Inhaler and nebuliser technique for people with a learning disability

Healthcare professionals who support people who require an inhaler or nebuliser need to know how to use the devices, monitor and assess patients’ inhaler techniques effectively. Often, people have inadequate inhaler techniques, which can lead to poor management of their respiratory condition, increased signs and symptoms, reduced quality of life and increased use of primary/secondary care services and treatment costs. This article explains how to use inhalers and nebulisers appropriately and considers some of the challenges for children and adults with a learning disability. It also describes some devices and assessment tools, and explores assessment/review methods to help ensure people use their inhalers/nebulisers successfully

Clinical effectiveness and cost-effectiveness results from the randomised, Phase IIB trial in previously untreated patients with chronic lymphocytic leukaemia to compare fludarabine, cyclophosphamide and rituximab with fludarabine, cyclophosphamide, mitoxantrone and low-dose rituximab: the Attenuated dose Rituximab with ChemoTherapy In Chronic lymphocytic leukaemia (ARCTIC) trial

Background: The conventional frontline therapy for fit patients with chronic lymphocytic leukaemia (CLL) is fludarabine, cyclophosphamide and rituximab (FCR). Rituximab (Mabthera®, Roche Products Ltd) targets the CD20 antigen, which is expressed at low levels in CLL. The standard dose of rituximab in CLL (375 mg/m2 in cycle 1 and 500 mg/m2 in cycles 2–6) was selected based on toxicity data only. Small doses of rituximab (as low as 20 mg) have biological activity in CLL, with an immediate reduction in circulating CLL cells and down-regulation of CD20. Phase II trials had suggested improved efficacy with the addition of mitoxantrone to FCR. The key assumption for the Attenuated dose Rituximab with ChemoTherapy In CLL (ARCTIC) trial was that the addition of mitoxantrone to fludarabine, cyclophosphamide and low-dose rituximab would be more effective than conventional FCR. Objectives: To assess whether fludarabine, cyclophosphamide, mitoxantrone and low-dose rituximab (FCM-miniR) (100 mg of rituximab per cycle) was non-inferior to FCR in frontline CLL. Complete response (CR) rate was the primary end point, with the secondary end points being progression-free survival (PFS), overall survival (OS), overall response rate, eradication of minimal residual disease (MRD), safety and cost-effectiveness. Design: ARCTIC was a UK multicentre, randomised, controlled, open, Phase IIB non-inferiority trial in previously untreated CLL. A total of 206 patients with previously untreated CLL who required treatment, according to the International Workshop on Chronic Lymphocytic Leukaemia criteria, were to be randomised to FCR or FCM-miniR. There was an independent Data Monitoring and Ethics Committee (DMEC) with a pre-planned interim efficacy assessment on 103 participants. Results: The DMEC’s interim analysis led to early trial closure. Although the response rates in both arms were higher than anticipated, FCM-miniR had a lower CR rate than FCR. This was partly attributable to the higher toxicity associated with mitoxantrone. A total of 100 participants completed FCR, 79 completed FCM-miniR and 21 commenced FCM-miniR but switched to FCR following DMEC recommendations. The CR rate for participants receiving FCR was 76%, compared with 55% for FCM-miniR (adjusted odds ratio 0.37; 95% confidence interval 0.19 to 0.73). Key secondary end points also showed that FCR was superior, with more participants achieving MRD negativity (57% for FCR vs. 46% for FCM-miniR). More participants experienced a serious adverse reaction with FCM-miniR compared with FCR (50% vs. 41%). At a median of 37.3 months’ follow-up, the PFS and OS rates are good compared with previous studies, with no significant difference between the treatment arms. The economic analysis indicates that because FCM-miniR is less effective than FCR, FCM-miniR is not expected to be cost-effective over a lifetime horizon, producing a mean cost-saving of –£7723, a quality-adjusted life-year loss of –0.73 and a resulting incremental net monetary loss of –£6780. Conclusions: FCM-miniR is less well tolerated, with poorer response rates, than FCR, partly owing to the additional toxicity associated with mitoxantrone. In view of this, FCM-miniR will not be taken forward into a larger definitive Phase III trial. The trial demonstrated that oral FCR yields extremely high response rates compared with historical series with intravenous chemotherapy. Future work: We shall compare the results of ARCTIC with those of the ADMIRE (Does the ADdition of Mitoxantrone Improve Response to FCR chemotherapy in patients with CLL?) trial, which compared FCR with FCM-R to assess the efficacy of low- versus standard-dose rituximab, allowing for the toxicity associated with mitoxantrone. Trial registration: Current Controlled Trials ISRCTN16544962. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 28. See the NIHR Journals Library website for further project information

PRImary care Streptococcal Management (PRISM) study:In vitro study, diagnostic cohorts and a pragmatic adaptive randomised controlled trial with nested qualitative study and cost-effectiveness study

Background: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. Objective: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. Design: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. Setting: The setting was UK primary care general practices. Participants: Participants were patients aged ≥ 3 years with acute sore throat. Interventions: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. Main outcome measures: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2-4 days). Results: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (-0.33; 95% confidence interval -0.64 to -0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (-0.30; -0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals' concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. Conclusions: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals' concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians' perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed

Use of varenicline for smoking cessation treatment in UK primary care: an association rule mining analysis

BACKGROUND: Varenicline is probably the most effective smoking cessation pharmacotherapy, but is less widely used than nicotine replacement therapy. We therefore set out to identify the characteristics of numerically important groups of patients who typically do, or do not, receive varenicline in the UK. METHODS: We used association rule mining to analyse data on prescribing of smoking cessation pharmacotherapy in relation to age, sex, comorbidity and other variables from 477,620 people aged 16 years and over, registered as patients throughout 2011 with one of 559 UK general practices in The Health Improvement Network (THIN) database, and recorded to be current smokers. RESULTS: 46,685 participants (9.8% of all current smokers) were prescribed any smoking cessation treatment during 2011, and 19,316 of these (4% of current smokers, 41% of those who received any therapy) were prescribed varenicline. Prescription of varenicline was most common among heavy smokers aged 31–60, and in those with a diagnosis of COPD. Varenicline was rarely used among smokers who were otherwise in good health, or were aged over 60, were lighter smokers, or had psychotic disorders or dementia. CONCLUSIONS: Varenicline is being underused in healthy smokers, or in older smokers, and in those with psychotic disorders or dementia. Since varenicline is probably the most effective available single cessation therapy, this study identifies under-treatment of substantial public health significance

The chronicity of self-injurious behaviour: A long-term follow-up of a total population study

Background: Self-injurious behaviour (SIB) is a relatively common problem for people with intellectual disabilities and it is known to be associated with various risk markers, such as degree of disability, sensory impairments, and autism (McClintock et al. 2003). Less is known about its long-term course however. Method: The present study was conducted to examine the quality of life and changes in behaviour for a cohort of 49 people with intellectual disabilities and SIB who were all part of a previous total population study conducted in the south of England by Oliver, Murphy and Corbett (1987). Assessment tools used in the original study, and an additional quality of life measure, the Life Experience Checklist (Ager, 1990), were carried out with informants in the participant's homes or places of day activity. Results: The results show that 84% of the sample continued to self-injure nearly 20 years on, with no significant mean changes in number of topographies or severity of SIB across the group. No one was living in hospital in this study (cf. many individuals in the first survey) but for those who had moved out of hospital, their SIB had not reduced. More people were receiving psychological treatment; more were also receiving anti-convulsant and anti-psychotic medications, though polypharmacy had reduced somewhat. The number of people accessing full-time day activities had decreased substantially, with 44% of people only accessing structured daily activities for 21/2 days per week or less. Conclusions: The results of the study add to the growing evidence of extreme chronicity for SIB and the relative lack of impact of treatment for people in whom self-injury has become well-established. They imply that early intervention is essential if such behaviour is to be eliminated long term

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid

PLEASANT: Preventing and Lessening Exacerbations of Asthma in School-age children Associated with a New Term - a cluster randomised controlled trial and economic evaluation.

BACKGROUND: Asthma episodes and deaths are known to be seasonal. A number of reports have shown peaks in asthma episodes in school-aged children associated with the return to school following the summer vacation. A fall in prescription collection in the month of August has been observed, and was associated with an increase in the number of unscheduled contacts after the return to school in September. OBJECTIVE: The primary objective of the study was to assess whether or not a NHS-delivered public health intervention reduces the September peak in unscheduled medical contacts. DESIGN: Cluster randomised trial, with the unit of randomisation being 142 NHS general practices, and trial-based economic evaluation. SETTING: Primary care. INTERVENTION: A letter sent (n = 70 practices) in July from their general practitioner (GP) to parents/carers of school-aged children with asthma to remind them of the importance of taking their medication, and to ensure that they have sufficient medication prior to the start of the new school year in September. The control group received usual care. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of children aged 5-16 years who had an unscheduled medical contact in September 2013. Supporting end points included the proportion of children who collected prescriptions in August 2013 and unscheduled contacts through the following 12 months. Economic end points were quality-adjusted life-years (QALYs) gained and costs from an NHS and Personal Social Services perspective. RESULTS: There is no evidence of effect in terms of unscheduled contacts in September. Among children aged 5-16 years, the odds ratio (OR) was 1.09 [95% confidence interval (CI) 0.96 to 1.25] against the intervention. The intervention did increase the proportion of children collecting a prescription in August (OR 1.43, 95% CI 1.24 to 1.64) as well as scheduled contacts in the same month (OR 1.13, 95% CI 0.84 to 1.52). For the wider time intervals (September-December 2013 and September-August 2014), there is weak evidence of the intervention reducing unscheduled contacts. The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children collecting prescriptions in August as well as having scheduled contacts in the same month. These unscheduled contacts in September could be a result of the intervention, as GPs may have wanted to see patients before issuing a prescription. The economic analysis estimated a high probability that the intervention was cost-saving, for baseline-adjusted costs, across both base-case and sensitivity analyses. There was no increase in QALYs. LIMITATION: The use of routine data led to uncertainty in the coding of medical contacts. The uncertainty was mitigated by advice from a GP adjudication panel. CONCLUSIONS: The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children both collecting prescriptions and having scheduled contacts in August. After September there is weak evidence in favour of the intervention. The intervention had a favourable impact on costs but did not demonstrate any impact on QALYs. The results of the trial indicate that further work is required on assessing and understanding adherence, both in terms of using routine data to make quantitative assessments, and through additional qualitative interviews with key stakeholders such as practice nurses, GPs and a wider group of children with asthma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03000938. FUNDING DETAILS: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 93. See the HTA programme website for further project information