Pain in IBD Patients: Very Frequent and Frequently Insufficiently Taken into Account.

Pain is a common symptom related to inflammatory bowel disease (IBD). In addition to abdominal pain, pain can also be an extraintestinal manifestation of IBD. Pain treatment is challenging and a substantial part of IBD patients are treated with opioids. Therefore, a better knowledge on pain symptoms is crucial for a better therapeutic approach to this clinical problem. Patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain intensity, pain localization and impact of pain on daily life and social activities. Furthermore, the questionnaire investigated the use of pain-specific medication. A vast majority of patients (71%) experienced pain during the disease course. For a substantial part of patients (49% in UC and 55% in CD) pain is a longstanding problem (>5 years). Pain in UC was of shorter duration compared to CD (p < 0.01). Abdominal pain (59.5%) and back pain (38.3%) were the main pain localizations. 67% of patients took pain medication; 24% received no pain treatment. The general quality of life was significantly lower in patients suffering of pain compared to those without pain (38 vs. 77; (-100 very bad; 100 very good) p<0.0001). Prevalence of pain is high in patients of the SIBDCS. It is a longstanding problem for the majority of the patients affected. Pain was found to be undertreated in the SIBDCS and was significantly associated with health-related quality of life. Thus, an increased awareness is mandatory to address this frequent complication in the course of IBD

Inflammatory Articular Disease in Patients with Inflammatory Bowel Disease: Result of the Swiss IBD Cohort Study

BACKGROUND Inflammatory bowel diseases (IBD) are systemic conditions that commonly display extraintestinal manifestations. Inflammatory articular disease (IAD: axial or peripheral) is the most common extraintestinal manifestation. The aim of this study was to evaluate the prevalence and the clinical characteristics associated with IAD in patients with IBD. METHODS We analyzed patients enrolled in the Swiss IBD cohort study. IAD was defined as persistent or recurrent joint pain with an inflammatory pattern (night pain, progressive relief during the day, morning stiffness lasting at least 30 minutes) or the presence of arthritis as diagnosed by the physicians. A multivariate logistic regression was performed to analyze which disease characteristics were independently associated with the presence of IAD. RESULTS A total of 2353 patients with IBD, 1359 with Crohn's disease, and 994 with ulcerative colitis (UC) were included. Forty-four percent of patients fulfilled the criteria for IAD, whereas 14.5% presented with other extraintestinal manifestations. IAD was associated with Crohn's disease, with female sex, with older age, and generally in patients with more active intestinal disease. Only in UC, IAD was further associated with tobacco smoking and with increasing body mass index. CONCLUSIONS This population of patients with IBD displays a high prevalence of IAD. IAD was more strongly associated with Crohn's disease than UC. Other risk factors for IAD were female sex, advanced age, active digestive disease, and tobacco consumption in patients with UC, which is interesting given the established association between smoking and other inflammatory arthritides

Sensing the (digital) pulse. Future steps for improving the secondary use of data for research in Switzerland.

INTRODUCTION Ensuring that the health data infrastructure and governance permits an efficient secondary use of data for research is a policy priority for many countries. Switzerland is no exception and many initiatives have been launched to improve its health data landscape. The country now stands at an important crossroad, debating the right way forward. We aimed to explore which specific elements of data governance can facilitate - from ethico-legal and socio-cultural perspectives - the sharing and reuse of data for research purposes in Switzerland. METHODS A modified Delphi methodology was used to collect and structure input from a panel of experts via successive rounds of mediated interaction on the topic of health data governance in Switzerland. RESULTS First, we suggested techniques to facilitate data sharing practices, especially when data are shared between researchers or from healthcare institutions to researchers. Second, we identified ways to improve the interaction between data protection law and the reuse of data for research, and the ways of implementing informed consent in this context. Third, we put forth ideas on policy changes, such as the steps necessary to improve coordination between different actors of the data landscape and to win the defensive and risk-adverse attitudes widespread when it comes to health data. CONCLUSIONS After having engaged with these topics, we highlighted the importance of focusing on non-technical aspects to improve the data-readiness of a country (e.g., attitudes of stakeholders involved) and of having a pro-active debate between the different institutional actors, ethico-legal experts and society at large

Association of IBD specific treatment and prevalence of pain in the Swiss IBD cohort study.

Extraintestinal manifestations (EIM) contribute significantly to the burden of disease in inflammatory bowel disease (IBD). Pain is a leading symptom in IBD and could be seen as an EIM itself. Treatment of IBD associated pain is challenging and insufficiently studied. A better knowledge on the association of pain and IBD specific treatment is warranted to improve the management of IBD patients. All patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain localization, pain character, and the use of IBD specific medication. 1263 completed questionnaires were received. Twenty-one out of 184 patients (10%) receiving anti-TNF treatment compared to 142 out of 678 patients (21%) not receiving anti-TNF medication reported elbow pain (p = 0.002) while 28 out of 198 patients (14%) receiving steroid treatment significantly more often reported elbow pain compared to 59 from 696 patients (8%) not receiving steroids (p = 0.021). Furthermore, we found significantly more female patients under anti-TNF treatment to report knee/ lower leg pain and ankle/ foot pain compared to their male counterparts (36% vs. 20% and 22% vs. 10%, respectively, p = 0.015 for both comparisons). The frequency of knee, lower leg, ankle and foot pain was especially low in male patients under anti-TNF treatment, indicating a high benefit of male patients from anti-TNF therapy regarding EIM. The frequency of elbow pain was lower in IBD patients treated with anti-TNF but higher in patients treated with steroids

Validation of a HLA-A2 tetramer flow cytometric method, IFNgamma real time RT-PCR, and IFNgamma ELISPOT for detection of immunologic response to gp100 and MelanA/MART-1 in melanoma patients

<p>Abstract</p> <p>Background</p> <p>HLA-A2 tetramer flow cytometry, IFNγ real time RT-PCR and IFNγ ELISPOT assays are commonly used as surrogate immunological endpoints for cancer immunotherapy. While these are often used as research assays to assess patient's immunologic response, assay validation is necessary to ensure reliable and reproducible results and enable more accurate data interpretation. Here we describe a rigorous validation approach for each of these assays prior to their use for clinical sample analysis.</p> <p>Methods</p> <p>Standard operating procedures for each assay were established. HLA-A2 (A*0201) tetramer assay specific for gp100_209(210M)and MART-1_26–35(27L), IFNγ real time RT-PCR and ELISPOT methods were validated using tumor infiltrating lymphocyte cell lines (TIL) isolated from HLA-A2 melanoma patients. TIL cells, specific for gp100 (TIL 1520) or MART-1 (TIL 1143 and TIL1235), were used alone or spiked into cryopreserved HLA-A2 PBMC from healthy subjects. TIL/PBMC were stimulated with peptides (gp100₂₀₉, gp100_pool, MART-1_27–35, or influenza-M1 and negative control peptide HIV) to further assess assay performance characteristics for real time RT-PCR and ELISPOT methods. Validation parameters included specificity, accuracy, precision, linearity of dilution, limit of detection (LOD) and limit of quantification (LOQ). In addition, distribution was established in normal HLA-A2 PBMC samples. Reference ranges for assay controls were established.</p> <p>Results</p> <p>The validation process demonstrated that the HLA-A2 tetramer, IFNγ real time RT-PCR, and IFNγ ELISPOT were highly specific for each antigen, with minimal cross-reactivity between gp100 and MelanA/MART-1. The assays were sensitive; detection could be achieved at as few as 1/4545–1/6667 cells by tetramer analysis, 1/50,000 cells by real time RT-PCR, and 1/10,000–1/20,000 by ELISPOT. The assays met criteria for precision with %CV < 20% (except ELISPOT using high PBMC numbers with %CV < 25%) although flow cytometric assays and cell based functional assays are known to have high assay variability. Most importantly, assays were demonstrated to be effective for their intended use. A positive IFNγ response (by RT-PCR and ELISPOT) to gp100 was demonstrated in PBMC from 3 melanoma patients. Another patient showed a positive MART-1 response measured by all 3 validated methods.</p> <p>Conclusion</p> <p>Our results demonstrated the tetramer flow cytometry assay, IFNγ real-time RT-PCR, and INFγ ELISPOT met validation criteria. Validation approaches provide a guide for others in the field to validate these and other similar assays for assessment of patient T cell response. These methods can be applied not only to cancer vaccines but to other therapeutic proteins as part of immunogenicity and safety analyses.</p

Effectiveness of national and subnational infection prevention and control interventions in high-income and upper-middle-income countries: a systematic review

Evidence-based guidance for national infection prevention and control (IPC) programmes is needed to support national and global capacity building to reduce health-care-associated infection and antimicrobial resistance. In this systematic review we investigate evidence on the effectiveness of IPC interventions implemented at national or subnational levels to inform the development of WHO guidelines on the core components of national IPC programmes. We searched CENTRAL, CINAHL, Embase, MEDLINE, and WHO IRIS databases for publications between Jan 1, 2000, and April 19, 2017. 29 studies that met the eligibility criteria (ie, economic evaluations, cluster-randomised trials, non-randomised trials, controlled before-and-after studies, and interrupted time-series studies exploring the effective of these interventions) were categorised according to intervention type: multimodal, care bundles, policies, and surveillance, monitoring, and feedback. Evidence of effectiveness was found in all categories but the best quality evidence was on multimodal interventions and surveillance, monitoring, and feedback. We call for improvements in study design, reporting of research, and quality of evidence particularly from low-income countries, to strengthen the uptake and international relevance of IPC interventions

Gender differences in inflammatory bowel disease

Immune-mediated diseases typically show a female preponderance. Looking at all autoimmune diseases combined, 8 of 10 patients are females. Although not as prominent, gender differences in inflammatory bowel disease (IBD) have been reported for epidemiology, disease presentation, disease course and complications, medical and surgical therapies, adherence, psychosocial functioning, and psychiatric co-disorders. While for some factors evidence is rather good, for others data are conflicting. Gastroenterologists dealing with IBD patients in daily clinical practice should be aware of gender-specific issues for the following reasons: (1) misperception of disease presentation potentially delays IBD diagnosis, which has been shown to have deleterious effects, and (2) awareness of gender-specific symptoms and disease severity allows initiation of early and adequately tailored treatment. This might prevent development of complications. And (3) insights into gender-specific differences in terms of treatment and adherence to treatment can improve disease management and foster a more individualized treatment approach. In this review, we summarize current knowledge about gender-specific differences in IBD and highlight the most clinically relevant aspects

The Influence of Breastfeeding, Cesarean Section, Pet Animals, and Urbanization on the Development of Inflammatory Bowel Disease: Data from the Swiss IBD Cohort Study.

Introduction The pathophysiology of inflammatory bowel disease (IBD) is incompletely understood. Current concepts imply that environmental factors (EFs) trigger disease onset as well as flares in genetically susceptible individuals. Objective The objective of this study is to analyze the association between IBD and various EFs, which may influence the pathogenesis of the disease. Methods 2,294 patients from the Swiss IBD Cohort Study (SIBDCS) received a questionnaire regarding EF including mode of delivery, breastfeeding, animals in household, and place of residence. The control group comprised patients' childhood friends, who grew up in a similar environment ("friends cohort"). Results A total of 1,111 questionnaires were returned from SIBDCS patients (response rate: 48.4%). Breastfeeding for <6 months was associated with a decreased risk for ulcerative colitis/indeterminate colitis (UC/IC) (OR: 0.473, p = 0.006). IBD patients reported less pet animals in the household than the control group (p = 0.004). The presence of cats or dogs (OR: 0.688, p = 0.015) and pet rodents (OR: 0.598, p = 0.001) in the household before the age of 20 was inversely associated with the risk for UC/IC. Conclusion The present study underlines the importance of EFs in the pathogenesis of IBD. Overall, the development of UC/IC seems to be more affected from environmental influences than from Crohn's disease. Our results imply a protective effect of possessing pet animals in household and short breastfeeding regarding the onset of UC/IC

Hand hygiene among physicians: performance, beliefs, and perceptions

BACKGROUND: Physician adherence to hand hygiene remains low in most hospitals. OBJECTIVES: To identify risk factors for nonadherence and assess beliefs and perceptions associated with hand hygiene among physicians. DESIGN: Cross-sectional survey of physician practices, beliefs, and attitudes toward hand hygiene. SETTING: Large university hospital. PARTICIPANTS: 163 physicians. MEASUREMENTS: Individual observation of physician hand hygiene practices during routine patient care with documentation of relevant risk factors; self-report questionnaire to measure beliefs and perceptions. Logistic regression identified variables independently associated with adherence. RESULTS: Adherence averaged 57% and varied markedly across medical specialties. In multivariate analysis, adherence was associated with the awareness of being observed, the belief of being a role model for other colleagues, a positive attitude toward hand hygiene after patient contact, and easy access to hand-rub solution. Conversely, high workload, activities associated with a high risk for cross-transmission, and certain technical medical specialties (surgery, anesthesiology, emergency medicine, and intensive care medicine) were risk factors for nonadherence. LIMITATIONS: Direct observation of physicians may have influenced both adherence to hand hygiene and responses to the self-report questionnaire. Generalizability of study results requires additional testing in other health care settings and physician populations. CONCLUSION: Physician adherence to hand hygiene is associated with work and system constraints, as well as knowledge and cognitive factors. At the individual level, strengthening a positive attitude toward hand hygiene and reinforcing the conviction that each individual can influence the group behavior may improve adherence among physicians. Physicians who work in technical specialties should also be targeted for improvement