St Thomas' Hospital

About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.

Diagnostic accuracy of (18)F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis

Abstract: Imaging or tissue biomarker evidence has been introduced into the core diagnostic pathway for Alzheimer's disease (AD). PET using (18)F-labelled beta-amyloid PET tracers has shown promise for the early diagnosis of AD. However, most studies included only small numbers of participants and no consensus has been reached as to which radiotracer has the highest diagnostic accuracy. First, we performed a systematic review of the literature published between 1990 and 2014 for studies exploring the diagnostic accuracy of florbetaben, florbetapir and flutemetamol in AD. The included studies were analysed using the QUADAS assessment of methodological quality. A meta-analysis of the sensitivity and specificity reported within each study was performed. Pooled values were calculated for each radiotracer and for visual or quantitative analysis by population included. The systematic review identified nine studies eligible for inclusion. There were limited variations in the methods between studies reporting the same radiotracer. The meta-analysis results showed that pooled sensitivity and specificity values were in general high for all tracers. This was confirmed by calculating likelihood ratios. A patient with a positive ratio is much more likely to have AD than a patient with a negative ratio, and vice versa. However, specificity was higher when only patients with AD were compared with healthy controls. This systematic review and meta-analysis found no marked differences in the diagnostic accuracy of the three beta-amyloid radiotracers. All tracers perform better when used to discriminate between patients with AD and healthy controls. The sensitivity and specificity for quantitative and visual analysis are comparable to those of other imaging or biomarker techniques used to diagnose AD. Further research is required to identify the combination of tests that provides the highest sensitivity and specificity, and to identify the most suitable position for the tracer in the clinical pathway.

Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women.

Abstract: Objective Osteoarthritis (OA) is recognized to have a genetic component, and in this study, we aimed to replicate in a case–control study of men and women with clinical knee OA genetic associations in 12 candidate genes previously reported to be associated with OA. Methods Twenty-five single-nucleotide polymorphisms were genotyped in 298 men and 305 women ages 50–86 who were diagnosed as having knee OA, as assessed both clinically and radiographically, and in 297 men and 299 women matched for age and ethnicity (controls). Standardized anteroposterior radiographs of the knee in extension were performed on each of the cases, and all cases met the American College of Rheumatology criteria for OA of the knee. Genotype and haplotype frequencies in cases and controls were compared separately in men and women. The 12 genes tested were AACT, ADAM12, BMP2, CD36, CILP, COX2, ESR1, NCOR2, OPG, TNA, TNFAIP6, and VDR. Results Eight of the candidate genes were associated in women and 5 in men, and only 3 genes (TNFAIP6, NCOR2, and CD36) were not significantly associated in either sex. The strongest associations in terms of odds ratios (ORs) were a haplotype in ADAM12 (OR 7.1 [95% confidence interval (95% CI) 3.3–33.8]) and a haplotype in ESR1 (OR 3.6 [95% CI 1.18–10.98]) in women. The same ADAM12 haplotype (OR 2.54 [95% CI 1.2–5.4]) and a haplotype in the CILP gene (OR 0.38 [95% CI 0.23–0.62]) were the strongest associations in men. Conclusion We found that genes previously identified by their association with subclinical features of knee OA or progression were also associated with clinical knee OA. These genetic associations may identify individuals at a particularly high risk of developing knee OA.

Heritable components of the human fecal microbiome are associated with visceral fat.

Abstract: Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures. We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity. Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies.

A Mutation in COL9A1 Causes Multiple Epiphyseal Dysplasia: Further Evidence for Locus Heterogeneity

Abstract: Multiple epiphyseal dysplasia (MED) is an autosomal dominantly inherited chondrodysplasia. It is clinically highly heterogeneous, partially because of its complex genetic background. Mutations in four genes, COL9A2, COL9A3, COMP, and MATR3, all coding for cartilage extracellular matrix components (i.e., the α2 and α3 chains of collagen IX, cartilage oligomeric matrix protein, and matrilin-3), have been identified in this disease so far, but no mutations have yet been reported in the third collagen IX gene, COL9A1, which codes for the α1(IX) chain. MED with apparently recessive inheritance has been reported in some families. A homozygous R279W mutation was recently found in the diastrophic dysplasia sulfate transporter gene, DTDST, in a patient with MED who had a club foot and double-layered patella. The series consisted of 41 probands with MED, 16 of whom were familial and on 4 of whom linkage analyses were performed. Recombination was observed between COL9A1, COL9A2, COL9A3, and COMP and the MED phenotype in two of the families, and between COL9A2, COL9A3, and COMP and the phenotype in the other two families. Screening of COL9A1 for mutations in the two probands from the families in which this gene was not involved in the recombinations failed to identify any disease-causing mutations. The remaining 37 probands were screened for mutations in all three collagen IX genes and in the COMP gene. The probands with talipes deformities or multipartite patella were also screened for the R279W mutation in DTDST. The analysis resulted in identification of three mutations in COMP and one in COL9A1, but none in the other two collagen IX genes. Two of the probands with a multipartite patella had the homozygous DTDST mutation. The results show that mutations in COL9A1 can cause MED, but they also suggest that mutations in COL9A1, COL9A2, COL9A3, COMP, and DTDST are not the major causes of MED and that there exists at least one additional locus.

What does the BDI measure in chronic pain

Abstract: The Beck Depression Inventory (BDI) has been widely used to document the prevalence of depressive symptomatology in samples of chronic pain patients and as an outcome measure in studies of the psychological management of chronic pain. Several BDI items have a somatic content (sleep disturbance, fatigue, etc). Since chronic pain may have similar somatic effects, the significance of the total BDI score in this population is unclear. Two hundred and forty mixed chronic pain patients completed the BDI at screening interview for a psychologically based pain management programme; of these, 207 (mean age 50.1 years; 63% female) were later admitted to the programme when the BDI was readministered along with measures of pain, anxiety, pain-related cognitions, and physical performance. The mean BDI score of the sample was 18.1, with 71.7% meeting criteria (scoring 13 or more) for at least mild depression. A principal-components analysis of the BDI yielded 3 meaningful factors labelled: sadness about health, self-reproach, and somatic disturbance. Among the most frequently endorsed items were those loading on the somatic factor. The pattern of relationships between individual factor scores and measures of pain, mood, cognition, and physical functioning indicated that the use of the total BDI score may give a misleading impression of the nature and degree of affective disturbance in this group of patients. The implications of these findings for our understanding of BDI scores obtained by chronic pain patients are discussed.