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Genome Medicine Sep 2023Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic...
BACKGROUND
Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer.
METHODS
This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken.
RESULTS
Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing.
CONCLUSIONS
These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.
Topics: Humans; Prospective Studies; Neoplastic Syndromes, Hereditary; Oncogenes; Genetic Testing; Germ Cells
PubMed: 37723522
DOI: 10.1186/s13073-023-01223-1 -
Trials Apr 2022The aim of the paper is to discuss how a pragmatic definition could change our conception of diagnosis, using gestational diabetes mellitus (GDM) as an example. (Review)
Review
OBJECTIVE
The aim of the paper is to discuss how a pragmatic definition could change our conception of diagnosis, using gestational diabetes mellitus (GDM) as an example.
STUDY DESIGN
We review the diagnostic controversy that followed an observational study showing a linear relationship between maternal glycaemia and adverse pregnancy outcomes and the resolution proposed 15 years later by a recent pragmatic trial comparing two screening approaches (one- vs two-step) with different diagnostic thresholds.
RESULTS
The pragmatic trial involved approximately 24,000 women. The one-step screening strategy using lower GDM thresholds diagnosed twice as many women with GDM, but pregnancy outcomes were not different. We examine how the pragmatic approach integrates research into practice and defines the meaning of a diagnosis according to patient outcomes. The approach is ethically and scientifically sound as compared to the previous methodology, where observational research separated from care gave a theoretical definition of GDM that may have misled medical practice for two decades.
CONCLUSION
Pragmatic research integrated into practice can revolutionize our conception of medical diagnosis in the best medical interest of patients.
Topics: Blood Glucose; Diabetes, Gestational; Female; Humans; Mass Screening; Observational Studies as Topic; Pregnancy; Pregnancy Outcome
PubMed: 35365186
DOI: 10.1186/s13063-022-06169-0 -
Journal of Genetic Counseling Jun 2023Elective genetic testing (EGT) to identify disease risk in individuals who may or may not meet clinical criteria for testing is increasingly being offered in clinical...
Elective genetic testing (EGT) to identify disease risk in individuals who may or may not meet clinical criteria for testing is increasingly being offered in clinical practice. However, little is known about how EGT is currently implemented and how genetics professionals perceive this type of testing. We conducted a mixed-methods survey study to evaluate genetics professionals' perspectives and attitudes about EGT and describe the current landscape of EGT practices in the United States (U.S.) and Canada. Six clinical geneticists and 131 genetic counselors responded to the online survey, among whom 44% reported offering EGT in their practice. Over 84% of survey respondents agreed that EGT may improve health outcomes and understanding of genotype-phenotype correlations, and 85% agreed that potential risks include result misinterpretation and contribution to economic health disparities. Though most respondents felt comfortable providing pretest (77%) and post-test (86%) counseling for EGT, lack of provider resources (such as time and personnel) and prioritization of diagnostic testing were cited most frequently in free-text responses as reasons for not offering EGT. Of those offering EGT, 88% reported positive overall experiences. Qualitative analysis of open-ended questions identified benefits of EGT as expanding access to genetic testing, providing potential health benefits, and providing psychological benefits for patients. Disadvantages included prohibitive costs, limited clinical utility, and strain on resources. Overall, we found that genetics providers perceive both potential benefits and harms of EGT and that those offering this testing had generally positive experiences, although ethical reservations and practical limitations exist.
Topics: Humans; Genetic Counseling; Genetic Testing; Counseling; Attitude; Counselors
PubMed: 36575824
DOI: 10.1002/jgc4.1666 -
The Lancet. Infectious Diseases Feb 2020Globally, high rates (and in the WHO European region an increasing prevalence) of co-infection with tuberculosis and HIV and HIV and hepatitis C virus exist. In eastern... (Review)
Review
Globally, high rates (and in the WHO European region an increasing prevalence) of co-infection with tuberculosis and HIV and HIV and hepatitis C virus exist. In eastern European and central Asian countries, the tuberculosis, HIV, and viral hepatitis programmes, including diagnostic services, are separate vertical structures. In this Personal View, we consider underlying reasons for the poor integration for these diseases, particularly in the WHO European region, and how to address this with an initial focus on diagnostic services. In part, this low integration has reflected different diagnostic development histories, global funding sources, and sample types used for diagnosis (eg, typically sputum for tuberculosis and blood for HIV and hepatitis C). Cooperation between services improved as patients with tuberculosis needed routine testing for HIV and vice versa, but financial, infection control, and logistical barriers remain. Multidisease diagnostic platforms exist, but to be used optimally, appropriate staff training and sensible understanding of different laboratory and infection control risks needs rapid implementation. Technically these ideas are all feasible. Poor coordination between these vertical systems remains unhelpful. There is a need to increase political and operational integration of diagnostic and treatment services and bring them closer to patients.
Topics: Asia, Central; Coinfection; Diagnostic Services; Diagnostic Tests, Routine; Europe, Eastern; HIV Infections; Health Policy; Hepatitis C; Humans; Tuberculosis
PubMed: 31740252
DOI: 10.1016/S1473-3099(19)30524-9 -
The Journal of Allergy and Clinical... Jul 2022Genetic testing is a state-of-the-art and readily accessible diagnostic tool and is increasingly indicated in the evaluation process when relevant and possible, although...
Genetic testing is a state-of-the-art and readily accessible diagnostic tool and is increasingly indicated in the evaluation process when relevant and possible, although incorporation of this modality into the daily practice of allergists-immunologists in both academic and nonacademic or community settings is still a challenge. Educational sessions and resources support the use of genetic testing in the diagnosis and management of primary immunodeficiency by both the American Academy of Allergy, Asthma & Immunology and the Clinical Immunology Society. Genetic testing for primary immunodeficiency has become much more convenient and affordable over the past decade; allergist-immunologists in private practice are now able to offer patients high-quality and comprehensive genetic testing panels to help diagnose or characterize underlying immune abnormalities among patients with recurrent infections, and even patients with allergic disorder and noninfectious complications. Although genetic testing has not been a commonplace consideration in day-to-day practice for many nonacademic specialists, a shift toward adopting this into our standard toolkit should be taking place. Most of the commercial genetic testing is aiming for a panel of genes ranging anywhere from just a few to several hundred, so the specialist can feel comfortable clearly interpreting the data. As the panels are analyzing data from next-generation sequencing and deletion/duplication assays, this evaluation may need to be repeated when panels expand and include new relevant genes. Ultimately, for undiagnosed cases, whole-exome and whole-genome sequencing can be the next step; however, involvement of genetic counselors may be needed to interpret the data. The value of genetic testing is that it may bring the clinician closer to an accurate diagnosis; therefore, we can keep treating our patients more accurately and effectively, which may result in less frequent follow-ups for unresolved or recurrent problems. In addition, we can then provide patients and their families with important information about the root cause of their disease state, risks to other family members, and offer genetic counseling services. Genetic testing results may also aid in recognizing when a referral to expert colleagues for more advanced and specialized treatments is indicated.
Topics: Exome; Genetic Counseling; Genetic Testing; Humans; Referral and Consultation; United States
PubMed: 35643275
DOI: 10.1016/j.jaip.2022.05.017 -
Clinical Microbiology Reviews Jun 2021The variety and complexity of ocular infections have increased significantly in the last decade since the publication of , (L. D. Gray, P. H. Gilligan, and W. C.... (Review)
Review
The variety and complexity of ocular infections have increased significantly in the last decade since the publication of , (L. D. Gray, P. H. Gilligan, and W. C. Fowler, , , 2010). The purpose of this practical guidance document is to review, for individuals working in clinical microbiology laboratories, current tools used in the laboratory diagnosis of ocular infections. This document begins by describing the complex, delicate anatomy of the eye, which often leads to limitations in specimen quantity, requiring a close working bond between laboratorians and ophthalmologists to ensure high-quality diagnostic care. Descriptions are provided of common ocular infections in developed nations and neglected ocular infections seen in developing nations. Subsequently, preanalytic, analytic, and postanalytic aspects of laboratory diagnosis and antimicrobial susceptibility testing are explored in depth.
Topics: Clinical Laboratory Services; Clinical Laboratory Techniques; Eye Infections; Humans; Laboratories
PubMed: 34076493
DOI: 10.1128/CMR.00070-19 -
Malaria Journal Feb 2021In Ethiopia, malaria cases are declining as a result of proven interventions, and in 2017 the country launched a malaria elimination strategy in targeted settings....
BACKGROUND
In Ethiopia, malaria cases are declining as a result of proven interventions, and in 2017 the country launched a malaria elimination strategy in targeted settings. Accurate malaria diagnosis and prompt treatment are the key components of the strategy to prevent morbidity and stop the continuation of transmission. However, the quality of microscopic diagnosis in general is deteriorating as malaria burden declines. This study was carried out to evaluate the competency of microscopists and the performance of health facilities on malaria microscopic diagnosis.
METHODS
A cross-sectional study was conducted from 1 August to 30 September, 2019 in 9 regional states and one city administration. A standard checklist was used for on-site evaluation, archived patient slides were re-checked and proficiency of microscopists was tested using a WHO-certified set of slides from the national slide bank at the Ethiopian Public Health Institute (EPHI). The strength of agreement, sensitivity, specificity, and positive and negative predictive values were calculated.
RESULTS
In this study, 102 health facilities (84 health centres and 18 hospitals) were included, from which 202 laboratory professionals participated. In slide re-checking, moderate agreement (agreement (A): 76.0%; Kappa (K): 0.41) was observed between experts and microscopists on malaria detection in all health facilities. The sensitivity and specificity of routine slide reading and the re-checking results were 78.1 and 80.7%, respectively. Likewise, positive predictive value of 65.1% and negative predictive value of 88.8% were scored in the routine diagnosis. By panel testing, a substantial overall agreement (A: 91.8%; K: 0.79) was observed between microscopists and experts in detecting malaria parasites. The sensitivity and specificity in the detection of malaria parasites was 92.7 and 89.1%, respectively. In identifying species, a slight agreement (A: 57%; K: 0.18) was observed between microscopists and experts.
CONCLUSION
The study found significant false positive and false negative results in routine microscopy on slide re-checking of Plasmodium parasites. Moreover, reduced grade in parasite species identification was reported on the panel tests. Implementing comprehensive malaria microscopy mentorship, in-service training and supportive supervision are key strategies to improve the overall performance of health facilities in malaria microscopy.
Topics: Adult; Cross-Sectional Studies; Diagnostic Services; Diagnostic Tests, Routine; Ethiopia; Female; Health Facilities; Humans; Malaria; Male; Mentors; Microscopy; Middle Aged; Professional Competence; Sensitivity and Specificity; Young Adult
PubMed: 33632208
DOI: 10.1186/s12936-021-03655-9 -
Archives of Pathology & Laboratory... Oct 2020Convenience, avoidance of doctor's appointments, curiosity, and the desire to take control of one's health are driving interest toward direct-to-consumer (DTC) testing....
CONTEXT.—
Convenience, avoidance of doctor's appointments, curiosity, and the desire to take control of one's health are driving interest toward direct-to-consumer (DTC) testing. DTC is laboratory testing that is initiated by the consumer without a physician order. The results are reported back directly to the consumer. DTC testing is an exciting addition to the traditional healthcare model for consumers who want knowledge of their health status and disease risk, ancestry, and their body's expected response to certain medications based on their genotype.
OBJECTIVES.—
To discuss the perceived and potential benefits and risks involved in DTC testing.
DATA SOURCES.—
Recent published literature on DTC testing.
CONCLUSIONS.—
The benefits of DTC testing are enticing and are driving the DTC testing market. Consumers must weigh the perceived benefits with the potential risks, including privacy concerns, the possibility of receiving confusing health information, and/or information that could generate unexpected emotions, misdiagnosis, and over-testing.
Topics: Confidentiality; Direct-To-Consumer Screening and Testing; Genetic Testing; Humans; Risk Assessment
PubMed: 33002154
DOI: 10.5858/arpa.2020-0078-RA -
Journal of the Neurological Sciences Nov 2022Stroke screening tools should have good diagnostic performance for early diagnosis and a proper therapeutic plan. This paper describes and compares various diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stroke screening tools should have good diagnostic performance for early diagnosis and a proper therapeutic plan. This paper describes and compares various diagnostic tools used to identify stroke in emergency departments and prehospital setting.
METHODS
The meta-analysis was conducted according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. The PubMed and Scopus databases were searched until December 31, 2021, for studies published on stroke screening tools. These tools' diagnostic performance (sensitivity and specificity) was pooled using a bivariate random-effects model whenever appropriate.
RESULTS
Eleven screening tools for stroke were identified in 29 different studies. The various tools had a wide range of sensitivity and specificity in different studies. In the meta-analysis, the Cincinnati Pre-hospital Stroke Scale, Face Arm Speech Test, and Recognition of Stroke in the Emergency Room (ROSIER) had sensitivity (between 83 and 91%) but poor specificity (all below 64%). When comparing all the tools, ROSIER had the highest sensitivity 90.5%. Los Angeles Pre-hospital Stroke Screen performed best in terms of specificity 88.7% but had low sensitivity (73.9%). Melbourne Ambulance Stroke Screen had a balanced performance in terms of sensitivity (86%) and specificity (76%). Sensitivity analysis consisting of only prospective studies showed a similar range of sensitivity and specificity.
CONCLUSION
All the stroke screening tools included in the review were comparable, but no clear superior screening tool could be identified. Simple screening tools like Cincinnati prehospital stroke scale (CPSS) have similar performance compared to more complex tools.
Topics: Humans; Prospective Studies; Severity of Illness Index; Stroke; Emergency Service, Hospital; Mass Screening; Sensitivity and Specificity; Emergency Medical Services
PubMed: 36201961
DOI: 10.1016/j.jns.2022.120423 -
Journal of Family Psychology : JFP :... Jun 2022Reports an error in "High sensitivity and specificity screening for clinically significant intimate partner violence" by Richard E. Heyman, Katherine J. W. Baucom, Shu...
Reports an error in "High sensitivity and specificity screening for clinically significant intimate partner violence" by Richard E. Heyman, Katherine J. W. Baucom, Shu Xu, Amy M. Smith Slep, Jeffery D. Snarr, Heather M. Foran, Michael F. Lorber, Alexandra K. Wojda and David J. Linkh (, 2021[Feb], Vol 35[1], 80-91). In the article, the affiliation of Heather M. Foran was incorrectly listed as "Family Translational Research Group, New York University." Her correct affiliation is "Institute for Psychology, University of Klagenfurt, and Institute for Psychology, University of Braunschweig." In addition, there were two errors in Table 3 whereby the last row of column 1 should have been labeled "Any of the two items" rather than "Both items," and the final subheading should have read "Female → Male psychological CS-IPV (Male report) rather than "Male → Female psychological CS-IPV (Male report)." Finally, in the Supplemental Material, the second item of the "Screener for Clinically Significant IPV-Psychological" questionnaire should have been deleted. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2020-51524-001). The U.S. Preventive Services Task Force has recommended that clinicians screen patients for intimate partner violence (IPV). This article aims to develop and test the first screeners for clinically significant physical and psychological IPV (i.e., acts meeting criteria in the International Classification of Diseases (11th ed.; ICD-11; World Health Organization, 2019) and the (5th ed.; DSM-5; American Psychiatric Association, 2013). The goal was to derive screeners that (1) are maximally brief, while still achieving high sensitivity and specificity; (2) assess perpetration and victimization when either men or women are reporting; and (3) use ICD-11/ criteria as the reference standard. Random samples of active duty service members at 82 installations worldwide were obtained via e-mail invitation (2006: = 54,543; 2008: = 48,909); their response rates were excellent for long general population surveys with no payment (2006: 44.7%, 2008: 49.0%). The population of spouses at the participating installation was invited by mailed postcard (2006: = 19,722; 2008: = 12,127; response rates-2006: 12.3%, 2008: 10.8%). Clinically significant physical intimate partner violence can be effectively screened with as few as four items, with sensitivities > 90% and specificities > 95%; clinically significant psychological intimate partner violence can be screened with two items. Men and women can be screened with equivalent accuracy, as can those committing the violence and those victimized by it. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Topics: Bullying; Crime Victims; Female; Humans; Intimate Partner Violence; Male; Mass Screening; Surveys and Questionnaires
PubMed: 35311319
DOI: 10.1037/fam0000974