How should health policy and practice respond to the increased genetic risk associated with close relative marriage? results of a UK Delphi consensus building exercise

Objectives: (1) To explore professional and lay stakeholder views on the design and delivery of services in the area of consanguinity and genetic risk. (2) To identify principles on which there is sufficient consensus to warrant inclusion in a national guidance document. (3) To highlight differences of opinion that necessitate dialogue. (4) To identify areas where further research or development work is needed to inform practical service approaches.Design: Delphi exercise. Three rounds and one consensus conference.Setting: UK, national, web-based and face-to-face.Participants: Recruitment via email distribution lists and professional networks. 42 participants with varied professional and demographic backgrounds contributed to at least one round of the exercise. 29 people participated in statement ranking across both rounds 2 and 3.Results: Over 700 individual statements were generated in round 1 and consolidated into 193 unique statements for ranking in round 2, with 60% achieving 80% or higher agreement. In round 3, 74% of statements achieved 80% or higher agreement. Consensus conference discussions resulted in a final set of 148 agreed statements, providing direction for both policy-makers and healthcare professionals. 13 general principles were agreed, with over 90% agreement on 12 of these. Remaining statements were organised into nine themes: national level leadership and coordination, local level leadership and coordination, training and competencies for healthcare and other professionals, genetic services, genetic literacy, primary care, referrals and coordination, monitoring and evaluation and research. Next steps and working groups were also identified.Conclusions: There is high agreement among UK stakeholders on the general principles that should shape policy and practice responses in this area: equity of access, cultural competence, coordinated inter-agency working, co-design and empowerment and embedded evaluation. The need for strong national leadership to ensure more efficient sharing of knowledge and promotion of more equitable and consistent responses across the country is emphasised

Engagement barriers and service inequities in the NHS Breast Screening Programme: Views from British-Pakistani women

Objectives: Previous research has largely attempted to explore breast screening experiences of South Asian women by combining opinions from Pakistani, Bangladeshi and Indian women. This research often fails to reach the most underserved sub-groups of this population, with socioeconomic status not routinely reported and English fluency being a participation requirement. With uptake low amongst British-Pakistani women, this study explores the experiences these women encounter when accessing the NHS Breast Screening Programme.Setting: Participants were from East Lancashire, UK. Methods: Nineteen one-to-one semi-structured interviews were carried out with British-Pakistani women. Fourteen interviews were conducted via an interpreter. Results: Data were analysed using thematic analysis. Three themes were identified: ‘Absence of autonomy in screening and healthcare access’ describes how currently the screening service does not facilitate confidentiality or independence. Access requires third-party intervention, with language barriers preventing self-expression. ‘Appraisal of information sources’ makes distinctions between community and NHS communication. Whereas community communication was invaluable, NHS materials were deemed inaccessible due to translation incongruences and incomprehensible terminology. ‘Personal suppositions of breast screening’ explores the subjective issues associated with disengagement, including, the cultural misalignment of the service and perceiving screening as a symptomatic service.Conclusions: British-Pakistani women face some unique challenges when accessing breast screening. To promote uptake, the service needs to address the translation of screening materials and optimise upon community networks to disseminate knowledge, including knowledge of the screening environment within the context of culture to promote informed choice about attendance

The introduction of risk stratified screening into the NHS breast screening Programme: views from British-Pakistani women

From Springer Nature via Jisc Publications RouterHistory: received 2019-12-16, accepted 2020-05-13, registration 2020-05-14, pub-electronic 2020-05-20, online 2020-05-20, collection 2020-12Publication status: PublishedFunder: NIHR Programme Grants for Applied Research (GB); Grant(s): RP-PG-1214-200016Funder: Manchester Biomedical Research Centre; doi: http://dx.doi.org/10.13039/100014653; Grant(s): IS-BRC-1215-20007Abstract: Background: UK national guidelines suggest women at high-risk of breast cancer should be offered more frequent screening or preventative medications. Currently, only 1 in 6 high-risk women are identified. One route to identify more high-risk women is via multifactorial risk assessment as part of the UK’s NHS Breast Screening Programme (NHSBSP). As lower socioeconomic and minority ethnic populations continue to experience barriers to screening, it is important that any new service does not exacerbate issues further. To inform service development, this study explored views of women from underserved backgrounds regarding the introduction of risk stratification into the NHSBSP. Methods: Nineteen semi-structured interviews were conducted with British-Pakistani women from low socioeconomic backgrounds from East Lancashire, UK. Fourteen interviews were conducted via an interpreter. Results: Thematic analysis produced three themes. Attitudes toward risk awareness concerns the positive views women have toward the idea of receiving personalised breast cancer risk information. Anticipated barriers to accessibility emphasises the difficulties associated with women’s limited English skills for accessing information, and their I.T proficiency for completing an online risk assessment questionnaire. Acceptability of risk communication strategy highlights the diversity of opinion regarding the suitability of receiving risk results via letter, with the option for support from a healthcare professional deemed essential. Conclusions: The idea of risk stratification was favourable amongst this underserved community. To avoid exacerbating inequities, this new service should provide information in multiple languages and modalities and offer women the opportunity to speak to a healthcare professional about risk. This service should also enable completion of personal risk information via paper questionnaires, as well as online

The role of knowledge, primary care and community engagement to improve breast-screening access for Pakistani women in the United Kingdom: a secondary analysis of a qualitative study

Objective: Breast cancer incidence is rising among Pakistani women in the United Kingdom. However, uptake of breast screening remains low. This study aimed to improve access to breast screening for British-Pakistani women by exploring their knowledge of breast cancer and the role of primary care and community networks to support screening access amongst British-Pakistani women. Methods: We undertook a secondary qualitative analysis of 18 semi-structured interviews with British-Pakistani women from East Lancashire in the United Kingdom. Anonymized transcripts of the interviews were used for a thematic analysis. Results: Three themes were identified in the interviewees’ responses: (i) ‘Women’s knowledge of breasts and breast cancer’, which described how a cultural taboo exists around Pakistani women’s bodies and around breast cancer; (ii) ‘Role of primary care’, which detailed how General Practitioners can support informed decisions and offer a trusted and valued information source; (iii) ‘Community engagement’, which described the potential to disseminate breast-screening information through the whole community, including primary care providers, all family members and mosques. Conclusions: Our analysis suggested three main targets for future interventions to improve access to breast screening for British-Pakistani women: (i) co-produced strategies to increase knowledge of breasts and breast screening; (ii) greater collaboration with local General Practitioners to support women to make informed choices about screening; and (iii) community engagement involving General Practitioners and community leaders, to inform everyone – not just screening-age women – about breast cancer and screening

Developing and evaluating a culturally appropriate genetic service for consanguineous South Asian families

Blackburn with Darwen Primary Care Trust (PCT) provides services to a substantial Asian population in which the practice of consanguineous marriage is common and there is a high incidence of autosomal recessive disorders. The aim was to provide and evaluate a genetic service accessible to consanguineous families from the South Asian community who had a child affected by an autosomal recessive disorder. Information on genetic risk was provided along with the offer of genetic testing for members of the extended family to identify gene carriers and facilitate informed reproductive choices. An Urdu-speaking health visitor was employed to establish a community-based, hospital-linked genetic service in conjunction with local paediatric and regional genetic services offered to parents who had an affected child and 71 of their relatives. The service was evaluated using a specifically designed questionnaire. There was a high uptake of the service (95% of index parents and 92% of relatives to whom it was offered) and a high uptake of carrier testing (94% of relatives to whom it was offered). Eight requests for prenatal diagnosis were made during the course of the service development. Many individuals stated they would consider genetic risk when making future marriage and reproductive plans. Input from a health care worker from the same ethnic background who provided information in their own language was highly valued. Family orientated genetic services for ethnic groups practicing consanguinity can be acceptable and effective when provided in a culturally appropriate manner

The introduction of risk stratified screening into the NHS Breast Screening Programme: Views from British-Pakistani women

Background: UK national guidelines suggest women at high-risk of breast cancer should be offered more frequent screening or preventative medications. Currently, only 1 in 6 high-risk women are identified. One route to identify more high-risk women is via multifactorial risk assessment as part of the UK’s NHS Breast Screening Programme (NHSBSP). As lower socioeconomic and minority ethnic populations continue to experience barriers to screening, it is important that any new service does not exacerbate issues further. To inform service development, this study explored views of women from underserved backgrounds regarding the introduction of risk stratification into the NHSBSP. Methods: Nineteen semi-structured interviews were conducted with British-Pakistani women from low socioeconomic backgrounds from East Lancashire, UK. Fourteen interviews were conducted via an interpreter. Results: Thematic analysis produced three themes. Attitudes toward risk awareness concerns the positive views women have toward the idea of receiving personalised breast cancer risk information. Anticipated barriers to accessibility emphasises the difficulties associated with women’s limited English skills for accessing information, and their I.T proficiency for completing an online risk assessment questionnaire. Acceptability of risk communication strategy highlights the diversity of opinion regarding the suitability of receiving risk results via letter, with the option for support from a healthcare professional deemed essential. Conclusions: The idea of risk stratification was favourable amongst this underserved community. To avoid exacerbating inequities, this new service should provide information in multiple languages and modalities and offer women the opportunity to speak to a healthcare professional about risk. This service should also enable completion of personal risk information via paper questionnaires, as well as online

Role of reverse phenotyping in interpretation of next generation sequencing data and a review of INPP5E related disorders

Introduction Next Generation Sequencing (NGS) is a useful tool in diagnosis of rare disorders but the interpretation of data can be challenging in clinical settings. We present results of extended studies on a family of multiple members with global developmental delay and learning disability, where another research group postulated the underlying cause to be a homozygous RABL6 missense variant. Methods and results Using data from the Exome Variant Server, we show that missense RABL6 variants are unlikely to cause early onset rare developmental disorder. Protein structural analysis, cellular functional studies and reverse phenotyping proved that the condition in this family is due to a homozygous INPP5E mutation. An in-depth review of mutational and phenotypic spectrum associated with INPP5E demonstrated that mutations in this gene lead to a range of cilliopathy-phenotypes. Discussion We use this study as an example to demonstrate the importance of careful clinical evaluation of multiple family members, reverse phenotyping, considering the unknown phenotypic variability of rare diseases, utilizing publically available genomic databases and conducting appropriate bioinformatics and functional studies while interpreting results from NGS in uncertain cases. We emphasize that interpretation of NGS data is an iterative process and its dynamic nature should be explained to patients and families. Our study shows that developmental delay, intellectual disability, hypotonia and ocular motor apraxia are common in INPP5E-related disorders and considerable intra-familial phenotypic variability is possible. We have compiled the INPP5E mutational spectrum and provided novel insights into their molecular mechanisms