BackgroundHomozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown.MethodsWe used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306).ResultsTwenty-nine patients were included in the phase 3 study. During the first 26 weeks, 15 (51%) and eight (28%) reached LDL-C targets of 100 mg/dL and 70 mg/dL, respectively, at least once. Fourteen (74%) and 11 (58%) of the 19 patients who remained in the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the entire study period. Only two MACE were reported in the lomitapide trials (one cardiac death and one coronary artery bypass graft (CABG)) – equivalent to 1.7 events per 1000 patient months of treatment. MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of HoFH patients pre- and post-mipomersen, and receiving evolocumab. On treatment LDL-C levels were 166, 331 and 286 mg/dL for lomitapide, mipomersen and evolocumab, respectively.ConclusionsApproximately three quarters and half of patients who took lomitapide for at least 2 years reached LDL-C goals of 100 mg/dL and 70 mg/dL, respectively. There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further.Trial registrationNCT00730236 (registered 8 Aug 2008) and NCT00943306 (registered 22 July 2009).
BackgroundThere are an estimated 125,000 deaf people in the UK who use British Sign Language (BSL) as their main form of communication, but there are no child mental health screening instruments that are accessible to deaf children whose first or main language is BSL (or to deaf adults reporting on children). This study sought to develop a new BSL translation of a commonly used mental health screening tool (Strengths and Difficulties Questionnaire, SDQ), with versions available for deaf young people (aged 11–16 years), parents and teachers. The psychometric properties of this translation, and its validity for use with the deaf signing UK population, were also investigated.Objectives(1) To translate the SDQ into BSL; and (2) to use this new version with a cohort of deaf children, deaf parents and deaf teachers fluent in BSL across England, and validate it against a ‘gold standard’ clinical interview.MethodsThis study was split into two broad phases: translation and validation. The BSL SDQ was developed using a rigorous translation/back-translation methodology with additional checks, and we have defined high-quality standards for the translation of written/oral to visual languages. We compared all three versions of the SDQ (deaf parent, deaf teacher and deaf young person) with a gold standard clinical interview by child mental health clinicians experienced in working with deaf children. We also carried out a range of reliability and validity checks.ResultsThe SDQ was successfully translated using a careful methodology that took into account the linguistic and cultural aspects of translating a written/verbal language to a visual one. We recruited 144 deaf young people (aged 11–16 years), 191 deaf parents of a child aged either 4–10 or 11–16 years (the child could be hearing or deaf) and 77 deaf teachers and teaching assistants. We sought deaf people whose main or preferred language was BSL. We also recruited hearing participants to aid cross-validation. We found that the test–retest reliability, factor analysis and internal consistency of the three new scales were broadly similar to those of other translated versions of the SDQ. We also found that using the established multi-informant SDQ scoring algorithm there was good sensitivity (76%) and specificity (73%) against the gold standard clinical interview assessment. The SDQ was successfully validated and can now be used in clinical practice and research. Factor analysis suggests that the instrument is good for screening for mental health problems but not for the identification of specific disorders, and so should be used as a screening instrument. It will also enable outcomes to be monitored.ConclusionsA BSL version of the SDQ can now be used for national studies screening for mental health problems in deaf children. This will help us better understand the needs of deaf children and will enable earlier detection of mental health difficulties. It can also be used within clinical settings to monitor outcomes.Future workFuture work may focus on using the SDQ in epidemiological research, and developing new assessment instruments for deaf children to improve assessment methods in the deaf population.FundingThe National Institute for Health Research Health Services and Delivery Research programme.
BACKGROUND: Lomitapide is a lipid-lowering agent indicated as adjunct therapy for homozygous familial hypercholesterolemia (HoFH) in adults.OBJECTIVE: The Lomitapide Observational Worldwide Evaluation Registry is an international, observational registry assessing long-term safety, tolerability, and effectiveness of lomitapide.
We report a Delphi Consensus modification and first validation study of the Autism Diagnostic Observation Schedule – 2 with deaf children and young people (ADOS-2 Deaf adaptation). Validation included 122 deaf participants (aged 2–18 years), 63 with an Autism Spectrum Disorder (ASD). This was compared to a National Institute for Health and Clinical Excellence (NICE) guideline standard clinical assessment by blinded independent specialist clinicians. Results showed overall sensitivity 73% (95%CI 60%, 83%); specificity 71% (95%CI 58%, 82%), and for the more common modules 1–3 (combined as in previous studies) sensitivity 79% (95% CI 65–89%); specificity 79% (95% CI 66–89%) suggesting this instrument will be a helpful addition for use with deaf children and young people.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.