A comparison of graft and patient outcomes following kidney transplantation in extended hour and conventional haemodialysis patients

Differences in early graft function between kidney transplant recipients previously managed with either haemodialysis (HD) or peritoneal dialysis are well described. However, only two single-centre studies have compared graft and patient outcomes between extended hour and conventional HD patients, with conflicting results.This study compared the outcomes of all extended hour (≥24 hours/week) and conventional HD patients transplanted in Australia and New Zealand between 2000 and 2014. The primary outcome was delayed graft function (DGF), defined in an ordinal manner as either a spontaneous fall in serum creatinine of less than 10% within 24 hours, or the need for dialysis within 72 hours following transplantation. Secondary outcomes included the requirement for dialysis within 72 hours post-transplant, acute rejection, estimated glomerular filtration rate at 12 months, death-censored graft failure, all-cause and cardiovascular mortality, and a composite of graft failure and mortality.A total of 4,935 HD patients (378 extended hour HD, 4,557 conventional HD) received a kidney transplant during the study period. Extended hour HD was associated with an increased likelihood of DGF compared with conventional HD (adjusted proportional odds ratio 1.33; 95% confidence interval 1.06-1.67). There was no significant difference between extended hour and conventional HD in terms of any of the secondary outcomes.Compared to conventional HD, extended hour HD was associated with DGF, although long-term graft and patient outcomes were not different

Domestication of Campylobacter jejuni NCTC 11168

Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterized isolates among laboratories has run in parallel with research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. Campylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first Campylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C . jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates, identified previously to have aberrant phenotypes, varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37 °C, invasion of chicken and human cell lines, and susceptibility to ampicillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. This article contains data hosted by Microreact

Factors Associated with the Performance of a Blood-Based Interferon-γ Release Assay in Diagnosing Tuberculosis

Background: Indeterminate results are a recognised limitation of interferon-γ release assays (IGRA) in the diagnosis of latent tuberculosis (TB) infection (LTBI) and TB disease, especially in children. We investigated whether age and common co-morbidities were associated with IGRA performance in an unselected cohort of resettled refugees. Methods: A retrospective cross-sectional study of refugees presenting for their post-resettlement health assessment during 2006 and 2007. Refugees were investigated for prevalent infectious diseases, including TB, and for common nutritional deficiencies and haematological abnormalities as part of standard clinical screening protocols. Tuberculosis screening was performed by IGRA; QuantiFERON-TB Gold in 2006 and QuantiFERON-TBGold In-Tube in 2007. Results: Complete data were available on 1130 refugees, of whom 573 (51%) were children less than 17 years and 1041 (92%) were from sub-Saharan Africa. All individuals were HIV negative. A definitive IGRA result was obtained in 1004 (89%) refugees, 264 (26%) of which were positive; 256 (97%) had LTBI and 8 (3%) had TB disease. An indeterminate IGRA result was obtained in 126 (11%) refugees (all failed positive mitogen control). In multivariate analysis, younger age (linear OR = 0.93 [95% CI 0.91-0.95],

Anticipated and experienced discrimination amongst people with schizophrenia, bipolar disorder and major depressive disorder: a cross-sectional study.

BACKGROUND: The unfair treatment of individuals with severe mental illness has been linked to poorer physical and mental health outcomes. Additionally, anticipation of discrimination may lead some individuals to avoid participation in particular life areas, leading to greater isolation and social marginalisation. This study aimed to establish the levels and clinical and socio-demographic associations of anticipated and experienced discrimination amongst those diagnosed with a schizophrenia and comparator severe mental illnesses (bipolar and major depressive disorders). METHODS: This study was a cross-sectional analysis of anticipated and experienced discrimination from 202 individuals in South London (47% with schizophrenia, 32% with depression and 20% with bipolar disorder). RESULTS: 93% of the sample anticipated discrimination and 87% of participants had experienced discrimination in at least one area of life in the previous year. There was a significant association between the anticipation and the experience of discrimination. Higher levels of experienced discrimination were reported by those of a mixed ethnicity, and those with higher levels of education. Women anticipated more discrimination than men. Neither diagnosis nor levels of functioning were associated with the extent of discrimination. Clinical symptoms of anxiety, depression and suspiciousness were associated with more experienced and anticipated discrimination respectively. CONCLUSIONS: The unfair treatment of individuals with severe mental illnesses remains unacceptably common. Population level interventions are needed to reduce levels of discrimination and to safeguard individuals. Interventions are also required to assist those with severe mental illness to reduce internalised stigma and social avoidance

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Identifying geospatial “hot spots” of glomerular diseases: opportunities and challenges

Canney et al. discovered significant geographic clustering of incident glomerular diseases by applying geospatial modeling techniques to routinely collected information. The results provide further evidence to support the role of environmental triggers in the pathogenesis of glomerular diseases. The study highlights the largely untapped capacity to exploit routinely collected administrative data with appropriate analyses to explore disease pathogenesis and inform health service planning

Monitoring nutritional status accurately and reliably in children with anorexia nervosa

Aim:Accurate assessment of nutritional status is a vital aspect of caring for individuals with anorexia nervosa (AN) and body mass index (BMI) is considered an appropriate and easy to use tool. Because of the intense fear of weight gain, some individuals may attempt to mislead the physician. Mid-upper arm circumference (MUAC) is a simple, objective method of assessing nutritional status. The setting is an eating disorders clinic in a tertiary paediatric hospital in Western Australia. The aim of this study is to evaluate how well MUAC correlates with BMI in adolescents with AN. Methods: Prospective observational study to evaluate nutritional status in adolescents with AN. Results: Fifty-five adolescents aged 12-17 years with AN were assessed between January 1, 2004 and January 1, 2006. MUAC was highly correlated with BMI (r = 0.79, P < 0.001) and individuals with MUAC ≥20 cm rarely required hospitalisation (negative predictive value 93%). Conclusions: MUAC reflects nutritional status as defined by BMI in adolescents with AN. Lack of consistency between longitudinal measurements of BMI and MUAC should be viewed suspiciously and prompt a more detailed nutritional assessment