Assessment of long-term psychosocial outcomes in N-methyl-D-aspartate receptor encephalitis - the SAPIENCE study protocol.

BACKGROUND: N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a rare neurological autoimmune disease with severe neuropsychiatric symptoms during the acute phase. Despite good functional neurological recovery, most patients continue to experience cognitive, psychiatric, psychological, and social impairments years after the acute phase. However, the precise nature and evolving patterns over time of these long-term consequences remain unclear, and their implications for the well-being and quality of life of predominantly young patients have yet to be thoroughly examined. METHODS: SAPIENCE is a European multi-center (n = 3) prospective observational cohort study studying the long-term cognitive, psychiatric, psychological, and social outcome in patients with NMDAR encephalitis. The study consists of three interconnected levels. Level 1 comprises a qualitative interview and focus groups with patients and their caregivers. Level 2 consists of a condensed form of the interview, standardized questionnaires, and a detailed neuropsychological examination of patients. Level 3 involves an online survey that will be open to patients world-wide and explores patient-reported outcomes (PROMs), and patient-reported experiences (PREMs) in association with clinical and cognitive outcomes. Levels 1 to 3 will progressively contribute developing of structured interviews, survey questions, and treatment guidelines by informing one another. DISCUSSION: SAPIENCE is an in-depth study of the long-term effects of NMDAR encephalitis and bridges the gap between standardized assessments and individual patient experiences, intending to improve patient care and to increase awareness of the psychosocial long-term consequences of the disease. Through collaboration of experts in clinical neurology and social and health psychology across Europe, SAPIENCE aims to create online assessment tools and formulate guidelines for patient-centered post-acute care that will help enhance the quality of life for patients and caregivers.

Global Public Perceptions of Genomic Data Sharing: What Shapes the Willingness to Donate DNA and Health Data?

Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this.

Return of genomic results does not motivate intent to participate in research for all: Perspectives across 22 countries.

PURPOSE: The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally. METHODS: We analyzed the "Your DNA, Your Say" online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date. RESULTS: There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States. CONCLUSION: There is substantial international variation in the extent to which the RoR may motivate people's intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants' preferences for return of genomic results globally should be considered.

Between responsibility and desire: Accounts of reproductive decisions from those at risk for or affected by late-onset neurological diseases.

This paper explores ways in which genetic risk foregrounds forms of responsibility while dealing with reproduction. We analyzed individual and family semi-structured interviews (n = 35) with people at-risk for or affected by transthyretin-related familial amyloid polyneuropathy (TTR-FAP) and Machado-Joseph disease (MJD), which are late-onset neurological diseases. Although generally considered as rare diseases, some areas in Portugal present the world's highest frequency for MJD and TTR-FAP. Thematic analysis of the data revealed that participants drew on various - sometimes ambivalent and competing - understandings of their genetic risk and their wish to have children. Some participants perceived the avoidance of genetic risk to be responsible behavior, while, for others, responsibility entailed accepting risks because they prioritized values such as parenthood, family relationships and the value of life, above any question of genetic disease. Some participants shared accounts that were fraught with ambivalence, repentance and guilt, especially when children were born before participants knew of their own or their partner's risk. Participants' accounts also showed they make continued efforts to see themselves as responsible persons and to appear responsible in the eyes of others. We discuss findings in the context of participants' negotiation between genetic risk and their sense of responsibility toward themselves and others; we conclude that "genetic responsibility" is present not only in accounts of those who chose not to have children but also in those who make an informed decision to have at-risk children.

Communication of Information about Genetic Risks: Putting Families at the Center.

Genetic information is a family affair. With the expansion of genomic technologies, many new causal genes and variants have been established and the potential for molecular diagnoses increased, with implications not only for patients but also their relatives. The need for genetic counseling and intrafamilial circulation of information on genetic risks grew accordingly. Also, the amount and, particularly, the complexity of the information to convey multiplied. Sharing information about genetic risks with family members, however, has never been an easy matter and often becomes a source of personal and familial conflicts and distress. Ethical requisites generally prevent healthcare professionals from directly contacting their consultands' relatives (affected or still at risk), who often feel unsupported throughout that process. We discuss here the communication of genetic risks to family members. We first consider genomic testing as a basis for family-centered health care, as opposed to a predominant focus on the individual. We reviewed the literature on sharing genetic risk information with family members, and the associated ethical issues for professionals. Some clinical cases are presented and discussed, and key issues for meeting the needs of individuals and families are addressed. We argue that genetic information is inextricably linked to the family and that communicating about genetic risks is a process grounded within the broader milieu of family relationships and functioning. We conclude for the need for a more family-centered approach and interventions that can promote sensitive attitudes to the provision of genetic information to and within the family, as well as its inclusion in educational and training programmes for genetic healthcare professionals.

"That Should Be Left to Doctors, That's What They are There For!"-Exploring the Reflexivity and Trust of Young Adults When Seeking Health Information.

This paper explores the health information-seeking practices of healthy young adults and how they assess and rank sources of information through a qualitative study. The findings show that participants (a) are strongly committed to searching for information about health and lifestyle, especially via the Internet; (b) healthcare professionals were perceived as the most reliable source of health information and advice; (c) online health information, although frequently accessed and experienced as empowering, is seen as a potentially unreliable source. Findings evidence how becoming better informed about health-related topics plays a pivotal role in individuals' lives, most notably by using the Internet. Participants were able to reflect about what it means to know about health. The construction of trust regarding health information involved a heuristic process vis-à-vis source reliability and perceived credibility that places doctors as the most trustworthy medium of medical advice and health information. We conclude that participants' trust toward professionals suggests the preference and need for more personalized care; and it is a response to the ambiguity and uncertainty that permeates the health information landscape, particularly that which is web-based.

Genetic Counseling in Portugal: Education, Practice and a Developing Profession.

Portugal is one of the European countries where genetic counseling is emerging as an independent clinical and scientific field, paralleling the international expansion of this profession. Important steps have been consistently made towards establishing safe and ethical genetic counseling, delivered by adequately trained professionals. In 1998, Clinical Genetics was recognized in Portugal as a medical specialty. Eleven years later, the first generation of Portuguese (non MD) genetic counselors started a master level training programme at the University of Porto.

Disclosure of genetic risk to family members: A qualitative study on healthcare professionals' perceived roles and responsibilities.

This paper presents the perspectives of healthcare professionals regarding their roles and responsibilities in supporting patients with the disclosure of genetic risk to their families. The study involved eight focus groups and two individual interviews with 34 healthcare professionals working in medical genetics services across Portugal. The data were analyzed thematically, resulting in three primary themes: i) informing patients about the risk to relatives; ii) ensuring patient confidentiality; and iii) encouraging family communication. Participants believed it is their responsibility to inform patients about the genetic risk to their relatives, with patients bearing a moral responsibility to convey this information. They explained that the principles of medical confidentiality of the patient take precedence over any direct responsibility to patients' relatives. Treating personal and familial genetic information separately was perceived as challenging to implement and potentially problematic. While most participants reported encouraging patients to inform their relatives, the extent to which they facilitate this communication varies and is also constrained by lack of resources and concerns about complying with legal requirements. Some participants called for clearer national guidelines. These results contribute for ongoing discussions regarding the scope of practice and the roles and responsibilities of healthcare professionals in appropriately cascading pertinent information to at-risk relatives.

Health-related roles of older generations in families with inherited genetic conditions: a scoping review.

Inherited genetic conditions are family diseases. They affect consanguineous relatives, in lineage for several generations, and impact the family dynamics. Older generations have been considered highly influential in the health management of families with inherited genetic conditions. To our knowledge, no reviews so far addressed the health-related roles of older generations in these families. This scoping review aims to fill that gap by mapping the existent research about the health-roles roles performed by the older generations in families living with autosomal dominant inherited genetic conditions. Four electronic databases were searched: Scopus, Web of Science, PubMed, PsycInfo. Eleven studies were included, and relevant findings were extracted. Main roles included: informers vs. blockers of disease-related information; encouragers vs. discouragers of health screening or genetic testing; (non-)supporters; and role models in living and coping with the disease. The roles played by older generations are relevant to the health management of other family members and can be beneficial to themselves (reciprocal interactions). Acknowledging and understanding these roles is important for professionals and health-services. Results suggest the relevance of an intergenerational perspective when working with families with inherited genetic conditions.

From stigma to increased social acceptance? Living with Machado-Joseph disease in São Miguel, Azores, Portugal.

This study describes the experiences with the stigma attached to Machado-Joseph disease (MJD) in São Miguel Island, the Azores (Portugal). We draw on semi-structured interviews with persons with MJD, family members, healthcare professionals, and direct care providers recruited through the local patient's association (n = 28). Qualitative thematic analysis revealed three main themes: (i) the intense stigma associated with MJD in the past; (ii) the current tendency towards increased openness; and (iii) increased availability of information about MJD and support. The findings suggest that stigmatization was more frequent and intense in the past. Still, there is currently a decrease in the intensity of perceived stigma, accompanied by an increasing awareness about MJD within the community. The local patient's association is noted for playing a pivotal role in raising awareness about MJD in the community and fostering the confidence of individuals with MJD and their families to engage socially, which may help to reduce or mitigate feelings of stigma. This raises questions about whether the diminished stigma towards MJD in São Miguel results from heightened awareness about the condition, a decrease in the social acceptability of stigma, or a gradual internalization and normalization of stigma among individuals with MJD as a coping mechanism.

"Living with a question mark": psychosocial experience of Portuguese young adults at risk for hereditary amyloid transthyretin amyloidosis with polyneuropathy.

This study is the first to explore the psychosocial experience of young Portuguese adults at genetic risk for hereditary amyloid transthyretin amyloidosis with polyneuropathy (hATTR-PN). The work focuses on the developmental peculiarities of their experience with the disease. Sixteen semi-structured interviews were conducted with young adults coming for pre-symptomatic testing (PST) at a single genetics outpatient center in Portugal. The data were analyzed qualitatively. The main findings suggest that four themes mark the psychosocial experience of the young adults interviewed. The first refers to the development of psychological representations, namely beliefs, mental representations, and social perceptions about hATTR-PN. The second regards the experienced and anticipated psychosocial impacts, namely, suffering, anxiety, and relief related to the disease. The third is related to using strategies such as performing PST, strategies focused on emotional regulation and the meaning of hATTR-PN, and social strategies to deal with these impacts over time. Finally, the fourth aspect concerns the perceived and expected support for the participants' needs provided by social contexts, that is, family and genetic counseling. In a period of life also marked by qualitatively different characteristics and developmental tasks from other life cycle stages (e.g., identity explorations, instability, and independent decision-making), experience with the disease can add psychosocial challenges to young adults at risk for hATTR-PN. Genetic counseling practices and health policies can be optimized to respond to the psychosocial needs of young adults. Future research should deepen the understanding of the psychosocial experience of individuals and families with late-onset hATTR-PN to improve the clinical response in this population.

From constraints to opportunities? Provision of psychosocial support in portuguese oncogenetic counseling services.

Although available guidelines for familial cancer risk counseling clearly state the need to provide adequate psychosocial assessments and support, this feature of care is only available in part for individuals and families in oncogenetic counseling protocols in Portugal. The purpose of this study was to examine the psychosocial aspects of oncogenetic counseling provided by a sample of Portuguese genetics professionals. We sought to ascertain perceived need for the provision of psychosocial services and ways to enhance the psychosocial focus in service delivery. A qualitative study was designed; semi-structured focus groups and individual interviews were performed with 30 professionals from Portuguese healthcare institutions where oncogenetic counseling is offered. Findings suggest: current practice is aligned with the teaching model, with a mainly information-based focus; use of psychosocial counseling techniques and psychosocial support is limited throughout the genetic counseling timeline; there is a limited workforce of adequately trained psychosocial professionals, who are disadvantaged by structural and organizational constraints. These factors are considered to be serious barriers for psychosocial delivery. Development of multidisciplinary teams working in oncogenetics, and need for further counselling skills and training for genetics healthcare professionals were identified as priorities. Implications for practice and policy are discussed. Portuguese genetic counselors who have recently completed their training, may therefore contribute to enhanced psychosocial services delivery.

From older to younger generations: Intergenerational transmission of health-related roles in families with Huntington's disease.

BACKGROUND AND OBJECTIVES: Older generations play relevant roles in the well-being of younger generations, namely by influencing their health management. Literature regarding the influence in families affected by highly incapacitating hereditary diseases, such as Huntington's disease (HD), however, is scarce. This study addresses the intergenerational flow of health-related roles, from older to younger generations in families with HD, that is, who plays what roles towards whom while considering age, gender, kinship and genetic status in both generations. RESEARCH DESIGN AND METHODS: This qualitative exploratory study adopted the critical incidents technique, applied through semi-structured interviews. Ten participants reported 189 critical incidents. Thematic analysis was applied to transcript data from the interviews to glean common themes. RESULTS: The main findings suggested two main roles performed by older generations: "shaping awareness" and "influencing management". The intergenerational flow involved mainly women, in contiguous generations (usually mother-to-daughter); it was more frequent from either older non-biological or affected relatives aged ≥60 years towards younger members aged 20-29 years, who were still at-risk or non-carriers. DISCUSSION AND IMPLICATIONS: Older generations are relevant influencers in the health management of their younger relatives and they create illness-related legacies. The results are relevant for healthcare services and professionals, as they bring further insight into how older relatives may be involved in genetic counselling, as well as insight into the provision of psychological support to affected families.

Short Communication: Restrictions in care following the COVID-19 pandemic severely impacted Machado-Joseph disease patients: a study in the Azores Islands, Portugal.

This qualitative study describes how the restrictions imposed by the COVID-19 pandemic impacted on Machado-Joseph disease (MJD) patients and their care, in the island of São Miguel (the Azores, Portugal). In-person semi-structured interviews were conducted with 11 participants, including patients, family members, healthcare professionals, and care providers. Main findings highlighted the key role played by the local association in psychosocial and healthcare for MJD patients and families, and the adverse effects on their care following the onset of the COVID-19 pandemic. In particular, hindered access to the day-care centre increased isolation and had a negative impact on mental health and disease progression. For persons with a progressive and severe neurological disease, there is no "back to normal." Future restrictive measures ensuing need to be accompanied by a careful definition of daily care routines for patients.

Short Communication: Restrictions in care following the COVID-19 pandemic severely impacted Machado-Joseph disease patients: a study in the Azores Islands, Portugal.

This qualitative study describes how the restrictions imposed by the COVID-19 pandemic impacted on Machado-Joseph disease (MJD) patients and their care, in the island of São Miguel (the Azores, Portugal). In-person semi-structured interviews were conducted with 11 participants, including patients, family members, healthcare professionals, and care providers. Main findings highlighted the key role played by the local association in psychosocial and healthcare for MJD patients and families, and the adverse effects on their care following the onset of the COVID-19 pandemic. In particular, hindered access to the day-care centre increased isolation and had a negative impact on mental health and disease progression. For persons with a progressive and severe neurological disease, there is no "back to normal." Future restrictive measures ensuing need to be accompanied by a careful definition of daily care routines for patients.

A clinical photogrammetric method to measure dental arch dimensions and mesio-distal tooth size.

The aim of this research was to evaluate the reliability and validity of measurements obtained from clinical standardized occlusal photographs compared with dental cast measurements. This study comprised a consecutive sample of 16 patients (eight males and eight females, aged 15-24 years) in the permanent dentition without agenesis and/or tooth loss. A paired t-test and intraclass correlation coefficient (ICC) were used to examine validity and reliability. Both statistics were applied for intra- and inter-methods error analysis, at P < 0.05. Random error for the photogrammetric method (less than 0.48 mm) was similar to that for the dental cast measurements (less than 0.43 mm). ICC revealed excellent reliability for both methods (P < 0.01) and no significant difference for any variables, with the exception of upper inter-canine width obtained on the dental casts (P = 0.0038) and photogrammetry (P = 0.01). However, differences were less than 1 per cent of the mean inter-canine width. Inter-method analysis showed a significant correlation for all variables (P < 0.001), with good to excellent reliability (r = 0.66-0.93). A significant mean inter-method difference was consistently observed for the upper first molars (0.33 mm, P < 0.01). For the remaining teeth (left to right second premolars), the largest mean difference was approximately equal to the resolution of the human eye (0.2 mm or less). Minor differences (around 2 per cent of the mean) and an excellent ICC (0.75-0.93, P < 0.01) were observed for arch dimensions. Except for the mesio-distal width of the upper first molars, the recently developed photogrammetric method showed accuracy, validity, and reliability acceptable for clinical and scientific purposes.

Role of older generations in the family's adjustment to Huntington disease.

Genetic diseases are a family matter, requiring adjustment and management from the family system, particularly when the diagnosis is recent. Literature has evidenced the importance of the role of older relatives in families dealing with some genetic diseases; however, knowledge is scarce regarding rare incurable genetic disorders, such as Huntington disease. Therefore, this exploratory qualitative study aims at describing how adjustment to Huntington disease occurs, from a family perspective, considering the roles performed by older generations, in the Portuguese context. It adopts the critical incidents technique, administered based on semi-structured interviews, and comprises 10 participants, aged 28 to 72 years (8 females), from seven families. Participants reported 130 critical incidents. The interviews were audiotaped, transcribed, and submitted to thematic analysis. Findings portray participants and their families as "beginners" in understanding and incorporating Huntington disease in their lives, due to recent diagnosis. In addition, data suggest that older relatives play two relevant roles in the creation of family narratives: (1) "shaping awareness about HD" (68 critical incidents) and (2) "influencing HD management" (62 critical incidents). Genetic counseling and family-centered interventions aimed at supporting families with a history of hereditary genetic diseases, should consider a narrative approach involving older relatives, since they have a great influence in sustaining family stories.

Opportunistic genomic screening. Recommendations of the European Society of Human Genetics.

If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that 'actionable' genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings-so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.

Demonstrating trustworthiness when collecting and sharing genomic data: public views across 22 countries.

BACKGROUND: Public trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this. METHODS: We analyse the 'Your DNA, Your Say' online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures. RESULTS: Providing transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data-endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented. CONCLUSIONS: Our findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.

Effects of low-level laser therapy and orthodontic tooth movement on dental pulps in rats.

OBJECTIVES: To describe the microscopic pulpal reactions resulting from orthodontically induced tooth movement associated with low-level laser therapy (LLLT) in rats. MATERIALS AND METHODS: Forty-five young male Wistar rats were randomly assigned to three groups. In group I (n = 20), the maxillary right first molars were submitted to orthodontic movement with placement of a coil spring. In group II (n = 20), the teeth were submitted to orthodontic movement plus LLLT at 4 seconds per point (buccal, palatal, and mesial) with a GaAlAs diode laser source (830 nm, 100 mW, 18 J/cm(2)). Group III (n = 5) served as a control (no orthodontic movement or LLLT). Groups I and II were divided into four subgroups according to the time elapsed between the start of tooth movement and sacrifice (12 hours, 24 hours, 3 days, and 7 days). RESULTS: Up until the 3-day period, the specimens in group I presented a thicker odontoblastic layer, no cell-free zone of Weil, pulp core with differentiated mesenchymal and defense cells, and a high concentration of blood vessels. In group II, at the 12- and 24-hour time points, the odontoblastic layer was disorganized and the cell-free zone of Weil was absent, presenting undifferentiated cells, intensive vascularization with congested capillaries, and scarce defense cells in the cell-rich zone. In groups I and II, pulpal responses to the stimuli were more intense in the area underneath the region of application of the force or force/laser. CONCLUSIONS: The orthodontic-induced tooth movement and LLLT association showed reversible hyperemia as a tissue response to the stimulus. LLLT leads to a faster repair of the pulpal tissue due to orthodontic movement.