Marks D, Thorogood M, Neil S M, Humphries S E, Neil H A W
London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
J Med Screen. 2006;13(3):156-9. doi: 10.1258/096914106778440617.
To determine what proportion of cases of heterozygous familial hypercholesterolaemia would be identified by cascade screening conducted by a specialist hospital clinic, and by how much this would increase the prevalence of diagnosed cases.
Hospital clinic serving a population of 605,900 in Oxfordshire, UK.
A specialist nurse obtained details of living first-degree relatives from 227 adult patients with heterozygous familial hypercholesterolaemia currently or previously attending Oxford lipid clinic after excluding 79 adults without relatives living in Oxfordshire and 48 children. Index cases were asked to invite relatives resident in Oxfordshire for testing.
A total of 227 index cases had 1075 first-degree relatives, including 442 adults and 117 children aged < 18 years resident in Oxfordshire. We excluded 171 previously screened adults and 46 for other reasons. Among 225 eligible adult relatives, 28 responders (12%) planned to consult their general practitioner and 52 (23%) attended the clinic for testing. Parents of 113 children (97%) wanted them tested. The positive diagnostic rate was 29% (15/52) in adults and 32% (36/113) in children. Screening increased prevalence by 14.4%, from 0.58/1000 (95% confidence intervals [CI] 0.52-0.65) to 0.67/1000 (95% CI 0.60-0.73), representing 33.5% of predicted cases.
Cascade screening conducted by a specialist hospital clinic within its population catchment area did not substantially increase the prevalence of diagnosed familial hypercholesterolaemia. To maximize response rates, clinic staff need to approach relatives directly. Validated age, sex and country-specific diagnostic criteria should be defined, possibly with access to DNA-based tests, to help resolve diagnostic uncertainty.
确定专科医院门诊进行的级联筛查能够识别出多大比例的杂合子家族性高胆固醇血症病例，以及这将使确诊病例的患病率提高多少。
为英国牛津郡605,900人口提供服务的医院门诊。
一名专科护士从227名目前或曾经在牛津血脂门诊就诊的成年杂合子家族性高胆固醇血症患者那里获取了在世一级亲属的详细信息，排除了79名在牛津郡没有亲属的成年人和48名儿童。索引病例被要求邀请居住在牛津郡的亲属前来检测。
总共227例索引病例有1075名一级亲属，其中包括442名成年人和117名居住在牛津郡的18岁以下儿童。我们排除了171名之前已接受筛查的成年人以及46名因其他原因被排除的人。在225名符合条件的成年亲属中，28名（12%）计划咨询他们的全科医生，52名（23%）到门诊进行检测。113名儿童的父母中97%希望为他们进行检测。成年人的阳性诊断率为29%（15/52），儿童为32%（36/113）。筛查使患病率提高了14.4%，从0.58/1000（95%置信区间[CI]0.52 - 0.65）提高到0.67/1000（95%CI 0.60 - 0.73），占预测病例的33.5%。
专科医院门诊在其服务区域内进行的级联筛查并未显著提高确诊家族性高胆固醇血症的患病率。为了使响应率最大化，门诊工作人员需要直接联系亲属。应定义经过验证的年龄、性别和特定国家的诊断标准，可能需要借助基于DNA的检测，以帮助解决诊断不确定性问题。
