Feasibility study for supporting medication adherence for adults with cystic fibrosis: mixed-methods process evaluation

Objectives: To undertake a process evaluation of an adherence support intervention for people with cystic fibrosis (PWCF), to assess its feasibility and acceptability. Setting: Two UK cystic fibrosis (CF) units. Participants: Fourteen adult PWCF; three professionals delivering adherence support (‘interventionists’); five multi-disciplinary CF team members. Interventions: Nebuliser with data recording and transfer capability, linked to a software platform, and strategies to support adherence to nebulised treatments facilitated by interventionists over 5 months (± 1 month). Primary and secondary measures: Feasibility and acceptability of the intervention, assessed through semistructured interviews, questionnaires, fidelity assessments and click analytics. Results: Interventionists were complimentary about the intervention and training. Key barriers to intervention feasibility and acceptability were identified. Interventionists had difficulty finding clinic space and time in normal working hours to conduct review visits. As a result, fewer than expected intervention visits were conducted and interviews indicated this may explain low adherence in some intervention arm participants. Adherence levels appeared to be >100% for some patients, due to inaccurate prescription data, particularly in patients with complex treatment regimens. Flatlines in adherence data at the start of the study were linked to device connectivity problems. Content and delivery quality fidelity were 100% and 60%–92%, respectively, indicating that interventionists needed to focus more on intervention ‘active ingredients’ during sessions. Conclusions: The process evaluation led to 14 key changes to intervention procedures to overcome barriers to intervention success. With the identified changes, it is feasible and acceptable to support medication adherence with this intervention. Trial registration number: ISRCTN13076797; Results

Supporting medication adherence for adults with cystic fibrosis:a randomised feasibility study

Background Preventative medication reduces hospitalisations in people with cystic fibrosis (PWCF) but adherence is poor. We assessed the feasibility of a randomised controlled trial of a complex intervention, which combines display of real time adherence data and behaviour change techniques. Methods Design: Pilot, open-label, parallel-group RCT with concurrent semi-structured interviews. Participants: PWCF at two Cystic Fibrosis (CF) units. Eligible: aged 16 or older; on the CF registry. Ineligible: post-lung transplant or on the active list; unable to consent; using dry powder inhalers. Interventions: Central randomisation on a 1:1 allocation to: (1) intervention, linking nebuliser use with data recording and transfer capability to a software platform, and behavioural strategies to support self-management delivered by trained interventionists (n = 32); or, (2) control, typically face-to-face meetings every 3 months with CF team (n = 32). Outcomes: RCT feasibility defined as: recruitment of ≥ 48 participants (75% of target) in four months (pilot primary outcome); valid exacerbation data available for ≥ 85% of those randomised (future RCT primary outcome); change in % medication adherence; FEV1 percent predicted (key secondaries in future RCT); and perceptions of trial procedures, in semi-structured interviews with intervention (n = 14) and control (n = 5) participants, interventionists (n = 3) and CF team members (n = 5). Results The pilot trial recruited to target, randomising 33 to intervention and 31 to control in the four-month period, June–September 2016. At study completion (30th April 2017), 60 (94%; Intervention = 32, Control =28) participants contributed good quality exacerbation data (intervention: 35 exacerbations; control: 25 exacerbation). The mean change in adherence and baseline-adjusted FEV1 percent predicted were higher in the intervention arm by 10% (95% CI: -5.2 to 25.2) and 5% (95% CI -2 to 12%) respectively. Five serious adverse events occurred, none related to the intervention. The mean change in adherence was 10% (95% CI: -5.2 to 25.2), greater in the intervention arm. Interventionists delivered insufficient numbers of review sessions due to concentration on participant recruitment. This left interventionists insufficient time for key intervention procedures. A total of 10 key changes that were made to RCT procedures are summarised. Conclusions With improved research processes and lower monthly participant recruitment targets, a full-scale trial is feasible

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Cardiopulmonary exercise testing with supramaximal verification produces a safe and valid assessment of V̇o2max in people with cystic fibrosis: a retrospective analysis

The validity and safety of using supramaximal verification (Smax) to confirm a maximal effort during cardiopulmonary exercise testing (CPET) in people with cystic fibrosis (CF) and/or those with severe disease has been questioned. Therefore, this study aimed to investigate these concerns in children, adolescents, and adults with mild-to-severe CF lung disease. Retrospective analysis of 17 pediatric and 28 adult participants with CF [age range: 9.2-62.9 y; forced expiratory volume in 1 s: 66.7% (range: 29.9%-102.3%); 30 men] who completed a routine ramp-incremental cycling test to determine peak oxygen uptake (V̇o2peak) was studied. Maximal oxygen uptake (V̇o2max) was subsequently confirmed by Smax at 110% of peak power output. All participants satisfied the criteria to verify a maximal effort during CPET. However, Smax-V̇o2peak exceeded ramp-V̇o2peak in 3/14 (21.4%) of pediatric and 6/28 (21.4%) adult exercise tests. A valid measurement of V̇o2max was attained in 85.7% of pediatric and 96.4% of adult exercise tests, as Smax-V̇o2peak did not exceed ramp-V̇o2peak by &gt;9%. Adults ( n = 9) experienced a ≥5% reduction in arterial O2 saturation during CPET, 4 during both the ramp and Smax, 3 during only the ramp, and 2 during only Smax. Smax did not significantly worsen perceived breathing effort, chest tightness, throat narrowing, or exertion compared with ramp-incremental testing. Given the clinical importance of aerobic fitness in people with CF, incorporating Smax is recommended to provide a safe and valid measure of V̇o2max in children, adolescents, and adults who span the spectrum of CF disease severity. NEW &amp; NOTEWORTHY Incorporating supramaximal verification into cardiopulmonary exercise testing protocols did not increase the frequency of adverse events or perceived discomfort versus a single-phase incremental exercise test in people with mild-to-severe cystic fibrosis. Furthermore, a valid measure of maximal oxygen uptake (V̇o2max) was obtained from 85.7% of pediatric and 96.4% of adult exercise tests, whereas peak oxygen uptake underestimated aerobic fitness in comparison with V̇o2max in 21.4% of cases (by up to 24.4%).</p