The National CKD Audit: a primary care condition that deserves more attention.

Chronic kidney disease (CKD) is a common condition, with an estimated prevalence in the UK of around 5–7%, and a GP recorded prevalence in the England Quality and Outcomes Framework (QOF) in 2017 of 4.1%,3 which is higher than the prevalence of coronary heart disease. The majority of people with CKD are detected and managed in primary care rather than by kidney specialists. Early identification in primary care, particularly among populations with risk factors such as diabetes and hypertension, enables appropriate management of blood pressure, cardiovascular risk and lifestyle factors. There is evidence that progression of CKD can be delayed by such interventions, and that implementation of these interventions can be improved by use of quality improvement tools in primary care. However CKD as a long-term condition has not had an easy ride. Since its definition in 2002 there have been concerns about overdiagnosis, described as ‘when people without symptoms are diagnosed with a disease that ultimately will not cause them symptoms or early death’, and anxieties about the disclosure of early-stage CKD to patients, along with the work of reassurance and increased monitoring that this might entail. This debate within general practice has left some practitioners uncertain about the importance of naming, coding and managing CKD in primary care

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis

Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). Conclusion: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis

How do primary care doctors in England and Wales code and manage people with chronic kidney disease? Results from the National Chronic Kidney Disease Audit.

BACKGROUND: In the UK, primary care records are electronic and require doctors to ascribe disease codes to direct care plans and facilitate safe prescribing. We investigated factors associated with coding of chronic kidney disease (CKD) in patients with reduced kidney function and the impact this has on patient management. METHODS: We identified patients meeting biochemical criteria for CKD (two estimated glomerular filtration rates 90 days apart) from 1039 general practitioner (GP) practices in a UK audit. Clustered logistic regression was used to identify factors associated with coding for CKD and improvement in coding as a result of the audit process. We investigated the relationship between coding and five interventions recommended for CKD: achieving blood pressure targets, proteinuria testing, statin prescription and flu and pneumococcal vaccination. RESULTS: Of 256 000 patients with biochemical CKD, 30% did not have a GP CKD code. Males, older patients, those with more severe CKD, diabetes or hypertension or those prescribed statins were more likely to have a CKD code. Among those with continued biochemical CKD following audit, these same characteristics increased the odds of improved coding. Patients without any kidney diagnosis were less likely to receive optimal care than those coded for CKD [e.g. odds ratio for meeting blood pressure target 0.78 (95% confidence interval 0.76-0.79)]. CONCLUSION: Older age, male sex, diabetes and hypertension are associated with coding for those with biochemical CKD. CKD coding is associated with receiving key primary care interventions recommended for CKD. Increased efforts to incentivize CKD coding may improve outcomes for CKD patients

Accounting for overdispersion when determining primary care outliers for the identification of chronic kidney disease: learning from the National Chronic Kidney Disease Audit.

Background: Early diagnosis of chronic kidney disease (CKD) facilitates best management in primary care. Testing coverage of those at risk and translation into subsequent diagnostic coding will impact on observed CKD prevalence. Using initial data from 915 general practitioner (GP) practices taking part in a UK national audit, we seek to apply appropriate methods to identify outlying practices in terms of CKD stages 3-5 prevalence and diagnostic coding. Methods: We estimate expected numbers of CKD stages 3-5 cases in each practice, adjusted for key practice characteristics, and further inflate the control limits to account for overdispersion related to unobserved factors (including unobserved risk factors for CKD, and between-practice differences in coding and testing). Results: GP practice prevalence of coded CKD stages 3-5 ranges from 0.04 to 7.8%. Practices differ considerably in coding of CKD in individuals where CKD is indicated following testing (ranging from 0 to 97% of those with and glomerular filtration rate  <60 mL/min/1.73 m 2 ). After adjusting for risk factors and overdispersion, the number of  'extreme' practices is reduced from 29 to 2.6% for the low-coded CKD prevalence outcome, from 21 to 1% for high-uncoded CKD stage and from 22 to 2.4% for low total (coded and uncoded) CKD prevalence. Thirty-one practices are identified as outliers for at least one of these outcomes. These can then be categorized into practices needing to address testing, coding or data storage/transfer issues. Conclusions: GP practice prevalence of coded CKD shows wide variation. Accounting for overdispersion is crucial in providing useful information about outlying practices for CKD prevalence

Designing informative warning signals: Effects of indicator type, modality, and task demand on recognition speed and accuracy

An experiment investigated the assumption that natural indicators which exploit existing learned associations between a signal and an event make more effective warnings than previously unlearned symbolic indicators. Signal modality (visual, auditory) and task demand (low, high) were also manipulated. Warning effectiveness was indexed by accuracy and reaction time (RT) recorded during training and dual task test phases. Thirty-six participants were trained to recognize 4 natural and 4 symbolic indicators, either visual or auditory, paired with critical incidents from an aviation context. As hypothesized, accuracy was greater and RT was faster in response to natural indicators during the training phase. This pattern of responding was upheld in test phase conditions with respect to accuracy but observed in RT only in test phase conditions involving high demand and the auditory modality. Using the experiment as a specific example, we argue for the importance of considering the cognitive contribution of the user (viz., prior learned associations) in the warning design process. Drawing on semiotics and cognitive psychology, we highlight the indexical nature of so-called auditory icons or natural indicators and argue that the cogniser is an indispensable element in the tripartite nature of signification

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

Comparative (Meta)genomic Analysis and Ecological Profiling of Human Gut-Specific Bacteriophage φB124-14

Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape within the human gut microbiome