Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised.

OBJECTIVES: Cystic fibrosis (CF) limits survival and negatively affects health-related quality of life (HRQOL). Cost-effectiveness analysis (CEA) may be used to make reimbursement decisions for new CF treatments; nevertheless, generic utility measures used in CEA, such as EQ-5D, are insensitive to meaningful changes in lung function and HRQOL in CF. Here we develop a new, CF disease-specific, preference-based utility measure based on the adolescent/adult version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely used, CF-specific, patient-reported measure of HRQOL. METHODS: Blinded CFQ-R data from 4 clinical trials (NCT02347657, NCT02392234, NCT01807923, and NCT01807949) were used to identify discriminating items for a classification system using psychometric (eg, factor and Rasch) analyses. Thirty-two health states were selected for a time trade-off (TTO) exercise with a representative sample of the UK general population. TTO utilities were used to estimate a preference-based scoring algorithm by regression analysis (tobit models with robust standard errors clustered on participants with censoring at -1). RESULTS: A classification system with 8 dimensions (CFQ-R-8 dimensions; physical functioning, vitality, emotion, role functioning, breathing difficulty, cough, abdominal pain, and body image) was generated. TTO was completed by 400 participants (mean age, 47.3 years; 49.8% female). Among the regression models evaluated, the tobit heteroscedastic-ordered model was preferred, with a predicted utility range from 0.236 to 1, no logical inconsistencies, and a mean absolute error of 0.032. CONCLUSION: The CFQ-R-8 dimensions is the first disease-specific, preference-based scoring algorithm for CF, enabling estimation of disease-specific utilities for CEA based on the well-validated and widely used CFQ-R.

Inspiratory muscle training enhances recovery post-COVID-19: a randomised controlled trial.

BACKGROUND: Many people recovering from coronavirus disease 2019 (COVID-19) experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). METHODS: 281 adults (age 46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a "usual care" waitlist control arm. Health-related quality-of-life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (K-BILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength, and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary end-point was K-BILD total score, with the K-BILD domains and TDI being key secondary outcomes. RESULTS: According to intention to treat, there was no difference between groups in K-BILD total score post-intervention (control: 59.5±12.4; IMT: 58.2±12.3; p<0.05) but IMT elicited clinically meaningful improvements in the K-BILD domains for breathlessness (control: 59.8±12.6; IMT: 62.2±16.2; p<0.05) and chest symptoms (control: 59.2±18.7; IMT: 64.5±18.2; p<0.05), along with clinically meaningful improvements in breathlessness according to TDI (control: 0.9±1.7 versus 2.0±2.0; p<0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness. CONCLUSIONS: IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long COVID, further research is warranted on the individual responses to rehabilitation; the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.

Weight a minute: Exploring the effect on weight and body composition after the initiation of elexacaftor/tezacaftor/ivacaftor in adults with CF.

BACKGROUND: Life expectancy for people with CF (PwCF) continues to increase. However, a trend of overweight and obesity is emerging along with concern of developing comorbitities. Body composition (BC) is associated with several health indices. However, body mass index (BMI) does not provide information on BC. METHODS: BMI, fat mass (FM), fat free mass (FFM), using bioelectrical impedance, lung function and sweat chloride (SwCl) were assessed in adult PwCF in routine clinic before and after commencement of the CFTR modulator Elexacaftor/Tezacaftor/Ivacaftor. RESULTS: 109 PwCF (76 male) underwent assessments at both time points. In all PwCF a significant upward trend in BMI was observed (p < 0.001). Males significantly gained more FFM compared to females (p0.03), whilst prevalence of normal weight obesity increased primarily in females (25-38%). CONCLUSION: Routine BC assessment identifies individuals with elevated FM or depleted FFM enabling individualised care with the focus of optimising BC.

Gaining an Understanding of Pneumocystosis in Wales.

Pneumocystis pneumonia (PcP) is a serious complication of many significant immunocompromising conditions. Prior incidence estimates in Wales are based on PcP's presentation in the HIV and transplant populations. The objectives were to describe the incidence of PcP in Wales using laboratory reporting measures and assess the impact of underlying immunosuppression cause on mortality. All positive PCR results for PcP between 2015 and 2018 were identified. The total number of unique positives with clinical and radiological correlation was 159 patients, a mean of 39.75 annually. The healthcare records of these patients were reviewed. The mortality at one month was 35.2% and 49.1% at one year. HIV remains the commonest cause of immunosuppression but has lower mortality than non-HIV conditions (12% vs. 59% at one year, p < 0.00001). Non-HIV conditions were categorised as life-threatening and non-life threatening but had a non-significant mortality (66% vs. 54%; p = 0.149), highlighting the negative impact of PcP. An incidence of PcP in Wales of 1.23-1.26 cases per 100,000 has been identified, 32-35% greater than the upper limit previously estimated. There is high mortality in non-HIV patients regardless of immunosuppression cause. A heightened awareness of PcP in these groups will hasten diagnosis and potentially improve mortality.

Triple quadrupole LC/MS method for the simultaneous quantitative measurement of cefiderocol and meropenem in serum.

Background: therapeutic drug monitoring is a crucial aspect of the management of hospitalized patients. The correct dosage of antibiotics is imperative to ensure their adequate exposure specially in critically ill patients. The aim of this study is to establish and validate a robust and fast liquid chromatography-tandem mass spectrometry (LC/MS) method for the simultaneous quantification of two important antibiotics in critically ill patients, cefiderocol and meropenem in human plasma. Methods: sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using triple quadrupole LC/MS. The mobile phase was consisted of 55% methanol in water +0.1% formic acid, with flow rate of 0.4 ml min-1. Antibiotics stability was assessed at different temperatures. Serum protein binding was assessed using ultrafiltration devices. Results: chromatographic separation was achieved within 1.5 minutes for all analytes. Validation has demonstrated the method to be linear over the range 0.0025-50 mg L-1 for cefiderocol and 0.00028-50 mg L-1 for meropenem, with accuracy of 94-101% and highly sensitive, with LLOQ ≈ 0.02 mg L-1 and 0.003 mg L-1 for cefiderocol and meropenem, respectively. Both cefiderocol and meropenem showed a good stability at room temperature over 6 h, and at (4 °C) over 24 h. Cefiderocol and meropenem demonstrated a protein binding of 49-60% and 98%, respectively in human plasma. Conclusion: the developed method is simple, rapid, accurate and clinically applicable for the quantification of cefiderocol and meropenem.

Sharing decisions on reproductive goals: A mixed-methods study of the views of women who have cystic fibrosis.

BACKGROUND: There are complex medical, psychological, social and economic aspects to becoming a parent with Cystic Fibrosis (CF). A shared decision-making (SDM) approach could help women with CF make informed decisions about their reproductive goals that are sensitive to their individual values and preferences. This study investigated capability, opportunity, and motivation to participate in SDM from the perspective of women with CF. METHODS: Mixed-methods design. An international online survey was completed by 182 women with CF, to investigate participation in SDM in relation to reproductive goals, and measures of capability (information needs), opportunity (social environment) and motivation (SDM attitudes and self-efficacy) to engage in SDM. Twenty-one women were interviewed using a visual timelines method to explore their SDM experiences and preferences. Qualitative data were analysed thematically. RESULTS: Women with higher decision self-efficacy reported better experiences of SDM relating to their reproductive goals. Decision self-efficacy was positively associated with social support, age, and level of education, highlighting inequalities. Interviews indicated that women were highly motivated to engage in SDM, but their capability was compromised by lack of information, perception of insufficient opportunities for focused discussions about SDM. CONCLUSIONS: Women with CF are keen to engage in SDM about reproductive health, but currently lack sufficient information and support to do so. Interventions at patient, clinician and system levels are needed to support capability, opportunity and motivation to engage equitably in SDM in relation to their reproductive goals.

Heterogeneous Treatment Effects after Inspiratory Muscle Training during Recovery from Postacute COVID-19 Syndrome.

PURPOSE: The objective of this study is to investigate whether heterogeneous treatment effects occur for changes in inspiratory muscle strength, perceived dyspnea, and health-related quality of life after 8 wk of unsupervised home-based inspiratory muscle training (IMT) in adults with postacute coronavirus disease 2019 (COVID-19) syndrome. METHODS: In total, 147 adults with self-reported prior COVID-19 either completed an 8-wk home-based IMT intervention ( n = 111, 92 females, 48 ± 11 yr, 9.3 ± 3.6 months postacute COVID-19 infection) or acted as "usual care" wait list controls ( n = 36, 34 females, 49 ± 12 yr, 9.4 ± 3.2 months postacute COVID-19 infection). RESULTS: Applying a Bayesian framework, we found clear evidence of heterogeneity of treatment response for inspiratory muscle strength: the estimated difference between standard deviations (SD) of the IMT and control groups was 22.8 cm H 2 O (75% credible interval (CrI), 4.7-37.7) for changes in maximal inspiratory pressure (MIP) and 86.8 pressure time units (75% CrI, 55.7-116.7) for sustained MIP (SMIP). Conversely, there were minimal differences in the SD between the IMT and the control group for changes in perceived dyspnea and health-related quality of life, providing no evidence of heterogeneous treatment effects. Higher cumulative power during the IMT intervention was related to changes in MIP ( ß = 10.9 cm H 2 O (95% CrI, 5.3-16.8) per 1 SD) and SMIP ( ß = 63.7 (32.2-95.3) pressure time units per 1 SD), clearly indicating an IMT dose response for changes in inspiratory muscle strength. Older age (>50 yr), a longer time postacute COVID-19 (>3 months), and greater severity of dyspnea at baseline were also associated with smaller improvements in inspiratory muscle strength. CONCLUSIONS: Heterogeneous individual responses occurred after an 8-wk home-based IMT program in people with postacute COVID-19 syndrome. Consistent with standard exercise theory, larger improvements in inspiratory muscle strength are strongly related to a greater cumulative dose of IMT.

Investigating Pseudomonas aeruginosa population structure and frequency of cross-infection in UK cystic fibrosis clinics - a reference laboratory perspective.

BACKGROUND: We aimed to describe the UK Pseudomonas aeruginosa population structure amongst people with cystic fibrosis (PWCF), and to examine evidence for cross-infection. METHODS: Variable Number Tandem Repeat (VNTR) typing was performed on 4640 isolates from 2619 PWCF received from 55 hospital laboratories between 2017 and 2019. A combination of whole genome sequence (WGS)-based analysis of four clusters from one hospital, and epidemiological analysis of shared strains in twelve hospitals evaluated cross-infection. RESULTS: Of 2619 PWCF, 1324 (51%) harboured common clusters or known transmissible strains, while 1295 carried unique strains/those shared among small numbers of patients. Of the former, 9.5% (250 patients) harboured the Liverpool epidemic strain (LES), followed in prevalence by clone C (7.8%; 205 patients), cluster A (5%;130 patients), and cluster D (3.6%; 94 patients). WGS analysis of 10 LES isolates, 9 of cluster D and 6 isolates each of cluster A and clone C from one hospital revealed LES formed the tightest cluster (between 7 and 205 SNPs), and cluster D the loosest (between 53 and 1531 SNPs). Hospital-specific shared strains were found in some centres, although cross-infection was largely historical, with few new acquisitions. Fifty-nine PWCF (2.3%) harboured "high-risk" clones; one ST235 isolate carried a blaIMP-1 allele. CONCLUSION: Of 2619 PWCF who had P. aeruginosa isolates submitted for VNTR, 51% harboured either common clusters or known transmissible strains, of which LES was the most common. Limited evidence of recent patient-to-patient strain transmission was found, suggesting cross-infection prevention measures and surveillance effectively reduce transmission.

Systemic comorbidities in bronchiectasis.

Bronchiectasis is a chronic inflammatory lung disease, which has similarities to chronic obstructive pulmonary disease (COPD). Comorbidities of COPD include increased risk of cardiovascular (CV) disease, loss of bone mineral density (BMD) and loss of skeletal muscle mass and function, all linked to systemic inflammation. The potential for such comorbidities has not been explored in bronchiectasis. We hypothesised that patients with bronchiectasis would have similar increased comorbidities. A total of 20 patients with noncystic fibrosis bronchiectasis were compared to 20 controls similar in age, gender and smoking exposure. Assessments included aortic pulse wave velocity (PWV; (a measure of arterial stiffness and an independent predictor of CV risk), blood pressure (BP) as well as levels of interleukin-6 (IL-6), albumin, fasting glucose and lipids. Body composition (fat free mass index (FFMI)), BMD, the 6-min walk distance (6MWD) and self-reported physical activity were also determined. Patients with bronchiectasis had increased aortic PWV, 10.5 (3.0) m/second, when compared with controls, 8.8 (1.6) m/second (p < 0.05), despite similar central and peripheral BP and lipid profile. Patients also had increased IL-6 and reduced albumin and glucose. Although mean body mass index, FFMI and BMD were similar in patients and controls, only 20% of patients had a healthy BMD compared with 50% of controls. Patients had reduced 6MWD and reported less physical activity (p < 0.05). Patients with bronchiectasis had increased arterial stiffness (an indicator of increased CV risk), increased inflammation, reduced exercise capacity and bone thinning. These additional comorbidities require further evaluation for their management in these patients.

Cefiderocol to manage chronic, multi-drug-resistant Burkholderia cepacia complex infection in a patient with cystic fibrosis: a case report.

In cystic fibrosis (CF) patients, Gram-negative Burkholderia cepacia complex (Bcc) infections are associated with recurrent pulmonary exacerbations. Bcc organisms are innately resistant to many antibiotics, and infection with B. cenocepacia is a contraindication to lung transplantation. We report a CF patient with severe lung disease, colonized with Bcc, with a history of around nine exacerbations per year for over 10 years, for whom antibiotic regimens (including targeted and broad-spectrum antibiotics) had not cleared infection or extended the interval between exacerbations. After receiving a 2 week cefiderocol-containing regimen, the patient remained stable for more than 5 months without the need for additional antibiotics or hospital admissions for respiratory exacerbations.

Adverse Childhood Experiences (ACEs) in Adults with Cystic Fibrosis.

Objective: This exploratory study examines the prevalence of adverse childhood experiences (ACEs) in adults with cystic fibrosis (CF). Design: Childhood exposure to 16 ACEs was measured during an annual review assessment (N = 80). Methods: CF patients (n = 80) attending the All Wales Adult CF Service for a routine annual review assessment completed an adapted version of the Centers for Disease Control and Prevention (CDC) short-form ACE questionnaire alongside measures of psychological well-being. Results: In this sample, 65 (78%) reported at least one type of childhood adversity and 11 (14%) experienced four or more ACEs. Parental divorce or separation and verbal abuse were the most frequently reported ACEs. Illness related trauma in childhood was also prevalent with 52 (64%) reporting having experienced a painful or frightening medical procedure and 23 (28%) feeling forced to have treatment or a procedure. Conclusion: Individuals with CF reported a number of childhood traumas including trauma relating to medical procedures. Those with a history of ACEs may have increased risks of emotional and physical difficulties and may benefit from additional support from the CF psychosocial team.

The Presence of Exophiala dermatitidis in the Respiratory Tract of Cystic Fibrosis Patients Accelerates Lung Function Decline: A Retrospective Review of Lung Function.

Exophiala dermatitidis is increasingly isolated from cystic fibrosis (CF) respiratory samples. The decision to treat is hampered by limited evidence demonstrating the clinical significance of isolating E. dermatitidis. The objective was to assess the impact of E. dermatitidis isolation on the lung function of CF patients. The rate of lung function decline in the local CF population was calculated using historic lung function data. A control population who had never had E. dermatitidis cultured from the respiratory tract was compared with the E. dermatitidis group, calculating their rate of lung function decline before and after the first isolation of the organism. A total of 1840 lung function measurements were reviewed between the 31 E. dermatitidis group patients and 62 control patients. Their demographics were similar. The control group declined at a rate of −0.824 FEV1%/year. The rate of decline in the E. dermatitidis group prior to infection was −0.337 FEV1%/year (p = 0.2). However, post infection with E. dermatitidis, there was a significant increase in the rate of decline in lung function (−1.824 FEV1%/year, p < 0.01). The results suggest E. dermatitidis has a temporal relationship with accelerated rate of lung function decline. It is not clear if this is a cause or effect, but this accelerated rate of decline indicates a need for further investigation.

A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients.

BACKGROUND: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. METHODS: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. DISCUSSION: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. TRIAL REGISTRATION: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered).

Perceptions of inspiratory muscle training in adults recovering from COVID-19.

Post COVID-19 condition can occur following infection with SARS-CoV-2 and is characterised by persistent symptoms, including fatigue, breathlessness and cognitive dysfunction, impacting everyday functioning. This study explored how people living with post COVID-19 experienced an eight-week inspiratory muscle training (IMT) rehabilitation programme. Individualised semi-structured interviews with 33 adults (29 female; 49 ± 10 years; 6-11 months post-infection) explored expectations of IMT prior to the intervention, and post intervention interviews explored perceptions of IMT and its impact on recovery. Inductive thematic analysis was used to analyse the data. IMT helped many to feel proactive in managing their symptoms and was associated with perceived improvements in respiratory symptoms, exercise and work capacity, and daily functioning. IMT was well perceived and offers significant potential for use as part of a holistic recovery programme, although it is important to consider the complex, varied symptoms of post COVID-19, necessitating an individually tailored rehabilitation approach.

Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial.

BACKGROUND: Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation. METHODS: We conducted a multicentre, randomised, double-blind, active-controlled, phase 3b trial of elexacaftor plus tezacaftor plus ivacaftor at 35 medical centres in Australia, Belgium, Germany, and the UK. Eligible participants were those with cystic fibrosis homozygous for the F508del-CFTR mutation, aged 12 years or older with stable disease, and with a percent predicted FEV1 of 40-90% inclusive. After a 4-week run-in period, in which participants received tezacaftor 100 mg orally once daily and ivacaftor 150 mg orally every 12 h, participants were randomly assigned (1:1) to receive 24 weeks of either elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h (elexacaftor plus tezacaftor plus ivacaftor group) or tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h (tezacaftor plus ivacaftor group). Randomisation was stratified by percent predicted FEV1, age at screening visit, and whether the participant was receiving CFTR modulators at the time of the screening visit. Patients, investigators, and sponsor's study execution team were masked to treatment assignment. The primary endpoint was the absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline (ie, at the end of the tezacaftor plus ivacaftor run-in period) up to and including week 24. The key secondary endpoint was the absolute change from baseline in percent predicted FEV1 up to and including week 24; other secondary endpoints were the absolute change from baseline in sweat chloride concentrations up to and including week 24, and safety and tolerability. All endpoints were assessed in all randomised patients who had received at least one dose of their assigned regimen. This study is registered with ClinicalTrials.gov, NCT04105972. FINDINGS: Between Oct 3, 2019, and July 24, 2020, 176 participants were enrolled. Following the 4-week tezacaftor plus ivacaftor run-in period, 175 participants were randomly assigned (87 to the elexacaftor plus tezacaftor plus ivacaftor group and 88 to the tezacaftor plus ivacaftor group) and dosed in the treatment period. From baseline up to and including week 24, the mean CFQ-R respiratory domain score increased by 17·1 points (95% CI 14·1 to 20·1) in the elexacaftor plus tezacaftor plus ivacaftor group and by 1·2 points (-1·7 to 4·2) in the tezacaftor plus ivacaftor group (least squares mean treatment difference 15·9 points [95% CI 11·7 to 20·1], p<0·0001), the mean percent predicted FEV1 increased by 11·2 percentage points (95% CI 9·8 to 12·6) in the elexacaftor plus tezacaftor plus ivacaftor group and by 1·0 percentage points (-0·4 to 2·4) in the tezacaftor plus ivacaftor group (least squares mean treatment difference 10·2 percentage points [8·2 to 12·1], p<0·0001), and the mean sweat chloride concentration decreased by 46·2 mmol/L (95% CI 43·7 to 48·7) in the elexacaftor plus tezacaftor plus ivacaftor group and by 3·4 mmol/L (1·0 to 5·8) in the tezacaftor plus ivacaftor group (least squares mean treatment difference -42·8 mmol/L [-46·2 to -39·3], nominal p<0·0001). Most participants (70 [80%] in the elexacaftor plus tezacaftor plus ivacaftor group and 74 [84%] in the tezacaftor plus ivacaftor group) had adverse events that were mild or moderate in severity; serious adverse events occurred in five (6%) of 87 participants in the elexacaftor plus tezacaftor plus ivacaftor group and 14 (16%) of 88 participants in the tezacaftor plus ivacaftor group. One (1%) participant in the elexacaftor plus tezacaftor plus ivacaftor group discontinued treatment due to an adverse event of anxiety and depression. Two (2%) participants in the tezacaftor plus ivacaftor group discontinued treatment due to adverse events of psychotic disorder (n=1) and obsessive-compulsive disorder (n=1). INTERPRETATION: The elexacaftor plus tezacaftor plus ivacaftor regimen was safe and well tolerated, and led to significant and clinically meaningful improvements in respiratory-related quality of life and lung function, as well as improved CFTR function, changes that were durable over 24 weeks and superior to those seen with tezacaftor plus ivacaftor in this patient population. FUNDING: Vertex Pharmaceuticals.

Are We Missing the Opportunity to Measure Muscle Mass on Computed Tomography Thorax?

Hand grip strength (HGS) and fat free mass index (FFMI) are important indicators of skeletal muscle mass and correlate with prognosis in patients with respiratory diseases. It is also possible to estimate muscle mass by measuring muscle density and volume on cross sectional imaging. We reviewed all patients of the All Wales Cystic Fibrosis Centre who had a computed tomography thorax as part of routine clinical care between 2013 and 2017. By multiplying the volume and average Hounsfield units of the paraspinal muscles at T4 and T12 levels we were able to estimate the patients skeletal muscle mass. This was compared with their FFMI, HGS and forced expiratory volume in 1 second. Measurements of muscle mass at T4 and T12 showed significant correlation with HGS and FFMI, and T12 also showed significant correlation with forced expiratory volume in 1 second. This method may provide further prognostic information for patient with cystic fibrosis, particularly where equipment for HGS and FFMI assessments are lacking.

Real-World Outcomes of Ivacaftor Treatment in People with Cystic Fibrosis: A Systematic Review.

Cystic fibrosis (CF) is a rare, progressive, multi-organ genetic disease. Ivacaftor, a small-molecule CF transmembrane conductance regulator modulator, was the first medication to treat the underlying cause of CF. Since its approval, real-world clinical experience on the use of ivacaftor has been documented in large registries and smaller studies. Here, we systematically review data from real-world observational studies of ivacaftor treatment in people with CF (pwCF). Searches of MEDLINE and Embase identified 368 publications reporting real-world studies that enrolled six or more pwCF treated with ivacaftor published between January 2012 and September 2019. Overall, 75 publications providing data from 57 unique studies met inclusion criteria and were reviewed. Studies reporting within-group change for pwCF treated with ivacaftor consistently showed improvements in lung function, nutritional parameters, and patient-reported respiratory and sino-nasal symptoms. Benefits were evident as early as 1 month following ivacaftor initiation and were sustained over long-term follow-up. Decreases in pulmonary exacerbations, Pseudomonas aeruginosa prevalence, and healthcare resource utilization also were reported for up to 66 months following ivacaftor initiation. In studies comparing ivacaftor treatment to modulator untreated comparator groups, clinical benefits similarly were reported as were decreases in mortality, organ-transplantation, and CF-related complications. The safety profile of ivacaftor observed in these real-world studies was consistent with the well-established safety profile based on clinical trial data. Our systematic review of real-world studies shows ivacaftor treatment in pwCF results in highly consistent and sustained clinical benefit in both pulmonary and non-pulmonary outcomes across various geographies, study designs, patient characteristics, and follow-up durations, confirming and expanding upon evidence from clinical trials.

'I Live a Kind of Shadow Life': Individual Experiences of COVID-19 Recovery and the Impact on Physical Activity Levels.

Understanding of strategies to support individuals recovering from coronavirus disease 2019 (COVID-19) is limited. 'Long COVID' is a multisystem disease characterised by a range of respiratory, gastrointestinal, cardiovascular, neurological, and musculoskeletal symptoms extending beyond 12 weeks. The aim of this study was to explore individuals' experiences of recovering from COVID-19 to provide a better understanding of the acute and long-term impact of the disease on physical activity (PA). Individualised semi-structured interviews were conducted with 48 adults recovering from COVID-19 at 6-11 months post-infection. An inductive thematic analysis approach was used, reaching saturation at 14 interviews (10 female; 47 ± 7 years). Four overarching themes were identified: (i) Living with COVID-19, including managing activities of daily living; (ii) Dealing with the Unknown and self-management strategies; (iii) Re-introducing physical activity; and (iv) Challenges of returning to work. The return to PA, whether through activities of daily living, work or exercise, is often associated with the exacerbation of symptoms, presenting a range of challenges for individuals recovering from COVID-19. Individually tailored support is therefore required to address the unique challenges posed by COVID-19.