The communication chain of genetic risk: analyses of narrative data exploring proband-provider and proband-family communication in hereditary breast and ovarian cancer

Low uptake of genetic services among members of families with hereditary breast and ovarian cancer (HBOC) suggests limitations of proband-mediated communication of genetic risk. This study explored how genetic information proceeds from healthcare providers to probands and from probands to relatives, from the probands' perspectives. Using a grounded-theory approach, we analyzed narrative data collected with individual interviews and focus groups from a sample of 48 women identified as carriers of HBOC-associated pathogenic variants from three linguistic regions of Switzerland. The findings describe the "communication chain", confirming the difficulties of proband-mediated communication. Provider-proband communication is impacted by a three-level complexity in the way information about family communication is approached by providers, received by probands, and followed-up by the healthcare system. Probands' decisions regarding disclosure of genetic risk are governed by dynamic and often contradictory logics of action, interconnected with individual and family characteristics, eventually compelling probands to engage in an arbitrating process. The findings highlight the relevance of probands' involvement in the communication of genetic risk to relatives, suggesting the need to support them in navigating the complexity of family communication rather than replacing them in this process. Concrete actions at the clinical and health system levels are needed to improve proband-mediated communication

Relatives from Hereditary Breast and Ovarian Cancer and Lynch Syndrome Families Forgoing Genetic Testing: Findings from the Swiss CASCADE Cohort.

Cascade genetic testing of relatives from families with pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) has important implications for cancer prevention. We compared the characteristics of relatives from HBOC or LS families who did not have genetic testing (GT (-) group) with those who had genetic testing (GT (+) group), regardless of the outcome. Self-administered surveys collected cross-sectional data between September 2017 and December 2021 from relatives participating in the CASCADE cohort. We used multivariable logistic regression with LASSO variable selection. Among n = 115 relatives who completed the baseline survey, 38% (n = 44) were in the GT (-) group. Being male (OR: 2.79, 95% CI: 1.10-7.10) and without a previous cancer diagnosis (OR: 4.47, 95% CI: 1.03-19.42) increased the odds of being untested by almost three times. Individuals from families with fewer tested relatives had 29% higher odds of being untested (OR: 0.71, 95% CI: 0.55-0.92). Reasons for forgoing cascade testing were: lack of provider recommendation, lack of time and interest in testing, being afraid of discrimination, and high out-of-pocket costs. Multilevel interventions designed to increase awareness about clinical implications of HBOC and LS in males, referrals from non-specialists, and support for testing multiple family members could improve the uptake of cascade testing

Intention to Inform Relatives, Rates of Cascade Testing, and Preference for Patient-Mediated Communication in Families Concerned with Hereditary Breast and Ovarian Cancer and Lynch Syndrome: The Swiss CASCADE Cohort.

Cascade screening for Tier 1 cancer genetic conditions is a significant public health intervention because it identifies untested relatives of individuals known to carry pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). The Swiss CASCADE is a family-based, open-ended cohort, including carriers of HBOC- and LS-associated pathogenic variants and their relatives. This paper describes rates of cascade screening in relatives from HBOC- and LS- harboring families, examines carriers' preferences for communication of testing results, and describes theory-based predictors of intention to invite relatives to a cascade screening program. Information has been provided by 304 index cases and 115 relatives recruited from September 2017 to December 2021. On average, 10 relatives per index case were potentially eligible for cascade screening. Approximately 65% of respondents wanted to invite relatives to the cohort, and approximately 50% indicated a preference for patient-mediated communication of testing results, possibly with the assistance of digital technology. Intention to invite relatives was higher for first- compared to second- and third-degree relatives, but was not different between syndromes or based on relatives' gender. The family environment and carrying pathogenic variants predicts intention to invite relatives. Information helps optimize delivery of tailored genetic services

Values and health risks: An editorial

This special issue is the second in a four-part series Health Care Through the ‘Lens of Risk’ focussing on risk categorisation, valuing, expecting and time-framing, respectively, and published or to be published in 2012–2013. The present editorial introduces the issue of risk valuing in relation to an interview-based article and five substantial research papers (one appearing in a subsequent issue (14.6) due to space limitations). It will be argued that the notion of ‘adverse event’ projects negative value onto events themselves, directing attention away from the observer's active judgemental role. The relocation of value judgements in the perspectives of social actors allows their potential variability to be more clearly recognised. This issue will be explored in the editorial which introduces papers concerned with hard drug consumption, self-hurting, the community rehabilitation of forensic mental health service users who have committed serious offences against other persons, the treatment of anal cancer and the perspectives of young pregnant women. A common theme linking these papers is the positive valuing of risk-taking officially designated as unacceptable

Living with Gitelman disease: an insight into patients' daily experiences

Background. Gitelman disease presents with musculos-keletal complaints and fatigue. Surprisingly, there is no clear-cut correlation between biochemical abnormalities and symptoms. Methods. Starting from the hypothesis that the way patients comprehend their illness within their sociocultur-al frameworks reflects on their way of adapting to it, this study investigated how adult patients experience the disease in everyday life. We conducted a qualitative analysis based on interviews with 12 patients. Interviews were audio recorded, fully transcribed and analyzed using the constant comparative method described by Strauss and Corbin. Results. A typology of the experiences emerged from the data and was tested on each transcript with an explicit search for disconfirming cases. Patients fell into four main groups: (i) those considering Gitelman disease a disabling illness, (ii) those considering it a normalized illness, (iii) those considering it a different normality and (iv) those considering it an episodic disability. Each pattern of experience was characterized by particular (i) ways of interpreting symptoms (ii) ways of managing Gitelman disease in everyday life, (iii) general lifestyles and (iv) risks for the patient’s psychosocial life. Conclusions. These findings suggest that health care providers should take advantage of considering patients’ own perception of the disease in order to adjust the care and advice provided

Prevalence and molecular characterisation of carbapenemase-producing Enterobacterales in an outbreak-free setting in a single hospital in Uruguay

Objectives: This study aimed to characterise all carbapenemase-producing enterobacteria (CPE) isolates obtained from an outbreak-free setting in Uruguay. Methods: We studied 12 CPE isolated from Hospital de Clínicas between 2012–2016. Bacterial identification and antibiotic susceptibility testing were performed using VITEK®2 and Sensititre or agar dilution, respectively. Antimicrobial resistance genes and mobile genetic elements were identified by PCR and sequencing. Multilocus sequence typing was performed for Klebsiella pneumoniae. Plasmid conjugation was assessed, plasmid size was estimated by S1-PFGE and plasmid incompatibility groups were sought by PCR. Results: Among 8364 enterobacteria, 12 CPE were isolated from urine, blood culture, wound, peritoneal fluid and punch samples. NDM-1 was the most prevalent carbapenemase, followed by VIM-2 and KPC-2. All isolates were resistant to gentamicin, cefotaxime, ceftazidime, trimethoprim/sulfamethoxazole, ciprofloxacin and imipenem and were susceptible to fosfomycin. We characterised six class 1 integrons: dfrA12–orfF–aadA2; aacA4–blaOXA-2–orfD; aadB–aadA2; dfrA1; aadB–blaOXA-10–aadA1; and blaVIM-2-dfrA7. An association between various aminoglycoside, β-lactam and fluoroquinolone resistance genes were observed, some of them located in transferable plasmids belonging to incompatibility groups IncC, IncHI1 and IncM1. We described a new composite transposon (assigned Tn6935) including blaNDM-1 flanked by two directly-oriented copies of a Tn3-like element ISKox2-like family transposase. The sequence types of K. pneumoniae isolates were ST11, ST14 and ST661. Conclusions: The presence of CPE is sporadic and could be due to measures taken by the Public Health Committee. Nevertheless, the coexistence of several resistance mechanisms and their presence in conjugative plasmids and high-risk clones is worrisome

Predicting Openness of Communication in Families With Hereditary Breast and Ovarian Cancer Syndrome: Natural Language Processing Analysis

BackgroundIn health care research, patient-reported opinions are a critical element of personalized medicine and contribute to optimal health care delivery. The importance of integrating natural language processing (NLP) methods to extract patient-reported opinions has been gradually acknowledged over the past years. One form of NLP is sentiment analysis, which extracts and analyses information by detecting feelings (thoughts, emotions, attitudes, etc) behind words. Sentiment analysis has become particularly popular following the rise of digital interactions. However, NLP and sentiment analysis in the context of intrafamilial communication for genetic cancer risk is still unexplored. Due to privacy laws, intrafamilial communication is the main avenue to inform at-risk relatives about the pathogenic variant and the possibility of increased cancer risk. ObjectiveThe study examined the role of sentiment in predicting openness of intrafamilial communication about genetic cancer risk associated with hereditary breast and ovarian cancer (HBOC) syndrome. MethodsWe used narratives derived from 53 in-depth interviews with individuals from families that harbor pathogenic variants associated with HBOC: first, to quantify openness of communication about cancer risk, and second, to examine the role of sentiment in predicting openness of communication. The interviews were conducted between 2019 and 2021 in Switzerland and South Korea using the same interview guide. We used NLP to extract and quantify textual features to construct a handcrafted lexicon about interpersonal communication of genetic testing results and cancer risk associated with HBOC. Moreover, we examined the role of sentiment in predicting openness of communication using a stepwise linear regression model. To test model accuracy, we used a split-validation set. We measured the performance of the training and testing model using area under the curve, sensitivity, specificity, and root mean square error. ResultsHigher “openness of communication” scores were associated with higher overall net sentiment score of the narrative, higher fear, being single, having nonacademic education, and higher informational support within the family. Our results demonstrate that NLP was highly effective in analyzing unstructured texts from individuals of different cultural and linguistic backgrounds and could also reliably predict a measure of “openness of communication” (area under the curve=0.72) in the context of genetic cancer risk associated with HBOC. ConclusionsOur study showed that NLP can facilitate assessment of openness of communication in individuals carrying a pathogenic variant associated with HBOC. Findings provided promising evidence that various features from narratives such as sentiment and fear are important predictors of interpersonal communication and self-disclosure in this context. Our approach is promising and can be expanded in the field of personalized medicine and technology-mediated communication

Using a Tailored Digital Health Intervention for Family Communication and Cascade Genetic Testing in Swiss and Korean Families With Hereditary Breast and Ovarian Cancer: Protocol for the DIALOGUE Study.

BACKGROUND In hereditary breast and ovarian cancer (HBOC), family communication of genetic test results is essential for cascade genetic screening, that is, identifying and testing blood relatives of known mutation carriers to determine whether they also carry the pathogenic variant, and to propose preventive and clinical management options. However, up to 50% of blood relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively within family networks. Technology can facilitate communication and genetic education within HBOC families. OBJECTIVE The aims of this study are to develop the K-CASCADE (Korean-Cancer Predisposition Cascade Genetic Testing) cohort in Korea by expanding an infrastructure developed by the CASCADE (Cancer Predisposition Cascade Genetic Testing) Consortium in Switzerland; develop a digital health intervention to support the communication of cancer predisposition for Swiss and Korean HBOC families, based on linguistic and cultural adaptation of the Family Gene Toolkit; evaluate its efficacy on primary (family communication of genetic results and cascade testing) and secondary (psychological distress, genetic literacy, active coping, and decision making) outcomes; and explore its translatability using the reach, effectiveness, adoption, implementation, and maintenance framework. METHODS The digital health intervention will be available in French, German, Italian, Korean, and English and can be accessed via the web, mobile phone, or tablet (ie, device-agnostic). K-CASCADE cohort of Korean HBOC mutation carriers and relatives will be based on the CASCADE infrastructure. Narrative data collected through individual interviews or mini focus groups from 20 to 24 HBOC family members per linguistic region and 6-10 health care providers involved in genetic services will identify the local cultures and context, and inform the content of the tailored messages. The efficacy of the digital health intervention against a comparison website will be assessed in a randomized trial with 104 HBOC mutation carriers (52 in each study arm). The translatability of the digital health intervention will be assessed using survey data collected from HBOC families and health care providers. RESULTS Funding was received in October 2019. It is projected that data collection will be completed by January 2023 and results will be published in fall 2023. CONCLUSIONS This study addresses the continuum of translational research, from developing an international research infrastructure and adapting an existing digital health intervention to testing its efficacy in a randomized controlled trial and exploring its translatability using an established framework. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Culturally sensitive web-based interventions that enhance family communication and understanding of genetic cancer risk are timely. This collaboration creates a research infrastructure between Switzerland and Korea that can be scaled up to cover other hereditary cancer syndromes. TRIAL REGISTRATION ClinicalTrials.gov NCT04214210; https://clinicaltrials.gov/ct2/show/NCT04214210 and CRiS KCT0005643; https://cris.nih.go.kr/cris/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/26264