Age-related macular degeneration and nutritional supplementation:a review of randomised controlled trials

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in the developed world. The lack of effective treatment modalities, coupled with evidence supporting an oxidative pathogenesis, has increased interest in the potential preventative role of nutritional supplementation. This article reviews seven randomised controlled trials (RCTs) that have investigated the role of nutritional supplementation in AMD. Three of these trials reported a positive effect of nutritional supplementation on AMD; the Age-related eye study (AREDS), the Lutein Antioxidant Supplementation Trial (LAST), and the oral zinc trial by Newsome et al. (1988). However, the oral zinc trial by Newsome et al. (1988) was unlikely to detect any difference between treatments smaller than 72%, and the AREDS results were based on a subgroup of their study population. Lutein was considered for the AREDS formulation, but was not commercially available at that time. The findings of the LAST support a possible therapeutic role of lutein in AMD. © 2004 The College of Optometrists.

Systematic review investigating the reporting of comorbidities and medication in randomized controlled trials of people with dementia

Objectives: dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which reduces social and occupational performance. This population frequently presents with medical co-morbidities such as hypertension, cardiovascular disease and diabetes. The CONSORT statement outlines recommended guidance on reporting of participant characteristics in clinical trials. It is, however, unclear how much these are adhered to in trials assessing people with dementia. This paper assesses the reporting of medical co-morbidities and prescribed medications for people with dementia within randomised controlled trial (RCT) reports. Design: a systematic review of the published literature from the databases AMED, CINAHL, MEDLINE, EMBASE and the Cochrane Clinical Trial Registry from 1 January 1997 to 9 January 2014 was undertaken in order to identify RCTs detailing baseline medical co-morbidities and prescribed medications . Eligible studies were appraised using the Critical Appraisal Skills Programme (CASP) RCT appraisal tool, and descriptive statistical analyses were calculated to determine point prevalence. Results: nine trials, including 1474 people with dementia, were identified presenting medical co-morbidity data. These indicated neurological disorders ( prevalence 91%), vascular disorders (prevalence 91%), cardiac disorders ( prevalence 74%) and ischaemic cerebrovascular disease ( prevalence 53%) were most frequently seen. Conclusions: published RCTs poorly report medical co-morbidities and medications for people with dementia. Future trials should include the report of these items to allow interpretation of whether the results are generalisable to frailer older populations.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia:the ECLIPSE trial

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena(®), Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. 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. 88. See the NIHR Journals Library website for further project information.

Reducing the time before consulting with symptoms of lung cancer:a randomised controlled trial in primary care

Background: Most individuals with lung cancer have symptoms for several months before presenting to their GP. Earlier consulting may improve survival. Aim: To evaluate whether a theory-based primary care intervention increased timely consulting of individuals with symptoms of lung cancer. Design and setting: Open randomised controlled trial comparing intervention with usual care in two general practices in north-east Scotland. Method: Smokers and ex-smokers aged ≥55 years were randomised to receive a behavioural intervention or usual care. The intervention comprised a single nurse consultation at participants' general practice and a self-help manual. The main outcomes were consultations within target times for individuals with new chest symptoms (≤3 days haemoptysis, ≤3 weeks other symptoms) in the year after the intervention commenced, and intentions about consulting with chest symptoms at 1 and 6 months. Results: Two hundred and twelve participants were randomised and 206 completed the trial. The consultation rate for new chest symptoms in the intervention group was 1.19 (95% confidence interval [CI] = 0.92 to 1.53; P = 0.18) times higher than in the usual-care group and the proportion of consultations within the target time was 1.11 (95% CI = 0.41 to 3.03; P = 0.83) times higher. One month after the intervention commenced, the intervention group reported intending to consult with chest symptoms 31 days (95% CI = 7 to 54; P = 0.012) earlier than the usual care group, and at 6 months this was 25 days (95% CI = 1.5 to 48; P = 0.037) earlier. Conclusion: Behavioural intervention in primary care shortened the time individuals at high risk of lung disease intended to take before consulting with new chest symptoms (the secondary outcome of the study), but increases in consultation rates and the proportions of consultations within target times were not statistically significant. © British Journal of General Practice.

A randomised controlled trial investigating the effect of lutein and antioxidant dietary supplementation on visual function in healthy eyes

Background & aims It has been suggested that retinal lutein may improve visual acuity for images that are illuminated by white light. Our aim was to determine the effect of a lutein and antioxidant dietary supplement on visual function. Methods A prospective, 9- and 18-month, double-masked randomised controlled trial. For the 9-month trial, 46 healthy participants were randomised (using a random number generator) to placebo (n=25) or active (n=21) groups. Twenty-nine of these subjects went on to complete 18 months of supplementation, 15 from the placebo group, and 14 from the active group. The active group supplemented daily with 6mg lutein combined with vitamins and minerals. Outcome measures were distance and near visual acuity, contrast sensitivity, and photostress recovery time. The study had 80% power at the 5% significance level for each outcome measure. Data were collected at baseline, 9, and 18 months. Results There were no statistically significant differences between groups for any of the outcome measures over 9 or 18 months. Conclusion There was no evidence of effect of 9 or 18 months of daily supplementation with a lutein-based nutritional supplement on visual function in this group of people with healthy eyes. ISRCTN78467674.

Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis

OBJECTIVES: To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences, and costs. DESIGN: Randomised controlled trial. SETTING: Eight general practices in south Birmingham. PARTICIPANTS: 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg. INTERVENTIONS: Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level. Patients in the control group received usual care (blood pressure monitoring by their practice). MAIN OUTCOME MEASURES: Primary outcome: change in systolic blood pressure at six months and one year in both intervention and control groups. Secondary outcomes: change in health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences of method of blood pressure monitoring, and costs. RESULTS: 400 (91%) patients attended follow up at one year. Systolic blood pressure in the intervention group had significantly reduced after six months (mean difference 4.3 mm Hg (95% confidence interval 0.8 mm Hg to 7.9 mm Hg)) but not after one year (mean difference 2.7 mm Hg (- 1.2 mm Hg to 6.6 mm Hg)). No overall difference was found in diastolic blood pressure, anxiety, health behaviours, or number of prescribed drugs. Patients who self monitored lost more weight than controls (as evidenced by a drop in body mass index), rated self monitoring above monitoring by a doctor or nurse, and consulted less often. Overall, self monitoring did not cost significantly more than usual care (251 pounds sterling (437 dollars; 364 euros) (95% confidence interval 233 pounds sterling to 275 pounds sterling) versus 240 pounds sterling (217 pounds sterling to 263 pounds sterling). CONCLUSIONS: Practice based self monitoring resulted in small but significant improvements of blood pressure at six months, which were not sustained after a year. Self monitoring was well received by patients, anxiety did not increase, and there was no appreciable additional cost. Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care.

Psychological therapies for chronic pelvic pain:systematic review of randomized controlled trials

Chronic pelvic pain (CPP), a common cause of disability in women, is a condition best viewed in the biopsychosocial framework. Psychological interventions are frequently considered alongside medical and surgical treatments. Our objective was to evaluate the effectiveness of psychological therapies for the treatment of CPP. Electronic literature searches were conducted in Medline, Embase, PsycInfo and DARE databases from database inception to April 2010. Reference lists of selected articles were searched for further articles. The studies selected were randomized controlled trials of psychological therapies in patients with CPP compared with no treatment, standard gynecological treatment or another form of psychological therapy. Two reviewers independently selected articles without language restrictions and extracted data covering study characteristics, study quality and results. Reduction in pain, measured using visual analog scales or other measurements, was the main outcome measure. Of the 107 citations identified, four studies satisfied the inclusion criteria. Compared with no psychological intervention, therapy produced a standardized mean pain score of -3.27 [95% confidence interval (CI) -4.52 to -2.02] and 1.11 (95% CI -0.05 to 2.27) at 3 months and -3.95 (95% CI -5.35 to -2.55) and 0.54 (95% CI -0.78 to 1.86) at 6 months and greater, based on a visual analog scale score of 0-10. The current evidence does not allow us to conclude whether psychological interventions have an effect on self-reported pain scores in women with CPP.

Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study):a cluster randomised controlled trial

Background - Delivery of high-quality, evidence-based health care to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive, enhanced care package in UK general practices for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes. Methods - In this cluster randomised controlled trial, 21 inner-city practices in the UK were assigned by simple randomisation to intervention (enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [nine practices; n=868]) or control (standard care [12 practices; n=618]) groups. All adult patients of south Asian origin with type 2 diabetes were eligible. Prescribing algorithms with clearly defined targets were provided for all practices. Primary outcomes were changes in blood pressure, total cholesterol, and glycaemic control (haemoglobin A1c) after 2 years. Analysis was by intention to treat. This trial is registered, number ISRCTN 38297969. Findings - We recorded significant differences between treatment groups in diastolic blood pressure (1·91 [95% CI -2·88 to -0·94] mm?Hg, p=0·0001) and mean arterial pressure (1·36 [-2·49 to -0·23] mm?Hg, p=0·0180), after adjustment for confounders and clustering. We noted no significant differences between groups for total cholesterol (0·03 [-0·04 to 0·11] mmol/L), systolic blood pressure (-0·33 [-2·41 to 1·75] mm?Hg), or HbA1c (-0·15% [-0·33 to 0·03]). Economic analysis suggests that the nurse-led intervention was not cost effective (incremental cost-effectiveness ratio £28?933 per QALY gained). Across the whole study population over the 2 years of the trial, systolic blood pressure, diastolic blood pressure, and cholesterol decreased significantly by 4·9 (95% CI 4·0–5·9) mm?Hg, 3·8 (3·2–4·4) mm?Hg, and 0·45 (0·40–0·51) mmol/L, respectively, and we recorded a small and non-significant increase for haemoglobin A1c (0·04% [-0·04 to 0·13]), p=0·290). Interpretation - We recorded additional, although small, benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes. Funding - Pfizer, Sanofi-Aventis, Servier Laboratories UK, Merck Sharp & Dohme/Schering-Plough, Takeda UK, Roche, Merck Pharma, Daiichi-Sankyo UK, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Bristol-Myers Squibb, Solvay Health Care, and Assurance Medical Society UK.

The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy - a randomised controlled trial

Lutein and zeaxanthin are lipid-soluble antioxidants found within the macula region of the retina. Links have been suggested between increased levels of these carotenoids and reduced risk for age-related macular disease (ARMD). Therefore, the effect of lutein-based supplementation on retinal and visual function in people with early stages of ARMD (age-related maculopathy, ARM) was assessed using multi-focal electroretinography (mfERG), contrast sensitivity and distance visual acuity. A total of fourteen participants were randomly allocated to either receive a lutein-based oral supplement (treated group) or no supplement (non-treated group). There were eight participants aged between 56 and 81 years (65·50 (sd 9·27) years) in the treated group and six participants aged between 61 and 83 years (69·67 (sd 7·52) years) in the non-treated group. Sample sizes provided 80 % power at the 5 % significance level. Participants attended for three visits (0, 20 and 40 weeks). At 60 weeks, the treated group attended a fourth visit following 20 weeks of supplement withdrawal. No changes were seen between the treated and non-treated groups during supplementation. Although not clinically significant, mfERG ring 3 N2 latency (P= 0·041) and ring 4 P1 latency (P= 0·016) increased, and a trend for reduction of mfERG amplitudes was observed in rings 1, 3 and 4 on supplement withdrawal. The statistically significant increase in mfERG latencies and the trend for reduced mfERG amplitudes on withdrawal are encouraging and may suggest a potentially beneficial effect of lutein-based supplementation in ARM-affected eyes. Copyright © 2012 The Authors.

A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes:design and methodology [ISRCTN78467674]

Background: Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. Methods: The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. Discussion: A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition.