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Journal of Medical Genetics Dec 2023Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond...
BACKGROUND
Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on MGP-NGS in patients with suspicion of hereditary cancer reveals these incidental findings (IFs).
METHODS
MGP-NGS was performed in patients who fulfilled the clinical criteria to undergo genetic testing according to the Catalan Health Service guidelines. Variants were classified following the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and the Cancer Variant Interpretation Group UK guidelines.
RESULTS
IFs were identified in 10 (1.22%) of the 817 patients who underwent MGP-NGS. The mean age at cancer diagnosis was 49.4±9.5 years. Three IFs (30.0%) were detected in , two (20.0%) in and and one (10.0%) in and . Seven (70.0%) IFs were single-nucleotide substitutions, two (20.0%) were deletions and one (10.0%) was a duplication. Three (30.0) IFs were located in intronic regions, three (30.3%) were nonsense, two (20.0%) were frameshift and two (20.0%) were missense variations. Six (60.0%) IFs were classified as PVs and four (40.0%) as LPVs.
CONCLUSIONS
Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops.
Topics: Humans; Adult; Middle Aged; Early Detection of Cancer; Genetic Testing; Neoplasms; Phenotype; Genetic Predisposition to Disease; Germ-Line Mutation
PubMed: 37591735
DOI: 10.1136/jmg-2023-109389 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Dec 2023Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and...
Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.
Topics: Infant, Newborn; Humans; Neonatal Screening; Phenylketonurias; Genetic Testing; Congenital Hypothyroidism; China
PubMed: 38115737
DOI: 10.3724/zdxbyxb-2023-0467 -
The Journal of Molecular Diagnostics :... May 2020Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities. Protocols to develop screening tests are well... (Review)
Review
Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities. Protocols to develop screening tests are well established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a truth set cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for likely pathogenic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Herein, we review basic test design principles and apply them to genetic screening.
Topics: Genetic Association Studies; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genetic Testing; Genetic Variation; Humans; Mass Screening; Research Design
PubMed: 32092541
DOI: 10.1016/j.jmoldx.2020.01.014 -
Journal of Clinical Virology : the... Sep 2019For some well-known pathogens like influenza or RSV, diagnostic and epidemiological data is available and continuously complement each other. For most other pathogens... (Review)
Review
For some well-known pathogens like influenza or RSV, diagnostic and epidemiological data is available and continuously complement each other. For most other pathogens however, data is not always available or severely delayed. Furthermore, clinical data is needed to assess the burden of disease, which will enhance awareness and help to gain knowledge on emerging pathogens. In this position paper, we discuss the interdependence of diagnostics and epidemiology from a European perspective. In 2004, the European Centre for Disease Prevention and Control (ECDC) was founded to coordinate European wide surveillance and control. At present however, the ECDC still relies on university hospitals, public health institutions and other diagnostic institutions. Close collaboration between all stakeholders across Europe is therefore complex, but necessary to optimize the system for the individual patient. From the diagnostic side, data on detected pathogens should be shared with relevant health institutions in real-time. From the public health side, collected information should be made accessible for diagnostic and clinical institutions in real-time. Subsequently, this information needs to be disseminated across relevant medical disciplines to reach its full potential.
Topics: Communicable Disease Control; Diagnostic Services; Epidemiological Monitoring; Europe; Humans; Information Dissemination; International Cooperation; Virus Diseases; Viruses
PubMed: 31301517
DOI: 10.1016/j.jcv.2019.07.002 -
Radiology. Imaging Cancer Mar 2020Lung cancer remains the overwhelmingly greatest cause of cancer death in the United States, accounting for more annual deaths than breast, prostate, and colon cancer... (Review)
Review
Lung cancer remains the overwhelmingly greatest cause of cancer death in the United States, accounting for more annual deaths than breast, prostate, and colon cancer combined. Accumulated evidence since the mid to late 1990s, however, indicates that low-dose CT screening of high-risk patients enables detection of lung cancer at an early stage and can reduce the risk of dying from lung cancer. CT screening is now a recommended clinical service in the United States, subject to guidelines and reimbursement requirements intended to standardize practice and optimize the balance of benefits and risks. In this review, the evidence on the effectiveness of CT screening will be summarized and the current guidelines and standards will be described in the context of knowledge gained from lung cancer screening studies. In addition, an overview of the potential advances that may improve CT screening will be presented, and the need to better understand the performance in clinical practice outside of the research trial setting will be discussed. © RSNA, 2020.
Topics: Early Detection of Cancer; Humans; Lung Neoplasms; Mass Screening; Tomography, X-Ray Computed; United States
PubMed: 32300760
DOI: 10.1148/rycan.2020190058 -
Medicina (Kaunas, Lithuania) Mar 2022Genetic carrier screening has been successfully used over the last decades to identify individuals at risk of transmitting specific DNA variants to their newborns, thus... (Review)
Review
Genetic carrier screening has been successfully used over the last decades to identify individuals at risk of transmitting specific DNA variants to their newborns, thus having an affected child. Traditional testing has been offered based on familial and/or ethnic backgrounds. The development of high-throughput technologies, such as next-generations sequencing, able to allow the study of large genomic regions in a time and cost-affordable way, has moved carrier screening toward a more comprehensive and extensive approach, i.e., expanded carrier screening (ECS). ECS simultaneously analyses several disease-related genes and better estimates individuals' carrier status. Indeed, it is not influenced by ethnicity and is not limited to a subset of mutations that may arise from poor information in some populations. Moreover, if couples carry out ECS before conceiving a baby, it allows them to obtain a complete estimation of their genetic risk and the possibility to make an informed decision regarding their reproductive life. Despite these advantages, some weakness still exists regarding, for example, the number of genes and the kind of diseases to be analyzed and the interpretation and communication of the obtained results. Once these points are fixed, it is expectable that ECS will become an ever more frequent practice in clinical settings.
Topics: Child; Ethnicity; Genetic Carrier Screening; Genetic Counseling; Humans; Infant, Newborn; Mass Screening; Mutation
PubMed: 35334631
DOI: 10.3390/medicina58030455 -
BMC Health Services Research Mar 2020People with young-onset dementia (YOD) can often struggle getting the right treatment. This is because of their frequently different characteristics and needs compared...
BACKGROUND
People with young-onset dementia (YOD) can often struggle getting the right treatment. This is because of their frequently different characteristics and needs compared to people with late-onset dementia. The aim of this project was to assess a memory service for its adaptation to the needs and wishes of people with YOD and their carers.
METHODS
This project evaluated a memory service in the North West of England by performing two focus groups with clinical staff and six semi-structured interviews with people with YOD and carers. The focus groups took place on site and lasted one hour each. People with YOD and their carers were identified via the memory clinics caseload and via the local Alzheimer's Society charity organisation. Both focus groups and interviews were audio-recorded and transcribed, and data were analysed using thematic analysis. The public (a person living with YOD and his carer) were involved from the design stages of the project through to the analysis and dissemination.
RESULTS
Eleven members of staff with different clinical backgrounds participated in the focus groups and six interviews were held with people with YOD and their carers. Both indicated that whilst the diagnostic process is relatively well conducted at the service, the post-diagnostic service has many gaps. These include limited post-diagnostic support by the service, better enabling peer support, as well as providing meaningful activities, as some activities provided might be more suitable to older adults with dementia.
CONCLUSIONS
Post-diagnostic services and support for people with YOD and their carers need to be improved. The next step will be to implement the findings from this service evaluation in practice and improve service satisfaction and relevance to people with YOD.
Topics: Age of Onset; Caregivers; Dementia; England; Female; Focus Groups; Health Services Research; Humans; Male; Middle Aged
PubMed: 32143694
DOI: 10.1186/s12913-020-5027-8 -
JAMA Network Open Oct 2021Recognition of iron deficiency anemia (IDA) is important to initiate timely evaluation for gastrointestinal tract cancer. Retrospective studies have reported delays in...
IMPORTANCE
Recognition of iron deficiency anemia (IDA) is important to initiate timely evaluation for gastrointestinal tract cancer. Retrospective studies have reported delays in diagnostic evaluation of IDA as a common factor associated with delayed diagnosis of colorectal cancer.
OBJECTIVE
To assess how US primary care physicians (PCPs) approach testing for anemia, interpret iron laboratory studies, and refer patients with IDA for gastrointestinal endoscopy.
DESIGN, SETTING, AND PARTICIPANTS
This survey study, conducted in August 2019, included members of the American College of Physicians Internal Medicine Insiders Panel, a nationally representative group of American College of Physicians membership, who self-identified as PCPs. Participants completed a vignette-based survey to assess practices related to screening for anemia, interpretation of laboratory-based iron studies, and appropriate diagnostic evaluation of IDA.
MAIN OUTCOMES AND MEASURES
Descriptive statistics based on survey responses were evaluated for frequency of anemia screening, correct interpretation of iron laboratory studies, and proportion of patients with new-onset IDA referred for gastrointestinal tract evaluation.
RESULTS
Of 631 PCPs who received an invitation to participate in the survey, 356 (56.4%) responded and 31 (4.9%) were excluded, for an adjusted eligible sample size of 600, yielding 325 completed surveys (response rate, 54.2%). Of the 325 participants who completed surveys, 180 (55.4%) were men; age of participants was not assessed. The mean (SD) duration of clinical experience was 19.8 (11.2) years (range, 1.0-45.0 years). A total of 250 participants (76.9%) screened at least some patients for anemia. Interpretation of iron studies was least accurate in a scenario of a borderline low ferritin level (40 ng/mL) with low transferrin saturation (2%); 86 participants (26.5%) incorrectly responded that this scenario did not indicate IDA, and 239 (73.5%) correctly identified this scenario as IDA. Of 312 participants, 170 (54.5%) recommended bidirectional endoscopy (upper endoscopy and colonoscopy) for new IDA for women aged 65 years; of 305 respondents, 168 (55.1%) recommended bidirectional endoscopy for men aged 65 years.
CONCLUSIONS AND RELEVANCE
In this survey study, US PCPs' self-reported testing practices for anemia suggest overuse of screening laboratory tests, misinterpretation of iron studies, and underuse of bidirectional endoscopy for evaluation of new-onset IDA. Both misinterpretation of iron studies and underuse of bidirectional endoscopy can lead to delayed diagnosis of gastrointestinal tract cancers and warrant additional interventions.
Topics: Adult; Anemia, Iron-Deficiency; Clinical Laboratory Techniques; Female; Humans; Male; Mass Screening; Middle Aged; Physicians, Primary Care; Retrospective Studies; Surveys and Questionnaires; United States
PubMed: 34596670
DOI: 10.1001/jamanetworkopen.2021.27827 -
BMC Medical Ethics Apr 2020Preconception Expanded Carrier Screening (ECS) is a genetic test offered to a general population or to couples who have no known risk of recessive and X-linked genetic...
BACKGROUND
Preconception Expanded Carrier Screening (ECS) is a genetic test offered to a general population or to couples who have no known risk of recessive and X-linked genetic diseases and are interested in becoming parents. A test may screen for carrier status of several autosomal recessive diseases at one go. Such a program has been piloted in the Netherlands and may become a reality in more European countries in the future. The ethical rationale for such tests is that they enhance reproductive autonomy. The dominant conception of autonomy is individual-based. However, at the clinic, people deciding on preconception ECS will be counselled together and are expected to make a joint decision, as a couple. The aim of the present study was to develop an understanding of autonomous decisions made by couples in the context of reproductive technologies in general and of preconception ECS in particular. Further, to shed light on what occurs in reproductive clinics and suggest concrete implications for healthcare professionals.
MAIN TEXT
Based on the shift in emphasis from individual autonomy to relational autonomy, a notion of couple autonomy was suggested and some features of this concept were outlined. First, that both partners are individually autonomous and that the decision is reached through a communicative process. In this process each partner should feel free to express his or her concerns and preferences, so no one partner dominates the discussion. Further, there should be adequate time for the couple to negotiate possible differences and conclude that the decision is right for them. The final decision should be reached through consensus of both partners without coercion, manipulation or miscommunication. Through concrete examples, the suggested notion of couple autonomy was applied to diverse clinical situations.
CONCLUSIONS
A notion of couple autonomy can be fruitful for healthcare professionals by structuring their attention to and support of a couple who is required to make an autonomous joint decision concerning preconception ECS. A normative implication for healthcare staff is to allow the necessary time for decision-making and to promote a dialogue that can increase the power of the weaker part in a relationship.
Topics: Decision Making; Europe; Female; Genetic Carrier Screening; Genetic Testing; Humans; Netherlands; Parents; Personal Autonomy
PubMed: 32334575
DOI: 10.1186/s12910-020-00470-w -
Value in Health : the Journal of the... Jun 2022Clinical genomics is emerging as a diagnostic tool in the identification of blood relatives at risk of developing heritable diseases. Our objective was to identify how... (Review)
Review
OBJECTIVES
Clinical genomics is emerging as a diagnostic tool in the identification of blood relatives at risk of developing heritable diseases. Our objective was to identify how genetic cascade screening has been incorporated into health economic evaluations.
METHODS
A scoping review was conducted to identify how multiple generations of a family were included in economic evaluations of clinical genomic sequencing, how many and which relatives were included, and uptake rates. Databases were searched for full economic evaluations of genetic interventions that screened multiple generations of families and were in English language, and no restrictions were made for disease or publication type. Data were synthesized using a narrative approach.
RESULTS
Twenty-five studies were included covering a range of diseases in various countries. Markov cohort models were mostly used with hypothetical populations and unsupported by clinical evidence. Cascade testing was either the primary intervention or secondary to the index cases. The number and type of relatives were based on assumptions or identified through population or family records, clinical registry data, or clinical literature. Studies included only immediate family members and the uptake of testing ranged between 20% and 100%. All interventions were reported as cost-effective, and a higher number of relatives was a key driver.
CONCLUSIONS
Several economic evaluations have considered the impacts of cascade testing interventions within clinical genomics. Ideally, models supported with high-quality clinical data are needed and, in their absence, transparent and justifiable assumptions of uptake rates and choices about including relatives. Consideration of more appropriate modeling types is required.
Topics: Cost-Benefit Analysis; Genetic Testing; Genomics; Humans
PubMed: 35667782
DOI: 10.1016/j.jval.2021.11.1353