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Background: Elexacaftor–tezacaftor–ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing. Methods: We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor–tezacaftor–deutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftor–tezacaftor–deutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftor–deutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)–tezacaftor–deutivacaftor or tezacaftor–ivacaftor active control for 4 weeks, following a 4-week tezacaftor–ivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete. Findings: In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3·1 percentage points (95% CI –0·8 to 7·0) and 2·7 percentage points (–1·0 to 6·5) from baseline at week 12, respectively, versus –0·8 percentage points (–6·2 to 4·7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)–tezacaftor–deutivacaftor (n=9), vanzacaftor (10 mg)–tezacaftor–deutivacaftor (n=19), vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4·6 percentage points (−1·3 to 10·6), 14·2 percentage points (10·0 to 18·4), 9·8 percentage points (5·7 to 13·8), and 1·9 percentage points (−4·1 to 8·0), respectively, in sweat chloride concentration of −42·8 mmol/L (–51·7 to –34·0), −45·8 mmol/L (95% CI –51·9 to –39·7), −49·5 mmol/L (–55·9 to –43·1), and 2·3 mmol/L (−7·0 to 11·6), respectively, and in CFQ-R respiratory domain score of 17·6 points (3·5 to 31·6), 21·2 points (11·9 to 30·6), 29·8 points (21·0 to 38·7), and 3·3 points (−10·1 to 16·6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=18) and tezacaftor–ivacaftor (n=10) had mean changes relative to baseline (taking tezacaftor–ivacaftor) at day 29 in ppFEV1 of 15·9 percentage points (11·3 to 20·6) and −0·1 percentage points (−6·4 to 6·1), respectively, in sweat chloride concentration of −45·5 mmol/L (−49·7 to −41·3) and −2·6 mmol/L (−8·2 to 3·1), respectively, and in CFQ-R respiratory domain score of 19·4 points (95% CI 10·5 to 28·3) and −5·0 points (−16·9 to 7·0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftor–tezacaftor–deutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity. Interpretation: Once-daily dosing with vanzacaftor–tezacaftor–deutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftor–tezacaftor–deutivacaftor in phase 3 clinical trials compared with elexacaftor–tezacaftor–ivacaftor. Funding: Vertex Pharmaceuticals.

Background: Cystic Fibrosis is the most common autosomal recessive genetic condition in the Caucasian population. Oral health in adults with Cystic Fibrosis is an area lacking in research, due to their historic low life expectancy. The age profile of people with Cystic Fibrosis (CF) is increasing, due in part to improved therapies. Further study is needed in order to ascertain their dental needs and improve provision of care to these medically vulnerable individuals.Methods: A cross sectional survey was carried out. A structured, anonymous online questionnaire, with both quantitative and qualitative aspects, was used to obtain information regarding their feelings towards dentists and dental appointments. The final version of the questionnaire was based on a collaborative effort between researchers at Cork University Dental School and Hospital and Cystic Fibrosis patient advocates from Cystic Fibrosis Ireland. The inclusion criteria were people over the age of 18 years with a diagnosis of CF. Participants were recruited via CF Ireland’s mailing list and social media channels. The quantitative portion of the questionnaire underwent statistical analysis using IBM SPSS. The qualitative portion underwent inductive thematic analysis.Results: A total of 71 adults with CF responded to the survey. 54.9% of respondents were unhappy with their teeth. 63.4% felt that CF had an impact on oral health. 33.8% were anxious about attending their dentist. 54.9% felt that dentists should be part of the multidisciplinary team. Respondents believed that CF has impacted on their oral health due to the medications and dietary requirements involved, as well as tiredness and other side effects of CF. Some reasons for being anxious about attending the dentist involve cross infection concerns, issues with the dentist, with tolerating treatment, and with the teeth themselves. They wanted dentists to be aware of the practicalities of dental treatment for people with CF, especially their discomfort with lying back. They also want the dentist to be aware of the impact that their medication, treatment and diet has on their oral health.Conclusions: Over a third of PWCF reported anxiety about attending the dentist. Reasons for this included fear, embarrassment, cross infection concerns and problems with treatment, especially being in the supine position. PWCF want dentists to be aware of the impact that CF can have upon dental treatment and oral health care.

To evaluate the dental attendance, oral hygiene habits, and dietary habits of adults with Cystic Fibrosis in the Republic of Ireland.A cross-sectional study was carried out using a structured anonymous questionnaire. A total of 71 adults with Cystic Fibrosis responded. While the majority of respondents (66.2%) saw a dentist in the preceding year, 15.5% had not attended a dentist for over 2 years. Smoking and alcohol consumption levels were low. 63.4% brushed twice or more daily, with 70.4% using a Fluoride containing toothpaste. 62% did not use any interdental cleaning aid. 5.6% changed their toothbrush at least once a month, but for 22.5% it was over 6 months. 70.4% used fluoride toothpaste. 38% snacked three or more times daily and 29.5% consumed fizzy drinks at least once daily.The alcohol and tobacco consumption in this study group was low. However, a large proportion frequently consumed sugar-rich foods, and they did not change their toothbrush, brush their teeth, or attend the dentist as regularly as is advised. More targeted advice may be necessary to improve the oral hygiene habits of adults with Cystic Fibrosis.

Emily O’Reilly,1 Deborah Casey,1 Hisham Ibrahim,1 Alice McGrath,1 Tomás McHugh,1 Punitha Vairamani,1 Jill Murphy,1 Barry Plant,1,2 Desmond M Murphy1,2 1Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland; 2Health Research Board Clinical Research Facility, University College Cork, Cork, IrelandCorrespondence: Desmond M Murphy, Department of Respiratory Medicine, Cork University Hospital, Wilton, Cork, Ireland, Email desmond.murphy@hse.ie

Cystic Fibrosis (CF) patients need to meet with their Multidisciplinary Team (MDT) approximately every four months. In-between these scheduled visits, patients may contact the Multidisciplinary Team (MDT) via phone to express any health-related concerns. This often requires a phone evaluation before organizing an unscheduled appointment. Due to the sporadic nature of these phone calls, resources and time are often heavily affected. With the predicted increase of the adult CF patient population, there is a need for better ways to manage and educate patients on their condition. The aim of this ICT intervention is to reduce this effect by creating an online virtual Dr, that can be accessed by the patient from their own home. This Virtual Doctor (Dr) will generate a report and an initial evaluation that will be sent to the MDT to action. The patient is also provided with a response outlining when the team will be in contact. The system includes a Dr avatar with facial animations and 3D scene. The voice of the avatar is generated using Node.js along with the Amazon Web Services Polly. The Web Speech API speech recognition is used to provide the ability to recognize voice context from an audio input; in this case the patient's computer microphone. This allows for the patient's interaction with the avatar and the documentation of the answers. These answers are scored and used as a comparison to the patient's baseline health status. The patient's answers and scores are stored within a database and sent via email to the MDT for evaluation. The score informs the Virtual Dr's response and MDT report. It is anticipated that this tool will be of benefit to both patients and medical staff. By creating such a system, patients can learn about their own condition and health status, while improving time and resource management. A prototype of the system has been created in preparation for pilot testing with adult CF patients.

For those diagnosed with a chronic condition at an early age, such as Cystic Fibrosis, transition from a paediatric care facility to an adult orientated facility is often inevitable. Patients can feel anxious and nervous as they are unfamiliar with their new surroundings and healthcare team. Research has shown that these symptoms would be reduced if patients were given the opportunity to meet their new healthcare team and become familiar with the new process and surroundings prior to transitioning. This research explores the possibility of using Virtual Reality as a means of complementing the transition process. By allowing patients to explore and learn of their new surroundings and meet their healthcare team virtually prior to transitioning, it is anticipated that their will be an improvement on patient education and experience. A 3D model of the Adult CF Day Unit, Specialist Inpatient Unit, and other common testing labs is created for exploration in the Unreal Engine 4. This 3D environment is then prepared for use in a HTC Vive. The environment also includes interest points, audio, and welcome video introducing the adult CF healthcare team. Throughout the development process this system is tested with five technical researchers. The feedback received from these evaluators primarily focused on the use of a UI and other features such as a bread-crumb trail and audio to assist in the educational content at interest points. This feedback has now been implemented in preparation for patient testing. It is anticipated that this will enhance the patients experience and educate them on the transition process.

Schools in Australia and internationally are responding to calls to offer new and innovative learning opportunities in STEM. STEM stands for Science, Mathematics, Engineering and Mathematics, but when amalgamated into the acronym ‘STEM’ can potentially mean more than the sum of the four parts. In choosing how to respond to the STEM ‘push’, schools must first navigate through the many ‘versions’ of STEM emerging within the education community, and then face the task of upskilling teachers in content and language, teaching approaches, and new technology and equipment. Professional development of teachers plays an important part in assisting teachers and schools in this period of innovation and change. This chapter describes one such professional development project where teachers from ten schools in regional Victoria, Australia, were supported in developing new knowledge, language, pedagogy, and curriculum to support their development of a ‘STEM vision’ for their schools. The activities developed by these schools are outlined to illustrate that they each have taken a different approach to STEM, with case studies showing how these activities were developed. The factors critical to the success of the program are outlined, which have implications for a policy response, as well as challenges that may threaten the sustainability of such initiatives.

Background: Patient education is an integral part of management and care. For adults with Cystic Fibrosis, new procedures and devices may arise. Studies have shown that patients forget between 40%-80% provided during a consultation, hence other accessible platforms for disseminating this knowledge is required. Aim: This paper aims to outline the design, creation and evaluation of three patient e-learning tools. These tools are available online so that they can be accessed by patients via bedside tablets in a hospital ward and personal devices. This research will then investigate usage data from those users accessing the tools in a hospital and non-hospital context. Methodologies: Three education tools were developed which focus on Portacaths, Gastrostomy Tubes, and Bronchoscopies. All educational multimedia was developed and validated by the Cork CF Multidisciplinary team. The information is presented to the user in a FAQ (Frequently Asked Questions) format, where users can navigate through content via buttons with a series of commonly asked questions. These questions are identified by CF nurse specialists with over 25 years’ experience in educating CF adults on these devices and procedures. The web tools are developed using HTML, CSS, AJAX, PHP and JavaScript. Once the user visits an e-learning tool, a unique identifier is generated and stored in the browser's local storage as well as a text file on the server. Each button click and respective time stamp is then stored in the text file. This data is then analysed to determine the most frequently viewed content as well as time spent viewing content and visiting the e-learning tool. Results: Overall, all three e-learning tools were accessed more frequently by personal devices. Generally, users tended to spend less time using the e-learning tools via the bedside tablet. There was also a tendency for users to visit more general information on the bedside tablets, whereas users who access the e-learning tools from personal devices tended to spend more time exploring the web tools and focused more on care information. Conclusion: Patient education is an integral part of care. From the pilot study conducted by this research, it would appear that patients exhibit different motivations when visiting e-learning material in a hospital and non-hospital setting. As such it is advised that e-learning content is made available to patients in each context.

This chapter describes the use and modification of the tools of the STEPS Interpretive Framework as part of a teacher professional development program for STEM teachers. The tools were used to assist with establishing partnerships with schools that were important for determining the content, timing and nature of the professional learning program cycles. The use of the Interpretive Framework as a mediating tool that both changes the nature of the activity and is also changed by the activity is discussed.

The current STEM education agenda is driven by the belief that STEM skills are crucial to innovation and development in our contemporary, technological, knowledge-based, competitive global economy (Office of the Chief Scientist, Science, technology, engineering and mathematics: Australia’s future. Australian Government, Canberra, 2014; Australia’s STEM workforce: science, technology, engineering and mathematics. Australian Government, Canberra, 2016). This chapter articulates a comprehensive, multifaceted and coherent STEM vision that addresses the subtle and complex challenge of preparing “twenty-first-century” citizens within the constraints of a traditional school system and curriculum. For STEM education to be incorporated effectively and sustainably in schools, a STEM vision needs to be inclusive of school-specific needs. In this chapter, we report on our preliminary insights from a teacher professional development programme operating in ten schools in Victoria, Australia, designed to develop year 7 and 8 science, technology and mathematics teachers’ capacity to teach STEM. Evaluative data from the first year of this three-year programme is presented to illustrate the variety of classroom activities that can arise from a comprehensive STEM vision. The research is showing that a STEM vision needs to be more than discrete STEM-related activities slotted into an already bulging curriculum to be sustainable.

Cystic Fibrosis is the most common life limiting genetic disease affecting Caucasians. The life expectancy of this cohort has increased and is predicted to reach retirement age. As most CF patients are diagnosed from birth, they undergo educational and management programs throughout their lives. However numerous studies have identified various knowledge gaps. This paper presents a scoping literature review of the available educational interventions for adult CF patients. This review follows the framework as outlined by Arksey et al. [9]. A search string is entered into four databases and the resulting literature is downloaded into the academic reference manager software, Mendeley version 1.16.1. The manuscripts are then subjected to title, abstract, and introduction refinement. The remaining manuscripts are then reviewed under the following headings: 1) Aims/Objective, 2) Patient Demographic, 3) Educational Focus, 4) Research Type Conducted, 5) Methodologies, 6) Results, and 7) Author Noted Limitations. Of the 3649 manuscripts, only eight remained after the refinement stages. A significant amount of the papers that were excluded focused on CF pediatric patients only. Of the remaining papers, four manuscripts focused solely on CF adults. Seven of the papers identified a range of issues with CF education, including anxiety, knowledge gaps, and a lack of educational teams. Five papers introduced an educational intervention, only one was for CF adults only. Two of the interventions were ICT based. Of the manuscripts, one intervention that targeted both children and adults was reported as being implemented into the hospital services long term. From the final papers reviewed, it is apparent that there appears to be an issue with adult CF education and knowledge gaps. With CF survival rates rising and a new aging CF population emerging, there is a need for educational programs and interventions to meet the changing needs of the CF adult population.

Despite the growth of e-learning, its methods have yet to be incorporated into all educational modules within the discipline of medicine. As such, its integration into some educational methods for the study of complex diseases may benefit both students and trainees. In particular, the strategies demonstrated in blended, multimedia and web-based interactive platforms may enhance its overall communication. Cystic Fibrosis is a complex genetic disease which affects various parts of the body. These effects prove difficult to communicate through the written form alone and visual media elements are often incorporated to encourage a better understanding. However this foundational understanding of the disease has the potential to be enhanced further through the utilisation of e-learning techniques. In this paper, current content and resources in the field of e-learning for the disease Cystic Fibrosis and other complex lung diseases are compared and interrogated for possible areas of improvement and expansion. It was found that there was a lack of e-learning visualisers and simulators that demonstrated the mucus effects caused by Cystic Fibrosis within the lungs. As such, a Cystic Fibrosis visualiser and simulator was created using both 3D and web technologies and presented to medical students for evaluation. It was found that the visualiser aided in initial primary understanding of the mucus effects on the lungs, however, it was also found that it could not be used for further advanced teaching without improvements. In this way, it was established that the visualiser, in its simplicity, could be used to educate patients and families about Cystic Fibrosis mucus effects on the lungs.

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