1.
Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study).
Marwood, L, Taylor, R, Goldsmith, K, Romeo, R, Holland, R, Pickles, A, Hutchinson, J, Dietch, D, Cipriani, A, Nair, R, et al
BMC psychiatry. 2017;(1):231
Abstract
BACKGROUND Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group. METHODS The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects. DISCUSSION The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies. TRIAL REGISTRATION ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.
2.
Trials and tribulations of recruiting 2,000 older women onto a clinical trial investigating falls and fractures: Vital D study.
Sanders, KM, Stuart, AL, Merriman, EN, Read, ML, Kotowicz, MA, Young, D, Taylor, R, Blair-Holt, I, Mander, AG, Nicholson, GC
BMC medical research methodology. 2009;:78
Abstract
BACKGROUND Randomised, placebo-controlled trials are needed to provide evidence demonstrating safe, effective interventions that reduce falls and fractures in the elderly. The quality of a clinical trial is dependent on successful recruitment of the target participant group. This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration. The characteristics of study participants at baseline are also described for this study. METHODS The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm, adapted from identified risk factors for hip fracture. Participants were randomised to orally receive either 500,000 IU vitamin D3 (cholecalciferol) or placebo every autumn for five consecutive years. A variety of recruitment strategies were employed to attract potential participants. RESULTS Of the 2,317 participants randomised onto the study, 74% (n = 1716/2317) were consented onto the study in the last five months of recruiting. This was largely due to the success of a targeted mail-out. Prior to this only 541 women were consented in the 18 months of recruiting. A total of 70% of all participants were recruited as a result of targeted mail-out. The response rate from the letters increased from 2 to 7% following revision of the material by a public relations company. Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods. CONCLUSION The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies. The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres. Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates. In our experience, and others direct mail-outs work best although rights to privacy must be respected. TRIAL REGISTRATION ISRCTN83409867 and ACTR12605000658617.
3.
The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Home-based compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.
Jolly, K, Taylor, R, Lip, GY, Greenfield, S, Raftery, J, Mant, J, Lane, D, Jones, M, Lee, KW, Stevens, A
Health technology assessment (Winchester, England). 2007;(35):1-118
Abstract
OBJECTIVES To evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes. DESIGN An individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes. SETTING Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002. PARTICIPANTS A total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks. INTERVENTIONS All the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English. MAIN OUTCOME MEASURES Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks. RESULTS No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost 198 pounds versus 157 pounds for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to 182 pounds. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual. CONCLUSIONS A home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term.
4.
Effect of lowering tumour necrosis factor-alpha on vascular endothelial function in Type II diabetes.
Bilsborough, W, O'Driscoll, G, Stanton, K, Weerasooriya, R, Dembo, L, Taylor, R, Green, D
Clinical science (London, England : 1979). 2002;(2):163-9
Abstract
Tumour necrosis factor-alpha (TNF alpha) is a mediator of reactive oxygen species, which are implicated in endothelial dysfunction and atherosclerosis. Type II diabetes is associated with endothelial dysfunction and elevated circulating TNF alpha. We hypothesized that reducing serum levels of TNFalpha, using pentoxifylline, would improve endothelial function. Thirteen subjects [age 58+/-2 (S.E.M.) years] with Type II diabetes (disease duration 74+/-13 months) undertook a randomized, crossover study of 8 weeks pentoxifylline and 8 weeks placebo. Endothelium-dependent and-independent vasodilation in resistance arteries was assessed via bilateral forearm venous occlusion plethysmography during intra-brachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA). High-resolution ultrasound of the brachial artery in response to ischaemia was used to determine endothelium-dependent conduit vessel flow-mediated dilation (FMD), and endothelium-independent conduit function was assessed by sublingual administration of glyceryl trinitrate (GTN). Serum concentrations of TNF alpha were also determined. Pentoxifylline lowered serum TNF alpha from 4.1+/-0.7 to 2.9+/-0.6 pg x ml(-1) (P=0.001). Forearm blood flow (FBF) responses at each dose of ACh did not differ with treatment (P=0.4). Similarly, FBF responses to SNP (P=0.8) and L-NMMA (P=0.2) did not differ. There was also no significant difference in brachial artery diameter during FMD (P=0.2) or GTN administration (P=0.06). Despite lowering serum TNF alpha concentration, pentoxifylline at a dose of 400 mg three times a day for 8 weeks did not improve vascular function in either conduit or resistance vessels in this group of Type II diabetic subjects.