Withdrawal of inhaled corticosteroids in individuals with COPD - a systematic review and comment on trial methodology

Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately.     

Preventing injuries in children: cluster randomised controlled trial in primary care

ObjectiveTo assess the effectiveness of safety advice at child health surveillance consultations, provision of low cost safety equipment to families receiving means tested state benefits, home safety checks, and first aid training on frequency and severity of unintentional injuries in children at home.DesignCluster randomised controlled trial.Setting36 general practices in Nottingham.SubjectsAll children aged 3-12 months registered with participating practices.InterventionsA package of safety advice at child health surveillance consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety equipment to families on means tested state benefits; and home safety checks and first aid training by health visitors.ResultsAt baseline, both groups had similar risk factors for injury, sociodemographic characteristics, safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk. No significant difference was found in frequency of at least one medically attended injury (odds ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an accident and emergency department for injury (1.02, 0.76 to 1.37), at least one primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital admission for injury (0.69, 0.42 to 1.12). No significant difference in the secondary outcome measures was found between the intervention and control groups. ConclusionsThe intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home, and larger trials are required to assess the effect on more severe injuries.

Key messages

• A package of activities for preventing injuries, as suggested by the Health of the Nation, delivered to families with children aged under 3 in primary care did not reduce the frequency of minor injuries
• The findings were consistent with a reduction in the frequency of more severe injuries, and larger primary care based studies are required to test this hypothesis
• The effectiveness of each of the interventions, delivered singly, is not known

     

Befriending carers of people with dementia: randomised controlled trial

Objective To evaluate the effectiveness of a voluntary sector based befriending scheme in improving psychological wellbeing and quality of life for family carers of people with dementia.Design Single blind randomised controlled trial.Setting Community settings in East Anglia and London.Participants 236 family carers of people with primary progressive dementia.Intervention Contact with a befriender facilitator and offer of match with a trained lay volunteer befriender compared with no befriender facilitator contact; all participants continued to receive “usual care.”Main outcome measures Carers’ mood (hospital anxiety and depression scale—depression) and health related quality of life (EuroQoL) at 15 months post-randomisation.Results The intention to treat analysis showed no benefit for the intervention “access to a befriender facilitator” on the primary outcome measure or on any of the secondary outcome measures.Conclusions In common with many carers’ services, befriending schemes are not taken up by all carers, and providing access to a befriending scheme is not effective in improving wellbeing.Trial registration Current Controlled Trials ISRCTN08130075.     

Low intensity,long-term outpatient rehabilitation in COPD: a randomised controlled trial

Background

Most pulmonary rehabilitation programmes currently involve 2–3 sessions per week as recommended by international guidelines. We aimed to investigate whether relevant improvements in physical capabilities and quality of life in patients with chronic obstructive pulmonary disease (COPD) could be achieved by a long-term, low intensity, once weekly rehabilitation programme using limited resources.

Methods

100 patients with moderate to severe COPD were randomised to a continuous outpatient interdisciplinary rehabilitation programme or standard care. Physiotherapy-led supervised outpatient training sessions were performed once weekly in addition to educational elements. Outcome measures at baseline and after 26 weeks were 6-minute-walk-test, cycle ergometry, and health-related quality of life.

Results

37 patients in the training group and 44 patients in the control group completed the study. After 26 weeks there were clinically significant differences between the groups for 6 minute-walk-distance (+59 m, 95% CI 28–89 m), maximum work load (+7.4 Watt, 95% CI 0.5-13.4 Watt) and St. George’s Respiratory Questionnaire score (−5 points, 95% CI −10 to −1 points). Total staff costs of the programme per participant were ≤ €625.

Conclusion

Clinically meaningful improvements in physical capabilities and health-related quality of life may be achieved using long-term pulmonary rehabilitation programmes of lower intensity than currently recommended. Trial registration: clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01195402","term_id":"NCT01195402"}}NCT01195402.     

Nordic Walking improves daily physical activities in COPD: a randomised controlled trial

Background

In patients with COPD progressive dyspnoea leads to a sedentary lifestyle. To date, no studies exist investigating the effects of Nordic Walking in patients with COPD. Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages. Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients'' daily physical activity pattern as well as on patients exercise capacity.

Methods

Sixty COPD patients were randomised to either Nordic Walking or to a control group. Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV₁: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention. Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD). Assessment time points in both groups: baseline, after three, six and nine months.

Results

After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s²) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01). Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01). These significant improvements were sustained six and nine months after baseline. In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points.

Conclusions

Nordic Walking is a feasible, simple and effective physical training modality in COPD. In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.

Clinical trial registration

Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632     

Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial.

OBJECTIVES: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: Community based study in Southampton. SUBJECTS: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. INTERVENTIONS: After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. RESULTS: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 1; adjusted difference 0.09 1 (95% confidence interval 0.04 to 0.14); P = 0.001) and methacholine PD20 12.8 v 7.2 mumol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P = 0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups. CONCLUSIONS: Although lung function is improved with regular beclomethasone dipropionate 400 micrograms/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection.     

Multifactorial day hospital intervention to reduce falls in high risk older people in primary care: a multi-centre randomised controlled trial [ISRCTN46584556]

Background

There are many barriers to patient participation in randomised controlled trials of cancer treatments. To increase participation in trials, strategies need to be identified to overcome these barriers. Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in randomised controlled trials (RCTs) of cancer treatments.

Methods

A systematic review was conducted. Published and unpublished studies in any language were searched for in fifteen electronic databases, including MEDLINE, EMBASE, CINAHL and PsycINFO, from inception to the end of 2004. Studies of any interventions to improve cancer patient participation in RCTs, which reported the change in recruitment rates, were eligible for inclusion. RCTs and non-randomised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included. Data were extracted by one reviewer into structured summary tables and checked for accuracy by a second reviewer. Each included study was assessed against a checklist for methodological quality by one reviewer and checked by a second reviewer. A narrative synthesis was conducted.

Results

Eight studies were identified that met the inclusion criteria: three RCTs, two non-randomised controlled trials and three observational studies. Six of the studies had an intervention that had some relevance to the UK. There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs, though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer. Although there was no evidence of an effect in any of the studies, the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work.

Conclusion

There is not a strong evidence-base for interventions that increase cancer patient participation in randomised trials. Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials.     

Developing a register of randomised controlled trials in primary care.

OBJECTIVE--To determine the number, nature, site of publication, and feasibility of identifying randomised controlled trials relevant to primary care. DESIGN--Review of literature using three strategies: approaching journal editors, Medline search, and manual search of individual journals. SETTING--Journals containing publications of studies based in primary care. MAIN OUTCOME MEASURES--The number, site of publication, and subject of trials identified. RESULTS--No journal had a system which enabled identification of all the randomised controlled trials it published. 266 trials relevant to primary care were identified from 110 different journals during 1987-91 by Medline. Of these, only 62 trials were published in primary care journals. Hand searching of seven major primary care research journals showed that between 13% and 38% of the trials had been missed by the Medline search. Of the trials identified, 47 (18%) were concerned with mental disease (including neuroses, tobacco misuse and alcohol misuse) and 43 (16%) were concerned with hypertension. CONCLUSION--Given the diversity of publication sources and topics, this supports the need for a centrally based register of randomised controlled trials that may be relevant to primary care overviews in the future.     

Evaluation of a stroke family care worker: results of a randomised controlled trial.

OBJECTIVE: To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers. DESIGN: Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation. SETTING: A well organised stroke service in an Edinburgh teaching hospital. SUBJECTS: 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period. MAIN OUTCOME MEASURES: Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire. RESULTS: The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support. CONCLUSIONS: The introduction of a stroke family care worker improved patients'' and their carers'' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients'' physical wellbeing.     

Single and dual task gait training in people with Parkinson's Disease: A protocol for a randomised controlled trial

Background  

Difficulty performing more than one task at a time (dual tasking) is a common and disabling problem experienced by people with Parkinson disease (PD). If asked to perform another task when walking, people with PD often take shorter steps or walk more slowly. Currently there is uncertainty about whether clinicians should teach people with PD to avoid dual tasking or whether they should encourage them to practice dual tasking with the hope that practice will lead to enhanced performance. This study will address this issue by comparing single to dual task gait training.     

Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO)

Background

It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations. The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.

Methods

914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV₁>50% predicted, and <2 exacerbations/year were recruited. Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients). FEV₁, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.

Results

816 patients (89.3%) concluded the study. FEV₁, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6. We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.

Conclusions

We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators.     

A randomised controlled trial and economic evaluation of a referrals facilitator between primary care and the voluntary sector

ObjectivesTo compare outcome and resource utilisation among patients referred to the Amalthea Project, a liaison organisation that facilitates contact between voluntary organisations and patients in primary care, with patients receiving routine general practitioner care.DesignRandomised controlled trial with follow up at one and four months.Setting26 general practices in Avon.Participants161 patients identified by their general practitioner as having psychosocial problems.ResultsThe Amalthea group showed significantly greater improvements in anxiety (average difference between groups after adjustment for baseline −1.9, 95% confidence interval −3.0 to −0.7), other emotional feelings (average adjusted difference −0.5, −0.8 to −0.2), ability to carry out everyday activities (−0.5, −0.8 to −0.2), feelings about general health (−0.4, −0.7 to −0.1), and quality of life (−0.5, −0.9 to −0.1). No difference was detected in depression or perceived social support. The mean cost was significantly greater in the Amalthea arm than the general practitioner care arm (£153 v £133, P=0.025).ConclusionReferral to the Amalthea Project and subsequent contact with the voluntary sector results in clinically important benefits compared with usual general practitioner care in managing psychosocial problems, but at a higher cost.     

Consequences of assessment and intervention among elderly people: a three year randomised controlled trial.

Over three years 285 randomly selected subjects aged 75 years or more and living in a suburb of Copenhagen were visited every three months in their own homes (the intervention group) to assess whether scheduled medically and socially preventive intervention would influence the number of admissions to hospitals or nursing homes, the number of contacts with general practice, or mortality. A randomly selected group of 287 people of the same age and sex were visited during the final three months of the study (the control group). Two hundred and nineteen admissions to hospitals (4884 bed days) were registered for the intervention group compared with 271 (6442 bed days) for the control group. Especially during the second half of the study, a significant reduction in the number of admissions to hospitals was seen in the intervention group. Twenty people in the intervention group and 29 in the control group moved into nursing homes (p greater than 0.05). The corresponding numbers of deaths were 56 and 75 (p less than 0.05). No difference was seen in the number of contacts with general practice. Significantly fewer emergency medical calls, however, were registered for the intervention group. Subjects in the intervention group benefited from the regular visits and the increased distribution of aids and modifications to their homes to which these led. The regular visits probably also produced an important increase in confidence.     

Home based care and standard hospital care for patients with severe mental illness: a randomised controlled trial.

OBJECTIVE--To compare the efficacy of home based care with standard hospital care in treating serious mental illness. DESIGN--Randomised controlled trial. SETTING--South Southwark, London. PATIENTS--189 patients aged 18-64 living in catchment area. 92 were randomised to home based care (daily living programme) and 97 to standard hospital care. At three months'' follow up 68 home care and 60 hospital patients were evaluated. MAIN OUTCOME MEASURES--Use of hospital beds, psychiatric diagnosis, social functioning, patients'' and relatives'' satisfaction, and activity of daily living programme staff. RESULTS--Home care reduced hospital stay by 80% (median stay six days in home care group, 53 days in hospital group) and did not increase the number of admissions compared with hospital care. On clinical and social outcome there was a non-significant trend in favour of home care, but both groups showed big improvements. On the global adjustment scale home care patients improved by 26.8 points and the hospital group by 21.6 points (difference 5.2; 95% confidence interval -1.5 to 12). Other rating scales showed similar trends. Home care patients required a wide range of support in areas such as housing, finance, and work. Only three patients dropped out from the programme. CONCLUSIONS--Home based care may offer some slight advantages over hospital based care for patients with serious mental illness and their relatives. The care is intensive, but the low drop out rate suggests appreciation. Changes to traditional training for mental health workers are required.     

Effectiveness of out-of-home day care for disadvantaged families: randomised controlled trial

Objective To assess the effects of providing daycare facilities for young children on the health and welfare of disadvantaged families.Design Randomised controlled trial. Eligible children from the application list to a daycare facility were randomly allocated to receive a daycare place or not.Setting Early Years daycare centre in Borough of Hackney, London.Participants 120 mothers and 143 eligible children (aged between 6 months and 3.5 years).Intervention A place at the centre, which provided high quality day care. Control families used other child care that they secured for themselves.Main outcome measures Maternal paid employment, household income, child health and development.Results At 18 months'' follow up, 67% of intervention group mothers and 60% of control group mothers were in paid employment (adjusted risk ratio 1.23 (95% confidence interval 0.99 to 1.52)), but were no more likely to have a weekly household income of above £200 (risk ratio 0.88 (0.70 to 1.09)). Intervention group children had more otitis media with effusion (risk ratio 1.74 (1.02 to 2.96)) and used more health services (1.58 (1.05 to 2.38)), but both estimates were imprecise.Conclusion The provision of child day care may have increased maternal employment, but it did not seem to increase household income. The results suggest that providing day care may be insufficient as a strategy to reduce poverty. The study shows how random allocation can be used to ration and evaluate interventions where demand exceeds supply.     

Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial

ObjectiveTo evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care.DesignRandomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months.SettingPopulation of residential facility in Sydney living in self care units and hostels.Participants220 depressed residents aged ⩾65 without severe cognitive impairment.InterventionThe shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care.ResultsIntention to treat analysis was used. There was significantly more movement to “less depressed” levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011).ConclusionsThe outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.

Key messages

• Large numbers of depressed elderly people live in residential care but few receive appropriate management
• A population based, multifaceted shared care intervention for late life depression was more effective than routine care in improving depression outcome
• The outcome of late life depression can be improved by enhancing the clinical skills of general practitioners and care staff and by providing depression related health education and activity programmes for residents
• The intervention needs further refining and evaluation to improve its effectiveness and to determine how best to implement it in other residential care settings