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European Journal of Paediatric... Jan 2022To clarify the diagnostic utility and the cost-effectiveness of whole-exome sequencing (WES) as a routine early-diagnostic tool in children with progressive neurological...
OBJECTIVES
To clarify the diagnostic utility and the cost-effectiveness of whole-exome sequencing (WES) as a routine early-diagnostic tool in children with progressive neurological disorders.
METHODS
Patients with infantile-onset severe neurological diseases or childhood-onset progressive neurological disorders were prospectively recruited to this WES study, in the pediatric neurology clinic at Helsinki University Hospital during 2016-2018. A total of 48 patients underwent a singleton WES. A control group of 49 children underwent traditional diagnostic examinations and were retrospectively collected from the hospital records. Their use of health care services, related to the diagnostic process, was gathered. Incremental cost-effectiveness ratio (ICER) per additional diagnosis was calculated from the health care provider perspective. Bootstrapping methods were used to estimate the uncertainty of cost-effectiveness outcomes.
RESULTS
WES provided a better diagnostic yield (38%) than diagnostic pathway that did not prioritize WES in early diagnosis (25%). WES outperformed other diagnostic paths especially when made early, within one year of first admission (44%). Cost-effectiveness in our results are conservative, affected by WES costs during 2016-18.
CONCLUSIONS
WES is an efficient and cost-effective diagnostic tool that should be prioritized in early diagnostic path of children with progressive neurological disorders. The progressively decreasing price of the test improves cost-effectiveness further.
Topics: Child; Cost-Benefit Analysis; Genetic Testing; Humans; Nervous System Diseases; Retrospective Studies; Exome Sequencing
PubMed: 34852981
DOI: 10.1016/j.ejpn.2021.11.006 -
European Radiology Jan 2022During the COVID-19 pandemic, there was a temporary cessation of mammography screening. However, in some facilities, diagnostic breast imaging services continued for...
OBJECTIVE
During the COVID-19 pandemic, there was a temporary cessation of mammography screening. However, in some facilities, diagnostic breast imaging services continued for patients with a high clinical suspicion of breast cancer. The objective of this study was to evaluate changes in the diagnostic interval (DI) of non-screening patients presenting for diagnostic mammography during the first wave of the COVID-19 pandemic.
METHODS
Retrospective chart review was performed on patients presenting for non-screening diagnostic mammography from April 1 to June 30, 2020 (pandemic group) and April 1 to June 30, 2019 (pre-pandemic group). Age, reason for referral, number and type of imaging studies/biopsies necessary for a final diagnosis were recorded. Diagnostic interval (DI) was defined as the number of days from the date of the diagnostic mammogram to the date of the final diagnosis.
RESULTS
Compared to the pre-pandemic group (n = 64), the pandemic group (n = 77) showed a reduction in DI of the entire cohort (pandemic: 1 day; pre-pandemic: 15 days, p < 0.0001) for patients not requiring tissue sampling (pandemic: 1 day; pre-pandemic: 11 days, .p < 0.0001) and those requiring tissue sampling with benign pathology (pandemic 9 days; pre-pandemic, 33 days, p = 0.0002). A higher percentage of patients in the pandemic group had their assessment completed during the initial visit (pandemic: 50.6%; pre-pandemic: 23.4%, p = 0.0009).
CONCLUSION
During the first wave of the COVID-19 pandemic, the DI for patients with non-screening-related diagnostic mammography was significantly shorter, with a higher percentage of patients completing their assessments on the initial visit, compared to one year prior.
KEY POINTS
• Despite reductions in manpower and clinical services, during pandemic times, it is possible to maintain a diagnostic breast imaging service for women at high clinical suspicion for breast cancer. • During pandemic times, breast imaging departments should consider restructuring to a Rapid Diagnostic Unit model with a navigation team that follows patients through the assessment process to a final diagnosis. • Departmental restructuring and patient navigation during pandemic times could either maintain or shorten the diagnostic interval for patients presenting for diagnostic mammography.
Topics: Breast Neoplasms; COVID-19; Early Detection of Cancer; Female; Humans; Mammography; Mass Screening; Pandemics; Retrospective Studies; SARS-CoV-2
PubMed: 34143286
DOI: 10.1007/s00330-021-08117-z -
Journal of Clinical Oncology : Official... Apr 2024Pharmacogenomics (PGx), the study of inherited genomic variation and drug response or safety, is a vital tool in precision medicine. In oncology, testing to identify PGx... (Review)
Review
Pharmacogenomics (PGx), the study of inherited genomic variation and drug response or safety, is a vital tool in precision medicine. In oncology, testing to identify PGx variants offers patients the opportunity for customized treatments that can minimize adverse effects and maximize the therapeutic benefits of drugs used for cancer treatment and supportive care. Because individuals of shared ancestry share specific genetic variants, PGx factors may contribute to outcome disparities across racial and ethnic categories when genetic ancestry is not taken into account or mischaracterized in PGx research, discovery, and application. Here, we examine how the current scientific understanding of the role of PGx in differential oncology safety and outcomes may be biased toward a greater understanding and more complete clinical implementation of PGx for individuals of European descent compared with other genetic ancestry groups. We discuss the implications of this bias for PGx discovery, access to care, drug labeling, and patient and provider understanding and use of PGx approaches. Testing for somatic genetic variants is now the standard of care in treatment of many solid tumors, but the integration of PGx into oncology care is still lacking despite demonstrated actionable findings from PGx testing, reduction in avoidable toxicity and death, and return on investment from testing. As the field of oncology is poised to expand and integrate germline genetic variant testing, it is vital that PGx discovery and application are equitable for all populations. Recommendations are introduced to address barriers to facilitate effective and equitable PGx application in cancer care.
Topics: Humans; Pharmacogenomic Testing; Precision Medicine; Pharmacogenetics; Genetic Testing; Medical Oncology
PubMed: 38386947
DOI: 10.1200/JCO.23.01748 -
Clinics in Laboratory Medicine Mar 2024Syndromic respiratory panels are now widely available in clinical microbiology laboratories and health care institutions. These panels can rapidly diagnose infections... (Review)
Review
Syndromic respiratory panels are now widely available in clinical microbiology laboratories and health care institutions. These panels can rapidly diagnose infections and detect antimicrobial resistance genes allowing for more rapid therapeutic optimization compared to standard microbiology approaches. However, given reimbursement concerns and limitations of multiplex molecular testing and results interpretation, maximum clinical utility and positive clinical outcomes depend on active diagnostic stewardship. Here, the authors review clinical outcomes of both upper and lower respiratory panels and present diagnostic stewardship strategies for optimal use of respiratory panels.
Topics: Anti-Infective Agents; Molecular Diagnostic Techniques; Antimicrobial Stewardship; Clinical Laboratory Services
PubMed: 38280797
DOI: 10.1016/j.cll.2023.10.001 -
The International Journal of... Feb 2021
Topics: Africa; Diagnostic Services; Dyspnea; Humans; Plant Leaves
PubMed: 33656418
DOI: 10.5588/ijtld.20.0853 -
Journal of Public Health Management and...By providing timely services at all steps along the continuum of the early hearing detection and intervention (EHDI) process, providers may be able to lessen potential...
CONTEXT
By providing timely services at all steps along the continuum of the early hearing detection and intervention (EHDI) process, providers may be able to lessen potential adverse effects of late identification of hearing loss on children's language development.
OBJECTIVE
To examine the timeliness of key events in the EHDI process from birth through diagnosis of hearing loss among different populations.
DESIGN
Retrospective, cross-sectional.
SETTING
Data pooled from 9 states' EHDI information systems were used to determine the extent to which timely screening and diagnosis were achieved by 754 613 infants born in calendar year 2017. Enrollment into early intervention for children diagnosed is not examined here due to incomplete data.
PARTICIPANTS
Nine state EHDI programs were selected to participate in this study for their successful experience in using EHDI-IS to collect detailed child-level data.
MAIN OUTCOME MEASURES
Age of service, rate of service receipt.
RESULTS
Median age of newborn hearing screening was 1 day, and median age of hearing loss diagnosis was 68 days. Early completion of newborn hearing screening was associated with maternal education, maternal race/ethnicity, and admission into a neonatal intensive care unit (NICU). Receiving and completing follow-up diagnostic services were associated with maternal education, maternal race/ethnicity, age of screening, and enrollment into the Women, Infants, and Children program.
CONCLUSIONS
Timely completion of the newborn hearing screening is achieved by most of the population among the participating states. Increased efforts may be considered by state EHDI programs to provide additional follow-up and education to underrepresented racial/ethnic groups, mothers with less education, and NICU infants and their families as these groups appear to be at an increased risk for delayed diagnostic testing for hearing loss.
Topics: Cross-Sectional Studies; Diagnostic Services; Female; Hearing; Humans; Infant; Infant, Newborn; Neonatal Screening; Retrospective Studies
PubMed: 32956290
DOI: 10.1097/PHH.0000000000001232 -
Human Genetics May 2022Genetic carrier screening for reproductive purposes has existed for half a century. It was originally offered to particular ethnic groups with a higher prevalence of... (Review)
Review
Genetic carrier screening for reproductive purposes has existed for half a century. It was originally offered to particular ethnic groups with a higher prevalence of certain severe recessive or X-linked genetic conditions, or (as carrier testing) to those with a family history of a particular genetic condition. Commercial providers are increasingly offering carrier screening on a user-pays basis. Some countries are also trialing or offering public reproductive genetic carrier screening with whole populations, rather than only to those known to have a higher chance of having a child with an inherited genetic condition. Such programs broaden the ethical and practical challenges that arise in clinical carrier testing. In this paper we consider three aspects of selecting genes for population reproductive genetic carrier screening panels that give rise to important ethical considerations: severity, variable penetrance and expressivity, and scalability; we also draw on three exemplar genes to illustrate the ethical issues raised: CFTR, GALT and SERPINA1. We argue that such issues are important to attend to at the point of gene selection for RGCS. These factors warrant a cautious approach to screening panel design, one that takes into account the likely value of the information generated by screening and the feasibility of implementation in large and diverse populations. Given the highly complex and uncertain nature of some genetic variants, careful consideration needs to be given to the balance between delivering potentially burdensome or harmful information, and providing valuable information to inform reproductive decisions.
Topics: Child; Family; Genetic Carrier Screening; Genetic Testing; Humans
PubMed: 34426854
DOI: 10.1007/s00439-021-02341-9 -
JAMA Pediatrics Feb 2022The number of adolescents who are diagnosed with a genetic disorder is increasing as genome sequencing becomes the standard of clinical diagnostic testing. However, the... (Review)
Review
IMPORTANCE
The number of adolescents who are diagnosed with a genetic disorder is increasing as genome sequencing becomes the standard of clinical diagnostic testing. However, the experience of receiving a diagnosis of a genetic condition has not been extensively studied in adolescents.
OBJECTIVE
To identify how adolescents with a genetic condition engage with genetic or genomic counseling services as well as interpret, adapt to, and experience their diagnosis.
EVIDENCE REVIEW
A literature search of MEDLINE, Embase, CINAHL, and PsycINFO was undertaken. Articles (primary literature, knowledge syntheses, and gray literature) in English that investigated the experiences of adolescents between 10 and 19 years of age who received genetic or genomic counseling were included. Data were extracted from 45 eligible articles and analyzed descriptively.
FINDINGS
A total of 45 studies were included, most of which were quantitative in nature (21 of 45 [47%]) and conducted in the US (n = 13), followed by the UK (n = 8), Australia (n = 8), and Canada (n = 6). A total of 29 distinct monogenic disorders were investigated. Sample sizes ranged from 1 to 930, with a median of 23 participants, and the year of publication ranged from 1977 to 2019. Included studies addressed all aspects of genetic counseling, but a preponderance of articles assessed knowledge about genetic conditions (n = 17) and challenges of communication within families (n = 16). Fewer articles addressed the experiences of adolescents adapting to their genetic conditions (n = 8) and the genetic counseling process (n = 4). Only 1 study addressed any aspect of genetic counseling in relation to genome sequencing.
CONCLUSIONS AND RELEVANCE
This scoping review found that most of the included studies focused on adolescents' knowledge about their genetic condition and communication about genetic risks, whereas fewer studies explored their adaptation to the condition and the genetic counseling process. A systematic reconsideration of the genetic counseling process may be undertaken to provide an evidence-informed health care service that is tailored to the needs of this adolescent population.
Topics: Adolescent; Communication; Female; Genetic Counseling; Genetic Diseases, Inborn; Genetic Testing; Humans; Male
PubMed: 34807246
DOI: 10.1001/jamapediatrics.2021.4290 -
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 -
Clinica Chimica Acta; International... Apr 2020
Review
Topics: Clinical Laboratory Services; Specimen Handling; Transportation
PubMed: 31790699
DOI: 10.1016/j.cca.2019.11.026