Real-World experience of interictal burden and treatment in migraine: a qualitative interview study.

BACKGROUND: The debilitating nature of migraine attacks is widely established; however, less is known about how the interictal burden (i.e., how patients are affected in-between migraine episodes) of migraine impacts on patients' health-related quality of life (HRQL). Acute and preventive treatments may lift the burden of the disease, but they often have unwanted side effects and limited effectiveness. The objective of this study was to understand the interictal burden of migraines, from the patient perspective, and to explore patient experience with migraine treatments. METHODS: Participants (n=35) with a self-reported diagnosis of migraine were recruited in the US, UK and Canada, including a subgroup of patients who had taken calcitonin gene-related peptide monoclonal antibody (CGRP mAb) treatment for at least three months. Participants completed a background questionnaire, followed by a semi-structured interview via telephone or video call. The interviews explored patients' migraine symptoms, perception of interictal burden and treatment experience. The interview transcripts were analysed using thematic analysis. RESULTS: The most reported migraine symptom was migraine pain, followed by aura, sensory sensitivity and nausea. Most participants reported interictal impact on HRQL, lifestyle changes they made to avoid triggers or in anticipation of an attack, impacts on work, career, daily activities and relationships. Emotional impacts were reported by all participants, including anger, depression, anxiety and hopelessness. Many participants who took preventive treatments reported improvements in HRQL and functioning but still experienced breakthrough attacks. Among patients who took CGRP mAbs, participants noted varying consistency of treatment effectiveness between treatment administrations. CONCLUSION: This study detailed the additional HRQL impact of migraine in-between migraine attacks and described the unmet need for effective treatment options to prevent and mitigate migraine attacks.

Impact of developmental and epileptic encephalopathies on caregivers: A literature review.

OBJECTIVES: Developmental and epileptic encephalopathies (DEEs) are rare neurodevelopmental disorders characterized by early-onset seizures and numerous comorbidities. Due to the complex requirements for the care of a child with a DEE, these disorders would be expected to impact health-related quality of life (HRQL) for caregivers as well as for patients. The objective of this literature review was to describe the impact of DEEs on the HRQL, emotional wellbeing, and usual activities (social, work, relationships, etc.) of caregivers, including the wider impact on other family members such as siblings. METHODS: A literature search was conducted in May 2020 using MEDLINE® and Embase® databases. Quantitative and qualitative studies were identified using search terms related to family, disease type (including >20 specific DEEs), and quality of life/methodology. Each study was assessed for relevance and was graded using customized critical appraisal criteria. Findings from studies that were given the highest quality ratings were summarized and used to develop a conceptual model to illustrate the complex impact of DEEs on caregiver HRQL. RESULTS: Sixty-seven relevant studies were identified, of which 39 (27 quantitative, 12 qualitative) met the highest appraisal criteria. The studies recruited caregivers of patients with one of eight individual DEEs, or pediatric intractable or refractory epilepsy. Most studies reported negative impacts on HRQL and emotional wellbeing in caregivers. The wide-ranging impact of a DEE was highlighted by reports of negative effects on caregivers' physical health, daily activities, relationships, social activities, leisure time, work, and productivity. Factors that influenced the perceived impact included demographic characteristics (e.g., child's age, living arrangements, family income) and clinical factors (e.g., feeding or sleep difficulties, disease severity). Few studies evaluated the impact on siblings. CONCLUSIONS: There is evidence that DEEs can impact HRQL and emotional wellbeing and can limit usual activities for the primary caregiver and their wider family. However, no research was identified regarding many individual DEEs, and only limited research assessed the impact on different family members with most studies focusing on mothers. Further research is required to understand the influence of certain factors such as the age of the patient, disease severity, and seizures on caregiver burden. Furthermore, the review highlighted the lack of appropriate measurement tools to assess caregiver HRQL in this population.

Peanut allergy impact on productivity and quality of life (PAPRIQUA): Caregiver-reported psychosocial impact of peanut allergy on children.

BACKGROUND: Limited research has examined the impact of peanut allergy (PA) on children using validated instruments to assess psychosocial burden and the factors influencing burden. OBJECTIVE: The PAPRIQUA study aimed to assess the caregiver-reported impact of living with PA on children's health-related quality of life (HRQL), correlations between PA severity and child's sex, and associations of caregivers' sex and anxiety with the proxy report of their child's HRQL and to identify significant predictors of a child's HRQL. METHODS: A cross-sectional survey of caregivers of children with mild, moderate and severe PA, based on caregiver perception, was conducted in the United Kingdom. Participants were recruited through a survey recruitment panel; a maximum quota of 20% who rated their child's PA as mild was set to ensure population diversity; however, the quota was not required as few participants considered their child's PA mild. The survey, funded by Aimmune Therapeutics, included sociodemographic and clinical questions, the EQ-5D-Y, Hospital Anxiety and Depression Scale, Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and Food Allergy Independent Measure (FAIM). RESULTS: One hundred caregivers of children with PA (aged 4-15 years) completed the survey. Child's sex was not associated with proxy-reported burden. For younger children (aged 4-10 years), there was no effect of PA severity; parents of older children (aged 11-15 years) reported low to higher burden for their child on the EQ-5D-Y and FAQLQ-PF dependent upon PA severity. For all measures of child burden except the EQ-5D-Y, two or more reactions in the past 12 months and parental anxiety significantly predicted higher levels of burden for the child (P < .05-P < .001). Experiencing a life-threatening event in the past 12 months significantly predicted EQ-5D-Y proxy utility (P < .01). CONCLUSIONS AND CLINICAL RELEVANCE: Caregivers report that children with PA experience high levels of psychosocial burden, particularly those with more severe PA and a reaction history. Interventions to decrease caregiver anxiety and reaction frequency may help reduce the child's burden. Self-report studies in children with PA would help confirm these findings.

APPEAL-2: A pan-European qualitative study to explore the burden of peanut-allergic children, teenagers and their caregivers.

BACKGROUND: Allergy to Peanuts ImPacting Emotions And Life (APPEAL-1) was a recent European multi-country questionnaire survey that highlighted the negative impacts of peanut allergy (PA) on quality of life. A follow-on qualitative study, APPEAL-2, further assessed the burden of PA and associated coping strategies through semi-structured interviews. OBJECTIVE: To gain qualitative insight on the strategies used to cope with and manage PA and the impact of these strategies on the quality of life of children, teenagers and caregivers. METHODS: This cross-sectional qualitative study was conducted in eight European countries: the United Kingdom, France, Germany, Ireland, Spain, Italy, Denmark and the Netherlands. Semi-structured interviews were conducted with children (aged 8-12 years) and teenagers (aged 13-17 years) with self-/proxy-reported moderate or severe PA and with parents/caregivers of children or teenagers (aged 4-17 years) with moderate or severe PA. Data were analysed using thematic analysis; data saturation was assessed. Two conceptual models were developed to illustrate the impacts of PA and coping strategies used to manage them for (a) individuals with PA and (b) parents/caregivers of children with PA. RESULTS: 107 participants were interviewed: 24 children, 39 teenagers and 44 caregivers. The conceptual models illustrated themes related to coping and control, driven by the fear of PA reactions, and the associated emotional, social, relationship and work impacts. Factors moderating these impacts included social attitudes and support, child-caregiver relationship and coping strategies used. CONCLUSIONS AND CLINICAL RELEVANCE: The APPEAL-2 results substantiate the findings of APPEAL-1; the results also suggest that the severity of experience with PA may not correlate with perception of its overall burden and show variable impacts by country.

A Novel Patient-Derived Conceptual Model of the Impact of Celiac Disease in Adults: Implications for Patient-Reported Outcome and Health-Related Quality-of-Life Instrument Development.

BACKGROUND: Celiac disease is a chronic inflammatory condition with wide ranging effects on individual's lives caused by a combination of symptoms and the burden of adhering to a gluten-free diet (GFD). OBJECTIVES: To further understand patients' experience of celiac disease, the impact it has on health-related quality of life (HRQOL), and to develop a conceptual model describing this impact. METHODS: Adults with celiac disease on a GFD reporting symptoms within the previous 3 months were included; patients with refractory celiac disease and confounding medical conditions were excluded. A semistructured discussion guide was developed exploring celiac disease symptoms and impact on patients' HRQOL. An experienced interviewer conducted in-depth interviews. The data set was coded and analyzed using thematic analysis to identify concepts, themes, and the inter-relationships between them. Data saturation was monitored and concepts identified formed the basis of the conceptual model. RESULTS: Twenty-one participants were recruited, and 32 distinct gluten-related symptoms were reported and data saturation was reached. Analysis identified several themes impacting patients' HRQOL: fears and anxiety, day-to-day management of celiac disease, physical functioning, sleep, daily activities, social activities, emotional functioning, and relationships. The conceptual model highlights the main areas of impact and the relationships between concepts. CONCLUSIONS: Both symptoms and maintaining a GFD have a substantial impact on patient functioning and HRQOL in adults with celiac disease. The conceptual model derived from these data may help to design future patient-reported outcomes as well as interventions to improve the quality of life in an individual with celiac disease.

A qualitative investigation of patients' and caregivers' experiences of severe sepsis*.

OBJECTIVES: To explore and describe the subjective experiences and long-term impact of severe sepsis on survivors of severe sepsis and their informal caregivers (e.g., spouse or family member) through qualitative research methods. DESIGN: A qualitative exploratory study using semi-structured interviews with survivors of severe sepsis and their informal caregivers in the United Kingdom and United States. Participants also completed a demographic background form and sites provided medical history details. Transcripts were analyzed using a thematic analysis approach. SETTING: Patients were recruited from a large National Health Service hospital in the United Kingdom and a level 1 trauma center hospital in the United States. Caregivers were recruited through eligible patients. Interviews were conducted either face to face in participant's homes or another convenient location or over the telephone. PATIENTS: Patients who were 18 years old or older and had experienced an episode of severe sepsis in the previous 12 months were recruited by clinical staff in each hospital. Caregivers were family members or friends who had provided informal care for the patient after their episode of severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine interviews were conducted with 22 patients and 17 informal caregivers (of these 28 were conducted face-to-face and 11 by telephone). Five main themes were identified in the qualitative analysis: awareness and knowledge of severe sepsis; experience of hospitalization, ongoing impact of severe sepsis; impact on caregivers; and support after severe sepsis. Experiences varied depending on the patients' health prior to the severe sepsis, with the worst affected reporting lasting impacts on multiple aspects of their life. CONCLUSIONS: The study extends what was understood about severe sepsis from the patients' and caregivers' perspectives from the previous limited literature. Caregivers as well as patients reported enduring impact. The study also identified problems of lack of awareness of diagnosis and understanding of severe sepsis by patients and caregivers and difficulties accessing appropriate healthcare providers and ancillary services after discharge from hospital.

A qualitative evaluation of the validity of published health utilities and generic health utility measures for capturing health-related quality of life (HRQL) impact of differentiated thyroid cancer (DTC) at different treatment phases.

PURPOSE: This study explored the impact of differentiated thyroid cancer (DTC) on health-related quality of life (HRQL) at different treatment phases and evaluated the validity of published DTC utilities and generic health utility measures (EQ-5D and SF-6D) for economic evaluation of treatments for radio-iodine (RAI) refractory DTC. METHODS: Focus groups and interviews were conducted with DTC patients grouped by treatment phase. Qualitative thematic analysis was conducted on interview/focus group transcripts. A thematic coding framework was developed to compare experiences between treatment phases and inform development of a conceptual model. Model concepts were mapped to EQ-5D and SF-6D domains/items. RESULTS: Eight focus groups and 11 individual interviews were conducted with 52 DTC patients. Fifty symptoms and HRQL concepts were identified. The impact of DTC and DTC treatment on emotional and cognitive functioning was reported across the treatment phases. The impact on daily activities, mobility, and energy levels was greatest for patients with recurring/persistent or RAI-refractory DTC. Of the 50 concepts, 25 and 27 mapped directly onto domains/items in the EQ-5D and SF-6D, respectively. The SF-6D covered a broader range of DTC impact on emotional/physical problems and daily/social activities than did the EQ-5D. CONCLUSIONS: The conceptual model summarizes the wide-ranging impact of DTC and its treatment on patients' HRQL, particularly for those with recurring/persistent or RAI-refractory DTC. Findings suggest that published DTC utilities lack validity for RAI-refractory DTC and that the SF-6D may be more sensitive to HRQL impact of DTC than the EQ-5D.

Estimating the Health-Related Quality of Life Benefit of Prophylactic Treatment for COVID-19 in Immunocompromised People: A Multimethod Valuation Study.

Background: Pre-exposure prophylaxis (PrEP) for COVID-19 provides additional protection, beyond vaccines alone, for individuals who are immunocompromised (IC). This may reduce the need for preventative behavioral modification, such as shielding-a behavioral restriction limiting an IC individual to minimize face-to-face interactions and/or crowded places. Therefore, PrEP may improve psychosocial well-being and health-related quality of life (HRQoL) for individuals with IC conditions. Objective: To estimate the potential HRQoL and utility benefit of PrEP for prevention of COVID-19 in individuals with IC conditions who may not have an adequate response of full vaccination (and therefore are at "highest risk" of severe COVID-19) that can be used in future economic evaluations of preventative therapies against COVID-19. Methods: Vignettes describing HRQoL associated with 2 pre-PrEP states (shielding and semi-shielding behavioral restrictions) and a post-PrEP state were developed from a literature review and tested through interviews with clinicians (n = 4) and individuals with IC conditions (n = 10). Vignettes were valued by a general population sample (N = 100) using a visual analog scale (VAS), time trade-off (TTO), and EQ-5D-5L. A sample of individuals with IC conditions (n = 48) valued their current HRQoL and a post-PrEP vignette using VAS and EQ-5D-5L. Results: Individuals with IC conditions reported a mean current EQ-5D-5L score of 0.574, and 0.656 for post-PrEP based on the vignette. PrEP would lead to behavior changes for 75% (30/40) of individuals with IC conditions and an emotional benefit for 93% (37/40) of individuals with IC conditions. Mean values from the general population valuation based on EQ-5D-5L ranged from 0.606 ("shielding") to 0.932 ("post-PrEP"). Conclusion: This study quantified the expected health state utility benefit of reduced psychosocial burden and behavioral restriction. PrEP would potentially result in a utility gain between 0.082 and 0.326, dependent on valuation approach and expected change in behavioral restrictions, leading to improvements in daily activities and emotional well-being.

Estimating utility values for non-alcoholic steatohepatitis health states: a discrete choice experiment.

Background: This study estimated utility values for non-alcoholic steatohepatitis (NASH). Previous studies have assumed that health-related quality of life does not vary between the early stages of NASH. Materials & Methods: Discrete choice experiment (DCE) surveys estimated the value of avoiding fibrosis progression. Patients also completed the EQ-5D-5L. Marginal rates of substitution estimated utility change associated with fibrosis progression. Results: DCE surveys were completed by the UK general public (n = 520) and patients with NASH (n = 154). The utility decline between fibrosis stages F1 and F4 decompensated was between -0.521 to -0.646 (depending on method). Conclusion: Three methods were used to estimate utilities for NASH, each one showed sensitivity to advancing fibrosis, including in the early stages, which is often considered asymptomatic.

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.

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.

Quality of Life with Late-Onset Pompe Disease: Qualitative Interviews and General Public Utility Estimation in the United Kingdom.

Background: Late-onset Pompe disease (LOPD) is a rare, progressive neuromuscular condition typically characterized by weakness of skeletal muscles, including those involved in respiration and diaphragmatic dysfunction. Individuals with LOPD typically eventually require mobility and/or ventilatory support. Objectives: This study aimed to develop health state vignettes and estimate health state utility values for LOPD in the United Kingdom. Methods: Vignettes were developed for 7 health states of LOPD with states defined in terms of mobility and/or ventilatory support. Vignettes were drafted based on patient-reported outcome data from the Phase 3 PROPEL trial (NCT03729362) and supplemented by a literature review. Qualitative interviews with individuals living with LOPD and clinical experts were conducted to explore the health-related quality-of-life (HRQoL) impact of LOPD and to review the draft vignettes. Vignettes were finalized following a second round of interviews with individuals living with LOPD and used in health state valuation exercises with people of the UK population. Participants rated the health states using the EQ-5D-5L, visual analogue scale, and time trade-off interviews. Results: Twelve individuals living with LOPD and 2 clinical experts were interviewed. Following the interviews, 4 new statements were added regarding dependence on others, bladder control problems, balance issues/fear of falling, and frustration. One hundred interviews with a representative UK population sample were completed. Mean time trade-off utilities ranged from 0.754 (SD = 0.31) (no support) to 0.132 (SD = 0.50) (invasive ventilatory and mobility support-dependent). Similarly, EQ-5D-5L utilities ranged from 0.608 (SD = 0.12) to -0.078 (SD = 0.22). Discussion: The utilities obtained in the study are consistent with utilities reported in the literature (0.670-0.853 for nonsupport state). The vignette content was based on robust quantitative and qualitative evidence and captured the main HRQoL impacts of LOPD. The general public rated the health states consistently lower with increasing disease progression. There was greater uncertainty around utility estimates for the severe states, suggesting that participants found it harder to rate them. Conclusion: This study provides utility estimates for LOPD that can be used in economic modeling of treatments for LOPD. Our findings highlight the high disease burden of LOPD and reinforce the societal value of slowing disease progression.

How do children and their caregivers perceive the benefits of inhaled asthma therapy?

OBJECTIVE: Although well reported in adults, there is relatively little data on how children with asthma and their parents describe their attitudes to the disease, expectations of therapy, and perception of treatment benefit. We investigated this to determine if they differed from reports by adults with asthma. METHODS: We recruited families with an asthmatic child (4-11 years) who had recently been prescribed a change in treatment [starting inhaled corticosteroid monotherapy (ICS) or changing from ICS to inhaled corticosteroid/long-acting ß(2)-agonist combination therapy (ICS/LABA)]. Semi-structured interviews were conducted with the parents and the children if aged 7-11 years. RESULTS: We interviewed 28 parents and 13 children. All children on ICS/LABA had been changed from ICS monotherapy because of poor asthma control. Pediatric asthma had a significant impact on the whole family and both parents and children hoped the new medication would improve symptoms, increase their participation in physical activities, and decrease unscheduled visits to the GP (General Practitioner)/hospital. Positive effects of treatment change were reported by both parents and children, particularly in those changing from ICS to ICS/LABA. The most commonly reported benefits were reduced cough and wheeze, increased participation in sport or play activities, and reduced rescue medication use. These effects resulted in fewer visits to the GP/hospital and better attendance at school. CONCLUSIONS: While asthma symptoms prevent adults and children from participating in different types of activities (e.g., school, employment), children and their parents report the same benefits as previously reported in adults with asthma.

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.

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.

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.

Estimation Of The Quality Of Life Benefits Associated With Treatment For Spinal Muscular Atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, genetic, progressive neuromuscular disorder characterized by severe muscle atrophy and weakness and is a leading genetic cause of death in infants and children. Nusinersen was the first treatment targeting the underlying cause of disease approved by the FDA, EMA and other countries for patients with SMA. There are currently very limited data available on the health-related quality of life (HRQoL) burden of SMA suitable for use in a cost-effectiveness analysis. OBJECTIVE: This study was designed to estimate quality of life weights or utilities for different SMA states. METHODS: SMA case studies were developed describing Type I (infantile onset) and Type II (later-onset) patients and different outcomes from treatment. These were developed so that quality of life weights or utilities (where the value of health ranges from 1 - full health to 0 - dead) could be estimated for cost-effectiveness analysis. Clinical experts (n=5) rated each of the case studies using standardized HRQoL instruments - the EQ-5D-Y and PedsQL-NMM (baseline states only). RESULTS: The SMA Type I utilities ranged from -0.33 (requires ventilation) to 0.71 (Type I patient reclassified as Type III following treatment), with quite substantial differences between some states. Most Type I states had a utility score below zero indicating the severity of the states. The SMA Type II utilities ranged from -0.13 (worsened) to 0.72 (stands/walks unaided). In general, the results showed HRQoL improved in line with better health states. CONCLUSION: The utility scores obtained in this study highlight the very substantial burden experienced by SMA patients. Despite the limitations in the methods used, this study produced data with face validity and is a useful starting point for understanding the burden of SMA Types I and II in cost-effectiveness analysis.

NMDA receptor antagonists and pain relief: A meta-analysis of experimental trials.

OBJECTIVE: We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of NMDA receptor (NMDAR) antagonists. METHODS: Six major databases were systematically searched (to March 2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis. RESULTS: Searches identified 70 eligible trials (n = 1,069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in hyperalgesic area (standardized mean difference 0.54, 95% confidence interval [CI] 0.34, 0.74, p < 0.001) and a 1.2-point decrease (95% CI 0.88, 1.44, p < 0.001) in pain ratings from 4.6 to 3.4 on a 0-10 scale (a 26% reduction). Similar analgesia was observed for acute and hyperalgesic models and was constant across the dosing range (0.03-1.00 mg/kg). Moderate to high variability in effect size was observed and mild side effects (e.g., sedation, sensory disturbance) were common. No effects of dextromethorphan were found. CONCLUSIONS: Findings provide robust evidence for analgesic and antihyperalgesic effects of ketamine, supporting its utility for acute and chronic pain management. However, pain relief was modest, suggesting ketamine may potentially be most useful when opioids are contraindicated, rapid analgesia is required, or for pain resistant to conventional medication.

Disutility Study for Adult Patients with Moderate to Severe Crohn's Disease.

BACKGROUND: Crohn's disease (CD) treatments and associated adverse events (AEs) can be burdensome for patients. However, specific values which quantify the impact on health-related quality of life (HRQL) for economic evaluation are lacking. OBJECTIVES: This study aimed to elicit health utility values for AEs related to biologic treatment and surgical complications for CD in the UK. METHODS: Health states were developed by literature review and interviews with CD patients (n=6) and gastroenterologists (n=3). Draft health states were validated in cognitive debrief interviews with patients (n=4) and gastroenterologists (n=2). Treatment AEs were described with moderate-severe CD (reference state) and included hypersensitivity, injection site reactions, serious infection, lymphoma, and tuberculosis. Surgical complications were described following bowel surgery (reference state) and included anastomotic leak, wound infection, prolonged ileus/bowel obstruction, and intra-abdominal abscess. Health states were valued by 100 members of the general public who completed background questions, EQ-5D-3L, visual analogue scale rating task and time trade-off (TTO) interviews. RESULTS: The mean TTO value for reference states 'moderate to severe CD' and 'bowel surgery' were 0.70 (SD=0.28) and 0.69 (SD=0.28). Participants rated lymphoma as the worst AE/surgical complication state (0.44, SD=0.37), followed by tuberculosis (0.47, SD=0.85) and anastomotic leak (0.48, SD=0.38). Values of other AE/surgical complication states ranged from 0.76 (hypersensitivity) to 0.56 (intra-abdominal abscess). CONCLUSIONS: This study provides utility estimates for AE and surgical complication health states not previously assessed in the context of CD. As new treatments are emerging, it is important to include these influences on quality of life in any economic evaluation of treatments.