A novel cystic fibrosis-pregnancy service: Two-year review after introduction of elexacaftor/tezacaftor/ivacaftor

Background: As a quality service improvement response since elexacaftor/ tezacaftor/ivacaftor (ELX/TEZ/IVA) became available and the yearly average number of cystic fibrosis (CF) pregnancies (n = 7 pre-2020, n = 33 in 2021) increased significantly at an adult CF center (~600 people with CF), a monthly multidisciplinary CF-maternal health virtual clinic was established with antenatal virtual CF exercise classes dedicated to providing adaptive, specialist support to this cohort, aswell as outreach guidance and education to local obstetric teams. Method(s): This was a single-center retrospective reviewof Royal Brompton Hospital CF-Maternal Health multidisciplinary team clinic records and a patient survey from March 2020 to March 2022. Result(s): Of 47 pregnancies in 41 women (median age 30;) eligible for ELX/ TEZ/IVA at start of pregnancy, 40% (n = 19) were unplanned, and 19% (n = 9) used assisted conception. Three women with a history of infertility conceived naturally, having required assisted conception for previous pregnancies, and five women had multiple pregnancies during the study period. ELX/TEZ/IVA was continued in 60% (n = 28), delayed in 28% (n = 13), and stopped in 13% (n = 6) of pregnancies through maternal choice and careful clinical counselling. Pre-pregnancy pulmonary status was poorer in women who continued than in those who delayed or stopped (Table 1). Of those who stopped, 85% (n = 5) restarted because of pulmonary deterioration by the third trimester. Prenatal CF complications included at least one episode of minor hemoptysis in 21% (n = 9/41) of women, at least one infective exacerbation in 55% of pregnancies (n = 26/47), and noninvasive ventilation in one woman. Other pregnancy-associated complications included one case of ovarian hyperstimulation syndrome, one case of sub-segmental pulmonary embolism, and two cases of pregnancy-induced hypertension. Excluding 10 first trimester terminations, 10 current pregnancies, and one patient relocation, obstetric outcomes available for 26 pregnancies confirmed a live birth rate of 85% (n = 22/26) and a 15% first-trimester miscarriage rate (n = 4). Obstetric complications included preterm delivery rate of 23% (n = 6/26), including two cases of COVID infection resulting in two neonatal intensive care unit admissions, one case of endometritis after cesarean section, and a fourthdegree perineal tear. There were no ectopic pregnancies, maternal or neonatal deaths, or reports of infant cataracts or congenital malformations. Median gestational age was 37/40 weeks (range 29-40). Mode of delivery was via cesarean section in 45% (n = 10/22, of which twowere emergency) and vaginal in 55% (n = 12/22), of which 83% (n = 10/12) were via induction of labor for diabetes (CF or gestational) indication. Deliveries were supported and occurred equally at local obstetric units and in tertiarycare obstetric hospital settings (50%, n = 11/22). Patient-experience survey responses cited high levels of confidence in health optimization and prioritization during pregnancy and praised excellent inter-health care provider communication and peer-to-peer emotional support provided among expectant mothers in the virtual prenatal exercise groups. Table 1. Baseline demographic and clinical characteristics of elexacaftor/tezacaftor/ivacaftoreligible expectant mothers according to therapeutic decision (Table Presented) Conclusion(s): In the absence of clinical trial safety data, the novel approach of a dedicated CF-maternal health multidisciplinary team clinic with local obstetric outreach support has ensured regular specialist clinical and emotional peer-to-peer support for this cohort of women eligible for ELX/ TEZ/IVA to ensure optimal outcomes and experiences of their pregnancies, where appropriate, close to home.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Remote respiratory sampling and unusual Pseudomonas growths in adults with cystic fibrosis: Is there a link?

P71 Table 1 2019 cohort n=20 2021 cohort n=46 p value* Remote samples 0 (0) 31 (67.4) - Age – years, mean (SD) 36.90 (9.65) 36.98 (13.25) NS Sex – Female n (%) 14 (70) 28 (60.9) NS F508del/F508del mutation n (%) 6 (30) 19 (41) NS Maintenance inhaled antibiotic therapy n (%) 13 (65) 27 (58.7) NS CFTR modulator therapy n (%) 7 (35) 40 (87) <0.001 Unusual Pseudomonas species (n) Pseudomonas putida (4)Pseudomonas fluorescens (4)Pseudomonas rhodesiae (2)Pseudomonas synxantha (2)Other (8) Pseudomonas putida (12)Pseudomonas fluorescens (11)PseudomonasMonteilii (4)Pseudomonas libanensis (3)Pseudomonas proteolytica (3)Other (13) <0.001(See text) Clinical intervention n (%)Patient symptomatic and new therapy prescribedPatient well and no action takenPatient well and new therapy prescribedNew long-term prophylaxis initiatedIncomplete data 5 (25)3 (15)7 (35)0 (0)5 (25) 10 (21.7%)15 (32.6)8 (17.4)4 (8.7)13 (28.2) NSNSNSNSNS Regrowth of unusual Pseudomonas species on subsequent samples n (%) 1 (5) 2 (4.3) NS *Tests performed = Mann Whitney Test for processing time,t test for mean age, Chi square for ratios (Yates’ correction where data size less than 5). NS=not significantConclusionDespite nearly 50% reduction in respiratory sampling (likely a result of Covid19 and the introduction of the CFTR modulator ‘Kaftrio’), our study demonstrated more than a 2-fold increase in growths of unusual Pseudomonas species in 2021. We found an association with longer processing times, which were more common with remote sampling. Mechanisms underlying this, such as contamination, require further investigation. Importantly, our data suggest that growths may be transient and treatment not always indicated. Our results suggest caution should be exercised when interpreting samples with long processing times, but further prospective studies are required.

Implementing tablet-based ototoxicity screening in adults with cystic fibrosis

Introduction: People with cystic fibrosis (PwCF) regularly receive antibiotics for treatment of lung infections, which can include intravenous aminoglycosides (IVAG) resulting in potential ototoxicity. Sound booth audiometry is costly, time-consuming, and requires further outpatient visits and audiologists. A quality improvement project delivered by specialist pharmacists to implement a tablet audiometry ototoxicity monitoring programme was launched in PwCF receiving IVAG therapy. Objectives: To implement a tablet ototoxicity screening programme in adults with CF. Methods: PwCF receiving IVAG completed tablet-based audiometry (0.25– 16 kHz) (Shoebox MD) alongside validated ototoxicity questionnaires at the beginning and end of treatment. Following a clinical pathway, clinicians undertook shared decision-making processes regarding continuation of AG if abnormality was detected, alongside referral for sound-booth audiometry. Results: Data were collected from April–Dec 2021. Thirty-eight patients (median [IQR] age 28.5 ([15.5] years;mean [SD] ppFEV1 62.3 [26.5]) were screenedwhowere on IVAG. Fifteen patients (39%)were referred for formal audiometry due to abnormal baseline results, of which 5 had symptoms of hearing loss identified through questionnaires. 3% (1/38) stopped AG therapy due to identified potential ototoxic risk. Twenty-two patients received screening at beginning and end of IVAG therapy: significant ototoxic effects were seen in 2 of these patients (9%);20 patients (91%) had no significant change from baseline audiometry. Conclusions: We present pilot results to show feasibility of tablet-based ototoxicity screening. More IV courses were completed at home than anticipated (due to Covid19) limiting end of IV testing. Further 3-month testing is planned to detect potential delayed ototoxic change. Nevertheless, our results show tablet audiometry to be an effective and practical screening tool used by non-audiologists for accurate, early identification of hearing loss and ototoxicity.

116 Implementing a digital clinic review service in a national lockdown

Background: In the United Kingdom, the national COVID lockdown was legally enforced on the March 26, 2020. As a result, people with CF were classed as clinically extremely vulnerable and were advised to shield at home. In this hospital outpatient clinics were halted;however, the adultCF service had started using the NuvoAir Home remote monitoring solution with 162 patients already established with home spirometry, video consultations, and data sharing with the clinical team. Our aim was to evaluate our experience of replacing all face-to-face clinical reviews with video consultations supported by self-monitoring, at pace and scale during the COVID-19 pandemic. Methods:FromApril2020, 2 members of the CF MDT started contacting all patients not on the NuvoAir Home platform (n=418)to discuss the virtual service and askiftheywere interested in joining. Onconsent, patients were given access to the platform, taught how to download the app, and told how to set up the spirometers (which were posted to them) and how often to perform spirometry. A dedicated email address and telephone line were set up for technical support. Patients were sent an SMS reminder via the platform to complete their spirometry prior to a video clinic appointment but also encouraged to monitor their spirometry at other times to build a personalized trend. Results: To date (March 31, 2021) 558 patients have been onboarded to the remote monitoring program. Pre-pandemic (month of March 2020), 417 spirometry sessions were recorded and 82 video consultations performed. Midway through (in the month of August 2020) n = 539 spirometry sessions had been recorded, with n = 325 video consultations, and in the month of March 2021, n = 609 spirometry sessions and n = 438 video consultations were recorded. Twenty-eight percent of spirometry sessions were unrelated to a video clinic. Total spirometry sessions for April 1, 2020, through March 31, 2021, were n = 6,969. Using ATS criteria n = 5,264 (76%) sessions were graded acceptable (A-D), and n = 1,705 (24%) sessions graded E+F. Reasons patients performed extra spirometry included: checking the effectiveness of treatment change, pre-clinic consultation, feeling unwell, and recovery after an exacerbation. Conclusion: We now have 558 adults with CF onboarded to the virtual platform. Although patients are reminded to do spirometry before an appointment, many also choose to self-monitor their health between clinic consultations. Clinician confidence in self-monitoring is supported by the grading of spirometry sessions using ATS criteria;the best is selected by the software. The platform is now also widely used by the CF MDT for one-to-one or small group support and education sessions. There are a small number of patients (n = 5) who do not wish to use this service for various reasons, including reluctance to change the status quo, hearing impairment, and access to technology. Alternatives are in place for those individuals. Moving the service forward we have added weighing scales and activity trackers, and organized postal, self-administered finger prick blood tests (e.g., liver function tests) and sputum samples. Patients have reported high satisfaction with the service as they are gaining more time for work, education, and family life, as well as saving money. However, they have also reported missing face-to-face contact. We are therefore working closely with patients to devise a hybrid virtual/face-to-face service for the future.

Managing metabolic issues: Evaluation of a short-term comparative implementation project introducing a dietitian to an HIV service

Background: Persons living with HIV (PLWH) face a number of nutritional issues including dyslipidaemia, non-alcoholic steatohepatitis, diabetes, and obesity that can be attributed to HIV infection/medications. Poor management of these complications can reduce quality of life and increase health costs. We implemented a dietetic service within our HIV clinic for 6 months and evaluated the outcomes. Method: Twice weekly dietetic clinics were established. Eligible patients were offered group, face-to- face or telephone consultations. Medical records and our database were used to obtain demographics, treatments and co-morbidities. Cholesterol markers were measured along with weight, height, and body mass index (BMI). Results: 84 (total clinic cohort 3308) PLWH were referred. 61/84 attended their appointment;36 selected face-to- face, 25 selected telephone for their first appointment. Patients did not opt for group sessions. DNA rates were similar in both groups (31% and 28% respectively). In attendees median age was 54y, 59% male, 34% Black African origin. Eighty-five per cent of patients were diagnosed before 2010. 95.1% had undetectable viral load and 82% had CD4 count ≥400 cells/mm3 at most recent consultation. 82% of patients were on ≥1 NRTI and 36% were on a PI. Major reason for referral (40/61) was weight management;other reasons included type II diabetes management (7/61), irritable bowel syndrome (IBS) (8/61) and poor appetite (5/61). 15% of patients had an HbA1c of ≥48mmol/L and 11% of patients were pre-diabetic (HbA1c 42-48 mmol/L), 50% had TChol>5.0mmol/L, 11% had TChol:HDL ratio >5 and 38% had a LDL level >3mmol/L. Of the patients with available BMI, 32% (13/41) were classed as overweight and 56% (23/41) were classed as obese. 18% of attendees were ≥55y female and post-menopause could have been a contributing factor for weight gain. 28% of telephone and 31% of face-to- face consultations were scheduled for at least one follow up. Conclusion: PLWH are at risk of complex metabolic conditions, which can be difficult to manage. A dietician was able to provide expert and personalised advice to our patients and helped to empower them to take care of their own health. Patients engaged with both telephone and face-to- face consultations. Due to the short-term funding available in addition to the COVID-19 pandemic, longer term impact could not be evaluated.

SARS-CoV-2 driving rapid change in cystic fibrosis services: the role of the clinical nurse specialist

Objective: COVID-19 led to rapid changes in healthcare services across the globe. At this adult CF service, much of the CF multidisciplinary team (MDT) were re-deployed and the CF ward, ambulatory care and outpatients were closed. However, a small team remained, including the nurse specialists (CF-CNS). The CF-CNSs quickly adapted their role and as well as providing support and advice by phone and email, they implemented an emergency service in an area previously not used for this to ensure patients did not feel abandoned, provide treatment for exacerbation and prevent disease decline. Methods: All patient contacts and reasons for contact were recorded. QI methodology was used (Plan, Do, Study, Act) alongside process mapping to design the emergency service. Success was measured by the reduction in number of contacts and the number of patients reviewed with or without intervention in the emergency service. Results: In the first two weeks of the emergency service the CF-CNSs had assessed (by phone), reviewed (face-to-face) and consequently started two patients on home intravenous antibiotics. Twelve weeks later, 36 patients had been taken through the same process, medically reviewed ± intervention. There were 1,187 patient contacts in March (mostly related to COVID-19, unwell, medication), 904 in April and 870 in May (related to blood test results, unwell, medication). Conclusion: The motivation of the CF-CNSs was pivotal to the success of this initiative. They were supported by the remaining CF MDT and CF consultants who provided phone advice.

Rollout of Kaftrio® to adult cystic fibrosis patients at the Royal Brompton Hospital during a global pandemic

Objectives: To review the rollout process for Kaftrio® at this large adult CF Centre following approval by the European Medicines Agency (EMA) in June 2020, EMA marketing authorisation and commissioning by NHS England on 21st August 2020, taking into consideration the limitations imposed on clinical services due to COVID-19. Methods: Recent rollout of Symkevi® meant that this adult CF service had already developed processes for the identification of suitable patients and medication distribution. Due to COVID-19 restrictions, innovative methods for clinical review, patient discussion, testing for liver function and occasionally genotype were developed. Furthermore, contract extensions and new paperwork for Homecare companies had to be produced as medication was delivered to patients’ homes. This established process involving multidisciplinary digital consultations, Bluetooth spirometry and self-administered postal blood tests was therefore replicated. Additionally, to ensure access for as many patients as possible we re-checked some genetic mutation results, especially where diagnosis pre-dated current testing technology. Results: This table shows the rate at which our patients were able to access Kaftrio®. Two thirds of patients had access to Kaftrio® a month after it was commissioned and 265 of the 348 eligible patients were taking Kaftrio® within 2 months. [Table presented] Conclusion: Using our experience from the launch of Symkevi®, we were able to adapt to this much larger rollout to despite the limitations imposed by the pandemic. To ensure that patients would benefit from early access we started putting processes in place before Kaftrio® was licensed by the EMA. As soon as commissioning was announced by NHS England, we were ready to start prescribing. This allowed our patients to access Kaftrio® very quickly with 144 out of 348 eligible patients taking their initial dose just over 2 weeks later and 286 patients on treatment after just over 2 months.