Job satisfaction and intent to stay in neonatal nursing in England and Wales: a study protocol.

BACKGROUND: Nursing shortages are an ongoing concern for neonatal units, with many struggling to meet recommended nurse to patient ratios. Workforce data underlines the high proportion of neonatal nurses nearing retirement and a reduced number of nurses joining the profession. In order to recommend strategies to increase recruitment and retention to neonatal nursing, we need to understand the current challenges nurses are facing within the profession. The aim of this study is to investigate current job satisfaction, burnout, and intent to stay in neonatal nursing in England and Wales. METHODS: This study has two parts: (1) a systematic review exploring job satisfaction, burnout and intent to stay in neonatal nursing, and any previous interventions undertaken to enhance nurse retention, (2) an online survey of neonatal nurses in England and Wales exploring job satisfaction, burnout and intent to stay in neonatal nursing. We will measure job satisfaction using the McCloskey Mueller Satisfaction Scale (MMSS), burnout using the Copenhagen Burnout Inventory (CBI) and the Nurse Retention Index (NRI) will be used to measure intent to stay. All nurses working in neonatal units in England and Wales will be eligible to participate in the nursing survey. DISCUSSION: Retention of neonatal nurses is a significant issue affecting neonatal units across England and Wales, which can impact the delivery of safe patient care. Exploring job satisfaction and intent to stay will enable the understanding of challenges being faced and how best to support neonatal nurses. Identifying localised initiatives for the geographical areas most at risk of nurses leaving would help to improve nurse retention.

Evaluating parental personal utility of pediatric genetic and genomic testing in a diverse, multilingual population.

There is increasing evidence of the clinical utility of genetic and genomic testing (GT); however, factors influencing personal utility of GT, especially in diverse, multilingual populations, remain unclear. We explored these factors in a diverse cohort of parents/guardians (participants) whose children received clinical GT through the NYCKidSeq program. A total of 847 participants completed surveys at baseline, post-results disclosure, and 6 months (6m) post-results. The largest population groups were Hispanic/Latino(a) (48%), White/European American (24%), and Black/African American (16%). Personal utility was assessed using the Personal Utility (PrU) scale, adapted for pediatric populations and included on the surveys. Three PrU subscales were identified using factor analysis: practical, educational, and parental psychological utility. Overall personal utility summary score and the three subscales significantly decreased after receiving results and over time. Hispanic/Latino(a) participants identified greater overall personal utility than European American and African American participants at all time points (p < 0.001) as did participants whose children received positive/likely positive results compared with those with negative and uncertain results (post-results: p < 0.001 and p < 0.001; 6m post-results: p = 0.002 and p < 0.001, respectively). Post-results, higher subscale scores were associated with lower education levels (practical, parental psychological: p ≤ 0.02) and higher levels of trust in the healthcare system (practical, parental psychological: p ≤ 0.04). These findings help to understand the perspectives of diverse parents/guardians, which is critical to tailoring pre- and post-test counseling across a variety of populations and clinical settings.

'I don't want him to always be so far behind': Parental perceptions of child independence in the context of extreme prematurity; a qualitative study.

This study addresses the paucity of research on parents of extremely preterm adolescents (born <27 weeks of gestation) and their experiences within the framework of parental determinism. We conducted semi-structured interviews with twenty-two mothers and one father. Data were analysed thematically, revealing three overarching themes and eight subthemes shaping parental accounts. These themes centred on parental ambitions for their children, their perceptions of their child's abilities, and the parenting behaviours employed to support parental aspirations. Parents' actions were influenced by their ambitions and the belief that they could impact their child's future independence. While some parents adopted 'trusting', non-intensive parenting behaviours, those anticipating challenges for their child's future independence resorted to intensive parenting practices. These findings align with the concept of parental determinism, emphasising the perceived causal link between present parental actions and future child outcomes. In the context of extreme prematurity, a nuanced understanding of parental perceptions regarding their child's future independence aligned with a delicate balance between hope and realistic aspiration is crucial for enhancing parental support and well-being.

Correction: Investigating Father or Partner Involvement in Family Integrated Care in Neonatal Units: Protocol for a Prospective, Multicenter, Multiphase Study.

[This corrects the article DOI: 10.2196/53160.].

Investigating Father or Partner Involvement in Family Integrated Care in Neonatal Units: Protocol for a Prospective, Multicenter, Multiphase Study

BACKGROUND: Neonatal unit (NU) admissions for premature babies can last for months, which can significantly impact parental mental health (MH) with symptoms of depression, stress, and anxiety. Literature suggests fathers experience comparable MH symptoms to mothers. Family integrated care (FICare) is a culture where parents are collaborators and partners in caring for their hospitalized newborns. FICare improves infant outcomes and maternal MH. Similar reports on fathers are limited. OBJECTIVE: The primary aim of this study is to investigate the impact of supporting father or partner engagement in FICare of preterm infants on their MH up to 6 weeks postdischarge. The secondary aim is to investigate the impact on maternal MH. METHODS: This is a 2-phase study: phase 1 to gather baseline information and phase 2 to assess the impact of enhanced father or partner engagement in FICare on their MH, involving 2 NUs (tertiary and level 2). Enhanced FICare will be developed and introduced (eg, information booklet, workbook, classes, and a father peer-support group) alongside standard FICare practices. Father or partner MH will be assessed with semistructured qualitative interviews and validated questionnaires: Generalized Anxiety Disorder Assessment, Patient Health Questionnaire, and Parental Stressor Scale: Neonatal Intensive Care Unit from NU admission to 6 weeks postdischarge. Mothers will be assessed by focus groups and the same questionnaires. Descriptive statistics and appropriate comparative tests, such as the 2-tailed t test, will be used to analyze and compare phase 1 and 2 data. Qualitative data will be coded line by line with the use of NVivo (Lumivero) and thematically analyzed. Simultaneously, systematic reviews (SRs) of fathers' experiences of FICare and their MH outcomes will be conducted. The study was approved by the National Research Ethics Committee (22/EM/0140) in August 2022. A parent advisory group was formed to advise on the study methodology, materials, involvement of participant parents, and dissemination of study findings. RESULTS: A recent SR demonstrated that data saturation is likely to be achieved by interviewing 9 to 17 participants. We will study a maximum of 20 parents of infants born at less than 33 weeks' gestation in each phase. As of October 2023, the study was ongoing. The SR studies are registered with the PROSPERO database (324275 and 306760). The projected end date for data collection is July 2024; data analysis will be conducted in November 2024 and publication will occur in 2025. CONCLUSIONS: The study aims to demonstrate the feasibility of using a father or partner-sensitive FICare model for parents of premature babies with a positive impact on their MH. It will demonstrate the feasibility of providing FICare to extremely premature babies receiving intensive care. This study may support the development of inclusive FICare guidelines for nonbirthing parents and their extremely premature infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06022991; https://classic.clinicaltrials.gov/ct2/show/NCT06022991. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53160.

Epigenetic Priming Enhances Chondrogenic Potential of Expanded Chondrocytes.

Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure, such as matrix-induced autologous chondrocyte implantation. Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to (1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists after the transfer to a three-dimensional (3D) culture; and (2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded bovine chondrocytes, used as a model system. Chromatin architecture remodeling of H3K27me3 and H3K9me3 was observed at 0 population doublings, 8 population doublings, and 16 population doublings (PD16) in a two-dimensional (2D) culture and after encapsulation of the expanded chondrocytes in a 3D hydrogel culture. Chondrocytes were treated with inhibitors of epigenetic modifiers (epigenetic priming) for PD16 and then encapsulated in 3D hydrogels. Chromatin architecture of chondrocytes and gene expression were evaluated before and after encapsulation. We observed a change in chromatin architecture of epigenetic modifications H3K27me3 and H3K9me3 during chondrocyte dedifferentiation. Although inhibiting enzymes that modify H3K27me3 and H3K9me3 did not alter the dedifferentiation process in 2D culture, applying these treatments during the 2D expansion did increase the expression of select chondrogenic genes and protein deposition of type II collagen when transferred to a 3D environment. Overall, we found that epigenetic priming of expanded bovine chondrocytes alters the cell fate when chondrocytes are later encapsulated into a 3D environment, providing a potential method to enhance the success of cartilage regeneration procedures.

Hazard Assessment and Remediation Tool for Simulation-Based Healthcare Facility Design Testing.

OBJECTIVES: To develop an objective, structured observational tool to enable identification and measurement of hazards in the built environment when applied to audiovisual recordings of simulations by trained raters. BACKGROUND: Simulation-based facility design testing is increasingly used to optimize safety of healthcare environments, often relying on participant debriefing or direct observation by human factors experts. METHODS: Hazard categories were defined through participant debriefing and detailed review of pediatric intensive care unit in situ simulation videos. Categories were refined and operational definitions developed through iterative coding and review. Hazard detection was optimized through the use of structured coding protocols and optimized camera angles. RESULTS: Six hazard categories were defined: (1) slip/trip/fall/injury risk, impaired access to (2) patient or (3) equipment, (4) obstructed path, (5) poor visibility, and (6) infection risk. Analysis of paired and individual coding demonstrated strong overall reliability (0.89 and 0.85, Gwet's AC1). Reliability coefficients for each hazard category were >0.8 for all except obstructed path (0.76) for paired raters. Among individual raters, reliability coefficients were >0.8, except for slip/trip/fall/injury risk (0.68) and impaired access to equipment (0.77). CONCLUSIONS: Hazard Assessment and Remediation Tool (HART) provides a framework to identify and quantify hazards in the built environment. The tool is highly reliable when applied to direct video review of simulations by either paired raters or trained single clinical raters. Subsequent work will (1) assess the tool's ability to discriminate between rooms with different physical attributes, (2) develop strategies to apply HART to improve facility design, and (3) assess transferability to non-ICU acute care environments.

The NeoPACE study: study protocol for the development of a core outcome set for neonatal palliative care.

BACKGROUND: Neonatal death is the leading category of death in children under the age of 5 in the UK. Many babies die following decisions between parents and the neonatal team; when a baby is critically unwell, with the support of healthcare professionals, parents may make the decision to stop active treatment and focus on ensuring their baby has a 'good' death. There is very little evidence to support the clinical application of neonatal palliative care and/or end-of-life care, resulting in variation in clinical provision between neonatal units. Developing core outcomes for neonatal palliative care would enable the development of measures of good practice and enhance our care of families. The aim of this study is to develop a core outcome set with associated tools for measuring neonatal palliative care. METHOD: This study has four phases: (1) identification of potential outcomes through systematic review and qualitative interviews with key stakeholders, including parents and healthcare professionals (2) an online Delphi process with key stakeholders to determine core outcomes (3) identification of outcome measures to support clinical application of outcome use (4) dissemination of the core outcome set for use across neonatal units in the UK. Key stakeholders include parents, healthcare professionals, and researchers with a background in neonatal palliative care. DISCUSSION: Developing a core outcome set will standardise minimum reported outcomes for future research and quality improvement projects designed to determine the effectiveness of interventions and clinical care during neonatal palliative and/or end-of-life care. The core outcome set will provide healthcare professionals working in neonatal palliative and/or end-of-life support with an increased and consistent evidence base to enhance practice in this area. TRIAL REGISTRATION: The study has been registered with the COMET initiative ( https://www.comet-initiative.org/Studies/Details/1470 ) and the systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023451068).

The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families.

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.

The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic counseling in racially and ethnically diverse families.

Background: Digital solutions are needed to support rapid increases in the application of genetic and genomic tests (GT) in diverse clinical settings and patient populations. We developed GUÍA, a bi-lingual web-based platform that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial evaluated GUÍA's impact on understanding of GT results. Methods: NYCKidSeq enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GT. Families were randomized to genetic counseling with GUÍA (intervention) or standard of care (SOC) genetic counseling for results disclosure. Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6-months later. Survey measures assessed the primary study outcomes of perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. We used regression models to evaluate the association between the intervention and the study outcomes. Results: The analysis included 551 participants, 270 in the GUÍA arm and 281 in SOC. Participants' mean age was 41.1 years and 88.6% were mothers. Most participants were Hispanic/Latino(a) (46.3%), White/European American (24.5%), or Black/African American (15.8%). Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR=2.8, CI[1.004,7.617], P=0.049) and maintained higher objective understanding over time (OR=1.1, CI[1.004, 1.127], P=0.038) compared to those in the SOC arm. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR=3.9, CI[1.6, 9.3], P=0.003), confidence (OR=2.7, CI[1.021, 7.277], P=0.046), and objective understanding (OR=1.1, CI[1.009, 1.212], P=0.032) compared to SOC . Conclusions: This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions. These findings build a case for utilizing GUÍA to deliver complex and often ambiguous genetic results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics. Trial Registration: Clinicaltrials.gov identifier NCT03738098.

Neonatal organ donation: Retrospective audit into potential donation in a single neonatal unit.

BACKGROUND: Research has shown that many babies who die in neonatal units could have been potential tissue and/or organ donors. Despite the existence of guidelines supporting its implementation, the incidence of neonatal donation remains rare in the United Kingdom. AIM: The aim of this audit was to retrospectively determine potential eligibility for neonatal tissue and/or organ donation referral in infants who died in a single UK tertiary-level neonatal unit between 2012 and 2021. Cause of death and documentation of any discussions held regarding referral for donation were also explored. STUDY DESIGN: An audit was undertaken to identify all neonatal deaths at a single tertiary-level NICU in London from 2012-2021. Infants who retrospectively could have been referred as potential tissue and/or organ donors were identified using current NHS Blood and Transplant inclusion and exclusion criteria. RESULTS AND CONCLUSION: A significant missed potential for neonatal tissue and/or organ donation referrals was identified, which is likely not just limited to the unit audited. Causes of death were as expected for a tertiary level neonatal unit and centre for therapeutic cooling of babies born with hypoxic perinatal brain injuries. Only one documented conversation was found regarding neonatal donation. RELEVANCE TO CLINICAL PRACTICE: To enable conversations regarding neonatal donation to become a routine part of end-of-life care discussions with families as appropriate, good links between neonatal healthcare professionals and Specialist Nurses in Organ Donation need to be established. This will facilitate the referral of all suitable neonates as potential donors and ensure that neonatal staff feel supported to care for babies identified as potential donors.

Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.

Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.

Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.

PURPOSE: Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions. METHODS: Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design. RESULTS: A total of 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs TGPs in Hispanic/Latino(a) (17.2% vs 9.5%, P < .001) and White/European American (19.8% vs 7.9%, P < .001) but not in Black/African American (11.5% vs 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS. CONCLUSION: GS may yield up to twice as many diagnoses in pediatric patients compared with TGP testing but not yet across all population groups.

National priority setting partnership using a Delphi consensus process to develop neonatal research questions suitable for practice-changing randomised trials in the UK.

BACKGROUND: The provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically, neonatal research topics have been selected by researchers; prioritisation processes involving wider stakeholder groups have generally identified research themes rather than specific questions amenable to interventional trials. OBJECTIVE: To involve stakeholders including parents, healthcare professionals and researchers to identify and prioritise research questions suitable for answering in neonatal interventional trials in the UK. DESIGN: Research questions were submitted by stakeholders in population, intervention, comparison, outcome format through an online platform. Questions were reviewed by a representative steering group; duplicates and previously answered questions were removed. Eligible questions were entered into a three-round online Delphi survey for prioritisation by all stakeholder groups. PARTICIPANTS: One hundred and eight respondents submitted research questions for consideration; 144 participants completed round one of the Delphi survey, 106 completed all three rounds. RESULTS: Two hundred and sixty-five research questions were submitted and after steering group review, 186 entered into the Delphi survey. The top five ranked research questions related to breast milk fortification, intact cord resuscitation, timing of surgical intervention in necrotising enterocolitis, therapeutic hypothermia for mild hypoxic ischaemic encephalopathy and non-invasive respiratory support. CONCLUSIONS: We have identified and prioritised research questions suitable for practice-changing interventional trials in neonatal medicine in the UK at the present time. Trials targeting these uncertainties have potential to reduce research waste and improve neonatal care.

Global Policy and Practice for Intrauterine Fetal Resuscitation During Fetal Surgery for Open Spina Bifida Repair.

Importance: Globally accepted recommendations suggest that a woman should be between 19 weeks and 25 weeks plus 6 days of pregnancy to be considered eligible for fetal closure of open spina bifida. A fetus requiring emergency delivery during surgery is therefore potentially considered viable and thus eligible for resuscitation. There is little evidence, however, to support how this scenario is addressed in clinical practice. Objective: To explore current policy and practice for fetal resuscitation during fetal surgery for open spina bifida in centers undertaking fetal surgery. Design, Setting, and Participants: An online survey was designed to identify current policies and practices in place to support fetal surgery for open spina bifida, exploring experiences and management of emergency fetal delivery and fetal death during surgery. The survey was emailed to 47 fetal surgery centers in 11 countries where fetal spina bifida repair is currently performed. These centers were identified through the literature, the International Society for Prenatal Diagnosis center repository, and an internet search. Centers were contacted between January 15 and May 31, 2021. Individuals volunteered participation through choosing to complete the survey. Main Outcomes and Measures: The survey comprised 33 questions of mixed multiple choice, option selection, and open-ended formats. Questions explored policy and practice supporting fetal and neonatal resuscitation during fetal surgery for open spina bifida. Results: Responses were obtained from 28 of 47 centers (60%) in 11 countries. Twenty cases of fetal resuscitation during fetal surgery during the last 5 years were reported across 10 centers. Four cases of emergency delivery during fetal surgery after maternal and/or fetal complications during the last 5 years were reported across 3 centers. Fewer than half the 28 centers (n = 12 [43%]) had policies in place to support practice in the event of either imminent fetal death (during or after fetal surgery) or the need for emergency fetal delivery during fetal surgery. Twenty of 24 centers (83%) reported preoperative parental counseling on the potential need for fetal resuscitation prior to fetal surgery. The gestational age at which centers would attempt neonatal resuscitation after emergency delivery varied from 22 weeks and 0 days to more than 28 weeks. Conclusions: In this global survey study of 28 fetal surgical centers, there was no standard practice about how fetal resuscitation or subsequent neonatal resuscitation was managed during open spina bifida repair. Further collaboration between professionals and parents is required to ensure sharing of information to support knowledge development in this area.

Parental experiences of live video streaming technology in neonatal care in England: a qualitative study.

BACKGROUND: The use of bedside cameras in neonatal units facilitates livestreaming of infants to support parental and family bonding when they are unable to be physically present with their baby. This study aimed to explore the experiences of parents of infants previously admitted for neonatal care and who used live video streaming to view their baby in real-time. METHODS: Qualitative semi-structured interviews were conducted after discharge with parents of infants admitted for neonatal care on a tertiary level neonatal unit in the UK in 2021. Interviews were conducted virtually, transcribed verbatim and uploaded into NVivo V12 to facilitate analysis. Thematic analysis by two independent researchers was undertaken to identify themes representing the data. RESULTS: Seventeen participants took part in sixteen interviews. Thematic analysis identified 8 basic themes which were grouped into 3 organizational themes: (1) family integration of the baby including parent-infant, sibling-infant, and wider family-infant attachment facilitated through livestreaming, (2) implementation of the livestreaming service including communication, initial set up of the livestreaming service, and areas for improvement, and (3) parental control including emotional, and situational control. CONCLUSIONS: The use of livestreaming technology can provide parents with opportunities to integrate their baby into their wider family and friendship community and gain a sense of control over their baby's admission for neonatal care. On-going parental education around how to use, and what to expect from, livestreaming technology is required to minimise any potential distress from viewing their baby online.

The TeleKidSeq pilot study: incorporating telehealth into clinical care of children from diverse backgrounds undergoing whole genome sequencing.

BACKGROUND: The COVID-19 pandemic forced healthcare institutions and many clinical research programs to adopt telehealth modalities in order to mitigate viral spread. With the expanded use of telehealth, there is the potential to increase access to genomic medicine to medically underserved populations, yet little is known about how best to communicate genomic results via telehealth while also ensuring equitable access. NYCKidSeq, a multi-institutional clinical genomics research program in New York City, launched the TeleKidSeq pilot study to assess alternative forms of genomic communication and telehealth service delivery models with families from medically underserved populations. METHODS: We aim to enroll 496 participants between 0 and 21 years old to receive clinical genome sequencing. These individuals have a neurologic, cardiovascular, and/or immunologic disease. Participants will be English- or Spanish-speaking and predominantly from underrepresented groups who receive care in the New York metropolitan area. Prior to enrollment, participants will be randomized to either genetic counseling via videoconferencing with screen-sharing or genetic counseling via videoconferencing without screen-sharing. Using surveys administered at baseline, results disclosure, and 6-months post-results disclosure, we will evaluate the impact of the use of screen-sharing on participant understanding, satisfaction, and uptake of medical recommendations, as well as the psychological and socioeconomic implications of obtaining genome sequencing. Clinical utility, cost, and diagnostic yield of genome sequencing will also be assessed. DISCUSSION: The TeleKidSeq pilot study will contribute to innovations in communicating genomic test results to diverse populations through telehealth technology. In conjunction with NYCKidSeq, this work will inform best practices for the implementation of genomic medicine in diverse, English- and Spanish-speaking populations.

Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.

Purpose: Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions. Methods: Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design. Results: 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses ( P < .001). Yield was greater for GS vs . TGPs in Hispanic/Latino(a) (17.2% vs . 9.5%, P < .001) and White/European American (19.8% vs . 7.9%, P < .001), but not in Black/African American (11.5% vs . 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs . White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS. Conclusion: GS may yield up to twice as many diagnoses in pediatric patients compared to TGP testing, but not yet across all population groups.

Detection of mosaic variants using genome sequencing in a large pediatric cohort.

The increased use of next-generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total of eleven cases: nine in which mosaic variants detected by genome sequencing (GS) and/or targeted gene panels (TGPs) were considered to be causative for the proband's phenotype, and two of apparent parental mosaicism. Variants were identified in the following genes: PHACTR1, SCN8A, KCNT1, CDKL5, NEXMIF, CUX1, TSC2, GABRB2, and SMARCB1. In addition, we identified one large duplication including three genes, UBE3A, GABRB3, and MAGEL2, and one large deletion including deletion of ARFGAP1, EEF1A2, CHRNA4, and KCNQ2. All patients were enrolled in the NYCKidSeq study, a research program studying the communication of genomic information in clinical care, as well as the clinical utility and diagnostic yield of GS for children with suspected genetic disorders in diverse populations in New York City. We observed variability in the correlation between reported variant allele fraction and the severity of the patient's phenotype, although we were not able to determine the mosaicism percentage in clinically relevant tissue(s). Although our study was not sufficiently powered to assess differences in mosaicism detection between the two testing modalities, we saw a trend toward better detection by GS as compared with TGP testing. This case series supports the importance of mosaicism in childhood-onset genetic conditions and informs guidelines for laboratory and clinical interpretation of mosaic variants detected by GS.

End-of-Life Decision Making Between Doctors and Parents in NICU: The Development and Assessment of a Conversation Analysis Coding Framework.

We report the development and assessment of a novel coding framework in the context of research into neonatal end-of-life decision making conversations. Data comprised 27 formal conversations between doctors and parents of critically ill babies, recorded in two neonatal intensive care units. The coding framework was developed from a qualitative analysis of the recordings using the method of conversation analysis (CA). Codes underpinned by our qualitative analysis had in the main moderate to strong agreement (inter-rater reliability) between coders; three codes had lower agreement reflecting the use of euphemisms for death and disability. Coding these interactions confirmed the significance of the doctors' talk in terms of parental involvement in decision-making, whilst highlighting areas warranting further qualitative analysis. This quantifiable representation provides a novel outcome based on evidence that is internal to the conversation rather than influenced by other factors related to the baby's care or outcome.