Genomics and the Law

Consumers have many possibilities to undergo a form of screening to acquire health information via the Internet or otherwise by purchasing health checks, medical check-ups, total body scans and direct-to-consumer (DTC) genetic tests. More and more providers place screenings on the market before they have been assessed properly. In the Netherlands the Act on population screening ( __Wet op het bevolkingsonderzoek__) sets strict quality criteria for screening. In accordance with this Act a licence is required for offering and performing screening with ionising radiation or for detecting (risk factors of) cancer and untreatable diseases. This system, which aims to protect individuals against health damage and also to ensure patients (rights), wards off __commercial screening__ of the Dutch market. In society this meets with criticism. Individuals increasingly perceive the limited access to screening as an unnecessary restriction of their self-determination. However, the Dutch State has a special responsibility regarding the health of individuals. This thesis focuses on the following central question: __What are the normative criteria for the access to and supply of genetic screening from constitutional and European law perspectives?__ As a corollary the author will explore what this means for the Dutch legal framework regulating genetic screening, particularly DTC genetic tests.UBL - phd migration 201

Het medisch beroepsgeheim en kinderbescherming

Coherent privaatrech

Towards a Culture of Care

Editoriale per il numero 2/2020 della rivista JoLA-Journal of Landscape Architectur

Hebben mensen met uitgestelde zorg recht op schadevergoeding?

Coherent privaatrech

Good results at 2-year follow-up of a custom-made triflange acetabular component for large acetabular defects and pelvic discontinuity:a prospective case series of 50 hips

Background and purpose — Custom triflange acetabular components (CTACs) are suggested as good solutions for large acetabular defects in revision total hip arthroplasty. However, high complication rates have been reported and most studies are of limited quality. This prospective study evaluates the performance of a CTAC in patients with large acetabular defects including pelvic discontinuity. Patients and methods — Prospectively collected data of 49 consecutive patients (50 hips), who underwent an acetabular revision with a CTAC were analyzed. Follow-up (FU) was 2 years. The median age of the patients was 68 years (41–89) and 41 were women. Primary outcomes were re-revision of the CTAC and differences between the modified Oxford Hip Score (mOHS) preoperatively and at 2-year follow-up. Secondary outcomes included several patient-reported outcomes (PROMs), radiological results, complications, and a comparison between hips with and without pelvic discontinuity (PD). Results — 1 patient (1 hip) was lost to the 2-year FU. No CTAC needed re-revision. The preoperative and 2-year FU mOHS were available in 40 hips and improved statistically significantly. All of the other secondary outcomes improved over time. 5 hips (of 45 with radiological 2-year FU) had loosening of screws. 8 hips had complications, including 3 persistent wound leakage, 3 pelvic fractures, and 1 dislocation. The mOHS and complication rate were similar in hips with and without PD. Interpretation — Reconstruction of large acetabular defects with and without PD with this CTAC showed good improvement in patient-reported daily functioning, high patient-reported satisfaction, few complications, and no re-revisions at 2-year FU

The distanced city. Editorial

Editoriale per il numero 3/2020 della rivista JoLA-Journal of Landscape Architectur

Beyond mere illustration. Editorial

Editoriale per il numero 1/2021 della rivista JoLA-Journal of Landscape Architectur

Immunomodulator withdrawal from anti-TNF therapy is not associated with loss of response in inflammatory bowel disease

BACKGROUND AND AIMS: The benefit of concomitant immunomodulators (thiopurines or methotrexate) in patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor α (anti-TNF) (infliximab or adalimumab) maintenance therapy is debated. We compared outcomes after immunomodulator withdrawal vs continuation of combination therapy. METHODS: This was a retrospective cohort study in a general hospital and a tertiary referral center. We included adult IBD patients, receiving anti-TNF therapy for ≥4 months, plus an immunomodulator at baseline, between January 1, 2011, and January 1, 2019. The primary endpoints were loss of response (LOR) (ie, anti-TNF discontinuation because of disease activity) and anti-drug antibodies. Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis. RESULTS: We included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval [CI], 0.72-1.61), although anti-drug antibodies were detected more frequently (aHR, 2.14; 95% CI, 1.17-3.94), compared with continuation. Clinical remission at the time of withdrawal reduced the risk of LOR (aHR, 0.48; 95% CI, 0.25-0.93), while longer duration of combination therapy before withdrawal decreased the risk of anti-drug antibodies (HR per year, 0.56; 95% CI, 0.32-0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of anti-drug antibodies and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (P = .01). CONCLUSIONS: Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of LOR within the following 1-2 years, but an increase in anti-drug antibodies was observed. Our findings require prospective validation, preferably in adequately powered randomized controlled trials

Loss of response to anti-TNF alpha agents depends on treatment duration in patients with inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) is often managed with anti-tumour necrosis factor-α therapy (anti-TNFα), but treatment efficacy is compromised by high annual rates of loss of response (13%-21% per patient-year). Aims: To assess whether the incidence of loss of response decreases with longer treatment duration. Methods: This was a multicentre, retrospective cohort study of patients with ulcerative colitis (UC) or Crohn's disease (CD) who received anti-TNFα for at least 4 months between 2011 and 2019. We studied the incidence of loss of response as a function of treatment duration, employing parametric survival modelling. Predictors of loss of response were identified by Cox regression analysis. Secondary outcomes included overall anti-TNFα discontinuation and dose escalation. Results: We included 844 anti-TNFα treatment episodes in 708 individuals. Loss of response occurred in 211 (25.0%) episodes, with anti-drug antibodies detected in 66 (31.3%). During the first year, the incidence of loss of response was three-fold higher than after four years of treatment (17.2% vs 4.8% per patient-year, P < 0.001). The incidence of anti-TNFα discontinuation (28.6% vs 14.0% per patient-year, P < 0.001) and dose escalations (38.0% vs 6.8% per patient-year, P < 0.001) also decreased significantly from the first year to after four years, respectively. Predictors of loss of response included UC (vs CD, adjusted hazard ratio [aHR] 1.53, 95% CI 1.10-2.15) and, among patients with CD, stricturing or penetrating disease (aHR 1.68, 95% CI 1.15-2.46) and male sex (aHR 0.55, 95% CI 0.38-0.78). Immunomodulators were protective against loss of response with anti-drug antibodies (aHR 0.42, 95% CI 0.24-0.74). Conclusions: Patients with sustained benefit to anti-TNFα after 2 years are at low risk of subsequent loss of response