Marieke Verkleij

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with improvements in physical health and well‐being. However, there are growing concerns about side‐effects related to sleep, cognition and new, or worsening mental health in a subset. This study assessed healthcare providers' perceptions of the positive and negative impacts of ETI and compared provider ratings in Europe to the United States. Methods: The European CF Society's Mental Health Working Group adapted and distributed the survey developed by the CF Foundation's Mental Health Advisory Committee. It assessed healthcare providers' observations of the impacts of ETI in these domains: (1) positive and negative physical and psychological effects, (2) sleep difficulties, (3) cognitive difficulties, (4) worsening mental health, and (5) concerns about the future and finances. Results: Seventy‐eight healthcare providers across 21 European (EU) countries responded, endorsing similar percentages of positive physical and psychological effects as US providers. However, in Europe lower percentages of MH side‐effects (e.g., increased depression/anxiety, suicidal ideation, body image), and concerns about the future (e.g., copays, food insecurity) were found. Conclusions: Across international providers similar positive results were reported. A substantial proportion of PWCF across EU and United States experienced ETI side‐effects related to sleep, cognition, and new or worsening mental health. However, EU providers reported significantly fewer side‐effects related to mental health, negative body image, planning for the future and finances. MH side‐effects led to dosing changes in ETI and in the United States, they led to changes in MH medications. These international data document the importance of systematically assessing and managing these side‐effects.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with improvements in physical health and well-being. However, there are growing concerns about side-effects related to sleep, cognition and new or worsening mental health in a subset. This study assessed healthcare providers’ perceptions of the positive and negative impacts of ETI and compared provider ratings in Europe to the United States (US). Methods: The European CF Society’s Mental Health Working Group adapted and distributed the survey developed by the CF Foundation’s Mental Health Advisory Committee. It assessed healthcare providers’ observations of the impacts of ETI in these domains: 1) positive and negative physical and psychological effects, 2) sleep difficulties, 3) cognitive difficulties, 4) worsening mental health, and 5) concerns about the future and finances. Results: Seventy-eight healthcare providers across 21 European (EU) countries responded, endorsing similar percentages of positive physical and psychological effects as US providers. However, in Europe lower percentages of MH side-effects (e.g., increased depression/anxiety, suicidal ideation, body image), and concerns about the future (e.g., copays, food insecurity). Conclusions: Across international providers similar positive results were reported. A substantial proportion of PWCF across EU and US experienced ETI side-effects related to sleep, cognition, and new or worsening mental health. However, EU providers reported significantly fewer side-effects related to mental health, negative body image, planning for the future and finances. MH side-effects led to dosing changes in ETI and in the US, they led to changes in MH medications. These international data document the importance of systematically assessing and managing these side-effects.

Background: People with CF (pwCF) frequently have gastrointestinal symptoms (GI), including abdominal pain and irregular bowel movements. These are often embarrassing, difficult to report, and frequently missed. Thus, a GI Symptom Tracker was created and validated in the USA and translated and validated in Dutch. This questionnaire consists of four subscales: Eating Challenges, Stools, Adherence Challenges, and Abdominal Symptoms. The aim of this study was to investigate the relationship between GI symptoms, anxiety/depression, and health‐related quality of life (HRQoL) in Dutch pwCF.Methods: In this prospective, cross‐sectional single‐center pilot study, pwCF completed the Dutch GI Symptom Tracker, GAD‐7 (anxiety), PHQ‐9 (depression), and CFQ‐R (HRQoL) from September 2021 to June 2022. Regression analyses were used to analyze the univariable associations between GI symptoms, anxiety/depression, and HRQoL.Results: A total of 51 pwCF were enrolled consecutively (n = 41 adults, 66% female, mean age (y) [range] = 32.7 [19–71] and n = 10 adolescents, 70% female, mean age (y) [range] = 14.2 [12–17]). Elevated levels of anxiety (scores ≥ 10 on GAD‐7) were found in 17% of adults and 0% of adolescents. Elevated depression scores (≥ 10 on PHQ‐9) were found in 9% of adults and 20% of adolescents. GI scales “Abdominal Symptoms” and “Stools” were significantly, positively associated with elevated symptoms of anxiety and depression. Most GI scales were associated with lower HRQoL.Conclusion: This is the first study investigating the link between GI symptoms assessed by the Dutch GI Symptom Tracker and anxiety/depression and HRQoL in Dutch pwCF. More GI symptoms were associated with higher anxiety and depression scores and worse HRQoL. Additional research is needed to better understand how mental and physical health are linked in GI symptoms in CF.

Objective: In pediatric asthma care, currently used disease-specific legacy Patient Reported Outcome Measures (PROMs) are considered burdensome due to their length and irrelevant questions. PROMIS® measures could solve this problem. This study aims to investigate the psychometric properties of PROMIS measures in children with asthma. Methods: Dutch children (8-17 yrs) with asthma (GINA step 2-5) will complete 9 pediatric PROMIS measures as short-form or computerized adaptive test (Asthma Impact, Depressive Symptoms, Anxiety, Fatigue, Peer Relationships, Sleep Disturbance, Mobility, Global Health, Anger) & 3 legacy measures (Asthma Control Test, Pediatric Asthma QoL Questionnaire, PedsQLTM - Asthma module). We will investigate: 1) convergent validity by comparing PROMIS measures T-scores to scores of legacy measures using Pearson’s r, 2) reliability using Cronbach’s alpha and standard error of theta (SE(θ)), and 3) efficiency by calculating performance of the PROMIS and legacy measures relative to the number of items administered. PROMIS mean T-scores will be calculated to provide pediatric asthma reference data. Expected results: We aim to include 100 participants. High correlations (r>0.7) between PROMIS Asthma Impact and associated asthma impact subscales of the legacy measures, and good reliability (SE(θ)<0.32) for all PROMIS measures are expected. We expect PROMIS measures to be more efficient than legacy measures in number of items administered, while retaining a reliable measurement. Conclusions: If the pediatric PROMIS measures display good psychometric properties, PROMIS can be used in research and clinical care for children with asthma, and thus reduce PROM-related burden.

Background: People with CF (pwCF) frequently have gastrointestinal symptoms (GI), including abdominal pain and irregular bowel movements. These are often embarrassing, difficult to report, and frequently missed. Thus, a GI Symptom Tracker was created and validated in the US and translated and validated in Dutch. This questionnaire consists of four subscales: Eating Challenges, Stools, Adherence Challenges and Abdominal Symptoms. Aim of this study was to investigate the relationship between GI symptoms, anxiety/depression and health-related quality of life (HRQoL) in Dutch pwCF. Methods: In this prospective, cross-sectional single-center pilot study, pwCF completed the Dutch GI Symptom Tracker, GAD-7 (anxiety), PHQ-9 (depression), and CFQ-R (HRQoL) from Sept 2021-June 2022. Regression analyses were used to analyze the univariable associations between GI symptoms, anxiety/depression and HRQoL. Results: 51 pwCF were enrolled consecutively ( n = 41 adults, 66% female, mean age (y) [range]= 32.7 [19-71] & n =10 adolescents, 70% female, mean age (y) [range]= 14.2 [12-17]). Elevated levels of anxiety (scores ≥10 on GAD-7) were found in 17% of adults and 0% of adolescents. Elevated depression scores ( ≥10 on PHQ-9) were found in 9% of adults and 20% of adolescents. GI scales ‘Eating Challenges’ and ‘Stools’ were significantly, positively associated with elevated symptoms of anxiety and depression. Most GI scales were associated with lower HRQoL. Conclusion: This is the first study investigating the link between GI symptoms assessed by the Dutch GI Symptom Tracker and anxiety/depression and HRQoL in Dutch pwCF. More GI symptoms were associated with higher anxiety and depression scores and worse health-related quality of life. Additional research is needed to better understand how mental and physical health are linked in CF.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with unprecedented clinical improvements, transforming the management of cystic fibrosis (CF). However, side effects with implications for safety and well‐being have been reported, including neuropsychiatric changes. This study aimed to better characterize the emerging positive and negative impacts of ETI.Methods: The Cystic Fibrosis Foundation's Mental Health Advisory Committee distributed a 26‐item survey to US CF care teams to assess clinician observations of patient‐reported experiences with ETI. Survey responses measured the prevalence of these effects in five domains: (1) positive physical and psychological effects, (2) sleep difficulties, (3) cognitive difficulties, (4) worsening mental health, and (5) concerns about the future and finances.Results: Seventy‐five healthcare providers responded from a pediatric, adult, and combined centers. Positive physical effects of ETI and increased optimism were reported in the upper quartiles (50%–100%) and rated as having a significant impact on daily functioning. Sleep and cognitive difficulties were reported in 1%–24%, with slight impacts on functioning, and psychological symptoms (e.g., increased stress, depression, anxiety) and new psychiatric medications were reported in 1%–24%, with moderate impacts. Concerns about the future were reported in 1%–24%, with minimal impacts.Conclusion: Across US centers, providers most often observed positive physical effects of ETI. However, a variety of negative side effects were also reported, including sleep disruptions and worsening psychological functioning, which should be systematically monitored by CF teams. These national‐level data are a first step in evaluating the prevalence and consequences of these side effects and can directly inform future studies.

Background: eHealth CF‐CBT is the first digital mental health intervention for depression/anxiety in adults with cystic fibrosis (awCF); an 8‐session therapist‐guided internet‐delivered program that was developed in English and Dutch with stakeholder input and evaluation indicating high acceptability and usability.Methods: Dutch eHealth CF‐CBT was piloted in awCF with mild‐moderate symptoms of depression and/or anxiety. Feasibility, usability, acceptability, and preliminary efficacy were assessed, measuring pre‐post changes in depression (PHQ‐9), anxiety (GAD‐7), perceived stress (PSS), and health‐related quality of life (CFQ‐R).Results: All participants (n = 10, seven female, mean age 29 [range 21–43], mean FEV1 71%pred [range 31–115]) completed all sessions. Patient‐rated feasibility, usability, and acceptability of eHealth CF‐CBT were positive on validated scales, as were qualitative assessments of content and format. GAD‐7 improved in 90% of participants; in 50% by ≥the minimally important difference (MID) of four points. PHQ‐9 improved in 90%; 40% by ≥the MID of 5. PSS improved in 80%. CFQ‐R improved in the domain health perceptions (70%).Conclusions: eHealth CF‐CBT demonstrated feasibility, usability, acceptability, and promising preliminary efficacy in this pilot trial with Dutch awCF with mild to moderate symptoms of depression and anxiety.

Background: The COVID‐19 pandemic has spread across the world, leading to government measures associated with a negative impact on mental health. The aim of this study was to evaluate the impact of the pandemic on depression, anxiety and resilience in Dutch people with cystic fibrosis (PwCF) or primary ciliary dyskinesia (PwPCD) and their caregivers.Methods: Adolescents (12–17 years) and caregivers of children (0–17 years) with CF, and adolescents, adults and caregivers of children with PCD completed questionnaires on depression, anxiety and resilience between September 2020 and February 2021. The psychosocial impact of COVID‐19 was measured by the Exposure and Family Impact Survey (CEFIS) Part 2. Mixed model analyses compared depression and anxiety results to participants' prepandemic scores.Results: One hundred ten participants (10 PwCF, 31 PwPCD, 52 CF caregivers, 17 PCD caregivers) completed questionnaires during the pandemic. Prepandemic outcomes were available for 87 participants. The prevalence of symptoms of depression and anxiety (PHQ‐9 or GAD‐7 scores ≥5) in PwCF and PwPCD and their caregivers before and during the pandemic was high, with an increase in depression in PwCF (2.75; 95% confidence interval: 0.82–4.68) and increase in anxiety in CF caregivers (1.03; 0.09–1.96) during the pandemic. Resilience was within the normal range for all groups, CEFIS scores corresponded to a low to normal impact.Conclusion: PwCF and PwPCD and their caregivers were at risk of elevated depression and anxiety symptoms both before and during the pandemic, which emphasizes the importance of mental health screening and psychological care in CF and PCD.