Lower Healthcare Access and Its Association With Individual Factors and Health-Related Quality of Life in Adults With Rare Diseases in Switzerland.

Objectives: This study aims to determine clusters of access to healthcare among adults with rare diseases in Switzerland, identify associated individual characteristics of access, and impact on health-related quality of life (HRQoL). Methods: Swiss adults (N = 341) diagnosed with a rare disease completed an online survey including the Perception of Access to Healthcare Questionnaire (PAHQ) and Short Form Health Survey (SF-12). We employed partition around medoids algorithm to identify patient clusters based on the PAHQ. Various sociodemographic/disease-related factors and HRQoL were assessed. Results: We identified two patient clusters: higher (n = 227) and lower access (n = 114). Significantly associated with lower access were an unstable disease course (p < 0.05), increased number of misdiagnoses (p < 0.05), and diseases affecting the nervous system (p < 0.01). Membership in the lower access cluster was significantly associated with worse HRQoL (p < 0.05). Conclusion: Findings highlight the need for comprehensive assessment of healthcare access in adults with rare diseases and identifies potential targets for tailored interventions.

Latent profiles and predictors of barriers to care in Swiss children and adolescents with rare diseases.

OBJECTIVE: Children and adolescents with rare diseases face significant barriers when accessing healthcare. We aimed to assess and predict these barriers and investigate associations with health-related quality of life (HRQoL). METHOD: We conducted a cross-sectional survey of Swiss parents (N = 189) of children with rare diseases including the Barriers to Care Questionnaire (BCQ), containing six barriers and the Pediatric Quality of Life Inventory (PedsQL). Latent profile analysis (LPA) was used to uncover distinct classes, which were compared using chi-square tests and Mann-Whitney U tests. Relevant medical and sociodemographic class predictors were identified using Elastic Net regression, followed by regression analysis to investigate their role in predicting barriers to care and examine the effects of these classes on HRQoL. RESULTS: Two distinct groups were identified, a higher barriers class (59%) and a lower barriers class (41%). In the higher barriers class, participants showed elevated scores across all subscales and specifically on pragmatics and expectations. More barriers to care were linked to a nonstable disease course (OR = 2.27, p = .002) and a diagnosis after the age of 3 months (OR = 2.17, p = .006). Individuals in the higher barriers class exhibited more psychological comorbidities (p = .044), congenital malformations/deformations/chromosomal abnormalities (p=.042), and medical misdiagnoses (p = .006). Children in the higher barriers class had significantly lower PedsQL scores compared to the lower barriers class (p <.05). CONCLUSION: This study highlights the need for comprehensive assessment of barriers to pediatric care in rare diseases, offering potential entry points for targeted interventions.

Integrating genomics and precision health knowledge into practice: A guide for nurse practitioners.

ABSTRACT: Nurse practitioners (NPs) are the fastest growing group of health care providers, with an increase of 8.5% over the past year and anticipated growth of more than 40% by 2031. Improving NPs' knowledge of how genes influence health enables them to assess, diagnose, and manage patients in all states of health in a safe, efficient, and competent manner. Nurse practitioners may also care for patients who obtain direct-to-consumer (DTC) genetic tests without provider oversight and share their results; improved knowledge of genetics can provide NPs with the information and resources needed to interpret and understand DTC test results. The literature indicates that NPs have limited understanding of basic genetic concepts and guidelines for prescribing drugs affected by genomic variability. As a result, NPs report low confidence in their ability to accurately interpret and apply genetic test results, which inhibits genomics-informed precision health care. This article provides resources and clinical recommendations for using the 2021 American Association of Colleges of Nursing Essentials and the American Nurses Association Essentials of Genomic Nursing to facilitate the integration of genomics into NP curricula and practice. These resources will help future and practicing NPs integrate genomics into practice and improve precision health care.

Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive disorder caused by deficient secretion or action of gonadotropin-releasing hormone (GnRH) and is a hormonally treatable form of male infertility. Both pulsatile GnRH treatment and combined gonadotropin therapy effectively induce spermatogenesis in 75%-80% of males with CHH, albeit the ejaculate does not usually approach normal semen parameters by WHO criteria. This is in some contrast to the cumulative fertility outcomes in females with CHH on gonadotropin treatment that are indistinguishable from those of reproductively normal females. Emerging data provide insights into early life determinants of male fertility (i.e., minipuberty), and research has identified key predictors of outcomes for fertility-inducing treatment in men with CHH. Such developments provide mounting evidence for tailoring approaches to maximize fertility potential in CHH, although there is no clear consensus to date on the optimal approach to fertility-inducing treatment. This review provides an up-to-date review on the current evidence underpinning therapeutic approaches for inducing spermatogenesis in males with CHH. In the absence of evidence-based clinical guidelines, this synthesis of current evidence provides guidance for clinicians working with males with CHH seeking fertility.

"Identity theft" in BRCA1/2: impact of positive genetic test results and risk-reducing interventions.

Individuals harboring breast cancer gene 1/2 (BRCA1/2) pathogenic variants are at increased lifetime risk for developing cancer. Learning one's BRCA1/2 carrier status is a watershed moment that can result in psychological distress, anxiety, and depression, as well as feelings of vulnerability and stigma. However, emotional and coping responses to learning one's BRCA1/2 carrier status and after risk-reducing interventions (i.e., preventative bilateral mastectomy) are variable, and existing literature reveals mixed and sometimes contradictory results. Drawing on the concept of narrative identity from the field of psychology, we sought to examine if "identity theft" (the sudden overtaking of one's narrative agency by an external force) may help explain the heterogeneity of emotional and coping responses following the revelation of BRCA carrier status and the subsequent medical intervention one may receive. This Perspective explores BRCA related identity theft using two case studies. Narrative analysis of qualitative interviews uncover the ways that patients experience the disintegration (theft) of their identity as well as their efforts to build and reintegrate a new BRCA carrier identity. This initial qualitative exploration provides preliminary support for the relevance of narrative identity and identity theft to hereditary cancer. We posit that applying the lens of identity theft may hold promise as a unifying concept, integrating across the variable emotional and coping responses among BRCA carriers. Employing a lens of identity theft may help inform the development of tailored narrative interventions as part of precision healthcare to support active coping and psychosocial wellbeing.

Intersectionality, BRCA Genetic Testing, and Intrafamilial Communication of Risk: A Qualitative Study.

Significant health disparities exist in relation to pathogenic variants in BRCA1/2. This study aimed to better understand the barriers and facilitators to BRCA1/2 genetic testing and intrafamilial communication of risk in racially and ethnically diverse individuals. We conducted qualitative interviews with non-Hispanic White (n = 11) and Black, Indigenous, People of Color (BIPOC) individuals (n = 14) who underwent testing for pathogenic BRCA1/2 variants. We employed template analysis, case study analysis, and comparative case study analysis to examine healthcare experiences related to genetic testing as well as intrafamilial communication of risk. Applying an intersectional lens, we sought to inform more person-centered approaches to precision healthcare and help dismantle disparities in genomic healthcare. Template analysis revealed salient factors at the individual (psychosocial well-being), interpersonal/familial, and healthcare system levels. A two-part case study analysis provided insights into how race/ethnicity, cultural norms, and socioeconomic status interact with systemic and structural inequities to compound disparities. These findings underscore the need for person-centered, tailored, and culturally sensitive approaches to understanding and addressing the complexities surrounding testing and the communication of BRCA risk. Applying an intersectional lens can inform more person-centered approaches to precision healthcare and may help to surmount existing disparities.

Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres.

BACKGROUND: Although some male patients with congenital hypogonadotropic hypogonadism (CHH) undergo spontaneous reversal following treatment, predictors of reversal remain elusive. We aimed to assemble the largest cohort of male patients with CHH reversal to date and identify distinct classes of reversal. METHODS: This multicentre cross-sectional study was conducted in six international CHH referral centres in Brazil, Finland, France, Italy, the UK, and the USA. Adult men with CHH (ie, absent or incomplete spontaneous puberty by age 18 years, low serum testosterone concentrations, and no identifiable cause of hypothalamic-pituitary-gonadal [HPG] axis dysfunction) were eligible for inclusion. CHH reversal was defined as spontaneous recovery of HPG axis function off treatment. Centres provided common data elements on patient phenotype, clinical assessment, and genetics using a structured, harmonised data collection form developed by COST Action BM1105. Latent class mixture modelling (LCMM) was applied to establish whether at least two distinct classes of reversal could be identified and differentially predicted, and results were compared with a cohort of patients without CHH reversal to identify potential predictors of reversal. The primary outcome was the presence of at least two distinct classes of reversal. FINDINGS: A total of 87 male patients with CHH reversal and 108 without CHH reversal were included in the analyses. LCMM identified two distinct reversal classes (75 [86%] in class 1 and 12 [14%] in class 2) on the basis of mean testicular volume, micropenis, and serum follicle-stimulating hormone (FSH) concentration. Classification probabilities were robust (0·998 for class 1 and 0·838 for class 2) and modelling uncertainty was low (entropy 0·90). Compared with class 1, patients in class 2 had significantly larger testicular volume (p<0·0001), no micropenis, and higher serum FSH concentrations (p=0·041), consistent with the Pasqualini syndrome (fertile eunuch) subtype of CHH. Patients without CHH reversal were more likely to have anosmia (p=0·016), cryptorchidism (p=0·0012), complete absence of puberty (testicular volume <4 cm³; p=0·0016), and two or more rare genetic variants (ie, oligogenicity; p=0·0001). Among patients who underwent genetic testing, no patients (of 75) with CHH reversal had a rare pathogenic ANOS1 variant compared with ten (11%) of 95 patients without CHH reversal. Individuals with CHH reversal had a significantly higher rate of rare variants in GNRHR than did those without reversal (nine [12%] of 75 vs three [3%] of 95; p=0·025). INTERPRETATION: Applying LCMM to a large cohort of male patients with CHH reversal uncovered two distinct classes of reversal. Genetic investigation combined with careful clinical phenotyping could help surveillance of reversal after withdrawing treatment, representing the first tailored management approach for male patients with this rare endocrine disorder. FUNDING: National Institutes of Health National Center for Advancing Translational Sciences; Ministry of Health, Rome, Italy; Ministry of University, Rome, Italy; National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the Josiah Macy Jr Foundation. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Psychometric Evaluation of the German Version of the Perceived Access to Healthcare Questionnaire in a Sample of Individuals with Rare Chronic Diseases.

Access to healthcare is multifaceted and poses significant challenges for individuals with chronic and rare diseases (RDs). This study aimed to conduct a psychometric evaluation of the German version of the Perception of Access to Healthcare Questionnaire (PAHQ) among individuals with RDs. We conducted an evaluation of the PAHQ using a sample of 271 adults with an RD diagnosis. The 31-item instrument underwent evaluation including a comparison of three different confirmatory factor models (CFA). Subsequent steps involved item removal, reliability analysis (computation of Cronbach's alpha), and analysis of criterion-related validity. The six-factor model showed the best fit to the data and was selected for further examination. Subsequently, six items were removed. Fit indices for the final model were acceptable. Cronbach's alpha ranged from 0.75 to 0.91 for the six subscales, except for the availability subscale which exhibited the lowest value (0.64). In terms of criterion-related validity, different skills relating to the navigation of access dimensions were significantly correlated with corresponding PAHQ subscales, thus confirming validity. The capacity of the PAHQ to guide targeted interventions and facilitate cross-population comparisons positions it as a valuable instrument for advancing healthcare access research and promoting equitable access to care, particularly for individuals with rare and chronic diseases.

Current State of Genomics in Nursing: A Scoping Review of Healthcare Provider Oriented (Clinical and Educational) Outcomes (2012-2022).

In the 20 years since the initial sequencing of the human genome, genomics has become increasingly relevant to nursing. We sought to chart the current state of genomics in nursing by conducting a systematic scoping review of the literature in four databases (2012-2022). The included articles were categorized according to the Cochrane Collaboration outcome domains/sub-domains, and thematic analysis was employed to identify key topical areas to summarize the state of the science. Of 8532 retrieved articles, we identified 232 eligible articles. The articles primarily reported descriptive studies from the United States and other high-income countries (191/232, 82%). More than half (126/232, 54.3%) aligned with the "healthcare provider oriented outcomes" outcome domain. Three times as many articles related to the "knowledge and understanding" sub-domain compared to the "consultation process" subdomain (96 vs. 30). Five key areas of focus were identified, including "nursing practice" (50/126, 40%), "genetic counseling and screening" (29/126, 23%), "specialist nursing" (21/126, 17%), "nurse preparatory education" (17/126, 13%), and "pharmacogenomics" (9/126, 7%). Only 42/126 (33%) articles reported interventional studies. To further integrate genomics into nursing, study findings indicate there is a need to move beyond descriptive work on knowledge and understanding to focus on interventional studies and implementation of genomics into nursing practice.

What Are the Best Practices for Co-Creating Patient-Facing Educational Materials? A Scoping Review of the Literature.

Co-creating patient-facing educational materials (PEMs) can enhance person-centered care by responding to patient priorities and unmet needs. Little data exist on 'best practices' for co-creation. We followed the Arksey and O'Malley framework to conduct a systematic literature search of nine databases (MEDLINE, PubMed, EMBASE, CINAHL, PsycINFO, Web of Science, Cochrane Library, Joanna Briggs Institute, TRIP-April, 2022) to identify empirical studies published in English on PEM co-creation to distill 'best practices'. Following an independent dual review of articles, data were collated into tables, and thematic analysis was employed to synthesize 'best practices' that were validated by a patient experienced in co-creating PEMs. Bias was not assessed, given the study heterogeneity. Of 6998 retrieved articles, 44 were included for data extraction/synthesis. Studies utilized heterogeneous methods spanning a range of health conditions/populations. Only 5/45 (11%) studies defined co-creation, 14 (32%) used a guiding framework, and 18 (41%) used validated evaluation tools. Six 'best practices' were identified: (1) begin with a review of the literature, (2) utilize a framework to inform the process, (3) involve clinical and patient experts from the beginning, (4) engage diverse perspectives, (5) ensure patients have the final decision, and (6) employ validated evaluation tools. This scoping review highlights the need for clear definitions and validated evaluation measures to guide and assess the co-creation process. Identified 'best practices' are relevant for use with diverse patient populations and health issues to enhance person-centered care.

Glucose variability in 6-12-month-old healthy infants.

Background: Metabolic programming of glucose homeostasis in the first 1,000 days of life may impact lifelong metabolic and cardiovascular health. Continuous glucose monitoring (CGM) devices may help measure the impact of dietary intake on glucose rhythms and metabolism in infants during the complementary feeding period. Objectives: Demonstrate the feasibility of CGM to measure and quantify glucose variability in response to infant feeding and to evaluate associations between macronutrient meal composition and glucose variability. Methods: The "FreeStyle Libre Pro®" device interstitial glucose meter was applied to the anterior thigh of 10 healthy 6-12-month-old infants. Parents recorded food intake, time of feeding, and used daily dairies to record sleep time and duration. Descriptive statistics were employed for food intake, sleep and key glycemic parameters over three full days. Mixed linear models were used to assess glycemic changes. Results: Mid-day, afternoon, and evening feeds contained >30 g carbohydrate and induced higher 2-h iAUC (3.42, 3.41, and 3.50 mmol/L*h respectively) compared to early and mid-morning feedings with ≤25 g carbohydrates (iAUC 2.72 and 2.81 mmol/L*h, p < 0.05). Early morning and evening milk feedings contained approximately 9 g of fat and induced a longer time to reach maximal glucose value (Tmax; 75 and 68 min, respectively) compared to lower fat feedings (2.9-5.9 g; Tmax range: 34-60 min; p < 0.05). Incremental glucose value at time of food intake (C0) increased significantly from 0.24 ± 0.39 mM in early morning to 1.07 ± 0.57 mM in the evening (p < 0.05). Over the day, 70% of glucose values remained within the normal range (3.5-5.5 mmol/L), 10% were between 5.5-10 mmol/L, and 20% were < 3.5 mmol/L. Conclusion: Our data support the feasibility of using CGM to measure glucose in 6-12-month-old infants. The observation of possible diurnal glucose variability and typical glucose values may have implications for future studies investigating metabolic adaptation to nutritional intake in early life.

Racial and Ethnic Disparities in Genomic Healthcare Utilization, Patient Activation, and Intrafamilial Communication of Risk among Females Tested for BRCA Variants: A Mixed Methods Study.

This study aimed to gain a deeper understanding of genomic healthcare utilization, patient activation, and intrafamilial risk communication among racially and ethnically diverse individuals tested for BRCA variants. We employed an explanatory, sequential, mixed-methods study guided by the Theory of Planned Behavior. Participants completed an online survey, including sociodemographic, medical history, and several validated instruments. A subset of participants participated in in-depth, semi-structured interviews. A total of 242 women were included in the quantitative analyses. The majority of survey participants identified as non-Hispanic white (NHW) (n = 197, 81.4%) while 45/242 (18.5%) identified as black, Indigenous, and people of color (BIPOC). The NHW participants were more likely to communicate genetic test results with healthcare providers, family, and friends than BIPOC participants (p < 0.05). BIPOC participants had lower satisfaction with testing decisions and significantly higher ratings of personal discrimination, fatalism, resilience, uncertainty, and lower patient activation scores (p < 0.05). Participants with higher education, greater satisfaction with testing decisions, and lower resilience are more likely to communicate BRCA test results with family members through the mediating effect of patient activation. Bridging disparities to ensure that genomic healthcare benefits all people may demand theory-driven, multi-level interventions targeting the individual, interpersonal, and healthcare system levels.

Patient Assessment Chronic Illness Care (PACIC) and its associations with quality of life among Swiss patients with systemic sclerosis: a mixed methods study.

BACKGROUND: The Chronic Care Model (CCM) is a longstanding and widely adopted model guiding chronic illness management. Little is known about how CCM elements are implemented in rare disease care or how patients' care experiences relate to health-related quality of life (HRQoL). We engaged patients living with systemic sclerosis (SSc) to assess current care according to the CCM from the patient perspective and their HRQoL. METHODS: We employed an explanatory sequential mixed methods design. First, we conducted a cross-sectional quantitative survey (n = 101) using the Patient Assessment of Chronic Illness Care (PACIC) and Systemic Sclerosis Quality of Life (SScQoL) questionnaires. Next, we used data from individual patient interviews (n = 4) and one patient focus group (n = 4) to further explore care experiences of people living with SSc with a focus on the PACIC dimensions. RESULTS: The mean overall PACIC score was 3.0/5.0 (95% CI 2.8-3.2, n = 100), indicating care was 'never' to 'generally not' aligned with the CCM. Lowest PACIC subscale scores related to 'goal setting/tailoring' (mean = 2.5, 95% CI 2.2-2.7) and 'problem solving/contextual counselling' (mean = 2.9, 95% CI 2.7-3.2). No significant correlations were identified between the mean PACIC and SScQoL scores. Interviews revealed patients frequently encounter major shortcomings in care including 'experiencing organized care with limited participation', 'not knowing which strategies are effective or harmful' and 'feeling left alone with disease and psychosocial consequences'. Patients often responded to challenges by 'dealing with the illness in tailored measure', 'taking over complex coordination of care' and 'relying on an accessible and trustworthy team'. CONCLUSIONS: The low PACIC mean overall score is comparable to findings in patients with common chronic diseases. Key elements of the CCM have yet to be systematically implemented in Swiss SSc management. Identified gaps in care related to lack of shared decision-making, goal-setting and individual counselling-aspects that are essential for supporting patient self-management skills. Furthermore, there appears to be a lack of complex care coordination tailored to individual patient needs.

Reproductive Phenotypes and Genotypes in Men With IHH.

CONTEXT: Isolated hypogonadotropic hypogonadism (IHH) is phenotypically and genetically heterogeneous. OBJECTIVE: This work aimed to determine the correlation between genotypic severity with pubertal and neuroendocrine phenotypes in IHH men. METHODS: A retrospective study was conducted (1980-2020) examining olfaction (Kallmann syndrome [KS] vs normosmic IHH [nHH]), baseline testicular volume (absent vs partial puberty), neuroendocrine profiling (pulsatile vs apulsatile luteinizing hormone [LH] secretion), and genetic variants in 62 IHH-associated genes through exome sequencing (ES). RESULTS: In total, 242 men (KS: n = 131 [54%], nHH: n = 111 [46%]) were included. Men with absent puberty had significantly lower gonadotropin levels (P < .001) and were more likely to have undetectable LH (P < .001). Logistic regression showed partial puberty as a statistically significant predictor of pulsatile LH secretion (R2 = 0.71, P < .001, OR: 10.8; 95% CI, 3.6-38.6). Serum LH of 2.10 IU/L had a 95% true positive rate for predicting LH pulsatility. Genetic analyses in 204 of 242 IHH men with ES data available revealed 36 of 204 (18%) men carried protein-truncating variants (PTVs) in 12 IHH genes. Men with absent puberty and apulsatile LH were enriched for oligogenic PTVs (P < .001), with variants in ANOS1 being the predominant PTV in this genotype-phenotype association. Men with absent puberty were enriched for ANOS1 PTVs compared to partial puberty counterparts (P = .002). PTVs in other IHH genes imparted more variable reproductive phenotypic severity. CONCLUSION: Partial puberty and LH greater than or equal to 2.10 IU/L are proxies for pulsatile LH secretion. ANOS1 PTVs confer severe reproductive phenotypes. Variable phenotypic severity in the face of severe genetic variants in other IHH genes point to significant neuroendocrine plasticity of the HPG axis in IHH men.

ACCESS: an empirically-based framework developed by the International Nursing CASCADE Consortium to address genomic disparities through the nursing workforce.

Introduction: Efforts are needed across disciplines to close disparities in genomic healthcare. Nurses are the most numerous trained healthcare professionals worldwide and can play a key role in addressing disparities across the continuum of care. ACCESS is an empirically-based theoretical framework to guide clinical practice in order to ameliorate genomic disparities. Methods: The framework was developed by the International Nursing CASCADE Consortium based on evidence collected between 2005 and 2023 from individuals and families of various ethnic backgrounds, with diverse hereditary conditions, and in different healthcare systems, i.e., Israel, Korea, Switzerland, and several U.S. States. The components of the framework were validated against published scientific literature. Results: ACCESS stands for Advocating, Coping, Communication, cascadE Screening, and Surveillance. Each component is demonstrated in concrete examples of clinical practice within the scope of the nursing profession related to genomic healthcare. Key outcomes include advocacy, active coping, intrafamilial communication, cascade screening, and lifelong surveillance. Advocacy entails timely identification of at-risk individuals, facilitating referrals to specialized services, and informed decision-making for testing. Active coping enhances lifelong adaptation and management of disease risk. Effective intrafamilial communication of predisposition to hereditary disease supports cascade testing of unaffected at-risk relatives. Lifelong surveillance is essential for identifying recurrence, changes in health status, and disease trajectory for life-threatening and for life-altering conditions. Discussion: ACCESS provides a standardized, systematic, situational, and unifying guide to practice and is applicable for nursing and for other healthcare professions. When appropriately enacted it will contribute towards equitable access to genomic resources and services.

Reversible hypogonadotropic hypogonadism in men with the fertile eunuch/Pasqualini syndrome: A single-center natural history study.

Congenital hypogonadotropic hypogonadism (HH) is a heterogeneous genetic disorder characterized by disrupted puberty and infertility. In most cases, HH is abiding yet 10-15% undergo reversal. Men with HH and absent and partial puberty (i.e., testicular volume <4mL and >4mL respectively) have been well-studied, but the rare fertile eunuch (FE) variant remains poorly characterized. This natural history study of 240 men with HH delineates the clinical presentation, neuroendocrine profile, rate of reversal and genetics of the FE variant. We compared three HH groups: FE (n=38), absent puberty (n=139), and partial puberty (n=63). The FE group had no history of micropenis and 2/38 (5%) had cryptorchidism (p<0.0001 vs. other groups). The FE group exhibited higher rates of detectable gonadotropins, higher mean LH/FSH levels, and higher serum inhibin B levels (all p<0.0001). Neuroendocrine profiling showed pulsatile LH secretion in 30/38 (79%) of FE men (p<0.0001) and 16/36 (44%) FE men underwent spontaneous reversal of HH (p<0.001). The FE group was enriched for protein-truncating variants (PTVs) in GNRHR and FGFR1 and 4/30 (13%) exhibited oligogenic PTVs. Findings suggest men with the FE variant exhibit the mildest neuroendocrine defects of HH men and the FE sub-type represents the first identified phenotypic predictor for reversible HH.

Advancing qualitative rare disease research methodology: a comparison of virtual and in-person focus group formats.

BACKGROUND: Rare disease research is hampered in part by the fact that patients are geographically dispersed. Rare disease patient communities are recognized for their use of the internet to learn about their condition and find peer-to-peer support. As such, web-based technologies offer promise for overcoming geographic barriers in rare disease research for many. Qualitative focus groups (FGs) are a widely used methodology used to understand patients and parents/families 'lived experience' and unmet needs is important to improve care for rare diseases. It is unclear if web-enabled (virtual) FGs are comparable to traditional in-person approaches. We conducted in-person (n = 3) and virtual (n = 3) FGs with rare disease patients to determine if virtual FGs produce similar results in-person FGs. RESULTS: Three in-person (n = 33 participants) and three virtual (n = 25 participants) FGs were conducted examining attitudes and beliefs regarding genetic testing and family communication of risk. Participants included 30 males, 18 females, and 10 parents/guardians. Two independent investigators identified excerpts (meaningful sections of text) and coded themes/sub-themes using a codebook. Inter-coder agreement across identified excerpts (n = 530) in both FG formats was 844/875 (96.5%). Two additional investigators reviewed coded excerpts and did not identify additional themes/sub-themes-supporting data saturation across FG formats. Virtual FGs accounted for 303/530 (57.2%) of total excerpts and 957/1721 (55.7%) of all identified themes/sub-themes. Formats were similar in terms of overall number of excerpts (101 ± 7.8 vs. 75.7 ± 18.8, p = 0.26) and themes/sub-themes (319 ± 6.1 vs. 254.7 ± 103.6, p = 0.34) between virtual and in-person FGs. However, virtual FGs had significantly more coded excerpts specifically relating to sensitive/intimate topics including 'attitudes and beliefs' (n = 320 vs. n = 235, p < 0.001), 'information and support' (n = 184 vs. n = 99, p < 0.001), and 'family communication' (n = 208 vs. n = 114, p < 0.001). CONCLUSIONS: Virtual FGs yielded similar numbers of coded excerpts compared to traditional in-person FGs. Virtual FGs appear to support the relative anonymity of participants, resulting in richer discussion of highly sensitive, intimate topics. Findings support the validity and methodologic rigor of using web-enabled technologies for conducting FGs in rare diseases.

Health-related quality of life in women with primary ovarian insufficiency: a scoping review of the literature and implications for targeted interventions.

STUDY QUESTION: What is known about health-related quality of life (HR-QoL) in women with idiopathic primary ovarian insufficiency (POI)? SUMMARY ANSWER: Women with POI have a range of unmet psychosocial needs relating to three interrelated themes: 'diagnostic odyssey', 'isolation and stigma' and impaired 'ego integrity'. WHAT IS KNOWN ALREADY: Prior studies have reported increased depressive symptoms, diminished sexual function and altered body image/self-concept in women with POI. STUDY DESIGN, SIZE, DURATION: A systematic scoping review (11 databases) on HR-QoL in POI including published quantitative, qualitative and mixed-methods studies as well as unpublished gray literature (i.e. unpublished dissertations) through June, 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: After removing duplicates, 1244 articles underwent title and abstract review by independent reviewers. The remaining 72 relevant articles underwent dual full text review to determine inclusion criteria yielding 24 articles (100% concordance) for data extraction. Findings were summarized in tables by methodology and recurrent HR-QoL themes/sub-themes were mapped to define key aspects of HR-QoL in POI. Promoters of active coping were charted at the individual, interpersonal and healthcare system levels. Targets for tailored interventions supporting active coping and improved HR-QoL were mapped to the Theory of Planned Behavior (TPB). MAIN RESULTS AND THE ROLE OF CHANCE: Three interrelated themes affecting HR-QoL in POI emerged from the data synthesis. First, the theme 'diagnostic odyssey' comprised sub-themes of uncertainty, lack of control, knowledge gaps, discontinuous care and negative clinical interactions. The second theme 'isolation and stigma' included sub-themes of guilt, shame, concealment, feeling labeled as infertile, lack of social support and unsympathetic clinicians. The third theme, impaired 'ego integrity' captured sub-themes of decreased sexual function, altered body image, psychological vulnerability and catastrophizing. Targets promoting active coping at the individual (n = 2), interpersonal (n = 1) and healthcare system (n = 1) levels were mapped to the TPB to inform development of tailored interventions supporting active coping and improved HR-QoL in POI (i.e. narrative intervention, co-creating patient-facing materials, peer-to-peer support and provider resources). LIMITATIONS, REASONS FOR CAUTION: No studies using a POI-specific HR-QoL instrument were identified. No interventional studies aimed at improving HR-QoL in POI were identified. Only articles published in English were included in the study. WIDER IMPLICATIONS OF THE FINDINGS: Women with POI frequently have impaired HR-QoL related to the life-altering infertility diagnosis. The range of unmet psychosocial needs may be relevant for informing interventions for other populations with infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development 'Massachusetts General Hospital-Harvard Center for Reproductive Medicine' (1 P50 HD104224-01 NICHD). The authors have no conflicts to declare. REGISTRATION NUMBER: N/A.

Navigating Disrupted Puberty: Development and Evaluation of a Mobile-Health Transition Passport for Klinefelter Syndrome.

Klinefelter syndrome (KS) is the most common aneuploidy in men and has long-term sequelae on health and wellbeing. KS is a chronic, lifelong condition and adolescents/young adults (AYAs) with KS face challenges in transitioning from pediatric to adult-oriented services. Discontinuity of care contributes to poor outcomes for health and wellbeing and transition programs for KS are lacking. We aimed to develop and test a mobile health tool (KS Transition Passport) to educate patients about KS, encourage self-management and support successful transition to adult-oriented care. First, we conducted a retrospective chart review and patient survey to examine KS transition at a university hospital. Second, we conducted a systematic scoping review of the literature on AYAs with KS. Last, we developed a mobile health transition passport and evaluated it with patient support groups. Participants evaluated the tool using the System Usability Scale and Patient Education Materials Assessment Tool (PEMAT). Chart review identified 21 AYAs diagnosed between 3.9-16.8 years-old (median 10.2 years). The survey revealed only 4/10 (40%) were on testosterone therapy and fewer (3/10, 30%) had regular medical care. The scoping review identified 21 relevant articles highlighting key aspects of care for AYAs with KS. An interprofessional team developed the mobile-health KS transition passport using an iterative process. Support group members (n=35) rated passport usability as 'ok' to 'good' (70 ± 20, median 73.5/100). Of PEMAT dimensions, 5/6 were deemed 'high quality' (86-90/100) and participants knew what to do with the information (actionability = 83/100). In conclusion, many patients with KS appear to have gaps in transition to adult-oriented care. Iterative development of a KS transition passport produced a mobile health tool that was usable, understandable and had high ratings for actionability.