Determining Commonalities in the Experiences of Patients with Rare Diseases: A Qualitative Analysis of US Food and Drug Administration Patient Engagement Sessions.

BACKGROUND: Rare diseases are estimated to affect more than one in ten Americans. However, most patients with a rare disease face significant emotional, physical, and social challenges. To better understand the burden of disease and unmet needs, the US Food and Drug Administration (FDA) conducts and supports multiple patient engagement platforms. We analyzed summaries from these discussions to identify commonalities among patients with disparate rare diseases, the results of which could inform priorities for cross-disease policies and medical product development. METHODS: We conducted a qualitative analysis of patient engagement session summaries to investigate shared experiences across rare diseases. Cross-disease similarities were identified within four dimensions: product development/regulatory, clinical/physical, social/psychological, and economic/financial. Summaries from 29 rare diseases were included in our analyses. RESULTS: Within the product development/regulatory dimension, we observed that patients and caregivers across rare diseases shared the desire for development of medical products that cured their disease or improved their overall quality of life. In the clinical/physical dimension, we found that patients had numerous common symptoms, including pain and fatigue. In the social/psychological dimension, we observed significant negative impact on mental health. Within the economic/financial dimension, patients and caregivers shared that disease burden caused significant financial hardships. CONCLUSION: We found remarkable similarities among patients with rare diseases across all four dimensions. Our results indicate that, even among rare diseases with diverse etiologies, patients share numerous commonalties due to their diseases: a lack of effective treatment options, certain physical symptoms, mental health challenges, and financial concerns.

Treating rare diseases with the cinema: Can popular movies enhance public understanding of rare diseases?

BACKGROUND: Rare diseases (RDs) constitute an important public health issue. However, although public awareness campaigns focus on the improvement of undergraduate and postgraduate education, also popular culture may serve as an educational tool in this field. This study aims to analyse how rare genetic diseases are depicted in popular movies. METHODS: Twenty popular movies on RDs were analysed quantitatively. The main categories included in the coding frame were: disease, patient, physician/scientist and psychosocial issuses related to RDs. RESULTS: The majority of movies do not contain adequate scientific information on RDs. Consequently, their cinematic image is either inaccurate or simplified. However, the cinema does take up some important topics in the field of RDs and highlight their ethical, psychosocial, legal or economic dimension: the diagnostic and therapeutic odyssey, the role of RD patients' advocacy groups in the production of scientific knowledge, the problem of orphan drugs, the stigmatisation of and discrimination against RD patients, and the impact of diagnosis on one's concept of self and parents' feelings of guilt. CONCLUSION: Although popular movies mostly focus on RD patients' problems of daily living and rarely describe clinical aspects of RDs, they do have an educational potential. Thus, movies can help to raise the public's awareness on the psychospocial and economic problems faced by RD patients and their families.

Burden of care in families of patients with rare genetic diseases: analysis of a large Italian cohort.

In the last decade, the number of children and youth with special health care needs (CYSHCN) is increased as a result of the improvement of neonatal and pediatric assistance. The aim of our study was to describe the burden of care of the families caring a CYSHCN in our country, evaluating their living condition in order to explore socio-economic characteristics, health problems, needs and their adaptation processes trying to reach a balance between the needs of the disabled child and those of the other family members. We administered a questionnaire to the parents of CYSHCN during a routine clinical evaluation. From the analyses of questionnaires obtained, parents were the main caregiver of the children and 43,8% of them reported that they were not getting enough support. Burden of care fell on parents and indeed compilers reported an average level of stress of 3,2 (0-5) and more important, the main reported sources of stress were the concern about the future and health of their children. From the analyses of our population emerged unsatisfied needs of these families and their necessity to be effectively supported and integrated into the social fabric of the community. Social supporting is essential to help managing family stress and is evident the needed of these parents for interventions to directly target caregiver needs through the provision of tailored services, such as respite care opportunity, peer support, financial aid and medical home technologies to improve their quality of life.

Efficacy of a Brief, Peer-Delivered Self-management Intervention for Patients With Rare Chronic Diseases: A Randomized Clinical Trial.

Importance: Patients coping with rare diseases need psychosocial support. Objective: To evaluate the efficacy of a brief, transdiagnostic, peer-delivered intervention for patients with rare diseases in addition to care as usual (CAU) compared with CAU only. Design, Setting, and Participants: In this 2-group randomized clinical trial conducted from October 5, 2017, to July 12, 2019, patients were recruited via specialized clinics and patient organizations across Germany and participated from home. The study included consecutive adult patients with neurofibromatosis type 1, Marfan syndrome, primary sclerosing cholangitis, and pulmonary arterial hypertension who have limited functionality because of the disease. Exclusion criteria were a life-threatening health status and ongoing psychotherapeutic treatment. Of 143 patients screened for eligibility with a semistructured telephone interview, 54 were excluded, and 89 were randomized: 45 patients were randomly allocated to the peer-delivered intervention group, and 44 to the control group; 87 patients (98%) completed the 6-month follow-up assessment. The analysis was performed using an intention-to-treat principle. Data cleansing and analysis were conducted between April 25, 2019, and February 13, 2020. Interventions: The 6-week intervention consisted of a self-help book and telephone-based peer counseling in addition to CAU. The control group received CAU alone. Peer counselors received training, structured consultation guidelines, and supervision. Main Outcomes and Measures: The primary outcome was acceptance of the disease as assessed using the Illness Cognition Questionnaire (ICQ; mean sum scores range from 0 to 18, with higher values representing more acceptance) 6 months after the intervention. Secondary outcomes included self-reported coping strategies (Health Education Impact Questionnaire), illness cognition (ICQ and Illness Perception Questionnaire), depression severity (Patient Health Questionnaire 9-item depression scale), anxiety severity (Generalized Anxiety Disorder Scale), quality of life (12-Item Short-Form Health Survey), and social support (Social Support Questionnaire). Outcomes were assessed before the intervention, after the intervention, and at a 6-month follow-up. Results: The mean (SD) age of the 89 participating patients was 46.3 (14.9) years; 59 (66%) were women. There were no group differences regarding baseline variables. All patients allocated to the intervention group completed the intervention. Six months after the intervention, but not directly after completing the program, the intervention group had significantly higher rates of acceptance (ICQ) of the disease (primary outcome) compared with the CAU group. Mean (SD) baseline ICQ scores were 9.61 (3.79) in the control group and 9.86 (3.40) in the intervention group. Mean (SE) ICQ scores at 6 months were 10.32 (0.42) for the control group and 11.79 (0.42) for the intervention group, with a significant mean difference of -1.47 (95% CI, -2.63 to -0.31; P = .01). Several secondary outcomes, including different coping strategies, social support, and mental quality of life, were significantly higher after the intervention compared with the control group. Conclusions and Relevance: In this randomized clinical trial, a self-help and peer counseling intervention improved patients' acceptance of their rare chronic diseases. Self-management and peer support can efficiently address the unique care needs of patients with rare diseases. Trial Registration: isrctn.org Identifier: ISRCTN13738704.

Parent-authored memoirs: Lessons in the practice of narrative medicine.

Healthcare professionals, including practitioners of medical genetics and genetic counseling, have much to learn about the experiences of parents who are raising and caring for a child with a rare disease or developmental disability. Knowledge and understanding of the challenges in the care of a child with conditions such as Down syndrome and Wolf-Hirschhorn syndrome are at the core of the practice of genetic medicine. Insights into this experience can come from active listening to stories and from deep reading of memoirs and narratives authored by parents of children having these challenges. A recent book, Raising a rare girl: A memoir, by writer, poet, and teacher, Heather Lanier, represents a relevant and prototypic example of this genre. Spending the effort in the contemplation of the parental stories provides a valuable lesson in narrative medicine and the experience of empathy for the plight of the family.

Waiting for a diagnosis in Rubinstein-Taybi: The journey from "ignorance is bliss" to the value of "a label".

The journey to receiving a diagnosis for rare genetic disease can be long and emotionally impactful. This study describes parental experiences of receiving their child's diagnosis of Rubinstein-Taybi syndrome (RTS), a rare genetic condition characterized by growth and developmental delay together with dysmorphic features. Parents from the RTS Australia support group participated in qualitative, semi-structured phone interviews, which were transcribed verbatim and thematically analyzed. Questions focused on psychosocial challenges and benefits pre and post-diagnosis. Ten mothers and three fathers participated, with the mean age of diagnosis being 8 months. Parents reported positive psychological effects from a slight delay in diagnosis, and negative effects from an extended diagnostic delay, suggesting the ideal time for a parent to receive a diagnosis lies in the post attachment stage, prior to the development of significant parental concerns. This stage would vary depending on condition severity. Parents desired a diagnosis to reduce uncertainty; however, uncertainty remained post diagnosis, and shifted its focus from broadly encompassing etiology and prognosis, to specifically focusing on concerns regarding severity within the spectrum. Perceived benefits of a diagnosis mainly centered on the provision of a label. Parents articulated that a label increased social acceptance, enhanced coping, promoted communication, and improved access to medical, financial, and support services. This study provides insights into the experience of families prior to and following receipt of a diagnosis. It also highlights the possibility of an optimal time window to receive a diagnosis; in which bonding is maximized and parental distress is minimized.

Recruitment strategies and geographic representativeness for patient survey studies in rare diseases: Experience from the living with myeloproliferative neoplasms patient survey.

BACKGROUND: Recruitment of individuals with rare diseases for studies of real-world patient-reported outcomes is limited by small base populations. Myeloproliferative neoplasms (MPNs) are a group of rare, chronic, hematologic malignancies. In this study, recruitment strategies and geographic representativeness from the Living with MPNs survey are reported. METHODS: The Living with MPNs online cross-sectional survey was conducted between April and November 2016. Individuals 18 to 70 years of age living in the United States and diagnosed with an MPN were eligible to participate. Recruitment approaches included direct contact via emails and postcards; posts on MPN-focused social media and patient advocacy websites; postcard mailings to doctors' offices; and advertisements on medical websites, Google, and Facebook. Geographic representativeness was assessed based on the number of survey respondents living in each state or the District of Columbia and by the number of survey respondents per 10 million residents. RESULTS: A total of 904 respondents with MPNs completed the survey. The recruitment method yielding the greatest number of respondents was advertisements on MPN-focused social media (47.6% of respondents), followed by emails (35.1%) and postcards (13.9%) sent through MPN advocacy groups. Home state information was provided by 775 respondents from 46 states (range of respondents per state, 1-89). The number of respondents per 10 million residents in the 46 states with respondents ranged from 12.1 to 52.7. CONCLUSIONS: Recruitment using social media and communications through patient groups and advocacy organizations are effective in obtaining geographically representative samples of individuals with MPNs in the United States. These approaches may also be effective in other rare diseases.

Measuring parent proxy-reported quality of life of 11 rare diseases in children in Zhejiang, China.

BACKGROUND: It has become increasingly important to measure the health-related quality of life (HRQoL) of rare diseases in children and adolescents in recent decades. Much attention has been paid to investigate the HROoL of a specific rare disease by self-report in previous studies. This study aimed to evaluate and compare the HROoL of 11 rare diseases in Chinese children by parent proxy-report, to explore the factors associated with HROoL of patients, and to understand the problems of most concern. METHODS: A total of 651 children aged from 2 to 18 were enrolled from the Children's Hospital Affiliated Zhejiang University in 2018. Their parents completed the parent proxy-report version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0). Independent samples t-test, one-way ANOVA, or Kruskal-Wallis H test was used to compare HROoL scores between groups. Multilevel linear regression models with random intercept were applied to analyze the relationship between socioeconomic variables and both the total score and subdomain scores. RESULTS: The total PedsQL scores of Patent ductus arteriosus (PDA), Infantile agranulocytosis, Autoimmune thrombocytopenia (ITP), Polysyndactyly, Hirschsprung disease, Cleft lip and palate, Tetralogy of fallot, Myasthenia gravis, Guillain-barre syndrome, Glycogen storage disease, and Langerhans cell histiocytosis children were 79.65 ± 5.46, 95.88 ± 3.48, 71.39 ± 3.27, 91.77 ± 6.35, 76.18 ± 6.92, 96.33 ± 4.22, 77.85 ± 8.90, 95.99 ± 3.31, 85.77 ± 4.56, 82.97 ± 4.13 and 77.6 ± 5.15, respectively. Age was significantly associated with physical functioning, school functioning, and psychosocial health scores. The household registration place was significantly related to the total score. The most urgent desire of patients was to reduce the overall medical costs. CONCLUSIONS: This study showed that patients with PDA had the lowest physical functioning score, while patients with ITP scored the lowest in the emotional functioning, social functioning, school functioning, psychosocial health, and total scores. Incentive policies should be further adopted to improve orphan drug availability and reduce the economic burden of rare diseases.

Impact of COVID-19 pandemic on patients with rare disease in Hong Kong.

The COVID-19 pandemic has had significant health, social, and economic consequences internationally. While the pandemic has direct implications on infected patients and families, there is a need to examine the pandemic's effect on patients with non-COVID-19-related diseases. This study examines the impact of the COVID-19 pandemic on 272 rare disease patients with 89 distinct rare diseases in Hong Kong using a cross-sectional online survey between April 10 and April 29, 2020 from the patient and caregiver perspective. The pandemic has impacted patient's health status in 46%, service use patterns in 71%, mental health in 79%, daily living in 82%, social life in 92%, and financial status in 81% of patients. Patient's health status, medical and rehabilitation, and mental health were more impacted by the COVID-19 pandemic in the group of patients with any level of dependency according to the Barthel Index for Activities of Daily Living compared with that in the group of patients who are fully independent (p < 0.0001; p < 0.0001; p = 0.0420). This study is the first study to examine the impact of COVID-19 pandemic on the rare disease population in Hong Kong, and demonstrates the pandemic's effect on service and resource utilization, and patient's physical and mental well-being.

Young people's understanding, attitudes and involvement in decision-making about genome sequencing for rare diseases: A qualitative study with participants in the UK 100, 000 Genomes Project.

Genome sequencing (GS) will have a profound impact on the diagnosis of rare and inherited diseases in children and young people. We conducted 27 semi-structured interviews with young people aged 11-19 having GS through the UK 100, 000 Genomes Project. Participants demonstrated an understanding of the role and function of genes and DNA, however the terms 'genome' and 'genome sequencing' were less well understood. Participants were primarily motivated to take part to get a diagnosis or identify the gene causing their condition. The majority of participants understood they might not receive a diagnostic result. Most were unconcerned about data security or access, however anxieties existed around what the results might show and the potential for disappointment if the result was negative. Signing an assent form empowered young people, formalised the process and instilled a sense of responsibility for their choice to participate. Most young people (≥16 years) had consented to receive secondary findings and had come to that decision without parental influence. Our research suggests that at least some young people are capable of making informed decisions about taking part in GS, and that involving them in discussions about testing can empower them to take responsibility over healthcare decisions that affect them.

Patient and clinician opinions of patient reported outcome measures (PROMs) in the management of patients with rare diseases: a qualitative study.

BACKGROUND: Rare diseases may be life-threatening or chronically debilitating conditions. Patient care needs are often complex and challenging to coordinate and deliver effectively. Rare diseases and their clinical management may therefore substantially impact on patients' health-related quality of life (HRQOL). The use of patient-reported outcome measures (PROMs) may complement clinical assessments by elucidating patients' perspectives on their health status and care priorities. This study explored the opinions of patients and clinicians on the use of PROMs in the management of patients with rare diseases in routine clinical practice. METHODS: A total of 15 semi-structured one-to-one interviews were conducted with four patients with primary sclerosing cholangitis (PSC); five renal transplant recipients; and six PSC doctors from University Hospitals Birmingham (UHB) NHS Foundation Trust. A focus group session was also conducted with 10 clinical staff members (doctors, nurses and other allied health professionals from UHB). The suitability and acceptability of the Chronic Liver Disease Questionnaire (CLDQ) and the Short Form 12 (SF12) were assessed by patients with PSC and their doctors while the Paediatric quality of life inventory Transplant Module (PedsQL-TM) and the EuroQoL-5 dimensions (EQ. 5D) were evaluated by the renal transplant recipients and their doctors. The discussions were audio recorded and transcribed verbatim. Coding of the transcripts was done using the Nvivo 11 Plus software. Thematic analysis was conducted to identify the main themes and subthemes. RESULTS: Four themes were identified, namely: (i) potential benefits of PROMs in the management of rare diseases; (ii) views on selected questionnaires; (iii) practical considerations for implementation; and (iv) potential facilitators and barriers of implementation. Patients and clinicians suggested that the use of ePROMs may facilitate patient-centred care by promoting patient-clinician communication, highlighting aspects of HRQOL that are important to patients and encouraging patient involvement in their care. They also felt that the disease-specific CLDQ and PedsQL-TM were more relevant than the generic SF12 and EQ-5D. CONCLUSIONS: Patients with rare diseases often experience impaired HRQOL. The use of an ePROM system may enhance the routine management of patients with rare diseases.

Social support, stress, and life satisfaction among adults with rare diseases.

OBJECTIVE: The goal of this study was to examine the role of stress and four different types of social support in satisfaction with life (SWL) among adults with rare diseases (RDs). We examined whether support is directly related to SWL (main effects model) or related through moderating the inverse relationship between stress and SWL (stress-buffering hypothesis). METHOD: Data came from a cross-sectional survey of adults living in the United States diagnosed with any RD. Participants (n = 1,203) filled out measures of stress, four short-form scales of social support (emotional, informational, tangible, companionship), and SWL. Hierarchical multiple regression was used to test both the main effects model and stress-buffering hypothesis. RESULTS: Controlling for age, gender, years since diagnosis, and symptom severity, emotional support, but not informational or tangible support, positively predicted SWL. Companionship support was related to SWL over and above other factors. Stress negatively predicted SWL, but none of the types of support moderated this relationship. CONCLUSION: Results suggest companionship and emotional support are beneficial to individuals with RDs regardless of their stress levels. Intervention research should focus on ways to foster more companionship and emotional support to improve SWL in this underserved population. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Health-related quality of life and symptom burden of epithelioid hemangioendothelioma patients: a global patient-driven Facebook study in a very rare malignancy.

Purpose: Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with unique clinical features. EHE is characterized by an unpredictable, often protracted, clinical course and highly variable clinical presentation. Due to difficulty recruiting ultra-rare cancer patients, health-related quality of life (HRQoL) of EHE patients has not yet been studied. The aim of this study was to assess EHE symptom burden and its impact on HRQoL and psychological distress.Methods: The study was initiated after EHE patients' foundations approached our research group to study HRQoL. Patients were recruited from the international EHE Facebook group from May through October 2018. Data were collected using the online PROFILES registry. Latent class cluster analysis was performed to identify groups based on frequently reported symptoms. Differences in HRQoL (EORTC-QLQ-C30) and psychological distress (Hospital Anxiety and Depression Scale) between symptom-based clusters were examined.Results: Among 115 EHE patients from 20 countries, three clusters were identified, with low-, intermediate- and high-symptom burden, respectively. Highly symptomatic patients (33%) had clinically relevantly lower scores on HRQoL compared to the other two groups (p < 0.001). These patients suffered mostly from pain, insomnia and fatigue. Symptom burden significantly correlated with reduced daily functioning and high levels of psychological distress. Only for highly symptomatic patients, HRQoL and symptom levels were worse compared to healthy individuals.Conclusion: For the first time, we studied HRQoL in a large international cohort of ultra-rare cancer patients with distinct clinical characteristics, enabled by collaboration with patients and use of social media. We showed a considerable number of EHE patients were highly symptomatic, with a significant impact on HRQoL and psychological distress.

Use and importance of different information sources among patients with rare diseases and their relatives over time: a qualitative study.

BACKGROUND: Finding reliable information on one of more than 7000 rare diseases is a major challenge for those affected. Since rare diseases are defined only by the prevalence criterion, a multitude of heterogeneous diseases are included. Common to all, however, are difficulties regarding information access. Even though various quantitative studies have analyzed the use of different information sources for specific rare diseases, little is known about the use of information sources for different rare diseases, how users rate these information sources based on their experiences, and how the use and importance of these information sources change over time. METHODS: Fifty-five patients with a variety of rare diseases and 13 close relatives participated in qualitative interviews. For these interviews, a semi-structured guideline was developed, piloted, and revised. Data analysis involved a qualitative content analysis developed by Philipp Mayring. RESULTS: The participants considered internet as the most important and widespread information source, especially for early information. Although patients have difficulty dealing with information obtained online, they consider online searching a quick and practical option to gather information. During the course of the disease, personal contact partners, especially self-help associations and specialized doctors, become more important. This is also because information provided online is sometimes insufficiently detailed to answer their information needs, which can be complemented by information from doctors and self-help. CONCLUSIONS: People rarely use just one type of source, but rather refer to different sources and informants. The source used depends on the type of information sought as well as other person-related factors such as preexisting knowledge and the disease stage. To improve people's information searching and connect them with medical specialists in rare diseases, a central information portal on rare diseases might be a suitable access point to provide free and quality assured information for patients, caregivers, and physicians. This would allow not only patients but also doctors to find quality assured information on symptoms and therapies as well as patient associations and specialized doctors.

'Mapping' Health State Utility Values from Non-preference-Based Measures: A Systematic Literature Review in Rare Diseases.

BACKGROUND: The use of patient-reported outcome measures (PROMs) to monitor the effects of disease and treatment on patient symptomatology and daily life is increasing in rare diseases (RDs) (i.e. those affecting less than one in 2000 people); however, these instruments seldom yield health state utility values (HSUVs) for cost-utility analyses. In such a context, 'mapping' allows HSUVs to be obtained by establishing a statistical relationship between a 'source' (e.g. a disease-specific PROM) and a 'target' preference-based measure [e.g. the EuroQol-5 Dimension (EQ-5D) tool]. OBJECTIVE: This study aimed to systematically review all published studies using 'mapping' to derive HSUVs from non-preference-based measures in RDs, and identify any critical issues related to the main features of RDs, which are characterised by small, heterogeneous, and geographically dispersed patient populations. METHODS: The following databases were searched during the first half of 2019 without time, study design, or language restrictions: MEDLINE (via PubMed), the School of Health and Related Research Health Utility Database (ScHARRHUD), and the Health Economics Research Centre (HERC) database of mapping studies (version 7.0). The keywords combined terms related to 'mapping' with Orphanet's list of RD indications (e.g. 'acromegaly') in addition to 'rare' and 'orphan'. 'Very rare' diseases (i.e. those with fewer than 1000 cases or families documented in the medical literature) were excluded from the searches. A predefined, pilot-tested extraction template (in Excel®) was used to collect structured information from the studies. RESULTS: Two groups of studies were identified in the review. The first group (n = 19) developed novel mapping algorithms in 13 different RDs. As a target measure, the majority used EQ-5D, and the others used the Short-Form Six-Dimension (SF-6D) and 15D; most studies adopted ordinary least squares (OLS) regression. The second group of studies (n = 9) applied previously published algorithms in non-RDs to comparable RDs, mainly in the field of cancer. The critical issues relating to 'mapping' in RDs included the availability of very few studies, the relatively high number of cancer studies, and the absence of research in paediatric RDs. Moreover, the reviewed studies recruited small samples, showed a limited overlap between RD-specific and generic PROMs, and highlighted the presence of cultural and linguistic factors influencing results in multi-country studies. Lastly, the application of existing algorithms developed in non-RDs tended to produce inaccuracies at the bottom of the EQ-5D scale, due to the greater severity of RDs. CONCLUSIONS: More research is encouraged to develop algorithms for a broader spectrum of RDs (including those affecting young children), improve mapping study quality, test the generalisability of algorithms developed in non-RDs (e.g. HIV) to rare variants or evolutions of the same condition (e.g. AIDS wasting syndrome), and verify the robustness of results when mapped HSUVs are used in cost-utility models.

Understanding genetic learning needs of people affected by rare disease.

Nearly 350 million people worldwide are affected by a rare disease (RD) and ~80% of RDs have a genetic type, underscoring the need for access to reliable genomics education. Patient assistance in resource development can help ensure content is appropriate. The aim of this study was to define the needs and practical usage of the RD community to inform the scope and content of an online genetic course targeted toward the entire RD ecosystem. A high-level online survey (OS) was disseminated to 586 RD patients and family members/caregivers. A total of 251 individuals responded to the OS. Eight respondents were invited to participate in a follow-up focus group (FG). Nearly 87% of OS respondents have made efforts previously to learn more about genetics and 95.6% indicated a current interest in genetic education. Navigating healthcare systems, information sharing, and advocacy support were driving factors for this desire. Respondents indicated difficulty finding information on gene function, genetic testing, disease pathogenesis, and scientific advances. FG outcomes dove deeper into psychological needs including reducing emotional burden, alleviating fear of the unknown and seeking hope. Research identified high levels of interest in genetic education across all stages of the RD journey. Key themes identified in this study may help guide genetic counselors as they create their own patient and family-facing content.

Introduction: Rare and unusual andrologic syndromes that clinicians should be aware of.

There are conditions that are rare and that most providers are unaware of or conditions that consist of a series of symptoms for which there is no agreement that they are even a medical condition. These include painful nocturnal erections, post-orgasmic illness syndrome, body dysmorphic disorder, and post-finasteride syndrome. While some have a psychiatric basis, others clearly have an organic pathophysiology, while for others, there remains much controversy. This month's Views and Reviews will inform the reader of these conditions so they may recognize affected patients and direct them towards appropriate resources for their care.

Rare disorders of penile erection.

This literature review presents two unusual and mystifying disorders of penile erection: painful nocturnal erections, alternatively termed sleep-related painful erections, and idiopathic stuttering priapism, a variant of recurrent ischemic priapism in which no cause is discernible. The disorders are closely related although they are distinct clinically and pathologically. The main subject areas of discussion are recognition, clinical evaluation and management although current concepts surrounding their causes and mechanisms are also addressed. It is acknowledged that despite the perceived rarities of these disorders they are impactful in terms of their disease profiles and consequences. Future advances in their management will require continued development of evidence-based treatments.

Parents' motivations, concerns and understanding of genome sequencing: a qualitative interview study.

The 100,000 Genomes Project is a hybrid clinical and research project in which patients and parents are offered genome sequencing for cancer and rare and inherited disease diagnosis; all participants receive their main findings and contribute their data for research, and are offered optional secondary findings. Our aim was to explore participating parents' attitudes towards and understanding of genome sequencing in this hybrid context. We conducted in-depth telephone interviews with 20 parents of children with rare diseases participating in the 100,000 Genomes Project. Parents were positive about contributing to research, although some had needed reassurance about data protections. Although most felt positive about secondary findings, some could not recall or misunderstood key aspects. Some were also concerned about potential emotional impact of results and a few raised concerns about life insurance implications, and the impact of future legal changes. Participants were generally positive about consent appointments, but several raised concerns about 'information overload' because of deciding about secondary findings at the same time as about the main diagnostic genome sequencing and data contribution. Additional information resources, particularly online tools, were highlighted as potentially useful ways of supporting the consent process. We conclude that parents offered genome sequencing as part of a national hybrid clinical and research project report many positive attitudes and experiences, but also concerns and misunderstandings. Further research is needed on how best to support informed consent, particularly about secondary findings. Additional resources such as online tools might usefully support future genome sequencing consent processes.

Exploring broad consent in the context of the 100,000 Genomes Project: a mixed methods study.

The 100,000 Genomes Project (100kGP)-a hybrid clinical-research initiative-was set up to analyse whole-genome sequences (WGS) from patients living with a rare disease or cancer. The project positioned participant consent as being of central importance, but consent in the context of genomic testing raises challenging issues. In this mixed method study, we surveyed 1337 100kGP participants regarding their experiences of taking part in the project and conducted in-depth interviews with 24 survey respondents to explore these findings further. Survey responses were analysed using descriptive statistics and interview data were analysed thematically. The consent approach of the 100kGP resulted in a proportion of our study's participants not understanding the complexities of the project and what types of results they might receive; for example, 20% of participants who we surveyed from the cancer arm did not recall what decisions they had made regarding additional findings. It is not surprising that a project such as this, with such diverse aims and participant groups, would throw up at least some challenges. However, participants reported being satisfied with their experience of the project to date. Our study highlights that in the context of consent for more complex endeavours, such as the 100kGP, it is important to assess (and document) an agreement to take part, but complicated decisions about what and when to communicate may need revisiting over time in response to changing contexts. We discuss the implications of our findings with reference to participants of the 100kGP and the newly formed NHS Genomic Medicine Service.