Exploring perceptions of and decision-making about CFTR modulators.

INTRODUCTION: Cystic fibrosis (CF) treatment has increasingly focused on highly effective modulators. Despite measurable benefits of modulators, there is little guidance for CF care team members on providing education and support to patients regarding initiation of these therapies. We aimed to explore patient, caregiver, and clinician perceptions of modulators and influences on decisions about starting cystic fibrosis transmembrane regulator (CFTR) modulators. METHODS: We conducted semistructured interviews with CF clinicians, adults with CF, and caregivers of children with CF. We reviewed audio recordings and coded responses to identify central themes. RESULTS: We interviewed 8 CF clinicians, 9 adults with CF, and 11 caregivers of children with CF. Themes centered on emotional responses to modulator availability, influences on decision-making, concerns about side effects, impact of modulators on planning for the future, the benefits of the multidisciplinary CF care team in supporting treatment decisions, and the unique needs of people with CF who are not eligible for modulators. Clinicians described changes in conversations about modulators since the approval of elexacaftor/tezacaftor/ivacaftor, specifically greater willingness to prescribe with less nuanced conversations with patients and/or caregivers regarding their use. CONCLUSION: Based on perspectives and experiences of CF clinicians, adults with CF, and caregivers of children with CF, we suggest clinicians approach conversations about CFTR modulators thoughtfully and thoroughly, utilizing the multidisciplinary model of CF care in exploring patient and caregiver emotions while filling in knowledge gaps, asking about treatment goals beyond potential clinical benefit, and having compassionate conversations with those who are ineligible for modulators.

Symptoms and quality of life in adults with cystic fibrosis: A cross-sectional analysis of the InSPIRe:CF trial.

BACKGROUND: People living with cystic fibrosis (CF) experience a high symptom burden. Due to the changing landscape of CF in the era of modulator therapy, we sought to examine the epidemiology of symptoms and their association with quality of life, to help CF clinicians improve symptom screening in clinic. METHODS: Using baseline data from a trial of specialist palliative care in adults with CF, we examined symptom prevalence, distress, and association with quality of life (measured with the Functional Assessment of Chronic Illness Therapy Total Score). RESULTS: Among 262 participants, median age was 33, and 78% were on modulator therapy. The most common symptoms were lack of energy (n = 194, 74%) and cough (190, 73%), whereas the most distressing were difficulty sleeping (range 0-4, mean 2.19, SD 1.15) and pain (mean 2.04, SD 1.1). The symptoms that impaired quality of life the most were extrapulmonary: lack of energy (average quality of life score -29.8, 95% CI -36.8 to -22.8), feeling sad (-29.8, 95% CI -35.6 to -23.9) and worrying (-28.7, 95% CI -34.9 to -22.5). CONCLUSIONS: The symptoms that were associated with the lowest quality of life were extrapulmonary. CF clinicians may consider screening for common symptoms that affect quality of life the most (lack of energy, worrying, difficulty sleeping, feeling irritable, pain, and shortness of breath). These symptoms may identify people living with CF who are most at risk for a decreased quality of life and may benefit from additional support.

Changes in fecal elastase-1 following initiation of CFTR modulator therapy in pediatric patients with cystic fibrosis.

BACKGROUND: Improvement in exocrine pancreatic function in persons with CF (pwCF) on cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been documented in clinical trials using fecal pancreatic elastase-1 (FE-1). Our group endeavored to evaluate real-world data on FE-1 in children on CFTR modulator therapy at three pediatric cystic fibrosis (CF) centers. METHODS: Pediatric pwCF were offered FE-1 testing if they were on pancreatic enzyme replacement therapy (PERT) and on CFTR modulator therapy according to their center's guideline. FE-1 data were collected retrospectively. The primary outcome was absolute change in FE-1. RESULTS: 70 pwCF were included for analysis. 53 had baseline and post-modulator FE-1 values. There was a significant increase in FE-1 from median 25 mcg/g (IQR 25-60) at baseline to 57 mcg/g (IQR 20-228) post-modulator (p<0.001 by Wilcoxon matched pairs), with an absolute change in FE-1 of median 28 mcg/g (IQR -5-161) and mean 93.5 ± 146.8 mcg/g. Age was negatively correlated with change in FE-1 (Spearman r=-0.48, p<0.001). 15 pwCF (21%) had post-modulator FE-1 values ≥200 mcg/g, consistent with pancreatic sufficiency (PS). The PS group was significant for younger age at initiation of first CFTR modulator and a higher baseline FE-1. CONCLUSIONS: Most pwCF experienced an increase in FE-1 while receiving CFTR modulator treatment and a small percentage demonstrated values reflective of PS. These data suggest that PS may be attained in those that initiated modulator therapy at a younger age or had a higher baseline FE-1. FE-1 testing is suggested for children on any CFTR modulator therapy.

Clinician perspectives on barriers and solutions to symptom management in cystic fibrosis.

People living with cystic fibrosis (PLwCF) experience high symptom burden. 146 clinicians completed online surveys regarding barriers and solutions to symptom management between September and October 2020. The surveys contained both closed-ended and free-text entries. The symptom management specialists that CF clinicians most wished to consult included mental health (88, 65%), palliative care (59, 41%), and pain specialists (48, 33%). Barriers to symptom management included concerns about controlled substances prescribed for symptom control causing addiction and precluding transplantation, a lack of trust and collaboration among clinical specialties, a lack of symptom management specialists with CF expertise, and a worry about the affordability of specialist-level symptom management care. Potential solutions included non-pharmacological approaches, expanding access to affordable specialist symptom management care, the creation of clinical care guidelines for symptom management in CF, and having CF clinicians and symptom management specialists work alongside each other in CF clinic to build interdisciplinary trust and education.

Barriers of Acceptance to Hospice Care: a Randomized Vignette-Based Experiment.

BACKGROUND: The per diem financial structure of hospice care may lead agencies to consider patient-level factors when weighing admissions. OBJECTIVE: To investigate if treatment cost, disease complexity, and diagnosis are associated with hospice willingness to accept patients. DESIGN: In this 2019 online survey study, individuals involved in hospice admissions decisions were randomized to view one of six hypothetical patient vignettes: "high-cost, high-complexity," "low-cost, high-complexity," and "low-cost, low-complexity" within two diseases: heart failure and cystic fibrosis. Vignettes included demographics, prognoses, goals, and medications with costs. Respondents indicated their perceived likelihood of acceptance to their hospice; if likelihood was <100%, respondents were asked the barriers to acceptance. We used bivariate tests to examine associations between demographic, clinical, and organizational factors and likelihood of acceptance. PARTICIPANTS: Individuals involved in hospice admissions decisions MAIN MEASURES: Likelihood of acceptance to hospice care KEY RESULTS: N=495 (76% female, 53% age 45-64). Likelihoods of acceptance in cystic fibrosis were 79.8% (high-cost, high-complexity), 92.4% (low-cost, high-complexity), and 91.5% (low-cost, low-complexity), and in heart failure were 65.9% (high-cost, high-complexity), 87.3% (low-cost, high-complexity), and 96.6% (low-cost, low-complexity). For both heart failure and cystic fibrosis, respondents were less likely to accept the high-cost, high-complexity patient than the low-cost, high-complexity patient (65.9% vs. 87.3%, 79.8% vs. 92.4%, both p<0.001). For heart failure, respondents were less likely to accept the low-cost, high-complexity patient than the low-cost, low-complexity patient (87.3% vs. 96.6%, p=0.004). Treatment cost was the most common barrier for 5 of 6 vignettes. CONCLUSIONS: This study suggests that patients receiving expensive and/or complex treatments for palliation may have difficulty accessing hospice.

Prevalence of unmet pain and symptom management needs in adults with cystic fibrosis.

BACKGROUND: Although people living with CF (PLwCF) commonly report pain and other symptoms, little is known regarding their experiences of living with and accessing treatment for burdensome symptoms. METHODS: PLwCF completed online questionnaires assessing symptom prevalence and distress and were also asked about experiences accessing pain and symptom treatment, using both closed-ended and free-text entries. RESULTS: Pain was the most prevalent symptom experienced among the 55 participants (76%) and the symptom that most commonly caused distress (64%). PLwCF not on CFTR modulator therapy were likelier to endorse pain as distressing (p = 0.007). Respondents expressed that their pain was commonly underrecognized and undermanaged, they desired a multi-modal approach to treatment, and noted concerns about disease progression affecting their symptom management options. CONCLUSIONS: Our study suggests that PLwCF often have unmet symptom management needs that may impair quality of life.

Integrating specialist palliative care to improve care and reduce suffering: cystic fibrosis (InSPIRe:CF) - study protocol for a multicentre randomised clinical trial.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disorder estimated to affect more than 160 000 individuals and their families worldwide. People living with CF commonly experience significant physical and emotional symptom burdens, disruptions to social roles and complex treatment decision making. While palliative care (PC) interventions have been shown to relieve many such burdens in other serious illnesses, no rigorous evidence exists for palliative care in CF. Thus, this study aims to compare the effect of specialist palliative care plus usual CF care vs usual CF care alone on patient quality of life. METHODS AND ANALYSIS: This is a five-site, two-arm, partially masked, randomised superiority clinical trial. 264 adults with CF will be randomly assigned to usual CF care or usual CF care plus a longitudinal palliative care intervention delivered by a palliative care specialist. The trial's primary outcome is patient quality of life (measured with the Functional Assessment of Chronic Illness Therapy-Palliative care instrument). Secondary outcomes include symptom burden, satisfaction with care and healthcare utilisation. Outcomes will be measured at 12 months (primary endpoint) and 15 months (secondary endpoint). In addition, we will conduct qualitative interviews with patient participants, caregivers, and palliative care and CF care team members to explore perceptions of the intervention's impact and barriers and facilitators to dissemination. ETHICS AND DISSEMINATION: Human subjects research ethics approval was obtained from all participating sites, and all study participants gave informed consent. We will publish the results of this trial in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN53323164.

Associations between demographic characteristics and unmet supportive care needs in adults with cystic fibrosis.

CONTEXT: Patients living with cystic fibrosis (CF) report impaired quality of life. Little is known about unmet supportive care needs among adults living with CF and how they are associated with demographic characteristics. OBJECTIVES: The primary objective of this study was to identify associations between demographic variables and unmet supportive care needs regarding anxiety, sadness, pain and uncertainty about the future of living with CF. METHODS: We recruited 165 adults with CF from a single academic medical centre to complete a brief demographic survey and the Supportive Care Needs Survey (SCNS-34), a validated self-reported needs assessment that measures the prevalence of and preferences for support for 34 needs that commonly occur in patients with serious illness. RESULTS: Approximately half of the participant sample was male, with a median age of 29 years, varying income levels and a range of lung disease severity. We found statistically significant associations between insufficient income and increased odds of reporting need for support regarding anxiety (OR: 6.48; 95% CI 2.08 to 20.2), sadness (OR: 6.15; 95% CI 2.04 to 18.5), pain (OR: 7.06; 95% CI 2.22 to 22.4) and worries surrounding uncertainty about the future (OR: 3.43; 95% CI 1.18 to 9.99). CONCLUSION: Adults with CF report significant unmet needs for support in several physical and emotional domains. Many of these domains were associated with demographic characteristics, most notably, income. Our findings underscore the importance of developing treatment approaches that are sensitive to patient demographics when addressing unmet supportive care needs among adults with CF.

Development of an Advance Care Planning Protocol in a Cystic Fibrosis Outpatient Clinic.

Background: Advance care planning (ACP) is recommended for all patients with cystic fibrosis (CF), yet clear implementation guidelines do not exist. Methods: The University of North Carolina Adult CF Care Team developed a process to implement semistructured multidisciplinary outpatient ACP meetings as routine care for patients with CF. Premeeting and post-meeting surveys were used to elicit patients' attitudes toward ACP. Results: Twenty-seven adults with CF completed a face-to-face ACP meeting, and 13 completed both surveys. Following the multidisciplinary ACP meeting, overall scores for understanding of ACP topics improved by 4.5 points (p = 0.003). Conclusion: We successfully implemented sustainable ACP meetings for adults with CF and found increased comfort with ACP and documentation of wishes after ACP meetings. It is important for CF care providers to meet the needs of this patient population by ensuring that ACP is in place before crisis situations.

Semiparametric estimation of the proportional rates model for recurrent events data with missing event category.

Proportional rates models are frequently used for the analysis of recurrent event data with multiple event categories. When some of the event categories are missing, a conventional approach is to either exclude the missing data for a complete-case analysis or employ a parametric model for the missing event type. It is well known that the complete-case analysis is inconsistent when the missingness depends on covariates, and the parametric approach may incur bias when the model is misspecified. In this paper, we aim to provide a more robust approach using a rate proportion method for the imputation of missing event types. We show that the log-odds of the event type can be written as a semiparametric generalized linear model, facilitating a theoretically justified estimation framework. Comprehensive simulation studies were conducted demonstrating the improved performance of the semiparametric method over parametric procedures. Multiple types of Pseudomonas aeruginosa infections of young cystic fibrosis patients were analyzed to demonstrate the feasibility of our proposed approach.

Assessing Practices, Beliefs, and Attitudes about Palliative Care among People with Cystic Fibrosis, Their Caregivers, and Clinicians: Results of a Content Analysis.

Background: Individuals with cystic fibrosis (CF) experience symptoms affecting quality of life and may benefit from palliative care (PC). Objectives: To present results of content analysis from open-ended survey questions assessing knowledge and experiences with PC among CF stakeholders. Design, Setting, Subjects: Online surveys were sent to CF stakeholders through CF-specific listservs predominantly in the United States. Measurements: Responses to five open-ended questions about CF PC-delivery, health care provider training, and lung transplant-underwent content analysis. Responses were coded using NVivo12 Software™. Results: Forty-eight CF adults, 59 caregivers, and 229 providers responded to the open-ended survey questions. Analysis showed 5 primary categories related to CF PC: (1) stakeholder perceptions of PC for CF, (2) delivering PC to people with CF, (3) conversations about PC for CF, (4) perceptions that PC services are underutilized for people with CF, and (5) beliefs that PC services are critical for people with CF considering or pursuing lung transplant. Analysis showed variation among and within groups in defining PC for CF, when, and how to deliver it. Many respondents felt PC was underutilized in CF. Most saw PC as particularly important when considering lung transplant, managing anxiety around transplant, and for goals of care discussions. Some believed PC and lung transplant were mutually exclusive. Conclusion: Respondents felt PC is underutilized for CF, and that people with CF may miss out on the benefits of PC. Among stakeholders, respondents felt people with CF would benefit from access to primary and secondary PC services.

Models of Palliative Care Delivery for Individuals with Cystic Fibrosis: Cystic Fibrosis Foundation Evidence-Informed Consensus Guidelines.

Cystic fibrosis (CF) affects more than 70,000 individuals and their families worldwide. Although outcomes for individuals with CF continue to improve, it remains a life-limiting condition with no cure. Individuals with CF manage extensive symptom and treatment burdens and face complex medical decisions throughout the illness course. Although palliative care has been shown to reduce suffering by alleviating illness-related burdens for people with serious illness and their families, little is known regarding the components and structure of various delivery models of palliative care needed to improve outcomes for people affected by CF. The Cystic Fibrosis Foundation (CFF) assembled an expert panel of clinicians, researchers, individuals with CF, and family caregivers, to develop consensus recommendations for models of best practices for palliative care in CF. Eleven statements were developed based on a systematic literature review and expert opinion, and address primary palliative care, specialty palliative care, and screening for palliative needs. These recommendations are intended to comprehensively address palliative care needs and improve quality of life for individuals with CF at all stages of illness and development, and their caregivers.

Enhancing care for individuals with advanced cystic fibrosis lung disease.

While remarkable advances in cystic fibrosis (CF) care have led to improvements in survival and quality of life, many individuals with CF are living with advanced cystic fibrosis lung disease (ACFLD) and others will face continued disease progression and its associated complex treatments and choices. This review will provide a summary of recently published guidelines for ACFLD care and lung transplant referral and highlight ongoing work to enhance the care of those with ACFLD through improvements in medical and psychosocial care, palliative care, and care around lung transplantation.

Highlights from the 2019 North American Cystic Fibrosis Conference.

This review briefly summarizes presentations in several major topic areas at the conference: pathophysiology and basic science of cystic fibrosis lung disease, clinical trials, clinical quality improvement, microbiology and treatment of infection, and transition, advanced lung disease and transplant, mental health and psychosocial concerns. The review is intended to highlight several areas and is not a comprehensive summary of the conference. Citations from the conference are by the first author and abstract number or symposium number, as designated in the supplement.

Palliative care skills in CF: Perspectives of adults with CF, caregivers, and CF care team members.

BACKGROUND: The role of cystic fibrosis (CF) care team members in delivering palliative care (PC) remains undefined. We aimed to understand the PC skills of CF care teams. METHODS: CF care team members ("clinicians"), adults with CF ("patients"), and family caregivers ("caregivers") rated the ability of CF clinicians to provide aspects of PC using a five-point scale ("poor" to "excellent"). Median ratings were compared between groups. RESULTS: A total of 70 patients, 100 caregivers, and 350 clinicians participated. Clinicians consistently rated their PC skills higher than patients or caregivers rated them, particularly for advanced PC skills. While clinicians, patients, and caregivers rated clinicians as "very good" at basic pain assessment and "good" at discussing prognostic uncertainty, clinicians rated themselves more highly at providing most skills, including simultaneous PC and standard CF care (P < .0001), basic depression assessment (P < .001), and discussing transplant, advance directives, end of life, code status, and hospice (all P < .0001). Respondents affiliated with adult CF care teams rated clinicians more highly than respondents affiliated with pediatric CF care teams at discussing lung transplant (P < .001), end of life (P = .006), advance directives (P < .001), code status (P = .012), and hospice (P = .016). Most patients (69%) and caregivers (60%) felt CF clinicians should receive more PC training. CONCLUSIONS: Discrepancies exist among patient/caregiver and clinician perceptions of PC skills in CF, and skills of adult and pediatric teams may differ. Patients and caregivers feel clinicians' more advanced PC skills are lacking. CF clinicians may benefit from PC training to enhance skills and to understand how and when to utilize specialty PC services.

Cystic Fibrosis Foundation consensus guidelines for the care of individuals with advanced cystic fibrosis lung disease.

BACKGROUND: Advanced cystic fibrosis lung disease (ACFLD) is common, is associated with reduced quality of life, and remains the most frequent cause of death in individuals with cystic fibrosis (CF). These consensus guidelines provide recommendations to the CF community on management of both common and unique issues that arise when individuals reach a state of ACFLD. METHODS: The CF Foundation assembled a multidisciplinary expert panel consisting of three workgroups: Pulmonary management; Management of comorbid conditions; Symptom management and psychosocial issues. Topics were excluded if the management considerations did not differ in ACFLD from in the overall CF population or if already addressed in other published guidelines. Recommendations were based on a systematic literature review combined with expert opinion when appropriate. RESULTS: The committee formulated twenty-three recommendation statements specific to ACFLD that address the definition of ACFLD, pulmonary and intensive care unit management, management of selected comorbidities, symptom control, and psychosocial issues. CONCLUSIONS: These recommendations are intended to be paired with previously published management guidelines for the overall CF population, with the objective of reducing practice variability and improving overall care, quality of life, and survival in those with ACFLD.

Palliative Care Needs of Individuals with Cystic Fibrosis: Perspectives of Multiple Stakeholders.

Background: Studies suggest palliative care may be different in cystic fibrosis (CF) than in other conditions. To provide quality palliative care to individuals with CF, unique needs must be understood. Objective: To examine perceptions of how palliative care may be different in CF, top palliative needs of individuals with CF, and barriers to palliative care in CF. Methods: Online surveys with closed- and open-ended questions about palliative care needs were administered to multiple stakeholders in CF care, including adults with CF, caregivers of individuals with CF, and CF care team members from U.S. centers. We used descriptive statistics to report survey findings. Results: A total of 70 adults with CF, 100 caregivers, and 350 care team members completed surveys. While care team members reported they introduce palliative care to patients a majority of the time, adults with CF and caregivers rarely recalled learning about it. Very few reported having seen a palliative care specialist. A majority of participants reported that palliative care is valuable in CF care. Over 80% of participants felt palliative care is different in CF, most often citing the unpredictable disease course. Top palliative care needs identified include emotional support, emotional symptom management, and communication about treatment decisions. Major barriers to palliative care identified include perception that it is for dying people and lack of CF care team knowledge and training in palliative care. Conclusions: Participants felt palliative care is valuable in CF and identified many palliative care needs, and also barriers that can be addressed with education and training. Our findings will be used to develop interventions targeting specific needs and inform guidelines to enhance provision of palliative care in CF.

Prevalence of unmet palliative care needs in adults with cystic fibrosis.

BACKGROUND: Physical and emotional burdens impair quality of life (QoL) in many adults with cystic fibrosis (CF). Palliative care (PC) improves QoL in other serious illnesses, yet the full array of palliative needs amenable to PC are unknown in CF. METHODS: We surveyed 164 adults with CF using the Supportive Care Needs Survey 34 (SCNS-34) to assess unmet PC needs across five domains, the Edmonton Symptom Assessment System (ESAS) to assess symptom burden, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) to assess CF-specific QoL. We assessed associations between SCNS-34 domain scores and respondent characteristics, including symptom burden and FEV1. RESULTS: Median age was 29 years; 56% of respondents were male. Median FEV1 was 57% predicted. 78% of respondents reported ≥1 unmet PC need; physical and daily living (72%) and psychological (66%) needs were most prevalent. Symptom burden was correlated with all SCNS-34 domains scores, and strongly correlated with the physical (r = 0.79) and psychological (r = 0.72) domain scores. FEV1 was moderately inversely correlated with the physical domain score (r = -0.41). Forty-four of the 45 inverse correlations between SCNS-34 domain scores and CFQ-R domain scores were significant. Patient-reported depressive and anxiety symptoms were significantly associated with higher scores in five and four SCNS-34 domains, respectively. CONCLUSIONS: Adults with CF have substantial unmet PC needs. Patient-reported symptom burden is more strongly associated with reporting unmet PC needs than FEV1. Routine screening of unmet PC needs, using tools such as the SCNS-34, may enable CF care teams to optimize the provision of primary and specialist PC.