Development of data processing algorithm to calculate adherence for adults with cystic fibrosis using inhaled therapy - a multi-center observational study within the CFHealthHub learning health system.

OBJECTIVES: To develop a robust algorithm to accurately calculate 'daily complete dose counts' for inhaled medicines, used in percent adherence calculations, from electronically-captured nebulizer data within the CFHealthHub Learning Health System. METHODS: A multi-center, cross-sectional study involved participants and clinicians reviewing real-world inhaled medicine usage records and triangulating them with objective nebulizer data to establish a consensus on 'daily complete dose counts.' An algorithm, which used only objective nebulizer data, was then developed using a derivation dataset and evaluated using internal validation dataset. The agreement and accuracy between the algorithm-derived and consensus-derived 'daily complete dose counts' was examined, with the consensus-derived count as the reference standard. RESULTS: Twelve people with CF participated. The algorithm derived a 'daily complete dose count' by screening out 'invalid' doses (those <60s in duration or run in cleaning mode), combining all doses starting within 120s of each other, and then screening out all doses with duration < 480s which were interrupted by power supply failure. The kappa co-efficient was 0.85 (0.71-0.91) in the derivation and 0.86 (0.77-0.94) in the validation dataset. CONCLUSIONS: The algorithm demonstrated strong agreement with the participant-clinician consensus, enhancing confidence in CFHealthHub data. Publishingdata processing methods can encourage trust in digital endpoints and serve as an exemplar for other projects.

"I think most people feel like healthcare professionals tell them to take their treatments and judge them for not taking them": reflexive thematic analysis of the views of adults with cystic fibrosis on how treatment adherence is discussed in healthcare.

OBJECTIVE: Previous research exploring patient-practitioner communication in relation to adherence in cystic fibrosis (CF) is limited. This UK study explored the views of adults with CF on how treatment adherence (related to all CF treatments) is discussed in routine CF care. METHODS: 12 White British adults (ten females; aged 20-37 years; mean 30.1 years) with CF participated in semi-structured interviews. RESULTS: Three overarching themes were developed through reflexive thematic analysis: (1) 'The power of language'; (2) 'Healthcare professionals do not recognise the importance of context'; and (3) '"Admitting" non-adherence is difficult'. The way in which adherence is discussed in adult CF care is viewed as paternalistic and infantilising. Participants reported that healthcare professionals do not always consider the desire to balance treatment-taking with living a normal life. Unwelcome responses from healthcare professionals, and the inability to accurately self-report the amount of treatment taken made it difficult to 'admit' non-adherence. CONCLUSIONS: A culture change is needed in CF care such that people who struggle to take their treatments are not labelled as disobedient, wilfully disobeying orders from healthcare professionals in positions of authority. Instead, an open, honest, non-judgemental approach, as recommended by healthcare agencies for over a decade, should be adopted.

Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis.

BACKGROUND: Adherence to treatment, including inhaled therapies, is low in people with cystic fibrosis (CF). Although psychological interventions for improving adherence to inhaled therapies in people with CF have been developed, no previous published systematic review has evaluated the evidence for efficacy of these interventions. OBJECTIVES: The primary objective of the review was to assess the efficacy of psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (CF). The secondary objective was to establish the most effective components, or behaviour change techniques (BCTs), used in these interventions. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched databases (PubMed; PsycINFO; EBSCO; Scopus; OpenGrey), trials registries (World Health Organization International Clinical Trials Registry Platform; US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov), and the reference lists of relevant articles and reviews, with no restrictions on language, year or publication status. Date of search: 7 August 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different types of psychological interventions for improving adherence to inhaled therapies in people with CF of any age, or comparing psychological interventions with usual care. We included quasi-RCTs if we could reasonably assume that the baseline characteristics were similar in both groups. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and completed data extraction, risk of bias assessments, and BCT coding (using the BCT Taxonomy v1) for all included trials. We resolved any discrepancies by discussion, or by consultation with a third review author as necessary. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 10 trials (1642 participants) in the review (children and adolescents in four trials; adults in five trials; and children and adults in one trial). Nine trials compared a psychological intervention with usual care; we could combine data from some of these in a number of quantitative analyses. One trial compared a psychological intervention with an active comparator (education plus problem-solving (EPS)). We identified five ongoing trials. Psychological interventions were generally multi-component and complex, containing an average of 9.6 BCTs (range 1 to 28). The two most commonly used BCTs included 'problem-solving' and 'instruction on how to perform the behaviour'. Interventions varied in their type, content and mode of delivery. They included a problem-solving intervention; a paper-based self-management workbook; a telehealth intervention; a group training programme; a digital intervention comprising medication reminders and lung function self-monitoring; a life-coaching intervention; a motivational interviewing (MI) intervention; a brief MI intervention (behaviour change counselling); and a digital intervention combined with behaviour change sessions. Intervention duration ranged from 10 weeks to 12 months. Assessment time points ranged from six to eight weeks up to 23 months. Psychological interventions compared with usual care We report data here for the 'over six months and up to 12 months' time point. We found that psychological interventions probably improve adherence to inhaled therapies (primary outcome) in people with CF compared with usual care (mean difference (MD) 9.5, 95% confidence interval (CI) 8.60 to 10.40; 1 study, 588 participants; moderate-certainty evidence). There was no evidence of a difference between groups in our second primary outcome, treatment-related adverse events: anxiety (MD 0.30, 95% CI -0.40 to 1.00; 1 study, 535 participants), or depression (MD -0.10, 95% CI -0.80 to 0.60; 1 study, 534 participants), although this was low-certainty evidence. For our secondary outcomes, there was no evidence of a difference between groups in terms of lung function (forced expiratory volume in one second (FEV1) % predicted MD 1.40, 95% CI -0.20 to 3.00; 1 study, 556 participants; moderate-certainty evidence); number of pulmonary exacerbations (adjusted rate ratio 0.96, 95% CI 0.83 to 1.11; 1 study, 607 participants; moderate-certainty evidence); or respiratory symptoms (MD 0.70, 95% CI -2.40 to 3.80; 1 study, 534 participants; low-certainty evidence). However, psychological interventions may improve treatment burden (MD 3.90, 95% CI 1.20 to 6.60; 1 study, 539 participants; low-certainty evidence). The overall certainty of the evidence ranged from low to moderate across these outcomes. Reasons for downgrading included indirectness (current evidence included adults only whereas our review question was broader and focused on people of any age) and lack of blinding of outcome assessors. Psychological interventions compared with an active comparator For this comparison the overall certainty of evidence was very low, based on one trial (n = 128) comparing an MI intervention to EPS for 12 months. We are uncertain whether an MI intervention, compared with EPS, improves adherence to inhaled therapies, lung function, or quality of life in people with CF, or whether there is an effect on pulmonary exacerbations. The included trial for this comparison did not report on treatment-related adverse events (anxiety and depression). We downgraded all reported outcomes due to small participant numbers, indirectness (trials included only adults), and unclear risk of bias (e.g. selection and attrition bias). AUTHORS' CONCLUSIONS: Due to the limited quantity of trials included in this review, as well as the clinical and methodological heterogeneity, it was not possible to identify an overall intervention effect using meta-analysis. Some moderate-certainty evidence suggests that psychological interventions (compared with usual care) probably improve adherence to inhaled therapies in people with CF, without increasing treatment-related adverse events, anxiety and depression (low-certainty evidence). In future review updates (with ongoing trial results included), we hope to be able to establish the most effective BCTs (or 'active ingredients') of interventions for improving adherence to inhaled therapies in people with CF. Wherever possible, investigators should make use of the most objective measures of adherence available (e.g. data-logging nebulisers) to accurately determine intervention effects. Outcome reporting needs to be improved to enable combining or separation of measures as appropriate. Likewise, trial reporting needs to include details of intervention content (e.g. BCTs used); duration; intensity; and fidelity. Large trials with a longer follow-up period (e.g. 12 months) are needed in children with CF. Additionally, more research is needed to determine how to support adherence in 'under-served' CF populations.

Using a learning health system to understand the mismatch between medicines supply and actual medicines use among adults with cystic fibrosis.

BACKGROUND: Studies in separate cohorts suggest possible discrepancies between inhaled medicines supplied (median 50-60%) and medicines used (median 30-40%). We performed the first study that directly compares CF medicine supply against use to identify the cost of excess medicines supply. METHODS: This cross-sectional study included participants from 12 UK adult centres with ≥1 year of continuous adherence data from data-logging nebulisers. Medicine supply was measured as medication possession ratio (MPR) for a 1-year period from the first suitable supply date. Medicine use was measured as electronic data capture (EDC) adherence over the same period. The cost of excess medicines was calculated as whole excess box(es) supplied after accounting for the discrepancy between EDC adherence and MPR with 20% contingency. RESULTS: Among 275 participants, 133 (48.4%) were females and mean age was 30 years (95% CI 29-31 years). Median EDC adherence was 57% (IQR 23-86%), median MPR was 74% (IQR 46-96%) and the discrepancy between measures was median 14% (IQR 2-29%). Even with 20% contingency, mean potential cost of excess medicines was £1,124 (95% CI £855-1,394), ranging from £183 (95% CI £29-338) for EDC adherence ≥80% to £2,017 (95% CI £1,507-2,526) for EDC adherence <50%. CONCLUSIONS: This study provides a conservative estimate of excess inhaled medicines supply cost among adults with CF in the UK. The excess supply cost was highest among those with lowest EDC adherence, highlighting the importance of adherence support and supplying medicine according to actual use. MPR provides information about medicine supply but over-estimates actual medicine use.

Prospectively predicting Pseudomonas aeruginosa infection/s using routine data from the UK cystic fibrosis register.

RATIONALE AND AIMS: Lung health of people with cystic fibrosis (PwCF) can be preserved by daily use of inhaled therapy. Adherence to inhaled therapy, therefore, provides an important process measure to understand the success of care and can be used as a quality indicator. Defining adherence is problematic, however, since the number of prescribed treatments varies considerably between PwCF. The problem is less pronounced among those with Pseudomonas aeruginosa (PA), for whom at least three daily doses of nebulized therapy should be prescribed and who thus constitute a more homogeneous group. The UK CF Registry provides routine data on PA status, but data are only available 12 months after collection. In this study, we aim to prospectively identify contemporary PA status from historic registry data. METHOD: UK CF Registry data from 2011 to 2015 for PwCF aged ≥16 was used to determine a pragmatic prediction rule for identifying contemporary PA status using historic registry data. Accuracy of three different prediction rules was assessed using the positive predictive value (PPV). The number and proportion of adults predicted to have PA infection were determined overall and per center for the selected prediction rule. Known characteristics linked to PA status were explored to ensure the robustness of the prediction rule. RESULTS: Having CF Registry defined chronic PA status in the two previous years is the selected definition to predict a patient will have PA infection within the current year (population-level PPV = 96%-97%, centre level PPV = 85%-100%). This approach provides a subset of data between 1852 and 1872 patients overall and a range of 8 to 279 patients per center. CONCLUSION: Historic registry data can be used to contemporaneously identify a subgroup of patients with chronic PA. Since this patient group has a narrower treatment schedule, this can facilitate a better benchmarking of adherence across centers.

Tool-use and the left hemisphere: what is lost in ideomotor apraxia?

Impaired tool related action in ideomotor apraxia is normally ascribed to loss of sensorimotor memories for habitual actions (engrams), but this account has not been tested against a hypothesis of a general deficit in representation of hand-object spatial relationships. Rapid reaching for familiar tools was compared with reaching for abstract objects in apraxic patients (N=9) and in a control group with right hemisphere posterior stroke. The apraxic patients alone showed an impairment in rotating the wrist to correctly grasp an inverted tool but not when inverting the hand to avoid a barrier and grasp an abstract object, and the severity of the impairment in tool reaching correlated with pantomime of tool-use. A second experiment with two apraxic patients tested whether barrier avoidance was simply less spatially demanding than reaching for a tool. However, the patient with damage limited to the inferior parietal lobe still showed a selective problem for tools. These results demonstrate that some apraxic patients are selectively impaired in their interaction with familiar tools, and this cannot be explained by the demands of the task on postural or spatial representation. However, traditional engram theory cannot account for associated problems with imitation of novel actions nor the absence of any correlated deficit in recognition of the methods of grasp of common tools. A revised theory is presented which follows the dorsal and ventral streams model (Milner & Goodale, 2008) and proposes preservation of motor control by the dorsal stream but impaired modulating input to it from the conceptual systems of the left temporal lobe.