A qualitative study to explore the burden of disease in activated phosphoinositide 3-kinase delta syndrome (APDS).

BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare primary immunodeficiency, with only 256 cases reported globally. This study aimed to explore the disease burden of APDS from the perspective of individuals with APDS and their caregivers. METHODS: Qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers, to explore the symptoms and health-related quality of life (HRQoL) impact of APDS. Some individuals and caregivers also completed a narrative account exercise. All interviews were audio recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. RESULTS: Semi-structured qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers. Individuals and caregivers had the option of completing a narrative account exercise. Six HCPs participated in an interview. Seven participants completed the narrative account exercise (N = 5 caregivers and N = 2 individuals with APDS) and 12 took part in an interview (N = 4 caregivers and N = 8 individuals with APDS). Themes identified from HCPs interviews included symptoms, clinical manifestations, HRQoL impacts and treatments/management of APDS. The narrative account exercise identified similar themes, but with the addition to the journey to diagnosis. These themes were explored during the individual/caregiver interviews. Reported clinical manifestations and symptoms of APDS included susceptibility to infections, lymphoproliferation, gastrointestinal (GI) disorders, fatigue, bodily pain, and breathing difficulties. HRQoL impacts of living with APDS included negative impacts to daily activities, including work, education and social and leisure activities, physical functioning, as well as emotional well-being, such as concern for the future, and interpersonal relationships. Impacts to caregiver HRQoL included negative impacts to physical health, work, emotional well-being, interpersonal relationships and family life and holidays. The management of APDS included the use of healthcare services and medications including immunoglobulin replacement therapy (IRT), rapamycin, prophylactic antibiotics, leniolisib, as well as medical procedures due to complications. CONCLUSIONS: APDS has a high disease burden and there is an unmet need for licensed, more targeted treatments which modify disease progression. This study was the first to describe the day-to-day experience and HRQoL impact of APDS from the perspective of individuals living with the condition, caregivers and treating physicians.

Psychometric performance of the CFQ-R-8D compared to the EQ-5D-3L and SF-6D in people with cystic fibrosis.

OBJECTIVE: This study aimed to compare the psychometric performance of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions (CFQ-R-8D), a new, condition-specific, preference-based measure, with that of generic preference-based measures EQ-5D-3L and Short Form 6 dimensions (SF-6D). METHODS: Data from three trials of participants with CF aged ≥ 14 years who completed the CFQ-R and EQ-5D-3L or SF-6D were used. Analyses were undertaken to evaluate convergent validity based on correlations with CFQ-R domain scores. Known-group validity was assessed based on percent predicted forced expiratory volume in one second and pulmonary exacerbations. Responsiveness was based on correlation of change and sensitivity to change based on change in symptom severity. Effect sizes and standardized response means were estimated. RESULTS: CFQ-R-8D utilities and dimensions were strongly correlated with most of the overlapping CFQ-R domain scores (ρ > 0.5); EQ-5D-3L and SF-6D utilities and dimensions had moderate (ρ > 0.3) to strong correlations in dimensions capturing similar concepts. All measures showed evidence of known-group validity (P < 0.05). Change correlations were strong for CFQ-R-8D utilities and dimensions and CFQ-R, but they were moderate for SF-6D and mostly weak ((ρ > 0.1) for EQ-5D-3L. The SF-6D had the largest mean change over time and effect sizes, followed by CFQ-R-8D and then EQ-5D-3L. Neither CFQ-R-8D or SF-6D utility scores had ceiling effects (< 9% responses in full health) compared with those of EQ-5D-3L (61-62%). In participants classified as being in full health by EQ-5D-3L, CFQ-R-8D captured CF-specific health problems, particularly cough, abdominal pain, and breathing difficulty. CONCLUSIONS: The CFQ-R-8D reflected known-group differences and changes over time with stronger evidence of good psychometric performance than EQ-5D-3L and similar evidence as SF-6D. Additionally, the CFQ-R-8D captured more condition-specific symptoms than EQ-5D-3L or SF-6D, which are important determinants of health-related quality of life for people with CF.

Symptoms and impacts of familial chylomicronemia syndrome: a qualitative study of the patient experience.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare, hereditary, metabolic disorder. FCS causes high levels of triglycerides in the blood, which can lead to abdominal pain, xanthomas, and acute pancreatitis (AP). Volanesorsen, along with adherence to a very low-fat diet is used to reduce triglyceride levels in individuals with FCS. We aimed to understand the symptoms of FCS and their impact on health-related quality of life (HRQoL). METHODS: Interviews were conducted with individuals with genetically confirmed FCS in the UK and Spain, some of whom had been treated with volanesorsen. Interview guides were developed with input from a patient advocacy group to explore the symptoms, impacts and management of FCS. Interviews were conducted by telephone and were recorded and transcribed. Data were analyzed using thematic analysis and saturation was recorded. RESULTS: Seventeen interviews were conducted with individuals with FCS (aged 27-68 years), thirteen of whom were currently/previously treated with volanesorsen. Episodes of AP were the most impactful reported symptom, resulting in severe abdominal pain, nausea, vomiting, fever, bloating and appetite loss. Other symptoms and functional issues included abdominal pain, gastrointestinal symptoms, impaired cognitive function and fatigue. These had an impact on work, social activities, relationships and psychological wellbeing. These symptoms and impacts were illustrated in a conceptual model, including management strategies. The challenges of managing a low-fat diet and experience with volanesorsen were discussed. CONCLUSION: Individuals with FCS experience a range of interrelated symptoms and functional limitations which impact their broader HRQoL. Treatments which alleviate symptoms and reduce the incidence of AP episodes have the potential to improve the HRQoL of these individuals.

Exploring the impact of caring for an individual with neurogenic orthostatic hypotension: a qualitative study.

Aim: This study aimed to explore the impact of caring for an individual with neurogenic orthostatic hypotension (nOH). Methods: Informal caregivers of individuals with nOH and either Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies completed semi-structured interviews. Data were analyzed using thematic analysis; the identified concepts were used to develop a conceptual model. Results: Twenty informal caregivers were interviewed. Analysis identified several areas of caregiver impact due to nOH including impact on their time, particularly a need to supervise the patient to prevent falls as well as a lack of freedom and negative physical, work and social impacts. Many reported negative emotional impacts, including worry, stress or fear about the patient falling, depression and frustration. The conceptual model shows the relationships between concepts. Conclusion: The results highlight the wide-ranging impact of nOH, and the specific impact of the fear of falls on informal caregivers' lives.

Neurogenic orthostatic hypotension (nOH) is a type of hypotension (low blood pressure) which causes your blood pressure to fall when you stand up, meaning you can feel dizzy or lightheaded. This study looked at the experience of family members who provide day-to-day caregiving support to someone who has nOH as well as another condition which affects the brain and nerves (neurological condition). These neurological conditions included Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies. Interviews were conducted with informal caregivers (family members) of people with nOH. Caregivers discussed a range of ways in which caring for their family member impacts them, including needing to supervise their family member to make sure they do not fall, as well as having a lack of freedom and feeling worried, stressed, depressed and frustrated.

Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression.

Objective: Concurrent anxiety and/or insomnia symptoms in women with postpartum depression (PPD) are common and associated with more severe PPD. The effects of zuranolone on concurrent anxiety and/or insomnia symptoms and on patient-perceived functional health in women with PPD in the ROBIN study are reported.Methods: The phase 3, double-blind, randomized, placebo-controlled trial (conducted January 2017-December 2018) included women aged 18-45 years, ≤ 6 months postpartum, with PPD (onset of DSM-5-defined major depressive episode in the third trimester or ≤ 4 weeks postpartum) and baseline 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 26. Women were randomized 1:1 to once-daily oral zuranolone 30 mg (n = 77) or placebo (n = 76) for 14 days with follow-up through day 45. Concurrent remission of depressive and anxiety symptoms (Hamilton Anxiety Rating Scale total score ≤ 7 plus HDRS-17 total score ≤ 7 or Montgomery-Asberg Depression Rating Scale total score ≤ 10), improvement in insomnia symptoms, patient-perceived functional health, and treatment effect sizes described by number needed to treat (NNT) were assessed. Analyses were exploratory; P values are nominal.Results: Rates of concurrent remission of depressive and anxiety symptoms were higher with zuranolone versus placebo (P < .05) at days 3, 15, and 45; the rate of sustained concurrent remission (ie, at both days 15 and 45) was also higher with zuranolone (P < .05). Anxiety symptoms (assessed by HDRS-17 anxiety/somatization subscale and Edinburgh Postnatal Depression Scale anxiety subscale) improved with zuranolone versus placebo (P < .05) at days 3 through 45. Potential benefits on insomnia symptoms and patient-perceived functional health were observed. Day 15 NNTs were 5 for both HDRS-17 response and remission.Conclusions: Zuranolone was associated with concurrent improvements in depressive and anxiety symptoms, with beneficial effects on insomnia symptoms and patient-perceived functional health in adults with PPD.Trial Registration: ClinicalTrials.gov identifier: NCT02978326.

A survey exploring caregiver burden and health-related quality of life in hereditary transthyretin amyloidosis.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an ultra-rare, life-shortening disease with a high unmet need. This study examined ATTRv caregiver health-related quality of life (HRQoL) and productivity. METHODS: A cross-sectional online survey, including EQ-5D-3L, Hospital anxiety and depression scale (HADS), and caregiver and patient characteristics questions, was developed to assess ATTRv caregiver burden. A companion general population survey collected EQ-5D-3L, HADS and chronic health conditions data. Caregiver-control group differences in HRQoL were assessed using t-tests and chi-square tests. Ordinary Least Squares regression was used to estimate the disutility of being a caregiver compared to controls stratified by patient ambulatory status. RESULTS: Thirty-six caregivers and matched controls completed the survey (n = 72). The disease severity of patients they cared for was varied: 33% required no assistance walking, 58% required assistance with walking and 9% required a wheelchair/were bedridden. On average, caregivers spent 6 h daily on practical care and 4 h daily on emotional support. Fifty-six percent indicated that they had changed their employment due to providing ATTRv care. Caregivers reported lower HRQoL, as indicated by lower EQ-5D 3L utility scores (M = 0.772, SD = 0.178 vs. M = 0.849, SD = 0.218) and higher HADS anxiety (9.3 vs. 6.1, p < 0.01) and depression (7.6 vs. 4.4, p < 0.01) scores, compared with matched controls. Caregivers were also more likely to report sleep problems (33% vs. 8%, p < 0.01) and stress (42% vs. 0%, p < 0.001) as chronic conditions than controls. CONCLUSIONS: The study results indicate that caring for a person with ATTRv can have a considerable negative impact on caregivers' HRQoL and productivity. The study findings provide important information for economic evaluations of ATTRv treatments.

Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised.

OBJECTIVES: Cystic fibrosis (CF) limits survival and negatively affects health-related quality of life (HRQOL). Cost-effectiveness analysis (CEA) may be used to make reimbursement decisions for new CF treatments; nevertheless, generic utility measures used in CEA, such as EQ-5D, are insensitive to meaningful changes in lung function and HRQOL in CF. Here we develop a new, CF disease-specific, preference-based utility measure based on the adolescent/adult version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely used, CF-specific, patient-reported measure of HRQOL. METHODS: Blinded CFQ-R data from 4 clinical trials (NCT02347657, NCT02392234, NCT01807923, and NCT01807949) were used to identify discriminating items for a classification system using psychometric (eg, factor and Rasch) analyses. Thirty-two health states were selected for a time trade-off (TTO) exercise with a representative sample of the UK general population. TTO utilities were used to estimate a preference-based scoring algorithm by regression analysis (tobit models with robust standard errors clustered on participants with censoring at -1). RESULTS: A classification system with 8 dimensions (CFQ-R-8 dimensions; physical functioning, vitality, emotion, role functioning, breathing difficulty, cough, abdominal pain, and body image) was generated. TTO was completed by 400 participants (mean age, 47.3 years; 49.8% female). Among the regression models evaluated, the tobit heteroscedastic-ordered model was preferred, with a predicted utility range from 0.236 to 1, no logical inconsistencies, and a mean absolute error of 0.032. CONCLUSION: The CFQ-R-8 dimensions is the first disease-specific, preference-based scoring algorithm for CF, enabling estimation of disease-specific utilities for CEA based on the well-validated and widely used CFQ-R.

Health-related quality-of-life and burden for caregivers of individuals with neurogenic orthostatic hypotension.

Aim: This study explores the burden of caring for an individual with neurogenic orthostatic hypotension (nOH) and an underlying neurodegenerative disease (Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies). Materials & methods: A survey including several validated instruments was conducted with informal caregivers of individuals with Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies. Results: Caregivers of patients with nOH (n = 60) reported greater burden across all outcomes compared with those without nOH (n = 60). Receiving pharmacological treatment for nOH was the variable most consistently associated with significantly better caregiver health-related quality-of-life (p < 0.05). Conclusion: This study demonstrates the burden of nOH on informal caregivers and highlights the potential benefit of pharmacological treatment not only for patients but also indirectly, their caregivers.

Neurogenic orthostatic hypotension (nOH) causes blood pressure to fall when you stand up, meaning you can feel dizzy or lightheaded. This study looked at how providing day to day caregiving support to someone who has nOH as well as another neurological condition impacts the caregiver's health and wellbeing. These neurological conditions included Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies. A survey was conducted with informal caregivers (e.g., family members) of people with a neurological condition, with or without nOH. Caregivers completed questions about their own health-related quality-of-life, anxiety, depression and experience of caregiving. Caregivers of patients with nOH reported higher amounts of burden compared with those without nOH. Patients taking a treatment for nOH was most often associated with better caregiver health-related quality-of-life. This study shows the burden nOH can have on informal caregivers and highlights that treatment potentially benefits both patients and, indirectly, caregivers.

Exploring Health-Related Quality of Life Burden in Peanut Allergy and the Potential Benefit of Oral Immunotherapy: Estimation of Health State Utility Values for Children and Adolescents and Their Caregivers.

Purpose: This study aimed to estimate utility values for health states relating to oral immunotherapy (OIT) for peanut allergy (PA), for children with PA and their caregivers. Patients and Methods: Two methods were used: an online survey and structured interviews. Both methods assessed current utility/untreated PA (health-related quality of life, HRQoL) and HRQoL in different health states: "up-dosing phase of treatment", "maintenance phase" and "able to tolerate 6-8 peanuts if accidentally ingested". The survey was conducted in individuals with and without experience of OIT; data collected included the EQ-5D-Y (child states) and EQ-5D-5L (caregiver states). Results: In total, 100 caregivers and 38 adolescents completed the treatment-naïve survey, a separate sample of 50 caregivers participated in structured interviews. Seven caregivers and two adolescents with experience of OIT for PA completed the survey. Data from the three samples were pooled, the mean utility values were untreated PA: 0.796 (child), 0.855 (caregiver); up-dosing: 0.711 (child), 0.806 (caregiver); maintenance: 0.821 (child), 0.849 (caregiver), tolerate 6-8 peanuts: 0.859 (child), 0.884 (caregiver). The results show a gain in utility of 0.063 for children and 0.029 for caregivers between the untreated and tolerate 6-8 peanuts health states. Conclusion: This study is the first to assess utilities relating to OIT for PA. The results show the potential benefit of OIT for individuals with PA and their caregivers and provide values for use in cost-effectiveness evaluation.

Symptoms and impacts of aromatic L-amino acid decarboxylase (AADC) deficiency among individuals with different levels of motor function.

BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare neurological disorder associated with a range of symptoms and functional impairments. The aim of this study was to describe the experience of AADC deficiency across five different motor milestone health states. METHODS: Qualitative interviews were conducted with caregivers of individuals with AADC deficiency in Italy, Spain, Portugal and the United States. An interview guide was developed with input from clinical experts and caregivers, and explored the symptoms and impacts of AADC deficiency. Interviews were conducted by telephone and were recorded and transcribed. Data were analysed using thematic analysis and the symptoms and impacts were compared across health states. RESULTS: Fourteen caregivers took part, who provided care to 13 individuals with AADC deficiency aged 1-15 years. Six individuals were in the 'no motor function' health state, one in the 'sitting unsupported' health state, one in the 'standing/stepping when fully supported' health state and five in the 'walking with minimal support' health state. The results highlight a substantial impact of AADC deficiency, even among those who were able to walk with minimal support. Overall, those with better motor function also had better functional hand use, communication skills, ability to eat and perform other activities independently, and interact with their peers. The burden of caring was high across all health states, but caregivers of individuals in the walking health state were better able to participate in social and leisure activities. CONCLUSION: Individuals with higher levels of motor function had less severe symptoms and were better able to perform their daily, leisure and social activities. Treatments which improve motor function have the potential to improve other aspects of the lives of individuals with AADC deficiency and their caregivers.

Allergy to Peanuts imPacting Emotions And Life (APPEAL): The impact of peanut allergy on children, teenagers, adults and caregivers in the UK and Ireland.

The Allergy to Peanuts imPacting Emotions And Life study (APPEAL) explored the psychosocial burden of living with self-reported peanut allergy experienced by children, teenagers, adults and caregivers in the UK and Ireland. A two-stage (quantitative survey and qualitative interview [APPEAL-1]), cross-sectional study of the psychosocial burden of peanut allergy (APPEAL-2) was conducted. Quantitative data were evaluated using descriptive statistics and qualitative data were analysed using MAXQDA software. A conceptual model specific to UK and Ireland was developed using the concepts identified during the analysis. A total of 284 adults in the UK and Ireland completed the APPEAL-1 survey and 42 individuals participated in APPEAL-2. Respondents reported that peanut allergy restricts their choices in various situations, especially with regard to choosing food when eating out (87% moderately or severely restricted), choosing where to eat (82%), special occasions (76%) and when buying food from a shop (71%). Fifty-two percent of survey participants and 40% of interview participants reported being bullied because of PA. Psychological impact of peanut allergy included feeling at least moderate levels of frustration (70%), uncertainty (79%), and stress (71%). The qualitative analysis identified three different types of coping strategies (daily monitoring or vigilance, communication and planning) and four main areas of individuals' lives that are impacted by peanut allergy (social activities, relationships, emotions and work [adults and caregivers only]). The extent of the impact reported varied substantially between participants, with some reporting many negative consequences of living with peanut allergy and others feeling it has minimal impact on their health-related quality of life. This large survey and interview study highlight the psychosocial burden of peanut allergy for adults, teenagers, children and caregivers in the UK and Ireland. The analysis demonstrates the wide variation in level of impact of peanut allergy and the unmet need for those individuals who experience a substantial burden from living with peanut allergy.

A qualitative study on the impact of caring for an ambulatory individual with nonsense mutation Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy is a rare genetic neuromuscular disorder, which can result in early death due to disease progression. Ataluren is indicated for the treatment of nonsense mutation Duchenne muscular dystrophy, in ambulatory individuals aged two years and older. This study explored the impact of caring for an ambulatory individual with nonsense mutation Duchenne muscular dystrophy, as well as the impact of treatment with ataluren on the caregiver experience, using retrospective recall. METHODS: Qualitative interviews were conducted with caregivers in the UK. Interviews were conducted by telephone, were recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. RESULTS: Ten interviews were conducted with parents of individuals aged 4-19 years. Caregivers reported proximal impacts (physical, emotional, time-related), and distal impacts (work, relationships, social life) of caring for their sons. The relationships between these impacts were illustrated in a conceptual model. Changes to the caregiver experience since initiation with their son's treatment were discussed. CONCLUSION: Caring for an ambulatory individual with nonsense mutation Duchenne muscular dystrophy has a substantial multifaceted impact on caregivers. Treatments which have the potential to improve symptoms or delay progression, may also have a positive impact on the quality of life of caregivers.

Symptoms and impacts of ambulatory nonsense mutation Duchenne muscular dystrophy: a qualitative study and the development of a patient-centred conceptual model.

BACKGROUND: Duchenne muscular dystrophy is a rare genetic neuromuscular disorder, which can result in early death due to disease progression. Ataluren is indicated for the treatment of nonsense mutation Duchenne muscular dystrophy, in ambulatory individuals aged two years and older. This study explored the symptoms and impacts of nonsense mutation Duchenne muscular dystrophy and experience with ataluren. METHODS: Qualitative interviews were conducted with caregivers in the UK. Interviews were conducted by telephone, were recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. RESULTS: Ten interviews were conducted with parents of individuals aged 4-19 years. Key symptoms included muscle weakness and muscle breakdown, which were associated with limitations in physical function and pain. These impacted individuals' daily activities, social activities and emotional wellbeing. These concepts and relationships were illustrated in a conceptual model, along with positive and negative moderating factors. Experience with ataluren and changes since initiation with treatment were discussed. CONCLUSION: Individuals with nonsense mutation Duchenne muscular dystrophy experience a range of interrelated symptoms and functional issues which impact their broader health-related quality of life. Treatments which address this high unmet need have the potential to improve the health-related quality of life of these individuals.

The impact of caring for an individual with aromatic l-amino acid decarboxylase (AADC) deficiency: a qualitative study and the development of a conceptual model.

BACKGROUND: Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare neurological condition, associated with a wide range of symptoms and functional issues, such as profound motor impairment and learning disability. Most individuals with AADC deficiency are completely dependent on their caregivers. This study explored the impact of caring for an individual with AADC deficiency. METHODS: Qualitative interviews were conducted with caregivers of individuals with AADC deficiency in Italy, Portugal, Spain and the United States. An interview guide was developed with input from clinical experts and caregivers and included questions on the impact of caring for an individual with AADC deficiency. Interviews were conducted by telephone/videoconference and were recorded and transcribed. Data were analysed using thematic analysis. RESULTS: Fourteen caregivers took part who provided care to 13 individuals with AADC deficiency aged 1-15 years. Caregivers reported that their lives centred around the individual with AADC deficiency, due to their need for 24-hour care and regular healthcare appointments. They reported both proximal impacts (impact on time, planning, physical health and emotional wellbeing), and distal impacts (impact on social/leisure activities, relationships, work and finances). These concepts and relationships were illustrated in a conceptual model. CONCLUSIONS: This is the first qualitative study to report on the experience of caring for an individual with AADC deficiency. Caregivers reported that caring had a substantial multifaceted impact on their lives. These findings highlight the importance of considering the caregiver experience when evaluating the burden of AADC deficiency.

Symptoms and impact of aromatic l-amino acid decarboxylase (AADC) deficiency: a qualitative study and the development of a patient-centred conceptual model.

BACKGROUND: Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare neurological condition, with an estimated global prevalence of 1:32,000 to 1:90,000 live births. AADC deficiency is associated with a range of symptoms and functional impairments, but these have not previously been explored qualitatively. This study aimed to understand the symptoms of AADC deficiency and its impact on individuals' health-related quality of life. METHODS: Qualitative interviews were conducted with caregivers of individuals with AADC deficiency in Italy, Spain, Portugal and the United States. An interview guide was developed with input from clinical experts and caregivers, and explored the symptoms and impacts of AADC deficiency. Interviews were conducted by telephone and were recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. RESULTS: Fourteen caregivers took part, who provided care to 13 individuals with AADC deficiency aged 1-15 years. All individuals had impaired motor function, which was attributed to low muscle tone and muscle weakness. The level of motor function varied considerably, ranging from no motor function (no head control) to being able to take a few steps without support. Other impairments included cognitive impairment, communication difficulties, movement disorders (e.g. oculogyric crises), gastrointestinal symptoms, eating difficulties, fatigue and sleep disruption. Most individuals were completely dependent on their caregivers for all aspects of their lives. This limited function had a negative impact on their ability to socialise with their peers and on their emotional wellbeing. These concepts and relationships are illustrated in a conceptual model, and moderating factors (e.g. physiotherapy and medication) are discussed. CONCLUSION: This is the first qualitative study to report on the experience of living with AADC deficiency. Caregivers report individuals with AADC deficiency experience a wide range of symptoms and functional impairments, which have a substantial impact on their health-related quality of life.

Burden of allergic rhinitis and impact of MP-AzeFlu from the patient perspective: pan European patient survey.

OBJECTIVE: The aims of this survey were to (1) assess the burden of allergic rhinitis (AR) from the patient perspective, (2) investigate MP-AzeFlu use in real life and its impact on patients' lives and (3) explore factors associated with treatment satisfaction. METHODS: A cross-sectional, quantitative, online, questionnaire-based survey was conducted in seven European countries (March-June 2019). Questions explored AR burden and treatment satisfaction. Satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication 9-item (TSQM-9; max score = 100). Participants (aged ≥18 years) had a doctor/healthcare provider confirmed AR diagnosis and used MP-AzeFlu within the last year. RESULTS: Pre-MP-AzeFlu treatment, participants (n = 1004) reported an average of 3.3 (SD:3.5) doctor visits/year, 8.1 (SD:11.0) days/year absenteeism and 15.8 (SD:18.9) days/year presenteeism due to AR. Only 48% of participants used MP-AzeFlu twice/day as recommended. Post-MP-AzeFlu 57% of participants reported better QoL, 47% reported fewer doctor visits and 52% discontinued polypharmacy. Absenteeism and presenteeism were reduced by 2.5 (SD 10.0) and 7.3 (SD:16.0) days/year, respectively. 70% of participants were more/much more satisfied with MP-AzeFlu versus previous AR treatment(s), and ≥70% were satisfied/extremely satisfied with its ability to prevent/treat AR, relieve symptoms and with its onset of action. Mean global, effectiveness and convenience TSQM-9 scores were 70.0 (SD:19.8), 68.3 (SD:21.6) and 72.7 (SD:20.4), respectively. Treatment satisfaction and effectiveness were significantly improved when MP-AzeFlu was taken as recommended. CONCLUSIONS: The impact of AR on patients' lives remains high. Real-life use of MP-AzeFlu reduces that impact and is associated with a high level of effectiveness, convenience and global satisfaction.

Achieving clinical response in postpartum depression leads to improvement in health-related quality of life.

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) burden associated with postpartum depression (PPD), determine the extent to which clinical response impacts HRQoL, and estimate the impact of PPD and clinical response on healthcare resource utilization (HRU) and productivity. METHODS: Patient data (n = 127) from two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of brexanolone injection in adults with PPD were employed for these posthoc analyses. HRQoL and health utility was assessed with the SF-36-v2 Health Survey (SF-36v2) acute version. The 17-item Hamilton Rating Scale for Depression (HAMD-17) total score was used to identify clinical response (≥50% reduction in HAMD-17 total score). Baseline HRQoL burden was assessed by comparison to age- and gender-adjusted population normative data from the 2009 QualityMetric PRO Norming study. The impact of clinical response was evaluated by comparing day 7 and day 30 SF-36v2 scores between clinical responders and non-responders. Interpretations of the meaningfulness of clinical response were indirectly estimated via 2017 National Health and Wellness Survey data linking SF-36v2 mental component summary (MCS) scores to (HRU) and productivity. RESULTS: Baseline HRQoL of patients with PPD was significantly below normative values. Day 7 and day 30 clinical response were associated with large and statistically significant improvements in HRQoL, greater likelihood of meeting SF-36v2 responder definitions, and reduced impairment. MCS levels corresponding to those observed in clinical responders were linked to lower HRU and productivity loss relative to non-responders. CONCLUSIONS: PPD places a substantial burden on HRQoL. Achievement of rapid clinical response (at day 7) and clinical response sustained several weeks following the end of treatment (day 30) led to significant improvement in HRQoL, suggesting the importance of identifying women with PPD and providing effective treatment options.

Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making.

Background: Brexanolone (BRX) injection was approved by the United States Food and Drug Administration in 2019 for the treatment of adults with postpartum depression (PPD) based on two Phase 3 clinical trials. Materials and Methods: Data from the three trials were combined. PPD-specific 17-item Hamilton Rating Scale for Depression (HAMD-17) group-level minimal important difference (MID) and patient-level meaningful change (meaningful change threshold [MCT]) were estimated and applied to differences in BRX versus placebo (PBO) at hour 60 (primary endpoint) and day 30 (end of trial follow-up). Likelihood of HAMD-17 response and remission and Clinical Global Impression of Improvement (CGI-I) response for BRX versus PBO were assessed at hour 60 and as sustained through day 30 using relative risk. Associated number needed to treat (NNT) and number needed to harm (NNH) values were also estimated. Results: Two-hundred nine patients were included. The average HAMD-17 MID estimate was -2.1; the least-squared mean difference between BRX and PBO exceeded this at hour 60 and day 30. Minimal, moderate, and large MCTs were estimated to be -9, -15, and -20 points, respectively. Significantly more BRX-treated than PBO-treated patients achieved minimal, moderate, and large change (all ps < 0.05) at hour 60 and large meaningful response at day 30 (p < 0.05). BRX-treated patients were more likely to sustain HAMD-17 remission and CGI-I response through day 30 versus PBO. NNTs ranged from 4 to 8, with NNH of 97. Conclusions: BRX provided meaningful changes relative to PBO, rapid (hour 60), and sustained improvements (day 30) in PPD symptoms, low NNT, and large NNH. These results may help inform treatment decision-making. Clinicaltrials.gov registration numbers: NCT02614547, NCT02942004, and NCT02942017.

Allergy to Peanuts imPacting Emotions And Life (APPEAL): the impact of peanut allergy on children, adolescents, adults and caregivers in France.

BACKGROUND: Peanut allergy (PA) has increased in developed countries and can have a dramatic effect on quality of life but data surrounding this is limited in France. Allergy to Peanuts imPacting Emotions And Life study (APPEAL) investigated the experience and impact of living with PA in France. METHODS: Respondents affected by PA directly (children aged 8-12 years, teenagers aged 13-17 years, or adults aged ≥ 18 years) or indirectly (caregiver) completed either an online questionnaire (APPEAL-1, N = 198), or provided in-depth interviews (APPEAL-2, N = 32). Quantitative data was evaluated using descriptive statistics. Qualitative data was analysed thematically, using MAXQDA software. RESULTS: Of 198 responders in APPEAL-1, 88% stated that PA affects their daily activities, and 74% felt isolated as a result of living with PA. Feelings of worry about exposure to peanuts on social occasions where food is involved was reported by 91%. A total of 44% reported some restrictions in their job options, 85% in socializing. Psychological impact of PA included responders feeling emotions of frustration (89%), uncertainty (87%), and stress (93%) and 93% reporting encountering instances of feeling different due to their PA. Main factors that drove PA impact included social activities and relationships; whereas main coping strategies to avoid peanuts included monitoring, communication and planning. CONCLUSION: The analysis of French respondents from the APPEAL study demonstrates the impact and burden of PA on allergic children, teenagers, adults and their caregivers, and highlights the unmet need to be addressed.

Psychosocial and productivity impact of caring for a child with peanut allergy.

BACKGROUND: Limited previous research has assessed the psychosocial burden and productivity impact of caring for a child with peanut allergy and factors associated with burden. The objective of this research was to explore caregiver burden in terms of psychosocial and productivity impact of caring for a child with peanut allergy, the influence of caregiver and child gender on caregiver burden, and factors predicting caregiver burden in peanut allergy. METHODS: A cross-sectional survey of caregivers of children with peanut allergy was conducted in the United Kingdom, and included sociodemographic and clinical questions, EQ-5D, Hospital Anxiety and Depression Scale, Food Allergy Quality of Life-Parental Burden, Food Allergy Independent Measure, and productivity questions. RESULTS: One hundred caregivers (55% female) of children with peanut allergy (aged 4-15 years) completed the survey. Male and female caregivers reported mean levels of anxiety significantly higher than United Kingdom population norms. Caregivers of children with severe peanut allergy reported significant impacts on their careers and health-related quality of life. Neither caregiver nor child gender impacted burden, indicating that male and female caregivers are equally anxious and suffer the same level of negative career, productivity, and health-related quality-of-life impact due to their child's peanut allergy. Caregivers' perceived risk of outcomes related to their child's peanut allergy (e.g., death or severe reaction) as measured by the Food Allergy Independent Measure independently predicted burden. CONCLUSIONS: Caregivers of children with peanut allergy in the United Kingdom experience health-related quality-of-life, psychosocial, and productivity burden; this study demonstrates the high levels of anxiety reported by both male and female caregivers.