Left behind: The potential impact of CFTR modulators on racial and ethnic disparities in cystic fibrosis.

The advent of CFTR modulators, a genomic specific medication, revolutionized the treatment of CF for many patients. However, given that these therapeutics were only developed for specific CFTR mutations, not all people with CF have access to such disease-modifying drugs. Racial and ethnic minority groups are less likely to have CFTR mutations that are approved for CFTR modulators. This exclusion has the potential to widen existing health disparities.

Areas for improvement in community optometry: flashes and floaters take priority.

PURPOSE: A common response to rising demand for healthcare is to extend the role of health professionals and the range of their service provision. Community optometry in Scotland is a recent example of this. Within this context of innovation and change there are challenges to ensuring quality in optometry practice. The purpose of this research is to establish what the priorities are for practice improvement within community optometry and to start a programme to inform strategies to improve practice. METHODS: A four stage study was conducted: (1) a service-driven topic prioritisation exercise to identify priorities for optometry practice improvement; (2) a review of national and international guidance and UK protocols relating to the identified priority topic; (3) a national theory-based survey identifying current practice and the barriers and facilitators to the target behaviour; and (4) the identification of theory-based intervention options to improve practice. The Behaviour Change Wheel approach to behaviour change intervention development and Theoretical Domains Framework (TDF) provided the underlying theoretical framework. RESULTS: Stakeholders identified 'patients presenting with flashes and floaters' as an important priority for practice improvement. The decision about whether or not to refer patients on to secondary care for further examination is the target behaviour. Guidance for optometrists on this topic is lacking. Six TDF domains were related to the decision about whether or not to refer patients with flashes and floaters to secondary care - 'social influences', 'emotion', 'beliefs about capabilities', 'beliefs about consequences', 'behavioural regulation' and 'reinforcement'. CONCLUSIONS: This study has examined current practice in relation to the management of patients with flashes and floaters, identified the most salient targets for future strategies to improve optometry practice and highlighted what form these strategies may take. It demonstrates the use of a flexible, theory-informed approach, which can be used to engage with stakeholders and professionals to inform the design and development of efforts to improve practice in a variety of healthcare settings.

Improved detection of cystic fibrosis by the California Newborn Screening Program for all races and ethnicities.

BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) is universal in the United States. Protocols vary but include an immunoreactive trypsinogen (IRT) level and CFTR variant panel. California CF NBS has a 3-step screening: IRT level, variant panel, and CFTR sequencing if only one variant identified on panel. METHODS: This was a cohort study of infants with CF born in California (2007-2021) to examine racial and ethnic differences in having a false-negative NBS result for CF and at which step the false-negative occurred. We examined how different CFTR variant panels would improve detection of variants by race and ethnicity: original 39-variant panel, current 75-variant panel, and all 402 disease-causing CFTR variants in the CFTR2 database. RESULTS: Of the 912 infants born in California with CF, 84 had a false-negative result: 38 due to low IRT level and 46 with a high IRT value (but incomplete variant detection). Asian (OR 6.3) and Black infants (OR 2.5) were more likely to have a false-negative screening result than non-Hispanic white infants. The majority of false-negative screening (but CF diagnosis) cases among American Indian/Native Alaskan and non-Hispanic White infants were due to low IRT levels. The majority of Asian and Hispanic infants with false-negative screening had no variants detected. Detection of two CFTR variants was improved with the 75-variant panel in Black, Hispanic, and non-Hispanic White infants and with the 402-variant panel in Black, Hispanic, non-Hispanic White, and other race infants. CONCLUSIONS: Larger CFTR panels in NBS improved the detection of CF in all races and ethnicities.

Time to be blunt: Substance use in cystic fibrosis.

BACKGROUND: As the population of people with cystic fibrosis (pwCF) continues to age, attention is shifting towards addressing the unique challenges teenagers and adults face, including substance use. Changing attitudes and legality regarding marijuana and cannabidiol (CBD) may influence their use among pwCF, but data on the rate of use, reasons for use, and administration methods are lacking. OBJECTIVE: Investigate marijuana, CBD, e-cigarette, and cigarette usage among pwCF and explore differences in demographics, disease severity, and cystic fibrosis transmembrane receptor (CFTR) modulator use between recent users and nonusers. METHODS: This cross-sectional study used a one-time electronic survey to assess marijuana, CBD, e-cigarette, and cigarette use in pwCF aged >13 years. Demographic and clinical characteristics were compared between recent users and nonusers. The association between recent substance use and CFTR modulator use was analyzed using logistic regressions. RESULTS: Among 226 participants, 29% used marijuana, 22% used CBD, 27% used e-cigarettes, and 22% used cigarettes in the last 12 months. Users of all substances were more likely to be college-educated or aged 29-39 years than nonusers. E-cigarette users were 2.9 times more likely to use CFTR modulators (95% confidence interval [95% CI]: 0.98-11.00, p = .08) and marijuana users were 2.5 times more likely to use CFTR modulators compared to nonusers, adjusted for confounders. CBD, e-cigarettes, and cigarettes users were more likely to have an abnormal mental health screen compared to nonusers. A high proportion of never-users of marijuana and CBD expressed interest in using. CONCLUSION: Substance use is more prevalent among pwCF than previously reported and needs to be addressed by healthcare providers.

Food insecurity and mental health during the COVID-19 pandemic in cystic fibrosis households.

BACKGROUND: The COVID-19 pandemic impacted many households due to shelter-in-place orders and economic hardship. People with cystic fibrosis (CF) experienced increased food insecurity compared to the general population before the pandemic, even though adequate food access is needed to maintain nutrition goals associated with improved health-related outcomes. Little is known about the impact the pandemic had on the food insecurity of people with CF and their families. OBJECTIVE: To investigate how the COVID-19 pandemic impacted food insecurity, mental health, and self-care in people with CF. METHODS: Adults with CF and parents/guardians of children with CF were recruited via social media to complete online questionnaires from May 2020 to February 2021. Questionnaires in English and Spanish included USDA 2-question food insecurity screening, Patient Health Questionnaire-4 for mental health screening, and directed questions on the impact of the pandemic. RESULTS: Of 372 respondents, 21.8% of the households experienced food insecurity during the pandemic compared to 18.8% prepandemic (p < .001). More food insecure patients with CF reported weight loss (32.1% vs. 13.1%, p < .001), worse airway clearance adherence (13.6% vs. 5.8%, p < .01), and worse medication adherence (12.4% vs. 1.7%, p < .01) compared to food secure patients. Food insecure subjects were more likely to have an abnormal mental health screen compared to food secure subjects (53.1% vs. 16.2%, p < .001). CONCLUSION: Food insecurity increased in the CF population during the COVID-19 pandemic. Food insecure subjects reported worse mental health and self-care during the pandemic compared to food secure subjects.

Patient and Provider Experience With Cystic Fibrosis Telemedicine Clinic.

In response to the novel coronavirus (COVID-19) pandemic, all in-person cystic fibrosis (CF) appointments were converted to telemedicine visits at UCSF Benioff Children's Hospital. The purpose of our study was to learn about the experiences that patients, families, and providers had with telemedicine visits and to assess their interest in using telemedicine in the future. Our hypothesis was that most patients, families, and providers want to continue telemedicine visits in the future. An anonymous 11-question survey was distributed to patients, families, and providers in November and December 2020. The survey was completed by 46 of 72 families (64% response rate) and 24 of 25 providers (96% response rate). Thirty-seven families (80%) and 21 providers (88%) were satisfied with their telemedicine experience. Thirty-three families (72%) want to have telemedicine visits in the future. Thirty-five families (76%) and 22 providers (92%) were satisfied with their experience using Zoom. Forty families (87%) and 19 providers (90%) want 2 or more visits each year to be via telemedicine. Our study showed that most families and providers were satisfied with telemedicine, would like to continue using telemedicine, and prefer to have at least 2 of the 4 recommended annual CF visits via telemedicine. Our survey identified the following benefits to telemedicine: decreased travel time, decreased cost, and avoiding exposure to COVID. However, we need to ensure that we do not exacerbate existing health disparities for families that do not speak English and/or do not have the internet capabilities to support telemedicine technology.

Functional Profiling of CFTR-Directed Therapeutics Using Pediatric Patient-Derived Nasal Epithelial Cell Models.

Functional profiling of CFTR-directed therapeutics offers the potential to provide significant benefits to young people with cystic fibrosis (CF). However, the development of 2D airway epithelial cell models for individual response tests in CF children remains a central task. The objective of this study was to determine the utility of EpiXTM technology for expansion of nasal epithelial cells for use in electrophysiological CFTR function measurements. An initial harvest of as few as 20,000 cells was sufficient to expand up to 50 million cells that were used to generate air-liquid interface (ALI) cultures for ion transport studies with the Ussing assay. CFTR function was assessed by measuring responses to forskolin and the CFTR potentiator VX-770 (ivacaftor) in ALI cultures generated from passage 3 and 4 cells. Short-circuit current (Isc) measurements of blocked CFTR currents (ΔICFTRinh) discriminated CFTR function between healthy control (wild type, WT) and patients with intermediate (F508del/R117H-7T: 56% WT) and severe (F508del/F508del: 12% WT) CF disease. For the mixed genotypes, CFTR activity for F508del/c.850dupA was 12% WT, R334W/406-1G>A was 24% WT, and CFTRdele2,3(21 kb)/CFTRdele2,3(21 kb) was 9% WT. The CFTR correctors VX-809 (lumacaftor) and VX-661 (tezacaftor) significantly increased CFTR currents for F508del/R117H to 73 and 67% WT, respectively. Cultures with the large deletion mutation CFTRdele2,3(21 kb) unexpectedly responded to VX-661 treatment (20% WT). Amiloride-sensitive sodium currents were robust and ranged between 20-80 µA/cm2 depending on the subject. In addition to characterizing the electrophysiological profile of mutant CFTR activity in cultures for five genotypes, our study exemplifies the promising paradigm of bed-to-bench side cooperation and personalized medicine.

Qualitative study exploring the key determinants of information gathering to inform the management of over-the-counter (OTC) consultations in community pharmacies.

OBJECTIVES: Gathering relevant patient information during over-the-counter (OTC) consultations increases the likelihood of safe, effective and person-centred outcomes. The aim of this study was to explore the key determinants to information gathering during consultations for non-prescription medicine requests in community pharmacies in Scotland. DESIGN: Semi-structured interviews using the Theoretical Domains Framework (TDF), with community pharmacy teams across Scotland. Interviews explored participants' knowledge of current guidance, skills required to elicit information and barriers and facilitators associated with this behaviour. Theory-based content analysis was undertaken using the TDF as an initial coding framework to identify key determinants and map them to salient domains. Salience was determined by prominence or variation in views. Comparative analysis was undertaken by professional role. RESULTS: Thirty interviews were conducted with pharmacists (n=19) and medicine counter assistants (MCAs) (n=11). Eight salient domains were identified: environmental context and resources (privacy), beliefs about consequences (patient safety), skills (communication, decision-making), social influences (patient awareness of pharmacist role), knowledge (awareness and use of standard operating procedures), social professional role and identity (perception of own role), behavioural regulation (training) and intention (to gather information). Similar domains were salient for pharmacists and MCAs; however, different beliefs were associated with different roles. Overarching themes were identified: best practice, health literacy, decision-making and professionalism. CONCLUSIONS: Multiple influences and complexities affect the effective management of OTC consultations. While similar factors impact on both pharmacists and MCAs at a patient, professional and environmental level, subtle differences exist in how these influence their management of OTC consultations. This study highlights the importance of tailoring interventions to reflect different roles, functions and responsibilities of community pharmacy personnel.

Asthma, FEF25-75, and Hospitalizations in Children.

Asthma is a common chronic pediatric respiratory disease associated with significant morbidity. Current guidelines recommend monitoring forced expiratory volume in 1 s (FEV1) as part of the assessment of asthma severity and control; however, many children with asthma have a normal FEV1 despite significant symptoms. Reduced forced expiratory flow between 25%-75% of forced vital capacity (FEF25-75) may be an important measure of asthma severity and control in children with normal FEV1. This study examines the association between FEF25-75 and asthma-related hospitalizations. Pulmonary function tests and records of 925 children ≤19 years of age seen for an initial evaluation of physician-diagnosed asthma at a community-based asthma clinic between 1999 and 2011 were reviewed. FEV1 ≥80% predicted and FEF25-75 ≥60% were considered normal. The associations between FEV1 and FEF25-75 and asthma-related hospitalizations were examined using logistic regression models. Thirteen percent (n=118) of the children were hospitalized for asthma at least once in the previous year. Fifty four percent (n=501) of the children met criteria for uncontrolled asthma symptoms. Asthma-related hospitalization was associated with reducing categories of FEF25-75, but not FEV1. Among the 693 children with normal FEV1 (≥80%), those with FEF25-75 <60% were more likely to have been hospitalized in the previous year (odds ratio 2.50, confidence interval 1.17-5.35) as compared to those with FEF25-75 ≥60% of predicted. In a diverse urban cohort of children with asthma, asthma-related hospitalization in the previous year was associated with reduced FEF25-75 even among those with normal FEV1. Our results suggest that FEF25-75 may provide important information in the assessment and management of asthma in children.

The cultural competence of health care professionals: conceptual analysis using the results from a national pilot study of training and assessment.

The cultural competence of health professionals affects the satisfaction with, and outcomes of, patient care. Patient-centered cultural training was implemented with 76 trainees. Four months later, they were assessed using standardized patient scenarios and their performance compared to a control group. A questionnaire was used to evaluate the training. Assessment scores were analyzed using t tests to compare groups. Interrater reliability was calculated for individual scenarios. The cultural training received positive evaluations with many trainees indicating their intention to change future practice. Those who received cultural training gained higher scores upon assessment than those who had not. This difference was significant for three scenarios with nonclinical evaluators. Interrater reliability ranged from .913 to .427. The significant difference in performance between the groups supports the validity and educational impact of this approach. However, variable reliability highlights the difficulties with developing robust assessments in this area that are feasible within resource constraints.

Management of plastic bronchitis with topical tissue-type plasminogen activator.

Plastic bronchitis or cast bronchitis is a rare disease of unclear etiology characterized by formation of airway casts that can lead to life-threatening airway obstruction. There is currently limited data regarding optimal treatment of plastic bronchitis. Several therapies have been suggested, but recurrences are common and mortality remains high. We report the case of a 6-year-old boy with refractory eosinophilic bronchial casts, unresponsive to low-dose systemic corticosteroids, inhaled corticosteroids, azithromycin, and dornase alfa, who was treated successfully and safely with direct instillation of tissue-type plasminogen activator (tPA) to the obstructing casts during flexible bronchoscopy and inhaled tPA. Our case illustrates that the current therapy for plastic bronchitis remains inadequate. To our knowledge, this case is the first to show that direct instillation of tPA can be used safely for treatment of this disease. The use of tPA via direct administration into the airways during bronchoscopy and via a nebulizer appeared to be a safe and effective therapy for plastic bronchitis and should be considered early in the course of the disease to prevent complications of severe airway obstruction.