Interbeobachter-Reproduzierbarkeit der Beurteilung des Schweregrads von Beschwerden, der Griffstärke und der Druckschmerzschwelle bei Patienten mit lateraler Epikondylitis

The aim of the study was to evaluate the reproducibility of the assessment of severity of complaints, grip strength, and pressure pain threshold in patients with lateral epicondylitis in primary care. The interobserver reliability of severity of complaints and grip strength was excellent. The measurement of pressure pain threshold showed unsatisfactory reliability. Grip strength and the overall assessment of the severity of complaints are useful and reliable measures for the assessment of lateral epicondylitis. (aut.ref.

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Interobserver reproducibility of the assessment of severity of complaints, grip strength, and pressure pain threshold in patients with lateral epicondylitis

Objective: To evaluate the interobserver reproducibility of the assessment of severity of complaints, grip strength, and pressure pain threshold in patients with lateral epicondylitis in primary care. Design: Two physiotherapists assessed independently, and in randomized order, the severity of complaints scored on an 11-point numeric rating scale, pain-free grip strength, maximum grip strength, and pressure pain threshold. Setting: Primary care center in the Netherlands. Participants: Fifty patients were assessed by both physiotherapists. Interventions: Not applicable. Main Outcome Measures: Intraclass correlation coefficients (ICCs) and 95% confidence intervals (CIs) were calculated to assess interobserver reliability. The Bland and Altman method was used to assess interobserver agreement, which included calculation of the mean difference between the observers (d), the 95% CI for d, the standard deviation of the differences, and the 95% limits of agreement. Finally, the smallest detectable difference (SDD) was calculated. Results: The ICC for the severity of complaints was .90. The ICCs for the pain-free grip strength and maximum grip strength were .97 and .98, respectively. The pressure pain threshold showed a lower reliability (ICC=.77). The interobserver agreement for all outcome measures was good, but systematic differences in assessment between the physiotherapists were found for the maximum grip strength and pressure pain threshold. For pressure pain threshold, the SDD was clearly larger than the predefined acceptable difference of 10% of the total range of measurement. Conclusions: The interobserver reliability of severity of complaints and grip strength was excellent, whereas the pressure pain threshold showed unsatisfactory reliability. Grip strength and overall assessment of the severity of complaints are useful and reliable measures for the assessment of lateral epicondylitis. Pain-free grip strength, in particular, is relatively easy to perform and has been shown to be associated with other measures of functional disability in patients with lateral epicondylitis. We, therefore, recommend the use of pain-free grip strength in both research and clinical practice