A simple tool for comparing benefits and 'costs' of COVID-19 exit strategies.

BACKGROUND: Governments and health policymakers are now looking for strategies to lift the COVID-19 lockdown, while reducing risk to the public. METHODS: We propose the population attributable risk (PAR) as an established epidemiological tool that could support decision-making through quickly estimating the main benefits and costs of various exit strategies. RESULTS: We demonstrate the feasibility of use of PAR using pandemic data, that were publicly available in mid-May 2020 from Scotland and the US, to estimate the proportion of COVID-19 hospital admissions which might be avoided, and the proportion of adverse labour market effects - for various scenarios - based on maintaining the lockdown for those of certain ages with and without comorbidities. CONCLUSION: These calculations could be refined and applied in different countries to inform important COVID-19 policy decisions, using routinely collected data.

Nicolau Syndrome (Embolia Cutis Medicamentosa): A Rare and Poorly Recognized Iatrogenic Cause of Cutaneous Thrombotic Vasculopathy.

Nicolau syndrome is a rare form of iatrogenic cutaneous necrosis which affects injection sites. Although classically associated with intramuscular injections, it may develop after subcutaneous or other routes of parenteral drug administration. Clinically, it manifests as necrotic ulcers that often develop in a background of erythematous and livedoid reticular patches. The histopathologic characteristics of Nicolau syndrome are poorly documented in the dermatopathology literature and features only rarely as one of the obscure causes of cutaneous thrombotic vasculopathy. We report a case of Nicolau syndrome developing secondary to subcutaneous injection of cyclizine to familiarize the clinicians and pathologists to this unusual condition. Given that it is potentially avoidable, pathologists should alert the clinicians to the possibility of Nicolau syndrome when a skin biopsy from an injection site shows signs of extensive thrombotic vasculopathy.

Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival.

Systemic inflammation, as evidenced by elevated inflammatory cytokines, is a feature of advanced renal failure and predicts worse survival. Dialysate IL-6 concentrations associate with variability in peritoneal small solute transport rate (PSTR), which has also been linked to patient survival. Here, we determined the link between systemic and intraperitoneal inflammation with regards to peritoneal membrane function and patient survival as part of the Global Fluid Study, a multinational, multicenter, prospective, combined incident and prevalent cohort study (n=959 patients) with up to 8 years of follow-up. Data collected included patient demographic characteristics, comorbidity, modality, dialysis prescription, and peritoneal membrane function. Dialysate and plasma cytokines were measured by electrochemiluminescence. A total of 426 survival endpoints occurred in 559 incident and 358 prevalent patients from 10 centers in Korea, Canada, and the United Kingdom. On patient entry to the study, systemic and intraperitoneal cytokine networks were dissociated, with evidence of local cytokine production within the peritoneum. After adjustment for multiple covariates, systemic inflammation was associated with age and comorbidity and independently predicted patient survival in both incident and prevalent cohorts. In contrast, intraperitoneal inflammation was the most important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation and membrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinct processes and consequences in patients treated with peritoneal dialysis, so their prevention may require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation.

Chapter 7 Adequacy of haemodialysis in UK adult patients in 2010: national and centre-specific analyses.

BACKGROUND: Outcome in patients treated with haemodialysis (HD) is influenced by the delivered dose of dialysis. The UK Renal Association (RA) publishes clinical practice guidelines which include recommendations for dialysis dose. The urea reduction ratio (URR) is a widely used measure of dialysis dose. AIM: To determine the extent to which patients received the recommended dose of HD in the UK. METHODS: All seventy-two UK renal centres submitted data to the UK Renal Registry (UKRR). Two groups of patients were included in the analyses: the prevalent patient population on 31st December 2010 and the incident patient population for 2010. Centres returning data on <50% of their patient population or centres with <20 patients were excluded from centre-specific comparisons. RESULTS: Data regarding URR were available from 64 renal centres in the UK. Forty nine centres provided URR data on more than 90% of prevalent patients. The proportion of patients in the UK who met the UK clinical practice guideline for URR (>65%) increased from 56% in 1998 to 86% in 2010. There was persistent variation observed between centres, with 19 centres attaining the RA clinical practice guideline in >90% of patients and 39 centres attaining the guideline in 70-90%. The overall proportion of prevalent patients with a URR >65% has continued to improve over time. CONCLUSIONS: The delivered dose of HD for patients with established renal failure has increased over the last decade. Whilst the majority of UK patients achieved the target URR there was considerable variation between centres in the percentage of patients achieving the guideline.

Use of natural experimental studies to evaluate 20mph speed limits in two major UK cities.

INTRODUCTION: Reductions in traffic speed can potentially offer multiple health and public health benefits. In 2016, implementation of 20mph (30kph) speed limit interventions began in Edinburgh (city-wide) and Belfast (city centre). The aims of this paper are to describe 1) the broad theoretical approach and design of two natural experimental studies to evaluate the 20mph speed limits in Edinburgh and Belfast and 2) how these studies allowed us to test and explore theoretical mechanisms of 20mph speed limit interventions. METHODS: The evaluation consisted of several work packages, each with different research foci, including the political decision-making processes that led to the schemes, their implementation processes, outcomes (including traffic speed, perceptions of safety, and casualties) and cost effectiveness. We used a combination of routinely and locally collected quantitative data and primary quantitative and qualitative data. RESULTS: The evaluation identified many contextual factors influencing the likelihood of 20mph speed limits reaching the political agenda. There were substantial differences between the two sites in several aspects related to implementation. Reductions in speed resulted in significant reductions in collisions and casualties, particularly in Edinburgh, which had higher average speed at baseline. The monetary value of collisions and casualties prevented are likely to exceed the costs of the intervention and thus the overall balance of costs and benefits is likely to be favourable. CONCLUSIONS: Innovative study designs, including natural experiments, are important for assessing the impact of 'real world' public health interventions. Using multiple methods, this project enabled a deeper understanding of not only the effects of the intervention but the factors that explain how and why the intervention and the effects did or did not occur. Importantly it has shown that 20mph speed limits can lead to reductions in speed, collisions and casualties, and are therefore an effective public health intervention.

UK Renal Registry 12th Annual Report (December 2009): chapter 8: adequacy of haemodialysis in UK renal centres in 2008: national and centre-specific analyses.

BACKGROUND: Outcome in patients treated with haemodialysis (HD) is influenced by the delivered dose of dialysis. The UK Renal Association (RA) publishes Clinical Practice Guidelines which include recommendations for dialysis dose. The urea reduction ratio (URR) is a widely used measure of dialysis dose. AIM: To determine the extent to which patients received the recommended dose of HD in the UK. METHODS: Seventy-two renal centres in the UK submit data electronically to the UK Renal Registry (UKRR). Two groups of patients were included in the analyses: the prevalent patient population on 31st December 2008 and the incident patient population for 2008. Centres returning data on <50% of their patient population were excluded from centre-specific comparisons. RESULTS: Data regarding URR were available from 62 renal centres in the UK. Fifty-one centres provided URR data on more than 90% of prevalent patients. There has been an increase from 56% in 1998 to 83% in 2008 in the proportion of patients in the UK who met the UK Clinical Practice Guideline for URR (>65%). There was considerable variation from one centre to another, with 9 centres attaining the RA clinical practice guideline in >90% of patients and 5 centres attaining the standard in <70% of patients. The HD dose (URR) delivered to patients who had just started dialysis treatment was lower than that of patients who had been treated for longer and increased further with time. CONCLUSIONS: The delivered dose of HD for patients with established renal failure has increased over 10 years. Whilst the large majority of patients in the UK achieved the target URR there was considerable variation between centres in the percentage of patients achieving this.

UK Renal Registry 12th Annual Report (December 2009): chapter 11: blood pressure profile of prevalent patients receiving dialysis in the UK in 2008: national and centre-specific analyses.

INTRODUCTION: The UK Renal Registry (UKRR) assesses blood pressure (BP) control annually for patients receiving renal replacement therapy (RRT) at renal centres in England, Wales and Northern Ireland. METHODS: Patients alive and receiving RRT on 31st December 2008 with a BP reading in either the fourth or third quarter of 2008 were included. Summary statistics were calculated for each renal centre, nation and primary renal disease (PRD) category. Longitudinal analyses were performed to assess the long-term impact of treatment modality and PRD on BP control for incident and prevalent patients. RESULTS: In 2008, only 26.3% of peritoneal dialysis (PD) and 27.4% of transplant (Tx) patients achieved the Renal Association (RA) guidelines standard of BP <130/80 mmHg. Since the cessation of BP targets for haemodialysis (HD) patients, there has been a reduction (compared to 2007) in the number of HD patients achieving BP <130/80 mmHg. In 2008, 43.1% of patients achieved BP <140/90 mmHg pre-HD and 46.8% BP <130/ 80 mmHg post-HD. BP control varied significantly between renal centres for each treatment modality (p < 0.001). Adjusted mean systolic BP fell significantly during the first year on dialysis (6 mmHg for PD and 8 mmHg for HD). Hypertension was more common in HD patients with vascular disorders such as diabetes and renovascular disease (59.0%) than in patients with glomerulonephritis (51.9%) or tubular disorders (46.7%). CONCLUSIONS: In 2008, a minority of patients on RRT achieved the recommended BP standards. There remained a significant variation in achievement of standards between UK renal centres. Since the removal of specific BP targets for HD patients, there has been an increase in systolic BP pre-and post-HD. BP falls significantly during the first year after starting dialysis and patients with vascular disorders have significantly worse BP control.

UK Renal Registry 11th Annual Report (December 2008): Chapter 9 Haemoglobin, ferritin and erythropoietin amongst patients receiving dialysis in the UK in 2007: national and centre-specific analyses.

BACKGROUND: The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. AIMS: To determine the extent to which the guidelines for anaemia management are met in the UK. METHODS: Quarterly data (haemoglobin (Hb) and factors that influence Hb) extracts from renal centres in England, Wales and Northern Ireland (EWNI), and annual data from the Scottish Renal Registry for incident and prevalent renal replacement therapy (RRT) cohorts for 2007 were analysed by the UK Renal Registry (UKRR). RESULTS: In the UK, in 2007 58% of patients commenced dialysis therapy with Hb > or = 10.0 g/dl (median Hb 10.3 g/dl). Of incident patients 81% and 87% had a Hb > or = 10.0 g/dl by 3 and 6 months of dialysis treatment respectively. The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6-12.6 g/dl. Of HD patients 86% had a Hb > or = 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.9 g/dl (IQR 11.0-12.8 g/dl). 91% of UK PD patients had a Hb > or = 10.0 g/dl. The median ferritin in HD patients in EWNI was 417 microg/L (IQR 270-598) and 95% of HD patients had a ferritin > or = 100 microg/L. The median ferritin in PD patients was 255 microg/L (IQR 143-411) with 85% of PD patients having a ferritin > or = 100 microg/L. In EWNI the mean ESA dose was higher for HD than PD patients (9,300 vs. 6,100 IU/week). CONCLUSIONS: This year for the first time there has been a small fall (from 85.9% in 2006 to 85.6%) in the percentage of HD patients with an Hb of > or = 10 g/dl. This contrasts with previous annual improvements in this figure and is related to implementation of the new Hb Standard which has a target range of 10.5-12.5 g/dl.

UK Renal Registry 11th Annual Report (December 2008): Chapter 8 Adequacy of haemodialysis in UK renal centres in 2007: national and centre-specific analyses.

BACKGROUND: Outcome in patients treated with haemodialysis (HD) is influenced by the delivered dose of dialysis. The UK Renal Association (RA) publishes Clinical Practice Guidelines which include recommendations for dialysis dose. The urea reduction ratio (URR) is a widely used measure of dialysis dose. AIM: To determine the extent to which patients received the recommended dose of HD in the UK. METHODS: Seventy-one renal centres in the UK submit data electronically to the UK Renal Registry (UKRR). Two groups of patients were included in the analyses: the prevalent patient population on 31st December 2007 and the incident patient population for 2007. Centres returning data on <50% of their patient population were excluded from centre-specific comparisons. RESULTS: Data regarding URR were available from 61 renal centres in the UK. Forty six centres provided URR data on more than 90% of prevalent patients. 81% of prevalent HD patients met the UK Clinical Practice Guideline for URR (>65%) in 2007. There has been an increase from 56% in 1998 to 81% in 2007 in the proportion of patients in the UK who achieved a URR >65%. The HD dose (URR) delivered to patients who have just started dialysis treatment is lower than that of patients who have been treated for longer and increases further with time. CONCLUSIONS: The delivered dose of HD for patients with established renal failure has increased over 9 years. There was considerable variation from one centre to another, with 8 centres attaining the RA clinical practice guideline in >90% of patients and 7 centres attaining the standard in <60% of patients.

UK Renal Registry 11th Annual Report (December 2008): Chapter 11 Blood pressure profile of prevalent patients receiving dialysis in the UK in 2007: national and centre-specific analyses.

INTRODUCTION: Blood pressure (BP) control is assessed annually from patients on Renal Replacement Therapy at renal centres in England, Wales and Northern Ireland by the UK Renal Registry. METHODS: Patients alive and receiving RRT on 31st December 2007 with a BP reading in either the fourth or third quarter of 2007 were included. Summary statistics were calculated for each renal centre, nation and renal disease category. Linear regression analyses were performed for prevalent patients between 2000 and 2007. RESULTS: Significantly more haemodialysis patients achieved the BP standard (44.6% pre-HD and 48.8% post-HD) than peritoneal dialysis (32.8%) or renal transplant patients (26.7%). Median BP fell significantly between 2000 and 2007 for each treatment modality. There was significant variability in BP control between renal centres (p < 0.0001) for haemodialysis and transplant patients. Hypertension was significantly more common in haemodialysis patients with vascular disorders such as diabetes and renovascular disease (56.8%) than in glomerulonephritis (51.0%) or tubular disorders (45.1%). The effect was less prominent in peritoneal dialysis and not evident in transplant patients where few achieved the BP standard. CONCLUSION: A minority of patients on RRT achieved BP standards in 2007. There remained a significant variation in achievement of standards between renal centres.

Sensitivity and specificity of time resolved point dose measurements for patient specific quality assurance.

This study aimed to quantify the sensitivity and specificity of time-resolved point dose measurements. Criteria were defined to assess whether errors would cause a clinically relevant dose deviation during patient treatment. The sensitivity and specificity were determined based on verification measurements of five error-free plans and 84 intentional error plans. Receiver operator characteristic analysis was conducted to quantify the efficiency of the method. In addition, the specificity of the method was investigated in more detail by assessing its ability to identify different error modes. For measurements made at planning target volume locations, a moderate sensitivity (65% ± 13%), specificity (76% ± 12%), and an area under the curve (AUC) equal to 0.77 were obtained for a quality control (QC) acceptance criterion of 2%. Measurements made at organ at risk (OAR) locations had high sensitivity (80% ± 20%), but low specificity (54% ± 13%), and an AUC equal to 0.70. The low specificity for OAR locations could be traced to the impact of a small couch tilt on measurement locations at larger distances from the isocentre, resulting in increased shielding by multi-leaf collimator (MLC) leaves. Further analysis showed that output errors and errors affecting the penumbra region can be resolved on a per measurement basis with moderate to high sensitivity (100% and 67% for errors in output, and in the penumbra region, respectively) and high specificity (77% and 85% for errors in output, and in the penumbra region, respectively). This can potentially result in saving time investigating failing QC measurements.

Factors which may influence cardiovascular disease in dialysis and transplant patients--blood pressure (chapter 10).

Many renal units still fail to return blood pressure data to the Renal Registry. In England, Northern Ireland and Wales, the percentage of HD patients achieving the combined blood pressure standard (<140/90 pre-dialysis) averages 43% (inter unit range 16-60%) and post-dialysis (<130/80) average 48% (range 22-66%). On average 27% (range 12-48%) of PD patients achieve the standard of <130/80 and 26% of renal transplant patients (range 16-40%). Over the last 8 years there has been no significant change in systolic or diastolic blood pressure achievement. Better comorbidity data returns are required by the Registry to perform blood pressure survival analyses.

Measures of care in adult renal transplant recipients in the United Kingdom (chapter 11).

The total number of patients active on the transplant waiting list (adult and paediatric) on 31 December 2005 was 5736, an 8% increase from the previous year. On 31 December 2005, 45.7% of prevalent adult RRT patients in the UK, had a functioning renal transplant which equated to 19,074 patients. During 2005, the death rate in prevalent transplant patients was 2.7 per 100 patient years. An additional 3.1% of all prevalent transplants failed with patients returning to dialysis. During 2005, deceased heart beating donor numbers decreased by 18% compared to 2004. In comparison, non-heart beating donors and living kidney donors increased by 35% and 17%, respectively, in 2005. The proportion of renal transplants performed from deceased heart beating donors fell from 68% in 2004 to 60% in 2005. There is wide variation in prevalence per million population (pmp) of transplanted patients resident in each local authority area across the United Kingdom. Total 11.4% of incident transplants in 2005 were due to patients with diabetes. The median eGFR was 46.1 ml/min/1.73 m(2), with 18% of prevalent transplant recipients having an eGFR <30 ml/min/1.73 m(2). The median Hb in prevalent transplant recipients was 12.9 g/dl, with 10% of patients having an Hb <10 g/dl. The median systolic and diastolic BP was 136 and 79 mmHg, respectively, with only 25% of patients within guidelines. Transplant function analysed by CKD stages 1-2 (eGFR < 60), 3 (eGFR 30-59), 4 (eGFR 15-29) and 5 (eGFR < 15), shows that these categories account for 24%, 59%, 15% and 2.5% of patients, respectively. Haemoglobin values fall with decreasing eGFR such that of the 2.5% of transplant patients with eGFR <15 ml/min, 27% had an Hb <10 g/dl and 51% <11 g/dl. Control of iPTH was poor in transplant recipients in CKD stages 4 and 5, with 22% and 50% of patients, respectively, having a PTH > 32 pmol/l (=300 ng/l). Patients with failing transplants are less likely to achieve RA targets of key biochemical variables when compared to patients on dialysis. There is still wide variability in the completeness of data returns from individual units.

Lack of functional expression of NMDA receptors in PC12 cells.

PC12 cells are an established model for studying the role of N-methyl-d-aspartate (NMDA) receptors in excitotoxicity and function as multimeric assemblies of NR1 with at least one NR2(A-D) subunit. We examined NR1 splice variant and NR2 subunit expression in four PC12 cell-lines (ATCC, WEHI, Ordway and Flinders), correlated mRNA expression with protein expression, and used patch-clamp recordings to test functionality. PCR indicated strong expression of the NR1 splice variants NR1-2a and NR1-4a in all cell-lines, with the remainder weakly detected or absent. Real-time PCR showed variable levels of NR1 mRNA expression (all splice variants) between cell-lines and a significant increase in response to nerve growth factor in the WEHI and Ordway lines (NGF: 50ng/ml, 2.1- and 13.4-fold increases, respectively, P< or =0.05). mRNA for NR2A or NR2B was not detected in any PC12 cell-line. NR2C mRNA expression varied between lines and increased after NGF treatment (approximately 4-fold increase in WEHI and Ordway lines, P< or =0.05). In the Ordway line, NR2D mRNA was seen only after NGF treatment. Immunohistochemistry confirmed protein expression for NR1, NR2C and NR2D, and while fluorescence intensity changes in response to NGF paralleled mRNA responses, the degree of increase was of reduced magnitude. Whole-cell patch-clamping of NGF treated cells failed to detect functional NMDA receptors in any of the cell-lines. Our study demonstrates that in contrast to neurons from the CNS, PC12 cells do not express a normal complement of NMDA receptor-subunits, and this may be one factor limiting functional responses to NMDA/glutamate and consequently the use of PC12 cells as a neuronal model.

Use of HLA typing in diagnosing celiac disease in patients with type 1 diabetes.

OBJECTIVE: This study examines the use of HLA typing for the diagnosis of celiac disease in a group of Australians with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects included 131 sequential patients with type 1 diabetes (mean age 17 years [range 10-37]), 77 patients with biopsy-proven celiac disease (mean age 52 years [range 12-84]), and 162 healthy control subjects (mean age 17 years [range 2 months to 56 years]). Subjects were prospectively screened for celiac disease using endomysial antibodies (EMAs), tissue transglutaminase antibodies (TTGAs), and celiac disease-specific HLA typing. RESULTS: Celiac disease was diagnosed in 11 subjects after an intestinal biopsy (prevalence 8.4%). There was 95% agreement between TTGA and EMA for positive results and 100% for negative results. There was no significant difference for HLA DQ2 and DR4 among patients with type 1 diabetes with or without celiac disease. CONCLUSIONS: The prevalence of celiac disease among patients with type 1 diabetes is higher than previously estimated in Australia. TTGA is a valuable diagnostic tool that can be used for screening celiac disease in patients with type 1 diabetes. HLA typing should not be used in the diagnosis of celiac disease in patients with type 1 diabetes because of the similarities of HLA types between patients with type 1 diabetes and those with celiac disease.

UK Renal Registry 18th Annual Report: Chapter 8 Haemoglobin, Ferritin and Erythropoietin amongst UK Adult Dialysis Patients in 2014: National and Centre-specific Analyses.

In the UK in 2014: The median haemoglobin (Hb) of patients at the time of starting dialysis was 100 g/L with 50% of patients having a Hb 5100 g/L. The median Hb in patients starting haemodialysis (HD) was 97 g/L (IQR 87-106) and in patients starting peritoneal dialysis (PD) was 108 g/L (IQR 100-117). At start of dialysis, 54% of patients presenting early had Hb 5100 g/L whilst only 33% of patients presenting late had Hb 5100 g/L. The median Hb of prevalent patients on HD was 111 g/L with an IQR of 103-120 g/L. The median Hb of prevalent patients on PD was 112 g/L with an IQR of 103-121 g/L. 81% of HD patients and 83% of PD patients had Hb 5100 g/L. 58% of HD patients and 56% of PD patients had Hb 5100 and 4120 g/L. The median ferritin in HD patients was 432 mg/L (IQR 274­631) and 95% of HD patients had a ferritin 5100 mg/L. The median ferritin in PD patients was 292 mg/L (IQR 168­479) with 88% of PD patients having a ferritin 5100 mg/L. In England, Wales and Northern Ireland in 2014: The median erythropoietin stimulating agent (ESA) dose was higher for HD than PD patients (7,333 vs. 4,148 IU/week).

Prospective study of effect of androgens on serum inflammatory markers in men.

OBJECTIVE: Because male sex is an independent risk factor for the severity of atherosclerosis, it is possible that androgens may be proatherogenic. There is evidence that sex hormones, particularly estrogens, regulate (or modulate) inflammation, a process integral to atherogenesis. Because levels of serum inflammatory markers predict cardiovascular outcomes, we prospectively assessed the effects of androgen therapy on these markers in older men. METHODS AND RESULTS: Levels of high-sensitivity C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured from sera collected at baseline and at the end of 2 randomized double-blind placebo-controlled trials evaluating the effects of 3 months of androgen treatment with either dihydrotestosterone (DHT) or recombinant human chorionic gonadotropin (rhCG) in healthy men aged >60 years with partial androgen deficiency (serum testosterone levels <15 nmol/L). For the DHT study (70 mg transdermally daily), 33 men completed 3 months of treatment (16 men were treated with DHT, and there were 17 controls). For the rhCG (250 microg twice weekly) study, 20 men were treated with rhCG, and there were 20 controls. In both studies, groups were well matched for age and vascular risk factors. Androgen levels (DHT and testosterone) were consistently maintained at eugonadal levels throughout the trials, with estradiol markedly increased by rhCG but not DHT. Baseline CRP levels were 0.74 to 1.49 mg/L, sVCAM-1 levels were 847 to 950 ng/mL, and sICAM-1 levels were 256 to 292 ng/mL in all groups. Neither DHT nor rhCG resulted in significant changes in CRP, sVCAM-1, or sICAM-1 compared with placebo (P>0.3 in both studies). CONCLUSIONS: Exogenous androgen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women. These data provide a measure of reassurance concerning potential adverse cardiovascular effects of androgen therapy in older men.

UK Renal Registry 17th Annual Report: Chapter 7 Haemoglobin, Ferritin and Erythropoietin amongst UK Adult Dialysis Patients in 2013: National and Centre-specific Analyses.

BACKGROUND: The diagnosis and management of anaemia in chronic kidney disease and the standards to be achieved have been detailed in the UK Renal Association Anaemia of CKD guidelines. AIMS: To determine the attainment of standards for anaemia management in the UK. METHODS: Quarterly data were obtained for haemoglobin (Hb) and factors that influence Hb from renal centres in England,Wales, Northern Ireland (EW&NI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2013. RESULTS: In the UK, in 2013,50% of patients commenced dialysis therapy with Hb 5100 g/L (median Hb 100 g/L). Of patients presenting early, 53% started dialysis with Hb 5100 g/L compared to 36% of patients presenting late. The UK median Hb of haemodialysis (HD) & peritoneal dialysis (PD) patients was 112 g/L (inter-quartile range (IQR) 103­120 g/L) and 113 g/L(IQR 103­122 g/L) respectively with 83% of patients having Hb .100 g/L for both treatment modalities. The median ferritin in HD and PD patients was 424 mg/L (IQR 280­616 mg/L) and 285 mg/L (IQR 167­473 mg/L) respectively with the majority of patients achieving ferritin 5100 mg/L.In EW&NI the median ESA dose was higher for HD than PD patients (7,333 vs. 4,000 IU/week). The percentage of patients treated with an ESA and having Hb .120 g/L ranged between centres from 3­29% for HD and from 0­26% for PD. CONCLUSIONS: There continues to be significant variation between centres in the use of iron and ESAi n order to achieve the target Hb (100­120 g/L).

Revised Baux Score and updated Charlson comorbidity index are independently associated with mortality in burns intensive care patients.

PURPOSE: The purpose of the current study was to utilise established scoring systems to analyse the association of (i) burn injury severity, (ii) comorbid status and (iii) associated systemic physiological disturbance with inpatient mortality in patients with severe burn injuries admitted to intensive care. METHODS: Case notes of all patients with acute thermal injuries affecting ≥15% total body surface area (TBSA) admitted to the Burns Intensive Care Unit (BICU) at Chelsea and Westminster Hospital during a 10-year period were retrospectively reviewed. Revised Baux Score, Belgian Outcome in Burn Injury (BOBI) Score, Abbreviated Burn Severity Index (ABSI), APACHE II Score, Sequential Organ Failure Assessment (SOFA) Score and Updated Charlson Comorbidity Index (CCI) were computed for each patient and analysed for association with inpatient mortality. RESULTS: Ninety mechanically ventilated patients (median age 45.7 years, median % TBSA burned 36.5%) were included. 72 patients had full thickness burns and 35 patients had inhalational injuries. Forty-four patients died in hospital while 46 survived to discharge. In a multivariate logistic regression model, only the Revised Baux Score (p<0.001) and updated CCI (p=0.014) were independently associated with mortality. This gave a ROC curve with area under the curve of 0.920. On multivariate cox regression survival analysis, only the Revised Baux Score (p<0.001) and the updated CCI (p=0.004) were independently associated with shorter time to death. CONCLUSION: Our data suggest that the Revised Baux Score and the updated CCI are independently associated with inpatient mortality in patients admitted to intensive care with burn injuries affecting ≥15% TBSA. This emphasises the importance of comorbidities in the prognosis of patients with severe burn injuries.

Flow cytometry in the study of mitochondrial respiratory chain disorders.

We have developed a flow cytometric assay to measure the oxidative capacity of cultured lymphoblasts as a possible screening test for patients suspected of having a defect of the mitochondrial respiratory chain. Cells were incubated overnight in serum free media, followed by incubation with dihydroethidium with and without rotenone, and then analysed using flow cytometry to measure fluorescence. Inhibition with rotenone gave an increase in fluorescence compared to uninhibited cells. The change in fluorescence was significantly lower in four of the six patient cell lines, with a correlation between the activity of complex I and change in fluorescence. This method may be applicable to cell lines with defects in other complexes of the respiratory chain.