Secondary findings from next generation sequencing: Psychological and ethical issues. Family and patient perspectives.

Access to active search for actionable secondary findings (SF) in diagnostic practice is a major psychological and ethical issue for genomic medicine. In this study, we analyzed the preferences of patients and their families regarding SF and identified the reporting procedures necessary for informed consent. We interviewed parents of patients with undiagnosed rare diseases potentially eligible for exome sequencing and patients affected by the diseases listed in the ACMG recommendations. Four focus groups (FG) were formed: parents of patients with undiagnosed rare diseases (FG1, n = 5); patients with hereditary cancers (FG2, n = 10); patients with hereditary cardiac conditions (FG3, n = 3); and patients with metabolic diseases (FG4, n = 3). Psychologists presented three broad topics for discussion: 1. Favorable or not to SF access, 2. Reporting procedures, 3. Equity of access. Discussions were recorded and analyzed using simplified Grounded Theory. Overall, 8 participants declared being favorable to SF because of the medical benefit (mainly FG1); 11 were unfavorable because of the psychological consequences (mainly FG2, FG3, FG4); 2 were ambivalent. The possibility of looking for SF in minors was debated. The 4 key information-based issues for participants ranked as follows: explanation of SF issues, autonomy of choice, importance of a reflection period, and quality of interactions between patients and professionals. Examining equity of access to SF led to philosophical discussions on quality of life. In conclusion, individual experience and life context (circumstances) were decisive in participants' expectations and fears regarding access to SF. Additional longitudinal studies based on actual SF disclosure announcements are needed to establish future guidelines.

Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives. A review of the literature.

With the development of next generation sequencing, beyond identifying the cause of manifestations that justified prescription of the test, other information with potential interest for patients and their families, defined as secondary findings (SF), can be provided once patients have given informed consent, in particular when therapeutic and preventive options are available. The disclosure of such findings has caused much debate. The aim of this work was to summarize all opinion-based studies focusing on SF, so as to shed light on the concerns that this question generate. A review of the literature was performed, focusing on all PubMed articles reporting qualitative, quantitative or mixed studies that interviewed healthcare providers, participants, or society regarding this subject. The methodology was carefully analysed, in particular whether or not studies made the distinction between actionable and non-actionable SF, in a clinical or research context. From 2010 to 2016, 39 articles were compiled. A total of 14,868 people were interviewed (1259 participants, 6104 healthcare providers, 7505 representatives of society). When actionable and non-actionable SF were distinguished (20 articles), 92% of respondents were keen to have results regarding actionable SF (participants: 88%, healthcare providers: 86%, society: 97%), against 70% (participants: 83%, healthcare providers: 62%, society: 73%) for non-actionable SF. These percentages were slightly lower in the specific situation of children probands. For respondents, the notion of the «patient's choice¼ is crucial. For healthcare providers, the importance of defining policies for SF among diagnostic lab, learning societies and/or countries is outlined, in particular regarding the content and extension of the list of actionable genes to propose, the modalities of information, and the access to information about adult-onset diseases in minors. However, the existing literature should be taken with caution, since most articles lack a clear definition of SF and actionability, and referred to hypothetical scenarios with limited information to respondents. Studies conducted by multidisciplinary teams involving patients with access to results are sadly lacking, in particular in the medium term after the results have been given. Such studies would feed the debate and make it possible to measure the impact of such findings and their benefit-risk ratio.

[Studying dysfunctional personality trends among sex offenders]. / Étude des tendances dysfonctionnelles de la personnalité chez des auteurs d'infractions sexuelles.

OBJECTIVE: A review of the literature reveals a consensus on the high prevalence of personality disorders among sexual offenders. Studies show that there is no unique personality profile for sex offenders. In France, little research has been conducted on this population with standardized assessment tools. The objective of the present study is to identify the distribution of personality disorders among sexual offenders using a new French questionnaire, i.e. the TD12. In view of the literature, we postulate that this tool will identify the diversity of personality disorders observed by various authors, but with a higher proportion of cluster B disorders. METHODOLOGY: This study was conducted among 56 men, including 28 sex offenders aged from 21 to 70 years old, and a control group of 28 men without psychiatric disorders. The sex offenders in this study are men convicted or charged with sex offenses of various kinds: exhibitionism, the recording, distribution and possession of pornography depicting minors, aggravated corruption of a minor, sexual assault of a minor, or rape of a minor. They were examined using an inventory of dysfunctional trends recently developed by Rolland and Pichot with the aim of assessing dysfunctional personality styles. The TD-12 questionnaire is composed of 140 items describing thoughts, feelings and behaviors. It is based on the diagnostic criteria of Axis II of DSM IV-TR and consists of twelve scales that match the personality disorders described in this diagnostic manual (ten officially recognized disorders and two additional disorders). RESULTS: From a categorical viewpoint, results indicate rigid dysfunctional trends with regard to avoidant personality disorder in sex offenders compared to the control group (Chi(2)=9.16; P=0.005). However, there were no significant differences between the two groups regarding the number of rigid dysfunctional trends. Potentially controllable dysfunctional personality trends are identified for the dependent personality (Chi(2)=6.72; P=0.02) and the depressive personality (Chi(2)=9.63; P=0.004). Moreover, the results show differences related to type of crime. The mean score on the Docile-Dependent scale is higher among subjects who had only downloaded images of child pornography (n=8) compared to subjects who had committed at least one sexual offense against a victim (n=20) (58.75±8.43 versus 49.55±11.66, P=0.04). CONCLUSION: These results are somewhat in contradiction with previous studies. The often described cluster B personalities are not significantly observed in this study. These results show the prevalence of avoidant personality disorder, which in fact corresponds to a clinically observed sex offender profile characterized by inhibition, relationship difficulties with adults, fear of being judged or rejected, and social isolation. The study also shows the value of considering the personality profile in relation to the modus operandi. It is important to continue this research on larger groups in order to refine the results.