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1.  Inverse Association of Vitamin C with Cataract in Older People in India 
Ophthalmology  2011;118(10):1958-1965.e2.
Objective
To examine the association between vitamin C and cataract in the Indian setting.
Design
Population-based cross-sectional analytic study.
Participants
A total of 5638 people aged ≥60 years.
Methods
Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.
Main Outcome Measures
Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.
Results
Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51–0.74; P=1.1×10−6). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57–0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54–0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54–0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45–0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.
Conclusions
We found a strong association with vitamin C and cataract in a vitamin C–depleted population.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
doi:10.1016/j.ophtha.2011.03.016
PMCID: PMC3185206  PMID: 21705085
2.  Higher Levels and Intensity of Physical Activity Are Associated with Reduced Mortality among Community Dwelling Older People 
Journal of Aging Research  2011;2011:651931.
Introduction. There is limited evidence on physical activity and mortality in older people. Methods. People aged 75–84 years (n = 1449) participating in a randomized trial of health screening in UK general practice were interviewed about their physical activity (PA) and were assessed for a wide range of health and social problems. Mortality data were collected over 7 years of followup. Results. Full information on PA and potential confounders was available in 946 people. Those in the highest third of duration of PA had a lower mortality, confounder-adjusted Hazard Ratio (HR) = 0.74, and 95% Confidence Interval (CI) 0.56–0.97, compared to the lowest third. Similar benefits were seen when categorized by intensity of PA, with those in the highest group having a lower mortality, confounder-adjusted HR = 0.61, and 95% CI 0.47–0.79, compared to the lowest category. Conclusions. Our results suggest the importance of providing older people with opportunities for physical activity.
doi:10.4061/2011/651931
PMCID: PMC3062144  PMID: 21437004
3.  Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study 
This large, two-center, population-based study provides estimates of the prevalence of age-related macular degeneration in India.
Purpose.
To estimate the prevalence of early and late age-related macular degeneration (AMD) in India.
Methods.
Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System.
Results.
Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8–1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2–41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8–7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1–0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4–4.7); and early AMD: grade 1, 43.1(35.7–50.6); grade 2, 8.1 (4.3–12.0); and grade 3, 0.5 (0–1.5).
Conclusions.
The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated.
doi:10.1167/iovs.09-4114
PMCID: PMC2868454  PMID: 19696177
4.  Polymorphisms in ARMS2/HTRA1 and Complement Genes and Age-Related Macular Degeneration in India: Findings from the INDEYE Study 
Purpose.
Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India.
Methods.
Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1–3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center.
Results.
Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154), or CFB (rs438999) was not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13–1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15–2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02–1.23; P = 0.02); rs10490923 was not associated with early or late AMD.
Conclusions.
Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India.
We report results from a genetic association study of early AMD in an Indian population. Two variants in the ARMS/HTRA1 region were associated with early AMD but variants in C2, CFH, and CFB were not.
doi:10.1167/iovs.12-10073
PMCID: PMC3490538  PMID: 23060141
5.  Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies 
Human mutation  2011;32(12):1407-1416.
Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.
doi:10.1002/humu.21577
PMCID: PMC3217135  PMID: 21882290
age-related macular degeneration; AMD; apolipoprotein E; APOE; case-control association study
6.  Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older People 
American Journal of Epidemiology  2011;173(12):1357-1364.
Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ2 for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ2 for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.
doi:10.1093/aje/kwr015
PMCID: PMC3145394  PMID: 21498624
aged; apolipoprotein E2; apolipoprotein E3; apolipoprotein E4; apolipoproteins E; longevity; meta-analysis; multicenter study
7.  EPHA2 Polymorphisms and Age-Related Cataract in India 
PLoS ONE  2012;7(3):e33001.
Objective
We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.
Methods
We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.
Results
7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.
Conclusions
Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.
doi:10.1371/journal.pone.0033001
PMCID: PMC3297613  PMID: 22412971
8.  The estimated prevalence and incidence of late stage age related macular degeneration in the UK 
Background
UK estimates of age related macular degeneration (AMD) occurrence vary.
Aims
To estimate prevalence, number and incidence of AMD by type in the UK population aged ≥50 years.
Methods
Age-specific prevalence rates of AMD obtained from a Bayesian meta-analysis of AMD prevalence were applied to UK 2007–2009 population data. Incidence was estimated from modelled age-specific prevalence.
Results
Overall prevalence of late AMD was 2.4% (95% credible interval (CrI) 1.7% to 3.3%), equivalent to 513 000 cases (95% CrI 363 000 to 699 000); estimated to increase to 679 000 cases by 2020. Prevalences were 4.8% aged ≥65 years, 12.2% aged ≥80 years. Geographical atrophy (GA) prevalence rates were 1.3% (95% CrI 0.9% to 1.9%), 2.6% (95% CrI 1.8% to 3.7%) and 6.7% (95% CrI 4.6% to 9.6%); neovascular AMD (NVAMD) 1.2% (95% CrI 0.9% to 1.7%), 2.5% (95% CrI 1.8% to 3.4%) and 6.3% (95% CrI 4.5% to 8.6%), respectively. The estimated number of prevalent cases of late AMD were 60% higher in women versus men (314 000 cases in women, 192 000 men). Annual incidence of late AMD, GA and NVAMD per 1000 women was 4.1 (95% CrI 2.4% to 6.8%), 2.4 (95% CrI 1.5% to 3.9%) and 2.3 (95% CrI 1.4% to 4.0%); in men 2.6 (95% CrI 1.5% to 4.4%), 1.7 (95% CrI 1.0% to 2.8%) and 1.4 (95% CrI 0.8% to 2.4%), respectively. 71 000 new cases of late AMD were estimated per year.
Conclusions
These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments.
doi:10.1136/bjophthalmol-2011-301109
PMCID: PMC3329633  PMID: 22329913
Prevalence; incidence; AMD; UK; epidemiology; clinical trial
9.  Prevalence and Risk Factors for Vitamin C Deficiency in North and South India: A Two Centre Population Based Study in People Aged 60 Years and Over 
PLoS ONE  2011;6(12):e28588.
Background
Studies from the UK and North America have reported vitamin C deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are few data on vitamin C deficiency in resource poor countries.
Objectives
To investigate the prevalence of vitamin C deficiency in India.
Design
We carried out a population-based cross-sectional survey in two areas of north and south India. Randomly sampled clusters were enumerated to identify people aged 60 and over. Participants (75% response rate) were interviewed for tobacco, alcohol, cooking fuel use, 24 hour diet recall and underwent anthropometry and blood collection. Vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid. We categorised vitamin C status as deficient (<11 µmol/L), sub-optimal (11–28 µmol/L) and adequate (>28 µmol/L). We investigated factors associated with vitamin C deficiency using multivariable Poisson regression.
Results
The age, sex and season standardized prevalence of vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668 people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only 10.8% in the north and 25.9% in the south met the criteria for adequate levels. Vitamin C deficiency varied by season, and was more prevalent in men, with increasing age, users of tobacco and biomass fuels, in those with anthropometric indicators of poor nutrition and with lower intakes of dietary vitamin C.
Conclusions
In poor communities, such as in our study, consideration needs to be given to measures to improve the consumption of vitamin C rich foods and to discourage the use of tobacco.
doi:10.1371/journal.pone.0028588
PMCID: PMC3232233  PMID: 22163038
10.  A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799] 
Nutrition Journal  2011;10:22.
Background
Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain.
Methods
The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol.
Conclusions
In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.
doi:10.1186/1475-2891-10-22
PMCID: PMC3062585  PMID: 21396086
11.  Prevalence of Cataract in an Older Population in India 
Ophthalmology  2011;118(2-19):272-278.e2.
Purpose
To describe the prevalence of cataract in older people in 2 areas of north and south India.
Design
Population-based, cross-sectional study.
Participants
Randomly sampled villages were enumerated to identify people aged ≥60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination.
Methods
The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III).
Main Outcome Measures
Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract.
Results
The prevalence of unoperated cataract in people aged ≥60 was 58% in north India (95% CI, 56–60) and 53% (95% CI, 51–55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46–50) in north India and 38% (95% CI, 37–40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20–23) and 17% (95% CI, 16–19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7–9) and 10.2% (95% CI, 9–11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002).
Conclusions
We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
doi:10.1016/j.ophtha.2010.05.020
PMCID: PMC3146699  PMID: 20801514
12.  An Ecological Correlation Study of Late Age-Related Macular Degeneration and the Complement Factor H Y402H Polymorphism 
Based on published data, this ecological correlation study showed evidence to support the hypothesis that variation in the risk allele frequency of the Y402H polymorphism across ethnicities explains variation in prevalence of late AMD when data on people of African ancestry are excluded.
Purpose.
To investigate whether variation in the distribution of the risk allele frequency of the Y402H single-nucleotide polymorphism (SNP) across various ethnicities and geographic regions reflects differences in the prevalence of late age-related macular degeneration (AMD) in those ethnicities.
Methods.
Published data were obtained via a systematic search. Study samples were grouped into clusters by ethnicity and geographic location and the Spearman correlation coefficient of the prevalence of late AMD and risk allele frequencies was calculated across clusters.
Results.
Across all ethnicities, AMD prevalence was seen to increase with age. Populations of European descent had both higher risk allele frequencies and prevalence of late AMD than did Japanese, Chinese, and Hispanic descendants. Results for African descendants were anomalous: although allele frequency was similar to that in European populations, the age-specific prevalence of late AMD was considerably lower. The correlation coefficient for the association between allele frequency and AMD prevalence was 0.40 (95% confidence interval [CI] = −0.36 to 0.84, P = 0.28) in all populations combined and 0.71 (95% CI = 0.02–0.94, P = 0.04) when people of African descent were excluded.
Conclusions.
Evidence was found at the population level to support a positive association between the Y204H risk allele and the prevalence of AMD after exclusion of studies undertaken on persons of African ancestry. Data in African, Middle Eastern, and South American populations are needed to provide a better understanding of the association of late AMD genetic risk across ethnicities.
doi:10.1167/iovs.09-4228
PMCID: PMC2868481  PMID: 20042653
13.  Hospital admissions in older people with visual impairment in Britain 
BMC Ophthalmology  2008;8:16.
Background
We aimed to assess the risk of hospital admission associated with visual impairment in a representative sample of older people living in the community in Britain.
Methods
Design: Prospective study of hospital admission in a population-based sample of community dwelling people aged 75 years and above in Britain. Setting: 53 general practices. Participants: 14,394 participants in the MRC Trial of Assessment and Management of Older people in the Community. Main outcome measure: Hospital admission.
Results
Visually impaired older people had 238.7 admissions/1000 person-years compared to 169.7 admissions/1000 person-years in people with good vision: age and sex adjusted rate ratio (RR) 1.32 (95% CI 1.19 to 1.47). Adjusting for a wide range of potential explanatory factors largely eliminated this association: RR 1.06 (95% CI 0.94 to 1.20). However, adjusting for a more limited range of confounding factors, excluding those factors possibly a consequence of reduced vision, left a modest increased risk: RR 1.19 (95% CI 1.06 to 1.34).
Conclusion
The association between visual impairment and rate of hospital admission can be attributed to higher levels of co-morbidity and reduced functional ability among people with reduced vision. Visual impairment is likely to be an important contributor to reduced functional ability, but other factors may also be involved.
doi:10.1186/1471-2415-8-16
PMCID: PMC2564910  PMID: 18786264
14.  Years of sunlight exposure and cataract: a case-control study in a Mediterranean population 
BMC Ophthalmology  2007;7:18.
Background
We aimed to investigate the relation between sunlight exposure and risk of cataract.
Methods
We carried out a frequency-matched case-control study of 343 cases and 334 controls attending an ophthalmology outpatient clinic at a primary health-care center in a small town near Valencia, Spain.
All cases were diagnosed as having a cataract in at least one eye based on the Lens Opacification Classification system (LOCS II). Controls had no opacities in either eye. All cases and controls were interviewed for information on outdoor exposure, "usual" diet, history of severe episodes of diarrhea illness, life-style factors and medical and socio-demographic variables. Blood antioxidant vitamin levels were also analyzed. We used logistic regression models to estimate sex and age-adjusted odds ratios (ORs) by quintiles of years of occupational outdoor exposure, adjusting for potential confounders such as smoking, alcohol consumption, serum antioxidants and education.
Results
No association was found between years of outdoor exposure and risk of cataract. However, exploratory analyses suggested a positive association between years of outdoor exposure at younger ages and risk of nuclear cataract later in life.
Conclusion
Our study does not support an association with cataract and sunlight exposure over adult life.
doi:10.1186/1471-2415-7-18
PMCID: PMC2234085  PMID: 18039367
15.  Fracture risk and the use of a diuretic (indapamide sr) ± perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET) 
Trials  2006;7:33.
Background
The Hypertension in the Very Elderly Trial (HYVET) is a placebo controlled double blind trial of treating hypertension with indapamide Slow Release (SR) ± perindopril in subjects over the age of 80 years. The primary endpoints are stroke (fatal and non fatal). In view of the fact that thiazide diuretics and indapamide reduce urinary calcium and may increase bone mineral density, a fracture sub study was designed to investigate whether or not the trial anti-hypertensive treatment will reduce the fracture rate in very elderly hypertensive subjects.
Methods
In the trial considerable care is taken to ascertain any fractures and to identify risk factors for fracture, such as falls, co-morbidity, drug treatment, smoking and drinking habits, levels of activity, biochemical abnormalities, cardiac irregularities, impaired cognitive function and symptoms of orthostatic hypotension.
Potential results
The trial is expected to provide 10,500 patient years of follow-up. Given a fracture rate of 40/1000 patient years and a 20% difference in fracture rate, the power of the sub study is 58% to detect this difference at the 5% level of significance. The corresponding power for a reduction of 25% is 78%.
Conclusion
The trial is well under way, expected to complete in 2009, and on target to detect, if present, the above differences in fracture rate.
doi:10.1186/1745-6215-7-33
PMCID: PMC1769508  PMID: 17177983
16.  A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636] 
Nutrition Journal  2006;5:20.
The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK.
To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70–79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain.
The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance.
doi:10.1186/1475-2891-5-20
PMCID: PMC1564406  PMID: 16945130
17.  Is the NEI-VFQ-25 a useful tool in identifying visual impairment in an elderly population? 
BMC Ophthalmology  2006;6:24.
Background
The use of self-report questionnaires to substitute for visual acuity measurement has been limited. We examined the association between visual impairment and self reported visual function in a population sample of older people in the UK.
Methods
Cross sectional study of people aged more than 75 years who initially participated in a trial of health screening. The association between 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores and visual impairment (defined as an acuity of less than 6/18 in the better eye) was examined using logistic regression.
Results
Visual acuity and NEI-VFQ scores were obtained from 1807 participants (aged 77 to 101 years, 36% male), from 20 general practices throughout the UK. After adjustment for age, gender, practice and NEI-VFQ sub-scale scores, those complaining of poor vision in general were 4.77 times (95% CI 3.03 to 7.53) more likely to be visually impaired compared to those who did not report difficulty. Self-reported limitations with social functioning and dependency on others due to poor vision were also associated with visual impairment (odds ratios, 2.52, 95% CI 1.55 to 4.11; 1.73, 95% CI 1.05 to 2.86 respectively). Those reporting difficulties with near vision and colour vision were more likely to be visually impaired (odds ratios, 2.32, 95% CI 1.30 to 4.15; 2.25, 95% CI 1.35 to 3.73 respectively). Other NEI-VFQ sub-scale scores were unrelated to measures of acuity. Similar but weaker odds ratios were found with reduced visual acuity (defined as less than 6/12 in the better eye). Although differences in NEI-VFQ scores were small, scores were strongly associated with visual acuity, binocular status, and difference in acuity between eyes.
Conclusion
NEI-VFQ questions regarding the quality of general vision, social functioning, visual dependency, near vision and colour vision are strongly and independently associated with an objective measure of visual impairment in an elderly population.
doi:10.1186/1471-2415-6-24
PMCID: PMC1523367  PMID: 16764714
18.  Trends in influenza vaccination uptake among people aged over 74 years, 1997–2000: Survey of 73 general practices in Britain 
Background
Influenza vaccination policy for elderly people in Britain has changed twice since 1997 to increase protection against influenza but there is no information available on how this has affected vaccine uptake, and socioeconomic variation therein, among people aged over 74 years.
Methods
Vaccination information for 1997–2000 was collected directly from general practices taking part in a MRC-funded Trial of the Assessment and Management of Older People in the Community. This was linked to information collected during assessments carried out as part of the Trial. Regression modelling was used to assess relative probabilities (as relative risks, RR) of having vaccination according to year, gender, age, area and individual socioeconomic characteristics.
Results
Out of 106 potential practices, 73 provided sufficient information to be included in the analysis. Uptake was 48% (95% CI 45%, 55%) in 1997 and did not increase substantially until 2000 when the uptake was a third higher at 63% (50%, 66%). Vaccination uptake was lower among women than men (RR 0.9), people aged 85 or more compared to people aged under 80 (RR 0.9), those in the most deprived areas (RR 0.8) compared to the least deprived, and was relatively high for those in owner-occupied homes with central heating compared to other non-supported housing (RR for remainder = 0.9). This pattern did not change over the years studied.
Conclusions
Increased uptake in 2000 may have resulted from the additional financial resources given to practices; it was not at the expense of more disadvantaged socioeconomic groups but nor did they benefit disproportionately.
doi:10.1186/1471-2296-5-8
PMCID: PMC421730  PMID: 15099402
19.  Screening older people for impaired vision in primary care: cluster randomised trial 
BMJ : British Medical Journal  2003;327(7422):1027.
Objective To determine the effectiveness of screening for visual impairment in people aged 75 or over as part of a multidimensional screening programme.
Design Cluster randomised trial.
Setting General practices in the United Kingdom participating in the MRC trial of assessment and management of older people in the community.
Participants 4340 people aged 75 years or over randomly sampled from 20 general practices, excluding people resident in hospitals or nursing homes.
Intervention Visual acuity testing and referral to eye services for people with visual impairment. Universal screening (assessment and visual acuity testing) was compared with targeted screening, in which only participants with a range of health related problems were offered an assessment that included acuity screening.
Main outcome measures Proportion of people with visual acuity less than 6/18 in either eye; mean composite score of 25 item version of the National Eye Institute visual function questionnaire.
Results Three to five years after screening, the relative risk of having visual acuity < 6/18 in either eye, comparing universal with targeted screening, was 1.07 (95% confidence interval 0.84 to 1.36; P = 0.58). The mean composite score of the visual function questionnaire was 85.6 in the targeted screening group and 86.0 in the universal group (difference 0.4, 95% confidence interval -1.7 to 2.5, P = 0.69).
Conclusions Including a vision screening component by a practice nurse in a pragmatic trial of multidimensional screening for older people did not lead to improved visual outcomes.
PMCID: PMC261660  PMID: 14593039
20.  Improving the response rates to questionnaires  
BMJ : British Medical Journal  2002;324(7347):1168-1169.
PMCID: PMC1123146  PMID: 12016167
21.  Randomised comparison of three methods of administering a screening questionnaire to elderly people: findings from the MRC trial of the assessment and management of older people in the community 
BMJ : British Medical Journal  2001;323(7326):1403.
Objective
To compare three different methods of administering a brief screening questionnaire to elderly people: post, interview by lay interviewer, and interview by nurse.
Design
Randomised comparison of methods within a cluster randomised trial.
Setting
106 general practices in the United Kingdom.
Participants
32 990 people aged 75 years or over registered with participating practices.
Main outcome measures
Response rates, proportion of missing values, prevalence of self reported morbidity, and sensitivity and specificity of self reported measures by method of administration of questionnaire for four domains.
Results
The response rate was higher for the postal questionnaire than for the two interview methods combined (83.5% v 74.9%; difference 8.5%, 95% confidence interval 4.4% to 12.7%, P<0.001). The proportion of missing or invalid responses was low overall (mean 2.1%) but was greater for the postal method than for the interview methods combined (4.1% v 0.9%; difference 3.2%, 2.7% to 3.6%, P<0.001). With a few exceptions, levels of self reported morbidity were lower in the interview groups, particularly for interviews by nurses. The sensitivity of the self reported measures was lower in the nurse interview group for three out of four domains, but 95% confidence intervals for the estimates overlapped. Specificity of the self reported measures varied little by method of administration.
Conclusions
Postal questionnaires were associated with higher response rates but also higher proportions of missing values than were interview methods. Lower estimates of self reported morbidity were obtained with the nurse interview method and to a lesser extent with the lay interview method than with postal questionnaires.
What is already known on this topicThe optimum method of administering a brief multidimensional screening assessment to elderly people is not knownWhat this study addsPostal questionnaires produce a higher response rate than interviews by nurses or lay interviewers but also higher proportions of missing dataInterview by nurses and to a lesser degree by lay interviewers is associated with lower levels of self reported morbidity than are postal questionnaires
PMCID: PMC60986  PMID: 11744565
22.  How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2) 
Background
The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications.
Methods
After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide.
Results
Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients.
Conclusion
Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide.
doi:10.1186/cvm-2-6-298
PMCID: PMC64833  PMID: 11806817
calcium-channel blockers; elderly; isolated systolic hypertension

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