Symptom phenotyping in people with cystic fibrosis during acute pulmonary exacerbations using machine-learning K-means clustering analysis.

INTRODUCTION: People with cystic fibrosis (PwCF) experience frequent symptoms associated with chronic lung disease. A complication of CF is a pulmonary exacerbation (PEx), which is often preceded by an increase in symptoms and a decline in lung function. A symptom cluster is when two or more symptoms co-occur and are related; symptom clusters have contributed meaningful knowledge in other diseases. The purpose of this study is to discover symptom clustering patterns in PwCF during a PEx to illuminate symptom phenotypes and assess differences in recovery from PExs. METHODS: This study was a secondary, longitudinal analysis (N = 72). Participants at least 10 years of age and being treated with intravenous antibiotics for a CF PEx were enrolled in the United States. Symptoms were collected on treatment days 1-21 using the CF Respiratory Symptom Diary (CFRSD)-Chronic Respiratory Symptom Score (CRISS). K-means clustering was computed on day 1 symptom data to detect clustering patterns. Linear regression and multi-level growth models were performed. RESULTS: Symptoms significantly clustered based on severity: low symptom (LS)-phenotype (n = 42), high symptom (HS)-phenotype (n = 30). HS-phenotype had worse symptoms and CRISS scores (p< 0.01) than LS-phenotype. HS-phenotype was associated with spending 5 more nights in the hospital annually (p< 0.01) than LS-phenotype. HS-phenotype had worse symptoms over 21 days than LS-phenotype (p< 0.0001). CONCLUSION: Symptoms significantly cluster on day 1 of a CF-PEx. PwCF with HS-phenotype spend more nights in the hospital and are less likely to experience the same resolution in symptoms by the end of PEx treatment than LS-phenotype.

Qualitative Analysis of Perspectives on Lung Transplant among People with Cystic Fibrosis.

Rationale: Lung transplant (LTx) is a potentially lifesaving treatment option for individuals with advanced cystic fibrosis (CF), but more people with CF (PwCF) and advanced lung disease die each year than undergo transplant in the United States. Little is known about these individuals' LTx information needs and factors influencing their decision-making process related to transplant. Objectives: To examine PwCF's experiences with and preferences for provision of LTx information and to identify transplant information needs that CF clinicians are well positioned to address. Methods: We performed semistructured qualitative interviews in two separate cohorts: PwCF without LTx and PwCF with LTx between July 2019 and June 2020. Questions focused on awareness and knowledge about LTx, perspectives related to communication about transplant in the CF clinic, and experiences with LTx. Thematic analysis was used to organize the qualitative data. Exemplar quotes were chosen to llustrate domains that emerged pertaining to the research objectives. Results: Fifty-five PwCF, including 35 without LTx and 20 with LTx, participated. One-third of PwCF without LTx had normal or near-normal lung function. Key common domains among PwCF with and without LTx were identified, including information needs, connections with LTx recipients, and conversations with CF clinicians. For PwCF with and without transplant, concrete information needs were identified: success or survival, social support, surgery, recovery/pain, and quality of life post-transplant. The importance of connecting with LTx recipients to hear their stories and experiences was emphasized by both PwCF with and without transplant. Important considerations for timing and content of discussions with CF clinicians were identified, including having information presented early (before LTx referral is needed) and in limited detail at first. PwCF without LTx wanted to understand how LTx was relevant to them, with a focus on the unique experience of CF. PwCF with LTx emphasized the need for a centralized resource for LTx information. Conclusions: The findings provide content areas for CF clinicians to focus on as they proactively initiate conversations about LTx and support the development of tools to aid in discussions about LTx for PwCF.

A longitudinal analysis of respiratory symptoms in people with cystic fibrosis with advanced lung disease on and off ETI.

People with CF (PwCF), particularly those with advanced lung disease (ALD), experience frequent respiratory symptoms. A major CF breakthrough was the approval of elexacaftor/tezacaftor/ivacaftor (ETI) in 2019, which has been shown to improve symptoms and lung function in the CF population, and decrease pulmonary exacerbations. The purpose of this study was to analyze longitudinal changes in respiratory symptoms over 24 months in ETI-treated and untreated PwCF with ALD Symptoms were measured among CF adults with ppFEV1 < 40% (N = 48, 24 ETI-treated, 24 untreated) using the CFRSD-CRISS and the CFQ-R [respiratory]. Two multilevel growth models assessed the rate of change in symptoms overall and within the ETI-treated and untreated groups. PwCF on ETI had significantly lower symptom severity over 24 months than those not on ETI as measured by the CRISS and CFQ-R. The ETI-treated group maintained an -11.7 and +19.3 point difference(p<0.01) in CRISS and CFQ-R scores over the study compared to the non-ETI group, achieving minimal clinically important differences on average between groups on both instruments. No change in the symptom burden trajectory between groups was observed (p = 0.58). Even with ALD, ETI-treated PwCF have a lower respiratory burden than those not on ETI. This may be confounded by survivorship bias in the non-ETI group. Of note, in this ALD cohort, neither instrument demonstrated ceiling effects. Our results suggest that, while ETI has significantly improved the lived experience, PwCF with ALD are still plagued by respiratory symptoms.

Predicting return of lung function after a pulmonary exacerbation using the cystic fibrosis respiratory symptom diary-chronic respiratory infection symptom scale.

Background: Pulmonary exacerbations (PExs) in people with cystic fibrosis (PwCF) are associated with increased healthcare costs, decreased quality of life and the risk for permanent decline in lung function. Symptom burden, the continuous physiological and emotional symptoms on an individual related to their disease, may be a useful tool for monitoring PwCF during a PEx, and identifying individuals at high risk for permanent decline in lung function. The purpose of this study was to investigate if the degree of symptom burden severity, measured by the Cystic Fibrosis Respiratory Symptom Diary (CFRSD)- Chronic Respiratory Infection Symptom Scale (CRISS), at the onset of a PEx can predict failure to return to baseline lung function by the end of treatment. Methods: A secondary analysis of a longitudinal, observational study (N = 56) was conducted. Data was collected at four time points: year-prior-to-enrollment annual appointment, termed "baseline", day 1 of PEx diagnosis, termed "Visit 1", day 10-21 of PEx diagnosis, termed "Visit 2" and two-weeks post-hospitalization, termed "Visit 3". A linear regression model was performed to analyze the research question. Results: A regression model predicted that recovery of lung function decreased by 0.2 points for every increase in CRISS points, indicating that participants with a CRISS score greater than 48.3 were at 14% greater risk of not recovering to baseline lung function by Visit 2, than people with lower scores. Conclusion: Monitoring CRISS scores in PwCF is an efficient, reliable, non-invasive way to determine a person's status at the beginning of a PEx. The results presented in this paper support the usefulness of studying symptoms in the context of PEx in PwCF.

Patient perspectives on elexacaftor/tezacaftor/ivacaftor after lung transplant.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/tezacaftor/ivacaftor (ETI), significantly improve outcomes and quality of life for people with cystic fibrosis (CF). However, little is known about how lung transplant recipients (LTRs) perceive the use of ETI. We conducted a survey to assess perspectives on ETI among LTRs with CF at our lung transplant program. Of 81 CF LTRs, 46 participants (58 %) responded. The majority of respondents (88 %) were aware of ETI. Over 80 % considered treating non-lung symptoms of CF to be very important. Concerns regarding ETI included potential drug interactions with transplant medications (77 %), side effects (53 %), cost of medication (49 %), and lack of clinical trial data for LTRs (43 %). Half reported they would only consider taking ETI if their CF or transplant doctor recommended it. The findings suggest that CF LTRs seek informational support and shared decision-making about ETI from their clinicians.

Cognitive Impairment in Non-critical, Mild-to-Moderate COVID-19 Survivors.

IMPORTANCE: Previous studies of post-acute COVID-19 syndrome have focused on critical cases with severe disease. However, most cases are mild to moderate in disease severity. OBJECTIVE: We aimed to examine cognitive outcomes in cases of non-critical, mild-to-moderate COVID-19. Design, Setting, and Participants: In this cross-sectional study, we enrolled 72 adults aged 22 to 65 years in Central Texas who had non-critical, mild-to-moderate COVID-19 infection between 13 January 2021 and 20 April 2021. MAIN OUTCOMES AND MEASURES: We remotely administered cognitive-behavioral testing to determine the frequency of cognitive impairment and examine demographic, clinical, and psychosocial contributors to impairment. RESULTS: The frequency of objective cognitive impairment was 40%. The largest number of participants (24%) showed impairment on a measure of executive functioning. Attention and processing speed was more impaired in males (OR = 1.5, 95%CI = 0.23-2.9). Males endorsed lower adherence to social distancing guidelines (U = 590, p = 0.01), which was in turn associated with cognitive impairment across participants (r = -0.30, p = 0.01). Younger age was correlated with impairment (r = -0.26, p = 0.03) but was also associated with racial/ethnic minority status (r = -0.31, p = 0.01) and increased psychological symptoms (p < 0.04). Greater number of COVID-19 symptoms was correlated with lower subjective cognitive function (r = -0.38, p = 0.001) as well as psychosocial function (r > 0.24, p < 0.05). Moderate COVID-19 severity was associated with attention/processing speed impairment (r = 0.27, p = 0.03), increased pain (r = 0.31, p = 0.01), and higher number of COVID-19 symptoms (r = 0.32, p = 0.01). CONCLUSION AND RELEVANCE: Mild or moderate COVID-19 infection may be associated with cognitive impairments, especially in the domain of executive functioning. A subgroup of younger individuals may be more vulnerable to cognitive and psychosocial effects of COVID-19. HIGHLIGHTS: Question: How frequent is cognitive impairment among non-critical, mild-to-moderate COVID-19 survivors? FINDINGS: In this cross-sectional study of 72 adults, 40% demonstrated cognitive impairment, particularly in executive function. MEANING: Neurologic sequelae, such as cognitive impairment, may be common following COVID-19 infection.

Development and testing of a biobanking acceptability scale: A multistage effort to add a biobank to an existing longitudinal study.

BACKGROUND: More biobanks linked to demographic, phenotypic, and clinical data are needed to advance multiple sclerosis (MS) research; however, little is known about biobanking attitudes among persons with MS, broadly, as well as willingness of participants in an existing longitudinal study to donate biospecimens, specifically. METHODS: To assess biobanking attitudes in a cohort of MS patients in an ongoing longitudinal study, a new Biobanking Acceptability Scale (BAS) was developed, its reliability and predictive validity tested, and factors that influenced biobanking intent as well as behavior were explored. Analysis included descriptive statistics, factor analysis, Cronbach's α, and Pearson's bivariate correlation coefficients. RESULTS: In 2018, 227 participants completed the 10-item BAS. Biobanking attitudes were generally positive (BAS total score, M = 38.8 out of 50; SD = 6.7), and most participants expressed willingness to donate hair (87%), saliva (85%), and/or blood (72%). In 2019, 143 participants consented to biobanking and were mailed supplies; 110 individuals provided at least one biospecimen, resulting in 110 saliva samples and 89 hair samples. The 10-item BAS displayed good internal consistency (α = 0.81). Demographic and clinical variables were not significantly associated with BAS score nor actual donation. Total BAS score was related to consent (r = 0.36, p < .001) and to actual donation of hair or saliva samples (r = 0.24, p < .01). CONCLUSION: Overall, the participants had positive attitudes toward biobanking; the scale should be assessed in more diverse samples. The BAS predicted biobanking consent, and thus may be a useful measure to identify individuals most likely to donate biospecimens and/or identify potential barriers to biobanking that can be addressed through study design.

Describing cognitive function and psychosocial outcomes of COVID-19 survivors: A cross-sectional analysis.

BACKGROUND: Neurological and psychological symptoms are increasingly realized in the post-acute phase of COVID-19. PURPOSE: To examine and characterize cognitive and related psychosocial symptoms in adults (21-75 years) who tested positive for or were treated as positive for COVID-19. METHODS: In this cross-sectional study, data collection included a cognitive testing battery (Trails B; Digit Symbol; Stroop; Immediate and Delayed Verbal Learning) and surveys (demographic/clinical history; self-reported cognitive functioning depressive symptoms, fatigue, anxiety, sleep disturbance, social role performance, and stress). Results were compared with published norms, rates of deficits (more than 1 standard deviation (SD) from the norm) were described, and correlations were explored. RESULTS: We enrolled 52 participants (mean age 37.33 years; 78.85% female) who were, on average, 4 months post illness. The majority had a history of mild or moderate COVID-19 severity. Forty percent of participants demonstrated scores that were 1 SD or more below the population norm on one or more of the cognitive tests. A subset had greater anxiety (21.15%), depressive symptoms (23.07%), and sleep disturbance (19.23%) than population norms. Age differences were identified in Stroop, Digit Symbol, and Trails B scores by quartile ( p < .01), with worse performance in those 28-33 years old. CONCLUSIONS: Cognitive dysfunction and psychological symptoms may be present in the weeks or months after COVID-19 diagnosis, even in those with mild to moderate illness severity. IMPLICATIONS FOR PRACTICE: Clinicians need to be aware and educate patients about the potential late/long-term cognitive and psychological effects of COVID-19, even in mild to moderate disease.

Best Practices for Obtaining Genomic Consent in Pediatric Traumatic Brain Injury Research.

BACKGROUND: Precision health relies on large sample sizes to ensure adequate power, generalizability, and replicability; however, a critical first step to any study is the successful recruitment of participants. OBJECTIVES: This study seeks to explore how the enrollment strategies used in a parent study contributed to the high consent rates, establish current best practices that can be used in future studies, and identify additional factors that contribute to consent into pediatric traumatic brain injury biobanks. METHODS: Retrospective secondary analysis of data from a parent study with high consent rates was examined to explore factors affecting consent into biobanking studies. RESULTS: Of the 76 subjects who were approached, met the eligibility criteria, and reviewed the consent form, only 16 (21.1%) declined to participate. The consented group (n = 60) represents 64.5% of those who met the eligibility criteria upon initial screening (n = 93) and 78.9% of those with confirmed eligibility (n = 76). Analysis of screening data suggested there were no major barriers to consenting individuals into this pediatric traumatic brain injury biobank. DISCUSSION: There were no demographic or research-related characteristics that significantly explained enrollment. Ethically, to obtain true informed consent, parents need to understand only their child's diagnosis, prognosis, and medical care, as well as the purpose of the proposed research and its risks and benefits. Researchers need to implement best practices, including a comprehensive review of census data to identify eligible participants to approach, a prescreening protocol, and effective consenting process to obtain informed consent so that precision care initiatives can be pursued.