A single centre service evaluation of patients' experiences participating in radiotherapy clinical trials during and post COVID-19 in Northern Ireland, UK.

INTRODUCTION: Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important role in the management and care of RT trial patients. The COVID-19 pandemic caused major disruption to RT trial delivery. Measures to mitigate COVID-19 risk continue to have an effect on patient contact and communication within cancer centres in the United Kingdom (UK). This study aimed to explore patient perspectives regarding their recent RT trial experience in Northern Ireland (NI), UK. METHODS: A single centre service evaluation was conducted in NI. Patients who were recruited into a RT clinical trial from January 2020 to January 2023 were invited to participate. Surveys were posted to 50 participants in April 2023. Quantitative and qualitative data was captured and analysed using descriptive statistics and Braun and Clarke's six-step thematic analysis framework respectively. Ethical approval was obtained through Ulster University and the NHS Trust. RESULTS: Forty-three of the 50 invited participants responded (86%). Forty-two respondents (79%) had a prostate cancer diagnosis. Forty-one (98%) participants indicated that CRRs were always approachable, polite and courteous and would recommend taking part in a RT trial to friends and family. Identified areas for improvement included aspects regarding consent and participant decision-making. CONCLUSION: This study suggests that despite the implemented measures to suspend research and mitigate COVID-19 risk, patients remained highly satisfied with the quality of care that they received through their participation in RT trials. IMPLICATIONS FOR PRACTICE: The results of this service evaluation will facilitate maintenance and improvement of patient focused delivery of cancer trials within the host centre. This study builds on evidence highlighting the importance of the CRR role and role development for radiographers.

Atmospheric implications of large C2-C5 alkane emissions from the U.S. oil and gas industry.

Emissions of C2-C5 alkanes from the U.S. oil and gas sector have changed rapidly over the last decade. We use a nested GEOS-Chem simulation driven by updated 2011NEI emissions with aircraft, surface and column observations to 1) examine spatial patterns in the emissions and observed atmospheric abundances of C2-C5 alkanes over the U.S., and 2) estimate the contribution of emissions from the U.S. oil and gas industry to these patterns. The oil and gas sector in the updated 2011NEI contributes over 80% of the total U.S. emissions of ethane (C2H6) and propane (C3H8), and emissions of these species are largest in the central U.S. Observed mixing ratios of C2-C5 alkanes show enhancements over the central U.S. below 2 km. A nested GEOS-Chem simulation underpredicts observed C3H8 mixing ratios in the boundary layer over several U.S. regions and the relative underprediction is not consistent, suggesting C3H8 emissions should receive more attention moving forward. Our decision to consider only C4-C5 alkane emissions as a single lumped species produces a geographic distribution similar to observations. Due to the increasing importance of oil and gas emissions in the U.S., we recommend continued support of existing long-term measurements of C2-C5 alkanes. We suggest additional monitoring of C2-C5 alkanes downwind of northeastern Colorado, Wyoming and western North Dakota to capture changes in these regions. The atmospheric chemistry modeling community should also evaluate whether chemical mechanisms that lump larger alkanes are sufficient to understand air quality issues in regions with large emissions of these species.

The development and deployment of integrated electronic care records in a regional adult and paediatric cystic fibrosis unit.

BACKGROUND: Electronic care records (ECRs) for cystic fibrosis (CF) provide a basis for accurate, reliable capture of clinical measures and interventions, and epidemiological trends, providing the basis for improved efficiency and patient safety. METHODS: A primary care system was modified for hospital use and clinical codes devised for all aspects of CF care. Performance and usability were assessed. RESULTS: Of a total of 620 patients 619 consented to their data being recorded in the system. Five hundred and twenty three new codes were created and embedded behind 60 new templates. Following introduction of ECR, completion of annual assessments increased from 43% to 92%, retrieval of drug costs rose significantly and time to correspondence with primary care fell from 34days to <2days. Staff satisfaction was high. CONCLUSION: The system is fully operational allowing the unit to function as a paperless service. Efficiencies of staffing activity, process management and cost retrievals are evident. Sharing of coding structures is important in future care.

The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation.

BACKGROUND: Respiratory viruses have become increasingly recognised as important agents in pulmonary exacerbations in infants and children with CF. The aim of this study was to determine the prevalence of respiratory viruses during acute pulmonary exacerbations in adults and compare the severity of these exacerbations with non-viral associated exacerbations. METHODS: This was a retrospective case control study. Viral throat swabs were taken from all patients presenting with an acute pulmonary exacerbation requiring intravenous antibiotic treatment over a 12 month period. RESULTS: There were 432 pulmonary exacerbations in 180 adults. A positive viral PCR in 42 exacerbations indicated a prevalence of 9.7%. The commonest virus isolated was rhinovirus (n = 29, 69%) with influenza A/H1N1 in seven patients (16.7%). Exacerbations associated with a positive viral PCR had a greater fall in lung function at presentation with higher levels of inflammatory markers. They received more days of intravenous antibiotics, showed less response to treatment and had a shorter time to next pulmonary exacerbation compared to matched controls. CONCLUSION: Viral associated pulmonary exacerbations in adults with CF are associated with more severe pulmonary involvement and respond less well to standard treatment.

Enteral tube feeding in adults with cystic fibrosis; patient choice and impact on long term outcomes.

BACKGROUND: Enteral tube feeding (ETF) has been evaluated in paediatric and mixed child and adult populations with cystic fibrosis, demonstrating positive outcomes from 6 months to 2 years post insertion. No studies have examined the longer term nutritional and clinical outcomes in an exclusively adult population with cystic fibrosis or compared the outcomes for those who meet standard criteria and opt to undertake or decline ETF. METHODS: Twenty three out of 380 patients attending the Leeds Regional Adult CF unit fulfilled the standard criteria for commencing ETF (CF Trust, 2002) between 2004 and 2008. Weight, BMI, FEV1, FVC, CFRD, and number of intravenous antibiotic treatment days were collected at 1 year pre baseline, at baseline, and at 1, 2, and 3 years post baseline for all these patients whether they accepted or declined ETF. RESULTS: Seventeen of the 23 patients agreed to accept a programme of ETF, two of whom died within the first year of ETF. In the remaining patients (n=15), weight increased by 19.5% from baseline (p<0.001), BMI increased to within the normal range and lung function stabilised. There was no reduction in the requirement for intravenous antibiotic treatment. The six patients who declined ETF had a decline in lung function and no weight gain. CONCLUSION: Supplemental enteral tube feeding improves clinical outcomes when administered over 3 years, resulting in significant weight gain, a normal BMI and stabilisation of lung function. It does not reduce intravenous antibiotic treatment days. In contrast those patients eligible for, but who declined ETF, showed a deterioration in lung function and a failure to gain weight and to achieve normal BMI status.

Patient indicators of a pulmonary exacerbation: preliminary reports from school aged children map onto those of adults.

BACKGROUND: Despite the importance of identifying and managing a pulmonary exacerbation, and its use as an outcome measure in interventions, there is no standardised definition in cystic fibrosis. In achieving standardised criteria it is important to identify patient-reported indicators. METHODS: Interviews were undertaken with 35 school aged children. They reported symptoms experienced during a pulmonary exacerbation in two ways: the first symptoms they become aware of, and how they recognised when they were improving. Interviews were taped, transcribed verbatim and the data analysed thematically. RESULTS: For many children, the onset of an exacerbation was characterised by 'cold' symptoms, tiredness, and changes in cough. For those with moderate or severe disease, sleep disruption, activity induced breathlessness, changes in mood, sputum volume and lack of appetite were common. When describing improvement children focused initially on activities they were now able to perform accompanied by improvements in tiredness and cough. Those with moderate or severe disease also reported improvements in sleep and mood, breathlessness, sputum volume and colour. CONCLUSIONS: Child-reported indicators of a pulmonary exacerbation tend to map onto those reported by adults. These results provide the rationale for the development of a single scale for school age children and adults that could be sensitive to progressive stages of CF disease.

A protective role for periostin and TGF-ß in IgE-mediated allergy and airway hyperresponsiveness.

BACKGROUND: The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-ß. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown. OBJECTIVE: To determine the effect of periostin deficiency on airway responses to inhaled allergen. METHODS: In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed. RESULTS: Surprisingly, compared with wild-type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-ß1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4(+) CD25(-) cells into CD25(+) , Foxp3(+) T cells in vitro in a TGF-ß dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-ß-induced T regulatory cell differentiation.

Guideline on the design and conduct of cystic fibrosis clinical trials: the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN).

We describe the rationale for disease specific research networks in general as well as the aims and function of the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) specifically. The ECFS-CTN was founded in 2009 with the aim of improving the quality and quantity of clinical research in the area of cystic fibrosis (CF) in Europe. A network of 18 clinical trial sites in 8 European countries was established according to uniform state-of-the-art quality criteria. To support the ECFS-CTN in the acquisition, planning and conduct of clinical trials, the network is equipped with a coordinating centre, steering and executive committees, and committees for protocol review, standardization, training and networking as well as a data safety monitoring board. A strong partnership with European CF patient parent organizations aims to increase awareness of the need for efficient clinical research and the participation of patients in clinical trials.

Chronic Pseudomonas aeruginosa infection definition: EuroCareCF Working Group report.

Chronic pulmonary infection with P. aeruginosa develops in most patients with cystic fibrosis (CF); by adulthood 80% of patients are infected and chronic P. aeruginosa infection is the primary cause of increased morbidity and mortality in CF. Chronic infection is preceded by an intermittent stage of infection. The initial stage is characteristically followed by the gradual emergence of mucoid variants of the colonizing strains and a rise in anti-Pseudomonas antibodies. In addition to optimizing existing therapeutic strategies, effective new agents need to be identified. Studies in patients with CF are particularly challenging: the progressive nature of the disease and the wide variation in severity influence considerably the outcome of drug testing. A validated, universally accepted, and clinically useful classification of patients infected with P. aeruginosa, particularly those chronically infected, is needed that can be used as both a criterion for patient selection for clinical trials and as a study endpoint.

Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials.

Pulmonary exacerbations represent a key outcome variable in clinical trials of cystic fibrosis (CF). As there is variation in the trigger for use of intravenous antibiotics compared to the use of oral antibiotics or new nebulised therapy for treatment of exacerbations, the consensus view is that use of intravenous antibiotics cannot be regarded as the key defining character for an exacerbation on its own. The consensus view is that the clinical need for additional treatment as indicated by a recent change in clinical parameters provides the best definition of an exacerbation. Which parameters to include as well as the problems associated with the use of scoring systems and symptom clusters are being discussed.

Rapid desensitization for non-immediate reactions in patients with cystic fibrosis.

Non-immediate hypersensitivity reactions to antibiotics in patients with CF represent a real-life challenge for clinicians. Desensitization is often performed in patients who have exhausted all therapeutic options. Whilst desensitization is an established procedure for immediate reactions we assessed the outcomes and safety of desensitization for non-immediate reactions. We retrospectively reviewed 275 desensitization procedures in 42 patients with a range of non-immediate reactions to six commonly used antibiotics. Desensitization was performed using a 7-step rapid intravenous protocol on a normal medical ward. 250 (91%) of overall desensitization procedures were successful; however, this figure incorporates certain individuals having multiple successful procedures. Individual patient success ranged from 55% with tazocin through to 88% with tobramycin. In the 25 patients who failed desensitization the reactions were mild and the majority occurred within 48 h of starting treatment. Prophylactic anti-histamines and steroids did not reduce the risk of reaction. Whilst the mechanisms remain uncertain we can confirm that rapid desensitization is a safe and effective way of re-introducing an antibiotic to a patient with a non-immediate reaction.

Cystic fibrosis co-existing with trisomy 21.

Previous reports of children with co-existence of cystic fibrosis and full trisomy 21 suggest a very poor prognosis, with the majority of cases dying in infancy and the oldest reported survivor being 6 years of age. We report the case of a young man with genetically confirmed trisomy 21 and homozygous for the F508del cystic fibrosis mutation. Despite the diagnosis of cystic fibrosis being delayed until the age of 2 years he has transitioned to adult services and is now 25 years of age. Currently he has poor lung function and a continuous ambulatory oxygen requirement.

Serum tobramycin levels following delivery of tobramycin (Tobi) via eFlow advanced nebuliser in children with cystic fibrosis.

BACKGROUND: Safety and toxicity data for nebulised tobramycin are mainly derived from use of the Pari LC Plus nebuliser, yet many centres are now using advanced nebulisers, such as the eFlow. METHODS: Ten children (ages 2-16years) receiving 300mg TOBI via eFlow for clinical reasons participated. Serum tobramycin levels were obtained 1h post nebulisation. Nine provided samples for urinary NAG, and 10 underwent audiology. RESULTS: Tobramycin levels were >1mg/L in 3 children (maximum 3.8, 2 children aged 2years). Urine NAG/creatinine levels were raised (>0.94micromol/min/mmol) in 5 children, 1 of these had a tobramycin level of >1mg/L. One patient had high frequency hearing loss. CONCLUSION: Serum tobramycin levels over 1mg/L can occur 1h post 300mg TOBI delivered by eFlow. Raised urinary NAG levels suggest that some children may have some associated early renal toxicity.

Isolation of the fungus Geosmithia argillacea in sputum of people with cystic fibrosis.

We report the repeated isolation of the fungus Geosmithia argillacea from sputum samples of people with cystic fibrosis. Identification was based on morphology and DNA sequence analysis. Isolation of G. argillacea did not appear to be associated with clinical deterioration. The pathogenic potential of G. argillacea is discussed.

An aerobiological model of aerosol survival of different strains of Pseudomonas aeruginosa isolated from people with cystic fibrosis.

Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detected up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

What defines a pulmonary exacerbation? The perceptions of adults with cystic fibrosis.

BACKGROUND: There is no standardised definition of a pulmonary exacerbation in cystic fibrosis (CF). In attempting to achieve standardised criteria it is important to identify patient-reported indicators. METHODS: Interviews were undertaken with 47 adults with CF. Participants were asked to report symptoms experienced during a pulmonary exacerbation in two ways: the first symptoms they become aware of, and how they subsequently recognised when they were improving. RESULTS: A range of systemic and respiratory symptoms were reported. Their relative importance varied by severity of disease. The severity and subsequent improvement of an exacerbation was often described as limitations on their activities. CONCLUSION: These preliminary data suggest that patient-reported indicators of a pulmonary exacerbation may not be the same for all adults with CF. Whether different indicators are associated with specific demographic or clinical variables remains to be evaluated.

Acute Burkholderia cenocepacia pyomyositis in a patient with cystic fibrosis.

INTRODUCTION: Extra-pulmonary complications of Burkholderia cepacia complex (Bcc) infection in patients with cystic fibrosis are unusual. To the best of the authors' knowledge no case of pyomyositis secondary to Bcc infection has been reported previously. CASE PRESENTATION: We report a case of pyomyositis of the forearm caused by Bcc infection in a patient with CF. We also briefly discuss the management of pyomyositis. CONCLUSION: Pyomyositis is a potential extra-pulmonary complication of Bcc infection in patients with CF. A high index of clinical suspicion is required to make a prompt diagnosis. Final diagnosis may need MRI. An early diagnosis, aggressive medical therapy, multidisciplinary care and timely surgical intervention are all essential for proper management of this condition.

Nutritional decline in cystic fibrosis related diabetes: the effect of intensive nutritional intervention.

BACKGROUND: Reports indicate that nutritional and respiratory decline occur up to four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim was to establish whether intensive nutritional intervention prevents pre-diabetic nutritional decline in an adult population with CFRD. METHODS: 48 adult patients with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen status. Nutritional and other clinical indices were recorded at annual intervals from six years before until two years after diagnosis. Data were also analysed to examine the impact of early and late acquisition of CFRD. RESULTS: No important differences in weight, height, body mass index (BMI), lung function or intravenous treatment were found between groups in the six years prior to diagnosis, nor any significant deviation over time. In those who developed diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF Controls), OR 4.0, CI 1.3 to 16.4, p=0.01]. Age at onset of CFRD played a significant role in determining the pre-diabetic clinical course. Younger diabetics with continued growth at study onset (n=17) had a lower BMI from 2 years prior to diagnosis compared to controls [BMI 18.9 kg/m(2) (CFRD) v 20.8 kg/m(2) (CF Controls), diff=1.9, CI -0.1 to 3.7 p=0.04]. The BMI of older diabetics (completed growth at study onset) was equal to that of controls throughout. CONCLUSION: Pre-diabetic nutritional decline is not inevitable in adults with CFRD, but is influenced by age of onset. In the group overall, those with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite intensive nutritional intervention, patients who continue to grow throughout the pre-diabetic years, show a level of nutritional decline absent in older adults.