• Daily remote ischaemic conditioning following acute myocardial infarction: a randomised controlled trial.

      Chitkara, Kamal (2018-05)
      BACKGROUND: Remote ischaemic conditioning (rIC) is a cardioprotective tool which has shown promise in preclinical and clinical trials in the context of acute ischaemia. Repeated rIC post myocardial infarction may provide additional benefits which have not previously been tested clinically. METHODS: The trial assessed the role of daily rIC in enhancing left ventricular ejection fraction (LVEF) recovery in patients with impaired LVEF (<45%) after ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (P-PCI). Patients were recruited from four UK hospitals and randomised to receive either 4 weeks of daily rIC or sham conditioning using the autoRIC Device (CellAegis) starting on day 3 post P-PCI. The primary endpoint was the improvement in LVEF over 4 months assessed by cardiac MRI (CMR). Seventy-three patients (38 cases, 35 controls) completed the study. RESULTS: The treatment and control groups were well matched at baseline including for mean LVEF (42.8% vs 44.3% respectively, p=0.952). There was no difference in the improvement in LVEF over 4 months between the treatment and control groups (4.8%±7.8% vs 4.6%±5.9% respectively, p=0.924). No differences were seen in the secondary outcome measures including changes in infarct size and left ventricular end-diastolic and systolic volumes, major adverse cardiac and cerebral event, mean Kansas City Cardiomyopathy Questionnaire score and change in N-terminal pro-brain natriuretic peptide levels. CONCLUSIONS: Daily rIC starting on day 3 and continued for 4 weeks following successful P-PCI for STEMI did not improve LVEF as assessed by CMR after 4 months when compared with a matched control group. TRIAL REGISTRATION NUMBER: NCT0166461.
    • Decision-making for older patients undergoing Emergency Laparotomy: Defining Patient and Clinician Values and Priorities.

      Javanmard-Emamghissi, H (2020-05)
      AIM: There remains limited knowledge on what patients value and prioritise in their decision to undergo emergency laparotomy (ELap) and during their subsequent recovery. The aim of this study was to explore factors in decision-making, and to reach a consensus amongst patients on the ten most important priorities in decision-making in ELap. METHODS: Patients aged over 65 years who had required an ELap decision within the preceding 12 months (regardless of management) were identified and invited to attend a modified Delphi process focus group. RESULTS: A total of 20 participants attended: 8 patients, 4 relatives and 8 peri-operative specialists (POS). The POS group defined 12 important factors for peri-operative decision making. The patient group agreed only six (50%) of these factors were important; independence, post-operative complications, readmission to hospital, requirement for stoma formation and delirium (including long-term cognition). Open discussion refined multiple themes. Agreement was reached by patients and relatives about 10 factors that they valued as most important in their ELap patient journey: return to independence, realistic expectations, post-operative complications, what to expect post-operatively, readmission to hospital, nutrition, post-operative communication, stoma, follow-up and delirium. CONCLUSION: Patients and clinicians have different values and priorities when discussing the risks and implications of undergoing ELap. Patients value quality of life outcomes, in particular, the formation of a stoma, returning to their own home and remaining independent. This work is the first to combine both perspectives to guide future ELap research outcomes.
    • Defecation pain and coccydynia due to an anteverted coccyx: a case report.

      Salar, Omer (2012-07)
      INTRODUCTION: Defecation pain is a common problem with many etiologies implicated. Elucidating a cause requires a thorough medical history, examination and appropriate investigations, which may include endoscopy, barium enema, examination under anesthesia and magnetic resonance imaging or computed tomography. Coccydynia is a term used to describe pain in the region of the coccyx, often due to abnormal mobility of the coccyx. Non-surgical management options remain the gold-standard for coccydynia with surgery being reserved for complicated cases. CASE PRESENTATION: This is a case of a 67-year-old Caucasian man who presented with a two-and-a-half-year history of worsening rectal pain. CONCLUSION: To the best of our knowledge, we describe the first case in the literature of an abnormally mobile anteverted coccyx causing predominantly defecation pain and coccydynia, successfully treated by coccygectomy. When first-line investigations fail to elucidate a cause of defecation pain one must, in the presence of unusual symptoms, consider musculoskeletal pathologies emanating from the coccyx and an orthopedic consultation must then be sought for diagnostic purposes.
    • Defining improvement in chronic kidney disease: regression and remission.

      Taal, Maarten
      PURPOSE OF REVIEW: International definitions exist for chronic kidney disease (CKD) progression and kidney failure but despite evidence that kidney function may improve, there are no agreed definitions for regression and remission of CKD. In the light of recent novel kidney protective therapies and the promise of regenerative medicine to reverse kidney damage, it is time to critically examine these neglected aspects of CKD epidemiology. RECENT FINDINGS: We propose that CKD regression is viewed as a process of improvement defined as a sustained increase in glomerular filtration rate (GFR) by ≥25% and an improvement in GFR category or increase in GFR of 1≥ml/min/year, whereas remission is considered a category of improvement defined as GFR ≥60 ml/min/1.73m2 and urine albumin to creatinine ratio <30 mg/g. Several recent studies have reported improvement in kidney function in populations with CKD, even in the absence of specific therapy. Regression and remission of CKD are associated with increased likelihood of sustained improvement in kidney function as well as improved survival. SUMMARY: Further research is warranted to validate the proposed definitions and investigate associated mechanisms. We look to a future in which the goal of therapy is not merely to slow CKD progression but to improve kidney function and seek a cure.
    • Defining the cause of death in hospitalised patients with acute kidney injury.

      Selby, Nicholas; Kolhe, Nitin; McIntyre, Christopher; Packington, Rebecca; Fluck, Richard (2012-11)
      BACKGROUND: The high mortality rates that follow the onset of acute kidney injury (AKI) are well recognised. However, the mode of death in patients with AKI remains relatively under-studied, particularly in general hospitalised populations who represent the majority of those affected. We sought to describe the primary cause of death in a large group of prospectively identified patients with AKI. METHODS: All patients sustaining AKI at our centre between 1(st) October 2010 and 31(st) October 2011 were identified by real-time, hospital-wide, electronic AKI reporting based on the Acute Kidney Injury Network (AKIN) diagnostic criteria. Using this system we are able to generate a prospective database of all AKI cases that includes demographic, outcome and hospital coding data. For those patients that died during hospital admission, cause of death was derived from the Medical Certificate of Cause of Death. RESULTS: During the study period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6% had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859 patients). Cause of death could be identified in 93.4% of cases. There were three main disease categories accounting for three quarters of all mortality; sepsis (41.1%), cardiovascular disease (19.2%) and malignancy (12.9%). The major diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was largely a result of heart failure and ischaemic heart disease. AKI was the primary cause of death in only 3% of cases. CONCLUSIONS: Mortality associated with AKI remains high, although cause of death is usually concurrent illness. Specific strategies to improve outcomes may therefore need to target not just the management of AKI but also the most relevant co-existing conditions.
    • Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment.

      Eldehni, Mohamed; Odudu, Aghogho; Evans, Philip; McIntyre, Christopher (2014-12)
      Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.
    • Delayed presentation of small bowel injury during suprapubic catheterisation.

      Leeder, Paul; Jackson, Benjamin; Williams, J. Huw (2010-04)
      We present a case of small intestine injury resulting from suprapubic catheter insertion. This case is of particular interest for three reasons. Firstly, the presentation of the injury was delayed by three months, until the time of the first catheter exchange. Secondly, the injury was managed conservatively, without surgical exploration. Finally, the injury occurred using a newer, Seldinger-type suprapubic catheter insertion kit.
    • Delays between the onset of symptoms and first rheumatology consultation in patients with rheumatoid arthritis in the UK: an observational study.

      Deighton, Chris (2019-03)
      OBJECTIVE: To investigate delays from symptom onset to rheumatology assessment for patients with a new onset of rheumatoid arthritis (RA) or unclassified arthritis. METHODS: Newly presenting adults with either RA or unclassified arthritis were mrecruited from rheumatology clinics. Data on the length of time between symptom onset and first seeing a GP (patient delay), between first seeing a general practitioner (GP) and being referred to a rheumatologist (general practitioner delay) and being seen by a rheumatologist following referral (hospital delay) were captured. RESULTS: 822 patients participated (563 female, mean age 55 years). The median time between symptom onset and seeing a rheumatologist was 27.2 weeks (IQR 14.1-66 weeks); only 20% of patients were seen within the first 3 months following symptom onset. The median patient delay was 5.4 weeks (IQR 1.4-26.3 weeks). Patients who purchased over-the-counter medications or used ice/heat packs took longer to seek help than those who did not. In addition, those with a palindromic or an insidious symptom onset delayed for longer than those with a non-palindromic or acute onset. The median general practitioner delay was 6.9 weeks (IQR 2.3-20.3 weeks). Patients made a mean of 4 GP visits before being referred. The median hospital delay was 4.7 weeks (IQR 2.9-7.5 weeks). CONCLUSION: This study identified delays at all levels in the pathway towards assessment by a rheumatologist. However, delays in primary care were particularly long. Patient delay was driven by the nature of symptom onset. Complex multi-faceted interventions to promote rapid help seeking and to facilitate prompt onward referral from primary care should be developed.
    • Demographic associations of high estimated sodium intake and frequency of consumption of high-sodium foods in people with chronic kidney disease stage 3 in England.

      McIntyre, Natasha; McIntyre, Christopher; Willingham, Fiona; Taal, Maarten (2014-07)
      OBJECTIVE: The objective of this study was to investigate sodium intake in a cohort of people with chronic kidney disease (CKD) Stage 3 in England to identify demographic characteristics of subgroups with high sodium intake and specific foods that contribute to excessive sodium intake. DESIGN AND METHODS: Study subjects (N = 1,729) included CKD patients from 32 general practices in the Renal Risk in Derby study. Patients had a glomerular filtration rate between 30 and 59 mL/min per 1.73 m(2) on 2 or more occasions at least 3 months apart before recruitment. Sodium excretion (assumed to be equal to intake) was estimated from early morning urine specimens using an equation validated for this study population. The frequency of intake of 12 salty foods was assessed by a food frequency questionnaire. RESULTS: The mean estimated urinary sodium excretion was 110.5 ± 33.8 mmol/day; 60.1% had values above the National Kidney Foundation recommendation (<100 mmol/day). Subgroups with a greater percentage of participants having sodium excretion above the recommendation were as follows: men, those younger than 75 years of age, those with central obesity or diabetes, those with formal educational qualifications, and those who were previous or current smokers. In multivariable analysis, gender, younger age, waist-to-hip ratio, and diabetes mellitus status were the main independent determinants of excessive sodium excretion. Specific food items that contributed to excessive intake were table and cooking salt, salted snacks, hard cheeses, processed meat, and tinned fish. The most important source of sodium varied by subgroup. CONCLUSION: A high prevalence of sodium excretion above the recommended value was detected, and independent determinants were gender, age, waist-to-hip ratio, and diabetes mellitus. Specific food items that contributed to excessive intake were also identified and varied in different subgroups. These data will be helpful in informing strategies to target dietetic advice to those most likely to have high sodium intake and will allow dietitians to focus on the most likely sources of sodium in different subgroups.
    • Dental core training for the future GDP: is it worth it?

      Nazar, S (2019-04)
      In this article I highlight the benefits and shortfalls of the dental core trainee year for one who has no interest in specialising and sees their eventual future as a general dental practitioner (GDP). I conclude that the dental core trainee year has great advantages and adds value to the future GDP.
    • Design and Rationale of 'Tackling Acute Kidney Injury', a Multicentre Quality Improvement Study

      Selby, Nicholas (2016-11)
      Acute kidney injury (AKI) is common and associated with extremely poor outcomes. While strategies to tackle deficiencies in basic care delivery are advocated, robust testing of their effectiveness is also needed. The Tackling AKI study was designed to test whether a complex intervention (consisting of an e-alert, care bundle and education programme) can be successfully implemented across a range of UK hospitals, and whether this will deliver improved patient outcomes. This multicentre, pragmatic clinical trial will employ a cluster randomised stepped wedge design to study this in all adult patients who sustain AKI in the 5 participating hospitals over a 2-year period. The intervention will be supported by a comprehensive change management framework. Data collection will include patient outcomes, process measures and a qualitative assessment of barriers and enablers to implementation. This article describes the rationale and design behind the Tackling AKI study.
    • Determinants of arterial stiffness in chronic kidney disease stage 3.

      McIntyre, Natasha; Fluck, Richard; McIntyre, Christopher; Fakis, Apostolos; Taal, Maarten (2013-01)
      BACKGROUND: Early chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk but underlying mechanisms remain uncertain. Arterial stiffness (AS) is associated with increased CV risk in advanced CKD, but it is unclear whether AS is relevant to CV disease (CVD) in early CKD. STUDY DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: 1717 patients with previous estimated glomerular filtration rate (eGFR) 59-30 mL/min/1.73 m(2); mean age 73±9y, were recruited from 32 general practices in primary care. OUTCOMES: Increased arterial stiffness. MEASUREMENTS: Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Carotid to femoral pulse wave velocity (PWV) was determined as a measure of AS, using a Vicorder™ device. RESULTS: Univariate analysis revealed significant correlations between PWV and risk factors for CVD including age (r = 0.456; p<0.001), mean arterial pressure (MAP) (r = 0.228; p<0.001), body mass index (r = -0.122; p<0.001), log urinary albumin to creatinine ratio (r = 0.124; p<0.001), Waist to Hip ratio (r = 0.124, p<0.001), eGFR (r = -0.074; p = 0.002), log high sensitivity c-reactive protein (r = 0.066; p = 0.006), HDL (r = -0.062; p = 0.01) and total cholesterol (r = -0.057; p = 0.02). PWV was higher in males (9.6 m/sec vs.10.3 m/sec; p<0.001), diabetics (9.8 m/sec vs. 10.3 m/sec; p<0.001), and those with previous CV events (CVE) (9.8 m/s vs. 10.3 m/sec; p<0.001). Multivariable analysis identified age, MAP and diabetes as strongest independent determinants of higher PWV (adjusted R² = 0.29). An interactive term indicated that PWV increased to a greater extent with age in males versus females. Albuminuria was a weaker determinant of PWV and eGFR did not enter the model. LIMITATIONS: Data derived from one study visit, with absence of normal controls. CONCLUSION: In this cohort, age and traditional CV risk factors were the strongest determinants of AS. Albuminuria was a relatively weak determinant of AS and eGFR was not an independent determinant. Long-term follow-up will investigate AS as an independent risk factor for CVE in this cohort.
    • Determinants of change in arterial stiffness over 5 years in early chronic kidney disease.

      Shardlow, Adam; Fluck, Richard; Taal, Maarten (2019-09)
      BACKGROUND: Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care. METHODS: A total of 1741 persons with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device. RESULTS: 970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation). CONCLUSIONS: We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.
    • Developing an interactive booklet for patients with acute kidney injury

      Moreland, Jane; Phiri, Elita (2015-05)
      Providing renal patients with written information about their condition can encourage active care participation and promote recovery. Jane Moreland and Elita Phiri discuss the production of an interactive booklet for adults with acute kidney injury at Royal Derby Hospital.
    • The Development and Validation of the LIMPRINT Methodology.

      Keeley, Vaughan (2019-04)
      The acronym Limprint stands for Lymphedema IMpact and PRevalence INTernational and was run under the auspices of the International Lymphedema Framework (ILF), a charity dedicated to improving provision of care globally. The primary aim was to identify the number of people with chronic edema (chronic edema present for >3 months and due to a range of underlying etiologies and associated risk factors) within diverse health services in nine participating countries and to determine its impact using validated methods. An international protocol and sampling framework, online data capture system, and standard operating procedures were adopted. An international consensus was used to create a core data tool that covered 13 domains. Specialist data on demographics and disability, details of swelling, wounds, cancer, and health-related quality of life were also available for sites. The study protocol was designed to allow flexibility in the types of studies undertaken within complex health care systems. All cases were confirmed using the modified pitting test. Sensitivity and specificity for this method were determined in Japanese and European populations. Following confirmation of a chronic edema case, Lymphologists defined whether it was a primary of a secondary form. The study was designed to provide robust evidence that chronic edema is an important and unrecognized public health problem in health services with significant morbidity. Without evidence of the size and complexity, it will remain considered a rare phenomenon and people affected will be denied access to appropriate treatment that would allow them to have fulfilled and productive lives
    • Development of a trigger tool to detect harm during haemodialysis

      Fielding, Catherine; Rhodes, Carol; Chesterton, Lindsay; Fluck, Richard; Lambe, Georgina; Inacay, Geoff; Taal, Maarten (2016)
      Haemodialysis is a widely used renal replacement therapy that is associated with multiple risks for patients. Monitoring of harm associated with haemodialysis is often limited to reporting of critical incidents, which is reactive and does not provide a complete picture. Catherine Fielding et al discuss their modification of an existing trigger tool to monitor harm specific to haemodialysis.
    • Development of the Department of Medicine for the Elderly Liaison Team.

      Burn, Elinor; Evans, Barry; Gordon, Adam; Shah, Tanujah; Grant, Frances (2019-03)
    • Diabetes and pregnancy.

      Wilmot, Emma (2014-12)
      An increasing number of women who are pregnant have diabetes, whether gestational or pre-existing. Diabetes in pregnancy is associated with a number of adverse outcomes including birth trauma, neonatal hypoglycaemia, macrosomia and pre-eclampsia. Those with pre-existing diabetes have the additional risks which include congenital defects and increased perinatal mortality. This paper summarises the complications of diabetes in pregnancy and highlights some of the recent controversy surrounding the diagnosis of gestational diabetes.
    • Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK.

      Hooper, Philipa (2018-09)
      BACKGROUND & AIMS: There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals. METHODS: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103). RESULTS: Of 1267 patients (80% women, 91% Caucasian, age (median(range)) 55(8-86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking Nitrofurantoin and 0.7% Khat. Twenty-one percent had clinical decompensation and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was≥1 year in 19% and was longer in jaundiced vs non-jaundiced patients. HBV and HCV serology were undocumented in 4%, serum immunoglobulins in 31% and autoantibodies in 11%-27%. When documented, ≥1 antibody was present in 83%. LKM-1-positive and autoantibody-negative patients had more severe disease. Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University Hospitals compared to District General Hospitals, were more likely to report histological features of AIH. bCONCLUSIONS: This cohort from across the UK is older than other multicentre AIH cohorts. One-fifth had decompensation or MELD >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one-third and rosettes and emperipolesiswere infrequently reported.
    • DIY artificial pancreas systems: the clinician perspective.

      Wilmot, Emma (2020-03)
      We are witnessing a technological revolution in type 1 diabetes, with a race to bring commercial closed-loop (artificial pancreas) systems to market. However, only one automated insulin-delivery system, the Medtronic MiniMed 670G, has received both US Food and Drug Administration (FDA) and European CE mark approval and is commercially available in several countries. The French Diabeloop system, designed to work with several continuous glucose monitors and insulin pumps, has received a CE mark, and the FDA have awarded the Tandem Diabetes Care t:slim X2 the status of an alternate controller enabled interoperable pump, facilitating efficient premarket review; however, neither are commercially available yet. Meanwhile, in the European Union, new medical device regulations will be more demanding with respect to safety, potentially slowing access to commercial closed-loop systems. While waiting for these systems to come to market, people living with diabetes have taken development into their own hands, with the #WeAreNotWaiting movement supporting the use of do-it-yourself (DIY) artificial pancreas systems incorporating commercially available insulin pumps and continuous glucose monitors with automated control algorithms. Several DIY artificial pancreas systems are now available for people to build and use, integrating a range of different insulin pumps and glucose sensors.