Caroline Fairhurst

The REFORM study protocol: a cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people.

Introduction Falls and fall-related injuries are a serious cause of morbidity and cost to society. Foot problems and inappropriate footwear may increase the risk of falls; therefore podiatric interventions may play a role in reducing falls. Two Cochrane systematic reviews identified only one study of a podiatry intervention aimed to reduce falls, which was undertaken in Australia. The REFORM trial aims to evaluate the clinical and cost-effectiveness of a multifaceted podiatry intervention in reducing falls in people aged 65 years and over in a UK and Irish setting. Methods and analysis This multicentre, cohort randomised controlled trial will recruit 2600 participants from routine podiatry clinics in the UK and Ireland to the REFORM cohort. In order to detect a 10% point reduction in falls from 50% to 40%, with 80% power 890 participants will be randomised to receive routine podiatry care and a falls prevention leaflet or routine podiatry care, a falls prevention leaflet and a multifaceted podiatry intervention. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by patient self-report falls diary. Secondary self-report outcome measures include: the proportion of single and multiple fallers and time to first fall over a 12-month period; Short Falls Efficacy Scale—International; fear of falling in the past 4 weeks; Frenchay Activities Index; fracture rate; Geriatric Depression Scale; EuroQoL-five dimensional scale 3-L; health service utilisation at 6 and 12 months. A qualitative study will examine the acceptability of the package of care to participants and podiatrists. Ethics and dissemination The trial has received a favourable opinion from the East of England—Cambridge East Research Ethics Committee and Galway Research Ethics Committee. The trial results will be published in peer-reviewed journals and at conference presentations. Trial registration number Current Controlled Trials ISRCTN68240461assigned 01/07/2011.

Effects of a lifestyle intervention on endothelial function in men on long-term androgen deprivation therapy for prostate cancer

Background:Treatment of prostate cancer with androgen deprivation therapy (ADT) is associated with metabolic changes that have been linked to an increase in cardiovascular risk.Methods:This randomised controlled trial investigated the effects of a 12-week lifestyle intervention that included supervised exercise training and dietary advice on markers of cardiovascular risk in 50 men on long-term ADT recruited to an on-going study investigating the effects of such a lifestyle intervention on quality of life. Participants were randomly allocated to receive the intervention or usual care. Cardiovascular outcomes included endothelial function (flow-mediated dilatation (FMD) of the brachial artery), blood pressure, body composition and serum lipids. Additional outcomes included treadmill walk time and exercise and dietary behaviours. Outcomes were assessed before randomisation (baseline), and 6, 12 and 24 weeks after randomisation.Results:At 12 weeks, the difference in mean relative FMD was 2.2% (95% confidence interval (CI) 0.1–4.3, P=0.04) with an effect size of 0.60 (95% CI <0.01–1.18) favouring the intervention group. Improvements in skeletal muscle mass, treadmill walk time and exercise behaviour also occurred in the intervention group over that duration (P<0.05). At 24 weeks, only the difference in treadmill walk time was maintained.Conclusions:This study demonstrates that lifestyle changes can improve endothelial function in men on long-term ADT for prostate cancer. The implications for cardiovascular health need further investigation in larger studies over longer duration.

Does home oxygen therapy (HOT) in addition to standard care reduce disease severity and improve symptoms in people with chronic heart failure? A randomised trial of home oxygen therapy for patients with chronic heart failure

BACKGROUND Home oxygen therapy (HOT) is commonly used for patients with severe chronic heart failure (CHF) who have intractable breathlessness. There is no trial evidence to support its use. OBJECTIVES To detect whether or not there was a quality-of-life benefit from HOT given as long-term oxygen therapy (LTOT) for at least 15 hours per day in the home, including overnight hours, compared with best medical therapy (BMT) in patients with severely symptomatic CHF. DESIGN A pragmatic, two-arm, randomised controlled trial recruiting patients with severe CHF. It included a linked qualitative substudy to assess the views of patients using home oxygen, and a free-standing substudy to assess the haemodynamic effects of acute oxygen administration. SETTING Heart failure outpatient clinics in hospital or the community, in a range of urban and rural settings. PARTICIPANTS Patients had to have heart failure from any aetiology, New York Heart Association (NYHA) class III/IV symptoms, at least moderate left ventricular systolic dysfunction, and be receiving maximally tolerated medical management. Patients were excluded if they had had a cardiac resynchronisation therapy device implanted within the past 3 months, chronic obstructive pulmonary disease fulfilling the criteria for LTOT or malignant disease that would impair survival or were using a device or medication that would impede their ability to use LTOT. INTERVENTIONS Patients received BMT and were randomised (unblinded) to open-label LTOT, prescribed for 15 hours per day including overnight hours, or no oxygen therapy. MAIN OUTCOME MEASURES The primary end point was quality of life as measured by the Minnesota Living with Heart Failure (MLwHF) questionnaire score at 6 months. Secondary outcomes included assessing the effect of LTOT on patient symptoms and disease severity, and assessing its acceptability to patients and carers. RESULTS Between April 2012 and February 2014, 114 patients were randomised to receive either LTOT or BMT. The mean age was 72.3 years [standard deviation (SD) 11.3 years] and 70% were male. Ischaemic heart disease was the cause of heart failure in 84%; 95% were in NYHA class III; the mean left ventricular ejection fraction was 27.8%; and the median N-terminal pro-B-type natriuretic hormone was 2203 ng/l. The primary analysis used a covariance pattern mixed model which included patients only if they provided data for all baseline covariates adjusted for in the model and outcome data for at least one post-randomisation time point (n = 102: intervention, n = 51; control, n = 51). There was no difference in the MLwHF questionnaire score at 6 months between the two arms [at baseline the mean score was 54.0 (SD 18.4) for LTOT and 54.0 (SD 17.9) for BMT; at 6 months the mean score was 48.1 (SD 18.5) for LTOT and 49.0 (SD 20.2) for BMT; adjusted mean difference -0.10, 95% confidence interval (CI) -6.88 to 6.69; p = 0.98]. At 3 months, the adjusted mean MLwHF questionnaire score was lower in the LTOT group (-5.47, 95% CI -10.54 to -0.41; p = 0.03) and breathlessness scores improved, although the effect did not persist to 6 months. There was no effect of LTOT on any secondary measure. There was a greater number of deaths in the BMT arm (n = 12 vs. n = 6). Adherence was poor, with only 11% of patients reporting using the oxygen as prescribed. CONCLUSIONS Although the study was significantly underpowered, HOT prescribed for 15 hours per day and subsequently used for a mean of 5.4 hours per day has no impact on quality of life as measured by the MLwHF questionnaire score at 6 months. Suggestions for future research include (1) a trial of patients with severe heart failure randomised to have emergency oxygen supply in the house, supplied by cylinders rather than an oxygen concentrator, powered to detect a reduction in admissions to hospital, and (2) a study of bed-bound patients with heart failure who are in the last few weeks of life, powered to detect changes in symptom severity. TRIAL REGISTRATION Current Controlled Trials ISRCTN60260702. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 75. See the NIHR Journals Library website for further project information.

Use of the h-index to measure the quality of the output of health services researchers

Objective: To assess the use of the h-index to measure the quality of the output of health services researchers. Method: Online survey, with bibliometric analysis of a convenience volunteer sample of researchers mainly in the UK, North America and Australasia. Self-reported from Google Scholar: h-index; number of papers; number of citations; number of papers with ≥10 citations. Results: There were complete responses from 532 health services researchers of whom 371 (70%) were from the UK. Of the bibliometric measures, the h-index appeared to be the best discriminator between other measures of quality (e.g. seniority; entry into the last UK Research Assessment Exercise). The median h-index was 12, with 90th and 95th quantiles of 40 and 52, respectively. Statisticians had the highest h-index with qualitative researchers the lowest (median 16 and 7, respectively). The h-index was predicted to increase by approximately 1 point annually with the biggest increase in statisticians and smallest in qualitative researchers when estimated by quantile regression. Conclusions: The h-index is a useful summary measure of output and quality of health services researchers. However, any accurate interpretation of bibliometric measures needs to take into account a person’s research discipline.

Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial)

Background Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. Design Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. Results In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. Conclusion There was a small reduction in falls. The intervention may be cost-effective. Trial Registration ISRCTN ISRCTN68240461

Allocation concealment in randomised controlled trials: are we getting better?

Laura Clark and colleagues assess the allocation concealment methods in a sample of randomised controlled trial publications

Exposure to sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the QResearch primary care database

Introduction Metastasis from solid tumours is associated with significant morbidity and mortality, and is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. VGSCs are also present in cancer cells, where they regulate metastatic cell behaviours, including cellular movement and invasion. Treating cancer cells with the VGSC-inhibiting anticonvulsant phenytoin reduces cellular invasion and migration. Together, these suggest that VGSCs may be useful targets for inhibiting metastasis. The purpose of this study is to test the hypothesis that use of VGSC-inhibiting drugs will reduce metastasis, and therefore increase survival time in patients with cancer. Methods and analysis A cohort study based on primary care data from the QResearch database will include patients with one of the three common tumours: breast, bowel and prostate. The primary outcome will be overall survival from the date of cancer diagnosis. Cox proportional hazards regression will be used to compare the survival of patients with cancer taking VGSC-inhibiting drugs (including anticonvulsants and class I antiarrhythmic agents) with patients with cancer not exposed to these drugs, adjusting for age and sex. Exposure to VGSC-inhibiting drugs will be defined as having at least one prescription for these drugs prior to cancer diagnosis. High and low exposure groups will be identified based on the length of use. A number of sensitivity and secondary analyses will be conducted. Ethics and dissemination The protocol has been independently peer-reviewed and approved by the QResearch Scientific Board. The project has also been approved by the University of York Ethical Review Process. The results will be presented at international conferences and published in an open access peer-reviewed journal, in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial

BackgroundRandomised controlled trials are generally regarded as the ‘gold standard’ experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial.MethodsA three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial.ResultsSix thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77–1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71–1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65–1.31, p = 0.65)).ConclusionsThis embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study.Trial registrationInternational Standard Randomised Controlled Trials Number registry, ISRCTN68240461. Registered on 01 July 2011.

Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study

Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) regulate invasion and metastasis. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients taking VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs. A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Cox proportional hazards regression was used to compare the survival from cancer diagnosis of patients taking VGSC-inhibiting drugs with those not exposed to these drugs. Median time to death was 9.7 years in the exposed group and 18.4 years in the unexposed group, and exposure to these medications significantly increased mortality. Thus, exposure to VGSC-inhibiting drugs associates with reduced survival in breast, bowel and prostate cancer patients. This finding is not consistent with the preclinical data. Despite the strengths of this study including the large sample size, the study is limited by missing information on potentially important confounders such as cancer stage, co-morbidities and cause of death. Further research, which is able to account for these confounding issues, is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival.

Factor analysis of treatment outcomes from a UK specialist addiction service: relationship between the Leeds Dependence Questionnaire, Social Satisfaction Questionnaire and 10-item Clinical Outcomes in Routine Evaluation.

Introduction and Aims To examine the relationship between three outcome measures used by a specialist addiction service (UK): the Leeds Dependence Questionnaire (LDQ), the Social Satisfaction Questionnaire (SSQ) and the 10-item Clinical Outcomes in Routine Evaluation (CORE-10). Design and Method A clinical sample of 715 service user records was extracted from a specialist addiction service (2011) database. The LDQ (dependence), SSQ (social satisfaction) and CORE-10 (psychological distress) were routinely administered at the start of treatment and again between 3 and 12 months post-treatment. A mixed pre/post-treatment dataset of 526 service users was subjected to exploratory factor analysis. Parallel Analysis and the Hull method were used to suggest the most parsimonious factor solution. Results Exploratory factor analysis with three factors accounted for 66.2% of the total variance but Parallel Analysis supported two factors as sufficient to account for observed correlations among items. In the two-factor solution, LDQ items and nine of the 10 CORE-10 items loaded on the first factor >0.41, and the SSQ items on factor 2 with loadings >0.63. A two dimensional summary appears sufficient and clinically meaningful. Discussion and Conclusions Among specialist addiction service users, social satisfaction appears to be a unique construct of addiction and is not the same as variation due to psychological distress or dependence. Our interpretation of the findings is that dependence is best thought of as a specific psychological condition subsumed under the construct psychological distress. [Fairhurst C, Böhnke JR, Gabe R, Croudace TJ, Tober G, Raistrick D. Factor analysis of treatment outcomes from a UK specialist addiction service: Relationship between the Leeds Dependence Questionnaire, Social Satisfaction Questionnaire and 10-item Clinical Outcomes in Routine Evaluation. Drug Alcohol Rev 2014;33:643–650]