Sheila McCorkindale

Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice

BACKGROUND Evidence for the management of chronic obstructive pulmonary disease (COPD) comes from closely monitored efficacy trials involving groups of patients who were selected on the basis of restricted entry criteria. There is a need for randomized trials to be conducted in conditions that are closer to usual clinical practice. METHODS In a controlled effectiveness trial conducted in 75 general practices, we randomly assigned 2799 patients with COPD to a once-daily inhaled combination of fluticasone furoate at a dose of 100 μg and vilanterol at a dose of 25 μg (the fluticasone furoate-vilanterol group) or to usual care (the usual-care group). The primary outcome was the rate of moderate or severe exacerbations among patients who had had an exacerbation within 1 year before the trial. Secondary outcomes were the rates of primary care contact (contact with a general practitioner, nurse, or other health care professional) and secondary care contact (inpatient admission, outpatient visit with a specialist, or visit to the emergency department), modification of the initial trial treatment for COPD, and the rate of exacerbations among patients who had had an exacerbation within 3 years before the trial, as assessed in a time-to-event analysis. RESULTS The rate of moderate or severe exacerbations was significantly lower, by 8.4% (95% confidence interval, 1.1 to 15.2), with fluticasone furoate-vilanterol therapy than with usual care (P=0.02). There was no significant difference in the annual rate of COPD-related contacts to primary or secondary care. There were no significant between-group differences in the rates of the first moderate or severe exacerbation and the first severe exacerbation in the time-to-event analyses. There were no excess serious adverse events of pneumonia in the fluticasone furoate-vilanterol group. The numbers of other serious adverse events were similar in the two groups. CONCLUSIONS In patients with COPD and a history of exacerbations, a once-daily treatment regimen of combined fluticasone furoate and vilanterol was associated with a lower rate of exacerbations than usual care, without a greater risk of serious adverse events. (Funded by GlaxoSmithKline; Salford Lung Study ClinicalTrials.gov number, NCT01551758 .).

Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial

BACKGROUND Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice. METHODS We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioners diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 μg or 200 μg fluticasone furoate with 25 μg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198. FINDINGS Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70-2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3-2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups. INTERPRETATION In patients with a general practitioners diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care. FUNDING GlaxoSmithKline.

Monitoring safety in a phase III real‐world effectiveness trial: use of novel methodology in the Salford Lung Study

The Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once‐daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records.

The Evidence of Acute Kidney Injury in the Community and for Primary Care Interventions

Background: Almost two-thirds of patients with acute kidney injury (AKI) damage their kidneys whilst in the community. This paper aims to review existing data on incidence, mortality, and morbidity of AKI within the community and explore the evidence base for primary care strategies aimed at reducing incidence and improving early detection and management of AKI. Methods: A literature search was carried out using PubMed; key words including AKI, primary care, community acquired, and electronic alerts (e-alerts) were used to capture relevant data. Results: Incidence of AKI developing in the community is variable between studies due to differences in AKI definition. Community-acquired AKI (CA-AKI) but identified in hospital (CAH-AKI) is more prevalent than hospital-acquired AKI and increases short- and long-term mortality and length of stay in hospital. CA-AKI identified in primary care is less severe than CAH-AKI but is associated with increased mortality. The use of e-alerts has good diagnostic accuracy for detecting AKI but their impact on outcomes in secondary care remains uncertain; it is likely that they should be complemented with other interventions to improve management. Evidence has not yet emerged regarding the effects of e-alerts on outcomes in primary care. Conclusion: Given the significance of developing AKI in the community, strategies to aid early detection and promote prevention are warranted. A multifaceted approach combining e-alerts, educational programs, and care bundles across the interface between primary and secondary care has the potential to improve outcomes in the future.

Acute kidney injury in primary care: where are we now and where are we going?

Acute kidney injury (AKI) is defined as ‘a clinical and biochemical diagnosis reflecting abrupt kidney dysfunction’ .1 AKI is graded on a scale of 1–3 based on the size of the creatinine increase from baseline. Higher AKI scores are associated with higher mortality, longer length of stay, and less renal recovery.2 AKI complicates almost one in five hospital admissions and is associated with a 20–33% mortality rate, increased length of hospital stay, and an estimated annual cost to the NHS in England of £1.02 billion.3 Two-thirds of AKI cases identified in hospital start in the community.2 NHS England and the UK Renal Association Renal Registry’s Think Kidneys programme have supported changes and improvement in AKI identification, measurement, risk assessment, and education across UK health care including the implementation of a national electronic system that alerts clinicians to potential cases of AKI.1 Around 60% of all patients with AKI identified in hospital have it when they reach hospital.2 The mortality of these patients with community-acquired AKI detected in hospital (CAH-AKI) is 19.6% during hospitalisation, which increases to an alarming 45% 14 months post-discharge.4 Although CAH-AKI has a lower mortality rate than hospital-acquired AKI, CAH-AKI represents a noteworthy risk factor for death. The incidence of community-acquired AKI detected in primary care (CAP-AKI) varies according to the use of different AKI definitions and different methodologies for acquiring a baseline creatinine. Sawhney et al 5 used the official NHS AKI algorithm and reported that 1.4% of 50 835 patients in a Scottish registry who also had a known creatinine …

Understanding the implementation of ‘sick day guidance’ to prevent acute kidney injury across a primary care setting in England: a qualitative evaluation

Objectives The study sought to examine the implementation of sick day guidance cards designed to prevent acute kidney injury (AKI), in primary care settings. Design Qualitative semistructured interviews were conducted and comparative analysis informed by normalisation process theory was undertaken to understand sense-making, implementation and appraisal of the cards and associated guidance. Setting A single primary care health setting in the North of England. Participants 29 participants took part in the qualitative evaluation: seven general practitioners, five practice nurses, five community pharmacists, four practice pharmacists, two administrators, one healthcare assistant and five patients. Intervention The sick day guidance intervention was rolled out (2015–2016) in general practices (n=48) and community pharmacies (n=60). The materials consisted of a ‘medicine sick day guidance’ card, provided to patients who were taking the listed drugs. The card provided advice about medicines management during episodes of acute illness. An information leaflet was provided to healthcare practitioners and administrators suggesting how to use and give the cards. Results Implementation of sick day guidance cards to prevent AKI entailed a new set of working practises across primary care. A tension existed between ensuring reach in administration of the cards to at risk populations while being confident to ensure patient understanding of their purpose and use. Communicating the concept of temporary cessation of medicines was a particular challenge and limited their administration to patient populations at higher risk of AKI, particularly those with less capacity to self-manage. Conclusions Sick day guidance cards that focus solely on medicines management may be of limited patient benefit without adequate resourcing or if delivered as a standalone intervention. Development and evaluation of primary care interventions is urgently warranted to tackle the harm associated with AKI.

Rapid recruitment of large cohort to support trials in general practice: the role of FARSITE

There is increasing interest in the cohort multiple randomised controlled trial (cmRCT - Relton BMJ doi: 10.1136/bmj.c1066) as a model for pragmatic trials in general practice. We have adopted the design for our CLASSIC study of integrated care (http://www.nets.nihr.ac.uk/projects/hsdr/1213033). However, the cmRCT needs rapid recruitment of large patient cohorts, which can be a logistical challenge. Traditionally, general practices must make the initial approach to patients to take part in trials. This requires investment of time and resources, acting as a barrier to GPs who might be interested in research.