STOP- a training intervention to optimise treatment for smoking cessation in community pharmacies: cluster randomised controlled trial.

BACKGROUND: Community pharmacies serve people with high levels of tobacco-related illness, but throughput in NHS Stop Smoking Services in pharmacies remains relatively low. We investigated the effectiveness of a complex intervention to increase service uptake and retention. METHODS: We randomised 60 pharmacies in England and Wales to the STOP intervention or usual practice in a pragmatic, parallel-group, controlled trial over 11 months. Smokers were blind to the allocation. The intervention was theory-based consultation skills training for pharmacy staff with environmental prompts (badges, calendars and behavioural cues). The primary outcome was the number of smokers attending an initial consultation and setting a quit date. RESULTS: The intervention made no significant difference in setting a quit date, retention or quit rate. A total of 631 adult smokers (service users) enrolled and set a quit date in intervention pharmacies compared to 641 in usual practice pharmacies, a rate ratio of 0.75 (95% CI 0.46 to 1.23) adjusted for site and number of prescriptions. A total of 432 (68%) service users were retained at 4 weeks in intervention and 500 (78%) in usual practice pharmacies (odds ratio 0.80, 0.41 to 1.55). A total of 265 (42%) service users quit smoking at 4 weeks in intervention and 276 (43%) in usual practice pharmacies (0.96, 0.65 to 1.43). The pharmacy staff were positive about the intervention with 90% (56/62) stating that it had improved their skills. Sixty-eight per cent would strongly recommend the training to others although there was no difference in self-efficacy for service delivery between arms. Seventy of 131 (53%) service users did not complete the 6-month follow-up assessment. However, 55/61 (90%) service users who completed follow-up were satisfied or very satisfied with the service. All usual practice arm service users (n = 33) and all but one in the intervention arm (n = 27) would recommend the service to smokers. CONCLUSIONS: We found high levels of retention and acceptable quit rates in the NHS pharmacy stop smoking service. Despite pharmacy staff providing positive feedback on the STOP intervention, it made no difference to service throughput. Thus, other factors may currently limit service capacity to help smokers to quit. TRIAL REGISTRATION: ISRCTN, ISRCTN16351033 . Retrospectively registered.

Evaluating the effectiveness and cost-effectiveness of the Smoking Treatment Optimisation in Pharmacies (STOP) intervention: protocol for a cluster randomised controlled trial.

BACKGROUND: NHS community pharmacies provide effective smoking cessation services; however, there is scope for increasing throughput and improving quit rates. This trial examines whether the Smoking Treatment Optimisation in Pharmacies (STOP) intervention can improve smoker engagement to increase service throughput, retention and quitting. METHODS: This study is a pragmatic, cluster randomised controlled trial in 60 pharmacies in England and Wales. All workers in intervention pharmacies are offered STOP training while control pharmacies provide usual care. The STOP intervention, based on behavioural and organisational theories, comprises educational sessions for staff and environmental prompts in the pharmacy. Intervention fidelity is assessed by actors visiting pharmacies posing as smokers. The primary outcome is throughput, defined as the number of smokers who join the programme, set a firm quit date and undergo at least one stop smoking treatment session, and is measured using routinely collected data. Secondary outcomes include retention and quit rates at 4 weeks and continuous abstinence at 6 months verified by salivary cotinine. Cost-effectiveness is estimated using quality-adjusted life years and the probability that the intervention is effective at different levels of willingness to pay is calculated. DISCUSSION: The trial will generate evidence to inform the public health smoking cessation strategy in England and Wales, and may help to shape service commissioning decisions. The STOP intervention model may help inform the undertaking of a range of health behaviour change tasks in community pharmacies. TRIAL REGISTRATION: ClinicalTrials.gov, ISRCTN16351033. Retrospectively registered on 21 March 2017.

A randomized, open-label, single-visit, crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD.

Background: Administering maintenance COPD therapy with a combination of multiple inhalers may increase inhaler errors. This study evaluated the potential benefits of using a single Ellipta dry powder inhaler (DPI) compared with two combinations of DPIs commonly used to deliver triple maintenance therapy. Methods: Patients receiving inhaled COPD medication were enrolled in this multicenter, randomized, open-label, placebo-device, crossover study with a 2×2 complete block design (NCT0298218), which comprised two substudies: Ellipta vs Diskus + HandiHaler (substudy 1) or Turbuhaler + HandiHaler (substudy 2). Patients demonstrated inhaler use after reading the relevant patient information leaflet (PIL). A trained investigator assessed user errors (critical errors [errors likely to result in no or significantly reduced medication being inhaled] and overall errors). The primary endpoint was the proportion of patients making ≥1 critical error after reading the PIL. The secondary endpoints included error rates during ≤2 reassessments following investigator instruction (if required), instruction time, and patient preference. Results: After reading the PIL, significantly fewer patients made critical errors with Ellipta compared with Diskus + HandiHaler (9% [7/80] vs 75% [60/80], respectively; P<0.001) or Turbuhaler + HandiHaler (9% [7/79] vs 73% [58/79], respectively; P<0.001). The number of patients making overall errors was also lower with Ellipta vs tested inhaler combinations (P<0.001 for each substudy). The median instruction time needed for error-free use was shorter with Ellipta in substudies 1 and 2 (2.7 and 2.6 minutes, respectively) vs either combination (10.6 [Diskus + HandiHaler] and 11.3 minutes [Turbuhaler + HandiHaler], respectively). Significantly more patients preferred Ellipta over Diskus + HandiHaler or Turbuhaler + HandiHaler overall for taking their COPD medication (81% vs 9% and 84% vs 4%, respectively) and per the number of steps for taking their COPD medication (89% vs 8% and 91% vs 5%, respectively). Conclusion: Fewer patients with COPD made critical errors with the single DPI, and patients required less instruction time, compared with each dual DPI combination.

Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with Chronic Obstructive Pulmonary Disease in London, UK.

Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41-92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV1), % predicted forced vital capacity (FVC), the ratio of FEV1 to FVC (FEV1:FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50nmol/L). Lower vitamin D status was independently associated with higher body mass index (P=0.001), lower socio-economic position (P=0.037), lack of vitamin D supplement consumption (P<0.001), sampling in Winter or Spring (P for trend=0.006) and lack of a recent sunny holiday (P=0.002). Vitamin D deficiency associated with reduced % predicted FEV1 (P for trend=0.060) and % predicted FVC (P for trend=0.003), but it did not associate with FEV1:FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD.

Equipping community pharmacy workers as agents for health behaviour change: developing and testing a theory-based smoking cessation intervention.

OBJECTIVE: To develop a complex intervention for community pharmacy staff to promote uptake of smoking cessation services and to increase quit rates. DESIGN: Following the Medical Research Council framework, we used a mixed-methods approach to develop, pilot and then refine the intervention. METHODS: Phase I: We used information from qualitative studies in pharmacies, systematic literature reviews and the Capability, Opportunity, Motivation-Behaviour framework to inform design of the initial version of the intervention. Phase II: We then tested the acceptability of this intervention with smoking cessation advisers and assessed fidelity using actors who visited pharmacies posing as smokers, in a pilot study. Phase III: We reviewed the content and associated theory underpinning our intervention, taking account of the results of the earlier studies and a realist analysis of published literature. We then confirmed a logic model describing the intended operation of the intervention and used this model to refine the intervention and associated materials. SETTING: Eight community pharmacies in three inner east London boroughs. PARTICIPANTS: 12 Stop Smoking Advisers. INTERVENTION: Two, 150 min, skills-based training sessions focused on communication and behaviour change skills with between session practice. RESULTS: The pilot study confirmed acceptability of the intervention and showed preliminary evidence of benefit; however, organisational barriers tended to limit effective operation. The pilot data and realist review pointed to additional use of Diffusion of Innovations Theory to seat the intervention in the wider organisational context. CONCLUSIONS: We have developed and refined an intervention to promote smoking cessation services in community pharmacies, which we now plan to evaluate in a randomised controlled trial. TRIAL REGISTRATION NUMBER: UKCRN ID 18446, Pilot.

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

RATIONALE: Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. OBJECTIVES: To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. METHODS: Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting ß2-agonist fluticasone furoate/vilanterol 100/25 µg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. MEASUREMENTS AND MAIN RESULTS: There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. CONCLUSIONS: Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections. METHODS: We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873. FINDINGS: 240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0·81-2·62, p=0·21; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status). Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection (pinteraction=0·41). INTERPRETATION: Vitamin D3 supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation. FUNDING: UK National Institute for Health Research.

Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial.

BACKGROUND: Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD). Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity. The effect of withdrawing ICS from COPD patients in primary care is unknown. METHODS: In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132). Follow-up assessments took place at three monthly intervals for a year at the patients' practice. Our primary outcome was COPD exacerbation frequency. Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life. RESULTS: In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36). Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05). Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86). Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze. In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14). CONCLUSION: Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration. Patients with mild COPD may be at increased risk of exacerbation after withdrawal. TRIAL REGISTRATION: ClinicalTrials.gov NCT00440687.