Work participation in adults with rare genetic diseases - a scoping review.

BACKGROUND: Work participation is a crucial aspect of health outcome and an important part of life for most people with rare genetic diseases. Despite that work participation is a social determinant of health and seems necessary for understanding health behaviours and quality of life, it is an under-researched and under-recognized aspect in many rare diseases. The objectives of this study was to map and describe existing research on work participation, identify research gaps, and point to research agendas in a selection of rare genetic diseases. METHODS: A scoping review was performed by searching relevant literature in bibliographic databases and other sources. Studies addressing work participation in people with rare genetic diseases published in peer reviewed journals were assessed using EndNote and Rayyan. Data were mapped and extracted based on the research questions concerning the characteristics of the research. RESULTS: Of 19,867 search results, 571 articles were read in full text, and 141 satisfied the eligibility criteria covering 33 different rare genetic diseases; 7 were reviews and 134 primary research articles. In 21% of the articles the primary aim was to investigate work participation. The extent of studies varied between the different diseases. Two diseases had more than 20 articles, but most had only one or two articles. Cross-sectional quantitative studies were predominant, with few utilizing prospective or qualitative design. Nearly all articles (96%) reported information about work participation rate, and 45% also included information about factors associated with work participation and work disability. Due to differences in methodologies, cultures and respondents, comparison between and within diseases are difficult. Nevertheless, studies indicated that many people with different rare genetic diseases experience challenges related to work, closely associated to the symptoms of the disease. CONCLUSION: While studies indicate high prevalence of work disability in many patients with rare diseases, the research is scarce and fragmented. More research is warranted. Information about the unique challenges of living with different rare diseases is crucial for health and welfare systems to better facilitate work participation. In addition, the changing nature of work in the digital age, may also open up new possibilities for people with rare genetic diseases and should be explored.

Fatigue in patients with syndromic heritable thoracic aortic disease: a systematic review of the literature and a qualitative study of patients' experiences and perceptions.

INTRODUCTION: The purpose of this study was to explore the literature on fatigue in patients with syndromic heritable thoracic aortic disease (sHTAD), including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers Danlos syndrome (vEDS) and other sHTADs, critically appraise and synthesize the relevant literature. We also aimed to investigate how adults with sHTAD experience and perceive fatigue, and to discuss clinical implications and direction for further research. METHODS: First, a systematic review was performed by searching the published literature in all relevant databases and other sources until 20th October 2022. Second, a qualitative focus group interview study was conducted of 36 adults with sHTADs (LDS n = 11, MFS n = 14, vEDS n = 11). RESULTS: In the systematic review, 33 articles satisfied the eligibility criteria (3 reviews and 30 primary studies). Of the primary studies: 25 dealt with adults (MFS n = 17, MFS/EDS n = 1, EDS n = 2, LDS/vEDS n = 3, different sHTADs n = 2), 5 with children (MFS n = 4, different sHTADs n = 1). Twenty-two were cross-sectional quantitative studies, 4 prospective and 4 qualitative studies. The quality of the included studies was mostly good, but many had small sample sizes, low response rates and/or participants without verified diagnosis. Despite these limitations, studies indicated high prevalence of fatigue (ranging from 37 to 89%), and fatigue was associated with both health and psychosocial aspects. Few studies found that fatigue was associated with disease-related symptoms. In the qualitative focus groups most of the participants reported that they had experienced fatigue which influenced several aspects of life. Four themes related to fatigue were elucidated: (1) different diagnoses-different fatigue?, (2) the nature of fatigue, (3) searches for causes of fatigue, (4) dealing with fatigue in daily life. The four themes seemed mutually interrelated in terms of barriers, strategies and facilitators for dealing with fatigue. The participants experienced fatigue as a consistent dilemma between self-assertion and inadequacy. Fatigue seems to influence several aspects of daily life and may be one of the most debilitating symptoms of having a sHTAD. CONCLUSION: Fatigue seems to negatively impact the lives of people with sHTADs and should be recognized as an important aspect in the lifelong follow-up of these patients. The life-threatening complications of sHTADs may result in emotional stress, including fatigue and the risk of developing a sedentary lifestyle. Research and clinical initiatives should consider rehabilitation interventions aiming at postponing the onset or reducing symptoms of fatigue.

Patient involvement in rare diseases research: a scoping review of the literature and mixed method evaluation of Norwegian researchers' experiences and perceptions.

BACKGROUND: Patients' involvement (PI) in research is recognized as a valuable strategy for increasing the quality, developing more targeted research and to speed up more innovative research dissemination. Nevertheless, patient involvement in rare diseases research (PI-RDR) is scarce. The aims were: To study the Norwegian researchers` experiences and perceptions of PI-RDR and review the literature on PI-RDR. METHODS: 1. A systematic scoping review of the literature on PI-RDR. 2. A cross-sectional questionnaire study with close-ended and open-ended questions to investigate the researchers` experiences. RESULTS: In the scoping review 608 articles read in full-text and 13 articles (one review and twelve primary studies) were included. The heterogeneity of the design, methodology and results was large. Most studies described several benefits of PI, but few described methods for measuring impacts and effectiveness of PI-RDR. In the cross sectional part of this study, 145 of 251 employees working in the nine Norwegian Centers on Rare Diseases participated, of these 69 were researchers. Most (95%) of the researchers claimed that rare diseases research is more challenging than for the more common diseases. The majority (95%) argued that PI-RDR may increase the quality of the studies and the relevance, and most (89%) agreed that PI-RDR in dissemination may increase the awareness and public interest for rare diseases. In the open-ended questions several researchers also claimed challenges related to PI-RDR, and many had proposal for improving PI and promotion of rare disease research. CONCLUSION: Both the literature and researchers emphasized that PI-RDR is important for improving research quality and increase the public attention on rare diseases, but what constitutes effective PI-RDR still remain unclear. More research on the design, methodology and assessment for measuring the impact of PI-RDR is warranted.

Experienced fatigue in people with rare disorders: a scoping review on characteristics of existing research.

BACKGROUND: Experienced fatigue is an under-recognized and under-researched feature in persons with many different rare diseases. A better overview of the characteristics of existing research on experienced fatigue in children and adults with rare diseases is needed. The purpose of this review was to map and describe characteristics of existing research on experienced fatigue in a selection of rare diseases in rare developmental defects or anomalies during embryogenesis and rare genetic diseases. Furthermore, to identify research gaps and point to research agendas. METHODS: We applied a scoping review methodology, and performed a systematic search in March 2020 in bibliographic databases. References were sorted and evaluated for inclusion using EndNote and Rayyan. Data were extracted on the main research questions concerning characteristics of research on experienced fatigue (definition and focus on fatigue, study populations, research questions investigated and methods used). RESULTS: This review included 215 articles on ten different rare developmental defects/anomalies during embryogenesis and 35 rare genetic diseases. Of the 215 articles, 82 had investigation of experienced fatigue as primary aim or outcome. Included were 9 secondary research articles (reviews) and 206 primary research articles. A minority of articles included children. There were large differences in the number of studies in different diseases. Only 29 of 215 articles gave a description of how they defined the concept of experienced fatigue. The most common research-question reported on was prevalence and/ -or associations to fatigue. The least common was diagnostics (development or validation of fatigue assessment methods for a specific patient group). A large variety of methods were used to investigate experienced fatigue, impeding comparisons both within and across diagnoses. CONCLUSION: This scoping review on the characteristics of fatigue research in rare diseases found a large variety of research on experienced fatigue. However, the minority of studies had investigation of experienced fatigue as a primary aim. There was large variation in how experienced fatigue was defined and also in how it was measured, both within and across diagnoses. More research on experienced fatigue is needed, both in children and adults with rare diseases. This review offers a basis for further research.

Multidisciplinary aortopathy clinics: A systematic scoping review of the literature and evaluation of patient experiences from a newly started clinic in Norway.

BACKGROUND: International guidelines recommend hereditary thoracic aortic diseases (HTADs) to be managed in multidisciplinary aorta clinics. AIM: To study HTAD patient's experiences with a aortopathy clinic in Norway and to review the literature on aortopathy clinics. METHODS: (a) A systematic scoping review of research on multidisciplinary clinics for HTADs. (b) A cross-sectional postal questionnaire study to investigate patient experiences with the health-services. Fifty consecutive patients from the aortopathy clinic and 50 controls in usual care were invited to participate. RESULTS: The review identified eight publications on aortopathy clinics. Although the papers were not judged for quality, these showed promising results from such clinics in terms of diagnostics and increased adherence to guideline-directed therapy. The survey constituted thirty-seven (74%) patients and 22 (44%) controls who responded to postal questionnaires. Both groups reported delays in diagnostics and follow-up appointments prior to the start of the clinic. Patients indicated high satisfaction with the aortopathy clinic, whereas controls reported poor coordination of medical follow-up. Individuals in both groups struggled with disease self-management. CONCLUSION: Norwegian patient experiences found the aortopathy clinic beneficial. According to studies included in the review, disease management in aortopathy clinics may improve patient satisfaction, diagnostics and follow-up. Effect studies may further document the benefits of clinic organization, treatment, cost-efficiency and patient experiences.

A scoping review presenting a wide variety of research on paediatric and adolescent patients with Marfan syndrome.

AIM: The present study aimed to map and summarise the research on children, aged 0-18 years, with Marfan syndrome, identify research gaps and point to research agendas. METHODS: A scoping review was systematically performed by searching multiple databases from January 1996 to April 2019. Primary studies presenting results on at least six individuals aged 0-18 years with Marfan syndrome, diagnosed according to the Ghent nosology, were selected. RESULTS: From 2341 de-duplicated records, 92 papers were included, mapped and described. Their topics were diagnostics (12%), cardiovascular matters (50%), skeletal matters (22%), ocular matters (9%), other medical aspects (5%) and psychosocial perspectives (2%). Most studies were from Europe and North America and published between 1999 and 2019 in subject-specific or paediatric journals, while a few were published in genetics journals. All studies had quantitative designs, and very few were multicentre studies. Each study had six to 608 subjects for a total of approximately 5809. CONCLUSION: A wide range of research topics on adolescent and paediatric Marfan syndrome was found, but qualitative studies and a focus on psychosocial matters were lacking. Future investigations addressing noncardiovascular consequences and patient experiences are needed, as well as studies reaffirming or replicating existing intervention study results.

Fatigue and pain in children and adults with multiple osteochondromas in Norway, a cross-sectional study.

BACKGROUND: Multiple Osteochondromas (MO) is a rare skeletal disorder frequently needing orthopaedic surgery. High prevalence of pain has been reported, however fatigue has not previously been investigated. PURPOSE: Our aims were to investigate prevalence of fatigue and pain in Norwegian children and adults with MO. Furthermore to compare prevalence of fatigue with reported prevalence in other groups and explore some factors that may contribute to fatigue in this population. METHODS: Questionnaire data was obtained from 11 children and 21 adults, approximately one third of the estimated MO population in Norway. Fatigue and pain was measured with validated instruments. RESULTS: Children with MO reported significantly higher fatigue than healthy children. Adults reported significantly higher fatigue than the general Norwegian population. Six of 11 children and 20 of 21 adults reported pain. Severe fatigue was more prevalent in persons with high age, high pain intensity and many pain locations; however none of these differences were significant. CONCLUSION: High prevalence of fatigue was found in Norwegian children and adults with MO. Such findings have not been previously reported. Pain was prevalent in both children and adults. This implies that fatigue and pain warrant specific attention in clinical practice and further research regarding persons with MO.

Systematic review of quality of life in persons with hereditary thoracic aortic aneurysm and dissection diagnoses.

The purpose of this study was to explore the literature on quality of life (QoL) in patients with hereditary thoracic aortic aneurysm and dissection (HTAAD); including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS) and other HTAAD diagnoses, critically appraising and synthesizing the relevant literature. A systematic review was performed by searching the published literature using available medical, physical, psychological, social databases and other sources. Studies addressing QoL in persons with an HTAAD diagnosis, published in peer-reviewed journals were assessed. Of 227 search results, 20 articles satisfied the eligibility criteria. No studies of QoL in LDS, vEDS, or other HTAAD were found, only on MFS. Most studies had been published in the last 3 years. All were cross-sectional quantitative studies besides one pilot intervention study. Most studies were of small sample size, had low response rate or participants without verified diagnosis. Despite these limitations, most studies indicate that having an HTAAD diagnosis as MFS may negatively impact QoL, but few studies found any associations between the biomedical symptoms and decreased QoL. More research is needed on QoL in samples with verified HTAAD diagnosis to develop evidence-based knowledge and appropriate guidelines for these diagnoses.

Education and work participation among adults with congenital unilateral upper limb deficiency in Norway: A cross-sectional study.

OBJECTIVES: To describe level of education and work participation among adults with congenital unilateral upper limb deficiency (CUULD) in Norway and to explore associations between work participation and demographic and clinical factors. METHODS: Cross-sectional study. In 2012, a postal questionnaire was sent to 186 persons with congenital limb deficiency (CLD), age ≥ 20 years, registered at the TRS National Resource Center for Rare Disorders. In the original CLD study, 77 persons with CUULD responded. In this paper 64 persons with CUULD of working age (20-67 years) are included. Data on demographic factors as education level and work participation, and clinical factors including limb deficiency characteristics, chronic pain (Standardized Nordic Questionnaire), fatigue (Fatigue Severity Scale), physical and mental health (SF-36) were analyzed through descriptive and comparable statistics and logistic regression analyses. RESULTS: Sixty-four persons participated, mean age 43.4 (SD 13.7; range 20-67 years), 45 were women. Education level >13 years was reported by 34. Forty- three of the 64 participants were employed, 21 were prematurely retired (disability benefits). 11 of the 43 employed, and 6 of the 21 prematurely retired had completed vocational education. Physically demanding occupations (work activities that required standing, walking and lifting) were reported by 25 of the 43 employed and 13 of the 21 prematurely retired. 17 of the 64 reported need for further adaptions in their workplaces. The strongest predictors of work participation were younger age (OR 0.86) and good physical health (OR 1.21). CONCLUSION: Two thirds of persons with CUULD were employed; while one third was prematurely retired and had left work earlier than expected. This suggests that persons with CUULD may experience challenges in work participation. Although levels of education were relatively high, several had chosen careers that required physical strain. Younger age and good physical health were the most important factors mediating work participation.

Chronic pain and fatigue in adults with congenital unilateral upper limb deficiency in Norway. A cross-sectional study.

PURPOSE: To describe Norwegian adults with congenital unilateral upper limb deficiency (CUULD) regarding self-reported chronic pain (intensity, locations, impact on daily life) and fatigue. Analyze associations between chronic pain and demographic/clinical factors and associations between fatigue and demographic/ clinical factors. MATERIALS AND METHODS: Cross-sectional study. In 2012, a postal questionnaire was sent to 186 persons with congenital limb deficiency, age ≥ 20 years. Seventy seven persons with CUULD responded and are included in this paper. The questionnaire included questions on demographic and clinical factors, chronic pain (Brief Pain Inventory, Standardized Nordic Questionnaire) and fatigue (Fatigue severity scale (FSS)). RESULTS: Mean age was 42.7 (SD 16.0), 71% were women. Sixty tree % reported chronic pain, many had bilateral pain, most common pain locations were neck (78%) and shoulder/upper arm (78%). However, reported mean pain intensity (3.3 (SD 2.8)) and mean number of pain locations (3.0 (SD 2.5)) were moderate to low. Thirty seven persons reported that pain started in adult age (≥ 19 years). One third reported severe fatigue (FSS ≥ 5). Persons reporting cold sensitivity and severe fatigue were most likely to have chronic pain. CONCLUSIONS: Congenital upper limb deficiency increases the risk of self-reported pain in neck, shoulder/upper arm, cold sensitivity and severe fatigue. Pain, fatigue and cold sensitivity may individually affect function, and may together reinforce functional problems. This should be to taken into account when rehabilitation programs are developed. Further studies of more representative samples should be conducted to confirm our findings.

Satisfaction with life in adults with Marfan syndrome (MFS): associations with health-related consequences of MFS, pain, fatigue, and demographic factors.

PURPOSE: The objective with this study was to explore satisfaction with life (SWL) among adults with Marfan syndrome (MFS) compared to the general Norwegian population and other patient groups and further to examine the associations between SWL and demographic factors, contact with social and health services, MFS-related health problems, chronic pain, and fatigue. METHODS: This is a cross-sectional study with postal questionnaire, including the Satisfaction with Life Scale (SWLS), questions on demographic factors, health-related aspects of MFS, and validated instruments measuring chronic pain (Standardized Nordic Questionnaire) and fatigue (Fatigue Severity Scale). One hundred and seventeen adults with MFS were invited to participate, and 73 (62 %) participated. RESULTS: The SWLS mean score in adults with MFS was significantly lower than that reported for the general Norwegian population, but similar to or higher than that reported for other patient groups. Only fatigue, aortic dissection, and having regular contact with psychologist showed significant unique contribution to the SWLS score in the hierarchical multiple linear analyses. The total variance explained by the model was 45.2 % p ≤ 0.000, confirming that the combination of independent variables significantly predicted SWLS. CONCLUSIONS: The results reflect that MFS influences people's SWL and that particularly severe fatigue, aortic dissection, and psychological aspects are associated with lower SWL. This is important to take into account in the clinical work with people with MFS. Further investigation is needed, especially on larger sample groups. Studies with combination of qualitative and quantitative approaches are recommended to obtain more comprehensive and accurate knowledge about the consequences of MFS on satisfaction with life.

Work participation in adults with Marfan syndrome: Demographic characteristics, MFS related health symptoms, chronic pain, and fatigue.

Marfan syndrome (MFS) is a severe autosomal dominant connective tissue disorder that might influence peoples work ability. This cross sectional study aims to investigate work participation in adults with verified MFS diagnosis and to explore how the health related consequences of MFS and other factors might influence work participation. The prevalence of health problems in young adults compared to older adults with MFS was examined in association to work participation. A postal questionnaire including questions about work participation, demographic characteristics, MFS related health problems, chronic pain, and fatigue was sent to 117 adults with verified MFS (Ghent 1), and 62% answered. Fifty-nine percent were employed or students, significantly lower work participation than the General Norwegian Population (GNP), but higher than the Norwegian population of people with disability. Most young adults worked full-time despite extensive health problems, but the average age for leaving work was low. Few had received any work adaptations prior to retiring from work. In multiple logistic regression analysis, only age, lower educational level and severe fatigue were significantly associated with low work participation; not MFS related health problems or chronic pain. Fatigue appears to be the most challenging health problem to deal with in work, but the covariance is complex. Focus on vocational guidance early in life, more appropriate work adaptations, and psychosocial support might improve the possibility for sustaining in work for adults with MFS. More research about work challenges in adults with MFS is needed.

Fatigue in adults with Marfan syndrome, occurrence and associations to pain and other factors.

This study aims to investigate how fatigue affects adults with verified Marfan syndrome (MFS) in their daily lives, by examining fatigue levels and prevalence of severe fatigue compared to the general Norwegian population and individuals with other comparable chronic conditions. We investigated associations between socio-demographic characteristics, Marfan-related health problems, pain and fatigue. A cross-sectional study was conducted, using a postal questionnaire including the Fatigue Severity Scale (FSS) and questions on socio-demographic characteristics, Marfan-related health problems and pain. One hundred seventeen persons with MFS were invited to participate, 73 answered (62%). Participants reported significantly higher FSS scores and prevalence of severe fatigue compared to the general Norwegian population and patients with rheumatoid arthritis (RA), but lower than for other chronic conditions. Participants with chronic pain reported higher fatigue scores than those without chronic pain. Participants on disability benefits reported higher fatigue scores than participants who were working or enrolled in higher education. Marfan-related health problems like aortic dissection and use of blood pressure medication were not significantly associated with fatigue. In multivariable regression analyses chronic pain and employment status were significantly associated with fatigue. The final multivariable model explained 24% of the variance in fatigue scores. Our results show that fatigue is common in MFS patients and that it interferes with their daily lives. Chronic pain and employment status show significant associations to fatigue. This implies that fatigue is important to address when meeting MFS patients in clinical practice. There is need for more research on fatigue in Marfan syndrome.

Multidisciplinary treatment of disability in ehlers-danlos syndrome hypermobility type/hypermobility syndrome: A pilot study using a combination of physical and cognitive-behavioral therapy on 12 women.

Ehlers-Danlos Syndrome hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS) are two overlapping heritable connective tissue disorders. Patients with these conditions have many and various complaints; limitations in performing daily activities, reduced muscle strength and proprioception, kinesiophobia, and pain. There is a lack of evidence-based treatment approaches; a few studies have shown effect of physiotherapy. Many authors propose multidisciplinary treatment, but this has neither been described nor evaluated for this patient group. The aim of this pilot study was to investigate if a multidisciplinary rehabilitation program combining physical and cognitive-behavioral therapy was feasible, safe and effective for 12 women with EDS-HT/JHS. Intervention was offered as a group program and consisted of three parts: (1) Two and a half week in a rehabilitation unit with testing, physical training, group discussions and lectures. (2) Individual home exercises for three months with weekly guidance by local physiotherapist. (3) Readmission four days for retesting and further training advice. All participants completed the intervention. We found significant changes in perceived performance of daily activities, significant increase of muscle strength and endurance and a significant reduction of kinesiophobia. There were smaller changes in self-perceived pain. The participants also reported increased participation in daily life.