ABSTRACT
Recently, the use of polygenic risk scores in embryo screening (PGT-P) has been introduced on the premise of reducing polygenic disease risk through embryo selection. However, it has been met with extensive critique: considered "technology-driven" rather than "evidence-based", concerns exist about its validity, utility, ethics, and societal effects. Its scientific foundations and criticisms thus need to be carefully considered. However, seeing as PGT-P is already offered in some settings, further questions need to be addressed, in order to give due diligence to various aspects of PGT-P. By examining the complexities of clinical introduction of PGT-P, we discuss whether PGT-P could be responsibly implemented in the first place, what elements need to be addressed if PGT-P is clinically implemented, and subsequently how counselling and decision-making of its users could be envisaged. By dissecting these elements, we provide an overview of important practical questions of PGT-P and emphasize elements of PGT-P that we think have yet to be given sufficient attention. These questions and elements are for example related to the potential target group, scope, and decision-making possibilities of PGT-P. The aspects we raise are crucial to consider by the scientific community and policy makers for the development of guidelines and/or an ethical framework for PGT-P.
Subject(s)
Genetic Testing , Preimplantation Diagnosis , Humans , Preimplantation Diagnosis/ethics , Preimplantation Diagnosis/methods , Female , Genetic Testing/ethics , Genetic Testing/methods , Genetic Testing/trends , Multifactorial Inheritance/genetics , Pregnancy , Decision Making/ethicsABSTRACT
Nurses need to understand how clinical genetic and genomic applications affect newborn screening and advocate for parents and newborns.
Subject(s)
Neonatal Screening , Phenylketonurias , Humans , Infant, Newborn , Neonatal Screening/methods , Neonatal Screening/trends , Phenylketonurias/diagnosis , Genetic Testing/methods , Genetic Testing/trends , Neonatal Nursing/standards , Neonatal Nursing/methodsSubject(s)
Ethics, Medical , Genetic Testing , Humans , Genetic Testing/ethics , Genetic Testing/trendsSubject(s)
Genetic Testing , Genomics , High-Throughput Nucleotide Sequencing , Sequence Analysis, DNA , Genomics/methods , Genomics/trends , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/trends , Sequence Analysis, DNA/methods , Sequence Analysis, DNA/trends , Genetic Testing/methods , Genetic Testing/trends , HumansABSTRACT
BACKGROUND: Testing for epidermal growth factor receptor mutation (EGFRm) status is a prerequisite to identify eligible patients for tyrosine kinase inhibitors (TKI) treatment. However, EGFR testing of patients with non-small cell lung cancer (NSCLC) is suboptimal in many parts of the world. The aim of this study was to describe real-world EGFR testing practice, EGFRm prevalence, and subsequent TKI treatment patterns in Norway. PATIENTS AND METHODS: This retrospective, observational, cohort study included all incident locally advanced and metastatic non-squamous NSCLC patients registered in the Norwegian Cancer Registry during 2010-2017. A cohort with follow-up through 2018 was formed with linkage to nationwide registries on comorbidities, prescribed drugs and causes-of-death. RESULTS: A total of 10,717 patients were included, of which 35% (3782) with locally advanced NSCLC and 65% (6935) with metastatic disease. Mean age at diagnosis was 71 years and 47% were female. EGFR testing among patients with metastatic NSCLC increased from 41% to >64% between 2010 and 2017, with a relative stable incidence of EGFRm+ (â¼9%). More than 85% of EGFRm+ patients received TKI treatment. Patients with the most dismal prognosis (>80 age, comorbidities) and with diagnosis based on cytology/imaging were less likely to be tested. Differences in testing were observed between regions. CONCLUSION: Despite increased test rates over the study period, in Norway, a significant proportion of patients with non-squamous metastatic NSCLC are still not tested for EGFR. To maximize the identification of eligible patients for targeted therapies, increased testing is recommended, regardless of age, comorbidity rate and place of residence.
Subject(s)
Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Genetic Testing , Female , Humans , Male , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , /therapeutic use , Genetic Testing/methods , Genetic Testing/trends , Norway/epidemiologyABSTRACT
Over the past 40 years, since the publication of the original WHO Laboratory Manual for the Examination and Processing of Human Semen, the laboratory methods used to evaluate semen markedly changed and benefited from improved precision and accuracy, as well as the development of new tests and improved, standardized methodologies. Herein, we present the impact of the changes put forth in the sixth edition together with our views of evolving technologies that may change the methods used for the routine semen analysis, up-and-coming areas for the development of new procedures, and diagnostic approaches that will help to extend the often-descriptive interpretations of several commonly performed semen tests that promise to provide etiologies for the abnormal semen parameters observed. As we look toward the publication of the seventh edition of the manual in approximately 10 years, we describe potential advances that could markedly impact the field of andrology in the future.
Subject(s)
Andrology/trends , Infertility, Male , Men's Health/trends , Reproductive Health/trends , Semen Analysis/trends , Sexual Health/trends , Diffusion of Innovation , Fertility , Forecasting , Genetic Testing/trends , Genomics/trends , Humans , Infertility, Male/diagnosis , Infertility, Male/genetics , Infertility, Male/physiopathology , Infertility, Male/therapy , Male , Reproduction , Sexual BehaviorABSTRACT
OBJECTIVE: To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton pregnancy. DESIGN: A retrospective cohort study. SETTING: A university-affiliated fertility center. PATIENT(S): This cohort study included singleton live births resulting from PGT (n = 232) and IVF/ICSI singleton pregnancies (n = 2,829) with single frozen-thawed blastocyst transfer. Multiple baseline covariates were used for propensity score matching, yielding 214 PGT singleton pregnancies matched to 617 IVF/ICSI singleton pregnancies. INTERVENTION(S): Trophectoderm biopsy. MAIN OUTCOME MEASURE(S): The primary outcome was gestational hypertension, and various clinical perinatal secondary outcomes related to maternal and neonatal health were measured. RESULT(S): Compared with IVF/ICSI singleton pregnancy, PGT singleton pregnancy was associated with a significantly higher risk of gestational hypertension (adjusted odds ratio, 2.58; 95% confidence interval, 1.32, 5.05). In the matched sample, the risk of gestational hypertension remained higher with PGT singleton pregnancy (odds ratio, 2.33; 95% confidence interval, 1.04, 5.22) than with IVF/ICSI singleton pregnancy. No statistical differences were noted in any other measured outcomes between the groups. CONCLUSION(S): The perinatal outcomes of PGT and IVF/ICSI singleton pregnancies were similar except for the observed potentially higher risk of gestational hypertension with PGT singleton pregnancy. However, because the data on PGT singleton pregnancies are limited, this conclusion warrants further investigation.
Subject(s)
Cryopreservation/trends , Embryo Transfer/trends , Genetic Testing/trends , Live Birth/epidemiology , Preimplantation Diagnosis/trends , Propensity Score , Adult , Cohort Studies , Cryopreservation/methods , Embryo Transfer/methods , Female , Fertilization in Vitro , Freezing , Genetic Testing/methods , Humans , Hypertension, Pregnancy-Induced/diagnosis , Hypertension, Pregnancy-Induced/epidemiology , Infant, Newborn , Male , Pregnancy , Preimplantation Diagnosis/methods , Retrospective StudiesABSTRACT
Importance: In March 2018, Medicare issued a national coverage determination (NCD) for next-generation sequencing (NGS) to facilitate access to NGS testing among Medicare beneficiaries. It is unknown whether the NCD affected health equity issues for Medicare beneficiaries and the overall population. Objective: To examine the association between the Medicare NCD and NGS use by insurance types and race and ethnicity. Design, Setting, and Participants: A retrospective cohort analysis was conducted using electronic health record data derived from a real-world database. Data originated from approximately 280 cancer clinics (approximately 800 sites of care) in the US. Patients with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), or advanced melanoma diagnosed from January 1, 2011, through March 31, 2020, were included. Exposure: Pre- vs post-NCD period. Main Outcomes and Measures: Patients were classified by insurance type and race and ethnicity to examine patterns in NGS testing less than or equal to 60 days after diagnosis. Difference-in-differences models examined changes in average NGS testing in the pre- and post-NCD periods by race and ethnicity, and interrupted time-series analysis examined whether trends over time varied by insurance type and race and ethnicity. Results: Among 92â¯687 patients with aNSCLC, mCRC, mBC, or advanced melanoma, mean (SD) age was 66.6 (11.2) years, 51â¯582 (55.7%) were women, and 63â¯864 (68.9%) were Medicare beneficiaries. The largest racial and ethnic categories according to the database used and further classification were Black or African American (8605 [9.3%]) and non-Hispanic White (59 806 [64.5%]). Compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio [OR], 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03) compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not statistically significantly different compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). The NCD was not associated with statistically significant changes in NGS use trends by racial and ethnic groups within Medicare beneficiaries alone or across all insurance types. Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases among Asian individuals and those with other races and ethnicities were similar. Conclusions and Relevance: The findings of this study suggest that expansion of Medicare-covered benefits may not occur equally across insurance types, thereby further widening or maintaining disparities in NGS testing. Additional efforts beyond coverage policies are needed to ensure equitable access to the benefits of precision medicine.
Subject(s)
Genetic Predisposition to Disease , Genetic Testing/economics , High-Throughput Nucleotide Sequencing/economics , High-Throughput Nucleotide Sequencing/trends , Medicare/economics , Medicare/trends , Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Forecasting , Genetic Testing/statistics & numerical data , Genetic Testing/trends , High-Throughput Nucleotide Sequencing/statistics & numerical data , Humans , Insurance Coverage/standards , Insurance Coverage/statistics & numerical data , Insurance Coverage/trends , Male , Medicare/statistics & numerical data , Middle Aged , Retrospective Studies , United States , Young AdultSubject(s)
Genetic Testing/methods , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/genetics , State Medicine , Whole Genome Sequencing , Genetic Testing/economics , Genetic Testing/trends , Health Care Costs , Humans , Mitochondrial Diseases/economics , State Medicine/economics , State Medicine/trends , Time Factors , United Kingdom , Whole Genome Sequencing/economics , Whole Genome Sequencing/trendsABSTRACT
This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively reviewed. Overall, the most common subtypes include SCA1, SCA2, SCA3, and SCA6, but there are large differences in the relative prevalence of these and other SCA subtypes between Asian countries. Some subtypes such as SCA12 and SCA31 are rather specific to certain Asian populations. Second, we summarized distinctive phenotypic manifestations of SCA patients of Asian origin, for example a frequent co-occurrence of parkinsonism in some SCA subtypes. Lastly, we have conducted an exploratory survey study to map SCA-specific expertise, resources, and management in various Asian countries. This showed large differences in accessibility, genetic testing facilities, and treatment options between lower and higher income Asian countries. Currently, many Asian SCA patients remain without a final genetic diagnosis. Lack of prevalence data on SCA, lack of patient registries, and insufficient access to genetic testing facilities hamper a wider understanding of these diseases in several (particularly lower income) Asian countries.
Subject(s)
Asian People/statistics & numerical data , Disease Management , Spinocerebellar Ataxias/ethnology , Spinocerebellar Ataxias/epidemiology , Asia/epidemiology , Asian People/genetics , Genetic Testing/trends , Health Services Accessibility/trends , Healthcare Disparities/trends , Humans , Income , Phenotype , Prevalence , Spinocerebellar Ataxias/geneticsABSTRACT
We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer. METHODS: A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival. Two reviewers independently selected studies and assessed quality with the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group or the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies depending on the type of study being reviewed. RESULTS: Fourteen studies were included with a total of 3,328 patients with cancer. All studies included patients without standard-of-care treatment options and usually with multiple prior lines of therapy. In studies reporting response rates, patients receiving MTB-recommended therapy had overall response rates ranging from 0% to 67%. In the only trial powered on clinical outcome and including a control group, the group receiving MTB-recommended therapy had significantly improved rate of progression-free survival compared with those receiving conventional therapy. CONCLUSION: Although data quality is limited by a lack of prospective randomized controlled trials, MTBs appear to improve clinical outcomes for patients with cancer. Future research should concentrate on prospective trials and standardization of approach and outcomes.
Subject(s)
Biomarkers, Tumor/genetics , Medical Oncology/methods , Neoplasms/drug therapy , Patient Care Team/organization & administration , Precision Medicine/methods , Antineoplastic Agents/pharmacology , Clinical Decision-Making , DNA Mutational Analysis/standards , Genetic Testing/standards , Genetic Testing/trends , High-Throughput Nucleotide Sequencing/standards , Humans , Medical Oncology/organization & administration , Molecular Targeted Therapy , Mutation , Neoplasms/diagnosis , Neoplasms/geneticsABSTRACT
INTRODUCTION: There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation. METHODS: The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally. RESULTS: We identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial. CONCLUSION: There is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.
Subject(s)
Genetic Predisposition to Disease/genetics , Genetic Testing/trends , Laboratories, Clinical/statistics & numerical data , Parkinson Disease/genetics , Genetic Testing/methods , Genetic Testing/standards , Humans , Laboratories, Clinical/standardsABSTRACT
Parrots are considered the third most popular pet species, after dogs and cats, in the United States of America. Popular birds include budgerigars, lovebirds and cockatiels and are known for their plumage and vocal learning abilities. Plumage colour variation remains the main driving force behind breeder selection. Despite the birds' popularity, only two molecular genetic tests-bird sexing and pathogen screening-are commercially available to breeders. For a limited number of species, parentage verification tests are available, but are mainly used in conservation and not for breeding purposes. No plumage colour genotyping test is available for any of the species. Due to the fact that there isn't any commercial plumage genotype screening or parentage verification tests available, breeders mate close relatives to ensure recessive colour alleles are passed to the next generation. This, in turn, leads to inbreeding depression and decreased fertility, lower hatchability and smaller clutch sizes, all important traits in commercial breeding systems. This review highlights the research carried out in the field of pet parrot genomics and points out the areas where future research can make a vital contribution to understanding how parrot breeding can be improved to breed healthy, genetically diverse birds.
Subject(s)
Genetic Testing/trends , Parrots/genetics , Alleles , Animals , Feathers/metabolism , Genetic Testing/methods , Genome/genetics , Genomics/methods , Genomics/trends , Inbreeding Depression/genetics , Pigmentation/geneticsABSTRACT
Among all cancer types, pulmonary cancer has the highest mortality rate. Tobacco consumption remains the major risk factor for the development of lung cancer. However, many studies revealed a correlation between inherited genetic variants and predisposition to lung cancer, especially in nonsmokers. To date, genetic testing for the detection of germline mutations is not yet recommended in patients with lung cancer and testing is focused on somatic alterations given their implication in the treatment choice. Understanding the impact of genetic predisposition on the occurrence of lung cancer is essential to enable the introduction of accurate guidelines and recommendations that might reduce mortality. In this review paper, we describe familial lung cancer, and expose germline mutations that are linked to this type of cancer. We also report pathogenic genetic variants linked to syndromes associated with lung cancer.
Subject(s)
Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Germ-Line Mutation/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Genetic Predisposition to Disease/epidemiology , Genetic Testing/trends , Humans , Lung Neoplasms/epidemiologyABSTRACT
BACKGROUND: The global development and advancement of genomic medicine in the recent decade has accelerated the implementation of personalized medicine (PM) and pharmacogenomics (PGx) into clinical practice, while catalyzing the emergence of genetic testing (GT) with relevant ethical, legal, and social implications (ELSI). RESULTS: The perception of university undergraduates with regards to PM and PGx was investigated, and 80% of undergraduates valued PM as a promising healthcare model with 66% indicating awareness of personal genome testing companies. When asked about the curriculum design towards PM and PGx, compared to undergraduates in non-medically related curriculum, those studying in medically related curriculum had an adjusted 7.2 odds of perceiving that their curriculum was well-designed for learning PGx (95% CI 3.6-14.6) and a 3.7 odds of perceiving that PGx was important in their study (95% CI 2.0-6.8). Despite this, only 16% of medically related curriculum undergraduates would consider embarking on future education on PM. When asked about their perceptions on GT, 60% rated their genetic knowledge as "School Biology" level or below while 76% would consider undergoing a genetic test. As for ELSI, 75% of undergraduates perceived that they were aware of ethical issues of GT in general, particularly on "Patient Privacy" (80%) and "Data Confidentiality" (68%). Undergraduates were also asked about their perceived reaction upon receiving an unfavorable result from GT, and over half of the participants perceived that they would feel "helpless or pessimistic" (56%), "inadequate or different" (59%), and "disadvantaged at job seeking" (59%), while older undergraduates had an adjusted 2.0 odds of holding the latter opinion (95% CI 1.1-3.5), compared to younger undergraduates. CONCLUSION: Hong Kong undergraduates showed a high awareness of PM but insufficient genetic knowledge and low interest in pursuing a career towards PM. They were generally aware of ethical issues of GT and especially concerned about patient privacy and data confidentiality. There was a predominance of pessimistic views towards unfavorable testing results. This study calls for the attention to evaluate education and talent development on genomics, and update existing legal frameworks on genetic testing in Hong Kong.
Subject(s)
Genetic Testing/trends , Pharmacogenetics/trends , Precision Medicine/psychology , Adult , Attitude , Education, Medical, Undergraduate , Female , Genomic Medicine , Hong Kong/epidemiology , Humans , Male , Perception , Universities/trends , Young AdultABSTRACT
Importance: Genomic newborn screening (gNBS) may optimize the health and well-being of children and families. Screening programs are required to be evidence based, acceptable, and beneficial. Objectives: To identify what has been discovered following the reporting of the first gNBS pilot projects and to provide a summary of key points for the design of gNBS. Evidence Review: A systematic literature review was performed on April 14, 2021, identifying 36 articles that addressed the following questions: (1) what is the interest in and what would be the uptake of gNBS? (2) what diseases and genes should be included? (3) what is the validity and utility of gNBS? and (4) what are the ethical, legal, and social implications? Articles were only included if they generated new evidence; all opinion pieces were excluded. Findings: In the 36 articles included, there was high concordance, except for gene disease inclusion, which was highly variable. Key findings were the need for equitable access, appropriate educational materials, and informed and flexible consent. The process for selecting genes for testing should be transparent and reflect that parents value the certainty of prediction over actionability. Data should be analyzed in a way that minimizes uncertainty and incidental findings. The expansion of traditional newborn screening (tNBS) to identify more life-threatening and treatable diseases needs to be balanced against the complexity of consenting parents of newborns for genomic testing as well as the risk that overall uptake of tNBS may decline. The literature reflected that the right of a child to self-determination should be valued more than the possibility of the whole family benefiting from a newborn genomic test. Conclusions and Relevance: The findings of this systematic review suggest that implementing gNBS will require a nuanced approach. There are gaps in our knowledge, such as the views of diverse populations, the capabilities of health systems, and health economic implications. It will be essential to rigorously evaluate outcomes and ensure programs can evolve to maximize benefit.