The intertwining of discourses in the diagnostic construction of cystic fibrosis: a perspective on access and barriers. / A tessitura dos discursos na construção diagnóstica da fibrose cística: uma perspectiva sobre acesso e barreiras.

The complexities referred to in the search for "accuracy" in the diagnosis of cystic fibrosis (CF) point to reflections around "what is needed" in the current situation of "precision medicine". We analyzed the discourses of 19 social actors belonging to the community of specialists in cystic fibrosis, exploring the semantic meanings of the word "precision", and the barriers to diagnosis and innovations in therapeutics. We adopted the critical discourse analysis (CDA) of Norman Fairclough in order to achieve the discursive constructions around the integrality of care, the guarantee and equitable supply of basic social needs. Access was identified as an emic category when in the social arenas of dispute are health needs and the right to life.

As complexidades referidas na busca pela "exatidão" no diagnóstico da fibrose cística (FC) apontam para reflexões em torno de "o que é preciso" na atual conjuntura da "medicina de precisão". Analisamos os discursos de 19 atores sociais pertencentes à comunidade de especialistas na fibrose cística, explorando as acepções semânticas do vocábulo "precisão" e as barreiras ao diagnóstico e às inovações na terapêutica. Adotamos a análise crítica do discurso de Norman Fairclough a fim de alcançar as construções discursivas em torno da integralidade do cuidado, da garantia e oferta equitativa dos básicos sociais. O acesso foi identificado como categoria êmica quando nas arenas sociais de disputa estão as necessidades de saúde e o direito à vida.

International disparities in diagnosis and treatment access for cystic fibrosis.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment. However, previous research has demonstrated profound global disparities in diagnosis and treatment access. If unaddressed, these threaten to widen existing health inequities. Therefore, in this analysis we aimed to reappraise gaps and evaluate progress in diagnosis and treatment equity in high-income (HIC) versus low- and middle-income countries (LMICs). METHODS: Estimates of the global CF population were made in 158 countries using patient registries, systematic literature searches, and an international survey of 14 CF experts. Estimates of the global burden of undiagnosed CF were made using epidemiological studies identified in literature searches and registry coverage data. The proportion of people receiving ETI was estimated using publicly available revenue data and a survey of 23 national drug pricing databases. RESULTS: 188,336 (163,421-209,204) people are estimated to have CF in 96 countries. Of these, 111,767 (59%) were diagnosed and 51,322 (27%) received ETI. The undiagnosed patient burden is estimated to be 76,569 people, with 82% in LMICs. ETI is reimbursed in 35 HICs, but only one LMIC. Four years after approval, there are 13,723 people diagnosed with CF who live in a country where ETI is inaccessible. This increases to 76,199 when including the estimated undiagnosed population. CONCLUSIONS: Equitable access to CFTR modulators must become a top priority for the international CF community. ETI costs up to $322,000 per year but could be manufactured for $5000 to allow access under a voluntary license. Given the extent of disparities, other mechanisms to improve access that circumvent the manufacturer should also be considered.

Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Preventive service utilization among adults with cystic fibrosis covered by private insurance is comparable to the general population.

BACKGROUND: As the life expectancy of the cystic fibrosis (CF) population is lengthening with modulator therapies, diligent age-appropriate screening and preventive care are increasingly vital for long-term health and wellbeing. METHODS: We performed a retrospective analysis comparing rates of receiving age- and sex-appropriate preventive services by commercially insured adult people with CF (PwCF) and adults without CF from the general population (GP) via the Truven Health MarketScan database (2012-2018). RESULTS: We captured 25,369 adults with CF and 488,534 adults from the GP in the United States. Comparing these groups, we found that 43% versus 39% received an annual preventive visit, 28% versus 28% were screened for chlamydia, 38% versus 37% received pap smears every 3 years (21-29-year-old females), 33% versus 31% received pap smears every 5 years (30-64-year-old females), 55% versus 44% received mammograms, 23% versus 21% received colonoscopies, and 21% versus 20% received dyslipidemia screening (all screening rates expressed per 100 person-years). In age-stratified analysis, 18-27-year-old PwCF had a lower rate of annual preventive visits compared to adults in the same age group of the GP (27% versus 42%). CONCLUSIONS: We discovered a comparable-to-superior rate of preventive service utilization in adults with CF relative to the GP, except in young adulthood from 18-27 years. Our findings establish the importance of meeting the primary care needs of adults with CF and call for development of strategies to improve preventive service delivery to young adults.

Aiming to Improve Equity in Pulmonary Health: Cystic Fibrosis.

This review summarizes the evidence of health disparities in cystic fibrosis (CF), an autosomal recessive genetic disorder with substantial variation in disease progression and outcomes. We review disparities by race, ethnicity, socioeconomic status, geographic location, gender identity, or sexual orientation documented in the literature. We outline the mechanisms that generate and perpetuate such disparities across levels and domains of influence and assess the implications of this evidence. We then recommend strategies for improving equity in CF outcomes, drawing on recommendations for the general population and considering approaches specific to people living with CF.

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.

Factors associated with frequent high-cost individuals with cystic fibrosis and their healthcare utilization and cost patterns.

Cystic fibrosis (CF) is a progressive multi-organ disease with significant morbidity placing extensive demands on the healthcare system. Little is known about those individuals with CF who continually incur high costs over multiple years. Understanding their characteristics may help inform opportunities to improve management and care, and potentially reduce costs. The purpose of this study was to identify and understand the clinical and demographic attributes of frequent high-costing CF individuals and characterize their healthcare utilization and costs over time. A longitudinal study of retrospective data was completed in British Columbia, Canada by linking the Canadian CF Registry with provincial healthcare administrative databases for the period between 2009 and 2017. Multivariable Cox regression models were employed to identify baseline factors associated with becoming a frequent high-cost CF user (vs. not a frequent high-cost CF user) in the follow-up period. We found that severe lung impairment (Hazard Ratio [HR]: 3.71, 95% confidence interval [CI], 1.49-9.21), lung transplantation (HR: 4.23, 95% CI, 1.68-10.69), liver cirrhosis with portal hypertension (HR: 10.96, 95% CI: 3.85-31.20) and female sex (HR: 1.97, 95% CI: 1.13-3.44) were associated with becoming a frequent high-cost CF user. Fifty-nine (17% of cohort) frequent high-cost CF users accounted for more than one-third of the overall total healthcare costs, largely due to inpatient hospitalization and outpatient medication costs.

Cost-effectiveness analysis of genetic tools to predict treatment response in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies show variable efficacy for patients with CF. Patient-derived predictive tools may identify individuals likely to respond to CFTRs, but are not in routine use. We aimed to determine the cost-utility of predictive tool-guided treatment with CFTRs as add-on to standard of care (SoC) for individuals with CF. METHODS: This economic evaluation compared two strategies using an individual level simulation: (i) Treat All, where all patients received CFTRs plus SoC and (ii) Test→Treat, where patients who tested positive on predictive tools received CFTRs plus SoC and those who tested negative received SoC only. We simulated 50,000 individuals over their lifetime, and estimated costs (2020 CAD) per quality-adjusted life year (QALY) from the healthcare payer's perspective, discounted at 1.5% annually. The model was populated using Canadian CF registry data and published literature. Probabilistic and deterministic sensitivity were conducted. RESULTS: The Treat All and Test→Treat and strategies yielded 22.41 and 21.36 QALYs, and cost $4.21 M and $3.15 M respectively. Results of probabilistic sensitivity analysis showed that Test→Treat was highly cost-effective compared to Treat All in 100% of simulations at cost-effectiveness thresholds as high as $500,000 per QALY. Test→Treat may save between $931 K to $1.1 M per QALY lost, depending on sensitivity and specificity of predictive tools. CONCLUSION: The use of predictive tools could optimize the health benefits of CFTR modulators while reducing costs. Our findings support the use of pre-treatment predictive testing and may help inform coverage and reimbursement policies for individuals with CF.

A conceptual framework to develop a patient-reported experience questionnaire on the cystic fibrosis journey in France: the ExPaParM collaborative study.

BACKGROUND: The objective of the study was to elaborate a conceptual framework related to the domains of patient experience along the cystic fibrosis (CF) journey from the patients and parents of children with CF to inform the design of a patient-reported experience questionnaire. METHOD: A collaborative research group including patients and parents with clinicians and academic researchers was set up. They identified the situations along the CF care pathway from diagnosis to paediatric care, transition to adult care and adult follow-up, transfer to transplant centres and follow-up after transplantation. Participants were recruited by CF centres in metropolitan France and overseas departments. Semi-structured interviews were conducted, transcribed verbatim and subjected to an inductive analysis conducted in duos of researchers/co-researchers using NVivo®. The conceptual framework was discussed with the research group and presented to the CF centres during two video conferences. The protocol obtained a favourable opinion from the Ethics Evaluation Committee of INSERM (IRB00003888-no. 20-700). RESULTS: The analysis led to a conceptual framework composed of domains of the CF journey, each divided into several items. 1. CF care: Management of care by the CF centre team; in-hospital care; quality of care in the community; therapeutic education and self-management support; at-home care; new therapies and research; procreation; 2. Transplant care: management of transplant and CF care; coordination with other specialties; education and self-management support; at-home care; procreation; new therapies and research; 3. Turning points along the journey: diagnosis of CF, transition to adult care, transfer to transplantation; 4. Social life with CF: housing, employment and education, social relations, social welfare and family finances. The number of patients included and the diversity of situations made it possible to achieve a sufficient richness and saturation of codes by domain to develop patient experience questionnaires. CONCLUSION: This conceptual framework, resulting from the participants' experience, will inform the design of a patient-reported experience tool, whose construct will be tested during the next phase of the ExPaParM project to assess its fidelity, intelligibility, and ability to report patient experience of the CF journey.

Cost burden among the CF population in the United States: A focus on debt, food insecurity, housing and health services.

BACKGROUND: Advancements in the cystic fibrosis (CF) field have resulted in longer lifespans for individuals with CF. This has led to more responsibility for complex care regimens, frequent health care, and prescription medication utilization that are costly and may not be fully covered by health insurance. There are outstanding questions about unmet medical needs among the U.S. population with CF and how the financial burden of CF is associated with debt, housing instability, and food insecurity. METHODS: Researchers developed the CF Health Insurance Survey (CF HIS) to survey a convenience sample of people living with CF in the U.S. The sample was weighted to reflect the parameters of the 2019 Cystic Fibrosis Foundation Patient Registry Annual Data Report, and chi-square tests and multiple logistic regression models were conducted. RESULTS: A total of 1,856 CF patients in the U.S. were included in the study. Of these, 64% faced a financial burden: 55% of respondents faced debt issues, 26% housing issues, and 33% food insecurity issues. A third reported at least one unmet medical need: 24% faced unmet prescription needs, 12% delayed or shortened a hospitalization, and 10% delayed or skipped a care center visit as a result of the cost of care. CONCLUSIONS: People with CF in the U.S. experience high financial burden, which is associated with unmet medical needs. Income is the biggest risk factor for financial burden for people with CF, with people dually covered by Medicare and Medicaid particularly at risk.

Epidemiology and management of nontuberculous mycobacterial disease in people with cystic fibrosis, the Netherlands.

BACKGROUND: Nontuberculous mycobacteria (NTM) are opportunistic, difficult to treat pathogens. With increasing prevalence of NTM infections in people with cystic fibrosis (pwCF) and the improved life expectancy, the burden is expected to grow. METHODS: We assessed the epidemiology and management of NTM isolation and disease in pwCF in the Netherlands using a survey and retrospective, case-controlled data from the Dutch CF Registry. We determined the isolation prevalence, treatment and outcomes from 2013-2019. RESULTS: NTM isolation prevalence increased from 1.0% to 3.6% (2013-2019). This was a single NTM isolation in 53.7% of the adults and 60.0% of the children. M. abscessus and M. avium complex (MAC) were most frequent (47.1 and 30.9%). Of the treated pwCF, 48.5% attained culture conversion of M. abscessus; 54.5% for MAC. Children with an NTM isolation showed more infections with S. maltophilia and/or A. fumigatus (p < 0.001) compared to controls. In the year prior to NTM isolation, children in the NTM group had a lower mean FEV1% predicted (81.5 ± 16.7 vs. 88.6 ± 15.3, p = 0.024), while adults in the NTM group had more IV antibiotic days compared to controls (60 vs. 17, p = 0.047). In the following years, FEV1% predicted declined faster in pwCF with NTM than the control group (children: -3.8% vs. -1.6%, p = 0.023; adults: -0.7% and 0.4%, ns). CONCLUSIONS: The isolation prevalence of 3.6%, poor treatment outcomes and associated lung function decline emphasize that NTM pulmonary disease (NTM-PD) is a significant health issue among pwCF in the Netherlands. Its prevention and treatment require increased attention.

Longitudinal Assessment of Educational Risk for K-12 Students with Cystic Fibrosis.

OBJECTIVES: To assess the use of services provided by a cystic fibrosis (CF) center school specialist and evaluate relationships among student educational risk scores, family concerns for school engagement and performance, and disease severity. STUDY DESIGN: This was a retrospective review of medical records for 126 children with CF in grades K-12 who were screened for educational risk or used school intervention services during the 2017- 020 school years. Regression analyses were performed to identify and quantify predictors of educational risk, family concern for school performance and ability to advocate, and use of school specialist services. RESULTS: Most children with CF (62%-82%) were at moderate-to-high educational risk. Sixteen or more school absences, family concerns for their child's school performance or inability to advocate for their school needs, child mental health visits, and greater frequency of hospitalization predicted greater educational risk scores and more encounters with the school specialist. Better lung function and lower grade level were associated with lower educational risk. Number of encounters with the School Specialist remained high across three pre-coronavirus disease 2019 school years. CONCLUSIONS: Our experience illustrates a need to identify educational risk and support school experiences of children and youth with CF as a component of the care model. Tailored support, based on identification of risk predictors, has potential to improve educational outcomes.

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.

"What Are the Applications for Remote Rehabilitation Management in Cystic Fibrosis?": A Scoping Review Protocol.

BACKGROUND: Telemedicine is an effective, widely used strategy in the field of cystic fibrosis management. The objective of this scoping review is to summarize and analyze the scientific literature with the special focus on the tools and the strategies used in patients with a chronic disease, such as cystic fibrosis. METHODS: This scoping review will be performed in accordance with the Joanna Briggs Institute methodology. In this context, the planned scoping review is a research synthesis that will map the literature on the applications of telemedicine and telemonitoring to the management of cystic fibrosis, with the aim to identify key concepts in the research and work to be conducted that may impact clinical practice. Studies will be included if they meet the following population, concept, and context criteria: all patients with cystic fibrosis receiving treatment with the tools of telemedicine and telemonitoring. No study design, publication type, or data restrictions will be applied. MEDLINE, Scopus, CINHAL, Pedro, Embase, Web of Science, ACM Digital Library, Health Technology Assessment Database (HTA), and Cochrane Central will be searched up to September 2022. DISCUSSION: To the best of our knowledge, this will be the first scoping review to provide a comprehensive overview of the topic. The results could add meaningful information for future research and, especially, for clinical practice, when implementing telerehabilitation in cystic fibrosis treatment. Furthermore, we expect that our work may identify possible knowledge gaps on the topic. The results of this research will be published in a peer-reviewed journal and will be presented at relevant international scientific events, such as in congress or meetings.

Socioeconomic determinants of respiratory health in patients with cystic fibrosis: implications for treatment strategies.

INTRODUCTION: Great variation exists in the progression and outcomes of cystic fibrosis (CF) lung disease, due to both genetic and environmental influences. Social determinants mediate environmental exposures and treatment success; people with CF from socioeconomically disadvantaged backgrounds have worse health and die younger than those in more advantaged positions. AREAS COVERED: This paper reviews the literature on the mechanisms that are responsible for generating and sustaining disparities in CF health, and the ways by which social determinants translate into health advantages or disadvantages in people with CF. The authors make recommendations for addressing social risk factors in CF clinical practice. EXPERT OPINION: Socioeconomic factors are not dichotomous and their impact is felt at every step of the social ladder. CF care programs need to adopt a systematic protocol to screen for health-related social risk factors, and then connect patients to available resources to meet individual needs. Considerations such as daycare, schooling options, living and working conditions, and opportunities for physical exercise and recreation as well as promotion of self-efficacy are often overlooked. In addition, advocacy for changes in public policies on health insurance, environmental regulations, social welfare, and education would all help address the root causes of CF health inequities.

Methods of Sputum and Mucus Assessment for Muco-Obstructive Lung Diseases in 2022: Time to "Unplug" from Our Daily Routine!

Obstructive lung diseases, such as chronic obstructive pulmonary disease, asthma, or non-cystic fibrosis bronchiectasis, share some major pathophysiological features: small airway involvement, dysregulation of adaptive and innate pulmonary immune homeostasis, mucus hyperproduction, and/or hyperconcentration. Mucus regulation is particularly valuable from a therapeutic perspective given it contributes to airflow obstruction, symptom intensity, disease severity, and to some extent, disease prognosis in these diseases. It is therefore crucial to understand the mucus constitution of our patients, its behavior in a stable state and during exacerbation, and its regulatory mechanisms. These are all elements representing potential therapeutic targets, especially in the era of biologics. Here, we first briefly discuss the composition and characteristics of sputum. We focus on mucus and mucins, and then elaborate on the different sample collection procedures and how their quality is ensured. We then give an overview of the different direct analytical techniques available in both clinical routine and more experimental settings, giving their advantages and limitations. We also report on indirect mucus assessment procedures (questionnaires, high-resolution computed tomography scanning of the chest, lung function tests). Finally, we consider ways of integrating these techniques with current and future therapeutic options. Cystic fibrosis will not be discussed given its monogenic nature.