Qualitative research and content validity: developing best practices based on science and experience

Purpose  

Establishing content validity for both new and existing patient-reported outcome (PRO) measures is central to a scientifically sound instrument development process. Methodological and logistical issues present a challenge in regard to determining the best practices for establishing content validity.     

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: results of study CAO/ARO/AIO-94

PURPOSE: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. METHODS AND MATERIALS: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. RESULTS: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% +/- 7.8%; inadequate RT, 21.2% +/- 5.6%; adequate RT, 6.8% +/- 1.4%; p = 0.0001) and DFS (no RT, 55.1% +/- 9.1%; inadequate RT, 57.4% +/- 6.3%; adequate RT, 69.1% +/- 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. CONCLUSION: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.     

Association of the ASP299GLY TLR4 polymorphism with COPD

Bacterial infection and colonization plays an important role in COPD. The inflammatory response to these bacteria is mediated by Toll-like receptors. The Asp299Gly polymorphism of the Toll-like receptor-4 (TLR4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction resulting in impaired antimicrobial defense. Because altered TLR4 signalling may facilitate bacterial infection, we clinically phenotyped and genotyped 152 patients with COPD (including 24 non-smokers), and 444 healthy controls for the presence of the Asp299Gly polymorphism. Frequencies of the TLR4 Gly allele (4% vs. 8% in controls, odds ratio (OR) 2.24 (95% confidence interval (95%CI) 1.17-4.3)) as well as TLR4 Gly genotype (6% vs. 13% in controls, OR 2.39 (95%CI 1.20-4.79)) were significantly decreased among the patients with COPD. The TLR4 Gly allele was not detected at all in a subgroup of non-smoking patients (n=24). We conclude that the frequency of the Asp299Gly polymorphism is decreased in COPD patients. Unaltered LPS signal transduction by TLR4 may be important for the development of COPD.     

Diagnostic Challenges in Celiac Disease and the Role of the Tissue Transglutaminase–Neo-Epitope

The diagnosis of celiac disease (CD) remains a clinical challenge based on the incomplete specificity and sensitivity rates of current non-invasive tests. Furthermore, histological assessments fail to identify all overt cases and, in particular, do not manifest pathognomonic alterations in silent cases. Accordingly, the majority of CD cases are diagnosed with great delay. Recent research into the pathogenesis of CD, allowed us to identify a neo-antigen that appears to be the most promising serological tool for the detection of anti-tissue transglutaminase as well as anti-gliadin antibodies.     

Condensed cellular seeded collagen gel as an improved biomaterial for tissue engineering of articular cartilage

Three-dimensional autologous chondrocyte implantation based on collagen gel as matrix scaffold has become a clinically applied treatment for focal defects of articular cartilage. However, the low biomechanical properties of collagen gel makes intraoperative handling difficult and creates the risk of early damages to the vulnerable implant. The aim of the study was to create a stabilized form of collagen gel and to evaluate its biomechanical and biochemical properties.Collagen type-I gel was seeded with human articular chondrocytes. 20 samples were subject to condensation which was achieved mechanically by compression and filtration. Control samples were left uncondensed. From both types of gels 10 samples were used for initial biomechanical evaluation by means of unconfined compression and 10 samples were cultivated under standard conditions in vitro. Following cultivation the samples were evaluated by conventional histology and immunohistochemistry. The proliferation rate was calculated and matrix gene expression was quantified by real-time PCR.The biomechanical tests revealed a higher force carrying capacity of the condensed specimens. Strain rate dependency and relaxation was seen in both types of collagen gel representing viscoelastic material properties. Cells embedded within the condensed collagen gel were able to produce extracellular matrix proteins and showed proliferation.Condensed collagen gel represents a mechanically improved type of biomaterial which is suitable for three-dimensional autologous chondrocyte implantation.     

Adhesion of Candida albicans to various dental implant surfaces and the influence of salivary pellicle proteins

Dental implants may be considered a potential reservoir for (re)infection with oral Candida albicans. Our aim was to evaluate initial fungal adhesion to three differentially textured titanium and one zirconia implant surface, and to correlate these findings to differences in specific surface characteristics (surface roughness (R_a) and surface free energy (SFE)). Additionally, we investigated the influence of salivary protein films and two pellicle proteins (mucin and albumin). Implant surfaces were characterized by perthometer (R_a) and goniometer (SFE) measurements. Implant specimens were rinsed with human whole saliva, mucin, albumin, or phosphate buffered saline and incubated in C. albicans suspension for 2.5 h. Adherent fungi were quantified by means of a bioluminometric assay. The lowest amount of fungal cells was found on sand-blasted titanium, whereas zirconia implants did not show any reduced potential to adhere C. albicans. The influence of the implant SFE on fungal biofilm formation appears to be more important than the influence of R_a. The protein mucin enhanced C. albicans accumulation. In contrast, albumin is unlikely to be involved in the adhesion process of C. albicans.