• Study tips for medical students.

      Cooper, Nicola (2019-04)
    • Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome - Capturing the discrepancy.

      Regan, Marian (2016-12)
      BACKGROUND: There is a weak relationship between subjective symptoms and objective markers of disease activity in individuals with Primary Sjögren's Syndrome (PSS). This presents a significant barrier to developing treatments if modifying disease markers does not translate into reduced perception of symptoms. Little is known about the reasons for this discrepancy. OBJECTIVES: To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a 'Sensitivity' scale) and to explore predictors of dryness Sensitivity. METHODS: Archive data from the UK Primary Sjogren's Syndrome Registry (n=681) was used. Patients were classified on a scale from -5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease-related factors and symptoms of pain, fatigue, anxiety and depression. RESULTS: Patients were on average relatively stoical for both dryness symptoms (ocular mean±s.d. -0.42±2.2, oral mean±s.d. -1.24±1.6). Twenty-seven percent of patients were classified 'sensitive' to ocular dryness in contrast to 9% for oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness was self-reported pain and the strongest predictor of oral dryness was self-reported fatigue. CONCLUSIONS: Ocular and oral dryness sensitivity can be classified on a continuous scale. The two symptom types are predicted by different variables. A large number of factors remain to be explored that may impact on symptom-sensitivity in PSS and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.
    • Successive breaks in biliary stents

      Guerra, Maria (2016-04)
      A 64 year-old male, was diagnosed with obstructive jaundice due to a well-differentiated pancreatic neuroendocrine tumor with liver metastases. The patient underwent endoscopic placement of covered self-expanding biliary stent (10x60 mm, Hanaro) by ERCP. He was admitted with cholangitis one year later. The following ERCP revealed a fractured stent with loss of the distal end (duodenal) and partial migration of the remaining stent to the common bile duct. The fragmented stent was removed from the common bile duct and a new, similar one was inserted. Four months later the patient was admitted with cholangitis. A new ERCP was done and biliary stent was also fragmented. It was removed and an uncovered stent (Wallflex) was inserted.
    • Summertime and the patient is itchy

      Hewitt, Susanne; Tabner, Andrew (2014-11)
      A 21-year-old man presented to the emergency department with a 36 h history of a painful, itchy maculopapular rash and associated vesicles to his arms and neck. He had no history of exposure to new chemicals or hygiene products and no significant medical history. His physiological observations were normal and systemic examination was unremarkable. On close inspection the rash was noted to be present only on areas of skin exposed while wearing a polo shirt. On further questioning it transpired that he had been gardening 12 h prior to the development of the rash. A diagnosis of phytophotodermatitis was made. The patient was discharged with chlorphenamine, simple analgesia and the advice to wear a long-sleeved t-shirt and sunscreen when gardening in future. Phytophotodermatitis is a cutaneous reaction caused by contact with light-sensitising compounds found in plants and exposure to ultraviolet A radiation. It is self-limiting and can be managed symptomatically.
    • Supporting staff information: the role of the renal clinical librarian

      James, Cathryn (2015-07)
      The study investigates the role of the renal clinical librarian in an acute renal setting in supporting information needs of clinical staff by providing a literature searching service for the benefit of the multidisciplinary team.
    • Survival prediction algorithms for COVID-19 patients admitted to a UK district general hospital

      Fernandez, Ancy; Obiechina, Nonyelum; Koh, Justin; Hong, Anna; Nandi, Angela; Reynolds, Tim (2021-01)
      Objective: To collect and review data from consecutive patients admitted to Queen's Hospital, Burton on Trent for treatment of Covid-19 infection, with the aim of developing a predictive algorithm that can help identify those patients likely to survive. Design: Consecutive patient data were collected from all admissions to hospital for treatment of Covid-19. Data were manually extracted from the electronic patient record for statistical analysis. Results: Data, including outcome data (discharged alive/died), were extracted for 487 consecutive patients, admitted for treatment. Overall, patients who died were older, had very significantly lower Oxygen saturation (SpO2) on admission, required a higher inspired Oxygen concentration (IpO2) and higher CRP as evidenced by a Bonferroni-corrected (P < 0.0056). Evaluated individually, platelets and lymphocyte count were not statistically significant but when used in a logistic regression to develop a predictive score, platelet count did add predictive value. The 5-parameter prediction algorithm we developed was: [Formula: see text] CONCLUSION: Age, IpO2 on admission, CRP, platelets and number of lungs consolidated were effective marker combinations that helped identify patients who would be likely to survive. The AUC under the ROC Plot was 0.8129 (95% confidence interval 0.0.773 - 0.853; P < .001).
    • Symptom Onset in Aortic Stenosis: Relation to Sex Differences in Left Ventricular Remodeling

      Kelly, Damian (2017-12)
      OBJECTIVES: The aim of this study was to establish sex differences in remodeling and outcome in aortic stenosis (AS) and their associations with biomarkers of myocardial fibrosis. BACKGROUND: The remodeling response and timing of symptoms is highly variable in AS, and sex plays an important role. METHODS: A total of 174 patients (133 men, mean age 66.2 ± 13.3 years) with asymptomatic moderate to severe AS underwent comprehensive stress cardiac magnetic resonance imaging, transthoracic echocardiography, and biomarker analysis (matrix metalloproteinase [MMP]-2, -3, -7, -8, and -9; tissue inhibitor matrix metalloproteinases-1 and -4; syndecan-1 and -4; and N-terminal pro-B-type natriuretic peptide), and were followed up at 6-month intervals. A primary endpoint was a composite of typical AS symptoms necessitating referral for aortic valve replacement, cardiovascular death, or major adverse cardiovascular events. RESULTS: For a similar severity of AS, male patients demonstrated higher indexed left ventricular (LV) volumes and mass, more concentric remodeling (higher LV mass/volume), a trend to more late gadolinium enhancement (present in 51.1% men vs. 34.1% women; p = 0.057), and higher extracellular volume index than female patients (13.27 [interquartile range (IQR): 11.5 to 17.0] vs. 11.53 [IQR: 10.5 to 13.5] ml/m2, p = 0.017), with worse systolic and diastolic function and higher MMP-3 and syndecan-4 levels, whereas female patients had higher septal E/e'. Male sex was independently associated with indexed LV mass (β = 13.32 [IQR: 9.59 to 17.05]; p < 0.001). During median follow-up of 374 (IQR: 351 to 498) days, a primary outcome, driven by spontaneous symptom onset, occurred in 21.8% of male and 43.9% of female patients (relative risk: 0.50 [95% confidence interval: 0.31 to 0.80]; p = 0.004). Measures of AS severity were associated with the primary outcome in both sexes, whereas N-terminal pro-B-type natriuretic peptide, MMP-3, and mass/volume were only associated in men. CONCLUSIONS: In AS, women tolerate pressure overload with less concentric remodeling and myocardial fibrosis but are more likely to develop symptoms. This may be related to higher wall stress and filling pressures in women.
    • A Systematic Review of the Acute Effects of Hemodialysis on Skeletal Muscle Perfusion, Metabolism, and Function

      Hussain, Samia; Selby, Nicholas (2019-12)
      Introduction: The underlying mechanisms of skeletal muscle wasting in hemodialysis patients are complex. We performed a systematic review to summarize evidence on whether hemodialysis has acute effects on skeletal muscle perfusion, metabolism, and function. Methods: The protocol was registered on PROSPERO (Registration number CRD42018103682). A systematic search was performed in MEDLINE, PubMed, Cochrane, Embase, Scopus, and Web of Science. Citation, reference list, and gray literature searches were also performed. Studies were selected in 2 stages: title and abstract review, then full-text review. Results: A total of 65 full-text articles were reviewed, and 14 studies were eligible for inclusion. No studies were identified that assessed muscle perfusion during dialysis. Two studies used near-infrared spectroscopy to indirectly measure skeletal muscle oxygen consumption, which increased during dialysis in 1 study but only in patients with diabetes in the second. Metabolism was examined in 9 studies. A number of acute metabolic changes were reported (e.g., caspase-3 activity, polyubiquitin, and interleukin-6 protein increased in response to hemodialysis) as was a net negative protein balance over the dialysis session. Three studies examining muscle function did not produce consistent findings. Conclusion: Gaps remain in understanding the acute effects of hemodialysis on skeletal muscle, particularly for changes in perfusion and function, although there does appear to be an acute effect on muscle metabolism.
    • Takotsubo cardiomyopathy (Broken heart syndrome).

      Chitkara, Kamal (2015-11)
      Takotsubo cardiomyopathy is an acute reversible cardiomyopathy characterised by transient regional left ventricular (LV) motion abnormalities. It is diagnosed on a coronary angiography and left ventriculography. We report the case of a 50-year-old lady who presented with sudden onset of chest pain, with no history of cardiac disease and no risk factors. Remarkably though, she had lost her husband the previous night. Coronary and LV angiography was done which revealed findings typical of takotsubo cardiomyopathy. We report this case for its rarity. Informed consent was taken from the patient before undertaking and reporting this study.
    • Techniques to improve intradialytic haemodynamic stability.

      Selby, Nicholas (2018-08)
      PURPOSE OF REVIEW: Intra-dialytic hypotension (IDH) remains a significant problem for patients undergoing chronic haemodialysis. IDH causes symptoms that degrade patients' experience, compromises dialysis delivery and is strongly associated with adverse patient outcomes. Greater understanding of the link between IDH and dialysis-induced ischaemia in heart and brain has characterized mechanistic pathways, with repeated episodes of ischaemia resulting in organ dysfunction. This review provides updates from published evidence over the last 2 years across the range of potential interventions for IDH. RECENT FINDINGS: A literature search was undertaken to identify articles published in peer review journals between January 2016 and April 2018 using terms 'intradialytic hypotension,' 'haemodynamic instability,' 'ESRF,' 'renal replacement therapy,' 'dialysis' in Medline and EMBASE and identified 58 references from which 15 articles were included in this review. Interventions included: cooling the dialysate; sodium profiling; convective therapies; strategies to minimize inter-dialytic weight gain (IDWG) and improve accuracy of target weight assessment; prescribing of antihypertensive medications; and carnitine supplementation. SUMMARY: IDH remains a significant clinical problem. Recent evidence from the last 2 years does not support any major changes to current practice, with cooling of the dialysate and reduction of IDWG remaining cornerstones of management.
    • The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease.

      McIntyre, Christopher (2015-07)
      A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.
    • The burden of comorbidity in people with chronic kidney disease stage 3: a cohort study.

      Taal, Maarten; Fluck, Richard; Shardlow, Adam; McIntyre, Natasha; McIntyre, Christopher (2015-12)
      BACKGROUND: Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. Chronic kidney disease (CKD) is common but often considered in isolation. The extent and prognostic significance of its comorbidities is not well understood. This study aimed to assess the extent and prognostic significance of 11 comorbidities in people with CKD stage 3. METHODS: A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling. Comorbidity was defined by self-reported doctor-diagnosed condition, disease-specific medication or blood results (hemoglobin), and treatment burden as number of ongoing medications. Logistic regression was used to identify associations with greater treatment burden (taking >5 medications) and greater multimorbidity (3 or more comorbidities). Kaplan Meier plots and multivariate Cox proportional hazards models were used to investigate associations between multimorbidity and all-cause mortality. RESULTS: One thousand seven hundred forty-one people were recruited, mean age 72.9 +/-9 years. Mean baseline eGFR was 52 ml/min/1.73 m(2). Only 78/1741 (4 %) had no comorbidities, 453/1741 (26 %) had one, 508/1741 (29 %) had two and 702/1741 (40 %) had >2. Hypertension was common (88 %), 30 % had 'painful condition', 24 % anemia, 23 %, ischaemic heart disease, 17 % diabetes and 12 % thyroid disorders. Median medication use was 5 medications (interquartile range 3-8) and increased with degree of comorbidity. Greater treatment burden and multimorbidity were independently associated with age, smoking, increasing body mass index and decreasing eGFR. Treatment burden was also independently associated with lower education status. After median 3.6 years follow-up, 175/1741 (10 %) died. Greater multimorbidity was independently associated with mortality (hazard ratio 2.81 (95 % confidence intervals 1.72-4.58), p < 0.001) for 3 or more comorbidities vs 0 or 1). CONCLUSIONS: Isolated CKD was rare and multimorbidity the norm in this cohort of people with moderate CKD. Increasing multimorbidity was associated with greater medication burden and poorer survival. CKD management should include consideration of comorbidities.
    • The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study.

      Shardlow, Adam; McIntyre, Natasha; Fluck, Richard; Taal, Maarten (2017-10)
      BACKGROUND: To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45-59 ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed. METHODS AND FINDINGS: A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to 'no CKD' or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFRcys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFRcys to confirm the diagnosis in people classified as CKD G3aA1 by eGFRcreat. Mean eGFRcys was significantly lower than mean eGFRcreat (45.1 ml/min/1.73 m2, 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m2, 95% CI 53.0 to 54.1, P < 0.001). eGFRcys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFRcreat to eGFR ≥ 60 ml/min/1.73 m2. However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFRcreat-cys, but lower proportions were reclassified. Change in eGFRcreat and eGFRcys over 5 years were weakly correlated (r = 0.33, P < 0.001), but eGFRcys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFRcreat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFRcys. Use of eGFRcys or eGFRcreat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFRcreat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort. CONCLUSIONS: Implementation of current guidelines on eGFRcys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFRcreat. Use of eGFRcys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFRcys and eGFRcreat-cys.
    • The dietary management of patients with diabetes and renal disease: challenges and practicalities.

      Willingham, Fiona (2012-02)
      Diabetes mellitus is one of the major causes of chronic kidney disease and end-stage renal disease. Diet and lifestyle modification are vital components of optimal treatment for both conditions. This paper will address appropriate and often diverse treatment for each individual, understanding that advising changes which positively impact both conditions is a major challenge for health care professionals working within either speciality. It will also highlight where overlap can be contradictory rather than complementary, and offers practical guidance to support patients in making the necessary lifestyle changes to have maximal positive impact upon both conditions and their overall health.
    • The effects of acute kidney injury on long-term renal function and proteinuria in a general hospitalised population.

      Horne, Kerry; Packington, Rebecca; Monaghan, John; Reilly, Timothy; McIntyre, Christopher; Selby, Nicholas (2014-11)
      BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and is associated with adverse long-term consequences. There is an urgent need to understand these sequelae in general hospitalised patients utilising a prospective cohort-based approach. We aimed to test the feasibility of study methodology prior to commencing a large-scale study and investigate the effects of AKI on chronic kidney disease (CKD) progression and proteinuria. METHODS: Pilot study testing novel methodology for remote patient recruitment within a prospective case-control design. 300 cases (hospitalised patients with AKI) and controls (hospitalised patients without AKI) were matched 1:1 for age and baseline estimated glomerular filtration rate (eGFR). 70% of cases had AKI stage 1, 16% AKI stage 2 and 14% AKI stage 3. Renal function and proteinuria were measured 3 and 12 months after hospital admission. RESULTS: The study met pre-defined recruitment, withdrawal and matching criteria. Renal function was worse in the AKI group at 3 (eGFR 61 ± 20 vs. 74 ± 23 ml/min/1.73 m(2), p < 0.001) and 12 months (eGFR 64 ± 23 vs. 75 ± 25 ml/min/1.73 m(2), p < 0.001). More cases than controls had CKD progression at 3 months (14 vs. 0.7%, p < 0.001). This difference persisted to 12 months, but there was no significant change between 3 and 12 months. Proteinuria and albuminuria were more prevalent in the AKI group and associated with CKD progression. CONCLUSIONS: We describe a method of remote patient recruitment which could be employed more widely for prospective observational studies. Even mild AKI is associated with long-term renal dysfunction. Further investigation using this methodology is now underway.
    • The efficacy of unsupervised home-based exercise regimens in comparison to supervised laboratory-based exercise training upon cardio-respiratory health facets.

      Blackwell, James; Doleman, Brett; Williams, John P; Lund, Jonathan (2017-09)
      Supervised high-intensity interval training (HIIT) can rapidly improve cardiorespiratory fitness (CRF). However, the effectiveness of time-efficient unsupervised home-based interventions is unknown. Eighteen volunteers completed either: laboratory-HIIT (L-HIIT); home-HIIT (H-HIIT) or home-isometric hand-grip training (H-IHGT). CRF improved significantly in L-HIIT and H-HIIT groups, with blood pressure improvements in the H-IHGT group only. H-HIIT offers a practical, time-efficient exercise mode to improve CRF, away from the laboratory environment. H-IHGT potentially provides a viable alternative to modify blood pressure in those unable to participate in whole-body exercise.
    • The epidemiology of hospitalised acute kidney injury not requiring dialysis in England from 1998 to 2013: retrospective analysis of hospital episode statistics

      Kolhe, Nitin; Taal, Maarten (2016-04)
      Epidemiology studies of acute kidney injury (AKI) have focused on cases requiring dialysis but those not requiring dialysis represent the majority. To address this gap, we interrogated hospital episode statistics (HES) to investigate population trends in temporal epidemiology of AKI not requiring dialysis between 1998 and 2013. METHODOLOGY: In this retrospective observational study of HES data covering the entire English National Health Service, we identified 1,136,167 AKI events, not requiring dialysis, diagnosed between 1998 and 2013. We explored the effect of age, gender, ethnicity, Charlson's comorbidity score (CCS), method of admission, diagnosis period and AKI in diagnosis codes on temporal changes in the incidence and case-fatality of AKI with specific examination of its predictors. RESULT: The incidence of AKI increased from 15,463 cases (317 pmp) in 1998-1999 to 213,700 cases (3995 pmp) in 2012-2013. There was increase in proportion of people over 75 years from 51.1% in 1998-1999 to 63.4% in 2012-2013. Overall unadjusted case-fatality decreased from 42.3% in 1998-2003 to 27.1% in 2008-2013, p < 0.001. Compared with 1998-2003, the multivariable adjusted odds ratio for death was 0.64 in 2003-2008 (95% CI 0.63-0.65) and 0.35 in 2008-2013 (95% CI 0.34-0.35). Odds for death were higher for patients over 85 years (2.93; 95% CI 2.89-2.97), CCS of more than five (2.75; 95% CI 2.71-2.79), emergency admissions (2.14; 95% CI 2.09-2.18) and AKI in the secondary diagnosis code (1.35; 95% CI 1.33-1.36) and AKI in other diagnoses codes (2.17; 95% CI 2.15-2.20). CONCLUSIONS: In England, the incidence of AKI not requiring dialysis has increased and case-fatality has decreased over last 15 years. Efforts to reduce the incidence of AKI and improve survival should focus on elderly people, emergency admissions and those with multi-morbidity.