Progression of Retinopathy Secondary to Maternally Inherited Diabetes and Deafness – Evaluation of Predicting Parameters

PURPOSE: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to Maternally Inherited Diabetes and Deafness (MIDD) and to evaluate the application of these factors in clinical trial design. DESIGN: Retrospective observational case series. METHODS: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by two independent readers. A linear mixed effect model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm2/year revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm2/year/mm2, p<0.001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials. CONCLUSIONS: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design

Electrophysiological Characterization of Macular Telangiectasia Type 2 and Structure-Function Correlation

PURPOSE: To investigate the electrophysiological features of macular telangiectasia Type 2 and their relationship to structure as determined by optical coherence tomography imaging. METHODS: Forty-two eyes from 21 patients enrolled in the Macular Telangiectasia Natural History Observation Study were reviewed. All patients had full-field and pattern electroretinography (ERG; PERG) with some patients additionally having multifocal electroretinography (mfERG; N = 15) or electrooculography (N = 12). Multiple linear regression modeling assessed the relationship between the ellipsoid zone break size on optical coherence tomography and the central mfERG response. RESULTS: Full-field ERG and electrooculography were normal in all eyes. Six eyes (14%) from five patients had subnormal PERG P50 amplitudes. Twenty-two of 30 eyes (73%) had reduced central or paracentral stimulus on mfERG. There was a significant correlation between ellipsoid zone break size and both the P1 amplitude (R = 0.37, P = 0.002) and P1:N1 ratio (R = 0.32, P = 0.002) of the central response on mfERG. CONCLUSION: The electrophysiological findings in macular telangiectasia Type 2 are those of localized central dysfunction and are consistent with the structural data available from imaging and histologic studies. The ellipsoid zone break size correlates with mfERG reduction. The reduced mfERG P1:N1 ratio is consistent with inner retinal dysfunction

Epidemiological and economic burden of metabolic syndrome and its consequences in patients with hypertension in Germany, Spain and Italy; a prevalence-based model

<p>Abstract</p> <p>Background</p> <p>The presence of metabolic syndrome in patients with hypertension significantly increases the risk of cardiovascular disease, type 2 diabetes and mortality. Our aim is to estimate the epidemiological and economic burden to the health service of metabolic syndrome in patients with hypertension in three European countries in 2008 and 2020.</p> <p>Methods</p> <p>An age, sex and risk group structured prevalence based cost of illness model was developed using the United States Adult Treatment Panel III of the National Cholesterol Education Program criteria to define metabolic syndrome. Data sources included published information and public use databases on disease prevalence, incidence of cardiovascular events, prevalence of type 2 diabetes, treatment patterns and cost of management in Germany, Spain and Italy.</p> <p>Results</p> <p>The prevalence of hypertension with metabolic syndrome in the general population of Germany, Spain and Italy was 36%, 11% and 10% respectively. In subjects with hypertension 61%, 22% and 21% also had metabolic syndrome. Incident cardiovascular events and attributable mortality were around two fold higher in subjects with metabolic syndrome and prevalence of type 2 diabetes was around six-fold higher. The economic burden to the health service of metabolic syndrome in patients with hypertension was been estimated at €24,427, €1,900 and €4,877 million in Germany, Spain and Italy and forecast to rise by 59%, 179% and 157% respectively by 2020. The largest components of costs included the management of prevalent type 2 diabetes and incident cardiovascular events. Mean annual costs per hypertensive patient were around three-fold higher in subjects with metabolic syndrome compared to those without and rose incrementally with the additional number of metabolic syndrome components present.</p> <p>Conclusion</p> <p>The presence of metabolic syndrome in patients with hypertension significantly inflates economic burden and costs are likely to increase in the future due to an aging population and an increase in the prevalence of components of metabolic syndrome.</p

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. // Design: Multicenter, international, prospective cohort study. // Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. // Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. // Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells

Prescribing Data in General Practice Demonstration (PDGPD) project - a cluster randomised controlled trial of a quality improvement intervention to achieve better prescribing for chronic heart failure and hypertension

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1472-6963/12/273 Extent: 11p.Background: Research literature consistently documents that scientifically based therapeutic recommendations are not always followed in the hospital or in the primary care setting. Currently, there is evidence that some general practitioners in Australia are not prescribing appropriately for patients diagnosed with 1) hypertension (HT) and 2) chronic heart failure (CHF). The objectives of this study were to improve general practitioner’s drug treatment management of these patients through feedback on their own prescribing and small group discussions with peers and a trained group facilitator. The impact evaluation includes quantitative assessment of prescribing changes at 6, 9, 12 and 18 months after the intervention. Methods: A pragmatic multi site cluster RCT began recruiting practices in October 2009 to evaluate the effects of a multi-faceted quality improvement (QI) intervention on prescribing practice among Australian general practitioners (GP) in relation to patients with CHF and HT. General practices were recruited nationally through General Practice Networks across Australia. Participating practices were randomly allocated to one of three groups: two groups received the QI intervention (the prescribing indicator feedback reports and small group discussion) with each group undertaking the clinical topics (CHF and HT) in reverse order to the other. The third group was waitlisted to receive the intervention 6 months later and acted as a "control" for the other two groups. De-identified data on practice, doctor and patient characteristics and their treatment for CHF and HT are extracted at six-monthly intervals before and after the intervention. Post-test comparisons will be conducted between the intervention and control arms using intention to treat analysis and models that account for clustering of practices in a Network and clustering of patients within practices and GPs. Discussion: This paper describes the study protocol for a project that will contribute to the development of acceptable and sustainable methods to promote QI activities within routine general practice, enhance prescribing practices and improve patient outcomes in the context of CHF and HT. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR), Trial # 320870.Margaret Williamson, Magnolia Cardona-Morrell, Jeffrey D Elliott, James F Reeve, Nigel P Stocks, Jon Emery, Judith M Mackson and Jane M Gun

ISOLATED SYSTOLIC HYPERTENSION CHARACTERISTICS: DATA FROM THE BRISIGHELLA HEART STUDY (ITALY) AND THE ENAH STUDY (CROATIA)

Objective: Isolated systolic hypertension (ISH) in elderly is associated with increased global risk. It could be considered as a rough biomarker of increased arterial stiffness and advanced biological aging. In our study, we evaluate the association between ISH and other cardio-metabolic risk factors in two rural European populations from South Europe (Italy and Croatia). Design and method: In this international prospective long-term follow up study data on 5162 subjects from BrEnah cohort formed from original cohorts of Brisighella Heart Study (Italy) and ENAH Study (Croatia) were analized. Out of them 2253 subjects (694 from Croatia, 1559 from Italy; 980m, 1273f) were eligible for further analyses. BP was measured using Omron 6 device following the ESH guidelines. Fasting blood was analysed for glucose, lipids, uric acid, serum creatinine. Results: Results In general rural population from South Europe prevalence of ISH is high. Difference between Croatian and Italian subgroups was found (28.8% vs. 44.8%; p&lt;0.001; no gender differences) what is concordance with difference in age between two cohorts. Beside age, ISH was significantly associated with eGFR and various metabolic parameters including visceral obesity glucose intolerance and uric acid Conclusions: In this group of patients prevalence of ISH was high. Observed difference between Italian and Croatian subgroup is mostly due to difference in age. Metabolic disturbances are frequently associated with ISH additionally increasing global risk

Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation with Other Measures of Disease Severity

PURPOSE: Baseline visual fields to monitor the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. DESIGN: Cross-sectional study within a natural history study. SETTING: Multicenter, international STUDY POPULATION: Usher syndrome type 2 (USH2) (N=80) or autosomal recessive non-syndromic RP (ARRP) (N=47) associated with biallelic disease-causing sequence variants in USH2A. OBSERVATION PROCEDURES: Repeatability of full-field static perimetry (SP) and between-eye symmetry of kinetic perimetry (KP) were evaluated with intra-class correlation coefficients (ICC). The association of demographic and clinical characteristics with total hill of vision (VTOT) was assessed with general linear models. Associations between VTOT and other functional and morphologic measures were assessed using Spearman correlation coefficients and t-tests. MAIN OUTCOME MEASURES: VTOT (SP); III4e isopter area (KP). RESULTS: USH2 participants had more severe visual field loss than ARRP participants (P=.48; P<.05). Mean III4e isopter areas for left (4561±4426 deg2) and right eyes (4215±4300 deg2) were concordant (ICC=0.94). CONCLUSIONS: USH2 participants had more visual field loss than participants with USH2A-related ARRP, adjusting for duration of disease and age of enrollment. VTOT was repeatable and correlated with other functional and structural metrics, suggesting it may be a good summary measure of disease severity in patients with USH2A-related retinal degeneration