IntroductionHomozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis.MethodsThis case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18 years of age (mean 11.6 ± 1.1 years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.5 ± 4.3 mg/day; mean exposure 20.0 ± 2.9 months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5 mg or 5 mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care.ResultsIn the 11 cases, mean baseline LDL-C was 419 ± 74.6 mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 ± 46.3 mg/dL (58.4 ± 6.8% decrease). Six patients achieved recommended target levels for children below 135 mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose.ConclusionsLomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients.FundingAmryt Pharma.
BackgroundPatients with chronic kidney disease (CKD) have a high symptoms burden that is related to a poor health-related quality of life (HRQoL) and high costs of care. Validated instruments may be useful for assessing the symptoms and monitoring outcomes in these patients. The Palliative care Outcome Scale-Symptoms Renal (POS-S Renal) is a patient-reported outcome measure for assessing symptoms in CKD stage 4–5. This study is the first cross-cultural adaptation and psychometric analysis of this clinical tool. The purpose of this study is to carry out a cross-cultural adaptation of the POS-S Renal for Spanish-speaking patients, and to perform an analysis of the psychometric properties of this questionnaire.MethodsThe English version of the POS-S Renal was culturally adapted and translated into Spanish using a double forward and backward method. An expert panel evaluated the content validity. The questionnaire was pilot-tested in 30 patients. A total of 200 patients with CKD stage 4–5 filled in a modified Spanish version of the POS-S Renal and the MSAS-SF. Statistical analysis to evaluate the psychometric properties of the questionnaire was carried out.ResultsThe content validity index (CVI) was 0.97, which indicated that the content of the instrument is an adequate reflection of the symptoms in advanced CKD (ACKD). The factor analysis indicated a two-factor solution explaining 35.05% of total variance. The confirmatory factor analysis (CFA) demonstrated that the two factor model was well supported (comparative fit index = 0.98, root mean square error of approximation = 0.068). This assessment tool demonstrated a satisfactory test–retest reliability (r = 0.909 to factor 1, r = 0.695 to factor 2, r = 0.887 to total score), good internal consistency to factor 1 (α = 0.78) and moderate internal consistency to factor 2 (α = 0.56). Concurrent criterion-related validity with MSAS-SF was also demonstrated, with r = 0.860, which indicated a high degree of correlation with a validated instrument that has been used in patients with ACKD.ConclusionsThe Spanish modified version of the POS-S Renal is a reliable and valid instrument that can be used to assess symptoms in Spanish patients with CKD stage 4–5.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0402-8) contains supplementary material, which is available to authorized users.
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