scholarly journals Új lehetőség a szisztolés szívelégtelenség (HFrEF) kezelésében: omecamtiv-mecarbil

2021 ◽  
Vol 51 (2) ◽  
pp. 118-124
Author(s):  
Arnold Péter Ráduly ◽  
Attila Tóth ◽  
Zoltán Papp ◽  
Attila Borbély
Keyword(s):  
Genetic Testing ◽  
Expert Panel ◽  
Clinical Care ◽  
Cardiovascular Disorder ◽  
Chain Gene ◽  
Web Based ◽  
Inherited Cardiomyopathy ◽  
Omecamtiv Mecarbil ◽  
Next Generation Sequencing Ngs ◽  
Population Databases

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder worldwide which exhibits considerable genetic heterogeneity. Widespread utilization of next-generation sequencing (NGS) in HCM has uncovered substantial genetic variation and highlighted the importance of a standardized approach to variant interpretation. According to this, accurate and consistent interpretation of sequence variants is essential for effective clinical care for individuals and their families with HCM. With this regard, the 2015 guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) were widely applicable, but several elements lacked specificity for given genes or diseases. The latter guideline was adapted for the most frequent causative HCM gene, the beta myosin heavy chain gene (MYH7) by the ClinGen (Clinical Genome Resource) expert panel, the Inherited Cardiomyopathy Expert Panel. Due to the adaptation, the guideline became gene-specific, with general considerations which are widely adaptable for most of the causative genes in HCM. Based on the modified guideline, web-based interpretation algorithms have been developed which integrate data from population databases and define pathogenicity of different variants independent of the observer, therefore aiding standardized clinical interpretation of genetic testing. The latter approach serves as a basis for recommendation for genetic testing in the recent ACC/AHA HCM guideline published in 2020. The current review is meant to compile the latest advances in HCM genetic testing in clinical practice, while bringing into focus some of the ongoing challenges clinical geneticists are still facing. Although nowadays the interpretation of genetic findings is two steps closer to a more accurate approach due to gene adaptation and automatization, the multitude of putative causative genes have been once again reduced to the 8 sarcomere genes, a backward step.

scholarly journals Genetic diagnosis in hypertrophic cardiomyopathy: two steps forward, one step back

2021 ◽  
Vol 51 (2) ◽  
pp. 109-117
Author(s):  
Lidia Hategan ◽  
Beáta Csányi ◽  
János Borbás ◽  
Eszter Dalma Pálinkás ◽  
Hedvig Takács ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hypertrophic Cardiomyopathy ◽  
Expert Panel ◽  
Clinical Care ◽  
Genetic Diagnosis ◽  
Cardiovascular Disorder ◽  
Chain Gene ◽  
Web Based ◽  
Inherited Cardiomyopathy ◽  
Next Generation Sequencing Ngs

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder worldwide which exhibits considerable genetic heterogeneity. Widespread utilization of next-generation sequencing (NGS) in HCM has uncovered substantial genetic variation and highlighted the importance of a standardized approach to variant interpretation. According to this, accurate and consistent interpretation of sequence variants is essential for effective clinical care for individuals and their families with HCM. With this regard, the 2015 guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) were widely applicable, but several elements lacked specificity for given genes or diseases. The latter guideline was adapted for the most frequent causative HCM gene, the beta myosin heavy chain gene (MYH7) by the ClinGen (Clinical Genome Resource) expert panel, the Inherited Cardiomyopathy Expert Panel. Due to the adaptation, the guideline became gene-specific, with general considerations which are widely adaptable for most of the causative genes in HCM. Based on the modified guideline, web-based interpretation algorithms have been developed which integrate data from population databases and define pathogenicity of different variants independent of the observer, therefore aiding standardized clinical interpretation of genetic testing. The latter approach serves as a basis for recommendation for genetic testing in the recent ACC/AHA HCM guideline published in 2020. The current review is meant to compile the latest advances in HCM genetic testing in clinical practice, while bringing into focus some of the ongoing challenges clinical geneticists are still facing. Although nowadays the interpretation of genetic findings is two steps closer to a more accurate approach due to gene adaptation and automatization, the multitude of putative causative genes have been once again reduced to the 8 sarcomere genes, a backward step.

scholarly journals Framing Effects on Decision-Making for Diagnostic Genetic Testing: Results from a Randomized Trial

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 941
Author(s):  
Andrew A. Dwyer ◽  
Hongjie Shen ◽  
Ziwei Zeng ◽  
Matt Gregas ◽  
Min Zhao
Keyword(s):  
Genetic Testing ◽  
Behavioral Control ◽  
Clinical Care ◽  
Framing Effects ◽  
Web Based ◽  
Common Life ◽  
Decision Frames ◽  
Opt Out ◽  
Life Threatening ◽  
Individual Self

Genetic testing is increasingly part of routine clinical care. However, testing decisions may be characterized by regret as findings also implicate blood relatives. It is not known if genetic testing decisions are affected by the way information is presented (i.e., framing effects). We employed a randomized factorial design to examine framing effects on hypothetical genetic testing scenarios (common, life-threatening disease and rare, life-altering disease). Participants (n = 1012) received one of six decision frames: choice, default (n = 2; opt-in, opt-out), or enhanced choice (n = 3, based on the Theory of Planned Behavior). We compared testing decision, satisfaction, regret, and decision cognitions across decision frames and between scenarios. Participants randomized to ‘choice’ were least likely to opt for genetic testing compared with default and enhanced choice frames (78% vs. 83–91%, p < 0.05). Neither satisfaction nor regret differed across frames. Perceived autonomy (behavioral control) predicted satisfaction (B = 0.085, p < 0.001) while lack of control predicted regret (B = 0.346, p < 0.001). Opting for genetic testing did not differ between disease scenarios (p = 0.23). Results suggest framing can nudge individuals towards opting for genetic testing. These findings have important implications for individual self-determination in the genomic era. Similarities between scenarios with disparate disease trajectories point to possible modular approaches for web-based decisional support.

scholarly journals A framework for the evaluation of patients with congenital facial weakness

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bryn D. Webb ◽  
Irini Manoli ◽  
Elizabeth C. Engle ◽  
Ethylin W. Jabs
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Patient Population ◽  
Clinical Care ◽  
Diagnostic Algorithm ◽  
Accurate Diagnosis ◽  
Facial Weakness ◽  
The Core ◽  
Follow Up Studies

AbstractThere is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.

scholarly journals Long-Range PCR-Based NGS Applications to Diagnose Mendelian Retinal Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 1508
Author(s):  
Jordi Maggi ◽  
Samuel Koller ◽  
Luzy Bähr ◽  
Silke Feil ◽  
Fatma Kivrak Pfiffner ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Long Range ◽  
Copy Number Variants ◽  
Retinal Disease ◽  
Promoter Regions ◽  
Long Range Pcr ◽  
Cost Efficient ◽  
Nucleotide Resolution ◽  
Genomic Regions ◽  
Next Generation Sequencing Ngs

The purpose of this study was to develop a flexible, cost-efficient, next-generation sequencing (NGS) protocol for genetic testing. Long-range polymerase chain reaction (PCR) amplicons of up to 20 kb in size were designed to amplify entire genomic regions for a panel (n = 35) of inherited retinal disease (IRD)-associated loci. Amplicons were pooled and sequenced by NGS. The analysis was applied to 227 probands diagnosed with IRD: (A) 108 previously molecularly diagnosed, (B) 94 without previous genetic testing, and (C) 25 undiagnosed after whole-exome sequencing (WES). The method was validated with 100% sensitivity on cohort A. Long-range PCR-based sequencing revealed likely causative variant(s) in 51% and 24% of proband from cohorts B and C, respectively. Breakpoints of 3 copy number variants (CNVs) could be characterized. Long-range PCR libraries spike-in extended coverage of WES. Read phasing confirmed compound heterozygosity in 5 probands. The proposed sequencing protocol provided deep coverage of the entire gene, including intronic and promoter regions. Our method can be used (i) as a first-tier assay to reduce genetic testing costs, (ii) to elucidate missing heritability cases, (iii) to characterize breakpoints of CNVs at nucleotide resolution, (iv) to extend WES data to non-coding regions by spiking-in long-range PCR libraries, and (v) to help with phasing of candidate variants.

Challenges in genetic testing: clinician variant interpretation processes and the impact on clinical care

2021 ◽  
Author(s):  
Courtney Berrios ◽  
Emily A. Hurley ◽  
Laurel Willig ◽  
Isabelle Thiffault ◽  
Carol Saunders ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Care ◽  
Variant Interpretation ◽  
The Impact

scholarly journals Development of a tool to assess health applications for healthcare providers: A Delphi Expert Panel Study (Preprint)

2020 ◽  
Author(s):  
Immaculada Grau-Corral ◽  
Percy Efran Pantoja ◽  
Francisco J. Grajales III ◽  
Belchin Kostov ◽  
Valentí Aragunde ◽  
...  
Keyword(s):  
Literature Review ◽  
Health Care Providers ◽  
Expert Panel ◽  
Panel Study ◽  
Healthcare Providers ◽  
Care Providers ◽  
Web Based ◽  
Health Apps ◽  
Agreement Assessment ◽  
Health Applications

BACKGROUND The presence of the mobile phone and devices is generating knowledge about the use of applications to support patient care, but there are few recommendations for apps dedicated to healthcare professionals OBJECTIVE To establish a validated scale to assess healthcare mobile applications is the most efficient step for health care providers and systems. The main goal is to create and validate a tool to evaluate health apps destined to be used by health professionals. METHODS A five steps simplified methodology to assess of the scale was followed. The first step consists of building a scale for professionals based on a literature review. Next step would be an expert panel validation by a Delphi method, rating web-based questionnaires to evaluate inclusion and weight of the indicators. It was agreed to carry out, as many iterations as necessary, to reach a consensus of 75%. Finally, a pilot of the score was developed to evaluate the reliability of the scale. For the inter-rater agreement assessment during the pilot, the Cohen Kappa was used. RESULTS After the literature review, a first scale draft was developed. Two rounds of interactions of the local investigation group and the external panel of experts were needed to select final indicators. Seventeen indicators were included in the score. For the pilot test, 280 apps were evaluated and 66 meet the criteria. The interrater agreement was strong (higher than 82% with significant kappa >0.72 per app and item). CONCLUSIONS We have developed, with a reproducible methodology, a tool that allows us to evaluate health applications for clinical, surgical and general medical providers. The ISYScore-PRO scale to be reliable and reproducible. The assessment permitted to consolidate every step of the methodology. We were able to reach consensus on the dimensions and items on the scale with only two rounds. The process of validation included two robust methodologies. The ISYScore-PRO scale is reliable and reproducible.

scholarly journals Automated Monitoring of Suicidal Adolescents’ Digital Media Use: Qualitative Study Exploring Acceptability Within Clinical Care

10.2196/26031 ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. e26031
Author(s):  
Candice Biernesser ◽  
Jamie Zelazny ◽  
David Brent ◽  
Todd Bear ◽  
Christina Mair ◽  
...  
Keyword(s):  
Digital Media ◽  
Language Processing ◽  
Media Use ◽  
Clinical Care ◽  
Unintended Consequences ◽  
Text Messages ◽  
Suicidal Risk ◽  
Web Based ◽  
Automated Monitoring ◽  
Media Monitoring

Background Monitoring linguistic cues from adolescents’ digital media use (DMU; ie, digital content transmitted on the web, such as through text messages or social media) that could denote suicidal risk offers a unique opportunity to protect adolescents vulnerable to suicide, the second leading cause of death among youth. Adolescents communicate through digital media in high volumes and frequently express emotionality. In fact, web-based disclosures of suicidality are more common than in-person disclosures. The use of automated methods of digital media monitoring triggered by a natural language processing algorithm offers the potential to detect suicidal risk from subtle linguistic units (eg, negatively valanced words, phrases, or emoticons known to be associated with suicidality) present within adolescents’ digital media content and to use this information to respond to alerts of suicidal risk. Critical to the implementation of such an approach is the consideration of its acceptability in the clinical care of adolescents at high risk of suicide. Objective Through data collection among recently suicidal adolescents, parents, and clinicians, this study examines the current context of digital media monitoring for suicidal adolescents seeking clinical care to inform the need for automated monitoring and the factors that influence the acceptance of automated monitoring of suicidal adolescents’ DMU within clinical care. Methods A total of 15 recently suicidal adolescents (aged 13-17 years), 12 parents, and 10 clinicians participated in focus groups, qualitative interviews, and a group discussion, respectively. Data were recorded, transcribed, and analyzed using thematic analysis. Results Participants described important challenges to the current strategies for monitoring the DMU of suicidal youth. They felt that automated monitoring would have advantages over current monitoring approaches, namely, by protecting web-based environments and aiding adolescent disclosure and support seeking about web-based suicidal risk communication, which may otherwise go unnoticed. However, they identified barriers that could impede implementation within clinical care, namely, adolescents’ and parents’ concerns about unintended consequences of automated monitoring, that is, the potential for loss of privacy or false alerts, and clinicians’ concerns about liability to respond to alerts of suicidal risk. On the basis of the needs and preferences of adolescents, parents, and clinicians, a model for automated digital media monitoring is presented that aims to optimize acceptability within clinical care for suicidal youth. Conclusions Automated digital media monitoring offers a promising means to augment detection and response to suicidal risk within the clinical care of suicidal youth when strategies that address the preferences of adolescents, parents, and clinicians are in place.

P–551 Blastocyst cohort size is not associated with embryo aneuploidy: comprehensive multi-centre data from current preimplantation genetic testing cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Vassena ◽  
A Lorenzon ◽  
A L Lopes ◽  
D Sakkas ◽  
A Korkidakis ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Maternal Age ◽  
Age Groups ◽  
Ovarian Response ◽  
Cohort Size ◽  
Preimplantation Genetic Testing ◽  
Indirect Measure ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Euploid Embryo

Abstract Study question Does blastocyst cohort size impact aneuploidy rates, evaluated by next generation sequencing (NGS)? Summary answer Embryo aneuploidy rates were independent of blastocyst cohort size across all patient ages. What is known already The effects of ovarian response on oocyte and embryo quality remain controversial. Several studies have proposed that a high response to ovarian stimulation may negatively impact oocyte competence. Alternatively, irrespective of maternal age, a poor ovarian response may potentially compromise embryo quality. Using blastocyst cohort size as an indirect measure of ovarian response, previous studies applying array comparative genomic hybridisation (aCGH) have demonstrated that the number of embryos available for biopsy does not impact embryo aneuploidy rates. Nevertheless, these findings remain to be confirmed in a comprehensive cohort, using current approaches for preimplantation genetic testing for aneuploidies (PGT-A). Study design, size, duration Retrospective, international, cohort study of 3998 patients from 16 clinics undergoing PGT-A from 2016–2020. We evaluated 11665 blastocysts, tested using trophectoderm (TE) biopsy and next generation sequencing (NGS). To eliminate bias of multiple treatments, we considered only the first PGT-A cycle for all patients. Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated aneuploidy and mosaicism rates, as well as the proportion of patients who had at least one euploid embryo suitable for transfer. Findings were stratified according to SART-defined maternal age groups, &lt;35 (n = 698/2622 patients/blastocysts), 35–37 (n = 988/3141 patients/blastoycsts), 38–40 (n = 1447/3939 patients/blastocysts), 41–42 (653/1562 patients/blastocysts) and &gt;42 (212/401 patients/blastocysts) and blastoycst cohort size (1–2, 3–5, 6–9 and 10 or more biopsied blastocysts). Main results and the role of chance The mean maternal age was 37.0±3.7. The overall embryo aneuploidy rate was 50.6% (5904/11665), while mosaicism was established in 4.0% (469/11665) of blastocysts. As expected, the proportion of aneuploid embryos increased steadily with advancing maternal age (31.8%, 41.5%, 58.4%, 71.2%, 87.8%; p &lt; 0.0001), while mosaicism rates did not vary significantly (p = 0.2). Within each age group, we observed no association between the number of blastocysts biopsied and aneuploidy or mosaicism rates. However, as previously suggested, the chance of having at least one euploid embryo increased linearly with the number of embryos biopsied. We observed that young patients (&lt;35) with 1–2 blastocysts had a 70.4% of having at least one embryo suitable for transfer, which increased to 96.4% and 99.2% with 3–5 and 6–9 blastocysts, respectively. Similar trends were observed in the 36–38 and 39–40 age groups. Patients in the 40–41 age group had a significantly lower chance of having a suitable embryo for transfer. Nevertheless, the chance increased from 27.2% with 1–2 embryos to 61.2% with 3–5 blastocysts. Patients with &gt;10 embryos had at least one euploid embryo in 100% of cases, across all ages. Albeit, the numbers of patients within this category was low, and decreased significantly with advancing maternal age. Limitations, reasons for caution While blastocyst cohort size is considered to be an indirect measure of ovarian reserve, the number of oocytes retrieved was not evaluated. Our study only included the first PGT-A cycle for all patients. Subsequent, alterations in stimulation protocols may have resulted in an improved response in some patients. Wider implications of the findings: The comprehensive nature of the study, based on current PGT-A approaches and a large number of cycles across 16 centres increases clinical confidence in the notion that ovarian response is independent of embryo aneuploidy. Importantly, our findings may serve as a valuable clinical resource to guide patient counselling strategies. Trial registration number NA

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