Scoring and psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), an instrument to assess satisfaction and compliance with glaucoma treatment

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to ascertain the scoring and assess the psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), a 43-item Patient-Reported Outcome instrument developed to assess patients' satisfaction and compliance with glaucoma treatment.</p> <p>Methods</p> <p>The EDSQ was administered during an observational, retrospective study to 184 French patients treated for glaucoma. The hypothesized structure, including six dimensions (patient-clinician relationship; patient experience; patient-treatment interaction; apprehension; patient knowledge; travel), was tested by assessing the internal consistency reliability (Cronbach's alpha) and construct-related validity (item convergent and discriminant validity). As unsatisfactory results were demonstrated, another structure was defined using a principal component analysis (PCA) combined with content of items. Psychometric properties of this new structure were assessed. Scores were compared between low, moderate and high compliance profile groups defined using data collected with the Travalert electronic device.</p> <p>Results</p> <p>Analyses were performed with the 169 patients who completed at least half of the EDSQ items. The hypothesized structure showed a Cronbach's alpha lower than 0.70 for four dimensions out of six and an overall poor construct-related validity (range of item-scale correlations: 0.00-0.68). The new structure obtained with the PCA included six dimensions: concern about treatment (five items); concern about disease (two items); satisfaction with patient-clinician relationship (five items); positive beliefs (three items); treatment convenience (three items); and self-declared compliance (three items). A score ranging from 0 to 100 was calculated for each dimension, with higher scores indicating more of the attribute referred to in the dimension. Internal consistency reliability was good (Cronbach's alpha greater than 0.70 for five dimensions). The structure offered good construct-related validity (range of item-scale correlations: 0.36-0.82). Ceiling effects of 21% and 49%, were observed for the satisfaction with patient-clinician relationship and self-declared compliance scores. Patients in low compliance profile group reported the lowest score for the satisfaction with patient-clinician relationship, positive beliefs, treatment convenience and self-declared compliance dimensions, and the highest score for the concern about treatment dimension.</p> <p>Conclusions</p> <p>The scoring of the EDSQ was developed and the questionnaire proved to have satisfactory psychometric properties. EDSQ scores showed a promising relationship to compliance profiles. The EDSQ could be used in future studies.</p

Measuring benefits and patients' satisfaction when glasses are not needed after cataract and presbyopia surgery: scoring and psychometric validation of the Freedom from Glasses Value Scale (FGVS©)

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to reduce the number of items, create a scoring method and assess the psychometric properties of the Freedom from Glasses Value Scale (FGVS), which measures benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal intraocular lens (IOL) surgery.</p> <p>Methods</p> <p>The 21-item FGVS, developed simultaneously in French and Spanish, was administered by phone during an observational study to 152 French and 152 Spanish patients who had undergone cataract or presbyopia surgery at least 1 year before the study. Reduction of items and creation of the scoring method employed statistical methods (principal component analysis, multitrait analysis) and content analysis. Psychometric properties (validation of the structure, internal consistency reliability, and known-group validity) of the resulting version were assessed in the pooled population and per country.</p> <p>Results</p> <p>One item was deleted and 3 were kept but not aggregated in a dimension. The other 17 items were grouped into 2 dimensions ('global evaluation', 9 items; 'advantages', 8 items) and divided into 5 sub-dimensions, with higher scores indicating higher benefit of surgery. The structure was validated (good item convergent and discriminant validity). Internal consistency reliability was good for all dimensions and sub-dimensions (Cronbach's alphas above 0.70). The FGVS was able to discriminate between patients wearing glasses or not after surgery (higher scores for patients not wearing glasses). FGVS scores were significantly higher in Spain than France; however, the measure had similar psychometric performances in both countries.</p> <p>Conclusions</p> <p>The FGVS is a valid and reliable instrument measuring benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal IOL surgery.</p

Thomas Graham Brown (1882–1965): Behind the Scenes at the Cardiff Institute of Physiology

Thomas Graham Brown undertook seminal experiments on the neural control of locomotion between 1910 and 1915. Although elected to the Royal Society in 1927, his locomotion research was largely ignored until the 1960s when it was championed and extended by the distinguished neuroscientist, Anders Lundberg. Puzzlingly, Graham Brown's published research stopped in the 1920s and he became renowned as a mountaineer. In this article, we review his life and multifaceted career, including his active neurological service in WWI. We outline events behind the scenes during his tenure at Cardiff's Institute of Physiology in Wales, UK, including an interview with his technician, Terrence J. Surman, who worked in this institute for over half a century

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms of genes involved in the immunological recognition of <it>Helicobacter pylori </it>and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding <it>Angiotensin converting enzyme </it>(<it>ACE</it>), <it>Nod-like receptor 1 </it>(<it>NOD1</it>), <it>Toll-like receptor 4 </it>(<it>TLR4</it>) and <it>FAS/FASL</it>.</p> <p>Methods</p> <p>Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. <it>ACE I/D </it>(rs4646994), <it>NOD1 796G>A </it>(rs5743336), <it>TLR4 3725G>C </it>(rs11536889), <it>FAS 1377G>A </it>(rs2234767), <it>FAS 670A>G </it>(rs1800682) and <it>FASL 844T>C </it>(rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for <it>NOD1 796G/G </it>genotype to be associated with increased risk of HRAG (62.4% <it>vs</it>. 54.5% in controls, <it>p </it>= 0.082). <it>FAS 670G/G </it>genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (<it>p </it>= 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. <it>NOD1 796G>A </it>and <it>TLR4 3725G>C </it>gene polymorphisms were also not associated with <it>Helicobacter pylori </it>infection.</p> <p>Conclusions</p> <p><it>ACE, NOD1, TRL4 </it>and <it>FAS/FASL </it>gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.</p

MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the α- and β-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy

Induction of TLR-2 and TLR-5 Expression by Helicobacter pylori Switches cagPAI-Dependent Signalling Leading to the Secretion of IL-8 and TNF-α

Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI) encoding a type-IV secretion system (T4SS) for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs) and downstream signalling pathways in the development of different pathologies are widely unclear. Here, we explored the involvement of TLR-2 and TLR-5 in THP-1 cells and HEK293 cell lines (stably transfected with TLR-2 or TLR-5) during infection with wild-type H. pylori and isogenic cagPAI mutants. H. pylori triggered enhanced TLR-2 and TLR-5 expression in THP-1, HEK293-TLR2 and HEK293-TLR5 cells, but not in the HEK293 control. In addition, IL-8 and TNF-α cytokine secretion in THP-1 cells was induced in a cagPAI-dependent manner. Furthermore, we show that HEK293 cells are not competent for the uptake of T4SS-delivered CagA, and are therefore ideally suited for studying TLR signalling in the absence of T4SS functions. HEK293 control cells, which do not induce TLR-2 and TLR-5 expression during infection, only secreted cytokines in small amounts, in agreement with T4SS functions being absent. In contrast, HEK293-TLR2 and HEK293-TLR5 cells were highly competent for inducing the secretion of IL-8 and TNF-α cytokines in a cagPAI-independent manner, suggesting that the expression of TLR-2 or TLR-5 has profoundly changed the capability to trigger pro-inflammatory signalling upon infection. Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces IRAK-1 and IκB phosphorylation in a TLR-dependent manner, and this was required for activation of transcription factor NF-κB. Finally, NF-κB activation in HEK293-TLR2 and HEK293-TLR5 cells was confirmed by expressing p65-GFP which was translocated from the cytoplasm into the nucleus. These data indicate that H. pylori-induced expression of TLR-2 and TLR-5 can qualitatively shift cagPAI-dependent to cagPAI-independent pro-inflammatory signalling pathways with possible impact on the outcome of H. pylori-associated diseases

Multiple Peptidoglycan Modification Networks Modulate Helicobacter pylori's Cell Shape, Motility, and Colonization Potential

Helical cell shape of the gastric pathogen Helicobacter pylori has been suggested to promote virulence through viscosity-dependent enhancement of swimming velocity. However, H. pylori csd1 mutants, which are curved but lack helical twist, show normal velocity in viscous polymer solutions and the reason for their deficiency in stomach colonization has remained unclear. Characterization of new rod shaped mutants identified Csd4, a DL-carboxypeptidase of peptidoglycan (PG) tripeptide monomers and Csd5, a putative scaffolding protein. Morphological and biochemical studies indicated Csd4 tripeptide cleavage and Csd1 crosslinking relaxation modify the PG sacculus through independent networks that coordinately generate helical shape. csd4 mutants show attenuation of stomach colonization, but no change in proinflammatory cytokine induction, despite four-fold higher levels of Nod1-agonist tripeptides in the PG sacculus. Motility analysis of similarly shaped mutants bearing distinct alterations in PG modifications revealed deficits associated with shape, but only in gel-like media and not viscous solutions. As gastric mucus displays viscoelastic gel-like properties, our results suggest enhanced penetration of the mucus barrier underlies the fitness advantage conferred by H. pylori's characteristic shape

Guideline for diagnosis and treatment of subacromial pain syndrome

Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-operatively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears

NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system

Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life and survival are two important outcome measures in cancer research and practice. The aim of this paper is to examine the relationship between quality of life data and survival time in cancer patients.</p> <p>Methods</p> <p>A review was undertaken of all the full publications in the English language biomedical journals between 1982 and 2008. The search was limited to cancer, and included the combination of keywords 'quality of life', 'patient reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that appeared in the titles of the publications. In addition, each study was examined to ensure that it used multivariate analysis. Purely psychological studies were excluded. A manual search was also performed to include additional papers of potential interest.</p> <p>Results</p> <p>A total of 451 citations were identified in this rapid and systematic review of the literature. Of these, 104 citations on the relationship between quality of life and survival were found to be relevant and were further examined. The findings are summarized under different headings: heterogeneous samples of cancer patients, lung cancer, breast cancer, gastro-oesophageal cancers, colorectal cancer, head and neck cancer, melanoma and other cancers. With few exceptions, the findings showed that quality of life data or some aspects of quality of life measures were significant independent predictors of survival duration. Global quality of life, functioning domains and symptom scores - such as appetite loss, fatigue and pain - were the most important indicators, individually or in combination, for predicting survival times in cancer patients after adjusting for one or more demographic and known clinical prognostic factors.</p> <p>Conclusion</p> <p>This review provides evidence for a positive relationship between quality of life data or some quality of life measures and the survival duration of cancer patients. Pre-treatment (baseline) quality of life data appeared to provide the most reliable information for helping clinicians to establish prognostic criteria for treating their cancer patients. It is recommended that future studies should use valid instruments, apply sound methodological approaches and adequate multivariate statistical analyses adjusted for socio-demographic characteristics and known clinical prognostic factors with a satisfactory validation strategy. This strategy is likely to yield more accurate and specific quality of life-related prognostic variables for specific cancers.</p