Patients with moderate-to-severe plaque psoriasis preferred oral therapies to phototherapies: a preference assessment based on clinical scenarios with trade-off questions.

OBJECTIVE: The importance of validly identifying and incorporating patients' views for improving health care is generally acknowledged. Common approaches to assess patients' preferences are based on the quality adjusted life year (QALY) framework, but this ignores a number of aspects that may be relevant. As an alternative, we assessed patients' treatment preferences and trade-offs for five common systemic therapies for psoriasis. STUDY DESIGN AND SETTING: Twenty-nine patients with moderate-to-severe psoriasis expressed treatment preferences for five oral and phototherapies and indicated the relative importance of various treatment attributes, such as adverse effects, discomforts, and safety measures. In a structured interview, they were presented with clinical scenarios that contained descriptions of process and outcome characteristics and illustrations of the anticipated treatment benefit. RESULTS: Over all paired comparisons, methotrexate (33%), cyclosporin (30%), acitretin (15%), UV-B (14%), and PUVA (8%) were preferred to the other treatment. Patients were willing to trade-off their initial preference for more improvement of psoriasis. CONCLUSIONS: Psoriasis patients generally prefer oral to phototherapies and consider most adverse effects and several discomforts important for selecting treatment. Our scenario-based structured interview approach to treatment preferences allowed us to incorporate a broad spectrum of potentially relevant decision components in a clinically meaningful way.

Cyclosporin trough levels: is monitoring necessary during short-term treatment in psoriasis? A systematic review and clinical data on trough levels.

BACKGROUND: Cyclosporin is an effective treatment for severe plaque psoriasis. Unfortunately, its use may be limited by time- and dose-related nephrotoxicity. Serum trough levels may be useful for monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether monitoring of trough levels is necessary in psoriasis patients undergoing short-term treatment with cyclosporin. METHODS: A computerized and manual literature search identified studies on adults with plaque-type psoriasis treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in whole blood. Number of patients, treatment duration, formulation and dosage, renal function tests and trough levels were extracted. The association between renal function and trough levels was investigated. Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate in moderate to severe psoriasis, cyclosporin trough levels were measured frequently in 20 patients during 12 weeks of treatment. The Pearson correlation coefficient between serum creatinine and cyclosporin trough levels was calculated. RESULTS: Fifty-six articles were found concerning cyclosporin trough level measurements in psoriasis patients, of which eight were analysed. Many studies were excluded due to inappropriate cyclosporin dosages used. As data were heterogeneous and lacked various key parameters, a correlation study and a meta-analysis could not be performed. Instead, a quantitative description of the literature was given. No high mean trough levels or elevations of serum creatinine were described. In our clinical study, all the mean trough levels in 17 patients treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were seen. CONCLUSIONS: The literature does not provide a definitive answer on whether monitoring cyclosporin trough levels in patients with psoriasis should be standard practice. Our own data show no need for cyclosporin trough level monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be indicated.

RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems.

Hirschsprung disease (HSCR) is a congenital disorder characterised by intestinal obstruction due to an absence of intramural ganglia along variable lengths of the intestine. RET is the major gene involved in HSCR. Mutations in the GDNF gene, and encoding one of the RET ligands, either alone or in combination with RET mutations, can also cause HSCR, as can mutations in four other genes (EDN3, EDNRB, ECE1, and SOX10). The rare mutations in the latter four genes, however, are more or less restricted to HSCR associated with specific phenotypes. We have developed a novel comprehensive mutation detection system to analyse all but three amplicons of the RET and GDNF genes, based on denaturing gradient gel electrophoresis. We make use of two urea-formamide gradients on top of each other, allowing mutation detection over a broad range of melting temperatures. For the three remaining (GC-rich) PCR fragments we use a combination of DGGE and constant denaturing gel electrophoresis (CDGE). These two dual gel systems substantially facilitate mutation scanning of RET and GDNF, and may also serve as a model to develop mutation detection systems for other disease genes. In a screening of 95 HSCR patients, RET mutations were found in nine out of 17 familial cases (53%), all containing long segment HSCR. In 11 of 78 sporadic cases (14%), none had long segment HSCR. Only one GDNF mutation was found, in a sporadic case.

[Genes and genetics in Hirschsprung's disease]. / Genen en genetica bij de ziekte van Hirschsprung.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by intestinal obstruction due to the absence of intramural ganglia along variable lengths of the colon. Occurrence among family members and recurrence risks among siblings are indications for involvement of genetic predispositions. Mutations have been discovered in five different susceptibility genes. One of the most important findings is the detection of specific mutations in the so-called RET gene, which can also be responsible for the multiple endocrine neoplasia type 2A (MEN2A) syndrome. HSCR patients with such specific mutations run an increased risk of developing MEN type 2A related tumours.