Defining the content and delivery of an intervention to Change AdhereNce to treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the Theoretical Domains Framework, behavioural change techniques and stakeholder expert panels

BACKGROUND: Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients' adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3). METHODS: We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients' adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3). RESULTS: Eight TDF domains were perceived to influence patients' and HCPs' behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3). CONCLUSIONS: Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future

Treatment adherence and health outcomes in patients with bronchiectasis

BACKGROUND: We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. METHODS: Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as "adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. RESULTS: Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. CONCLUSIONS: Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies

Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the ‘review & revise’ experience

Background: We aimed to investigate and optimise the acceptability and usefulness of a patient leaflet about antibiotic prescribing decisions made during hospitalisation, and to explore individual patient experiences and preferences regarding the process of antibiotic prescription ‘review & revise’ which is a key strategy to minimise antibiotic overuse in hospitals. Methods: In this qualitative study, run within the feasibility study of a large, cluster-randomised stepped wedge trial of 36 hospital organisations, a series of semi-structured, think-aloud telephone interviews were conducted and data were analysed using thematic analysis. Fifteen adult patients who had experienced a recent acute medical hospital admission during which they had been prescribed antimicrobials and offered a patient leaflet about antibiotic prescribing were recruited to the study. Results: Participants reacted positively to the leaflet, reporting that it was both an accessible and important source of information which struck the appropriate balance between informing and reassuring. Participants all valued open communication with clinicians, and were keen to be involved in antibiotic prescribing decisions, with individuals reporting positive experiences regarding antibiotic prescription changes or stopping. Many participants had prior experience or knowledge of antibiotics and resistance, and generally welcomed efforts to reduce antibiotic usage. Overall, there was a feeling that healthcare professionals (HCPs) are trusted experts providing the most appropriate treatment for individual patient conditions. Conclusions: This study offers novel insights into how patients within secondary care are likely to respond to messages advocating a reduction in the use of antibiotics through the ‘review & revise’ approach. Due to the level of trust that patients place in their care provider, encouraging HCPs within secondary care to engage patients with greater communication and information provision could provide great advantages in the drive to reduce antibiotic use. It may also be beneficial for HCPs to view patient experiences as cumulative events that have the potential to impact future behaviour around antibiotic use. Finally, pre-testing messages about antibiotic prescribing and resistance is vital to dispelling any misconceptions either around effectiveness of treatment for patients, or perceptions of how messages may be received

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate

Patient Discomfort Associated with the Use of Intra-arterial Iodinated Contrast Media: A Meta-Analysis of Comparative Randomized Controlled Trials

<p>Abstract</p> <p>Background</p> <p>Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).</p> <p>Methods</p> <p>A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed to compare rates of discomfort associated with the use of the IOCM (iodixanol) vs. various LOCM agents in head-to-head RCTs. All trials with a Jadad score ≥2 that reported patient discomfort data following intra-arterial administration of CM were reviewed, coded, and extracted.</p> <p>Results</p> <p>A total of 22 RCTs (n = 8087) were included. Overall discomfort (regardless of severity) was significantly different between patients receiving IOCM and various LOCMs (risk difference [RD] -0.049; 95% confidence interval [CI]: -0.076, -0.021; p = 0.001). IOCM was favored over all LOCMs combined with a summary RD value of -0.188 (95% CI: -0.265, -0.112; p < 0.001) for incidence of pain, regardless of severity. A greater reduction in the magnitude of pain was observed with IOCM (iodixanol), particularly with selective limb and carotid/intracerebral procedures. Similarly, the meta-analysis of warmth sensation, regardless of severity, favored IOCM over LOCMs with an RD of -0.043 (95% CI: -0.074, -0.011; p = 0.008). A positive linear relationship was observed between the discomfort effect size and age and a negative relationship with increasing proportion of women. The opposite trends were observed with warmth sensation.</p> <p>Conclusions</p> <p>IOCM was associated with less frequent and severe patient discomfort during intra-arterial administration. These data support differences in osmolality as a possible determinant of CM discomfort.</p

Adherence to treatment in children and adolescents with cystic fibrosis:a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms

Background: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence. Methods: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Results: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence. Conclusions: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children

The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone