Prevalence of anaemia, iron, and vitamin deficiencies in the health system in the Republic of Ireland: a retrospective cohort study.

BACKGROUND: Anaemia is a common but treatable condition that predicts adverse clinical outcomes. However, standards of anaemia management vary considerably. AIM: To estimate the prevalence of anaemia and extent of screening for common underlying causes in the healthcare system in the Republic of Ireland. DESIGN & SETTING: We conducted a retrospective cohort study of 112 181 adult patients, aged ≥18 years, who had a full blood count performed in 2013, using data from the National Kidney Disease Surveillance System. METHOD: The prevalence of anaemia was determined across demographic and clinical subgroups, according to World Health Organization (WHO) definitions. The proportion screened for iron, vitamin B12, and folate deficiency was determined within a 3-month follow-up period and the corresponding prevalence for each deficiency determined. RESULTS: The overall prevalence of anaemia was 12.0% (95% confidence interval [CI] = 11.8% to 12.2%) and was higher in women than men (13.2% versus 10.5%, P<0.001). Anaemia increased with advancing age (33.4% for those aged >75 years) and worsening kidney function (8.2%, 10.9%, 33.2%, and 63.8% for each estimated glomerular filtration rate [eGFR] categories >90, 60-89, 30-59 and <30 ml/min/1.73 m², respectively, P<0.001). After 3-months' follow-up, the proportion screened for iron deficiency was 11.2% based on transferrin saturation and 33.7% using serum ferritin. Screening for folate and B12 deficiency was 17.6% and 19.8%, respectively. Among screened patients, the prevalence of iron deficiency, B12, and folate deficiency was 37.0%, 6.3%, and 5.8%, respectively. CONCLUSION: The burden of anaemia in the healthcare system is substantial especially for older patients and those with advanced kidney disease. Low screening rates for iron, B12, and folate deficiency are common and warrant quality improvement initiatives.

Impact of serum sodium concentrations, and effect modifiers on mortality in the Irish Health System.

BACKGROUND: Abnormalities of serum sodium are associated with increased mortality risk in hospitalised patients, but it is unclear whether, and to what extent other factors influence this relationship. We investigated the impact of dysnatraemia on total and cause-specific mortality in the Irish health system while exploring the concurrent impact of age, kidney function and designated clinical work-based settings. METHODS: A retrospective cohort study of 32,666 participants was conducted using data from the National Kidney Disease Surveillance System. Hyponatraemia was defined as < 135 mmol/L and hypernatraemia as > 145 mmol/L with normal range 135-145 mmol/L. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR's) and 95% Confidence Intervals (CIs) while penalised spline models further examined patterns of risk. RESULTS: There were 5,114 deaths (15.7%) over a median follow up of 5.5 years. Dysnatraemia was present in 8.5% of patients overall. In multivariable analysis, both baseline and time-dependent serum sodium concentrations exhibited a U-shaped association with mortality. Hyponatremia was significantly associated with increased risk for cardiovascular [HR 1.38 (1.18-1.61)], malignant [HR: 2.49 (2.23-2.78)] and non-cardiovascular/non-malignant causes of death [1.36 (1.17-1.58)], while hypernatremia was significantly associated with cardiovascular [HR: 2.16 (1.58-2.96)] and non-cardiovascular/ non-malignant deaths respectively [HR: 3.60 (2.87-4.52)]. The sodium-mortality relationship was significantly influenced by age, level of kidney function and the clinical setting at baseline (P < 0.001). For hyponatraemia, relative mortality risks were significantly higher for younger patients (interaction term P < 0.001), for patients with better kidney function, and for patients attending general practice [HR 2.70 (2.15-3.36)] than other clinical settings. For hypernatraemia, age and kidney function remained significant effect modifiers, with patients attending outpatient departments experiencing the greatest risk [HR 9.84 (4.88-18.62)] than patients who attended other clinical locations. Optimal serum sodium thresholds for mortality varied by level of kidney function with a flattening of mortality curve observed for patients with poorer kidney function. CONCLUSION: Serum sodium concentrations outside the standard normal range adversly impact mortality and are associated with specific causes of death. The thresholds at which these risks appear to vary by age, level of kidney function, and are modified in specific clinical settings within the health system.

Ferric Carboxymaltose in Iron-Deficient Patients with Hospitalized Heart Failure and Reduced Kidney Function.

BACKGROUND: Reduced kidney function is common among patients with heart failure. In patients with heart failure and/or kidney disease, iron deficiency is an independent predictor of adverse outcomes. In the AFFIRM-AHF trial, patients with acute heart failure with iron deficiency treated with intravenous ferric carboxymaltose demonstrated reduced risk of heart failure hospitalization, with improved quality of life. We aimed to further characterize the impact of ferric carboxymaltose among patients with coexisting kidney impairment. METHODS: The double-blind, placebo-controlled AFFIRM-AHF trial randomized 1132 stabilized adults with acute heart failure (left ventricular ejection fraction <50%) and iron deficiency. Patients on dialysis were excluded. The primary end point was a composite of total heart failure hospitalizations and cardiovascular death during the 52-week follow-up period. Additional end points included cardiovascular hospitalizations, total heart failure hospitalizations, and days lost to heart failure hospitalizations or cardiovascular death. For this subgroup analysis, patients were stratified according to baseline eGFR. RESULTS: Overall, 60% of patients had an eGFR <60 ml/min per 1.73 m 2 (the lower eGFR subgroup). These patients were significantly older, more likely to be female and to have ischemic heart failure, and had higher baseline serum phosphate levels and higher rates of anemia. For all end points, event rates were higher in the lower eGFR group. In the lower eGFR group, the annualized event rates for the primary composite outcome were 68.96 and 86.30 per 100 patient-years in the ferric carboxymaltose and placebo arms, respectively (rate ratio, 0.76; 95% confidence interval, 0.54 to 1.06). The treatment effect was similar in the higher eGFR subgroup (rate ratio, 0.65; 95% confidence interval, 0.42 to 1.02; Pinteraction = 0.60). A similar pattern was observed for all end points ( Pinteraction > 0.05). CONCLUSIONS: In a cohort of patients with acute heart failure, left ventricular ejection fraction <50%, and iron deficiency, the safety and efficacy of ferric carboxymaltose were consistent across a range of eGFR values. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF), NCT02937454 .

Differential Impact of Central Venous Catheters versus Arteriovenous Fistulae on Quality of Life among Irish Haemodialysis Patients.

Background: Arteriovenous fistulae (AVF) have superior clinical outcomes compared with central venous catheters (CVC) among patients undergoing hemodialysis (HD). Yet, there is increasing recognition that health-related quality of life (HRQoL) may be more important to patients than survival and that differences may exist between AVF and CVCs in this regard. This study compared HRQoL between AVF and CVC in an Irish cohort. Methods: We conducted a cross-sectional survey among prevalent patients undergoing hemodialysis (N=119) dialyzing with either an AVF or CVC at a regional program. The Short Form 36 (SF-36) and a validated Vascular Access Questionnaire (SF-VAQ) compared QoL between AVF and CVC in domains of physical functioning, social functioning, and dialysis complications. Multivariable logistic regression compared differences between groups for outcomes of physical functioning, social functioning, and dialysis complications expressed as adjusted odds ratios and 95% CI. Results: Mean age was 66.6 years; 52% were using an AVF and 48% had a CVC. Patients dialyzing with an AVF were more satisfied with their access when asked directly (6.2 versus 5.0; P<0.01). Physical functioning scores for bleeding, swelling, and bruising were significantly higher for AVF than CVC (P=0.001, P=0.001, and P<0.001, respectively). In contrast, patients with a CVC reported greater difficulties in bathing and showering than those using an AVF (4.4 versus 2.0; P<0.001), whereas patients with an AVF expressed greater concerns with physical appearances. Compared with AVF, CVC users were less likely to report difficulties in physical functioning (OR=0.35; 95% CI, 0.12 to 0.94; P=0.04) but more likely to report dialysis complications (OR=1.94; 95% CI, 0.69 to 5.87; P=0.22). Conclusions: Vascular access contributes to HRQoL in hemodialysis. CVCs are associated with fewer difficulties from bleeding and bruising but greater negative effect on social activities, including bathing and showering. Overall, patients with a CVC had lower dissatisfaction scores than patients with an AVF when all three domains were added. Innovation in vascular access design and engineering may confer benefits and improve patient comfort on HD.

Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia.

BACKGROUND: Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4-62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. METHODS: Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30-5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. CONCLUSIONS: This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

Iron Deficiency in CKD Without Concomitant Anemia.

The physiological role of iron extends well beyond hematopoiesis. Likewise, the pathophysiological effects of iron deficiency (ID) extend beyond anemia. Although inextricably interrelated, ID and anemia of chronic kidney disease (CKD) are distinct clinical entities. For more than 3 decades, however, nephrologists have focused primarily on the correction of anemia. The achievement of target hemoglobin (Hgb) concentrations is prioritized over repletion of iron stores, and iron status is generally a secondary consideration only assessed in those patients with anemia. Historically, the correction of ID independent of anemia has not been a primary focus in the management of CKD. In contrast, ID is a key therapeutic target in the setting of heart failure (HF) with reduced ejection fraction (HFrEF); correction of ID in this population improves functional status and quality of life and may improve cardiovascular (CV) outcomes. Given the strong interrelationships between HF and CKD, it is reasonable to consider whether iron therapy alone may benefit those with CKD and evidence of ID irrespective of Hgb concentration. In this review, we differentiate anemia from ID by considering both epidemiologic and pathophysiological perspectives and by reviewing the evidence linking correction of ID to outcomes in patients with HF and/or CKD. Furthermore, we discuss existing gaps in evidence and provide proposals for future research and practical considerations for clinicians.

Serum uric acid and mortality thresholds among men and women in the Irish health system: A cohort study.

BACKGROUND: Elevation of serum uric acid (SUA) is associated with increased mortality; however, controversy exists regarding the nature of the relationship and differences between men and women. We explored relationships of SUA levels with all-cause mortality in a large cohort of patients within the Irish health system. METHODS: A retrospective cohort study of 26,525 participants was conducted using data from the National Kidney Disease Surveillance System. SUA was modelled in increments of 59.48 µmol/L (1 mg/dL), Cox's proportional hazards model estimated hazard ratios (HRs) and 95% Confidence Intervals (CI), median lifetimes were also computed separately for men and women. Mortality patterns were further explored using penalised splines. RESULTS: There were 1,288 (4.9%) deaths over a median follow-up of 5.1 years. In men, the risk of mortality was greatest for the lowest (<238 µmol/L) and highest (>535 µmol/L) categories [HR 2.35 (1.65-3.14) and HR 2.52 (1.87-3.29) respectively]; the corresponding median lifetimes for men were reduced by 9.5 and 11.7 years respectively compared to the referent. In women, mortality risks were elevated for SUA >416 mol/L [HR 1.69 (1.13-2.47) and beyond; the corresponding median lifetime for women were reduced by 5.9 years compared to the referent. Spline analysis revealed a U-shaped association between SUA and mortality in men, while for women, the pattern of association was J-shaped. CONCLUSION: Mortality patterns attributed to SUA differ between men and women. Optimal survival was associated with SUA concentrations of 304-454 µmol/L for men and < 409 µmol/L for women.

Evolution of Vascular Access Use among Incident Patients during the First Year on Hemodialysis: A National Cohort Study.

Background: Although the arteriovenous fistula (AVF) confers superior benefits over central venous catheters (CVCs), utilization rates remain low among prevalent patients on hemodialysis (HD). The goal of this study was to determine the evolution of vascular access type in the first year of dialysis and identify factors associated with conversion from CVC to a functioning AVF. Methods: We studiedadult patients (n=610) who began HD between the January 1, 2015 and December 31, 2016 and were treated for at least 90 days, using data from the National Kidney Disease Clinical Patient Management System in the Irish health system. Prevalence of vascular access type was determined at days 90 and 360 after dialysis initiation and at 30-day intervals. Multivariable logistic regression explored factors associated with CVC at day 90, and Cox regression evaluated predictors of conversion from CVC to AVF on day 360. Results: CVC use was present in 77% of incident patients at day 90, with significant variation across HD centers (from 63% to 91%, P<0.001), which persisted after case-mix adjustment. From day 90 to day 360, AVF use increased modestly from 23% to 41%. Conversion from CVC to AVF increased over time, but the likelihood was lower for older patients (for age >77 years versus referent, adjusted hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.96), for patients with a lower BMI (per unit decrease in BMI, HR, 0.95; 95% CI, 0.93 to 0.98), and varied significantly across HD centers (from an HR of 0.25 [95% CI, 0.08 to 0.74] to 2.09 [95% CI, 1.04 to 4.18]). Conclusion: CVCs are the predominant type of vascular access observed during the first year of dialysis, with low conversion rates from CVC to AVF. There is substantial center variation in the Irish health system that is not explained by patient-related factors alone.

Dapagliflozin Added to Verinurad Plus Febuxostat Further Reduces Serum Uric Acid in Hyperuricemia: The QUARTZ Study.

CONTEXT: Combining a sodium-glucose cotransporter 2 inhibitor with a xanthine oxidase inhibitor (XOI) and a urate transporter 1 (URAT1) inhibitor may enhance serum uric acid (sUA) lowering. However, concerns exist regarding high urinary UA (uUA) excretion rates and subsequent crystallization in renal tubules. OBJECTIVE: To assess whether dapagliflozin added to verinurad, a selective URAT1 inhibitor, and febuxostat, an XOI, increases uUA excretion. DESIGN: Randomized, placebo-controlled, 2-way crossover study (NCT03316131). PATIENTS: Adults with asymptomatic hyperuricemia. INTERVENTIONS: Subjects (N = 36) were randomized to oral once-daily 9 mg verinurad plus 80 mg febuxostat plus 10 mg dapagliflozin for 7 days and 7 days of oral once-daily 9 mg verinurad plus 80 mg febuxostat plus placebo with an intervening 7- to 21-day washout period. MAIN OUTCOME MEASURE: Difference in peak uUA excretion between groups from baseline to day 7. Secondary outcomes included changes in sUA levels and 24-h uUA excretion. RESULTS: Both regimens lowered mean peak uUA excretion (least squares mean changes from baseline: -12.9 mg/h [95% confidence interval (CI): -21.0 to -4.7], dapagliflozin; -13.2 mg/h [95% CI -21.3 to -5.0], placebo). sUA concentrations were lower with dapagliflozin (mean treatment difference -62.3 µmol/L [95% CI -82.8 to -41.8]). Dapagliflozin did not impact verinurad pharmacokinetics, its main metabolites, or febuxostat or fasting plasma glucose levels vs verinurad plus febuxostat. There were no clinically relevant changes in safety parameters. CONCLUSIONS: Dapagliflozin further reduced sUA without influencing uUA excretion, suggesting that its combination with verinurad and febuxostat at the doses tested does not adversely affect kidney function. CLINICAL TRIAL REGISTRATION NUMBER: NCT03316131.

Effect of Intensive Urate Lowering With Combined Verinurad and Febuxostat on Albuminuria in Patients With Type 2 Diabetes: A Randomized Trial.

RATIONALE & OBJECTIVE: Hyperuricemia has been implicated in the development and progression of chronic kidney disease. Verinurad is a novel, potent, specific urate reabsorption inhibitor. We evaluated the effects on albuminuria of intensive urate-lowering therapy with verinurad combined with the xanthine oxidase inhibitor febuxostat in patients with hyperuricemia and type 2 diabetes mellitus (T2DM). STUDY DESIGN: Phase 2, multicenter, prospective, randomized, double-blind, parallel-group, placebo-controlled trial. SETTING & PARTICIPANTS: Patients 18 years or older with hyperuricemia, albuminuria, and T2DM. INTERVENTION: Patients randomly assigned 1:1 to verinurad (9mg) plus febuxostat (80mg) or matched placebo once daily for 24 weeks. OUTCOMES: The primary end point was change in urinary albumin-creatinine ratio (UACR) from baseline after 12 weeks' treatment. Secondary end points included safety and tolerability and effect on glomerular filtration. RESULTS: 60 patients were enrolled (n=32, verinurad and febuxostat; n=28, placebo). UACRs after treatment with verinurad plus febuxostat were lower than after placebo at 1, 12, and 24 weeks: -38.6% (90% CI, -60.9% to-3.6%), -39.4% (90% CI, -61.8% to-3.8%), and-49.3% (90% CI, -68.2% to-19.0%), respectively. Serum urate levels after treatment with verinurad plus febuxostat were 59.6% and 63.7% lower than after placebo at 12 and 24 weeks, respectively. No clinically meaningful changes were observed in estimated glomerular filtration rate or serum creatinine or serum cystatin C concentrations. Verinurad plus febuxostat was well tolerated. LIMITATIONS: Sample size and study duration were insufficient to evaluate definitive effects of verinurad plus febuxostat on UACR and glomerular filtration. Generalizability was limited by exclusion of patients with stages 4 and 5 chronic kidney disease. CONCLUSIONS: Verinurad plus febuxostat reduced albuminuria and lowered serum urate concentrations in patients with T2DM, albuminuria, and hyperuricemia. Definitive assessment of their combined impact on preservation of kidney function awaits larger clinical studies. FUNDING: This study was supported by AstraZeneca. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03118739.

High Rate of Adherence to Urate-Lowering Treatment in Patients with Gout: Who's to Blame?

INTRODUCTION: Gout is commonly associated with low adherence rates, thus limiting the effectiveness of treatment. Nevertheless, informed and empowered patients may be more likely to achieve high adherence. We intend to demonstrate that adherence in clinical practice may reach that achieved in clinical trials. METHODS: This was a transversal study within an inception cohort of patients with gout prospectively followed up. Patients were informed at entrance in the cohort of outcomes, targets, and means to implement for successful treatment. Adherence was evaluated through electronic medication possession ratio (MPR) for urate-lowering medication and oral medications for hypertension, diabetes, and hyperlipidemia for comparison. Factors associated with nonadherence, and the relation between nonadherence and serum urate levels while on treatment were analyzed. RESULTS: Data were retrieved from 336 patients, who showed a mean MPR of 87.5%, with 82.1% of patients showing MPR ≥ 0.8. Rates of adherence for hypertension, hyperlipidemia, and diabetes were quite similar (88%, 87%, and 83%, respectively), although MPR > 0.8 was significantly lower for oral medications for diabetes. Adherence was lower, but nevertheless quite fair, during the first year of follow-up, and increasing over time. Active follow-up and comorbidity were associated with good adherence, and adherence and long-term follow-up were associated with higher rates of achieving serum urate within therapeutic target. CONCLUSION: Patients with gout show high rates of adherence if empowered. Active follow-up and comorbidity are associated with high rates of adherence. Adherence is strongly associated with higher rates of achievement of therapeutic serum urate target.

Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.

During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.

Propensity score matched mortality comparisons of peritoneal and in-centre haemodialysis: systematic review and meta-analysis.

BACKGROUND: Accurate comparisons of haemodialysis (HD) and peritoneal dialysis (PD) survival based on observational studies are difficult due to substantial residual confounding that arises from imbalances between treatments. Propensity score matching (PSM) comparisons confer additional advantages over conventional methods of adjustment by further reducing selection bias between treatments. We conducted a systematic review of studies that compared mortality between in-centre HD with PD using a PSM-based approach. METHODS: A sensitive search strategy identified all citations in the PubMed, Cochrane and EMBASE databases from inception through November 2018. Pooled PD versus HD mortality hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. A subsequent meta-regression explored factors to account for between-study variation. RESULTS: The systematic review yielded 214 citations with 17 cohort studies and 113 578 PSM incident dialysis patients. Cohort periods spanned the period 1993-2014. The pooled HR for PD versus HD was 1.06 (95% CI 0.99-1.14). There was considerable variation by country, however, mortality risks for PD versus HD remained virtually unchanged when stratified by geographical region with HRs of 1.04 (95% CI 0.94-1.15), 1.14 (95% CI 0.99-1.32) and 0.98 (0.87-1.10) for European, Asian and American cohorts, respectively. Subgroup meta-analyses revealed similar risks for patients with diabetes [HR 1.09 (95% CI 0.98-1.21)] and without diabetes [HR 0.99 (95% CI 0.90-1.09)]. Heterogeneity was substantial (I2 = 87%) and was largely accounted for by differences in cohort period, study type and country of origin. Together these factors explained a substantial degree of between-studies variance (R2 = 90.6%). CONCLUSIONS: This meta-analysis suggests that PD and in-centre HD carry equivalent survival benefits. Reported differences in survival between treatments largely reflect a combination of factors that are unrelated to clinical efficacy.

Interns as medical educators: student and intern experiences from the intern-delivered teaching program at University Hospital Limerick.

BACKGROUND: The acquisition and assimilation of knowledge through history-taking and clinical skills practice are core aspects of training for medical students. Interns, who have recently graduated and have entered into clinical practice, are uniquely positioned to assume a pivotal role in student education. AIMS: The goal of this study was to evaluate feedback from both students as well as intern tutors on the intern-delivered teaching program at University Hospital Limerick (UHL) from 2015 to 2016. METHODS: Eighty-five interns participated in the program at UHL in 2015 and 2016, aiming to deliver four 1-h tutorials to 285 Year 3 or Year 4 students from UL Graduate Entry Medical (GEMS) Program. A flexible schedule focused on practical skills and knowledge translation was created with oversight from Lead Interns and Professor of Medicine, with administrative support. Feedback was assessed using anonymous survey questionnaires. RESULTS: The survey response rate was 74% in 2015 and 75% in 2016. Student feedback on the performance of intern tutors was positive. More than 50% of students deemed tutorials on history-taking and clinical examination as the most valuable. Over 76% of students indicated a desire to participate as tutors after graduation. Logistical issues in agreeing mutually suitable timeslots were identified as the major barrier for delivery of teaching. From the intern perspective, over 85% reported benefits in areas of professional development and knowledge consolidation. CONCLUSIONS: Participation in intern-delivered teaching leads to clinical and educational benefits for both students and interns. However, several logistical barriers were identified and require refinement.

Temporal trends in acute kidney injury across health care settings in the Irish health system: a cohort study.

BACKGROUND: Complete ascertainment of the true rates of acute kidney injury (AKI) and emerging trends are essential for planning of preventive strategies within health systems. METHODS: We conducted a retrospective cohort study from 2005 to 2014 using data from regional laboratory information systems to determine incidence rates of AKI and severity Stages 1-3 in the Irish health system. Multivariable models were developed to explore annual trends and the contributions of demographic factors, clinical measures, geographic factors and location of medical supervision expressed as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: From 2005 to 2014, incidence rates of AKI increased from 6.1% (5.8-6.3) to 13.2% (12.7-13.8) per 100 patient-years in men and from 5.0% (4.8-5.2) to 11.5% (11.0-12.0) in women, P < 0.001. Stage 1 AKI accounted for the greatest growth in incidence, from 4.4% (95% CI 4.3-4.6) in 2005 to 10.1% (95% CI 9.8-10.5) in 2014 (P < 0.001 for trend). Compared with 2005, patients in 2014 were more likely to experience AKI [OR 4.53 (95% CI 4.02-5.1) for Stage 1, OR 5.22 (4.16-6.55) for Stage 2 and OR 4.11 (3.05-5.54) for Stage 3], adjusting for changing demographic and clinical profiles. Incidence rates of AKI increased in all locations of medical supervision during the period of observation, but were greatest for inpatient [OR 19.11 (95% CI 17.69-20.64)] and emergency room settings [OR 5.97 (95% CI 5.56-6.42)] compared with a general practice setting (referent). CONCLUSION: Incidence rates of AKI have increased substantially in the Irish health system, which were not accounted for by changing demographic patterns, clinical profiles or location of medical supervision.

Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality.

Objective: To determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout. Methods: Prospective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs. Results: Of 1193 patients, 92% were men with a mean age of 60 years, 6.8 years' disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45). Conclusions: Failure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.