scholarly journals Quality Assessment of the Genetic Test for Familial Hypercholesterolemia in The Netherlands

Cholesterol ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Iris Kindt ◽  
Roeland Huijgen ◽  
Marieke Boekel ◽  
Kristiaan J. van der Gaag ◽  
Joep C. Defesche ◽  
...  
Keyword(s):  
The Netherlands ◽  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Reference Laboratory ◽  
Test Results ◽  
Cascade Screening ◽  
Dna Test ◽  
Increased Risk ◽  
A Prospective Study ◽  
Positive Results

Introduction. Familial hypercholesterolemia (FH) is an inherited disorder associated with a severely increased risk of cardiovascular disease. Although DNA test results in FH are associated with important medical and ethical consequences, data on accuracy of genetic tests is scarce. Methods. Therefore, we performed a prospective study to assess the overall accuracy of the DNA test used in the genetic cascade screening program for FH in The Netherlands. Individuals aged 18 years and older tested for one of the 5 most prevalent FH mutations, were included consecutively. DNA samples were analyzed by the reference and a counter-expertise laboratory following a standardized procedure. Results. 1003 cases were included. In the end, 317 (32%) carried an FH mutation, whereas in 686 (69%) samples no mutation was found. The overall accuracy of the reference laboratory was 99.8%, with two false positive results identified by the counter-expertise laboratory. Conclusion. The currently used mutation analysis is associated with a very low error rate. Therefore, we do not recommend routine use of duplicate testing.

scholarly journals Stakeholder Views on Active Cascade Screening for Familial Hypercholesterolemia

Healthcare ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 108 ◽  
Author(s):  
Carla van El ◽  
Valentina Baccolini ◽  
Peter Piko ◽  
Martina Cornel
Keyword(s):  
The Netherlands ◽  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Family Members ◽  
Preventive Strategy ◽  
Cascade Screening ◽  
Privacy Regulation ◽  
Psychological Burden ◽  
Roles And Responsibilities ◽  
Screening Programs

In familial hypercholesterolemia (FH), carriers profit from presymptomatic diagnosis and early treatment. Due to the autosomal dominant pattern of inheritance, first degree relatives of patients are at 50% risk. A program to identify healthy relatives at risk of premature cardiovascular problems, funded by the Netherlands government until 2014, raised questions on privacy and autonomy in view of the chosen active approach of family members. Several countries are building cascade screening programs inspired by Dutch experience, but meanwhile, the Netherlands’ screening program itself is in transition. Insight in stakeholders’ views on approaching family members is lacking. Literature and policy documents were studied, and stakeholders were interviewed on pros and cons of actively approaching healthy relatives. Sociotechnical analysis explored new roles and responsibilities, with uptake, privacy, autonomy, psychological burden, resources, and awareness as relevant themes. Stakeholders agree on the importance of early diagnosis and informing the family. Dutch healthcare typically focuses on cure, rather than prevention. Barriers to cascade screening are paying an own financial contribution, limited resources for informing relatives, and privacy regulation. To benefit from predictive, personalized, and preventive medicine, the roles and responsibilities of stakeholders in genetic testing as a preventive strategy, and informing family members, need to be carefully realigned.

Population-Based Screening in Children For Early Diagnosis and Treatment of Familial Hypercholesterolemia: Design of The VRONI Study

2021 ◽  
Author(s):  
Veronika Sanin ◽  
Raphael Schmieder ◽  
Sara Ates ◽  
Lea Dewi Schlieben ◽  
Jens Wiehler ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Molecular Genetic ◽  
Population Based ◽  
Molecular Genetic Analysis ◽  
Cascade Screening ◽  
Screening Programs ◽  
Pathogenic Variants ◽  
Risk Indices ◽  
Training Courses

Abstract Background: Heterozygous Familial Hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce.Methods: In the VRONI study children aged 5 to 14 years in Bavaria are invited to participate in a FH screening program during regular pediatric visits. The screening is based on LDL-C measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first degree relatives, reverse cascade screening is recommended to identify and treat affected family members.Results: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data-safety, legal and organisational aspects, which will be outlined in this paper. Recruitment started in January of 2021, within two months more than 280 pediatricians screened over 1,150 children. Approximately 60,000 children are expected to be enrolled in the VRONI study until 2024. Conclusion: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nation-wide FH screening infrastructure. Further we aim to validate genetic variants of unclear significance, detect novel causative mutations, and contribute to polygenic risk indices. (German Clinical Trials Register: DRKS00022140; registered August 21st2020.)

scholarly journals Retrospective analysis of feline intestinal parasites: trends in testing positivity by age, USA geographical region and reason for veterinary visit

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarah Sweet ◽  
Donald Szlosek ◽  
Donald McCrann ◽  
Michael Coyne ◽  
David Kincaid ◽  
...  
Keyword(s):  
Intestinal Parasites ◽  
Geographical Region ◽  
Reference Laboratory ◽  
Western Region ◽  
Test Results ◽  
True Prevalence ◽  
Increased Risk ◽  
Parasite Detection ◽  
The Usa ◽  
Fecal Tests

Abstract Background The goals of this retrospective study were to estimate parasite positivity in samples from cats using zinc sulfate fecal flotation by centrifugation (“centrifugation”) and coproantigen and examine trends with age, geographical region and reason for visit to veterinarian. Common methods of parasite detection, such as centrifugal flotation, passive flotation, or direct smear, may underrepresent the true prevalence of intestinal parasites in cats. Coproantigen testing detects more positive samples than traditional methods alone. Methods Feline fecal test results from the continental USA containing results for fecal exams performed using centrifugation paired with coproantigen results for ascarid, hookworm, whipworm and Giardia were obtained from the database of a national commercial reference laboratory comprised of multiple regional sites. Results Parasite positivity was highest in samples from young cats and decreased with cat age. The western region of the USA had lower total parasite positivity than other regions for all parasites except Giardia. Cats receiving fecal tests during veterinary wellness visits had only slightly lower parasite positivity than samples from cats during sick clinical visits. Conclusions This study showed a larger population of cats are at increased risk of parasitism than commonly believed and coproantigen testing produces more positive test results for the four parasites that antigen can detect than centrifugation of feline fecal samples.

scholarly journals Women’s experiences of the renewed National Cervical Screening Program in Australia 12 months following implementation: a qualitative study

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e039041 ◽  
Author(s):  
Rachael H Dodd ◽  
Olivia A Mac ◽  
Kirsten J McCaffery
Keyword(s):  
Screening Program ◽  
Cervical Screening ◽  
Test Results ◽  
Women’S Experiences ◽  
Women's Experiences ◽  
Hpv Status ◽  
Increased Risk ◽  
Qualitative Interview Study ◽  
History Of ◽  
Abnormal Results

ObjectiveTo explore women’s experiences of the renewed National Cervical Screening Program in Australia from the perspective of women who have received different human papillomavirus (HPV) test results. Women aged 25 to 74 are now screened every 5 years with primary HPV screening.DesignQualitative interview study.SettingAustralia.ParticipantsWomen in Australia aged 25 to 74 who reported participating in cervical screening since December 2017, purposively sampled by test result (HPV positive, HPV negative and HPV status unknown).Methods26 interviews with women aged 25 to 74 were conducted and analysed thematically.ResultsThree main themes emerged: knowledge and attitudes about the programme changes, information dissemination, the meaning and responses to test results and the new cervical screening test (CST). Some women showed little awareness of the changes, but others understood that HPV is detected earlier than abnormal cells. Some expressed positive attitudes towards the CST and were not anxious about less frequent screening. Most women envisaged the changes would have minimal impact on their screening behaviour. Women mainly wanted more information about the changes and the possible results from the new CST. Overall women could recall their HPV results and understand the implications for future cervical screening. Anxiety about being at ‘increased risk’ was more apparent in women who were HPV positive without history of abnormal results.ConclusionsWomen show some understanding of HPV and the new CST, but more written and public communication about the changes and possible results are warranted. Efforts are needed to ensure that women who are HPV positive without history of abnormal results receive the information needed to alleviate anxiety.

scholarly journals Unresolved Discrepancies between Cannabinoid Test Results for Infant Urine

2012 ◽  
Vol 58 (9) ◽  
pp. 1364-1367 ◽  
Author(s):  
Vilte E Barakauskas ◽  
Rebecka Davis ◽  
Matthew D Krasowski ◽  
Gwendolyn A McMillin
Keyword(s):  
Similar Rate ◽  
Urine Samples ◽  
Drug Screen ◽  
Reference Laboratory ◽  
Data Sets ◽  
Independent Data ◽  
Test Results ◽  
Hospital Laboratory ◽  
Positive Screen ◽  
Positive Results

Abstract BACKGROUND False-positive drug screen results for tetrahydrocannabinol (THC) have been observed. This study investigated the rate of unconfirmed positive screen results in infant and noninfant urine samples and evaluated possible reasons for differences. METHODS The rate of unconfirmed positive THC screen results for urine samples was determined retrospectively in 2 independent data sets (n = 14 859, reference laboratory; n = 21 807, hospital laboratory) by comparing positive immunoassay-based drug screen results with the associated results of confirmation tests. We then assessed the rate of positive THC screens for samples with varying likelihoods of cannabinoid presence to evaluate the contribution of infant-specific urine constituents to positive results. Finally, a method to detect a THC metabolite (11-hydroxy-Δ9-THC) that occurs in meconium was developed to determine its prevalence in infant urine. RESULTS Positive screen results failed to confirm more frequently in samples from infants (47%) than in noninfants (0.8%). The hospital laboratory observed a similar discrepancy with a different immunoassay. Infant samples with a high likelihood of containing cannabinoids despite negative confirmatory results had a similar rate of positive screening results (50%, n = 20), whereas all samples with a low likelihood of containing cannabinoids screened negative (n = 23). 11-Hydroxy-Δ9-THC was not detected in any infant urine sample tested (n = 16). CONCLUSIONS Conventional confirmatory methods for THC may be inappropriate for urine samples from infants. Our results suggest that one or more currently unrecognized THC-associated compounds are responsible for positive THC screen results for infant urine, as opposed to an infant-associated interference.

Cascade screening program for familial hypercholesterolemia

2018 ◽  
Vol 65 (5) ◽  
pp. 280-286
Author(s):  
Patricia Rubio-Marín ◽  
Alfredo Michán-Doña ◽  
Juan Maraver-Delgado ◽  
Raquel Arroyo-Olivares ◽  
Rosalía Barrado Varea ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Cascade Screening

Abstract 15779: Quality of Life in a Cohort of Familial Hypercholesterolemia Patients Undergoing Molecular Cascade Screening in Brazil

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ana Cristina Souto ◽  
Alexandre Pereira ◽  
Cinthia E Jannes ◽  
Julia Fukushima ◽  
Jose E Krieger ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Familial Hypercholesterolemia ◽  
Linear Models ◽  
Screening Program ◽  
Short Form ◽  
Smoking Habit ◽  
Genetic Diagnosis ◽  
Cascade Screening ◽  
Social Demographic

Introduction:: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated disease associated with elevated risk of early cardiovascular disease (CVD) and thus can reduce quality of life. The present health related quality of life (HRQL) investigation, evaluated patients personal interpretation of morbidity burden in daily life. Methods: The study included a total of 1,032 adult individuals participating in a FH molecular cascade-screening program. The involved individuals were index cases (IC n=363), with genetic diagnosis or FH and their first-degree relatives (FDR, n=669). All patients were evaluated at the first session of the molecular diagnosis process. HRQL measurements, mental (MCS) and physical (PCS) component scores, was carried out with the Medical Outcomes Study (MOS) 12-Item Short-Form Health Survey (SF-12) questionnaire. Results: IC were older (52±13.1 vs. 46±16.2 years, P<0.05) and presented lower PCS than FDR (44.7±9.3 vs. 49.2±8.4, P<0.05). No differences were seen on the MCS component. Overall, generalized linear models showed that smoking habit (11.9% prevalence, P=0.006), previous diagnosis of hyperlipidemia (78.6%, P=0.020) and depression (13.5% prevalence, P<0.000) were significant predictors of MCS. The presence of heart failure (6.5%, P=0.018), angina pectoris (12.9%, P=0.005), previous myocardial infarction (12.3%, P=0.012), hypertension (33.9%, P=0.018) and obesity (12.8%, P<0.000) were all predictors of PCS. The presence of arrhythmias (10.7% prevalence) predicted both MCS and PCS (P=0.042 and P=0.00, respectively). Male gender (42.4%, P<0.000) and education level (< 9 years of background, 28% P<0.000) were social-demographic aspects predictive of differences in MCS and PCS, respectively. Conclusions: Reductions in the individuals’ reported quality of life were explained by differences in social-demographic characteristics but mainly by inadequate health/disease status, such as risk factors and previous CVD. Active FH genetic cascade diagnosis by promoting early and adequate medical care and thus preventing early CVD, may improve substantially the subjective appraisal of HRQL.

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