• Safety and effectiveness of Do-It-Yourself Artificial Pancreas System (DIYAPS) compared with continuous subcutaneous insulin infusions (CSII) in combination with Free Style Libre (FSL) in people with Type 1 diabetes.

      Crabtree, T; Taylor, Nick; Langeland, L; Wilmot, Emma; Idris, Iskandar
      The use of do-it-yourself artificial pancreas systems (DIYAPS) amongst people with type 1 diabetes is increasing. At present, it is unclear DIYAPS comepares to other technologies such as FreeStyle Libre (FSL) and continuous subcutaneous insulin infusion (CSII). The aim of this analysis is to compare safety, effectiveness and quality of life outcomes of DIYAPS use with the addition of FSL to CSII. METHOD: Data from two large UK hospitals were extracted from the Association of British Clinical Diabetologists (ABCD) DIYAPS and FSL audits. Outcomes included HbA1c, glucose TBR (time-below-range), TIR (time-in-range), Diabetes Distress Scores (DDS) and Gold hypoglycaemia Score. Any adverse events were noted. Changes at follow-up were assessed using paired t-tests and ANOVA in Stata; TIR/TBR at follow-up assessed using unpaired T-Tests; Chi-square tests assessed the change in frequency of health utilisation (e.g. hospital admissions). RESULTS: DIYAPS (n=35) and FSL+CSII (n=149) users, with median follow-up duration of 1.4 (IQR 0.8-2.1) and 1.3 (IQR 0.7-1.8) years respectively, were included. HbA1c with DIYAPS use changed by -10mmol/mol [0.9%] (p<0.001, 95% CI 5, 14 [0.5, 1.3%]) significantly lower (p<0.001) than in the FSL+CSII group -3 mmol/mol [0.25%] (p<0.001, 95% CI 1, 4 [0.1, 0.4%]). TIR was higher and TBR was lower in the DIYAPS group. Adverse events were rare in both groups and no significant differences were observed in the frequency of healthcare utilisation. CONCLUSION: DIYAPS use was associated with a lower HbA1c levels, higher TIR and lower TBR compared to FSL+CSII. There was no significant increase in adverse events, although this should be interpreted cautiously given the low numbers of users. Full results from the ABCD DIYAPS audit are awaited.
    • The serological diagnosis of coeliac disease - a step forward.

      Holmes, Geoffrey (2018-07)
      The development of highly performing serological tests to identify patients with coeliac disease (CD), allowed large scale screening studies to be carried out and the results transformed our understanding of the prevalence of the condition in the general population. The next logical step was to ask whether CD could be reliably diagnosed by these tests without the need for small intestinal biopsies. This was shown to be the case. Studies from Derby, UK, indicated that about half of adult patients can be diagnosed in this way and similar figures have been provided for children. When considering this approach, it is essential that laboratories only use highly performing test kits that they have validated to measure tissue transglutaminase antibodies because all kits do not function to the same high standard. There remains a place for biopsy when criteria for serological diagnosis are not met, if the diagnosis of CD is strongly suspected but serological tests are negative or in patients not showing the expected responses to gluten free diet or otherwise causing concern, when not only small bowel biopsy will be indicated but also other investigations. Those with refractory CD should not be compromised by this diagnostic strategy. As serological tests become more refined and information accumulates, it is likely that this mode of diagnosis will gather momentum for the benefit of patients and carers. This brief review looks at the evidence for making the diagnosis of CD in some cases by serological tests alone.
    • Service provision for liver disease in the UK: a national questionnaire-based survey.

      Scott, Robert; Williams, M; Austin, Andrew; Freeman, Jan (2012-04)
      The National Plan for Liver Services in 2009 called for a review of current liver services across the UK to identify areas of good and poor provision. We present the results of a national questionnaire survey of liver services, which focussed on staffing and training, access to key facilities and clinical management of liver disease. Areas of good practice include the increased proportion of consultants who trained at a liver centre, the introduction of specific liver clinics and the widespread use of terlipressin and antibiotics for variceal bleeding. Areas of poor practice include limited access to alcohol psychiatry services and transjugular intrahepatic portosystemic shunts (TIPS) and limited recording of outcome measures or patient databases. Wide variation in the clinical management of serious liver diseases supports the need for managed clinical networks. These results will help to guide the development of standards of care for liver services across the UK.
    • Sex differences in acute kidney injury requiring dialysis.

      Kolhe, Nitin (2018-06)
      BACKGROUND: Female sex has been included as a risk factor in models developed to predict the risk of acute kidney injury (AKI) associated with cardiac surgery, aminoglycoside nephrotoxicity and contrast-induced nephropathy. The commentary acompanying the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury concludes that female sex is a shared susceptibility factor for acute kidney injury based on observations that female sex is associated with the development of hospital-acquired acute kidney injury. In contrast, female sex is reno-protective in animal models. In this context, we sought to examine the role of sex in hospital-associated acute kidney injury in greater detail. METHODS: We utilized the Hospital Episode Statistics database to calculate the sex-stratified incidence of AKI requiring renal replacement therapy (AKI-D) among 194,157,726 hospital discharges reported for the years 1998-2013. In addition, we conducted a systematic review of the English literature to evaluate dialysis practices among men versus women with AKI. RESULTS: Hospitalized men were more likely to develop AKI-D than hospitalized women (OR 2.19 (2.15, 2.22) p < 0.0001). We found no evidence in the published literature that dialysis practices differ between men and women with AKI. CONCLUSIONS: Based on a population of hospitalized patients which is more than 3 times larger than all previously published cohorts reporting sex-stratified AKI data combined, we conclude that male sex is associated with an increased incidence of hospital-associated AKI-D. Our study is among the first reports to highlight the protective role of female gender in AKI.
    • Short-term adverse remodeling progression in asymptomatic aortic stenosis

      Kelly, Damian (2020-11)
      Objectives: Aortic stenosis (AS) is characterised by a long and variable asymptomatic course. Our objective was to use cardiovascular magnetic resonance imaging (MRI) to assess progression of adverse remodeling in asymptomatic AS. Methods: Participants from the PRIMID-AS study, a prospective, multi-centre observational study of asymptomatic patients with moderate to severe AS, who remained asymptomatic at 12 months, were invited to undergo a repeat cardiac MRI. Results: Forty-three participants with moderate-severe AS (mean age 64.4 ± 14.8 years, 83.4% male, aortic valve area index 0.54 ± 0.15 cm2/m2) were included. There was small but significant increase in indexed left ventricular (LV) (90.7 ± 22.0 to 94.5 ± 23.1 ml/m2, p = 0.007) and left atrial volumes (52.9 ± 11.3 to 58.6 ± 13.6 ml/m2, p < 0.001), with a decrease in systolic (LV ejection fraction 57.9 ± 4.6 to 55.6 ± 4.1%, p = 0.001) and diastolic (longitudinal diastolic strain rate 1.06 ± 0.2 to 0.99 ± 0.2 1/s, p = 0.026) function, but no overall change in LV mass or mass/volume. Late gadolinium enhancement increased (2.02 to 4.26 g, p < 0.001) but markers of diffuse interstitial fibrosis did not change significantly (extracellular volume index 12.9 [11.4, 17.0] ml/m2 to 13.3 [11.1, 15.1] ml/m2, p = 0.689). There was also a significant increase in the levels of NT-proBNP (43.6 [13.45, 137.08] pg/ml to 53.4 [19.14, 202.20] pg/ml, p = 0.001). Conclusions: There is progression in cardiac remodeling with increasing scar burden even in asymptomatic AS. Given the lack of reversibility of LGE post-AVR and its association with long-term mortality post-AVR, this suggests the potential need for earlier intervention, before the accumulation of LGE, to improve the long-term outcomes in AS. Key points: • Current guidelines recommend waiting until symptom onset before valve replacement in severe AS. • MRI showed clear progression in cardiac remodeling over 12 months in asymptomatic patients with AS, with near doubling in LGE. • This highlights the need for potentially earlier intervention or better risk stratification in AS.
    • Similarities and differences in health-related behavior clustering among older adults in Eastern and Western countries: A latent class analysis of global aging cohorts.

      Mawditt, C (2019-07)
      AIM: To quantify variations in health-related behaviors (HRB) clustering of older adults in Western and Eastern countries. METHODS: Using six aging cohorts from the USA, England, Europe, Japan, Korea and China, latent class analysis was applied to access the clustering of smoking, alcohol consumption, physical activity and social activity. RESULTS: A total of 104 552 participants (55% women) aged ≥50 years in 2010 were included. Despite a different number of clusters identified, three consistent cluster profiles emerged: "Multiple-HRB" (ex-/never smoking, moderate drinking, frequent physical and social activity); "Inactives" (socially and physically inactive without other risk behaviors); and "(ex-)Smokers with Risk Behaviors". Sex and cohort variations were shown. For men in Western cohorts, "Multiple-HRB" was the predominant cluster, whereas their Asian counterparts were more likely to be members of the "Smokers with risk behavior" and "Inactives" clusters. Most women, particularly those in Asian cohorts, were never smokers and non-drinkers, and most of them belonged to the socially "Inactives" cluster. CONCLUSIONS: We provide a person-centered understanding of HRB clustering of older adults over selected countries by sex, informing tailored health promotion for the target population.
    • Simultaneous multifocal intracranial haemorrhage (ICH) and subarachnoid haemorrhage (SAH) in the setting of long-term cocaine usage.

      Basi, Saajan
      A 45-year-old Caucasian man was admitted to hospital following a collapse at home. On admission, this patient was noted to have a Glasgow Coma Scale (GCS) Score of 9 out of 15, fever and tachypnoea. The patient was identified to have bilateral limb weakness, predominately on the left side, with associated dysphagia. Radiological imaging demonstrated bilateral multifocal intracranial haemorrhage and subarachnoid haemorrhage. Neurosurgical input was sought; the outcome of this was a decision to manage the patient conservatively, without surgical intervention. Of note, his urine drug testing revealed a positive result for a cocktail of drugs including cocaine, benzoylecgonine (cocaine metabolite), methadone, heroin, norbuprenorphine and benzodiazepine. Throughout the admission, the patient was monitored in an intensive care setting. The patient received support with feeding, speech and mobilisation. The patients' GCS improved throughout the admission. Following a 30-day admission, the patient walked home.
    • Sister Mary Joseph´s nodule

      Guerra, Maria (2016-02)
    • Skin autofluorescence and all-cause mortality in stage 3 CKD.

      Taal, Maarten; Fluck, Richard; McIntyre, Christopher; McIntyre, Natasha (2014-08)
      BACKGROUND AND OBJECTIVES: Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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 for biochemistry, and measurement of skin autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality. RESULTS: In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P<0.001) on Kaplan-Meier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P<0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin. CONCLUSIONS: Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD.
    • Skin autofluorescence and the association with renal and cardiovascular risk factors in chronic kidney disease stage 3.

      McIntyre, Natasha; Fluck, Richard; McIntyre, Christopher; Taal, Maarten (2011-10)
      BACKGROUND AND OBJECTIVES: Tissue advanced glycation end products (AGE) accumulation is a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluorescence (SAF) correlates well with cardiovascular (CV) outcomes in diabetic, transplant, and dialysis patients, and may be a useful marker of CV risk in earlier stages of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 1707 patients with estimated GFR 59 to 30 ml/min per 1.73 m(2) were recruited from primary care practices for the Renal Risk In Derby (RRID) study. Detailed medical history was obtained, and each participant underwent clinical assessment as well as urine and serum biochemistry tests. SAF was assessed (mean of three readings) as a measure of skin AGE deposition using a cutaneous AF device (AGE Reader™, DiagnOptics, Groningen, The Netherlands). RESULTS: Univariate analysis revealed significant correlations between AF readings and several potential risk factors for cardiovascular disease (CVD) and progression of CKD. SAF readings (arbitrary units) were also significantly higher among males (2.8 ± 0.7 versus 2.7 ± 0.6), diabetics (3.0 ± 0.7 versus 2.7 ± 0.6), patients with evidence of self-reported CVD (2.9 ± 0.7 versus 2.7 ± 0.6), and those with no formal educational qualifications (2.8 ± 0.6 versus 2.6 ± 0.6; P < 0.01 for all). Multivariable linear regression analysis identified hemoglobin, diabetes, age, and eGFR as the most significant independent determinants of higher SAF (standardized coefficients -0.16, 0.13, 0.12, and -0.10, respectively; R(2) = 0.17 for equation). CONCLUSION: Increased SAF is independently associated with multiple CV and renal risk factors in CKD 3. Long-term follow-up will assess the value of SAF as a predictor of CV and renal risk in this population.
    • Skin autofluorescence: an emerging biomarker in persons with kidney disease.

      Taal, Maarten (2019-11)
      PURPOSE OF REVIEW: Skin autofluorescence (SAF) is a measure of the accumulation of advanced glycation end-products (AGEs) proposed to act as a marker of 'cumulative metabolic stress'. This article discusses mechanisms of AGE formation and reviews published literature on SAF as a biomarker and risk factor across the spectrum of kidney disease. RECENT FINDINGS: SAF is elevated in adults and children on dialysis. Higher SAF is an independent risk factor for cardiovascular and all-cause mortality in persons receiving haemodialysis and for all-cause mortality in persons performing peritoneal dialysis, though the increase in discrimination when SAF was added to traditional risk factors was modest. In less advanced chronic kidney disease, higher SAF predicts all-cause mortality and progression. SAF is elevated in renal transplant recipients, but to a lesser extent than in dialysis patients. In one study, higher SAF predicted graft loss and mortality. SAF has been reported to be increased in patients with acute kidney injury. SUMMARY: A growing body of evidence attests that SAF, a marker of AGE accumulation, is a risk factor for mortality and kidney function decline in multiple types of kidney disease. Further studies are warranted to evaluate interventions to reduce SAF and the impact on clinical outcomes.
    • Sleep-wake regularity and cardiovascular events.

      Sahibzada, Salman (2019-07)
      Comment on Nocturnal heart rate variability moderates the association between sleep-wake regularity and mood in young adults. [Sleep. 2019]
    • Special Low Protein Foods Prescribed in England for PKU Patients: An Analysis of Prescribing Patterns and Cost.

      Mackenzie, A (2021)
      Patients with phenylketonuria (PKU) are reliant on special low protein foods (SLPFs) as part of their dietary treatment. In England, several issues regarding the accessibility of SLPFs through the national prescribing system have been highlighted. Therefore, prescribing patterns and expenditure on all SLPFs available on prescription in England (n = 142) were examined. Their costs in comparison to regular protein-containing (n = 182) and 'free-from' products (n = 135) were also analysed. Similar foods were grouped into subgroups (n = 40). The number of units and costs of SLPFs prescribed in total and per subgroup from January to December 2020 were calculated using National Health Service (NHS) Business Service Authority (NHSBSA) ePACT2 (electronic Prescribing Analysis and Cost Tool) for England. Monthly patient SLPF units prescribed were calculated using patient numbers with PKU and non-PKU inherited metabolic disorders (IMD) consuming SLPFs. This was compared to the National Society for PKU (NSPKU) prescribing guidance. Ninety-eight percent of SLPF subgroups (n = 39/40) were more expensive than regular and 'free-from' food subgroups. However, costs to prescribe SLPFs are significantly less than theoretical calculations. From January to December 2020, 208,932 units of SLPFs were prescribed (excluding milk replacers), costing the NHS £2,151,973 (including milk replacers). This equates to £962 per patient annually, and prescribed amounts are well below the upper limits suggested by the NSPKU, indicating under prescribing of SLPFs. It is recommended that a simpler and improved system should be implemented. Ideally, specialist metabolic dietitians should have responsibility for prescribing SLPFs. This would ensure that patients with PKU have the necessary access to their essential dietary treatment, which, in turn, should help promote dietary adherence and improve metabolic control.
    • Splinter haemorrhages and brain infarcts as an unusual presentation of sarcoidosis

      Ayub, Shazeen; Hawari, Rand; Mahmood-Rao, Hamzah
      We present an interesting case of a healthy 47-year-old woman who presented to the acute take with symptoms of visual apraxia, splinter haemorrhages and extreme fatigue. This was a diagnostic challenge with other unusual features to this case, which includes brain infarcts on MRI, raised troponin and oeosinophilia. Naturally endocarditis was the top differential but this was ruled out by serial negative blood cultures and a negative transthoracic echocardiogram. Several medical specialties were involved and the initial working diagnosis was ANCA vasculitis (oeosinophilic granulomatosis with polyangiitis). Early administration of intravenous steroids clouded our judgement further and sarcoidosis was not thought as a possible differential. We illustrate the immensely challenging and complicated clinical course involving multiple specialties and investigations. In the end, a complete steroid wean was required to reach an accurate histological diagnosis.
    • Spontaneous Rupture of a Pseudoaneurysm of the Right Hepatic Artery Causing Massive Upper Gastrointestinal Bleeding

      MHK Farid, Bahrin (Derby NHS, 2018-08)
      We describe the case of an 84-year-old woman who presented with right lower chest pain, anaemia and newly deranged liver function which was followed by massive upper gastrointestinal (GI) bleeding with no source of bleeding found on upper GI endoscopy. CT angiography of the GI tract confirmed rupture of a pseudoaneurysm of the right hepatic artery (RHA) that was treated successfully with trans-arterial embolization of the RHA.LEARNING POINTS: If upper gastrointestinal (GI) endoscopy fails to identify the source of upper GI bleeding, CT angiography is required to search for rare causes such as pseudoaneurysm of the right hepatic artery (RHA) with fistula formation with the GI and biliary tract, along with other causes such as aorto-enteric fistula.Pseudoaneurysm of the RHA is commonly secondary to recent surgery or trauma and spontaneous occurrence is very rare.Endovascular repair using transcatheter arterial embolization is the treatment of choice but if it fails, emergency laparotomy should be considered.
    • Standardizing the Early Identification of Acute Kidney Injury: The NHS England National Patient Safety Alert.

      Selby, Nicholas; Fluck, Richard (2015-09)
      Whilst varying standards of care for patients with acute kidney injury (AKI) continue to contribute to poor outcomes, a strong focus on strategies to drive quality improvement is paramount. To this end, a national Patient Safety Alert was issued in June 2014 to all healthcare providers in England entitled 'Standardising the Early Identification of Acute Kidney Injury'. The aim was to embed an automated AKI detection system in the biochemistry laboratories of all acute hospitals. In addition to the direct clinical benefits that may come from earlier and more systematic recognition of AKI, it has also helped position AKI as a patient safety issue and will feed a national AKI registry, the latter a potent tool for future measurement and improvement initiatives.