Risk of candidiasis associated with interleukin-17 inhibitors:A real-world observational study of multiple independent sources

BACKGROUND: Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti-Candida host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility. METHODS: A comprehensive analysis of multiple independent sources reporting Candida adverse events during biologics inhibiting the Th17 pathway was performed. Association between Th17 inhibitors and candidiasis was assessed using safety reports of (1) WHO and (2) EMA, (3) a population-based prescriptions registry, and (4) a psoriasis cohort. In a cohort of psoriasis patients experiencing candidiasis during Th17 inhibitors, Candida killing by immune cells and serum inflammatory proteome were analyzed. FINDINGS: A strong association between IL-17 inhibitors and candidiasis (ROR 10·20) was found in the WHO database, particularly for cutaneous (ROR 12·28), oropharyngeal (ROR 19·18), and esophageal candidiasis (ROR 21·20). Risk was higher relative to TNF-α inhibitors (4–10-fold, depending on candidiasis type), confirmed by EMA reports (16–33-fold), prescriptions registry (2–42-fold), and a psoriasis cohort (3–25-fold). After start of IL-17 inhibitors, patients’ risk of candidiasis requiring antifungals increased 2–16 fold. In the psoriasis cohort, 58% of IL-17 treatment episodes were associated with candidiasis. In Th17 inhibitor recipients, proteins involved in anti-Candida immunity and Candida killing by mononuclear leukocytes were impaired. INTERPRETATION: IL-17 inhibitors are associated with an increased risk of oropharyngeal, esophageal, and cutaneous candidiasis, posing a significant disease burden for IL-17 inhibitor recipients. FUNDING: RadboudUMC

Health and health care utilisation among asylum seekers and refugees in the Netherlands: design of a study

BACKGROUND: This article discusses the design of a study on the prevalence of health problems (both physical and mental) and the utilisation of health care services among asylum seekers and refugees in the Netherlands, including factors that may be related to their health and their utilisation of these services. METHODS/DESIGN: The study will include random samples of adult asylum seekers and refugees from Afghanistan, Iran and Somali (total planned sample of 600), as these are among the largest groups within the reception centres and municipalities in the Netherlands. The questionnaire that will be used will include questions on physical health (chronic and acute diseases and somatization), mental health (Hopkins Symptoms Checklist-25 and Harvard Trauma Questionnaire), utilisation of health care services, pre- and post-migratory traumatic experiences, life-style, acculturation, social support and socio-demographic background. The questionnaire has gone through a translation process (translation and back-translation, several checks and a pilot-study) and cross-cultural adaptation. Respondents will be interviewed by bilingual and bicultural interviewers who will be specifically trained for this purpose. This article discusses the selection of the study population, the chosen outcome measures, the translation and cross-cultural adaptation of the measurement instrument, the training of the interviewers and the practical execution of the study. The information provided may be useful for other researchers in this relatively new field of epidemiological research among various groups of asylum seekers and refugees

Pointing in entertainment-oriented environments: Appreciation versus performance

Multimedia applications for consumer entertainment often employ a point-and-select interaction style, borrowed from more task-oriented computer applications. The environment of use and the pointing devices involved are so different, however, that a higher importance should be attributed to the users' appreciation of the pointing device than to its efficiency or any other objective performance measure. We set up an experiment to investigate how appreciation and performance measures relate. The experiment involved six different input devices, two CD-i titles and 16 subjects making both voluntary and prescribed cursor control movements. For the mouse-like pointing devices we obtained a Fitts' Law-like dependence on target width and target distance. This was, however, not replicated for any of the other input devices, mainly owing to a positive influence of cursor constraints. Concerning the relation of the performance measures with the users' appreciation, we found that neither time-to-target nor relative-path-length on its own is a reliable indicator of the users' appreciation. Together, however, they might explain the appreciation scores to a considerable extent

Pointing in entertainment-oriented environments: Appreciation versus performance

Multimedia applications for consumer entertainment often employ a point-and-select interaction style, borrowed from more task-oriented computer applications. The environment of use and the pointing devices involved are so different, however, that a higher importance should be attributed to the users' appreciation of the pointing device than to its efficiency or any other objective performance measure. We set up an experiment to investigate how appreciation and performance measures relate. The experiment involved six different input devices, two CD-i titles and 16 subjects making both voluntary and prescribed cursor control movements. For the mouse-like pointing devices we obtained a Fitts' Law-like dependence on target width and target distance. This was, however, not replicated for any of the other input devices, mainly owing to a positive influence of cursor constraints. Concerning the relation of the performance measures with the users' appreciation, we found that neither time-to-target nor relative-path-length on its own is a reliable indicator of the users' appreciation. Together, however, they might explain the appreciation scores to a considerable extent

Pointing in entertainment-oriented environments : appreciation versus performance

Multimedia :Applications for consumer entertainment of I en employ a point-and-select interaction style, borrowed from more task-oriented computer applications. The environment afuse and the pointing devices involved are so different, however, that a higher importance should be attributed to the users' appreciation of the pointing device than to its efficiency or any other objective performance measure. We set up an experiment to investigate how appreciation and performance measures relate. The experiment involved six different input devices, two CD-i litles and 16 subjects making both voluntary and prescribed cursor control movements. For the mouse-like pointing devices we obtained a Fins' Law-like dependence on target width and target distance. This was, however, not replicated for any of the other input devices, mainly owing to a positive influence of cursor constraints. Concerning the relation of the performance measures with the users' appreciation, we found that neither time-to-target nor relative-path-length on its own is a reliable indicator of the users' appreciation. Together, however, they might explain the appreciation scores to a considerable extent