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Journal of Clinical Oncology : Official... Jan 2023Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food... (Review)
Review
Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food and Drug Administration. Many LDTs enter the market without US Food and Drug Administration or any regulatory review. The Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments focuses on analytic performance, but has limited oversight of the quality or utility of LDTs, including whether patients have been harmed as a result of their use. Increasingly, LDTs for cancer risk or early detection have been marketed directly to consumers, with many LDT developers depicting these tests, requested by patients but ordered by personal or company-associated physicians, as procedures falling under the practice of medicine. This patchwork of regulation and enforcement uncertainty regarding LDTs and public concerns about accuracy of tests given emergency authorization during the COVID-19 pandemic led to the Verifying Accurate Leading-edge IVCT (in vitro clinical test) Development Act of 2021. This pending federal legislation represents an opportunity to harmonize regulatory policies and address growing concerns over quality, utility, and safety of LDTs for cancer genomics, including tests marketed directly to consumers. We review here questions regarding the potential benefits and harms of some cancer-related LDTs for cancer risk and presymptomatic molecular diagnosis, increasingly marketed to oncologists or directly to the worried well. We offer specific proposals to strengthen oversight of the accuracy and clinical utility of cancer genetic testing to ensure public safety.
Topics: Aged; Humans; United States; COVID-19; Pandemics; Medicare; Clinical Laboratory Services; Neoplasms
PubMed: 35944238
DOI: 10.1200/JCO.22.00995 -
Annals of Laboratory Medicine Mar 2022The process of method development for a diagnostic assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) involves several disparate technologies and... (Review)
Review
The process of method development for a diagnostic assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) involves several disparate technologies and specialties. Additionally, method development details are typically not disclosed in journal publications. Method developers may need to search widely for pertinent information on their assay(s). This review summarizes the current practices and procedures in method development. Additionally, it probes aspects of method development that are generally not discussed, such as how exactly to calibrate an assay or where to place quality controls, using examples from the literature. This review intends to provide a comprehensive resource and induce critical thinking around the experiments for and execution of developing a clinically meaningful LC-MS/MS assay.
Topics: Chromatography, Liquid; Clinical Laboratory Services; Humans; Laboratories; Quality Control; Tandem Mass Spectrometry
PubMed: 34635606
DOI: 10.3343/alm.2022.42.2.121 -
PloS One 2020Federal Ministry of Health (FMoH) Ethiopia achieved significant declines in malaria mortality and incidence and has recently launched malaria elimination in selected low... (Clinical Trial)
Clinical Trial
BACKGROUND
Federal Ministry of Health (FMoH) Ethiopia achieved significant declines in malaria mortality and incidence and has recently launched malaria elimination in selected low transmission settings. Successful malaria elimination calls for rapid and accurate diagnosis of cases so that the patients can promptly be treated before the occurrence of transmission. Therefore, this study assessed the competency of malaria microscopists using panal slides, and laboratory service availability and readiness in terms of supplies and equipments in malaria elimination targeted districts in Ethiopia.
METHOD
A cross-sectional study was conducted from February to June 2018 in all hospitals, health centers and private clinics in 20 malaria elimination targeted districts, selected out of the 6 regional states in Ethiopia. All malaria microscopists available in the study health facilities during the study period were included in the study. Questionnaires were used for interviewing sociodemography of personnel and laboratory supplies. Per World Health Organization (WHO) criteria set for proficiency testing, 10 Giemsa stained malaria slide panels (8 positive low/high density pf/pv/Mixed and 2 negative slides) were administered to each study participant for performance assessment on malaria parasite detection, species identification and parasite count using light microscopy. The slide panels are PCR confirmed and WHO approved ones, which have been stored in the slide banks at the national reference laboratory in Ethiopian Public Health Institute.
RESULT
In this assessment, 17(16%) district hospitals, 71(67%) health centers (HCs) and 18(17%) private clinics (PCs) were included. Of the 18 PCs, only 10(55.6%) had license certificate. Of the study facilities, 91.5%(97) use light microscopy, 2.83%(3) use RDTs and 2.9%(3) use both microscopy and RDT to detect malaria. Accessible and appropriate storage of Giemsa was reported by 58.8%(10) hospitals, 81.7%(58) HCs & 72.2%(13) private clinics. Of the 1896 malaria positive & 474 negative slides administered to 237 study participants, 318(16.8%) slides reported falsely negative & 47(9.9%) reported falsely positive. The participants achieved "good" grade [Agreement(A): 84.6%, Kappa(K): 0.6] on parasite detection and "poor" agreement (A: 43.8%; K: 0.11) on every species identification. No or slight agreement seen on differentiation of P. falciparum from other species (A: 28.41%; K:0.29). Above 95%(201) of participants, did not count or used plus system of parasite estimation which is the least accurate and unreccomended method per WHO guideline.
CONCLUSION
In the current study, low performance of malaria microscopists particularly in species identification & poor to moderate capacity of laboratories observed. This is really a great obstacle to malaria elimination strategy of the country. Therefore, national malaria control and elimination program in collaboration with partners is supposed to provide comprehensive training for professionals giving laboratory service and to fulfill laboratory supplies to have the gold standard service.
Topics: Adult; Cross-Sectional Studies; Diagnostic Services; Ethiopia; Female; Humans; Laboratory Proficiency Testing; Malaria, Falciparum; Male; Microscopy; Middle Aged
PubMed: 32584866
DOI: 10.1371/journal.pone.0235151 -
Journal of Autism and Developmental... Nov 2021Research providing an evidence-base for autistic adult services is sparse. The Autism Spectrum Disorders in the European Union (ASDEU) network implemented an on-line...
Research providing an evidence-base for autistic adult services is sparse. The Autism Spectrum Disorders in the European Union (ASDEU) network implemented an on-line survey to determine gaps in autistic adult diagnostic evaluation and post-diagnostic support services. More than 55% in all groups experienced most of the recommended features for diagnostic evaluation for autistic adults. In contrast, < 2% of adults or carers, and < 21% of professionals experienced each of the recommended features for post-diagnostic support. In contrast to 61% of professionals, only about 30% of autistic adults and carers had knowledge of good local services models for autism diagnosis in adulthood. There are major differences between good practice guidelines for diagnostic and post-diagnostic care for autistic adults, and what is actually experienced by services users and professionals.
Topics: Adult; Autism Spectrum Disorder; Autistic Disorder; Diagnostic Services; European Union; Humans; Surveys and Questionnaires
PubMed: 33502713
DOI: 10.1007/s10803-021-04873-5 -
Journal of Healthcare Engineering 2022According to the latest data from the Bureau of Disease Control and Prevention of the National Health and Family Planning Commission, China currently has 199.6 million...
According to the latest data from the Bureau of Disease Control and Prevention of the National Health and Family Planning Commission, China currently has 199.6 million diabetic patients and has become the world's largest country with diabetes. The prevalence rate is as high as 14.3%, which is much higher than the world average of 5.8%. The primary-level ophthalmic screening service is one of the important tasks to improve primary-level medical services, and the corresponding ophthalmic imaging diagnosis technology is an important support for primary-level medical and health services. Therefore, it is very necessary for us to study the application of artificial intelligence image recognition technology for diabetic retinopathy under the medical consortium mode and to study the precise initial diagnosis, precise referral, and precise follow-up of diabetic retina under the medical conjoined mode, so as to better promote the transformation of the ophthalmology primary service model. Based on this background, in this article, we have proposed and carried out the following solution: (1) diabetes data collation. Based on medical artificial intelligence technology, this paper collected 2,265 electronic medical records from an eye hospital in Ningbo and selected 2,000 qualified medical records for data integration and preprocessing. The contents of electronic medical records mainly include age, gender, and examination records. (2) Establish diabetic retinopathy diagnosis model based on neural network algorithm. This article first uses the classic algorithm of BP neural network for modeling, chooses the Levenberg-Marquardt method as the training function, and selects 10 hidden layer units through comparison experiments. After that, ophthalmologists assessed 80 sets of test results and determined the right diagnosis rate. Finally, this article compares and analyzes the accuracy of the two routes in 80 tests.
Topics: Artificial Intelligence; Diabetes Mellitus; Diabetic Retinopathy; Humans; Mass Screening; Neural Networks, Computer; Retina
PubMed: 35083023
DOI: 10.1155/2022/2185547 -
International Journal For Equity in... Jan 2023Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10-13 million people live with these conditions. Increased use of chromosome... (Review)
Review
Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10-13 million people live with these conditions. Increased use of chromosome microarray assays, exome sequencing, and whole genome sequencing as first-tier testing techniques in suitable indications can shorten the diagnostic odyssey, eliminate unnecessary tests, procedures, and treatments, and lower healthcare expenditures. A selected panel of Brazilian experts in fields related to rare diseases was provided with a series of relevant questions to address before a multi-day conference. Within this conference, each narrative was discussed and edited through numerous rounds of discussion until agreement was achieved. The widespread adoption of exome sequencing and whole genome sequencing in Brazil is limited by various factors: cost and lack of funding, reimbursement, awareness and education, specialist shortages, and policy issues. To reduce the burden of rare diseases and increase early diagnosis, the Brazilian healthcare authorities/government must address the barriers to equitable access to early diagnostic methods for these conditions. Recommendations are provided, including broadening approved testing indications, increasing awareness and education efforts, increasing specialist training opportunities, and ensuring sufficient funding for genetic testing.
Topics: Humans; Exome Sequencing; Brazil; Rare Diseases; Whole Genome Sequencing; Genetic Testing
PubMed: 36639662
DOI: 10.1186/s12939-022-01809-y -
Chromosomes in the genomic age. Preserving cytogenomic competence of diagnostic genome laboratories.European Journal of Human Genetics :... Apr 2021Participation of clinical genetic laboratories in External Quality Assessment schemes (EQAs) is a powerful method to ascertain if any improvement or additional training... (Review)
Review
Participation of clinical genetic laboratories in External Quality Assessment schemes (EQAs) is a powerful method to ascertain if any improvement or additional training is required in the diagnostic service. Here, we provide evidence from recent EQAs that the competence in recognizing and interpreting cytogenetic aberrations is variable and could impact patient management. We identify several trends that could affect cytogenomic competence. Firstly, as a result of the age distribution among clinical laboratory geneticists (CLGs) registered at the European Board of Medical Genetics, about 25-30% of those with experience in cytogenetics will retire during the next decade. At the same time, there are about twice as many molecular geneticists to cytogeneticists among the younger CLGs. Secondly, when surveying training programs for CLG, we observed that not all programs guarantee that candidates gather sufficient experience in clinical cytogenomics. Thirdly, we acknowledge that whole genome sequencing (WGS) has a great attraction to biomedical scientists that wish to enter a training program for CLG. This, with a larger number of positions available, makes a choice for specialization in molecular genetics logical. However, current WGS technology cannot provide a diagnosis in all cases. Understanding the etiology of chromosomal rearrangements is essential for appropriate follow-up and for ascertaining recurrence risks. We define the minimal knowledge a CLG should have about cytogenomics in a world dominated by WGS, and discuss how laboratory directors and boards of professional organizations in clinical genetics can uphold cytogenomic competence by providing adequate CLG training programs and attracting sufficient numbers of trainees.
Topics: Clinical Competence; Cytogenetic Analysis; Genetic Testing; Genomics; Humans; Laboratories, Clinical
PubMed: 33311710
DOI: 10.1038/s41431-020-00780-y -
American Journal of Human Genetics Nov 2022Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing... (Review)
Review
Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.
Topics: Humans; Databases, Genetic; Laboratories; Genetic Variation; Australia; Genetic Testing
PubMed: 36332611
DOI: 10.1016/j.ajhg.2022.10.006 -
Tidsskrift For Den Norske Laegeforening... Feb 2017Transport to a radiology department can be a strain on nursing home patients, leading to less use of diagnostic imaging. The purpose of this study was to examine the use...
BACKGROUND
Transport to a radiology department can be a strain on nursing home patients, leading to less use of diagnostic imaging. The purpose of this study was to examine the use and benefit of a mobile X-ray service that enables imaging at nursing homes.
MATERIAL AND METHOD
In connection with 300 of a total of 326 referrals to a mobile X-ray service in Vestfold County in the period March to September 2015, 66 doctors at 33 nursing homes completed a questionnaire on the options patients would have had in the absence of the mobile service. A hundred of these referrals were followed up one to two weeks later with a further questionnaire on the implications of the X-ray scan for diagnosis, treatment and nursing. Eighty-seven questionnaires were completed.
RESULTS
In 219 cases (73 %), the patients would have been sent to a hospital radiology department if the mobile X-ray service had not been available. In 60 cases (20 %) the patients would not have had an X-ray examination. In the follow-up, doctors answered that the X-rays had yielded new diagnostic information in 81 cases (95 %), that 71 (83 %) of the X-ray results had had implications for further treatment and that 29 (34 %) had helped patients avoid hospitalisation. In 77 cases (89 %), the X-rays enabled important information to be given to patients and their families.
CONCLUSION
A mobile X-ray service makes it possible to avoid transports that place a strain on patients and to provide necessary diagnoses for patients who would not otherwise have been examined.
Topics: Humans; Mobile Health Units; Nursing Homes; Patient Admission; Patient Transfer; Physicians; Radiography; Surveys and Questionnaires; Transportation of Patients
PubMed: 28181756
DOI: 10.4045/tidsskr.16.0035 -
European Journal of Human Genetics :... Jun 2024Increasing use of diagnostic genomic sequencing is pushing health services to confront the issue of opportunistic genomic screening (OGS). To date, OGS has been offered...
Increasing use of diagnostic genomic sequencing is pushing health services to confront the issue of opportunistic genomic screening (OGS). To date, OGS has been offered concomitant with diagnostic testing. In contrast, we piloted a service offering OGS after return of diagnostic testing results. Evaluation was designed to provide insights for future models of service and included patient surveys at three time points, semi-structured interviews with genetic counsellors (GCs) and a focus group with medical scientists. Uptake was relatively low: 83 of 200 patients approached (42%) attended the OGS service, with 81 accepting OGS. Whilst many who declined to attend the service cited practical barriers, others gave reasons that indicated this was a considered decision. Despite specific genetic counselling, one third of patients did not understand the scope of re-analysis. Yet after post-test counselling, all respondents with novel pathogenic additional findings (AF) understood the implications and reported relevant follow-up. Recall was high: five months after last contact, 75% recalled being offered OGS without prompting. GC interviews and patient survey responses provide insights into complexities that influence patient support needs, including diagnostic status and AF result type. There was no consensus among patients or professionals about when to offer OGS. There was a clear preference for multiple, flexible methods of information provision; achieving this whilst balancing patient support needs and resource requirements is a challenge requiring further investigation. Decisions about whether, when and how to offer OGS are complex; our study shows the two-step approach warrants further exploration.
Topics: Humans; Genetic Testing; Female; Male; Adult; Genetic Counseling; Middle Aged; Aged
PubMed: 38528054
DOI: 10.1038/s41431-024-01592-0