primary outcome assessment, irrespective of baseline ACEi/ARB use. ACEi/ARB use in the subsequent year was 77.1% and 76.9% in the standard and enhanced prompt groups, respectively. In the subgroup of elderly patients with an eGFR <30 ml/min per 1.73 m(2), ACEi/ARB use was higher in the enhanced prompt group. Among 22,092 CKD patients, there was no difference in the likelihood of a composite clinical outcome (death, ESRD, doubling of serum creatinine, or hospitalization for myocardial infarction, heart failure, or stroke) over a median of 2.1 years. CONCLUSIONS In elderly patients with CKD and an indication for ACEi/ARB, an enhanced laboratory prompt did not increase use of these medications.

Clinical predictors of renal allograft histopathology: a comparative study of single-lesion histology versus a composite, quantitative scoring system.

Background. Progressive injury that is refractory to conventional immunosuppression remains the major hurdle to indefinite survival of transplanted organs. Several clinical risk factors of chronic renal allograft rejection have been identified; although some (e.g., acute rejection) are direct manifestations of immunological injury, others (e.g., donor age) have been more difficult to conceptually link with graft dysfunction. Methods. We conducted formal multivariate statistical analyses to reveal associations between established clinical risk factors and allograft histopathology. In a multicenter protocol biopsy-controlled study, 17 clinical risk factors were studied in relation to either the composite Chronic Allograft Damage Index (CADI) score or, to each of eight individual histological indices, using multiple linear regression with forward selection. Results. Nine clinical risk factors were not significantly associated with any histopathological index. Four (donor age, acute rejection, recipient age, and cold ischemia time) were associated both with the total CADI score and, to varying extents, with the individual histopathological indices. In our analysis, clinical risk factors accounted for, at best, only about 60% of the interindividual variation in histopathological score. Conclusions. Our study reveals a missing link between specific clinical risk factors and early histopathological findings that are known to presage accelerated failure of clinically healthy grafts. Given the complex relationship between clinical risk factors, early histopathological changes, and graft outcome, we conclude that composite, quantitative histological indices are best suited to for evaluation of the histological status of the transplant.

Academic Performance of Longitudinal Integrated Clerkship Versus Rotation-based Clerkship Students: A Matched-cohort Study

Purpose Prior studies suggest that students on a longitudinal integrated clerkship (LIC) have comparable academic performance to those on a rotation-based clerkship (RBC); however, most of these studies did not adjust for preclerkship academic performance. The objective of this study was to compare the academic performance of LIC and RBC students matched on prior academic performance over a three-year period. Method Each LIC student in the University of Calgary classes of 2009, 2010, and 2011 (n = 34) was matched with four RBC students (n = 136) of similar prior academic performance. Knowledge and clinical skills performance between the streams was compared. Knowledge was evaluated by internal summative examinations and the Medical Council of Canada Part 1 licensing exam. Clinical skills were evaluated via in-training evaluation report (ITERs) and performance on the clerkship objective structured clinical examination (OSCE). Meta-analysis was used to compare knowledge evaluations and clinical performance for all core clerkship disciplines, and pooled effect sizes from the fixed-effect models were reported. Results Meta-analyses showed no statistically significant heterogeneity. There were no differences between LIC and RBC students on knowledge evaluations (pooled effect size 0.019; 95% confidence interval [−0.155, 0.152], P = .8), ITERs (pooled effect size −0.015 [−0.157, 0.127], P = .8), or mean OSCE ratings (67.9 [SD = 4.6] versus 68.6 [SD = 5.8], P = .5). Conclusions After matching on prior academic performance, LIC and RBC students at one school had comparable performance on summative evaluations of knowledge, clinical performance, and clinical skills over three years.

Diagnosing technical competence in six bedside procedures: comparing checklists and a global rating scale in the assessment of resident performance.

Purpose To compare procedure-specific checklists and a global rating scale in assessing technical competence. Method Two trained raters used procedure-specific checklists and a global rating scale to independently evaluate 218 video-recorded performances of six bedside procedures of varying complexity for technical competence. The procedures were completed by 47 residents participating in a formative simulation-based objective structured clinical examination at the University of Calgary in 2011. Pass/fail (competent/not competent) decisions were based on an overall global assessment item on the global rating scale. Raters provided written comments on performances they deemed not competent. Checklist minimum passing levels were set using traditional standard-setting methods. Results For each procedure, the global rating scale demonstrated higher internal reliability and lower interrater reliability than the checklist. However, interrater reliability was almost perfect for decisions on competence using the overall global assessment (Kappa range: 0.84–1.00). Clinically significant procedural errors were most often cited as reasons for ratings of not competent. Using checklist scores to diagnose competence demonstrated acceptable discrimination: The area under the curve ranged from 0.84 (95% CI 0.72–0.97) to 0.93 (95% CI 0.82–1.00). Checklist minimum passing levels demonstrated high sensitivity but low specificity for diagnosing competence. Conclusions Assessment using a global rating scale may be superior to assessment using a checklist for evaluation of technical competence. Traditional standard-setting methods may establish checklist cut scores with too-low specificity: High checklist scores did not rule out incompetence. The role of clinically significant errors in determining procedural competence should be further evaluated.