• Randomized Controlled Trial of Individualized Dialysate Cooling for Cardiac Protection in Hemodialysis Patients.

      Odudu, Aghogho; Eldehni, Mohamed (2015-08)
      BACKGROUND AND OBJECTIVES: Cardiovascular disease is the most common cause of death in patients on hemodialysis (HD). HD-associated cardiomyopathy is appreciated to be driven by exposure to recurrent and cumulative ischemic insults resulting from hemodynamic instability of conventionally performed intermittent HD treatment itself. Cooled dialysate reduces HD-induced recurrent ischemic injury, but whether this confers long-term protection of the heart in terms of cardiac structure and function is not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between September 2009 and January 2013, 73 incident HD patients were randomly assigned to a dialysate temperature of 37°C (control) or individualized cooling at 0.5°C below body temperature (intervention) for 12 months. Cardiac structure, function, and aortic distensibility were assessed by cardiac magnetic resonance imaging. Mean between-group difference in delivered dialysate temperature was 1.2°C±0.3°C.Treatment effects were determined by the interaction of treatment group with time in linear mixed models. RESULTS: There was no between-group difference in the primary outcome of left ventricular ejection fraction (1.5%; 95% confidence interval, -4.3% to 7.3%). However, left ventricular function assessed by peak systolic strain was preserved by the intervention (-3.3%; 95% confidence interval, -6.5% to -0.2%) as was diastolic function (measured as peak diastolic strain rate, 0.18 s(-1); 95% confidence interval, 0.02 to 0.34 s(-1)). Reduction of left ventricular dilation was demonstrated by significant reduction in left ventricular end-diastolic volume (-23.8 ml; 95% confidence interval, -44.7 to -2.9 ml). The intervention was associated with reduced left ventricular mass (-15.6 g; 95% confidence interval, -29.4 to -1.9 g). Aortic distensibility was preserved in the intervention group (1.8 mmHg(-1)×10(-3); 95% confidence interval, 0.1 to 3.6 mmHg(-1)×10(-3)). There were no intervention-related withdrawals or adverse events. CONCLUSIONS: In patients new to HD, individualized cooled dialysate did not alter the primary outcome but was well tolerated and slowed the progression of HD-associated cardiomyopathy. Because cooler dialysate is universally applicable at no cost, the intervention warrants wider adoption or confirmation of these findings in a larger trial.
    • Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial.

      Kelly, Damian (2015-04)
      BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤ 3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival.
    • Rationale and design of a multi-centre randomised controlled trial of individualised cooled dialysate to prevent left ventricular systolic dysfunction in haemodialysis patients.

      Odudu, Aghogho; McIntyre, Christopher; Fakis, Apostolos; Eldehni, Mohamed (2012-07)
      BACKGROUND: The main hypothesis of this study is that patients having regular conventional haemodialysis (HD) will have a smaller decline in cardiac systolic function by using cooler dialysate. Cooler dialysate may also be beneficial for brain function. METHODS/DESIGN: The trial is a multicentre, prospective, randomised, un-blinded, controlled trial. Patients will be randomised 1:1 to use a dialysate temperature of 37°C for 12 months or an individualised cooled dialysate. The latter will be set at 0.5°C less than the patient's own temperature, determined from the mean of 6 prior treatment sessions with a tympanic thermometer, up to a maximum of 36°C. Protocol adherence will be regularly checked. Inclusion criteria are incident adult HD patients within 180 days of commencing in-centre treatment 3 times per week with capacity to consent for the trial and without contra-indications for magnetic resonance imaging. Exclusion criteria include not meeting inclusion criteria, inability to tolerate magnetic resonance imaging and New York Heart Association Grade IV heart failure. During the study period, resting cardiac and cerebral magnetic resonance imaging will be performed at baseline and 12 months on an inter-dialytic day. Cardiovascular performance during HD will also be assessed by continuous cardiac output monitors, intra-dialytic echocardiography and biomarkers at baseline and 12 months. The primary outcome measure is a 5% between-group difference in left ventricular ejection fraction measured by cardiac magnetic resonance imaging at 12 months compared to baseline. Analysis will be by intention-to-treat. Secondary outcome measures will include changes in cerebral microstructure and changes in cardiovascular performance during HD. A total of 73 patients have been recruited into the trial from four UK centres. The trial is funded by a Research for Patient Benefit Grant from the National Institute of Healthcare Research. AO is funded by a British Heart Foundation Clinical Research Training Fellowship Grant. The funders had no role in the design of the study. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysate temperature for preserving cardiac and cerebral function in HD patients. TRIAL REGISTRATION: ISRCTN00206012 and UKCRN ID 7422.
    • Recent developments in electronic alerts for acute kidney injury.

      Selby, Nicholas; Horne, Kerry (2015-12)
      PURPOSE OF REVIEW: Efforts to improve outcomes from acute kidney injury (AKI) have focussed on timely diagnosis and effective delivery of basic patient care. Electronic alerts (e-alerts) for AKI have attracted interest as a tool to facilitate this. Initial feasibility has already been demonstrated; this review will discuss recent advances in alert methodology, implementation beyond single centres and reported effect on outcomes. RECENT FINDINGS: On-going descriptions of e-alerts highlight increasing variation in both detection algorithms and alert processes. In England, this is being addressed by national rollout of a standardized detection algorithm; recent data have shown this to have good diagnostic performance. In critical care, fully automated detection systems incorporating both serum creatinine and urine output criteria have been developed. A recent randomized trial of e-alerts has also been reported, in which isolated use of a text message e-alert did not affect either clinician behaviour or patient outcome. SUMMARY: As e-alerts gain popularity, consideration must be given to both the method of AKI detection and the method by which results are communicated to end-users; these aspects influence the degree of these systems' effectiveness. This approach should be coupled to further work to study the effect on patient outcomes of those interventions that have been demonstrated to influence clinician behaviour.
    • Rectal adenocarcinoma with rectoprostatic fistula following prostate brachytherapy.

      Moss, BF; Peracha, A (2019-03)
      An 80-year-old man with history of prostate cancer successfully treated with brachytherapy was initially thought to have Fournier's gangrene until imaging detected a rectoprostatic fistula. Although this is known to be a rare complication of prostate brachytherapy, in this case the aetiology was a new primary rectal adenocarcinoma. It was not possible to catheterise per urethra owing to the fistula, so he was fitted with suprapubic catheter, and underwent palliative loop colostomy. Brachytherapy carries a low risk of second primary cancers, although two previous cases reported such cancers as radiation induced. This is, to our knowledge, the first case of rectal adenocarcinoma following prostate brachytherapy in the literature.
    • Recurrent chilblains in a child with neurological impairment.

      Mohandas, Padma; Bowker, R; Ravenscroft, J; Bleiker, T (2017-12)
    • Regional Variation in Acute Kidney Injury Requiring Dialysis in the English National Health Service from 2000 to 2015 - A National Epidemiological Study.

      Kolhe, Nitin; Fluck, Richard; Taal, Maarten (2016-10)
      BACKGROUND: The absence of effective interventions in presence of increasing national incidence and case-fatality in acute kidney injury requiring dialysis (AKI-D) warrants a study of regional variation to explore any potential for improvement. We therefore studied regional variation in the epidemiology of AKI-D in English National Health Service over a period of 15 years. METHOD: We analysed Hospital Episode Statistics data for all patients with a diagnosis of AKI-D, using ICD-10-CM codes, in English regions between 2000 and 2015 to study temporal changes in regional incidence and case-fatality. RESULTS: Of 203,758,879 completed discharges between 1st April 2000 and 31st March 2015, we identified 54,252 patients who had AKI-D in the nine regions of England. The population incidence of AKI-D increased variably in all regions over 15 years; however, the regional variation decreased from 3·3-fold to 1·3-fold (p<0·01). In a multivariable adjusted model, using London as the reference, in the period of 2000-2005, the North East (odd ratio (OR) 1·38; 95%CI 1·01, 1·90), East Midlands (OR 1·38; 95%CI 1·01, 1·90) and West Midlands (OR 1·38; 95%CI 1·01, 1·90) had higher odds for death, while East of England had lower odds for death (OR 0·66; 95% CI 0·49, 0·90). The North East had higher OR in all three five-year periods as compared to the other eight regions. Adjusted case-fatality showed significant variability with temporary improvement in some regions but overall there was no significant improvement in any region over 15 years. CONCLUSIONS: We observed considerable regional variation in the epidemiology of AKI-D that was not entirely attributable to variations in demographic or other identifiable clinical factors. These observations make a compelling case for further research to elucidate the reasons and identify interventions to reduce the incidence and case-fatality in all regions.
    • Relation of Aortic Stiffness to Left Ventricular Remodelling in Younger Adults with Type 2 Diabetes.

      Wilmot, Emma (2018-04)
      Individuals with type 2 diabetes have a three-to-five-fold increased risk of developing heart failure. Diabetic cardiomyopathy is typified by left ventricular (LV) concentric remodelling, which is a recognised predictor of adverse cardiovascular events. Although the mechanisms underlying LV remodelling in type 2 diabetes are unclear, progressive aortic stiffening may be a key determinant. The aim of this study was to assess the relationship between aortic stiffness and LV geometry in younger adults with type 2 diabetes, using multiparametric cardiovascular magnetic resonance imaging. We prospectively recruited 80 adults (aged 18-65 years) with type 2 diabetes and no cardiovascular disease and 20 age- and sex-matched healthy controls. All subjects underwent comprehensive bio-anthropometric assessment and cardiac magnetic resonance imaging, including measurement of aortic stiffness by aortic distensibility (AD). Type 2 diabetes was associated with increased LV mass, concentric LV remodelling and lower AD compared with controls. On multivariable linear regression, AD was independently associated with concentric LV remodelling in type 2 diabetes. Aortic stiffness may therefore be a potential therapeutic target to prevent the development of heart failure in type 2 diabetes.
    • Remote ischaemic conditioning-therapeutic opportunities in renal medicine.

      Crowley, Lisa; McIntyre, Christopher (2013-12)
      Following ischaemic insult, tissue damage is extended after reperfusion, known as an ischaemia reperfusion injury. Ischaemic conditioning-the application of transient, non-lethal, episodes of ischaemia-reduces the effect of a larger ischaemic insult, and limits the reperfusion injury. How this phenomenon might be exploited as a therapeutic treatment is now the subject of a number of clinical trials. From initial trials focusing on the mitigation of cardiac injury, interest has expanded to examine the potential for its use as an adjunctive therapy in different clinical scenarios, including renal medicine. In this Review, we discuss different forms of conditioning, potential molecular mechanisms underpinning its effect, and potential applications in the setting of acute kidney injury, chronic kidney disease and end-stage renal disease.
    • Renal arcuate vein microthrombi-associated AKI.

      Redfern, Andrew; Selby, Nicholas (2015-02)
      BACKGROUNDS AND OBJECTIVES: This report describes six patients with AKI stages 2-3 (median admission creatinine level, 2.75 mg/dl [range, 1.58-5.44 mg/dl]), hematuria (five with hemoproteinuria), and unremarkable imaging with an unusual and unexplained histologic diagnosis on renal biopsy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The patients were young adults who presented to two neighboring United Kingdom nephrology centers over a 40-month period (between July 2010 and November 2013). Four were male, and the median age was 22.5 years (range, 18-27 years). Their principal symptoms were flank pain or lower back pain. All had consumed alcohol in the days leading up to admission. RESULTS: Renal biopsy demonstrated microthrombi in the renal arcuate veins with a corresponding stereotypical, localized inflammatory infiltrate at the corticomedullary junction. All patients recovered to baseline renal function with supportive care (median, 17 days; range, 6-60 days), and none required RRT. To date, additional investigations have not revealed an underlying cause for these histopathologic changes. Investigations have included screening for thrombophilic tendencies, renal vein Doppler ultrasonographic studies, and testing for recreational drugs and alcohol (including liquid chromatography-mass spectrometry of urine) to look for so-called designer drugs. Inquiries to the United Kingdom National Poisons Information Centre have identified no other cases with similar presentation or histologic findings. CONCLUSIONS: Increased awareness and additional study of future cases may lead to a greater understanding of the underlying pathophysiologic mechanisms that caused AKI in these patients.
    • Repeatability of Contrast-Enhanced Ultrasound to Determine Renal Cortical Perfusion.

      Pham, A; Williams, John P
      Alterations in renal perfusion play a major role in the pathogenesis of renal diseases. Renal contrast-enhanced ultrasound (CEUS) is increasingly applied to quantify renal cortical perfusion and to assess its change over time, but comprehensive assessment of the technique's repeatability is lacking. Ten adults attended two renal CEUS scans within 14 days. In each session, five destruction/reperfusion sequences were captured. One-phase association was performed to derive the following parameters: acoustic index (AI), mean transit time (mTT), perfusion index (PI), and wash-in rate (WiR). Intra-individual and inter-operator (image analysis) repeatability for the perfusion variables were assessed using intra-class correlation (ICC), with the agreement assessed using a Bland-Altman analysis. The 10 adults had a median (IQR) age of 39 years (30-46). Good intra-individual repeatability was found for mTT (ICC: 0.71) and PI (ICC: 0.65). Lower repeatability was found for AI (ICC: 0.50) and WiR (ICC: 0.56). The correlation between the two operators was excellent for all variables: the ICCs were 0.99 for PI, 0.98 for AI, 0.87 for mTT, and 0.83 for WiR. The Bland-Altman analysis showed that the mean biases (± SD) between the two operators were 0.03 ± 0.16 for mTT, 0.005 ± 0.09 for PI, 0.04 ± 0.19 for AI, and -0.02 ± 0.11 for WiR.
    • Report from the kick-off meeting of the Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN).

      Sharma, Maulina (2016-02)
      A major obstacle of evidence-based clinical decision making is the use of nonstandardized, partly untested outcome measurement instruments. Core Outcome Sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcomes and outcome measurement instruments in clinical trials, in order to pool results of trials or to allow indirect comparison between interventions. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The international, multidisciplinary Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN) aims to develop and implement COSs in dermatology, thus making trial evidence comparable and, herewith, more useful for clinical decision making. The inaugural meeting of CSG-COUSIN was held on 17-18 March 2015 in Dresden, Germany, as the exclusive theme of the Annual Cochrane Skin Group Meeting. In total, 29 individuals representing a broad mix of different stakeholder groups, professions, skills and perspectives attended. This report provides a description of existing COS initiatives in dermatology, highlights current methodological challenges in COS development, and presents the concept, aims and structure of CSG-COUSIN.
    • Response to the NCEPOD report: development of a care bundle for patients admitted with decompensated cirrhosis-the first 24 h.

      Austin, Andrew (2016-01)
      Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions and deaths due to liver disease have also increased. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol-related liver disease (ARLD) found that less than half the number of patients who died from ARLD received 'good care', and avoidable deaths were identified. In order to improve the care of patients admitted with ARLD, the NCEPOD report recommended that a 'toolkit' for the acute management of patients admitted with decompensated ARLD be developed and made widely available. As a result, we have developed a 'care bundle' for patients admitted with decompensated cirrhosis (of all aetiologies) to ensure that effective evidence-based treatments are delivered within the first 24 h. This care bundle provides a checklist to ensure that all appropriate investigations are undertaken when a patient with decompensated cirrhosis presents and provides clinicians with clear guidance on the initial management of alcohol withdrawal, infection, acute kidney injury, gastrointestinal bleeding and encephalopathy. The first 24 h are particularly important, as early intervention can reduce mortality and shorten hospital stay, and specialist gastroenterology/liver advice is not always available during this period. This review will discuss the care bundle and the evidence base behind the treatment recommendations made.
    • Retrograde Fixation of the Ulna in Pediatric Forearm Fractures Treated With Elastic Stable Intramedullary Nailing.

      Rajan, Rohan (2020-05)
      Introduction This study analyzes the outcomes of retrograde fixation of the ulna in pediatric forearm fractures treated with elastic stable intramedullary nailing (ESIN). Materials and Methods A retrospective analysis was conducted by reviewing patient records of forearm fractures treated with ESIN by retrograde fixation. The study included 30 children (26 boys and 4 girls). The mean age at the time of injury was 11.7 years (range: 6.6 to 14.3 years). The technique is described. All patients were followed up until hardware removal. Results The mean time for fracture healing was 5.3 weeks (range: 4 to 8.8 weeks). The mean time for nail removal was 6.6 months (range: 5 to 10 months). There were five cases with rotation deficits, one of which was a re-fracture. Conclusions When antegrade nailing is performed, the ulna is sometimes complicated by non-union as well as entry point irritation. We did not encounter such complications. Retrograde fixation of the ulna in pediatric forearm fractures treated with ESIN is a safe and effective alternative to common fixation (antegrade ulnar fixation) and offers technical advantages.
    • Review article: coeliac disease in later life must not be missed.

      Holmes, Geoffrey (2018-01)
      BACKGROUND: The presenting symptoms of coeliac disease are often subtle and the diagnosis is frequently delayed or overlooked. Therefore, especially elderly patients may be denied the benefits conferred by gluten free diet which can be dramatically life-changing. AIM: To review the occurrence, clinical features, diagnosis and management in coeliac patients detected later in life. METHODS: To review manuscripts concerned with coeliac disease in the elderly and to derive subgroups of elderly people from publications on the disorder. RESULTS: Approximately a quarter of all diagnoses are now made at the age of 60 years or more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or above. Around 60% remain undetected, since their symptoms are often subtle: tiredness, indigestion, reduced appetite. Good compliance with gluten free diet, resolution of symptoms and improvement in laboratory indices can be achieved in over 90% of patients. CONCLUSIONS: Coeliac disease not uncommonly presents for the first time in older patients and is an important diagnosis to make.
    • Rheumatoid cachexia and cardiovascular disease.

      Summers, Greg (2010-08)
      Both cachexia and cardiovascular disease are strongly associated with rheumatoid arthritis (RA) and linked to the chronic inflammatory process. Typically, rheumatoid cachexia occurs in individuals with normal or increased BMI (reduced muscle mass and increased fat mass). Classic cachexia (reduced muscle mass and reduced fat mass) is rare in RA but is associated with high inflammatory activity and aggressive joint destruction in patients with a poor cardiovascular prognosis. Conversely, obesity is linked to hypertension and dyslipidemia but, paradoxically, lower RA disease activity and less cardiovascular disease-related mortality. Rheumatoid cachexia might represent the 'worst of both worlds' with respect to cardiovascular outcome, but until diagnostic criteria for this condition are agreed upon, its effect on cardiovascular disease risk remains controversial.
    • Risk factors and survival outcome for non-elective referral in non-small cell lung cancer patients--analysis based on the National Lung Cancer Audit.

      Beckett, Paul (2014-03)
      Survival after diagnosis of lung cancer is poor and seemingly lower in the UK than other Western countries, due in large part to late presentation with advanced disease precluding curative treatment. Recent research suggests that around one-third of lung cancer patients reach specialist care after emergency presentation and have a worse survival outcome. Confirmation of these data and understanding which patients are affected may allow a targeted approach to improving outcomes. Methods: We used data from the UK National Lung Cancer Audit in a multivariate logistic regression model to quantify the association of non-elective referral in non-small cell lung cancer patients with covariates including age, sex, stage, performance status, co-morbidity and socioeconomic status and used the Kaplan-Meier method and Cox proportional hazards model to quantify survival by source of referral. Results: In an analysis of 133,530 cases of NSCLC who presented 2006-2011, 19% of patients were referred non-electively (following an emergency admission to hospital or following an emergency presentation to A&E). This route of referral was strongly associated with more advanced disease stage (e.g. in Stage IV - OR: 2.34, 95% CI: 2.14-2.57, p< 0.001) and worse performance status (e.g. in PS 4 - OR: 7.28, 95% CI: 6.75-7.86, p< 0.001), but was also independently associated with worse socioeconomic status, and extremes of age. These patients were more likely to have died within 1 year of diagnosis (hazard ratio of 1.51 (95% CI: 1.49-1.54) after adjustment for key clinical variables. Conclusion: Our data confirm and quantify poorer survival in lung cancer patients who are referred non-electively to specialist care, which is more common in patients with poorer performance status, higher disease stage and less advantaged socioeconomic status. Work to tackle this late presentation should be urgently accelerated, since its realisation holds the promise of improved outcomes and better healthcare resource utilisation.
    • Risk of statin-induced rhabdomyolysis in patients with hepatic impairment.

      Kolhe, Nitin (2014-09)
      We describe a case of a 54-year-old man with a 2-month history of biliary colic associated with a common bile duct stone. He underwent laparoscopic cholecystectomy and developed postoperative acute kidney injury stage 3. A renal biopsy was performed and demonstrated myoglobin in the renal tubules. Retrospective creatine kinase analysis was suggestive of rhabdomyolysis. It is thought this was precipitated by simvastatin accumulation in the context of a period of hepatic impairment and elevated liver enzymes.