Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach.

Introduction: eHealth seems promising in addressing challenges in the provision of care for Huntington's disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients' home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations. Methods: This article describes the qualitative human-centered design process and first evaluations of the Huntington Support App prototype: a web-app aimed to support the quality of life (QoL) of HDGECs and their partners in Europe. Prospective end-users, i.e., HDGECs, their partners, and healthcare providers (HCPs), from different countries were involved throughout the development process. Through interviews, we captured people's experiences with the disease, quality of life (QoL), and eHealth. We translated their stories into design directions that were further co-designed and subsequently evaluated with the user groups. Results: The resulting prototype centralizes clear and reliable information on the disease, HD-related news and events, as well as direct contact possibilities with HCPs via an online walk-in hour or by scheduling an appointment. The app's prototype was positively received and rated as (very) appealing, pleasant, easy to use and helpful by both HDGECs and partners. Discussion: By involving end-users in every step, we developed a healthcare app that meets relevant needs of individuals affected by HD and therefore may lead to high adoption and retention rates. As a result, the app provides low-threshold access to reliable information and specialized care for HD in Europe. A description of the Huntington Support App as well as implications for further development of the app's prototype are provided.

Palliative care in advanced Huntington's disease: a scoping review.

BACKGROUND: As Huntington's disease (HD) is a progressive disease for which there is no cure yet, patients in the advanced stage of HD may benefit from palliative care. OBJECTIVE: To review the literature focusing on palliative care in advanced stage HD, and the level of evidence. METHODS: Publications between 1993 and October 29th, 2021 from 8 databases (Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier, PMC PubMed Central and Pubmed) were included. The literature was deductively classified based on topics that are part of the definition of palliative care, or as care-related topics that emerged from the literature. Levels of evidence I (high) - V (low) were determined as defined by the Joanna Briggs Institute. RESULTS: Our search resulted in 333 articles, 38 of which were included. The literature covered four domains of palliative care: physical care, psychological care, spiritual care, and social care. Four other topics in the literature were: advance care planning, end-of-life needs assessments, pediatric HD care, and need for health care services. Most literature was underpinned by a low level of evidence, except for the topics on social care (Level III-V), advance care planning (Level II-V) and end-of-life needs assessments (Level II-III). CONCLUSIONS: To deliver adequate palliative care in advanced HD, both general and HD-specific symptoms and problems need to be addressed. As the level of evidence in existing literature is low, further research is essential to improve palliative care and to meet patient's wishes and needs.

Quality of life, health-related quality of life, and associated factors in Huntington's disease: a systematic review.

BACKGROUND: Huntington's disease (HD) is a genetic, neurodegenerative disease. Due to the progressive nature of HD and the absence of a cure, (health-related) quality of life ((HR)QoL) is an important topic. Several studies have investigated (HR)QoL in HD, yet a clear synthesis of the existing literature is lacking to date. We performed a systematic review on self-reported (HR)QoL, and factors and intervention effects associated with (HR)QoL in premanifest and manifest HD gene expansion carriers (pHDGECs and mHDGECs, respectively). METHODS: PubMed, EMBASE, Web of Science, and PsycINFO were searched systematically from September 17th, 2021, up to August 11th, 2022. Methodological and conceptual quality of the included studies was assessed with two appraisal tools. RESULTS: 30 out of 70 eligible articles were included. mHDGECs experienced lower (HR)QoL compared to pHDGECs and controls, whereas mixed findings were reported when compared to other neurological diseases. Several factors were associated with (HR)QoL that might contribute to lower (HR)QoL in mHDGECs, including depressive symptoms, physical and psychological symptoms, lower functional capacity, lower support, and unmet needs. Multidisciplinary rehabilitation programs and a respiratory muscle training were beneficial for (HR)QoL in mHDGECs. DISCUSSION: (HR)QoL is experienced differently across the course of the disease. Although (HR)QoL is key for understanding the impact of HD and the effect of symptomatic treatment, there is a need to improve the methodological and conceptual shortcomings that were found in most studies, especially regarding the conceptual clarity when reporting on QoL and HRQoL. Suggestions for strengthening these shortcomings are provided in this review.

Nursing Approaches and Perceived Quality of Life in Advanced Stage Huntington's Disease Patients.

BACKGROUND: Long-term Huntington's disease (HD) care is offered in specialized inpatient nursing home units with a focus on individually perceived quality of life (QoL). This is shaped in daily care and interaction, which is often abstract and intangible. Furthermore, different perspectives are involved and may vary. OBJECTIVE: To explore and describe perceived QoL of HD patients from three perspectives: manifest HD patients, family members, and nursing staff. METHODS: 36 patients, 11 family members, and 30 nurses participated in this qualitative study by means of individual interviews and systematic qualitative observations on three units. RESULTS: Preservation of identity and autonomy is important for patients. Patients struggle with increasing dependence, and try to cope with the impact, uncertainty, and progressive nature of the disease. All participants emphasize the focus on "being human, not just a patient". Both patients and family members mention the difficulty of dealing with altered behavior and loss of control. Patients are reliant on a relational approach, and an attitude of unconditional acceptance, trust, and understanding support by the nurses. Nursing staff help patients to focus on preserved abilities, and to continue to engage in personalized preferred social activities. Specific qualifications of the nurses were of major influence on QoL for HD patients. CONCLUSION: This study shows, from the patient as well as family member and nursing staff perspectives, that caring for HD patients requires specific knowledge and skills. Particular nursing approaches and attitude and qualifications of the nursing staff in residential HD care improves the perceived QoL of patients.

Factors of Specialized Mental Health Care Use in the Netherlands: A Scoping Review Applying Andersen-Newman's Care Utilization Model.

As mental disorders impact quality of life and result in high costs for society, it is important patients receive timely and adequate care. This scoping review first aims to summarize which factors contribute to specialized mental health care (SMHC) use. Within the Dutch health care system, the general practitioner (GP) is the filter for SMHC and care use costs are relatively low. Second, to organize factors by Andersen and Newman's care utilization model in illness level, predisposing, and enabling factors. Third, to assess equity of access to SMHC in the Netherlands. A health care system is equitable when illness level and the demographic predisposing factors age and gender account for most variation in care use and inequitable when enabling factors and social predisposing factors such as education predominate. We identified 13 cross-sectional and cohort studies in the Netherlands published between 1970 and September 2020 with 20 assessed factors. Illness level factors, disease severity, diagnosis, personality, and comorbidity contributed the most to SMHC use. Predisposing factors related to a more solitary lifestyle contributed to a lesser degree. Enabling factors income and urbanicity contributed the least to SMHC use. These results imply inequity. Factors that did not fit the care utilization model were GP related, for example the ability to recognize mental disorders. This emphasizes their importance in a system where patients are dependent on GPs for access to SMHC. Focus should be on improving recognition of mental disorders by GPs as well as collaboration with mental health care professionals.

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home. Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts. Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD.

Incidence of completed suicide and suicide attempts in a global prospective study of Huntington's disease.

BACKGROUND: Risk of death from suicide in Huntington's disease is notably elevated relative to that in the general population, although the incidence within HD populations has not been precisely defined. Robust incidence estimates of suicidal behavior can serve as references for HD therapeutic research and post-marketing surveillance to help evaluate the suicidality risk of novel therapeutics. AIMS: To estimate the incidence rate of completed suicide and suicide attempt in the global, prospective HD cohort study Enroll-HD that records these events per protocol. METHOD: A total of 20 912 participants were available for analysis (HD gene-expansion carriers (HDGECs) n = 15 924; non-HDGECs n = 4988) representing a collective observation period of 53 390 participant-years. Each observed event was subject to clinical review and evaluation. We generated incidence rates (events per 100 000 person-years) for suicides and suicide attempts using all available data, as well as by year of study and geographical region. Proportionate mortality statistics for suicide and respective 95% confidence intervals were also generated. RESULTS: The overall incidence rate of suicide in HDGECs was 72 per 100 000 person-years, and 8 per 100 000 person-years in non-HDGECs. Proportionate mortality attributable to suicide in HDGECs was 4.6%. For suicide attempts, the global overall incidence rate observed in HDGECs was 306-375 per 100 000 person-years, and 23-38 per 100 000 person-years in non-HDGECs. CONCLUSIONS: The incidence estimates calculated here can be used as a reference to help evaluate drug safety and may also be useful in assessing progress in clinical care for HDGECs once therapeutic interventions become widely available.

Genetic Risk Underlying Psychiatric and Cognitive Symptoms in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized examination of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown. METHODS: We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by 1) constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders and of intelligence and 2) testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n = 5160) of patients with HD. RESULTS: Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence. CONCLUSIONS: Polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD.

[Psychological and psychiatric care for hereditary brain disorders]. / Psychologische en psychiatrische zorg bij erfelijke hersenziekten.

Hereditary neurological disorders are characterised by a combination of neurocognitive, neuropsychiatric and somatic symptoms, with average onset in mid-adulthood. Offspring of gene carriers is at risk of developing the disorder. Patients, partners and family members may present with various psychological problems that engender several care demands throughout life. For physicians and other medical professionals who occasionally come across these disorders it may be difficult to find adequate care. We describe two patients to illustrate the importance of specialised, multidisciplinary psychological and psychiatric care. First, we present a 43-year-old female patient with Huntington's disease who has had long-time psychiatric problems with a strong negative impact on her life and that of her spouse and children. Second, we present a 31-year-old female gene carrier of CADASIL who has psychological problems that are leading to uncertainty about whether the disease process has started.

Obsessive-Compulsive and Perseverative Behaviors in Huntington's Disease.

BACKGROUND: Neuropsychiatric symptoms are highly prevalent in Huntington's disease (HD). However, little is known of the prevalence and course of obsessive-compulsive behaviors (OCBs) and perseverative behaviors (PBs) during the progression of the disease. OBJECTIVE: This review provides a summary of the literature on OCBs and PBs in HD gene expansion carriers (HDGECs). METHODS: Pubmed database was searched for articles on OCBs and PBs in HD up to 2017. We used search terms, all synonyms for HD, and various terms for OCBs and PBs. RESULTS: We found 5 case series and 11 original articles that describe a prevalence range of 5 to 52% for OCBs and up to 75% for PBs depending on disease stage and measurement scale used. Premanifest HDGECs report more OCBs compared to controls, and manifest HDGECs report a higher rate of OCBs compared to premanifest HDGECs. OCBs and PBs are associated with a longer disease duration and disease severity in manifest HDGECs, but decrease in the most advanced stages. When HDGECs come closer to estimated motor onset, the companion ratings on OCBs appear to be higher than the self-ratings of HDGECs. CONCLUSIONS: Both OCBs and PBs are characteristic neuropsychiatric features of HD. Perseveration is probably best distinguished from OCBs as it occurs without the individual's full awareness or insight into their presence (and the behavior may not be distressing). Although these behaviors are seldom distinguished, we conclude that differentiating OCBs from PBs in HD is beneficial for the management and treatment of these symptoms in HDGECs.

Smartphone-based safety planning and self-monitoring for suicidal patients: Rationale and study protocol of the CASPAR (Continuous Assessment for Suicide Prevention And Research) study.

BACKGROUND: It remains difficult to predict and prevent suicidal behaviour, despite growing understanding of the aetiology of suicidality. Clinical guidelines recommend that health care professionals develop a safety plan in collaboration with their high-risk patients, to lower the imminent risk of suicidal behaviour. Mobile health applications provide new opportunities for safety planning, and enable daily self-monitoring of suicide-related symptoms that may enhance safety planning. This paper presents the rationale and protocol of the Continuous Assessment for Suicide Prevention And Research (CASPAR) study. The aim of the study is two-fold: to evaluate the feasibility of mobile safety planning and daily mobile self-monitoring in routine care treatment for suicidal patients, and to conduct fundamental research on suicidal processes. METHODS: The study is an adaptive single cohort design among 80 adult outpatients or day-care patients, with the main diagnosis of major depressive disorder or dysthymia, who have an increased risk for suicidal behaviours. There are three measurement points, at baseline, at 1 and 3 months after baseline. Patients are instructed to use their mobile safety plan when necessary and monitor their suicidal symptoms daily. Both these apps will be used in treatment with their clinician. CONCLUSION: The results from this study will provide insight into the feasibility of mobile safety planning and self-monitoring in treatment of suicidal patients. Furthermore, knowledge of the suicidal process will be enhanced, especially regarding the transition from suicidal ideation to behaviour.The study protocol is currently under revision for medical ethics approval by the medical ethics board of the Vrije Universiteit Medical centre Amsterdam (METc number 2017.512/NL62795.029.17).

Clinical Management of Neuropsychiatric Symptoms of Huntington Disease: Expert-Based Consensus Guidelines on Agitation, Anxiety, Apathy, Psychosis and Sleep Disorders.

BACKGROUND: In clinical practice, several strategies and pharmacological options are available to treat neuropsychiatric symptoms of Huntington disease (HD). However, there is currently insufficient data for evidence-based guidelines on the management of these common symptoms. OBJECTIVE: We aimed to develop expert-based recommendations regarding the management of agitation, anxiety, apathy, psychosis, and sleep disorders. METHODS: Guideline development was based on a modified Institute of Medicine guideline process that accounted for a lack of evidence base. An international committee of 11 multidisciplinary experts proposed a series of statements regarding the description and management of each symptom. Statement assessment and validation was performed using a web-based survey tool and 84 international HD experts (neurologists and psychiatrists) who assessed the statements and indicated their level of agreement. RESULTS: High-level agreement (≥85% experts strongly agreed or agreed) was reached for 107 of the 110 statements that have been incorporated into the expert-based clinical recommendations presented herein. CONCLUSIONS: Clinical statements to guide the routine management of agitation, anxiety, apathy, psychosis, and sleep disorders in HD have been developed. Although not specifically tested in the HD population, clinical experience has shown that most of the neuropsychiatric symptoms discussed, when considered in isolation are treatable using pharmacologic and non-pharmacologic strategies developed for use in other populations. However, the management of neuropsychiatric symptoms in HD can be complex because neuropsychiatric symptoms often co-exist and treatment decisions should be adapted to cover all symptoms while limiting polypharmacy.

Treatment results for severe psychiatric illness: which method is best suited to denote the outcome of mental health care?

BACKGROUND: The present study investigates the suitability of various treatment outcome indicators to evaluate performance of mental health institutions that provide care to patients with severe mental illness. Several categorical approaches are compared to a reference indicator (continuous outcome) using pretest-posttest data of the Health of Nation Outcome Scales (HoNOS). METHODS: Data from 10 institutions and 3189 patients were used, comprising outcomes of the first year of treatment by teams providing long-term care. RESULTS: Findings revealed differences between continuous indicators (standardized pre-post difference score ES and ΔT) and categorical indicators (SEM, JTRCI, JTCS, JTRCI&CS, JTrevised) on their ranking of institutions, as well as substantial differences among categorical indicators; the outcome according to the traditional JT approach was most concordant with the continuous outcome indicators. CONCLUSIONS: For research comparing group averages, a continuous outcome indicator such as ES or ΔT is preferred, as this best preserves information from the original variable. Categorical outcomes can be used to illustrate what is accomplished in clinical terms. For categorical outcome, the classical Jacobson-Truax approach is preferred over the more complex method of Parabiaghi et al. with eight outcome categories. The latter may be valuable in clinical practice as it allows for a more detailed characterization of individual patients.

Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study.

Background: Huntington's disease (HD) is characterized by motor and behavioral symptoms, and cognitive decline. HD gene carriers and their caregivers report the behavioral and cognitive symptoms as the most burdensome. Apathy is the most common behavioral symptom of HD and is related to clinical measures of disease progression, like functional capacity. However, it is unknown whether apathy is directly related to the neurodegenerative processes in HD. Objective: The aim is to investigate whether an association between atrophy of subcortical structures and apathy is present in HD, at baseline and after 2 years follow-up. Method: Volumes of 7 subcortical structures were measured using structural T1 MRI in 171 HD gene carriers of the TRACK-HD study and apathy was assessed with the Problem Behaviors Assessment-Short, at baseline and follow-up visit. At baseline, logistic regression was used to evaluate whether volumes of subcortical brain structures were associated with the presence of apathy. Linear regression was used to assess whether subcortical atrophy was associated with the degree of apathy at baseline and with an increase in severity of apathy over time. Results: At baseline, smaller volume of the thalamus showed a higher probability of the presence of apathy in HD gene carriers, but none of the subcortical structures was associated with the degree of apathy. Over time, no association between atrophy of any subcortical structures and change in degree of apathy was found. Conclusion: The presence of apathy is associated with atrophy of the thalamus in HD, suggesting that apathy has an underlying neural cause and might explain the high incidence of apathy in HD. However, no association was found between atrophy of these subcortical structures and increase in severity of apathy over a 2-year time period.

Huntington's Disease Gene Expansion Carriers Are Aware of Their Degree of Apathy.

Huntington's disease is characterized by motor and behavioral symptoms as well as cognitive decline. Apathy is a common behavioral symptom, and its severity is related to disease progression. It has been suggested that Huntington's disease gene expansion carriers (HDGECs) are unaware of the signs and symptoms of the disease, which may account for their own level of awareness of their apathy. Therefore, the authors investigated the level of agreement on the degree of apathy severity between HDGECs and their proxies by using a self-report questionnaire. A total of 109 REGISTRY participants (premotormanifest, N=31; early motormanifest, N=49; and late motormanifest, N=29) and their proxies completed the Apathy Evaluation Scale. The authors used the Wilcoxon signed-rank test to assess whether gene expansion carriers and their proxies agreed on apathy severity. Scores on the Apathy Evaluation Scale significantly increased from the early motormanifest stage to the late motormanifest stage. Premotormanifest carriers scored themselves significantly higher on the Apathy Evaluation Scale than their proxies, whereas no differences were found between all motormanifest carriers and their proxies. Apathy severity increases in the motormanifest stages of Huntington's disease. HDGECs can adequately assess their level of apathy on a self-report questionnaire. These results also suggest that slight changes in the degree of apathy among premotormanifest gene expansion carriers remain unnoticed by their proxies.

Correlates of sleep disturbances in depressed older persons: the Netherlands study of depression in older persons (NESDO).

OBJECTIVES: Sleep disturbances are common among depressed older persons. To gain insight into sleep disturbances in late-life depression, their occurrence and correlates were assessed. METHODS: Baseline data of 294 depressed older persons of the Netherlands Study of Depression in Older persons study were used. A diagnosis of current depression according to the diagnostic and statistical manual of mental disorders-IV (DSM-IV) was assessed with the Composite International Diagnostic Interview. Sleep disturbances were measured with the five-item Women's Health Initiative Insomnia Rating Scale, and considered present with a score of ≥10 points. RESULTS: Sleep disturbances were present in 59.9% of the depressed older persons. Bivariate linear regression analyses showed that presence of sleep disturbances was associated with fewer years of education, use of alcohol, the number of chronic diseases, higher pain intensity scores, use of more benzodiazepines, more anxiety and severity of depressive symptoms. In multivariate analyses, severity of depression appeared to be the only independent correlate. CONCLUSIONS: Sleep disturbances are highly prevalent in patients with late-life depression and independently correlated with the severity of depression. Treatment of depression may result in improvement of sleep disturbances, although cognitive behavioral interventions that focus on both depression and sleep disturbances may also be effective.

Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.

BACKGROUND: Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior. METHODS: We included 1451 HD gene expansion carriers (age 48.4 years (SD 14.0), 54.8% female) of the REGISTRY study of the European Huntington's Disease Network. Lifetime suicidal ideation and suicidal behavior were assessed with the Columbia-Suicidal Severity Rating Scale. Motor symptoms and disease stage were assessed using subscales of the Unified Huntington's Disease Rating Scale, and depressed mood and irritability were assessed by the Problem Behaviors Assessment. RESULTS: Lifetime passive suicidal ideation was reported by 21.2%. Participants in stage II showed the highest prevalence rate of suicidal ideation, while participants in stage IV/V showed the highest prevalence of suicidal behavior. A lifetime suicide attempt was reported by 6.5% of the HD gene expansion carriers. In multivariate regression analyses, both suicidal ideation and suicidal behavior were associated with a depressed mood, and to a lesser extend to irritability. LIMITATIONS: Results may have been affected by denial or recall bias and no conclusions can be made about the temporal and causal relationships with depressed mood and irritability because of the cross-sectional analyses. CONCLUSIONS: Given the high prevalence of suicidal ideation and suicidal behavior in all stages of HD, it is important to screen HD gene expansion carriers for suicidal ideation and suicidal behavior on a regular basis in clinical practice.