The impact of biologics on health-related quality of life in patients with inflammatory bowel disease

Lauran Vogelaar1, Adriaan van’t Spijker2, C Janneke van der Woude11Department of Gastroenterology and Hepatology, 2Department of Psychology and Psychotherapy, Erasmus Medical Centre, RotterdamBackground: Inflammatory bowel disease (IBD) is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL). A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.Objective: To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.Methods: We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH). Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.Results: Out of 202 identified articles, 8 randomized controlled trials (RCT) met the inclusion criteria. Two RCTs on infliximab showed significant improvement of HRQoL compared to placebo which was sustained over the long term. One RCT on adalimumab showed a significant and sustained improvement of HRQoL compared to placebo. This study showed also significant decrease of fatigue in the adalimumabtreated patients. Three RCTs on certolizumab showed a significant improvement of HRQoL in the intervention group compared to placebo. Two RCTs of natalizumab treatment were found. One study showed significant and sustained improvement compared to placebo, and also scores of HRQoL comparable to that in the general population, but in the other no significant results were found.Conclusion: The biologics infliximab, adalimumab, certolizumab, and natalizumab demonstrated significant improvement of HRQoL of IBD patients compared with placebo. However, we found differences in improvement of HRQoL between the different biologics.Keywords: inflammatory bowel disease, health-related quality of life, health care costs, biologic

Development of a new scale for perceived self-efficacy in manual wheeled mobility:a pilot study

Objective: To study the psychometric qualities of a perceived self-efficacy in wheeled mobility scale. Design: Questionnaires. Subjects: Forty-seven wheelchair users with spinal cord injury (elite athletes n= 25, recreational n= 22, from 6 different countries). Method: Based on the literature, and expert's and wheelchair user's comments, a new Self-Efficacy in Wheeled Mobility Scale (SEWM(1)) was developed. Internal consistency (split-half and Cronbach's alpha) and concurrent validity (correlating the Self-Efficacy in Wheeled Mobility Scale with the Generalized Perceived Self-efficacy Scale (GSE) and the spinal cord injury Exercise Self-Efficacy Scale (ESES)) were assessed. To evaluate the construct validity, age, lesion level and completeness and time since injury between groups of participants and their total scores were compared statistically. Results: Cronbach's alpha for the SEWM was 0.91, internal consistency was r=0.90. Significant correlations between pairs of scales of the entire sample (SEWM-ESES: 0.60; SEWM-GSE: 0.50 (p <0.05; n=47, 2-tailed) and of the subgroup comparison (SEWM-ESES recreational r= 0.61; elite r=0.73), demonstrated fair construct and concurrent validity of the SEWM. Conclusion: The SEWM was found to be reliable and valid in active spinal cord injury. A larger more diverse sample is needed to support the psychometric qualities of the SEWM scale

Eradication of invasive birds from tropical oceanic islands: lessons learned from studies of common mynas Acridotheres tristis

Feare, C., Greenwell, P., Edwards, H., Taylor, J., Van der Woude, J

Recovery of protein synthesis to assay DNA repair activity in transcribed genes in living cells and tissues

Transcription-coupled nucleotide excision repair (TC-NER) is an important DNA repair mechanism that protects against the negative effects of transcription-blocking DNA lesions. Hereditary TC-NER deficiencies cause pleiotropic and often severe neurodegenerative and progeroid symptoms. While multiple assays have been developed to determine TC-NER activity for clinical and research purposes, monitoring TC-NER is hampered by the low frequency of repair events occurring in transcribed DNA. ’Recovery of RNA Synthesis’ is widely used as indirect TC-NER assay based on the notion that lesion-blocked transcription only resumes after successful TC-NER. Here, we show that measuring novel synthesis of a protein after its compound-induced degradation prior to DNA damage induction is an equally effective but more versatile manner to indirectly monitor DNA repair activity in transcribed genes. This ‘Recovery of Protein Synthesis’ (RPS) assay can be adapted to various degradable proteins and readouts, including imaging and immunoblotting. Moreover, RPS allows real-time monitoring of TC-NER activity in various living cells types and even in differentiated tissues of living organisms. To illustrate its utility, we show that DNA repair in transcribed genes declines in aging muscle tissue of C. elegans. Therefore, the RPS assay constitutes an important novel clinical and research tool to investigate transcription-coupled DNA repair

Bifurcation Boundary Conditions for Switching DC-DC Converters Under Constant On-Time Control

Sampled-data analysis and harmonic balance analysis are applied to analyze switching DC-DC converters under constant on-time control. Design-oriented boundary conditions for the period-doubling bifurcation and the saddle-node bifurcation are derived. The required ramp slope to avoid the bifurcations and the assigned pole locations associated with the ramp are also derived. The derived boundary conditions are more general and accurate than those recently obtained. Those recently obtained boundary conditions become special cases under the general modeling approach presented in this paper. Different analyses give different perspectives on the system dynamics and complement each other. Under the sampled-data analysis, the boundary conditions are expressed in terms of signal slopes and the ramp slope. Under the harmonic balance analysis, the boundary conditions are expressed in terms of signal harmonics. The derived boundary conditions are useful for a designer to design a converter to avoid the occurrence of the period-doubling bifurcation and the saddle-node bifurcation.Comment: Submitted to International Journal of Circuit Theory and Applications on August 10, 2011; Manuscript ID: CTA-11-016

Professionals' perceptions of factors affecting implementation and continuation of a physical activity promotion programme in rehabilitation: A qualitative study

Objective: To describe professionals’ perceptions of factors that facilitate or hamper the implementation and continuation of a physical activity promotion programme in rehabilitation. Design: This study used a qualitative design. Methods: Semi-structured interviews (n = 22) were conducted with rehabilitation professionals (n = 28) involved in the implementation of a physical activity promotion programme. Two additional interviews were conducted with the programme coordinators (n = 2). The study involved 18 rehabilitation organizations implementing the programme that targets people with disabilities or chronic diseases. Organizations were supported in the implementation process by the programme coordinators. Results: Commonly perceived facilitating factors were: involvement of committed and enthusiastic professionals; agreement with their organizations’ vision/wishes; the perceived additional value of the programme; and opportunities to share knowledge and experience with professionals from other organizations. Commonly perceived hampering factors were: uncertainty about continuing the programme; limited flexibility; and lack of support from physicians and therapists to implement the programme. Conclusion: Professionals perceived a heterogeneous set of factors that facilitate and/or hamper the implementation and continuation of a physical activity promotion programme in rehabilitation. Based on these findings, recommendations were formulated to enhance embedding of physical activity promotion during and after rehabilitation