Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

To access full text version of this article. Please click on the hyperlink "View/open" at the bottom of this pageWe aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. The study population consisted of 4,994 persons aged ≥ 67 years, who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA(1c) ≥ 6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA(1c), insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.NIH N01-AG-12100 NIH/NIA, National Eye Institute (NEI) of the NIH ZIAEY000401, Hjartavernd (the Icelandic Heart Association), Althingi (the Icelandic Parliament), University of Iceland

Non-Sexual Transmission of Trichomonas vaginalis in Adolescent Girls Attending School in Ndola, Zambia

OBJECTIVES: To identify risk factors for trichomoniasis among young women in Ndola, Zambia. METHOD: The study was a cross-sectional study among adolescent girls aged 13-16 years in Ndola, Zambia. Study participants were recruited from schools in selected administrative areas that represented the different socio-economic strata in town. Consenting participants were interviewed about their socio-demographic characteristics; sexual behaviour; and hygiene practices. Self-administered vaginal swabs were tested for Trichomonas vaginalis. HSV-2 antibodies were determined on serum to validate the self-reported sexual activity. RESULTS: A total of 460 girls participated in the study. The overall prevalence of trichomoniasis was 27.1%, 33.9% among girls who reported that they had ever had sex and 24.7% among virgins. In multivariate analysis the only statistically significant risk factor for trichomoniasis was inconsistent use of soap. For the virgins, none of the risk factors was significantly associated with trichomoniasis, but the association with use of soap (not always versus always) and type of toilet used (pit latrine/bush versus flush toilet) was of borderline significance. CONCLUSION: We found a high prevalence of trichomoniasis in girls in Ndola who reported that they had never had sex. We postulate that the high prevalence of trichomoniasis in virgins in Ndola is due to non-sexual transmission of trichomoniasis via shared bathing water and inconsistent use of soap

Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people.population-based cohort study.the study population included 4,926 Icelandic individuals, aged ≥67 years, 43.4% male, who completed vision and hearing examinations between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) and were followed prospectively for mortality through 2009.participants were classified as having 'moderate or greater' degree of impairment for vision only (VI), hearing only (HI), and both vision and hearing (dual sensory impairment, DSI). Cox proportional hazard regression, with age as the time scale, was used to calculate hazard ratios (HR) associated with impairment and mortality due to all-causes and specifically CVD after a median follow-up of 5.3 years.the prevalence of HI, VI and DSI were 25.4, 9.2 and 7.0%, respectively. After adjusting for age, significantly (P < 0.01) increased mortality from all causes, and CVD was observed for HI and DSI, especially among men. After further adjustment for established mortality risk factors, people with HI remained at higher risk for CVD mortality [HR: 1.70 (1.27-2.27)], whereas people with DSI remained at higher risk of all-cause mortality [HR: 1.43 (1.11-1.85)] and CVD mortality [HR: 1.78 (1.18-2.69)]. Mortality rates were significantly higher in men with HI and DSI and were elevated, although not significantly, among women with HI.older men with HI or DSI had a greater risk of dying from any cause and particularly cardiovascular causes within a median 5-year follow-up. Women with hearing impairment had a non-significantly elevated risk. Vision impairment alone was not associated with increased mortality.National Institutes of Health, National Institute on Aging (NIA) N01-AG-12100 NIA Z01-AG007380 National Eye Institute (NEI) ZIAEY000401 National Institute on Deafness and Other Communication Disorders (NIDCD) Division of Scientific Programs/IAA Y2-DC-1004-02 Hjartavernd (Icelandic Heart Association) Althingi (Icelandic Parliament

Inflammatory, Hemostatic, and Other Novel Biomarkers for Diabetic Retinopathy: The Multi-Ethnic Study of Atherosclerosis

Objective&#8212; There are conflicting data regarding relationships of systemic biomarkers of inflammation, hemostasis, and homocysteine with diabetic retinopathy. We examined these relationships in the Multi-Ethnic Study of Atherosclerosis. Research design and methods&#8212; A total of 921 participants with diabetes were included. Diabetic retinopathy was graded from retinal photographs. We defined two outcomes: any diabetic retinopathy and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse). Systemic markers analyzed were C-reactive protein, homocysteine, fibrinogen, plasmin- 2-antiplasmin complex (PAP), interleukin-6, D-dimer, factor VIII, serum creatinine, and urinary albumin-to-creatinine (UAC) ratio. Results&#8212; Prevalence of diabetic retinopathy was 33.2% and vision-threatening diabetic retinopathy 7.1%. After adjusting for established risk factors (diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, and use of diabetes medications), fibrinogen (odds ratio 1.14 [95% CI 1.01&#8211;1.32], P 0.05) and PAP (1.25 [1.05&#8211;1.50], P0.01) were associated with any diabetic retinopathy, while PAP (1.54 [1.13&#8211;2.11], P 0.007) and homocysteine (1.57 [1.16&#8211; 2.11], P 0.003) were associated with vision-threatening diabetic retinopathy. Only PAP remained significant after additional adjustment for serum creatinine and UAC ratio. Area under receiver-operator characteristic curve (AUROC) for diabetic retinopathy was constructed for established and novel risk factors. Established risk factors accounted for a 39.2% increase of the AUROC, whereas novel markers (fibrinogen, PAP, homocysteine, serum creatinine, and UAC ratio) only accounted for an additional 2.2%. Conclusions&#8212; There were few associations of novel markers of inflammation, hemostasis, and homocysteine with diabetic retinopathy after controlling for established risk factors. These data suggest that there is limited clinical use of these biomarkers for prediction of diabetic retinopathy

Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of <it>Candida </it>in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth.</p> <p>Methods</p> <p>We used a prospective, randomized, open-label, blinded-endpoint (PROBE) study design. Pregnant women presenting at <20 weeks gestation with singleton pregnancies self-collected a vaginal swab. Those who were asymptomatic and culture positive for <it>Candida </it>were randomized to 6-days of clotrimazole vaginal pessaries (100mg) or usual care (screening result is not revealed, no treatment). The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth <37 weeks gestation was also assessed.</p> <p>Results</p> <p>Of 779 women approached, 500 (64%) participated in candidiasis screening, and 98 (19.6%) had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03.</p> <p>Conclusions</p> <p>A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609001052224.aspx">ACTRN12609001052224</a></p

Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts

Source at https://doi.org/10.3390/nu11010074.The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Source at http://doi.org/10.1371/journal.pone.0170791Background:Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality.Methods:In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488.Findings:We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and Interpretation:In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25610-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genomewide significant association

Protocol for a randomised controlled trial of treatment of asymptomatic candidiasis for the prevention of preterm birth [ACTRN12610000607077]

<p>Abstract</p> <p>Background</p> <p>Prevention of preterm birth remains one of the most important challenges in maternity care. We propose a randomised trial with: a simple <it>Candida </it>testing protocol that can be easily incorporated into usual antenatal care; a simple, well accepted, treatment intervention; and assessment of outcomes from validated, routinely-collected, computerised databases.</p> <p>Methods/Design</p> <p>Using a prospective, randomised, open-label, blinded-endpoint (PROBE) study design, we aim to evaluate whether treating women with asymptomatic vaginal candidiasis early in pregnancy is effective in preventing spontaneous preterm birth. Pregnant women presenting for antenatal care <20 weeks gestation with singleton pregnancies are eligible for inclusion. The intervention is a 6-day course of clotrimazole vaginal pessaries (100 mg) and the primary outcome is spontaneous preterm birth <37 weeks gestation.</p> <p>The study protocol draws on the usual antenatal care schedule, has been pilot-tested and the intervention involves only a minor modification of current practice. Women who agree to participate will self-collect a vaginal swab and those who are culture positive for Candida will be randomised (central, telephone) to open-label treatment or usual care (screening result is not revealed, no treatment, routine antenatal care). Outcomes will be obtained from population databases.</p> <p>A sample size of 3,208 women with <it>Candida </it>colonisation (1,604 per arm) is required to detect a 40% reduction in the spontaneous preterm birth rate among women with asymptomatic candidiasis from 5.0% in the control group to 3.0% in women treated with clotrimazole (significance 0.05, power 0.8). Analyses will be by intention to treat.</p> <p>Discussion</p> <p>For our hypothesis, a placebo-controlled trial had major disadvantages: a placebo arm would not represent current clinical practice; knowledge of vaginal colonisation with <it>Candida </it>may change participants' behaviour; and a placebo with an alcohol preservative may have an independent affect on vaginal flora. These disadvantages can be overcome by the PROBE study design.</p> <p>This trial will provide definitive evidence on whether screening for and treating asymptomatic candidiasis in pregnancy significantly reduces the rate of spontaneous preterm birth. If it can be demonstrated that treating asymptomatic candidiasis reduces preterm births this will change current practice and would directly impact the management of every pregnant woman.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12610000607077.aspx">ACTRN12610000607077</a></p

Modulatory effect of iron chelators on adenosine deaminase activity and gene expression in Trichomonas vaginalis

Trichomonas vaginalis is a flagellate protozoan that parasitises the urogenital human tract and causes trichomoniasis. During the infection, the acquisition of nutrients, such as iron and purine and pyrimidine nucleosides, is essential for the survival of the parasite. The enzymes for purinergic signalling, including adenosine deaminase (ADA), which degrades adenosine to inosine, have been characterised in T. vaginalis. In the evaluation of the ADA profile in different T. vaginalis isolates treated with different iron sources or with limited iron availability, a decrease in activity and an increase in ADA gene expression after iron limitation by 2,2-bipyridyl and ferrozine chelators were observed. This supported the hypothesis that iron can modulate the activity of the enzymes involved in purinergic signalling. Under bovine serum limitation conditions, no significant differences were observed. The results obtained in this study allow for the assessment of important aspects of ADA and contribute to a better understanding of the purinergic system in T. vaginalis and the role of iron in establishing infection and parasite survival