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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.

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.Patient data (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.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.

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 clin...

Zusammenfassung Hintergrund In Industrieländern sind bis zu 3 % aller Kinder von einer Erdnussallergie betroffen. Allergy to Peanuts imPacting Emotions And Life (APPEAL) ist die erste große Studie, die die Auswirkungen und Belastungen durch eine Erdnussallergie auf Betroffene und Angehörige untersucht. Material und Methoden Betroffene mit Erdnussallergie und deren Eltern/Betreuer nahmen entweder an einer Online-Umfrage teil (APPEAL‑1, n = 273) oder gaben detaillierte Interviews (APPEAL‑2, n = 32). Ergebnisse Von den Befragten der APPEAL-1-Studie (56 erwachsene Patienten mit Erdnussallergie und 217 Eltern/Betreuer von Personen mit Erdnussallergie) gaben 85 % an, dass die Erdnussallergie ihre täglichen Aktivitäten beeinflusst, 65 % fühlten sich deshalb isoliert. 91 % sorgten sich besonders bei gesellschaftlichen Anlässen vor einer potenziellen Erdnussexposition; 85 % verspürten Hindernisse beim Pflegen sozialer Kontakte. Die häufigsten psychologischen Auswirkungen der Erdnussallergie waren Frustration (89 %), Unsicherheit (86 %) und Stress (88 %). Ein Großteil der Befragten (84 %) beschrieb ein Gefühl der Andersartigkeit. Durch die Erdnussallergie kommt es häufig zu Beeinträchtigungen bei sozialen Aktivitäten, im schulischen Umfeld, im Beruf (bei Eltern und erwachsenen Betroffenen) sowie in Bezug auf emotionales Befinden und Beziehungen. Als wichtigste Bewältigungsstrategien nannten die Teilnehmer eine gute Überwachung von Nahrung und Hygiene, den Austausch mit anderen und eine akribische Planung von Aktivitäten. Schlussfolgerungen Dies ist die erste alltagsbezogene Umfrage in Deutschland, die die Auswirkungen und Belastungen einer Erdnussallergie bei betroffenen Kindern, Jugendlichen und deren Eltern/Betreuern sowie bei selbst betroffenen Erwachsenen aufzeigt.

Katy Gallop,1 Sarah Acaster,1 Jane de Vries,2 Richard Browne,2 Robert Ryan,2 Sarah Baker,3 George Du Toit4 1Acaster Lloyd Consulting Ltd, London, UK; 2Aimmune Therapeutics, London, UK; 3Anaphylaxis Campaign, Farnborough, UK; 4Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UKCorrespondence: Katy Gallop, Acaster Lloyd Consulting, 84 Theobalds Road, London, WC1X 8NL, UK, Tel +44 203 9781686, Email katy.gallop@acasterlloyd.com Robert Ryan, Aimmune Therapeutics, 10 Eastbourne Terrace, London, W2 6LG, UK, Email rryan@aimmune.comPurpose: 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.Keywords: peanut allergy, oral immunotherapy, health-related quality of life, health state utilities, caregiver

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.

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.

The objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms. Associations were assessed at day 30 (end-of-trial follow-up). Pearson correlation assessed the relationship between EPDS and PHQ-9 item and total scores and HAMD-17 total score. Cohen’s kappa assessed agreement of EPDS remission (score r = 0.71, p < 0.001; HAMD-17/PHQ-9: r = 0.75, p < 0.001). Individual EPDS and PHQ-9 items significantly correlated (r= 0.35 to 0.67, all p < 0.001) with HAMD-17 total score. EPDS had 79% sensitivity and 67% specificity to detect HAMD-17 remission; corresponding estimates for PHQ-9 were 76% and 78%. OLS models yielded the following equations: HAMD-17 total = 2.66 + (EPDS total × 0.87) and HAMD-17 total = 3.99 + (PHQ-9 total × 0.97). There were large and statistically significant associations between patient-reported outcomes (EPDS, PHQ-9) and clinician-reported outcomes (HAMD-17) as clinical improvements were associated with patient-reported symptom improvement. These results provide tools to help translate clinical trial data to clinical practice, thus aiding shared decision-making for this critical population.

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; however, 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.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).A classification system with 8 dimensions (CFQ-R-8D; 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.The CFQ-R-8D 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.

Aim: To describe the experience of nonsense mutation Duchenne muscular dystrophy (DMD) across different health states in the DMD natural history model. Materials and methods: Qualitative interviews were conducted with UK caregivers (n = 10) of individuals with nonsense mutation DMD treated with ataluren. Results: Interviews were conducted with caregivers of individuals in the early ambulatory (n = 6), late ambulatory (n = 3) and transfers (n = 3) health states. Increasing health state severity was related to decreased physical function, which impacted daily and social activities, emotional well-being and caregiver burden. Conclusion: Declining physical function can impair daily life and impact the health-related quality of life of individuals and their caregivers. Delaying progression between health states has the potential to prevent loss of function and decline in health-related quality of life.

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.

Background: Coeliac disease patients on a gluten-free diet experience reactions to gluten, but these are not well characterised or understood. Systemic cytokine release was recently linked to reactivation of gluten immunity in coeliac disease. Aim: To define the nature and time-course of symptoms and interleukin-2 changes specific for coeliac disease patients. Methods: 25 coeliac disease patients on a gluten-free diet and 25 healthy volunteers consumed a standardised 6 gram gluten challenge. Coeliac Disease Patient-Reported Outcome survey and global digestive symptom assessment were completed hourly up to 6 hours after gluten. Adverse events over 48 hours were recorded. Serum interleukin-2 was measured at baseline, and 2, 4 and 6 hours. Results: Serum interleukin-2 was always undetectable in healthy controls, whereas it was undetectable at baseline and elevated >0.5 pg/ml at 4 hours in 92% of coeliac disease patients. All patient-reported outcome severity scores increased significantly after gluten in coeliac disease patients (P

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.

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

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.

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.

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.

Introduction Postpartum depression (PPD) is a specifier of major depressive disorder (MDD) with peripartum onset. SAGE-217, an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator, demonstrated improvements in depressive and anxiety symptoms versus placebo in a Phase 3 trial in PPD (NCT02978326; ROBIN) and a pivotal trial in MDD (NCT03000530). In PPD and MDD, insomnia symptoms are key diagnostic features, comorbid sleep disorders are frequent, and insomnia is a common residual symptom. Here we conducted post-hoc analyses to assess insomnia symptoms in the ROBIN trial. Methods Women (n=151) ages 18-45, ≤6 months postpartum, with PPD (major depressive episode beginning in 3rd trimester or ≤4 weeks postpartum) and a Hamilton Rating Scale for Depression (HAM-D) total score ≥26, were randomized 1:1 to receive outpatient SAGE-217 30mg or placebo for two weeks, with 4 weeks follow-up. Change from baseline (CFB) in HAM-D score at Day 15 was the primary endpoint. Secondary endpoints included CFB in HAM-D at other time points and the Montgomery-Åsberg Depression Rating Scale (MADRS). Post-hoc analyses assessed HAM-D insomnia subscale (HAM-D-Ins) and MADRS individual insomnia item (MADRS-Ins) scores. HAM-D and MADRS measures were evaluated using a mixed-effects model for repeated measures. Safety and tolerability were assessed by adverse event (AE) reporting. Results SAGE-217 demonstrated statistically significant Day 15 CFB versus placebo in HAM-D (primary endpoint: -17.8 vs. -13.6, p=0.0028), MADRS (-22.1 vs. -17.6, p=0.0180), and associated insomnia sub-scales/items (difference SAGE-217 vs. placebo; HAM-D-Ins: -1.003, p=0.0038; MADRS-Ins: -0.773, p=0.0116). Significant CFB in insomnia sub-scales/items favoring SAGE-217 were observed by Day 3 (HAM-D-Ins: -0.841, p=0.0142; MADRS-Ins: -0.710, p=0.017) and at Day 45 (HAM-D-Ins: -0.730, p=0.0207; MADRS-Ins: -0.636, p=0.0221). Most common (≥5%) AEs were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. Conclusion SAGE-217 demonstrated improvements in depression symptoms, including insomnia symptoms, and was generally well tolerated. Support This study was sponsored by Sage Therapeutics, Inc.

Patients with schizophrenia report reduced pain sensitivity in clinical studies, but experimental studies are required to establish pain sensitivity as a potential endophenotype. We conducted a systematic review of electronic databases from database inception until April 15, 2015, including experimental studies investigating pain among patients with schizophrenia spectrum disorder vs healthy controls. A random-effect meta-analysis yielding Hedges' g ±95% confidence intervals (CIs) as the effect size (ES) measure was conducted. Primary outcome was a pooled composite of pain threshold and pain tolerance; secondary outcomes included these parameters individually, plus sensory threshold, physiological pain response, and pain intensity or unpleasantness. Across 17 studies, patients with schizophrenia spectrum disorder (n = 387; age, 30.7 ± 6.9 years; females, 31.9%; illness duration, 7.0 ± 5.7 years) were compared with controls (n = 483; age, 29.5 ± 7.4 years; females, 31.0%). Patients had elevated pain threshold/pain tolerance vs controls (ES = 0.583; 95% CI, 0.212-0.954; P = 0.002; studies = 15). Results were similar in antipsychotic-free individuals (ES = 0.599; 95% CI, 0.291-0.907; P < 0.0001; studies = 8), with trend-level significance in antipsychotic-treated individuals (ES = 0.566; 95% CI, -0.007 to 1.125; P = 0.047; studies = 9). Likewise, patients with schizophrenia had increased pain tolerance (ES = 0.566; 95% CI, 0.235-0.897; P = 0.0001; studies = 6), sensory threshold (ES = 1.16; 95% CI, 0.505-1.727; P < 0.0001; studies = 5), and pain threshold (ES = 0.696; 95% CI, 0.407-0.986; P < 0.001; studies = 9), as well as reduced physiological response to noxious stimuli (ES = 0.456; 95% CI, 0.131-0.783; P = 0.006) and pain intensity/unpleasantness ratings (ES = 0.547; 95% CI, 0.146-0.949; P = 0.008). Findings were similarly significant in antipsychotic-free patients with schizophrenia (analysable parameters = 4) and antipsychotic-treated individuals (analysable parameters = 2). Finally, greater psychiatric symptoms moderated increased pain threshold, and younger patient age moderated increased pain tolerance. Decreased pain sensitivity seems to be an endophenotype of schizophrenia spectrum disorders. How this alteration links to other dimensions of schizophrenia and physical comorbidity-related help-seeking behaviour/morbidity/mortality requires further study.

New therapies for relapsing/refractory Hodgkin lymphoma (R/R HL) and R/R systemic anaplastic large-cell lymphoma (sALCL) have emerged. This study captured utility values for R/R HL and sALCL to support economic evaluation. Health state "vignettes" were developed describing states associated with R/R HL and sALCL: treatment response (complete or partial response), stable and progressive disease and treatment-related adverse events (B-symptoms, acute/chronic graft-versus-host disease [GVHD] and peripheral neuropathy). Vignettes were evaluated by members of the public in the UK, Australia, Taiwan, Thailand, South Korea, Brazil and Mexico using the time trade-off method. Mean utilities varied substantially. Complete response utility scores were UK: 0.906, Australia: 0.889, Taiwan: 0.597, Thailand: 0.728, South Korea: 0.827, Brazil: 0.764, Mexico: 0.728. Adverse events were associated with disutility: acute GVHD, lowest mean utility value: Thailand 0.124; highest value: Mexico 0.467. Societal evaluation of health states for R/R HL and sALCL revealed a marked perceived benefit of a treatment response.

Incentive motivation theories of addiction suggest that behavioural concomitants of compromised mesocorticolimbic reward activity during abstinence might include decreased affective reactions to natural reinforcers. This study tested implications for hedonic reactions in abstinent smokers. It was hypothesised that positively valenced (pleasurable) film clips would elicit lower ratings of happiness in abstinent than satiated smokers. Twenty-nine smokers, randomly assigned to either an ‘abstinent’ or a ‘satiated’ condition, and 15 non-smokers took part in a single session in which they rated (i) signs and symptoms of nicotine withdrawal and (ii) affective responses to positively valenced, negatively valenced, and neutral film clips. Compared with satiated smokers, abstinent smokers rated positive clips as eliciting significantly lower levels of happiness, and this was independent of self-reported nicotine withdrawal symptoms; the scores of non-smokers fell between those of abstinent and satiated smokers, more closely approximating those of the latter. By contrast, sadness ratings in response to negative clips were not affected by smoking status, indicating that the effect on happiness was not simply due to general emotional blunting. These results suggest that, for regular smokers, stimuli that are motivationally salient for the general population may elicit reduced positive affective responses during periods of abstinence.

Background There are few published health technology assessments that have included the impact of a disease or treatment on caregivers’ health related quality of life (HRQL). The objectives of this study were to explore the overall HRQL of caregivers of people with Multiple Sclerosis compared to matched controls, and more specifically explore the impact of different levels of functioning in people with MS on caregivers’ HRQL scores. Methods A cross sectional observational study conducted as an online survey was undertaken in the UK. 200 caregivers of people with MS and 200 matched controls completed the EQ-5D, SF-36, HADS and a socio-demographic questionnaire. Caregivers also completed the Patient Determined Disease Steps questionnaire as a measure of MS severity. Differences in HRQL between caregivers and controls were assessed using t-tests and chi square analyses as appropriate. Ordinary Least Squares regression was also used to evaluate the disutility of being a caregiver compared to controls stratified by MS severity. Results Caregivers reported significantly lower HRQL, as measured by the SF-36, HADS and EQ-5D, compared to matched controls. A lower level of functioning in people with MS was mirrored by lower levels of caregivers’ HRQL. At the point at which mobility problems required wheelchair use caregivers reported better HRQL. Conclusions The potential impact of caregiving on HRQL is an important consideration for economic evaluations. In relation to MS, the results suggest that caregiver’s HRQL deteriorates as the people with MS lose functioning; thus treatments that delay loss of function may have a benefit for caregivers as well as patients.