• Carbohydrate counting and insulin dose adjustment: group education for people with type 2 diabetes.

      Shorrock, I (2011)
      A group education programme at the Royal Derby Hospital for type 2 diabetes patients. The impact of the programme, which provided information on carbohydrate and insulin, on patients' weight, HbA1c levels, and insulin dosage is described.
    • Cardiac Output assessed via Esophageal Doppler Monitoring Fails to Predict Changes in Renal Microvascular Perfusion

      Read, David; Doleman, Brett; Williams, John P (2019-10)
      Background: Vasoactive drugs are routinely used clinically to alter mean arterial blood pressure (MAP) and cardiac output (CO) and to maintain organ perfusion. However, the effect of such drugs on microvascular visceral blood flow (MiBF) is not fully understood. We aimed to track changes in renal MiBF, using the well-validated technique of Contrast Enhanced Ultrasound (CEUS), across a range of MAP and CO generated via the vasoactive drugs, phenylephrine and ephedrine. Methods: Baseline cardiovascular measurements were recorded, with renal MiBF determined via CEUS as renal microvascular transit time (RTT). Phenylephrine was then administered, via a standardized protocol, to increase MAP and CO, with repeat CEUS. Following return to baseline, the above was repeated using ephedrine. CEUS time-intensity curves were constructed and renal MiBF calculated. Results: In 11 male volunteers (median age 32), phenylephrine increased MAP (98.7 vs 110.8 mmHg, p<0.001), but not CO (4211 vs. 4089 ml.min-1, p=0.42), while ephedrine increased CO (4110 vs 6097, p<0.001) and MAP (95.6 vs 100.9, p=0.02). Phenylephrine reduced time to organ perfusion (TTOP) (22.3 vs 18.4 secs, p=0.009), but not RTT (14 vs 13.2 secs, p=0.46). Ephedrine decreased TTOP (21.1 vs 14.7 secs, p=0.003), and RTT (3.5 vs 9.6 secs, p=0.007). Change in CO predicted change in TTOP (r2=0.26, p=0.02), but not RTT (r2=0.04, p=0.43). Change in MAP did not predict change in TTOP (r2=0.02, p=0.58), or RTT (r2<0.001, p=0.89). Conclusion: Changes in MAP and CO fail to predict renal MiBF. Key points Question: Do macrovascular changes predict renal microvascular perfusion. Findings: Changes in cardiac output and mean arterial blood pressure fail to predict renal microvascular perfusion. Meaning: Clinical measurement of macrovascular indices may not correlate with microvascular indices.
    • Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes.

      Wilmot, Emma (2020-07)
      OBJECTIVE: To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS: Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2. RESULTS: A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodelling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO2 18.0 ± 6.6 vs. 27.8 ± 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (β = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e') (β = -0.388; P = 0.001) were independently associated with peak VO2 in subjects with T2D. CONCLUSIONS: In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure.
    • Care Bundles for Acute Kidney Injury: Do They Work?

      Selby, Nicholas; Kolhe, Nitin (2016-07)
      Acute kidney injury (AKI) is common and is associated with poor patient outcomes, which in some cases appear associated with deficiencies in the provision of care. Care bundles (CBs) are a structured set of practices designed to improve the processes of care delivery and ultimately patient outcomes, and there have been some demonstrations of their utility in areas such as ventilator-associated pneumonia and in sepsis management. While there is a strong rationale for their use, the evidence base around AKI CBs is small but growing. Here, we review the existing data on the effectiveness of AKI CB and discuss optimal approaches to their future study.
    • Carotid artery aneurysm: last among equals.

      Dhillon, Ajit Kaur; Rowlands, Timothy; McMahon, Greg (2016-05)
      A 66-year-old man presented initially with a swelling in the left side of the neck, which was confirmed to be a carotid artery aneurysm on ultrasonography. He was subsequently admitted reporting intermittent episodes of visual loss in the left eye and right arm weakness. Further imaging confirmed multiple, small acute infarcts in the left cerebral hemisphere. The patient underwent open repair of the aneurysm and made an uncomplicated recovery with no persisting neurological deficit.
    • Case of idiopathic isolated unilateral hypoglossal nerve palsy with spontaneous recovery

      Gurung, Binay; Chaudhry, Ismail; Karim, Nawazish; Nanda, Uttam (2018-05)
      Isolated hypoglossal nerve palsy is uncommon because of its intimate relationship with the other lower cranial nerves. Keane reported that tumours, predominantly malignant, were the most common cause of hypoglossal nerve palsy. We report a case of isolated idiopathic unilateral hypoglossal nerve palsy in a 45-year-old Caucasian male where no cause could be identified despite extensive investigations. There was uncertainty around prognosis at onset due to the rarity of this condition. In the absence of a cause, an early referral to the speech and language therapist was made and interestingly our patient made an almost complete recovery within 18 months of onset. In a small case series, it has been reported that though rare, idiopathic hypoglossal nerve palsy has an excellent outcome in most cases, similar to the more common idiopathic seventh cranial nerve palsy (Bell's Palsy).We recommend an early referral for physiotherapy in such cases.
    • A case of palpitation and pre-syncope

      Chatterjee, Debjit (2017)
      A 66 year old woman presented to the emergency department with episodes of palpitations, dizziness, and near fainting for a few hours. She had had a left atrial myxoma removed 15 years ago and had suffered from palpitations as a result of atrial tachycardia from time to time since then for which she took modified release verapamil 240 mg once daily. More recently she had started on sotalol 120 mg twice daily in addition to verapamil for better control of her tachycardia, and one week ago had undergone direct current cardioversion for persistent atrial tachycardia, which reverted her to sinus rhythm. She was admitted to the coronary care unit. Her ECG on admission is shown (fig 1⇓). Subsequently an echocardiogram showed normal left ventricular systolic function and no recurrence of left atrial myxoma. Urea and electrolytes including magnesium were all within normal limits.
    • Central venous oxygen saturation: a potential new marker for circulatory stress in haemodialysis patients?

      Harrison, Laura; Selby, Nicholas; McIntyre, Christopher (2014-10)
      BACKGROUND/AIMS: Haemodialysis causes recurrent haemodynamic stress with subsequent ischaemic end-organ dysfunction. As dialysis prescriptions/schedules can be modified to lessen this circulatory stress, an easily applicable test to allow targeted interventions in vulnerable patients is urgently required. METHODS: Intra-dialytic central venous oxygen saturation (ScvO2) and clinical markers (including ultrafiltration, blood pressure) were measured in 18 prevalent haemodialysis patients. RESULTS: Pre-dialysis ScvO2 was 63.5 ± 13% and fell significantly to 56.4 ± 8% at end dialysis (p = 0.046). Ultrafiltration volume, a key driver of dialysis-induced myocardial ischaemia, inversely correlated to ScvO2 (r = -0.680, p = 0.015). CONCLUSIONS: This initial study demonstrates ScvO2 sampling is practical, with a potential clinical utility as an indicator of circulatory stress during dialysis.
    • Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis.

      Odudu, Aghogho; Eldehni, Mohamed; Breidthardt, Tobias (2016-05)
      OBJECTIVES: Cardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD. METHODS: Fifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined. RESULTS: Global systolic function was reduced (EF 51 ± 10%, HD versus 59 ± 5%, controls, p < 0.001; PSS 15.9 ± 3.7% versus 19.5 ± 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 ± 0.33s(-1) versus 1.31 ± 0.38s(-1), p = 0.003). LV mass index was increased (63[54,79]g/m(2) versus 46[42,53]g/m(2), p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity. CONCLUSION: Patients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy. KEY POINTS: • First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients. • Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV. • Reductions in strain localised to the septal and anterior wall. • Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms. • Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes.
    • Cholestasis and biliary dilatation associated with chronic ketamine abuse: a case series.

      Lo, Robert; Krishnamoorthy, R; Freeman, Jan; Austin, Andrew (2011-03)
      Ketamine is a dissociative anaesthetic agent that is still widely used in veterinary and human medicine. It is increasingly being used as a recreational hallucinogenic drug. Chronic ketamine abuse is known to account for lower urinary tract symptoms and urinary bladder dysfunction. There is now emerging evidence that ketamine misuse is also associated with abnormal liver function tests and biliary tract abnormality. We report three cases of chronic ketamine misuse in three young men who all presented with obstructive jaundice and biliary tract abnormality. We also describe the clinical features, radiological findings and potential underlying mechanisms for this new entity.
    • Choosing life or limb. Improving survival in the multi-complex diabetic foot patient.

      Game, Frances (2012-02)
      Over two decades ago, the St. Vincent Declaration set a 50% reduction of lower-limb amputations as a principal target for patients with diabetes. During this time, enormous strides have been taken in our understanding of diabetic foot disease, the complexities of wound healing and the organization of care to prevent what is one of the most feared complications of the disease. Despite this, we are aware that worldwide, we have not achieved the target set in 1989, with current estimations being that a limb is lost to diabetes somewhere in the world every 30 s. However, it has to be remembered that amputation is a treatment and not a disease, and it is indeed a treatment usually prescribed at the end of a long chronic illness. It is well known that patients whose disease is severe enough for amputation to be considered frequently have other complications of their diabetes, cardiovascular and peripheral vascular diseases and end-stage renal disease, in particular. The life expectancy of the patients is therefore frequently reduced, and their functional status poor even prior to the intervention of surgeons. Just as the functional status of the patients is often a contra-indication to other disease treatments, chemotherapy for some cancers, for example, then we should be considering carefully whether we should be removing limbs from patients whose functional and medical status will not improve significantly as a result. Equally, there may be patients who may benefit from an early amputation and ambulation with a prosthesis.
    • Chronic kidney disease in general populations and primary care: diagnostic and therapeutic considerations.

      Taal, Maarten (2013-11)
      PURPOSE OF REVIEW: The majority of people with chronic kidney disease (CKD) are managed by primary care physicians and nurses, but much of the initial research on CKD care was based in secondary care. The purpose of this article is to review the important recent studies of CKD in primary care that are starting to provide an evidence base for the strategies to improve the management and outcomes of the unreferred majority of people with CKD. RECENT FINDINGS: People with CKD in primary care populations differ substantially from those familiar to nephrologists in secondary care by being older, having less reduction in glomerular filtration rate (GFR) and lower prevalence of proteinuria. These differences have important implications for management priorities. Detailed studies have identified widespread deficiencies in the care of patients with CKD in primary care (though these are also reported in secondary care). Interventions that may improve performance include automated reporting of estimated GFR, incentivizing primary care practitioners to achieve therapeutic goals and quality improvement strategies such as audit-based education. SUMMARY: Studies have identified a need for improved management of CKD in primary care as well as methods to achieve this. Future studies should focus on the promotion of self-management through telemedicine and the Internet.
    • Chronic kidney disease in older people - diagnosis, aetiology and consequences.

      Taal, Maarten (2015-11)
      PURPOSE OF REVIEW: The prevalence of chronic kidney disease (CKD) steeply rises with age but there is controversy regarding the diagnosis and clinical significance of CKD in older people. This article reviews recent advances in our understanding with respect to the diagnosis, aetiology and adverse outcomes associated with CKD in older people. RECENT FINDINGS: Comparisons with measured glomerular filtration rate in a cohort of older people found that the Chronic Kidney Disease Epidemiology Collaboration equation using creatinine and cystatin C performs at least as well as other equations developed to estimate glomerular filtration rate in older populations. Several studies have identified modifiable risk factors in earlier life that are associated with increased risk of developing CKD in later life, including blood pressure, biomarkers of cardiovascular disease and lower serum bicarbonate. Numerous studies have confirmed that CKD in older people is associated with an increased risk of multiple adverse outcomes including death, end-stage kidney disease, cardiovascular events, acute kidney injury, severe infections and cognitive decline. SUMMARY: CKD is associated with the same adverse outcomes in older people as younger people. Further studies are required to develop interventions to reduce the incidence of CKD in older people and improve the associated adverse outcomes.
    • Chronic Kidney Disease in Primary Care: Outcomes after Five Years in a Prospective Cohort Study.

      Shardlow, Adam; McIntyre, Natasha; Fluck, Richard; McIntyre, Christopher; Taal, Maarten (2016-09)
      BACKGROUND: Chronic kidney disease (CKD) is commonly managed in primary care, but most guidelines have a secondary care perspective emphasizing the risk of end-stage kidney disease (ESKD) and need for renal replacement therapy. In this prospective cohort study, we sought to study in detail the natural history of CKD in primary care to better inform the appropriate emphasis for future guidance. METHODS AND FINDINGS: In this study, 1,741 people with CKD stage 3 were individually recruited from 32 primary care practices in Derbyshire, United Kingdom. Study visits were undertaken at baseline, year 1, and year 5. Binomial logistic regression and Cox proportional hazards models were used to model progression, CKD remission, and all-cause mortality. We used Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define CKD progression and defined CKD remission as the absence of diagnostic criteria (estimated glomerular filtration rate [eGFR] >60 ml/min/1.73 m2 and urine albumin-to-creatinine ratio [uACR] <3 mg/mmol) at any study visit. Participants were predominantly elderly (mean ± standard deviation (SD) age 72.9 ± 9.0 y), with relatively mild reduction in GFR (mean ± SD eGFR 53.5 ± 11.8 mL/min/1,73 m2) and a low prevalence of albuminuria (16.9%). After 5 y, 247 participants (14.2%) had died, most of cardiovascular causes. Only 4 (0.2%) developed ESKD, but 308 (17.7%) evidenced CKD progression by KDIGO criteria. Stable CKD was observed in 593 participants (34.1%), and 336 (19.3%) met the criteria for remission. Remission at baseline and year 1 was associated with a high likelihood of remission at year 5 (odds ratio [OR] = 23.6, 95% CI 16.5-33.9 relative to participants with no remission at baseline and year 1 study visits). Multivariable analyses confirmed eGFR and albuminuria as key risk factors for predicting adverse as well as positive outcomes. Limitations of this study include reliance on GFR estimated using the Modification of Diet in Renal Disease study (MDRD) equation for recruitment (but not subsequent analysis) and a study population that was predominantly elderly and white, implying that the results may not be directly applicable to younger populations of more diverse ethnicity. CONCLUSIONS: Management of CKD in primary care should focus principally on identifying the minority of people at high risk of adverse outcomes, to allow intervention to slow CKD progression and reduce cardiovascular events. Efforts should also be made to identify and reassure the majority who are at low risk of progression to ESKD. Consideration should be given to adopting an age-calibrated definition of CKD to avoid labelling a large group of people with age-related decline in GFR and low associated risk as having CKD.
    • Chronic kidney disease: towards a risk-based approach.

      Taal, Maarten (2016-12)
      Chronic kidney disease (CKD) affects 8-16% of adults worldwide and is associated with multiple adverse outcomes. It includes a heterogeneous group of conditions with widely varied associated risks; risk stratification is therefore vital for clinical management. Use of the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) instead of the Modification of Diet in Renal Disease (MDRD) equation will reduce, though not eliminate, over-diagnosis of CKD. Cystatin C is recommended as an alternative measure of GFR but is not yet widely used. A new classification system for CKD, which includes GFR and albuminuria, has been endorsed by the National Institute for Health and Care Excellence to aid risk stratification and a recently validated formula, requiring only age, gender, eGFR and albuminuria, is useful to predict risk of end-stage kidney disease (ESKD). A risk-based approach will facilitate appropriate treatment for people at high risk of developing ESKD while sparing the majority, who are at low risk, from unnecessary intervention.
    • Circulating endotoxaemia and frequent haemodialysis schedules

      Jefferies, Helen; Crowley, Lisa; McIntyre, Christopher (2014-11)
      BACKGROUND/AIMS: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels. METHODS: A cross-sectional study of 86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP). RESULTS: Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels. CONCLUSION: More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion.
    • Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease.

      McIntyre, Christopher; Harrison, Laura; Eldehni, Mohamed; Jefferies, Helen; John, Stephen; Sigrist, Mhairi; Burton, James; Korsheed, Shvan; Owen, Paul (2011-01)
      BACKGROUND AND OBJECTIVES: Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival. RESULTS: Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality. CONCLUSIONS: CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.
    • Classification of diabetic foot ulcers.

      Game, Frances (2016-01)
      It is known that the relative importance of factors involved in the development of diabetic foot problems can vary in both their presence and severity between patients and lesions. This may be one of the reasons why outcomes seem to vary centre to centre and why some treatments may seem more effective in some people than others. There is a need therefore to classify and describe lesions of the foot in patients with diabetes in a manner that is agreed across all communities but is simple to use in clinical practice. No single system is currently in widespread use, although a number have been published. Not all are well validated outside the system from which they were derived, and it has not always been made clear the clinical purposes to which such classifications should be put to use, whether that be for research, clinical description in routine clinical care or audit. Here the currently published classification systems, their validation in clinical practice, whether they were designed for research, audit or clinical care, and the strengths and weaknesses of each are explored.
    • Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment

      Maddison, Paul (2015-05)
      This retrospective case series, describes the clinical, histochemical, molecular, and imaging findings of the first 4 such patients treated HIV infection and evidence of mitochondrial dysfunction. Patients 1, 2, and 3 had significant levels of COX-deficient skeletal muscle fibers consistent with mitochondrial myopathy. Although the overall frequency of COX-deficient fibers in patient 4 was low, the presence of somatic mtDNA mutations and abnormal muscle bioenergetics suggests he also had a mild mitochondrial myopathy. In all cases, the observed mtDNA defect comprised mtDNA deletions rather than an mtDNA depletion as reported historically. This argues for the importance of previous rather than current NRTI exposure. Therefore, it was suggest that in HIV infected patients presenting with neuromuscular symptoms, the possibility of an acquired mitochondrial defect should continue to be considered in those patients with a relevant treatment history. Those patients with historical exposure to the polymerase γ–inhibiting dideoxynucleoside analogs are particularly worthy of further investigation