The impact of 12 months treatment with ivacaftor on Scottish paediatric patients with cystic fibrosis with the G551D mutation : a review

We reviewed the impact of ivacaftor on Scottish paediatric cystic fibrosis (CF) patients ≥ 6 years of age after 12 months of treatment. Statistically significant improvements in FEV1 and BMI and a reduction in sweat chloride, all comparable with previously published data were observed. The findings also suggested reduced use of intravenous antibiotics and oral antibiotics. No significant adverse effects were observed but a possible association with cataract formation could not be excluded. This review suggests that, in the short term at least, ivacaftor is effective and safe in paediatric patients ≥ 6 years of age with G551

Differential diagnosis in pediatric radiology, 2nd ed. By Leonard E. Swischuk and Susan D. John. Baltimore: Williams & Wilkins, 1995, 482 pp

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38602/1/1950210305_ftp.pd

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

Funding Information: We thank the people with CF, and their families, for consenting to their data being included in the ECFSPR. We thank the centers and individual country representatives for allowing the use of the anonymized patient data. This work was supported by an unrestricted grant from Chiesi Farmaceutici SpA, Parma, Italy. The funder had no role in the design, conduct or reporting of this study. Datasets for the general population were provided by the European Centre for Disease Prevention and Control (ECDC) based on data provided by WHO and Ministries of Health from the affected countries. The views and opinions of the authors expressed herein do not necessarily state or reflect those of the ECDC. The accuracy of the authors' statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data. Funding Information: This work was supported by an unrestricted grant from Chiesi Farmaceutici SpA, Parma, Italy. The funder had no role in the design, conduct or reporting of this study. Publisher Copyright: © 2021Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.publishersversionPeer reviewe

Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations

<p>Abstract</p> <p>Background</p> <p>Cystic Fibrosis (CF) is a life-shortening genetic disease in which ~80% of deaths result from loss of lung function linked to inflammation due to chronic bacterial infection (principally <it>Pseudomonas aeruginosa</it>). Pulmonary exacerbations (intermittent episodes during which symptoms of lung infection increase and lung function decreases) can cause substantial resource utilization, morbidity, and irreversible loss of lung function. Intravenous antibiotic treatment to reduce exacerbation symptoms is standard management practice. However, no prospective studies have identified an optimal antibiotic treatment duration and this lack of objective data has been identified as an area of concern and interest.</p> <p>Methods</p> <p>We have retrospectively analyzed pulmonary function response data (as forced expiratory volume in one second; FEV₁) from a previous blinded controlled CF exacerbation management study of intravenous ceftazidime/tobramycin and meropenem/tobramycin in which spirometry was conducted daily to assess the time course of pulmonary function response.</p> <p>Results</p> <p>Ninety-five patients in the study received antibiotics for at least 4 days and were included in our analyses. Patients received antibiotics for an average of 12.6 days (median = 13, SD = 3.2 days), with a range of 4 to 27 days. No significant differences were observed in mean or median treatment durations as functions of either treatment group or baseline lung disease stage. Average time from initiation of antibiotic treatment to highest observed FEV₁was 8.7 days (median = 10, SD = 4.0 days), with a range of zero to 19 days. Patients were treated an average of 3.9 days beyond the day of peak FEV₁(median = 3, SD = 3.8 days), with 89 patients (93.7%) experiencing their peak FEV₁improvement within 13 days. There were no differences in mean or median times to peak FEV₁as a function of treatment group, although the magnitude of FEV₁improvement differed between groups.</p> <p>Conclusions</p> <p>Our results suggest that antibiotic response to exacerbation as assessed by pulmonary function is essentially complete within 2 weeks of treatment initiation and relatively independent of the magnitude of pulmonary function response observed.</p

Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis

Introduction Improved nutrition is the major proven benefit of newborn screening programmes for cystic fibrosis (CF) and is associated with better clinical outcomes. It was hypothesised that early pulmonary inflammation and infection in infants with CF is associated with worse nutrition. Methods Weight, height and pulmonary inflammation and infection in bronchoalveolar lavage (BAL) were assessed shortly after diagnosis in infants with CF and again at 1, 2 and 3 years of age. Body mass index (BMI) was expressed as z-scores. Inflammatory cells and cytokines (interleukin 1b (IL-1b), IL-6, IL-8 and tumour necrosis factor a (TNFa)), free neutrophil elastase activity and myeloperoxidase were measured in BAL. Mixed effects modelling was used to assess longitudinal associations between pulmonary inflammation, pulmonary infection (Staphylococcus aureus and Pseudomonas aeruginosa) and BMI z-score after adjusting for potential confounding factors. Results Forty-two infants were studied (16 (38%) male; 39 (93%) pancreatic insufficient); 36 were diagnosed by newborn screening (at median age 4 weeks) and six by early clinical diagnosis (meconium ileus). Thirty-one (74%) received antistaphylococcal antibiotics. More than two-thirds were asymptomatic at each assessment. Mean BMI z-scores wer

Prescribing practices for intravenous aminoglycosides in UK cystic fibrosis clinics: a questionnaire survey

Background: Intravenous aminoglycoside antibiotics are widely used to treat pulmonary infection with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF). Over the last decade evidence has accumulated showing that the choice of aminoglycoside and the dosing regimen may help reduce adverse effects such as nephrotoxicity. Methods: We undertook an online survey to determine current practice in UK CF Centres. Results: We received a response from 35/48 (73%) centres. A once daily regimen was used in 30/35 (86%) centres. Around one third had stopped using gentamicin in the last 10 years. In most cases respondents reported changing practice in response to new evidence or evidence based guidelines. Obstacles to introducing evidence based practice were identified both at the level of the CF Centre and the hospital trust. Conclusions: A once daily aminoglycoside regimen is now used in the majority of UK CF Centres. Tobramycin is first line and many centres have stopped using gentamicin. Obstacles to evidence based practice remain in a minority of centres

Adherence with tobramycin inhaled solution and health care utilization

<p>Abstract</p> <p>Background</p> <p>Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization.</p> <p>Methods</p> <p>We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to <4 cycles, and high ≥ 4 cycles per year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories.</p> <p>Results</p> <p>Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768).</p> <p>Conclusions</p> <p>Use of TIS did not reflect recommended guidelines and may impact other health care utilization.</p

Indicators of pulmonary exacerbation in cystic fibrosis: A Delphi survey of patients and health professionals

Background: There is uncertainty about the most important indicators of pulmonary exacerbations in CF. Methods: Two parallel Delphi surveys in 13 CF centres (UK and Ireland). Delphi 1: 31 adults with CF, ≥ one exacerbation over 12 months. Delphi 2: 38 CF health professionals. Rounds 1 and 2 participants rated their level of agreement with statements relating to indicators of exacerbation; Round 3 participants rated the importance of statements which were subsequently placed in rank order. Results: Objective measurements were of higher importance to health professionals. Feelings of increased debility were rated most important by adults with CF. Conclusions: There were clear differences in perspectives between the two groups as to the most important indicators of an exacerbation. This highlights that CF health professionals should take more cognisance of specific signs and symptoms reported by adults with CF, especially since these may be a precursor to an exacerbation

The feasibility of online video calling to engage patients with cystic fibrosis in exercise training.

Introduction Physical activity, including structured exercise, is an essential component in the management of cystic fibrosis. The use of telehealth such as video-calling may be a useful method for the delivery of exercise and physical activity interventions, though the feasibility of this remains unknown. Methods Nine patients with cystic fibrosis (three female, six male, 30.9 ± 8.7 years) volunteered to participate. Participants completed an eight-week exercise training intervention conducted via Skype, using personalised exercises, with all sessions supervised by an exercise therapist. Feasibility was assessed by demand, implementation, practicality and acceptability. Changes in anthropometric, pulmonary, physical activity and quality of life variables were also assessed. Results Two male participants withdrew from the study, citing lack of available time. The remaining participants found use of Skype useful, with a mean satisfaction rating of 9/10, and three participants requesting to continue the sessions beyond the duration of the study. Mean compliance with sessions was 68%, with mean duration of sessions being 20 min. A total of 25% of calls suffered from technical issues such as video or audio lags. Anthropometric, pulmonary, physical activity and quality of life variables remained unchanged over the course of the study period. Discussion The use of Skype to deliver an exercise intervention to patients withcystic fibrosis was found to be technologically feasible, and acceptable among participants. Findings have implications for clinical practice and could allow care teams to engage patients remotely in exercise. Further research is required to assess the efficacy of this modality on increasing physical activity and associated health outcomes