A RCT to explore the effectiveness of supporting adherence to nebuliser medication in adults with cystic fibrosis: fidelity assessment of study interventions.

BACKGROUND: A multi-component self-management intervention 'CFHealthHub' was developed to reduce pulmonary exacerbations in adults with Cystic Fibrosis (CF) by supporting adherence to nebuliser medication. It was evaluated in a randomized controlled trial (RCT) involving 19 CF centres, with 32 interventionists, 305 participants in the intervention group, and 303 participants in the standard care arm. Ensuring treatment fidelity of intervention delivery was crucial to ensure that the intervention produced the expected outcomes. METHODS: Fidelity of the CFHealthHub intervention and standard care was assessed using different methods for each of the five fidelity domains defined by the Borrelli framework: study design, training, treatment delivery, receipt, and enactment. Study design ensured that the groups received the intended intervention or standard care. Interventionists underwent training and competency assessments to be deemed certified to deliver the intervention. Audio-recorded intervention sessions were assessed for fidelity drift. Receipt was assessed by identifying whether participants set Action and Coping Plans, while enactment was assessed using click analytics on the CFHealthHub digital platform. RESULTS: Design: There was reasonable agreement (74%, 226/305) between the expected versus actual intervention dose received by participants in the CFHealthHub intervention group. The standard care group did not include focused adherence support for most centres and participants. Training: All interventionists were trained. Treatment delivery: The trial demonstrated good fidelity (overall fidelity by centre ranged from 79 to 97%), with only one centre falling below the mean threshold (> 80%) on fidelity drift assessments. Receipt: Among participants who completed the 12-month intervention, 77% (205/265) completed at least one action plan, and 60% (160/265) completed at least one coping plan. Enactment: 88% (268/305) of participants used web/app click analytics outside the intervention sessions. The mean (SD) number of web/app click analytics per participant was 31.2 (58.9). Additionally, 64% (195/305) of participants agreed to receive notifications via the mobile application, with an average of 53.6 (14.9) notifications per participant. CONCLUSIONS: The study demonstrates high fidelity throughout the RCT, and the CFHealthHub intervention was delivered as intended. This provides confidence that the results of the RCT are a valid reflection of the effectiveness of the CFHealthHub intervention compared to standard care. TRIAL REGISTRATION: ISRCTN registry: ISRCTN55504164 (date of registration: 12/10/2017).

A machine-learning assisted review of the use of habit formation in medication adherence interventions for long-term conditions.

Adherence to medication in long-term conditions is around 50%. The key components of successful interventions to improve medication adherence remain unclear, particularly when examined over prolonged follow-up periods. Behaviour change theories are increasingly interested in the utility of habit formation for the maintenance of health behaviour change, but there is no documentation on how habit has been conceptualised in the medication adherence intervention literature, or what effect the key technique identified in habit formation theory (context dependent repetition) has in these studies. To examine this, a machine-learning assisted review was conducted. Searches of MEDLINE, EMBASE and PSYCInfo and the reference list of a comprehensive systematic review of medication adherence interventions yielded 5973 articles. Machine learning-assisted title and abstract screening identified 15 independent RCTs published between 1976 and 2021, including 18 intervention comparisons of interest. Key findings indicate that conceptualisations of habit in the medication adherence literature are varied and behaviour change technique coding identified only six studies which explicitly described using habit formation. Future work should aim to develop this evidence base, drawing on contemporary habit theory and with explicit demonstration of what techniques have been used to promote habit formation.

Airway clearance techniques used by people with cystic fibrosis in the UK.

OBJECTIVES: To describe the current use of airway clearance techniques among people with cystic fibrosis (CF) in the UK, and the baseline characteristics for users of different airway clearance techniques. DESIGN: Analysis of the UK CF Registry 2011 data. SETTING AND PARTICIPANTS: All people with CF in the UK aged ≥11 years (n=6372). RESULTS: Of the 6372 people on the UK CF registry in 2011, 89% used airway clearance techniques. The most commonly used primary techniques were forced expiratory techniques (28%) and oscillating positive expiratory pressure (PEP) (23%). Postural drainage and high-frequency chest wall oscillation were used by 4% and 1% of people with CF, respectively. The male:female ratio of individuals who used exercise as their primary airway clearance technique was 2:1, compared with 1:1 for other techniques. Individuals with more severe lung disease tended to use devices such as non-invasive ventilation or high-frequency chest wall oscillation. CONCLUSIONS: Forced expiratory techniques and oscillating PEP are the most common airway clearance techniques used by people with CF in the UK, and postural drainage and high-frequency chest wall oscillation are the least common techniques. This is significant in terms of planning airway clearance technique trials, where postural drainage has been used traditionally as the comparator. The use of airway clearance techniques varies between countries, but the reasons for these differences are unknown.

Exploration of the impact of 'mild phenotypes' on median age at death in the U.K. CF registry.

BACKGROUND: The widespread availability of genetic testing allowing the identification of "milder" individuals with CF coincided with improvements in CF life expectancy but the relative contribution of case mix to that improved survival is uncertain. METHODS: Patients in the U.K. CF registry were divided into 'mild phenotype' defined as pancreatic sufficient and 'typical CF' defined as pancreatic insufficient. Distributions of age at death were compared with Mann-Whitney test. Temporal trends in incidence and prevalence were described. Jonckheere-Terpstra test was used to compare the trend for median age at death from 2007 to 2010. RESULTS: Patients with 'mild phenotype' had significantly higher age at death (32 years, interquartile range 14 years versus 27 years, interquartile range 29 years; Mann-Whitney test p-value = 0.026). The proportion of patients with 'mild phenotype' appeared to be increasing (0.128 in 2007, 0.144 in 2010). The trend for increasing age at death (from 25 years in 2007 to 29 years in 2010, Jonckheere-Terpstra test p-value = 0.012) was independent of the 'mild phenotype' patients. CONCLUSION: The impact of mild phenotypes on the improvement in the median age at death among people with CF was trivial.

Predicting mortality for patients with exacerbations of COPD and Asthma in the COPD and Asthma Outcome Study (CAOS).

INTRODUCTION: Decisions about the intensity of treatment for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are influenced by predictions about survival and quality of life. Evidence suggests that these predictions are poorly calibrated and tend to be pessimistic. AIM: The aim of this study was to develop an outcome prediction model for COPD patients to support treatment decisions. METHODS: A prospective multi-centre cohort study in Intensive Care Units (ICU) and Respiratory High Dependency Units (RHDU) in the UK recruited patients aged 45 years and older admitted with an exacerbation of obstructive lung disease. Data were collected on patients' characteristics prior to ICU admission, and on their survival and quality of life after 180 days. An outcome prediction model was developed using multivariate logistic regression and bootstrapping. RESULTS: Ninety-two ICUs (53% of those in the UK) and three RHDUs took part. A total of 832 patients were recruited. Cumulative 180-day mortality was 37.9%. Using data available at the time of admission to the units, a prognostic model was developed which had an estimated area under the receiver operating characteristic curve ('c') of 74.7% after bootstrapping that was more discriminating than the clinicians (P = 0.033) and was well calibrated. DISCUSSION: This study has produced an outcome prediction model with slightly better discrimination and much better calibration than the participating clinicians. It has the potential to support risk adjustment and clinical decision making about admission to intensive care.

Survival and quality of life for patients with COPD or asthma admitted to intensive care in a UK multicentre cohort: the COPD and Asthma Outcome Study (CAOS).

BACKGROUND: Non-invasive ventilation is first-line treatment for patients with acutely decompensated chronic obstructive pulmonary disease (COPD), but endotracheal intubation, involving admission to an intensive care unit, may sometimes be required. Decisions to admit to an intensive care unit are commonly based on predicted survival and quality of life, but the information base for these decisions is limited and there is some evidence that clinicians tend to be pessimistic. This study examined the outcomes in patients with COPD admitted to the intensive care unit for decompensated type II respiratory failure. METHODS: A prospective cohort study was carried out in 92 intensive care units and 3 respiratory high dependency units in the UK. Patients aged 45 years and older with breathlessness, respiratory failure or change in mental status due to an exacerbation of COPD, asthma or a combination of the two were recruited. Outcomes included survival and quality of life at 180 days. RESULTS: Of the 832 patients recruited, 517 (62%) survived to 180 days. Of the survivors, 421 (81%) responded to a questionnaire. Of the respondents, 73% considered their quality of life to be the same as or better than it had been in the stable period before they were admitted, and 96% would choose similar treatment again. Function during the stable pre-admission period was a reasonable indicator of function reported by those who survived 180 days. CONCLUSIONS: Most patients with COPD who survive to 180 days after treatment in an intensive care unit have a heavy burden of symptoms, but almost all of them-including those who have been intubated-would want similar intensive care again under similar circumstances.

Variation in intubation decisions for patients with chronic obstructive pulmonary disease in one critical care network.

BACKGROUND: Anecdotal evidence suggests variation in intubation decisions for chronic obstructive pulmonary disease (COPD) patients with respiratory failure, but little is known about the extent of or reasons for this variability. AIM: To describe clinician decision-making for patients with exacerbations of COPD considered for intubation. DESIGN: Telephone simulation study. METHODS: Consultants responsible for COPD admissions in the Heart of England Critical Care network were asked to decide whether or not to admit three patients with COPD to ICU on the basis of information conveyed over the telephone. Consultants were also asked to predict patients survival in ICU hospital and at 180 days on the assumption that the patient did receive ICU care. RESULTS: Of the 120 consultants, 98 (82%) took part; 89% would admit patient 1, 64% patient 2, and 40% patient 3. The prediction of survival if ICU admission had occurred differed significantly between admitters and non-admitters. Mean predicted post-ICU hospital survival for patient 1 was 46% (95%CI 43-49) for admitters, and 13% (95%CI 6-19) for non-admitters (p < 0.001). The respective figures for patient 2 were 38% (95%CI 34-42) vs. 12% (95%CI 8-15) (p < 0.001), and for patient 3, 28% (95%CI 24-33) vs. 13% (95%CI 10-16) (p < 0.001). For a housebound COPD patient in their mid 70s, the mean (SD) threshold of predicted hospital survival below which consultants would recommend not admitting to ICU was 22% (13.2%). CONCLUSIONS: Consultants differed markedly in their admitting decisions about identical patients. Objective outcome prediction models might improve equity in ICU bed use for patients with COPD.

Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort.

BACKGROUND: Some patients exposed to Q fever (Coxiella burnetii infection) may develop chronic fatigue. AIM: To determine whether subjects involved in the West Midlands Q fever outbreak of 1989 had increased fatigue, compared to non-exposed controls, 10 years after exposure. DESIGN: Matched cohort study comparing cases to age-, sex- and smoking-history-matched controls not exposed to Q fever. METHODS: A postal questionnaire was sent to subjects at home, followed by further assessment in hospital, including a physical examination and blood tests. RESULTS: Of 108 Q-exposed subjects, 70 (64.8%) had fatigue, 37 idiopathic chronic fatigue (ICF) (34.3%), vs. 29/80 (36.3%) and 12 (15.0%), respectively, in controls. In 77 matched pairs, fatigue was commoner in Q-exposed subjects than in controls: 50 (64.9%) vs. 27 (35.1%), p<0.0001. ICF was found in 25 (32.5%) of Q-exposed patients and 11(14.3%) of controls (p=0.01). There were 36 (46.8%) GHQ cases in Q-exposed subjects, vs. 18 (23.4%) controls (p=0.004). A matched analysis of those more intensively studied showed fatigue in 48 (66.7%) Q-exposed patients and 25 (34.7%) controls, (p<0.0001), ICF in 25 (34.7%) Q-exposed and 10 (13.9%) controls (p=0.004), and chronic fatigue syndrome (CFS) in 14 (19.4%) Q-exposed patients and three (4.2%) controls (p=0.003). Thirty-four (47.2%) Q-exposed patients were GHQ cases compared to 17 (23.6%) controls (p=0.004). DISCUSSION: Subjects who were exposed to Coxiella in 1989 had more fatigue than did controls, and some fulfilled the criteria for CFS. Whether this is due to ongoing antigen persistence or to the psychological effects of prolonged medical follow-up is uncertain.

RDX degradation using an integrated Fe(0)-microbial treatment approach.

RDX is a persistent and highly mobile groundwater contaminant that represents a major remediation challenge at numerous munitions manufacturing and load-assemblage-package facilities. This work presents proof of concept that permeable reactive iron barriers might be a viable approach to intercept and degrade RDX plumes. Specifically, RDX was rapidly reduced in aquifier microcosms amended with Fe(0) powder, and in flow-through columns packed with steel wool. The rate and extent of RDX degradation in microcosms was enhanced by anaerobic bacteria that feed on cathodic hydrogen (i.e., H2 produced during anaerobic Fe(0) corrosion by water). Apparently, the hydrogenotrophic consortium that exploits Fe(0) corrosion as a metabolic niche participated in the further degradation of heterocyclic intermediates produced by the reaction of RDX with Fe(0). Reductive treatment of RDX with Fe(0) also reduced its toxicity to microorganisms and enhanced its subsequent biodegradability under either anaerobic or anaerobic conditions. Therefore, a combined or sequential Fe(0)-biological treatment approach might improve treatment efficiency.