A Quality Improvement Project Determining if Dietitian Input with the UHS Lung Oncology Team Improved Patient Outcomes

Introduction: Unintentional weight loss is common in lung cancer, with 40-60% of patients presenting with this at diagnosis. Weight loss and depleted nutritional status have been identified as negative prognostic variables for survival and directly impact the effectiveness of cancer treatments. The Lung Oncology team at the University Hospital Southampton (UHS) received external funding from Bionical Solutions and AstraZeneca for a part time oncology Dietitian to join the team in treating this patient group. The aim was to determine if specialist Dietitian input improves patients’ nutritional outcomes in those diagnosed with Stage III Non-Small Cell Lung Carcinomas (NSCLC) undergoing radical treatment. Methods: Over 12 months (February 2021-February 2022) all patients with stage III NSCLC received specialist Dietitian input during their radiotherapy treatment. Non-patient identifiable data was collected, which included;whether patients were enterally fed, admission rates and reason, and their weights at the start, middle, end and 2 weeks post radiotherapy. This data was compared to previously collected data in 2018 with the same patient group. No ethical approval was required. Results: A total of 50 patient data sets and 11 feedback questionnaires were collected over 11 months. Between the start and end of radiotherapy, patients experienced;2.1% overall average weight loss, 64% experienced <3.0% unintentional weight loss and 0% experienced >9.6% unintentional weight loss. In 2021 patients reached their lowest weight earlier at 70% of their way through radiotherapy compared with 86% in 2018. Patients maximum unintentional weight loss was 3.2% in 2021 compared with 4.4% in 2018. This is likely due to closer monitoring and dietitian input in 2021. Admission rates were higher in 2021 (n=13, 26%) compared to 2018 (n=5, 18.5%). However, this may be due to changes to patients’ radiotherapy treatment plans in 2021 due to the covid pandemic, resulting in more intense treatments. Patients requiring nasogastric (NGT) feeding increased from 0 in 2018 to 6 in 2021. This is likely due to increased awareness of the importance of nutritional support attributable to dietetic involvement in the multidisciplinary team. All patients who completed the feedback questionnaire found dietetic consultations useful and were able to follow most, or all dietary advice. 91% felt well supported during their treatment with dietetic input. Final Outcomes: Patients experienced reduced weight loss during treatment with Dietitian input compared to 2018 data where there was minimal dietetic input. Increased number of patients required NGTs compared to 2018, therefore Dietitian input is required in this area of oncology. Most patients felt well supported receiving dietetic input during treatment. Increased admission rates compared to 2018, however more nutrition support related admissions in 2021. Conclusions: Overall, patients lost less weight during treatment with Dietitian involvement in their care which is a positive factor in the prognostic outcomes. In addition, most patients felt seeing a Dietitian during treatment improved their experience and felt well supported. The final outcomes support the British Dietetic Associations’ recommendation that there is a dedicated dietetic service for lung cancer patients’, and they are seen by a Dietitian during their treatment. Keywords: Dietitian involvement, Reduced weight loss, Improved patient outcomes

Evolution of dry powder inhaled colistimethate sodium (Colobreathe®) in a large adult cystic fibrosis centre

Objectives: Colobreathe® is a dry powder formulation of colistimethate sodium developed to reduce treatment burden for people with cystic fibrosis. In our centre initial experience revealed 45% discontinued this therapy within 12 months, of which 83% were due to tolerance or device issues. Capsuleswere reformulated in 2017 to address some of these issues. We aimed to assess the prescription rates of Colobreathe® over 3 time periods to assess whether prescription practices and tolerance changed. Methods: A retrospective review of antibiotic challenges in the one-year periods from Dec 2013, 2016 and 2020 was conducted. Key end points included tolerance of test dose and continued use at 1 and 3 months. The proportion of antibiotic challenges that were Colobreathe® at each time point was compared. Results: Therewas a significant difference in the proportion of all antibiotic challenges whichwere for Colobreathe® across the 3 periods (2013–65/186 (35%), 2016–8/136 (6%), 2020–22/55 (40%), p < 0.001). The majority of patients at all 3 time points had previously nebulised colistimethate sodium (98%, 88% and 100%, respectively). All patients had a successful test dose during each time period. Therewas no difference in the proportion of patients who commenced long-term prescription following a 1-month review at the 3 time periods (75%, 75% and 73% respectively, p = 0.97). Of those who received a long-term prescription, continuation rates were similar at 3 months (82%, 100% and 93%, respectively). Conclusions: There was a marked reduction in inhaled antibiotic challenges in 2020, likely due to COVID. There was a significant change in prescription of Colobreathe® over the 3 time frames. Colobreathe®waswell tolerated at initial challenge and continuation rates after a month appear to be consistent. A number of factors likely influenced prescription practices, including early experience and potentially changing airway physiology following CFTR modulation introduction.

Microbiological surveillance in cystic fibrosis – an emerging multifactorial challenge

Objectives: Accurate identification of airway pathogens with appropriate eradication and suppressive therapies is associated with improved health outcomes in cystic fibrosis (CF). From 2020, 2 key factors may have influenced the ability to carry out this monitoring effectively;1. the COVID- 19 pandemic accelerated a transition to ‘virtual’ clinic visits and 2. the introduction of ELX/TEZ/IVA. Methods:We retrospectively analysed out-patient clinic attendance in the month of November for the years 2017–2021 and microbiological samples received from adults with CF in the regional microbiology department. Results: The total number of microbiological samples reduced in 2020 and 2021 (Table 1). In 2017, 211 samples were generated from 261 clinic visits (80.8%). For subsequent years this was 80.0%, 71.0%, 51.2% and 72.2%, respectively. The proportion of cough swabs significantly increased in 2021, (p < 0.001). In 20216 postal sampleswere provided, indicating that yield of a sample from a virtual appointment was at most 8.3%. Table 1. Overview of microbiological samples and clinic visits November 2017–2021 (Table Presented)Conclusions: There has been a marked reduction in microbiological samples in the years 2020 and 2021 despite relative preservation of total clinic appointments. This appears to be partly due to an increase in virtual clinic attendance without adequate remote sampling. The disproportionate increase in cough swabs in 2021 can be attributed to ELX/TEZ/IVA availability resulting in decreased sputum burden. This work identifies challenges in monitoring patients established on highly effective modulator therapy in new clinic models

Effects of Sirolimus on Anti-Spike Protein Antibody Levels Following Vaccination of Patients with Lymphangioleiomyomatosis

Rationale: Lymphangioleiomyomatosis (LAM) is a rare multisystem disease, affecting mostly women, and associated with cystic lung destruction, abdominal tumors and lymphatic involvement. LAM occurs in a sporadic form (S-LAM) and a component of an autosomal-dominant, neurocutaneous syndrome, tuberous sclerosis complex (TSC). Lung destruction results from the proliferation of cancer-like LAM cells, which have mutations in one of the two TSC genes, resulting in activation of the mechanistic target of rapamycin (mTOR) pathway that drives increased cell growth and size. The mTOR inhibitor, rapamycin (sirolimus), stabilizes disease progression and is FDA-approved for treatment of LAM. COVID-19 may pose a greater risk to patients with lung disease and to those who are taking immunosuppressive medications, such as sirolimus. The impact of sirolimus on response to COVID-19 vaccination in patients with LAM is not well understood. Objectives: We conducted a multicenter observational study to determine if LAM patients treated with or without sirolimus, respond to the Pfizer and Moderna vaccines by production of antibodies against the SARS-CoV-2 Spike protein. Methods: Anti-Spike protein antibodies were measured using the Cobas 6000 Analyzer to determine response to vaccination. Anti-nucleocapsid antibodies, measured to assess infection, were only positive in one patient. Results: Serology was determined on 30 women with a confirmed diagnosis of LAM. The median age of our cohort was 53.5 years (range 37 -76years). Thirty-one patients were treated with sirolimus, and 7 patients were not on sirolimus. Of the 23 patients treated with sirolimus, 12 received the Moderna vaccine and 11 received the Pfizer vaccine. Of the patients not taking sirolimus, 4 received the Moderna vaccine and 3 received the Pfizer vaccine. Serology data were collected 94 days, +/-57 days after the second vaccination. Anti-Spike antibody levels, assessed on 2 patients following a third dose of the Pfizer vaccine, showed an increased antibody response. A widespread serological response was observed. The median anti-Spike antibody level was 1033U/ml in LAM patients on sirolimus, and was comparable to the level of 1077U/ml units in LAM patients not on sirolimus. Two LAM patients treated with sirolimus did not have detectable antibody titers following the Pfizer vaccination. Conclusions: Majority of the LAM patients on sirolimus mount a response to the COVID-19 vaccines at levels that are comparable to those of LAM patients not on sirolimus. Those patients taking sirolimus who have low or no serological response after two doses of mRNA vaccines may respond to a 3rd vaccination.

Increasing access to cognitive–behavioural therapy for patients with psychosis by evaluating the feasibility of a randomised controlled trial of brief, targeted cognitive–behavioural therapy for distressing voices delivered by assistant psychologists: the GiVE2 trial

Background Cognitive-behavioural therapy (CBT) is recommended for all patients with psychosis, but is offered to only a minority. This is attributable, in part, to the resource-intensive nature of CBT for psychosis. Responses have included the development of CBT for psychosis in brief and targeted formats, and its delivery by briefly trained therapists. This study explored a combination of these responses by investigating a brief, CBT-informed intervention targeted at distressing voices (the GiVE intervention) administered by a briefly trained workforce of assistant psychologists. Aims To explore the feasibility of conducting a randomised controlled trial to evaluate the clinical and cost-effectiveness of the GiVE intervention when delivered by assistant psychologists to patients with psychosis. Method This was a three-arm, feasibility, randomised controlled trial comparing the GiVE intervention, a supportive counselling intervention and treatment as usual, recruiting across two sites, with 1:1:1 allocation and blind post-treatment and follow-up assessments. Results Feasibility outcomes were favourable with regard to the recruitment and retention of participants and the adherence of assistant psychologists to therapy and supervision protocols. For the candidate primary outcomes, estimated effects were in favour of GiVE compared with supportive counselling and treatment as usual at post-treatment. At follow-up, estimated effects were in favour of supportive counselling compared with GiVE and treatment as usual, and GiVE compared with treatment as usual. Conclusions A definitive trial of the GiVE intervention, delivered by assistant psychologists, is feasible. Adaptations to the GiVE intervention and the design of any future trials may be necessary.

Implementation of a cystic fibrosis-specific virtual pulmonary rehab program

Objectives: Pulmonary rehabilitation (PR) is a key management strategy for people with chronic respiratory disease (BTS Guidelines, 2013). However, in cystic fibrosis (CF), despite the benefits of regular exercise being well documented (Radtke et al, 2017), there is limited uptake. Concerns regarding infection control, lack of CF education, and participating with an older age group may be contributing factors. A pilot study demonstrated good clinical benefits to participants in a CF-specific PR program (Bowen et al, 2019) and current CF Foundation guidelines advise that patients with advanced lung disease should be offered such programs (Kapnadak et al, 2020). We aimed to establish a CF-specific PR program at Manchester Adult CF Centre, as part of the CF Trust Physiotherapy Fellowship service development project. Method: Patients completed a bespoke 8-week program, comprised of biweekly 1:1 virtual exercise sessions. Each session included aerobic and strength training linked to patient goals and was progressed according to reported Borg and muscle fatigue scores. A 1-minute sit to stand test (STS) was performed pre-program and repeated at the end. Enrolled patients had access to an online educational website, which covered a range of CF-specific topics. Patient feedback was collected at the end of the program. Results: [Table Preseteed] Patient feedback indicated that 100% of participants felt their goals had been met and that they would recommend the program to other people with CF (PWCF). Conclusion: Some of the program design was in accordance with what was achievable during the COVID-19 pandemic. Alteration of outcome measures may be required as clinical services normalise. Although a small sample, initial feedback has been extremely positive, indicating that a virtual PR approach may be suitable in engaging PWCF in physical activity. Further data is needed to demonstrate if the program is of clinical benefit and to identify the optimum time-frame of the intervention.

Has the COVID-19 pandemic affected medication adherence to inhaled nebulised therapy for patients at a large adult cystic fibrosis centre?

Objectives: The COVID-19 pandemic has led to immense challenges for healthcare systems worldwide. People with cystic fibrosis (CF) were included in the clinically extremely vulnerable group for complications of coronavirus by the UK government and advised to shield during a national lockdown. Data suggests that pandemic-related restrictions have been linked to a reduction in pulmonary exacerbation events (PEx). We sought to explore whether an increase in medicine possession ratio and potentially adherence may be a factor in this finding. Methods: 50 patients who received medication through a homecare delivery system at a single large adult centre were randomly selected. Data from 12 months ‘pre-lockdown’ was compared to data for 9 months following start of shielding in March 2020. MPR was calculated and capped at 100%. Medications that were started or stopped during the pandemic were not included. Wilcoxon signed rank test was used to compare pre- and post-values. Results: 91 prescription medications were valid for analysis (45 nebulised antibiotics, 34 mucolytics and 12 CFTR modulators). MPR increased for 41 prescriptions (45.1%), decreased for 21 medications (23.1%) and remained unchanged for 29 medications (31.9%). Median MPR increased from 83% [57–100%] to 89% [66–100%], p = 0.037. MPR for nebulised antibiotics significantly increased (median 75% [54–100%] vs 89% [61–100%], p = 0.027). Median MPR for CFTR modulators was 100% throughout and did not change for mucolytics (75% [42–100%] vs 78% [53–100%], p = 0.419). Conclusion: We report a significant change in medication possession in adults with CF during the coronavirus pandemic in the UK. It is unclear whether this change translated to an increase in adherence but may be one factor in the reported decrease in PEx events described during this time. It is notable that increases were largely driven by inhaled antibiotics and this may represent a concerted effort to achieve maximal protection from infection.

Determining the effect of postage on the recovery of cystic fibrosis pathogens from respiratory samples

Objectives: Regular microbiological surveillance of sputum to detect pathogens is a cornerstone of CF care. In many CF centres, patients may be required to post samples to the clinic, due to difficulty producing sputum on demand or for enhanced surveillance outside of routine clinics. This is increasingly important in light of the COVID-19 pandemic where many CF patients are unable to come into clinic due to shielding. However, these samples may experience fluctuations in temperature and hence altering the microbiology of a sample before processing. Here we report the impact of posting on the detection of common CF pathogens, and hence reliability of the culture reports. Methods: Ninety-two sputum samples were collected from 72 adults with CF. Samples were weighed, mixed and split. One part was sent immediately to the microbiology lab and another was posted back to the lab through the post. Postal samples were returned and processed after a mean of 5 days. Aliquots at each stage were stored at -80oC for subsequent PCR-based analysis. In this study, we compared clinical microbiology reporting for the paired-sputum samples. Results: Overall prevalence for all organisms present in >10% of samples is shown in the Table. Sensitivity of the different sample types to each species is given as percent positive samples compared to all positive samples. Postal samples detected all Burkholderia cepacia complex, 92% of P. aeruginosa (versus 93% for the clinic sample) and 74% of Aspergillus spp. (versus 78% for the clinic sample). All other organisms were detected in postal samples at the same or higher rate as clinic samples. Conclusions: Despite being in the post for a median of 5 days, there was little difference in the culture-based microbiology results. Posting sputum samples therefore does not appear to reduce the identification of key CF microorganisms, which remain viable for several days after collection. PCR-based analyses of these same samples is ongoing.