OBJECTIVE. Newborn screening for cystic fibrosis remains controversial because improved pulmonary function has not been established. Studies to date have not accounted for differences in treatments delivered to clinically diagnosed children and newborn-screened controls. Here, we compare outcomes and treatment of patients clinically diagnosed within the newborn-screening reporting window (early-clinically diagnosed), those presenting after this period (late-clinically diagnosed), and patients diagnosed by newborn screening. PATIENTS AND METHODS. In a cross-sectional analysis of cohorts retrospectively ascertained, patients who were homozygous ΔF508 with cystic fibrosis, attending specialist cystic fibrosis centers, and 1 to 10 years of age between 2000 and 2002 were identified from the United Kingdom Cystic Fibrosis Database and stratified into newborn-screened, early-clinically diagnosed, or late-clinically diagnosed cohorts. Two analyses were performed: (1) after restricting to the most recent year of data collection, early-clinically diagnosed and late-clinically diagnosed cohorts were matched to newborn-screened patients by patient age and year of data collection (133 patients per cohort were identified); and (2) for all years of data collection, annual sets of data for early-clinically diagnosed and late-clinically diagnosed patients were matched to newborn-screened patients by patient age and year of data collection (291 data sets per cohort were identified). Median height and weight z scores, proportion of patients with height and weight <10th percentile, prevalence of chronic Pseudomonas aeruginosa infection, Shwachman-Kulczyki morbidity scores, percent predicted forced expiratory volume in 1 second, and numbers of long-term therapies were compared. RESULTS. In both analyses, newborn screening was associated with higher height z score, higher Shwachman-Kulczyki score, lower likelihood of height <10th percentile, and fewer long-term therapies compared with late-clinically diagnosed patients. No other differences were found. CONCLUSIONS. Newborn screening was associated with improved growth, reduced morbidity, and reduced therapy, yet generated equivalent pulmonary outcome compared with late clinical diagnosis, suggesting that newborn screening may slow cystic fibrosis lung disease progression.

Serious inhaler technique errors can impair drug delivery to the lungs. This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers. Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order. Patients inhaled through empty devices after reading the patient information leaflet. If serious errors potentially affecting dose delivery were recorded, they repeated the inhalations after watching a training video. Inhaler technique was assessed by a trained nurse observer and an electronic inhalation profile recorder. Baseline patient characteristics were similar between randomisation arms for the Pulmojet-Diskus (n = 277) and Pulmojet-Turbohaler (n = 144) comparisons. Non-inferiority in the proportions of patients recording no nurse-observed serious errors was demonstrated for both Pulmojet versus Diskus, and Pulmojet versus Turbohaler; therefore, superiority was tested. Patients were significantly less likely to make ≥1 nurse-observed serious errors using Pulmojet compared with Diskus (odds ratio, 0.31; 95 % CI, 0.19–0.51) or Pulmojet compared with Turbohaler (0.23; 0.12–0.44) after reading the patient information leaflet with additional video instruction, if required. These results suggest Pulmojet is easier to learn to use correctly than the Turbohaler or Diskus for current inhaler users switching to a new dry powder inhaler. ClinicalTrials.gov Identifier: NCT01794390 (February 14, 2013)

Health and social care provision for an ageing population is a global priority. Provision for those with dementia and hip fracture has specific and growing importance. Older people who break their hip are recognised as exceptionally vulnerable to experiencing confusion (including but not exclusively, dementia and/or delirium and/or cognitive impairment(s)) before, during or after acute admissions. Older people experiencing hip fracture and confusion risk serious complications, linked to delayed recovery and higher mortality post-operatively. Specific care pathways acknowledging the differences in patient presentation and care needs are proposed to improve clinical and process outcomes. This protocol describes a multi-centre, feasibility, cluster-randomised, controlled trial (CRCT) to be undertaken across ten National Health Service hospital trusts in the UK. The trial will explore the feasibility of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery intervention (PERFECT-ER), which acknowledges the differences in care needs of confused older patients experiencing hip fracture, with standard care. The trial will also have an integrated process evaluation to explore how PERFECT-ER is implemented and interacts with the local context. The study will recruit 400 hip fracture patients identified as experiencing confusion and will also recruit “suitable informants” (individuals in regular contact with participants who will complete proxy measures). We will also recruit NHS professionals for the process evaluation. This mixed methods design will produce data to inform a definitive evaluation of the intervention via a large-scale pragmatic randomised controlled trial (RCT). The trial will provide a preliminary estimate of potential efficacy of PERFECT-ER versus standard care; assess service delivery variation, inform primary and secondary outcome selection, generate estimates of recruitment and retention rates, data collection difficulties, and completeness of outcome data and provide an indication of potential economic benefits. The process evaluation will enhance knowledge of implementation delivery and receipt. ISRCTN, 99336264 . Registered on 5 September 2016.

Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists. In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients. Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05–6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80–1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09–0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25–3.54]). In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler. EudraCT 2013-004630-14 (registration date 23 January 2014); NCT02570425 .

Despite effective treatments and long-standing management guidelines, there are approximately 1400 hospital admissions for asthma weekly in the United Kingdom (UK), many of which could be avoided. In our previous research, a secondary analysis of the intervention (ARRISA) suggested an improvement in the management of at-risk asthma patients in primary care. ARRISA involved identifying individuals at risk of adverse asthma events, flagging their electronic health records, training practice staff to develop and implement practice-wide processes of care when alerted by the flag, plus motivational reminders. We now seek to determine the effectiveness and cost-effectiveness of ARRISA in reducing asthma-related crisis events. We are undertaking a pragmatic, two-arm, multicentre, cluster randomised controlled trial, plus health economic and process evaluation. We will randomise 270 primary care practices from throughout the UK covering over 10,000 registered patients with ‘at-risk asthma’ identified according to a validated algorithm. Staff in practices randomised to the intervention will complete two 45-min eLearning modules (an individually completed module giving background to ARRISA and a group-completed module to develop practice-wide pathways of care) plus a 30-min webinar with other practices. On completion of training at-risk patients’ records will be coded so that a flag appears whenever their record is accessed. Practices will receive a phone call at 4 weeks and a reminder video at 6 weeks and 6 months. Control practices will continue to provide usual care. We will extract anonymised routine patient data from primary care records (with linkage to secondary care data) to determine the percentage of at-risk patients with an asthma-related crisis event (accident and emergency attendances, hospitalisations and deaths) after 12 months (primary outcome). We will also capture the time to crisis event, all-cause hospitalisations, asthma control and any changes in practice asthma management for at-risk and all patients with asthma. Cost-effectiveness analysis and mixed-methods process evaluations will also be conducted. This study is novel in terms of using a practice-wide intervention to target and engage with patients at risk from their asthma and is innovative in the use of routinely captured data with record linkage to obtain trial outcomes. ISRCTN95472706 . Registered on 5 December 2014.