"I Had to Know About It, I Had to Find It, I Had to Know How to Access it": Experiences of Access to Rehabilitation Services Among People Living with Long COVID.

Purpose: The aim of this qualitative study is to understand the need for, access to, and quality of rehabilitation services for people living with Long COVID. Little is known about the experiences of people living with Long COVID accessing rehabilitation services. Therefore, we explored health concerns leading people living with Long COVID to seek help to address functional concerns and their experiences with accessing and participating in rehabilitation. Method: Interpretive description guided exploration of participants' experiences with Long COVID rehabilitation in Alberta, Canada. Semi-structured interviews were completed with 56 participants recruited from: three publicly funded Long COVID clinics, a specialized private physiotherapy clinic, a telephone-based rehabilitation advice line, and a Workers' Compensation Board-funded Long COVID rehabilitation program. Recruitment through mass media coverage allowed us to include people who did not access rehabilitation services. Data analysis was informed by Braun and Clarke's reflexive thematic analysis. Results: Four themes were identified: (1) the burden of searching for guidance to address challenges with functioning and disability; (2) supportive relationships promote engagement in rehabilitation; (3) conditions for participation in safe rehabilitation; and (4) looking forward - provision of appropriate interventions at the right time. Conclusions: Our findings highlight the experiences of accessing rehabilitation services for people living with Long COVID. Results suggest approaches to Long COVID rehabilitation should be accessible, multi-disciplinary, flexible, and person-centred.

Objectif: étude qualitative pour comprendre les besoins en services de réadaptation des personnes qui vivent avec la COVID longue, l'accès à ces services et leur qualité. On sait peu de choses sur les expériences des personnes qui vivent avec la COVID longue et accèdent à des services de réadaptation. C'est pourquoi les auteurs ont exploré les inquiétudes qui incitent ces personnes à demander de l'aide pour répondre à leurs problèmes fonctionnels et les expériences qu'elles ont vécues en matière d'accès à la réadaptation et de participation aux services qui y sont associés. Méthodologie: exploration guidée de la description interprétative des expériences des participants qui suivent une réadaptation à cause de la COVID longue en Alberta, au Canada. Les chercheurs ont procédé à des entrevues semi-structurées auprès de 56 participants recrutés dans trois cliniques de COVID longue financées par le gouvernement, une clinique de physiothérapie spécialisée privée, une ligne téléphonique de conseils en réadaptation et un programme de réadaptation après la COVID longue remboursé par la commission des accidents de travail. Le recrutement dans les médias de masse a permis d'inclure des personnes qui n'avaient pas accédé aux services de réadaptation. L'examen des données reposait sur l'analyse thématique réflexive de Braun et Clarke. Résultats: les chercheurs ont relevé quatre thèmes : 1) le fardeau de la recherche de conseils pour répondre aux problèmes de fonctionnement et d'incapacité; 2) les relations de soutien qui favorisent la participation à la réadaptation; 3) les conditions nécessaires pour participer à une réadaptation sécuritaire et 4) pour l'avenir, la prestation d'interventions appropriées au bon moment. Conclusions: les constatations des auteurs font ressortir les expériences d'accès aux services de réadaptation chez les personnes qui vivent avec la COVID longue. Selon les résultats, les approches de réadaptation après la COVID longue devraient être accessibles, multidisciplinaires, flexibles et axées sur l'individu.

"None of us are lying": an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID.

BACKGROUND: Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs. METHODS: Our study was informed by the Levesque et al.'s (2013) "conceptual framework of access to health care." We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed. RESULTS: Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants' Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants' attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and 'normal' results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants. CONCLUSION: With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.

A Systematic Review of the Clinical Efficacy and Safety of CFTR Modulators in Cystic Fibrosis.

Several placebo-controlled trials have been recently published evaluating novel therapies targeting the defective CFTR protein. This systematic review examines the clinical efficacy and safety of CFTR modulators in individuals with cystic fibrosis (CF) with specific genetic mutations. Online sources were searched for placebo-controlled, parallel-design clinical trials investigating CFTR modulators from January 1, 2005 to March 31, 2018. The primary outcome of interest was FEV1% predicted (ppFEV1). Fourteen RCTs met our eligibility criteria. The largest improvement in ppFEV1 favouring treatment was observed for ivacaftor (IVA) in G551D individuals (≥6 years old). Both tezacaftor-ivacaftor (TEZ-IVA) and lumacaftor-ivacaftor (LUM-IVA) also improved ppFEV1 in F508del homozygous individuals but there was increased reporting of respiratory adverse events with LUM-IVA compared to placebo. IVA also significantly improved ppFEV1 in a sub-group of individuals ≥18 years old with an R117H mutation. No significant improvements in ppFEV1 were observed for IVA, LUM, or TEZ in F508del homozygous individuals, LUM or LUM-IVA in F508del heterozygous individuals, or ataluren in individuals with a nonsense mutation. Significant improvements in ppFEV1 and other clinical outcomes were observed for IVA in G551D individuals, TEV-IVA and LUM-IVA in F508del homozygous individuals, and IVA in adults with a R117H mutation.

Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations.

Pulmonary exacerbations are common events in cystic fibrosis and have a profound impact on quality of life, morbidity, and mortality. Pulmonary exacerbation outcomes remain poor and a significant proportion of patients fail to recover their baseline lung function despite receiving aggressive treatment with intravenous antibiotics. This focused review provides an update on some of the recent advances that have taken place in our understanding of the epidemiology, pathophysiology, diagnosis, and management of pulmonary exacerbations in cystic fibrosis as well as direction for future study.

Group B streptococcus (GBS) is an important pathogen in human disease- but what about in cystic fibrosis?

BACKGROUND: Group B Streptococcus (GBS) is a common commensal capable of causing severe invasive infections. Most GBS infections occur in neonates (often as pneumonia). GBS can also cause infection in adults with diabetes and other immunological impairments but rarely leads to pneumonia in adults. GBS has occasionally been found in the sputum of Cystic Fibrosis (CF) patients, an inherited condition known for progressive lung disease. However, the epidemiology and clinical significance of GBS in CF are not understood. METHODS: We retrospectively reviewed a large single-centre adult CF population with an associated comprehensive, prospectively collected bacterial biobank beginning in 1978. We identified all individuals with GBS isolated from their sputum on at least one occasion. The primary outcome was risk of pulmonary exacerbation (PEx) at the time of the first GBS isolate compared to the preceding visit. Secondary outcomes included determining: prevalence of GBS infection in a CF population, whether GBS infections where transient or persistent, whether GBS strains were shared among patients, change in % predicted FEV1 at the time of GBS isolate compared to the preceding visit, PEx frequency after the first GBS isolate, change in % predicted FEV1 after the first GBS isolate, and complications of GBS infection. RESULTS: GBS was uncommon, infecting 3.5% (11/318) adults within our cohort. Only three individuals developed persistent GBS infection, all lasting > 12 months. There were no shared GBS strains among patients. PEx risk was not increased at initial GBS isolation (RR 5.0, CI 0.69-36.1, p=0.10). In the two years preceding initial GBS isolation compared to the two following years, there was no difference in PEx frequency (median 2, range 0-4 vs 1, range 0 to 5, respectively, p=0.42) or lung function decline, as measured by % predicted FEV1, (median -1.0%, range -19 to 7% vs median -6.0%, range -18 to 22%, p=0.86). There were no invasive GBS infections. CONCLUSION: In adults with CF, GBS is uncommon and is generally a transient colonizer of the lower airways. Despite the presence of structural lung disease and impaired innate immunity in CF, incident GBS infection did not increase PEx risk, PEx frequency, rate of lung function decline, or other adverse clinical outcomes.

Cryptococcal Lung Infections.

Cryptococcus is among the most common invasive fungal pathogens globally and is one of the leading causes of acquired immunodeficiency virus-related deaths. Cryptococcus neoformans and Cryptococcus gattii are the most clinically relevant species and account for most cryptococcal disease. Pulmonary manifestations can range from mild symptoms to life-threatening infection. Treatment is tailored based on the severity of pulmonary infection, the presence of disseminated or central nervous system disease, and patient immune status. Amphotericin B and flucytosine followed by fluconazole remain the standard agents for the treatment of severe cryptococcal infection.

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

RATIONALE: C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain. OBJECTIVES: To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response. METHODS: We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE). MEASUREMENTS AND MAIN RESULTS: 53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61-0.83; p<0.001). 23% of PEx events were characterized by an admission CRP of > 75 mg/L with a specificity of 90% for treatment non-response. CONCLUSIONS: Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes.

Nontuberculous Mycobacteria in Cystic Fibrosis.

Nontuberculous mycobacteria (NTM) are found in approximately 10 % of cystic fibrosis (CF) patients, but only a portion will develop NTM disease. The management of CF lung disease should be optimized, including antibiotic therapy targeted to the individual's usual airway bacteria, prior to considering treatment for NTM lung disease. Those who meet criteria for NTM lung disease may not necessarily require treatment and could be monitored expectantly if symptoms and radiographic findings are minimal. However, the presence of Mycobacterium abscessus complex (MABSC), severe lung disease, and/or anticipated lung transplant should prompt NTM therapy initiation. For CF patients with Mycobacterium avium complex (MAC), recommended treatment includes triple antibiotic therapy with a macrolide, rifampin, and ethambutol. Azithromycin is generally our preferred macrolide in CF as it is better tolerated and has fewer drug-drug interactions. MABSC treatment is more complex and requires an induction phase (oral macrolide and two IV agents including amikacin) as well as a maintenance phase (nebulized amikacin and two to three oral antibiotics including a macrolide). The induction phase may range from one to three months (depending on infection severity, treatment response, and medication tolerability). For both MAC and MABSC, treatment duration is extended 1-year post-culture conversion. However, in patients who do not achieve culture negative status but tolerate therapy, we consider ongoing treatment for mycobacterial suppression and prevention of disease progression.

Birt-Hogg-Dubé syndrome: a large single family cohort.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition characterized by dermatologic lesions, pulmonary manifestations, and renal tumors. The syndrome arises from germline mutations in the folliculin (FLCN) gene. We present findings from the single largest family BHD cohort described to date. Primary objectives were to characterize cystic lung changes on computed tomography (CT) chest scanning and identify features that stratify patients at higher risk of pneumothorax. Secondary objectives entailed description of the following: type and natural history of BHD-associated pneumothorax, pulmonary function characteristics, and relationship between cystic lung changes and pulmonary function. METHODS: The study was a retrospective chart review for a case series of a single family. Over 70 family members of a proband with documented BHD were identified, 68 of which consented to genetic testing. All those with confirmed BHD were offered a clinical assessment by the Medical Genetics and Pulmonary services which included a history, physical exam, complete pulmonary function tests, and computed tomography (CT) scan of the chest and abdomen. RESULTS: Thirty-six individuals had a heterozygous mutation in the FLCN gene (c.59delT). Of these, 100 % (28/28) had pulmonary cysts, 41 % (13/32) had spontaneous pneumothoraces, 26 % (8/31) had kidney cysts, 3 % (1/31) had renal tumors, and 53 % (18/34) had dermatologic manifestations. Recurrent pneumothoraces were common (40 %). Cyst size (OR 3.23, 95 % CI 1.35-7.73) and extent of lower lung zone disease (OR 6.43, 95 % CI 1.41-29.2) were the only findings associated with pneumothorax. The size or extent of cystic disease did not correlate with lung function results. CONCLUSIONS: This is the largest single family cohort of patients with BHD syndrome documented to date. We found that all individuals had pulmonary cysts, pneumothoraces were common, and cyst size and lower lobe predominant disease were associated with pneumothorax. Lung function was generally preserved and not affected by a high cyst burden.

Unclassifiable interstitial lung disease: A review.

Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD.

Clinical implications and characterization of Group A Streptoccoccus infections in adults with cystic fibrosis.

BACKGROUND: Persistent airway infection is a hallmark feature of cystic fibrosis (CF). However, increasingly it has been observed that non-classical pathogens may transiently infect CF lower airways. Streptococcus pyogenes (Group A Streptococcus; (GAS)) is an uncommon but potentially dangerous cause of community-acquired pneumonia. Our aim was to determine the incidence, natural history, and clinical impact of GAS infections in CF and phenotypically and genotypically characterize the isolates. METHODS: We retrospectively evaluated the Calgary Adult CF Clinic biobank to identify adults with at least one GAS isolate. Patient demographics, medical and pulmonary exacerbation (PEx) histories were evaluated. The primary outcome was PEx occurrence at incident GAS culture. Secondary outcomes evaluated were changes in lung function and PEx frequency following GAS isolation. Isolates were assessed for extra-cellular virulence factor production capacity and ability to produce quorum sensing (AI-2). Isolates were genotyped using pulse-field gel electrophoresis (PFGE). RESULTS: Fifteen individuals who cultured GAS twenty times were identified. At the time of GAS isolation, 47% (7/15) of subjects experienced a PEx and half of these (4/7) were severe. Individuals were more likely to have a PEx at the time of the index GAS isolate compared to the preceding visit (RR = 6.0, 95% CI 0.82-43.0, p = 0.08), particularly if GAS was the numerically dominant sputum pathogen (RR = 6.5, 95% CI 1.00-43.0, p = 0.009). There were no changes in PEx frequency or rate of lung function decline following GAS. None of the patients developed chronic airways infection, bacteremia, necrotizing pneumonia or empyema. Susceptibility was universal to common anti-Streptococcal antibiotics and anti-Pseudomonal antibiotics commonly used in CF, with the exception of azithromycin. GAS isolates varied in their production of protease, DNase, and AI-2 but these did not correlate with PEx, and none produced elastase, chrondrotin sulfatase or H202. One patient had prolonged carriage with the same isolate and two patients had isolates with similar PFGE patterns. CONCLUSIONS: GAS was an uncommon lower respiratory pathogen of adults with CF. Identification of GAS in sputum was frequently associated with PEx, particularly when numerically dominant. However, transient GAS infection did not result in chronic infection nor appreciably change long-term disease trajectory.