Adapting, restarting, and terminating a randomised control trial for people with cystic fibrosis: Reflections on the impact of the COVID-19 pandemic upon research in a clinical population.

Background: Habitual physical activity (PA) and exercise form a cornerstone of the management of cystic fibrosis (CF), a genetically inherited pulmonary and digestive condition - whereby telehealth platforms have been proposed as a mechanism to engage remotely people with CF in PA and exercise. Methods: To test this, in early 2020, the 'ActivOnline: Physical Activity in Cystic Fibrosis Trial' (ActiOn PACT) randomised control trial was established to examine whether an online intervention was effective at increasing PA in adolescents and adults with CF. Results: The emergence of the COVID-19 pandemic in 2020 forced this trial to be paused and modified, with the adoption of online recruitment and remote assessment of outcome measures. Despite such adaptations in accord with frameworks developed by the National Institute for Health Research, this trial failed to recruit and was subsequently terminated. Conclusions: This article details the authors reflections upon the proposed reasons for lack of recruitment, including improved technology and medications for people with CF, and contextualises this finding in relation to the wider issue of non-reporting of trial results in clinical research.

Information needs of ethnically diverse, vaccine-hesitant parents during decision-making about the HPV vaccine for their adolescent child: a qualitative study.

BACKGROUND: The English schools-based human papillomavirus (HPV) vaccination programme has the potential to eliminate HPV-related cancers if high uptake is achieved. However, unmet information needs among some parents may contribute to persisting lower uptake among minority ethnic groups. Through this study we aimed to understand the information needs of vaccine-hesitant, ethnically diverse parents during decision-making about the HPV vaccine for their adolescent child, to inform the future development of tailored communication materials. METHODS: Recruitment was facilitated thorough healthcare and community organisations within London and the South West of England. Semi-structured interviews took place between April and August 2023. Thematic analysis was undertaken, assisted by NVivo software. RESULTS: Of the 29 parents interviewed, the majority were mothers (79%), belonged to a minority ethnic group (88%), and had an adolescent child unvaccinated against HPV (72%). Five of the interviews were undertaken in the participants' primary language with translation support. Most parents interviewed had limited knowledge about the HPV vaccine and appeared conflicted as to whether vaccines could offer benefits to health. Misunderstanding around the potential of developing serious side-effects (e.g. fertility issues, developing cancer) were factors that could negatively impact decision-making by parents. Stigma associated with the sexual transmissibility of HPV did not always negatively impact decision-making. However, some parents chose not to vaccinate on the basis of perceptions of low risk and a preference to provide education about sexual behaviours to their adolescent child. CONCLUSIONS: Tailoring communication materials to address misunderstandings could support informed decision-making by vaccine hesitant parents for their adolescent children to be vaccinated against HPV. Future communication materials about the HPV vaccine should highlight the benefits of protection against cancer to increase parents' motivation for protect their adolescent child; provide accurate convincing information in relation to the excellent safety profile; and emphasise the importance of providing HPV vaccine at the recommended age, all alongside communicating the universality and commonality of HPV infection. TRIAL REGISTRATION: N/A.

Defining the elusive oncogenic role of the methyltransferase TMT1B.

Methyltransferases are enzymes fundamental to a wide range of normal biological activities that can become dysregulated during oncogenesis. For instance, the recent description of the methyltransferase-like (METTL) family of enzymes, has demonstrated the importance of the N6-adenosine-methyltransferase (m6A) modification in transcripts in the context of malignant transformation. Because of their importance, numerous METTL family members have been biochemically characterized to identify their cellular substrates, however some members such as METTL7B, recently renamed TMT1B and which is the subject of this review, remain enigmatic. First identified in the stacked Golgi, TMT1B is also localized to the endoplasmic reticulum as well as lipid droplets and has been reported as being upregulated in a wide range of cancer types including lung cancer, gliomas, and leukemia. Interestingly, despite evidence that TMT1B might act on protein substrates, it has also been shown to act on small molecule alkyl thiol substrates such as hydrogen sulfide, and its loss has been found to affect cellular proliferation and migration. Here we review the current evidence for TMT1B's activity, localization, and potential biological role in the context of both normal and cancerous cell types.

The Exeter Activity Unlimited statement on physical activity and exercise for cystic fibrosis: methodology and results of an international, multidisciplinary, evidence-driven expert consensus.

BACKGROUND: The roles of physical activity (PA) and exercise within the management of cystic fibrosis (CF) are recognised by their inclusion in numerous standards of care and treatment guidelines. However, information is brief, and both PA and exercise as multi-faceted behaviours require extensive stakeholder input when developing and promoting such guidelines. METHOD: On 30th June and 1st July 2021, 39 stakeholders from 11 countries, including researchers, healthcare professionals and patients participated in a virtual conference to agree an evidence-based and informed expert consensus about PA and exercise for people with CF. This consensus presents the agreement across six themes: (i) patient and system centred outcomes, (ii) health benefits, iii) measurement, (iv) prescription, (v) clinical considerations, and (vi) future directions. The consensus was achieved by a stepwise process, involving: (i) written evidence-based synopses; (ii) peer critique of synopses; (iii) oral presentation to consensus group and peer challenge of revised synopses; and (iv) anonymous voting on final proposed synopses for adoption to the consensus statement. RESULTS: The final consensus document includes 24 statements which surpassed the consensus threshold (>80% agreement) out of 30 proposed statements. CONCLUSION: This consensus can be used to support health promotion by relevant stakeholders for people with CF.

Sleep, Sedentary Time and Physical Activity Levels in Children with Cystic Fibrosis.

The aim of this study was to compare the use of generic and cystic fibrosis (CF)-specific cut-points to assess movement behaviours in children and adolescents with CF. Physical activity (PA) was assessed for seven consecutive days using a non-dominant wrist-worn ActiGraph GT9X in 71 children and adolescents (36 girls; 13.5 ± 2.9 years) with mild CF. CF-specific and generic Euclidean norm minus one (ENMO) cut-points were used to determine sedentary time (SED), sleep, light physical activity (LPA), moderate physical activity and vigorous physical activity. The effect of using a CF-specific or generic cut-point on the relationship between PA intensities and lung function was determined. Movement behaviours differed significantly according to the cut-point used, with the CF-specific cut-points resulting in less time asleep (−31.4 min; p < 0.01) and in LPA (−195.1 min; p < 0.001), and more SED and moderate-to-vigorous PA (159.3 and 67.1 min, respectively; both p < 0.0001) than the generic thresholds. Lung function was significantly associated with LPA according to the CF-specific cut-points (r = 0.52; p = 0.04). Thresholds developed for healthy populations misclassified PA levels, sleep and SED in children and adolescents with CF. This discrepancy affected the relationship between lung function and PA, which was only apparent when using the CF-specific cut-points. Promoting LPA seems a promising strategy to enhance lung function in children and adolescents with CF.

A Compositional Analysis of Physical Activity, Sedentary Time, and Sleep and Associated Health Outcomes in Children and Adults with Cystic Fibrosis.

This study sought to investigate the association of light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time (SED), and sleep with lung function in children and adults with CF. In total, 86 children (41 females; 13.6 ± 2.8 years; FEV1%predicted: 86 ± 1%) and 43 adults (21 females; 24.6 ± 4.7 years; FEV1%predicted: 63 ± 21%) with CF participated in this study. Wrist-worn accelerometery was used to assess PA, SED and sleep. Compositional linear regression models were conducted following normalisation via isometric log-ratio transformations. Sequential binary partitioning was applied to investigate the impact of reallocating 10 to 30 min between each behaviour on FEV1%predicted. A decline in FEV1%predicted was predicted with the reallocation of 30 min from MVPA to SED or LPA or sleep to any other behaviour in children (-3.04--0.005%) and adults (-3.58--0.005%). Conversely, improvements in FEV1%predicted were predicted when 30 min was reallocated to MVPA from LPA or SED in children (0.12-1.59%) and adults (0.77-2.10%), or when 30 min was reallocated to sleep from any other behaviour in both children (0.23-2.56%) and adults (1.08-3.58%). This study supports the importance of MVPA and sleep for maintaining and promoting lung function in people with CF.

Development of a multicomponent intervention to increase parental vaccine confidence and young people's access to the universal HPV vaccination programme in England: protocol for a co-design study.

INTRODUCTION: Persistent infection with HPV can result in cancers affecting men and, especially, women. Lower uptake exists by area and different population groups. Increasing parental confidence about, and adolescent access to, the universal HPV vaccination programme may help reduce inequalities in uptake. However, the evidence-base for interventions to address uptake for schools-based HPV vaccination programmes is currently lacking. This study protocol outlines how a multicomponent intervention to address this evidence gap will be codesigned with parents. METHODS AND ANALYSIS: The proposed research will be undertaken in localities covered by two immunisation teams in London and the south-west of England. The 'person-based approach' to intervention development will be followed. In the first phase, an exploratory qualitative study will be undertaken with key stakeholders (n=8) and parents (n=40) who did not provide consent for their adolescent child to be vaccinated. During the interviews, parents' views on ways to improve parental confidence about, and adolescents' access to, HPV vaccination will be sought. The findings will be used to inform the co-design of a preliminary plan for a targeted, multicomponent intervention. In the second phase, at least two parent working groups (n=8) will be convened and will work with creative designers to co-design communication materials aimed at increasing parents' confidence in vaccination. At least two workshops with each parent group will be organised to obtain feedback on the intervention plan and communication materials to ensure they are fit for purpose. These findings will inform a protocol for a future study to test the effectiveness of the intervention at increasing HPV vaccination uptake. ETHICS AND DISSEMINATION: The National Health Services Research Ethics Service and London School of Hygiene & Tropical Medicine Observational / Interventions Research Ethics Committee provided approvals for the study (reference 22/SW/0003 & 26902, respectively). We will work with parent advisory groups to inform our dissemination strategy and co-present our findings (eg, at community events or through social media). We will disseminate our findings with academics and healthcare professionals through webinars and academic conferences, as well as peer-reviewed publications.

The impact of physical activity and exercise interventions for physical health in people with cystic fibrosis: protocol for a systematic review.

BACKGROUND: Cystic fibrosis (CF) is a genetically inherited, life-limiting condition, affecting ~90,000 people globally. Physical activity (PA) and exercise form an integral component of CF management, and have been highlighted by the CF community as an area of interest for future research. Previous reviews have solely focused on PA or structured exercise regimens independent of one another, and thus a comprehensive assessment of the physical health benefits of all PA, including exercise, interventions, is subsequently warranted. Therefore, the purpose of this review is to evaluate the effects of both PA and exercise upon outcomes of physical health and healthcare utilisation in people with CF. METHODS: A systematic review has been registered and reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P guidelines. This will include randomised control trials on the effects of PA and exercise, relative to usual treatment, upon people with CF. Primary outcomes will include variables associated with fitness, PA, lung health, inflammation, body composition, glycaemic control and patient-reported outcomes. Secondary outcomes will include adverse events and healthcare utilisation. Searches will be undertaken in Ovid MEDLINE, OVID EMBASE, PsychINFO, ERIC, SPORTDiscus, ASSIA, CCTR, CINHAL and Web of Science databases, and will be searched from date of inception onwards. Two reviewers will independently screen citations and abstracts, and full-texts, for inclusion and data extraction, respectively. Methodological quality will be assessed using the Cochrane Risk of Bias-2 tool. If feasible, random-effects meta-analyses will be conducted where appropriate. Additional analyses will explore potential sources of heterogeneity, such as age, sex, and disease severity. DISCUSSION: This systematic review will build on previous research, by comprehensively assessing the impact of both PA and exercise upon physical health and healthcare utilisation in people with CF. Results of this review will be utilised to inform discussions that will ultimately result in a consensus document on the impact of physical activity and exercise for people with CF. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020184411.

Physical activity for cystic fibrosis: perceptions of people with cystic fibrosis, parents and healthcare professionals.

BACKGROUND: The benefits of physical activity (PA) for people with cystic fibrosis (pwCF) are widely accepted, yet how PA is promoted and utilised by pwCF is unclear. METHOD: An online questionnaire to explore attitudes, practices and promotion of PA in cystic fibrosis was completed by healthcare providers (HCP), pwCF and parents/caregivers. RESULTS: 351 respondents (105 HCP, 120 pwCF, and 126 parents/caregivers) from 12 countries completed the survey. Importance of PA was rated highly by the majority of respondents. Physical (e.g. health), psychological (e.g. enjoyment) and social (e.g. social interaction) factors were motives for PA for 82%, 49% and 37% of pwCF, respectively, irrespective of country. Common barriers to PA included time (49% and 36%) and tiredness (61% and 7%) for pwCF and parents/carers, respectively. pwCF also reported psychosocial barriers (e.g. stigma, demoralisation), while parents/caregivers reported structural barriers (e.g. cost). Clinical teams varied substantially in terms of the emphasis placed on PA, facilities available, staff and training, and advice given to pwCF. CONCLUSION: Despite the majority of participants rating the importance of PA highly, substantial variability was evident regarding the facilities and clinical support available to them, as well as why and how people were active. There remains a need to identify what constitutes "best practice" for PA promotion within clinics.

Barriers and facilitators to physical activity among children, adolescents, and young adults with cystic fibrosis: a systematic review and thematic synthesis of qualitative research.

OBJECTIVES: Physical activity is widely recommended in the treatment and management of cystic fibrosis (CF). Despite the numerous physical and psychological benefits, many young people with CF are not achieving the recommended levels of physical activity. The aim of this systematic review was to identify and synthesise available qualitative investigations exploring the motives for, barriers to and facilitators of physical activity among young people with CF. METHODS: The following six electronic databases were systematically searched: Applied Social Sciences Index and Abstracts (ASSIA), CINAH, EMBASE, MEDLINE, MEDLINE-in-process, PsycINFO up to August 2019. Keywords were used to identify qualitative research that explored engagement in physical activity among young people with CF. Titles and abstracts were screened by two independent reviewers, and potentially relevant articles were retrieved in full. Articles were eligible for inclusion if they employed any qualitative method and recruited participants under the age of 24 years with CF. Risk of bias of included studies was assessed via the Critical Appraisal Skills Programme. Results were synthesised using a thematic approach. RESULTS: Seven studies met our inclusion criteria and were included in the review. Overall, studies were of moderate to high quality. Thematic synthesis identified nine main themes that encompass motives for, barriers to and facilitators of physical activity among young people with CF. These were (1) Perceptions of physical activity. (2) Value attributed to physical activity. (3) Social influences. (4) Competing priorities. (5) Fluctuating health. (6) Normality. (7) Control beliefs. (8) Coping strategies. (9) Availability of facilities. Previous reviews have been unable to identify intervention characteristics that influence physical activity behaviour. CONCLUSIONS: This review provides detailed information on the physical (biological-clinical), psychological, social and environmental influences on physical activity behaviour, thus providing numerous targets for future interventions. This in turn could facilitate promotion of physical activity among young people with CF.

A web-based intervention to promote physical activity in adolescents and young adults with cystic fibrosis: protocol for a randomized controlled trial.

BACKGROUND: Regular participation in physical activity by people with cystic fibrosis (CF) promotes positive clinical and health outcomes including reduced rate of decline in lung function, fewer hospitalizations and greater wellbeing. However adherence to exercise and activity programs is low, in part due to the substantial daily therapy burden for young people with CF. Strict infection control requirements limit the role of group exercise programs that are commonly used in other clinical groups. Investigation of methods to promote physical activity in this group has been limited. The Active Online Physical Activity in Cystic fibrosis Trial (ActionPACT) is an assessor-blinded, multi-centre, randomized controlled trial designed to compare the efficacy of a novel web-based program (ActivOnline) compared to usual care in promoting physical activity participation in adolescents and young adults with CF. METHODS: Adolescents and young adults with CF will be recruited on discharge from hospital for a respiratory exacerbation. Participants randomized to the intervention group will have access to a web-based physical activity platform for the 12-week intervention period. ActivOnline allows users to track their physical activity, set goals, and self-monitor progress. All participants in both groups will be provided with standardised information regarding general physical activity recommendations for adolescents and young adults. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and at 3-months followup. Healthcare utilization will be assessed at 12 months from intervention completion. The primary outcome is change in moderate-to-vigorous physical activity participation measured objectively by accelerometry. Secondary outcomes include aerobic fitness, health-related quality of life, anxiety and depression and sleep quality. DISCUSSION: This trial will establish whether a web-based application can improve physical activity participation more effectively than usual care in the period following hospitalization for a respiratory exacerbation. The web-based application under investigation can be made readily and widely available to all individuals with CF, to support physical activity and exercise participation at a time and location of the user's choosing, regardless of microbiological status. TRIAL REGISTRATION: Clinical trial registered on July 13, 2017 with the Australian and New Zealand Clinical Trials Register at (ACTRN12617001009303).

Enhancing intrinsic motivation for physical activity among adolescents with cystic fibrosis: a qualitative study of the views of healthcare professionals.

OBJECTIVE: To explore the views of healthcare professionals from cystic fibrosis (CF) multidisciplinary teams (MDT) on physical activity for adolescents with CF, the specific strategies used for physical activity promotion and associated challenges. DESIGN: In this exploratory study, in-depth qualitative interviews were conducted with 15 healthcare professionals from CF MDTs to explore their views surrounding physical activity promotion for adolescents with CF. PARTICIPANTS: Eleven physiotherapists (nine female), two consultants (both male) and two dieticians (both female) provided written informed consent and participated in the study. SETTING: CF clinics in the UK. RESULTS: While healthcare professionals highlighted the importance of physical activity in the management of CF, they noted that very few patients were motivated solely by (CF or general) health reasons. Healthcare professionals discussed the need for physical activity to be an enjoyable and routine part of their life, undertaken with significant others, outside the clinic whenever possible. Adopted approaches for physical activity promotion focused on providing individualised recommendations that suit the patients' individual needs and goals and enhance intrinsic motivation for physical activity. CONCLUSION: Our research offers valuable information for those seeking to develop interventions to promote physical activity among adolescents with CF. Specifically, intervention developers should focus on developing individualised interventions that focus on enhancing intrinsic motivation and support the integration of physical activity into everyday life.

Understanding normality: a qualitative analysis of breast cancer patients concepts of normality after mastectomy and reconstructive surgery.

BACKGROUND: As survival rates increase, many people have to adjust to life after cancer. This includes adjusting to life after surgery. While previous research suggests that patients commonly strive to be 'normal' after mastectomy and reconstructive surgery, research surrounding individual perceptions of normality is lacking. AIM: The aim of this study was to explore concepts of normality within a sample of breast cancer patients eligible for reconstructive surgery following mastectomy. METHODS: A total of 35 semi structured interviews, with women who had undergone or were about to undergo breast reconstructive surgery following breast cancer, were analysed using thematic analysis. RESULTS: Four main themes emerged from the data. Women referred to looking normal (appearance); being able to fulfil everyday activities (behaviour); adapting to a new normal (reconstructing normality); and not being ill (health). The importance placed on each area of normality differed between patients. Additionally, patients used different standards to anchor concepts of normality. These included individual standards, social standards and clinical standards. DISCUSSION: The results indicate that although there are commonalities between patients' concepts of normality, it is important for health care professionals to recognise potential individual differences. This may usefully aid communication and help to manage expectations among patients considering surgical options.