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Van Der Valk M.E.,University Utrecht | Mangen M.-J.J.,University Utrecht | Leenders M.,University Utrecht | Dijkstra G.,University of Groningen | And 17 more authors.
Gut | Year: 2014

Objective The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. Design Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. Results A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625(95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. Conclusions We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.


Haeseker G.A.,Diaconessenhuis | Mureau M.A.,Erasmus Medical Center | Faber F.W.M.,Haga Ziekenhuis
Journal of Foot and Ankle Surgery | Year: 2010

In this study, clinical and radiological results after lateral column lengthening by calcaneocuboid distraction arthrodesis and calcaneus osteotomy were compared. Thirty-three patients (35 feet) treated with lateral column lengthening by distraction arthrodesis (14 patients, 16 feet; group I) or by calcaneus osteotomy (19 patients, 19 feet; group II) for adult-acquired flatfoot deformity caused by stage II posterior tibial tendon dysfunction were compared retrospectively. Mean follow-up was 42.4 months (range, 6-78 months) for group I and 15.8 months (range, 6-32 months) for group II (P < .001). The American Orthopaedic Foot & Ankle Society ankle-hindfoot score was determined, 4 variables were measured on preoperative and postoperative weight-bearing radiographs, and a number of independent and outcome variables, including patient satisfaction, were recorded. Group 2 had a significantly higher American Orthopaedic Foot & Ankle Society score compared with group I (mean, 85 vs. 72, respectively; P < .02) at time of last follow-up, and there were no dissatisfied patients in group I, whereas 2 patients in group II were dissatisfied with the result of the operation. All radiological results were significantly better at time of follow-up in both groups (except for talocalcaneal angle in group I), although no significant differences were noted in the amount of change in radiographic measurements between the groups. No significant correlation was found between follow-up time and radiographic improvement, indicating stable radiographic measurements over time. In group II, 13 mild calcaneocuboid subluxations were observed. In both groups, 1 nonunion and 1 wound complication occurred. Based on our experience with the patients described in this report, we recommend lateral column lengthening by means of calcaneus osteotomy rather than distraction arthrodesis of the calcaneocuboid joint, for correction of stage II posterior tibial tendon dysfunction. © 2010 American College of Foot and Ankle Surgeons.


Hoitsma E.,Diaconessenhuis | Hoitsma E.,Maastricht University | De Vries J.,Maastricht University | De Vries J.,University of Tilburg | And 2 more authors.
Respiratory Medicine | Year: 2011

Background: Small fiber neuropathy (SFN) appears to be relatively common in sarcoidosis patients. However, there is no golden standard to establish SFN and diagnostic tests for SFN are not widely available. There is a need for an easy to administer SFN screening instrument for clinical assessment, research or therapeutic trials. The aim of the present study was to develop a screening list to identify sarcoidosis patients with SFN in general clinical practice. Methods: We studied 139 sarcoidosis patients. The first consecutive 84 patients (Group 1) underwent temperature threshold testing (TTT) and completed an extensive SFN-symptoms-questionnaire. Based on data from Group 1 and using distribution measures and discriminant analyses, a screening list for SFN in sarcoidosis consisting of 21 questions was constructed: the Small Fiber Neuropathy Screening List (SFNSL). Subsequently, this SFNSL was crossvalidated in the next 55 consecutive patients (Group 2). Results: The same cut-off scores as found for Group 1 were appropriate in Group 2. The SFNSL was found to have high levels of internal consistency (Cronbach's alpha 0.90) and exploratory factor analysis showed that it measures only one underlying factor. Convergent validity seems good. Conclusion: To assess the presence of SFN in clinical practice the SFNSL, a brief and easy to administer questionaire, was developed in a sarcoidosis population. The results of the present study support the idea that SFN is a serious problem in chronic sarcoidosis. Future studies are needed to establish the broad usefulness of this SFN screening list and expand knowledge on the psychometric properties. © 2010 Elsevier Ltd. All rights reserved.


Wijnen P.A.,Maastricht University | Cremers J.P.,Gelderse Vallei Hospital | Nelemans P.J.,Maastricht University | Erckens R.J.,Maastricht University | And 5 more authors.
European Respiratory Journal | Year: 2014

Responsiveness to tumour necrosis factor (TNF) inhibitors has been associated with the TNF-α G-308A polymorphism in rheumatoid arthritis. The aim of this study was to examine the association between the presence of this polymorphism and the response to TNF inhibitors in patients with refractory sarcoidosis. Patients (n=111) who started TNF-inhibitor treatment (76 infliximab, 35 adalimumab) were followed for at least 1 year. The main symptoms in these patients were fatigue (n=100, 90.1%), small fibre neuropathy (n=91, 82.0%), pulmonary involvement (n=69, 62.2%), and/or uveitis (n=31, 27.9%). Patients were additionally genotyped for the presence of the TNF-α G-308A polymorphism. Treatment response was assessed using clinical outcome measures and questionnaires. Three-quarters (n=83, 74.8%) of the patients responded well. Of the patients without the variant A-allele 93.6% (73 out of 78, p0.001) improved, while 30.3% (10 out of 33) of variant A-allele carriers responded favourably to TNF inhibitors. For patients with the GG-genotype, the probability of improving compared with remaining stable or deteriorating was three times higher (risk ratio 3.09, 95% CI 1.84-5.20). Sarcoidosis patients without the TNF-α-308A variant allele (GG-genotype) had a three-fold higher response to TNF inhibitors (adalimumab or infliximab). Further research is needed to evaluate the value of genotyping for the TNF-α G-308A polymorphism in order to tailor TNF-inhibitor treatment. Copyright ©ERS 2014.


Wiggenraad R.,Radiotherapy Center West | Verbeek-De Kanter A.,Radiotherapy Center West | Mast M.,Radiotherapy Center West | Molenaar R.,Diaconessenhuis | And 4 more authors.
Strahlentherapie und Onkologie | Year: 2012

Purpose. The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases >3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases.Materials and methods. In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of >13 cm3 or metastases in the brainstem.Results. The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p=0.93) and pseudo progression (85% and 75%, p=0.25) were not significantly different. Overall survival rates were also not different.Conclusion. The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. © Springer-Verlag 2012.


Demirel F.,Isala Hospital | Adiyaman A.,Isala Hospital | Timmer J.R.,Isala Hospital | Dambrink J.-H.E.,Isala Hospital | And 3 more authors.
International Journal of Cardiology | Year: 2014

Objectives: We hypothesized that myocardial scar characterization using cardiac magnetic resonance imaging (CMR) may be associated with the occurrence of ventricular tachyarrhythmia (VT), appropriate implantable cardioverter-defibrillator (ICD) therapy and mortality.Background: Since a minority of patients with prophylactic ICD implantation receive appropriate ICD therapy, there is a need for more effective risk stratification for primary prevention in patients with ischemic cardiomyopathy.Methods: and results In 99 patients with ischemic cardiomyopathy, CMR was performed prior to ICD implantation. We assessed if CMR indices (cardiac mass, LVEF) and CMR scar characteristics (infarct core mass, peri-infarction mass and the ratio's between left ventricular mass, infarct core mass and peri-infarction mass) were associated with outcome. The primary endpoint was sustained VT and/or appropriate ICD therapy. The secondary endpoint was all-cause mortality. During a median follow-up of 5.4 years (IQR 4.5-6.6 years), 34 patients reached the primary end-point (17 appropriate ICD shocks) and 26 patients died. In multivariable Cox regression analysis, peri-infarction to core-infarction ratio (HR 2.01, 95%CI: 1.17-3.44, p = 0.01) was independently and significantly associated with the primary endpoint, whereas NYHA-class and lower LVEF were not. Conversely, age (HR 1.06, 95% CI: 1.01-1.12, p = 0.02) and lower LVEF (HR 0.95, 95% CI: 0.91-1.00, p = 0.04) were independently associated with all-cause mortality, mainly due to heart failure.Conclusion: A relatively large peri-infarction mass is associated with sustained VT and/or appropriate ICD therapy, whereas age and lower LVEF are associated with mortality. CMR based tissue characterization could aid in the prediction of specific outcome measures and in clinical decision making. © 2014 Elsevier Ireland Ltd. All rights reserved.


Fischer M.J.,Leiden University | Wiesenhaan M.E.,Leiden University | Heijer A.D.-D.,Diaconessenhuis | Kleijn W.C.,Leiden University | And 2 more authors.
British Journal of Health Psychology | Year: 2013

Objectives This study examined the cross-sectional and longitudinal relationships of illness perceptions, coping, and distress in women with breast cancer. Illness perceptions and coping at baseline and changes in these variables over time served as possible predictors of distress at two follow-up points. Design and methods Fifty-seven women with breast cancer who participated in a psychosocial aftercare programme completed a questionnaire before the start of the intervention, directly after the end of the intervention, and 1 year after the start of the intervention. Study variables were assessed with the Illness Perception Questionnaire-Revised (illness perceptions), the COPE (coping), and the Hopkins Symptom Check List (distress). Results Results showed that 43% of variance in distress at baseline was explained by participants' illness perceptions. Cyclical timeline perceptions were the strongest predictor of distress at baseline. Longitudinal data revealed that after the end of the intervention, the intensity of general distress and breast cancer-related emotions had decreased significantly. Partial correlations showed that baseline illness perceptions were unrelated to distress at follow-up. However, changes in illness perceptions (perceptions about the cyclical and chronic timeline and symptoms associated with breast cancer) showed significant associations with distress at both follow-up assessments. Associations of follow-up distress with coping styles were less consistent. Conclusions Our results suggest that changes in illness perceptions are related to an improvement or worsening of patients' emotional well-being over time. These findings hold promise for the development of interventions that specifically target patients' representations of their illness. Statement of contribution What is already known on this subject? Research has shown that 15%-30% of breast cancer survivors continue to experience elevated distress following treatment. Illness perceptions and coping have been found to contribute to distress in women with breast cancer. What does this study add? Cyclical timeline beliefs affect distress in breast cancer both in cross-sectional and longitudinal analyses. Baseline illness perceptions are less predictive of distress at follow-up than changes in illness perceptions. © 2012 The British Psychological Society.


Datema M.,Leiden University | Gert van Dijk J.,Leiden University | Hoitsma E.,Diaconessenhuis
Clinical Neurophysiology | Year: 2012

Objective: To investigate the diagnostic yield of two simple tests for small fiber neuropathy (SFN): Neuropads® and water immersion skin wrinkling (WISW). Methods: We studied 35 patients clinically diagnosed with SFN and 61 age- and sex-matched healthy controls. Wrinkling was judged as absent (abnormal), or present (normal) after immersion of the hands for 30. min. Neuropads® are plasters impregnated with cobalt blue that are applied with to the soles of the feet. These remain blue when feet are dry (abnormal) or turn pink when there is some moisture (normal). Results: The sensitivity of the Neuropad® was 29% and its specificity 93%. The sensitivity of WISW was 66% and its specificity 70%. Regarding abnormality of at least one test to define the combination as abnormal yielded a sensitivity of 71% and specificity 67%. When both tests had to be abnormal to judge the combination abnormal, sensitivity was 23% and specificity 97%. Conclusions: The Neuropad® has a high specificity, so an abnormal result can be used to confirm SFN. WISW has a moderate sensitivity and specificity. Combining these two tests can be helpful: when both tests are abnormal the diagnosis SFN is highly likely. Significance: The Neuropad® and WISW can be helpful in daily practice by supporting the diagnosis SFN. © 2012 International Federation of Clinical Neurophysiology.


Van Der Zee H.H.,Rotterdam University | De Ruiter L.,Rotterdam University | Boer J.,Deventer Hospital | Van Den Broecke D.G.,Diaconessenhuis | And 3 more authors.
British Journal of Dermatology | Year: 2012

Background Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. Objectives To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. Methods In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. Results Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. Conclusions Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin. © 2011 British Association of Dermatologists.


Van Der Zee H.H.,Erasmus Medical Center | De Ruiter L.,Erasmus Medical Center | Van Den Broecke D.G.,Diaconessenhuis | Dik W.A.,Erasmus Medical Center | And 2 more authors.
British Journal of Dermatology | Year: 2011

Background The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not known whether the levels of tumour necrosis factor (TNF)-α are aberrant in HS skin, anti-TNF-α biologics are used, with variable clinical efficacy. Objectives To determine the cytokine profile in lesional and perilesional HS skin. Methods We cultured 20 lesional and 10 normal-appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin. Results The proinflammatory cytokines interleukin (IL)-1β and TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL-1β, TNF-α and IL-10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL-2, IL-4, IL-5 and interferon-γ were hardly detectable in HS or healthy control skin. Conclusions This study shows for the first time that IL-1β, TNF-α and IL-10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF-α and IL-1. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

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