Fergus Daly

A Randomized Controlled Trial of Fall Prevention Strategies in Old Peoples’ Homes

Background: Falls are a major cause of morbidity in old age. A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective. This study set out to examine the preventability of falls in older people living in institutional care. Objective: To evaluate the effectiveness of falls risk factor assessment/modification and seated balance exercise training in reducing falls among elderly people living in residential care. Methods: 133 residents with a mean age of 84± (SD) 6.8 years were allocated at random by home to receive either a 6-month falls risk factor assessment/modification and seated balance exercise training programme (n = 77) or 6 months of reminiscence therapy (n = 56). The risk factors targeted were postural hypotension, polypharmacy, visual acuity, and ambient lighting levels. Falls risk factor assessments and recommendation for modifications were performed at baseline in the intervention group and assessments repeated at 6 months. Functional reach, reaction time, timed up-and- go, grip strength, spinal flexibility, and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘blind’ observer. Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period. Results: Only 90 of 133 (67.7%) residents completed the 6-month intervention period, and 84 (63.2%) completed the 7- to 12-month falls-monitoring follow-up period. Both prevalence of postural hypotension (p = 0.0005) and poor visual acuity (p = 0.04) were reduced in the intervention group. There was no difference between the groups in the number of falls sustained, the risk of falling [odds ratio 0.45 (95% CI 0.19–1.14)], or in the risk of recurrent falling [odds ratio 1.07 (95% CI 0.40–2.97)]. No significant differences were found between the groups with regard to change in other outcome measures. Conclusions: The high drop-out rate reduced the power of this study to detect any effect of the interventions used. It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed standing. Further research is required to identify effective fall prevention strategies for elderly people in residential settings.

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women

Objectives To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women. Patients and methods One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months. Trial registration: ISRCTN80031108. Results Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37). Conclusions Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.

A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell’s palsy: the BELLS study

OBJECTIVE To determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bells palsy, improves the chances of recovery at 3 and 9 months. DESIGN A 2 x 2 factorial randomised double-blind trial. Patients were randomly assigned to treatment by an automated telephone service using a permuted block randomisation technique with block sizes of four or eight, and no stratification. SETTING Mainland Scotland, with referrals mainly from general practice to 17 hospital trial sites. PARTICIPANTS Adults (aged 16 years or older) with unilateral facial nerve weakness of no identifiable cause presenting to primary care, the emergency department or NHS24 within 72 hours of symptom onset. INTERVENTIONS Patients were randomised to receive active preparations or placebo for 10 days: (1) prednisolone (50 mg per day, 2 x 25-mg capsules) and aciclovir (2000 mg per day, 5 x 400-mg capsules); (2) prednisolone and placebo (lactose, indistinguishable); (3) aciclovir and placebo; and (4) placebo and placebo. OUTCOME MEASURES The primary outcome was recovery of facial function assessed by the House-Brackmann scale. Secondary outcomes included health status, pain, self-perceived appearance and cost-effectiveness. RESULTS Final outcomes were available for 496 patients, balanced for gender; mean age 44 years; initial facial paralysis moderate to severe. One half of patients initiated treatment within 24 hours of onset of symptoms, one-third within 24-48 hours and the remainder within 48-72 hours. Of the completed patients, 357 had recovered by 3 months and 80 at 9 months, leaving 59 with a residual deficit. There were significant differences in complete recovery at 3 months between the prednisolone comparison groups (83.0% for prednisolone, 63.6% for no prednisolone, a difference of + 19.4%; 95% confidence interval (CI): + 11.7% to + 27.1%, p < 0.001). The number needed to treat (NNT) in order to achieve one additional complete recovery was 6 (95% CI: 4 to 9). There was no significant difference between the aciclovir comparison groups (71.2% for aciclovir and 75.7% for no aciclovir). Nine-month assessments of patients recovered were 94.4% for prednisolone compared with 81.6% for no prednisolone, a difference of + 12.8% (95% CI: + 7.2% to + 18.4%, p < 0.001); the NNT was 8 (95% CI: 6 to 14). Proportions recovered at 9 months were 85.4% for aciclovir and 90.8% for no aciclovir, a difference of -5.3%. There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months. Outcome differences by individual treatment (the four-arm model) showed significant differences. At 3 months the recovery rate was 86.3% in the prednisolone treatment group, 79.7% in the aciclovir-prednisolone group, 64.7% in the placebo group and 62.5% in the aciclovir group. At 9 months the recovery rates were respectively 96.1%, 92.7%, 85.3% and 78.1%. The increase in recovery rate conferred by the addition of prednisolone (both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir) is highly statistically significant (p < 0.001). There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 (HUI3) at 9 months in those treated with prednisolone. CONCLUSIONS This study provided robust evidence to support the early use of oral prednisolone in Bells palsy as an effective treatment which may be considered cost-effective. Treatment with aciclovir, either alone or with steroids, had no effect on outcome.

Nutritional Supplementation of Very Old People at Hospital Discharge Increases Muscle Strength: A Randomised Controlled Trial

Background: Undernutrition is common in older people admitted to hospital, but little is known about how nutritional state changes after discharge. Objective: This randomised controlled trial was designed to examine the effect of oral nutritional supplementation of undernourished very old people prepared to take supplements after hospital discharge following acute illness. Methods: Participants aged ≧75 years with a BMI ≤24 kg/m2 and triceps skin fold thickness or mid-arm muscle circumference below the 10th centile and/or weight loss ≧5% during an acute hospital stay were allocated at random to either oral nutritional supplementation for 8 weeks from hospital discharge or to usual care. Primary outcome was change in weight, secondary outcomes were handgrip strength and anthropometry. Results: Of 198 patients eligible to participate, 136 patients (mean age 85 years) were randomised and 76/136 (56%) completed the study. Twenty percent (13/66) of the intervention group withdrew after only 2 weeks, citing intolerance of the supplements. Using intention-to-treat analysis, body weight increased by a mean of 1.6 and 2.2% in the control and intervention groups, respectively, but this between-group difference was not significant (p = 0.188). However, handgrip strength increased more (p = 0.055) in the intervention group (13.9%) than in the control group (7.2%). Conclusions: Oral nutritional supplementation was associated with a greater increase in handgrip strength than in non-supplemented controls and this observation merits further study.

The use of Ginkgo biloba in Raynaud's disease: a double- blind placebo-controlled trial

Raynaud’s phenomenon (RP) is a common and painful condition characterized by episodic digital ischaemia produced by emotion and cold. Treatment of RP is notoriously difficult because of the high incidence of side effects. The aim of our study was to investigate the clinical efficacy of a standardized Ginkgo biloba extract (Seredrin) in the treatment of RP in patients with no apparent, associated condition such as systemic sclerosis. A two-week assessment period was done during which patients were asked to record frequency, severity and duration of attacks in diaries. Subjects were then randomized independently of the study centre to receive either active or placebo treatment for 10 weeks, during which time the same data were recorded in their diaries. Patients were seen after two and four weeks of treatment and at the end of the 10-week treatment phase. Blood samples pre- and post-treatment were taken for haemorrheology. Only in the number of attacks per day was there a significant effect of treatment over placebo. The number of attacks per week prior to treatment with Seredrin was 13.2 6 16.5 reducing to 5.8 6 8.3, a reduction of 56%, whereas placebo reduced the number by only 27% (p < 0.00001). There were no significant differences in haemorrheology between the two groups. Ginkgo biloba phytosome may be effective in reducing the number of Raynaud’s attacks per week in patients suffering from Raynaud’s disease.

The impact of a bodyweight and physical activity intervention (BeWEL) initiated through a national colorectal cancer screening programme: randomised controlled trial

Objective To evaluate the impact of a diet and physical activity intervention (BeWEL) on weight change in people with a body mass index >25 weight (kg)/height (m)2 at increased risk of colorectal cancer and other obesity related comorbidities. Design Multicentre, parallel group, randomised controlled trial. Setting Four Scottish National Health Service health boards. Participants 329 overweight or obese adults (aged 50 to 74 years) who had undergone colonoscopy after a positive faecal occult blood test result, as part of the national bowel screening programme, and had a diagnosis of adenoma confirmed by histopathology. 163 were randomised to intervention and 166 to control. Intervention Participants were randomised to a control group (weight loss booklet only) or 12 month intervention group (three face to face visits with a lifestyle counsellor plus monthly 15 minute telephone calls). A goal of 7% reduction in body weight was set and participants received a personalised energy prescription (2508 kJ (600 kcal) below that required for weight maintenance) and bodyweight scales. Motivational interviewing techniques explored self assessed confidence, ambivalence, and personal values concerning weight. Behavioural strategies included goal setting, identifying intentions of implementation, self monitoring of body weight, and counsellor feedback about reported diet, physical activity, and weight change. Main outcome measures The primary outcome was weight change over 12 months. Secondary outcomes included changes in waist circumference, blood pressure, fasting cardiovascular biomarkers, and glucose metabolism variables, physical activity, diet, and alcohol consumption. Results At 12 months, data on the primary outcome were available for 148 (91%) participants in the intervention group and 157 (95%) in the control group. Mean weight loss was 3.50 kg (SD 4.91) (95% confidence interval 2.70 to 4.30) in the intervention group compared with 0.78 kg (SD 3.77) (0.19 to 1.38) in the control group. The group difference was 2.69 kg (95% confidence interval 1.70 to 3.67). Differences between groups were significant for waist circumference, body mass index, blood pressure, blood glucose level, diet, and physical activity. No reported adverse events were considered to be related to trial participation. Conclusions Significant weight loss can be achieved by a diet and physical activity intervention initiated within a national colorectal cancer screening programme, offering considerable potential for risk reduction of disease in older adults. Trial registration Current Controlled Trials ISRCTN53033856.

Recruitment and retention in a multicentre randomised controlled trial in Bell's palsy: A case study

BackgroundIt is notoriously difficult to recruit patients to randomised controlled trials in primary care. This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window.Bells palsy, an acute unilateral paralysis of the facial nerve is just such a relatively rare condition. In this case study we describe the organisational issues presented in setting up a large randomised controlled trial of the management of Bells palsy across primary and secondary care in Scotland and how we managed to successfully recruit and retain patients presenting in the community.MethodsWhere possible we used existing evidence on recruitment strategies to maximise recruitment and retention. We consider that the key issues in the success of this study were; the fact that the research was seen as clinically important by the clinicians who had initial responsibility for recruitment; employing an experienced trial co-ordinator and dedicated researchers willing to recruit participants seven days per week and to visit them at home at a time convenient to them, hence reducing missed patients and ensuring they were retained in the study; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community; encouraging recruitment by payment to practices and reducing the workload of the referring doctors by providing immediate access to specialist care; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centresResultsAlthough the recruitment rate did not meet our initial expectations, enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale.ConclusionWhile difficult, recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence, establishing good relationships with practices, minimising the workload of those involved in recruitment and offering enhanced care to all participants. Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results.

Study protocol for BeWEL: The impact of a BodyWEight and physicaL activity intervention on adults at risk of developing colorectal adenomas

BackgroundColorectal cancer (CRC) is the third most commonly diagnosed cancer and the second highest cause of cancer death in the UK. Most cases occur in people over 50 years and CRC often co-exists with other lifestyle related disorders including obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). These diseases share risk factors related to the metabolic syndrome including large body size, abnormal lipids and markers of insulin resistance indicating common aetiological pathways.Methods/DesignThis 3 year study will be a two-arm, multicentre, randomised controlled trial comparing the BeWEL lifestyle (diet, physical activity and behaviour change) programme against usual care. The pre-trial development will take 6 months and participants will be recruited over a 12 month period and undertake the intervention and follow up for 12 months (total 24 months recruitment and intervention implementation) with a further 6 months for data collection, analysis and interpretation.Four hundred and fifty two participants who have had a colorectal adenoma detected and removed (through the national colorectal screening programme) will provide 80% power to detect a weight loss of 7% over 12 months.Primary outcomes are changes in body weight and waist circumference. Secondary outcomes will include cardiovascular risk factors, psycho-social measures and intervention costs.DiscussionThe results from this study will enhance the evidence base for lifestyle change in patients at higher risk of chronic disease including obesity related cancers.International Standard Randomised Controlled Trials No: ISRCTN53033856

Impact of clinical trial findings on Bell's palsy management in general practice in the UK 2001–2012: interrupted time series regression analysis

Objectives To measure the incidence of Bells palsy and determine the impact of clinical trial findings on Bells palsy management in the UK. Design Interrupted time series regression analysis and incidence measures. Setting General practices in the UK contributing to the Clinical Practice Research Datalink (CPRD). Participants Patients ≥16 years with a diagnosis of Bells palsy between 2001 and 2012. Interventions (1) Publication of the 2004 Cochrane reviews of clinical trials on corticosteroids and antivirals for Bells palsy, which made no clear recommendation on their use and (2) publication of the 2007 Scottish Bells Palsy Study (SBPS), which made a clear recommendation that treatment with prednisolone alone improves chances for complete recovery. Main outcome measures Incidence of Bells palsy per 100 000 person-years. Changes in the management of Bells palsy with either prednisolone therapy, antiviral therapy, combination therapy (prednisolone with antiviral therapy) or untreated cases. Results During the 12-year period, 14 460 cases of Bells palsy were identified with an overall incidence of 37.7/100 000 person-years. The 2004 Cochrane reviews were associated with immediate falls in prednisolone therapy (−6.3% (−11.0 to −1.6)), rising trends in combination therapy (1.1% per quarter (0.5 to 1.7)) and falling trends for untreated cases (−0.8% per quarter (−1.4 to −0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1% (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to 1.2)); falling trends in combination therapy (−1.7% per quarter (−2.2 to −1.3)); and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite improvements, 44% still remain untreated. Conclusions SBPS was clearly associated with change in management, but a significant proportion of patients failed to receive effective treatment, which cannot be fully explained. Clarity and uncertainty in clinical trial recommendations may change clinical practice. However, better ways are needed to understand and circumvent barriers in implementing clinical trial findings.

Improving recruitment to clinical trials with a register of a million patients who agree to the use of their clinical records for research in the Scottish Health Research Register (SHARE)

The UKs technical ability to identify people eligible for medical research is not yet matched by a practical capability to approach them directly to ask them to consider participation in those studies. The consequence is that recruitment to research is more difficult than necessary and some projects fail. This makes Britain a less attractive location to undertake clinical research than it should be. In order to overcome this increasingly important obstacle, we wanted to develop a register of Scottish residents who wish to be considered for participation in a range of studies. This was an oral presentation given at the Clinical Trials Methodology conference 2011, 4-5 October 2011, Bristol, UK.