Professionals' views on providing personalized recurrence risks for de novo mutations: Implications for genetic counseling.

When an apparent de novo (new) genetic change has been identified as the cause of a serious genetic condition in a child, many couples would like to know the risk of this happening again in a future pregnancy. Current practice provides families with a population average risk of 1%-2%. However, this figure is not accurate for any specific couple, and yet, they are asked to make decisions about having another child and/or whether to have prenatal testing. The PREcision Genetic Counseling And REproduction (PREGCARE) study is a new personalized assessment strategy that refines a couple's recurrence risk prior to a new pregnancy, by analyzing several samples from the parent-child trio (blood, saliva, swabs, and father's sperm) using deep sequencing and haplotyping. Overall, this approach can reassure ~2/3 of couples who have a negligible (<0.1%) recurrence risk and focus support on those at higher risk (i.e. when mosaicism is identified in one of the parents). Here we present a qualitative interview study with UK clinical genetics professionals (n = 20), which investigate the potential implications of introducing such a strategy in genetics clinics. While thematic analysis of the interviews indicated perceived clinical utility, it also indicates a need to prepare couples for the psychosocial implications of parent-of-origin information and to support their understanding of the assessment being offered. When dealing with personalized reproductive risk, a traditional non-directive approach may not meet the needs of practitioner and client(s) and shared decision-making provides an additional framework that may relieve some patient burden. Further qualitative investigation with couples is planned.

Using EMPOWER in daily life: a qualitative investigation of implementation experiences.

BACKGROUND: Digital self-management tools blended with clinical triage and peer support have the potential to improve access to early warning signs (EWS) based relapse prevention in schizophrenia care. However, the implementation of digital interventions in psychosis can be poor. Traditionally, research focused on understanding how people implement interventions has focused on the perspectives of mental health staff. Digital interventions are becoming more commonly used by patients within the context of daily life, which means there is a need to understand implementation from the perspectives of patients and carers. METHODS: Semi-structured one-on-one interviews with 16 patients who had access to the EMPOWER digital self-management intervention during their participation in a feasibility trial, six mental health staff members who supported the patients and were enrolled in the trial, and one carer participant. Interviews focused on understanding implementation, including barriers and facilitators. Data were coded using thematic analysis. RESULTS: The intervention was well implemented, and EMPOWER was typically perceived positively by patients, mental health staff and the carer we spoke to. However, some patients reported negative views and reported ideas for intervention improvement. Patients reported valuing that the app afforded them access to things like information or increased social contact from peer support workers that went above and beyond that offered in routine care. Patients seemed motivated to continue implementing EMPOWER in daily life when they perceived it was creating positive change to their wellbeing, but seemed less motivated if this did not occur. Mental health staff and carer views suggest they developed increased confidence patients could self-manage and valued using the fact that people they support were using the EMPOWER intervention to open up conversations about self-management and wellbeing. CONCLUSIONS: The findings from this study suggest peer worker supported digital self-management like EMPOWER has the potential to be implemented. Further evaluations of these interventions are warranted, and conducting qualitative research on the feasibility gives insight into implementation barriers and facilitators, improving the likelihood of interventions being usable. In particular, the views of patients who demonstrated low usage levels would be valuable.

Providing recurrence risk counselling for parents after diagnosis of a serious genetic condition caused by an apparently de novo mutation in their child: a qualitative investigation of the PREGCARE strategy with UK clinical genetics practitioners.

BACKGROUND: Diagnosis of a child with a genetic condition leads to parents asking whether there is a risk the condition could occur again with future pregnancies. If the cause is identified as an apparent de novo mutation (DNM), couples are currently given a generic, population average, recurrence risk of ~1%-2%, depending on the condition. Although DNMs usually arise as one-off events, they can also originate through the process of mosaicism in either parent; in this instance, the DNM is present in multiple germ cells and the actual recurrence risk could theoretically be as high as 50%. METHODS: Our qualitative interview study examined the views and reflections on current practice provided by UK practitioners working in clinical genetics (n=20) regarding the potential impact of PREcision Genetic Counselling And REproduction (PREGCARE)-a new preconception personalised recurrence risk assessment strategy. RESULTS: Those interviewed regarded PREGCARE as a very useful addition to risk management, especially for cases where it revised the risk downwards or clarified that a couple's personalised recurrence risk meets National Health Service thresholds for non-invasive prenatal testing, otherwise inaccessible based on the generic DNM recurrence risk. CONCLUSION: Participants said it could release some couples requiring reassurance from undergoing unnecessary invasive testing in future pregnancies. However, they regarded mosaicism and PREGCARE as complex concepts to communicate, requiring further training and additional appointment time for pre-test genetic counselling to prepare couples for all the possible outcomes of a personalised risk assessment, including potentially identifying the parental origin of the DNM, and to ensure informed consent.

Adoptees' views and experiences of direct-to-consumer (DTC) genomic testing: an exploratory interview study from the UK.

Direct-to-consumer (DTC) genomic testing for ancestry and health may appeal to adoptees looking to fill gaps in their family information. There are only a handful of published studies on adoptees' views and experiences of DTC testing and none of these is from the UK. The recent UK House of Commons Science and Technology Committee report (GB Parliament, House of Commons 2021) did not address the gains or challenges for adopted people specifically, although the Committee did consider that robust evidence of opportunities or risks for any user of a DTC testing kit is limited. In this study presented here, semi-structured interviews were conducted with ten UK adult adoptees recruited via social media. Reflexive thematic analysis (Braun and Clarke 2006, 2019) of the interview transcripts identified three main themes: Decisional influencers of longing, uncertainty and normalisation of DNA kit use; Informational drivers to gain clarity but avoid new worrisome information; and talk around Negotiating Visibility to birth family and commercial third parties. A further theme of Meaning Making related to adoptees' views of testing outcomes as bringing feelings of resolution or discordance. This study identified many challenging deliberations for adoptees in evaluating whether to take a DTC test and what to do when their results were returned. Additionally, adoptees' consideration of data privacy issues appears hampered by already having shared identifying information about themselves in their wider adoptee search. Further research is encouraged.

Perspectives of Trial Staff on the Barriers to Recruitment in a Digital Intervention for Psychosis and How to Work Around Them: Qualitative Study Within a Trial.

BACKGROUND: Recruitment processes for clinical trials of digital interventions for psychosis are seldom described in detail in the literature. Although trial staff have expertise in describing barriers to and facilitators of recruitment, a specific focus on understanding recruitment from the point of view of trial staff is rare, and because trial staff are responsible for meeting recruitment targets, a lack of research on their point of view is a key limitation. OBJECTIVE: The primary aim of this study was to understand recruitment from the point of view of trial staff and discover what they consider important. METHODS: We applied pluralistic ethnographic methods, including analysis of trial documents, observation, and focus groups, and explored the recruitment processes of the EMPOWER (Early Signs Monitoring to Prevent Relapse in Psychosis and Promote Well-being, Engagement, and Recovery) feasibility trial, which is a digital app-based intervention for people diagnosed with schizophrenia. RESULTS: Recruitment barriers were categorized into 2 main themes: service characteristics (lack of time available for mental health staff to support recruitment, staff turnover, patient turnover [within Australia only], management styles of community mental health teams, and physical environment) and clinician expectations (filtering effects and resistance to research participation). Trial staff negotiated these barriers through strategies such as emotional labor (trial staff managing feelings and expressions to successfully recruit participants) and trying to build relationships with clinical staff working within community mental health teams. CONCLUSIONS: Researchers in clinical trials for digital psychosis interventions face numerous recruitment barriers and do their best to work flexibly and to negotiate these barriers and meet recruitment targets. The recruitment process appeared to be enhanced by trial staff supporting each other throughout the recruitment stage of the trial.

Early Signs Monitoring to Prevent Relapse in Psychosis and Promote Well-Being, Engagement, and Recovery: Protocol for a Feasibility Cluster Randomized Controlled Trial Harnessing Mobile Phone Technology Blended With Peer Support.

BACKGROUND: Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions. OBJECTIVE: This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial. METHODS: We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants' own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support. RESULTS: Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation. CONCLUSIONS: The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15058.

A Socio-Technical Exploration for Reducing & Mitigating the Risk of Retained Foreign Objects.

A Retained Foreign Object (RFO) is a fairly infrequent but serious adverse event. An accurate rate of RFOs is difficult to establish due to underreporting but it has been estimated that incidences range between 1/1000 and 1/19,000 procedures. The cost of a RFO incident may be substantial and three-fold: (i) the cost to the patient of physical and/or psychological harm; (ii) the reputational cost to an institution and/or healthcare provider; and (iii) the financial cost to the taxpayer in the event of a legal claim. This Health Research Board-funded project aims to analyse and understand the problem of RFOs in surgical and maternity settings in Ireland and develop hospital-specific foreign object management processes and implementation roadmaps. This project will deploy an integrated evidence-based assessment methodology for social-technical modelling (Supply, Context, Organising, Process & Effects/ SCOPE Analysis Cube) and bow tie methodologies that focuses on managing the risks in effectively implementing and sustaining change. It comprises a multi-phase research approach that involves active and ongoing collaboration with clinical and other healthcare staff through each phase of the research. The specific objective of this paper is to present the methodological approach and outline the potential to produce generalisable results which could be applied to other health-related issues.

Maritime health: a review with suggestions for research.

International maritime health has largely developed within the sphere of occupational health services and international health problems. We reviewed publications in the journal International Maritime Health from 2000 to 2010 to establish the coverage of the journal and the scope of research in maritime health. We identified six thematic categories: healthcare access, delivery and integration; telehealth; non-communicable diseases and physical health problems; communicable diseases; psychological functioning and health; and safety-related issues. We describe the research within these themes and report on their publication prominence. We also analyse the research in terms of its geographical focus, the population groups addressed and the research methodologies used. We suggest a broadening of maritime research to include randomised controlled trials, longitudinal studies and more qualitative research; more research addressing the context for non-European seafarers; and research on seafarers spouses and family supports and obligations. We also recommend more research on psychosocial and cultural issues and on telehealth, as well as the development of a stronger systems perspective for promoting maritime health.

Evaluating the iterative development of VR/AR human factors tools for manual work.

This paper outlines the approach taken to iteratively evaluate a set of VR/AR (virtual reality / augmented reality) applications for five different manual-work applications - terrestrial spacecraft assembly, assembly-line design, remote maintenance of trains, maintenance of nuclear reactors, and large-machine assembly process design - and examines the evaluation data for evidence of the effectiveness of the evaluation framework as well as the benefits to the development process of feedback from iterative evaluation. ManuVAR is an EU-funded research project that is working to develop an innovative technology platform and a framework to support high-value, high-knowledge manual work throughout the product lifecycle. The results of this study demonstrate the iterative improvements reached throughout the design cycles, observable through the trending of the quantitative results from three successive trials of the applications and the investigation of the qualitative interview findings. The paper discusses the limitations of evaluation in complex, multi-disciplinary development projects and finds evidence of the effectiveness of the use of the particular set of complementary evaluation methods incorporating a common inquiry structure used for the evaluation - particularly in facilitating triangulation of the data.

Impact of plasmid size on cellular oxygen demand in Escherichia coli.

Escherichia coli DH5alpha harbouring either pBGS18, a 4.4 kb pUC-based plasmid, or pQR150, a 20 kb derivative of pBGS18, were grown in glucose-limited chemostat culture to investigate the effects of plasmid size and recombinant protein production on oxygen demand. Under non-induced conditions, where no recombinant protein was expressed, the cellular oxygen demand of cells harbouring pBGS18 and pQR150 was not significantly different, mean specific oxygen uptake rate (OUR) being 0.75+/-0.24 and 0.78+/-0.32 mmol/h per mg of plasmid respectively. Under isopropyl beta-D-thiogalactoside-induced conditions, where recombinant protein was expressed, cells harbouring pBGS18 demonstrated a statistically insignificant 37% increase in mean specific OUR while those harbouring pQR150 demonstrated a statistically significant 415% increase. It is concluded that plasmid size does not significantly affect oxygen demand and that increasing oxygen demand observed with increasing plasmid size is due to production of recombinant protein.