Idiopathic multiple retinal pigment epithelial detachments – A case report

Retinal pigment epithelial detachment, often asymptomatic is a common retinal finding. Multiple serous retinal pigment epithelial detachment especially in a female is very uncommon. We describe a case of multiple retinal pigment epithelial detachments throughout the fundus in a 51-year old female otherwise asymptomatic. Indocyanine green angiography and fundus auto fluorescence showed abnormalities with a normal systemic work-up. This is the first report of an asymptomatic patient correlating angiogram with auto fluorescence in multiple serous retinal pigment epithelial detachments.     

Vitrectomy with Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment following Acute Retinal Necrosis: Clinical Outcomes and Prognostic Factors

Purpose: The purpose of the study is to report the prognostic factors and outcomes of vitrectomy (PPV) with silicone oil tamponade in rhegmatogenous retinal detachment (RRD) secondary to acute retinal necrosis (ARN).

Methods: This retrospective, non-randomized, interventional comparative study included 38 eyes of 38 patients. All cases underwent PPV with silicone oil tamponade. The main outcome measure was improvement of final visual acuity relative to the presenting visual acuity and factors affecting the same Group A included eyes with favorable vision of 20/400 or better and Group B included the others.

Results: Group A included 16 eyes (42.10%), group B included 22 eyes (57.89%). In Group A 2 eyes out of 16 (12.5%) and in Group B 12 eyes out of 22 (54.54%) had RRD at presentation (p = 0.02, 95% CI for the difference 7.88–65.78%). The time interval between first presentation and development of RRD in Group A was 30.94 ± 38.8 days (median 30 days) whereas that in Group B was 10.81 ± 11.73 days (median 8 days) (p = 0.02). The odds of visual improvement post-vitrectomy when RRD occurred later was 8.4 (p = 0.01, 95% CI 1.53–46.1). The usage of systemic steroids (odds 5.2, p = 0.03, 95% CI 1.14–23.54) and oral valacyclovir (odds 4.33, p = 0.04, 95% CI 1.05–17.84) were associated with odds favoring a good visual outcome. Recurrent RRD was noted in 3/16 eyes (18.75%) in Group A and 13/22 eyes (59.09%) in Group B (p = 0.03).

Conclusion: Delayed occurrence of RRD after ARN is a good prognostic factor. Usage of systemic steroids and oral valacylocvir are associated with a favorable visual outcome when started before the onset of RRD.     

Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review

Purpose of Review

This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease.

Recent Findings

CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control.

Summary

Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

     

Dissolution Curve Comparisons Through the F2 Parameter,a Bayesian Extension of the f2 Statistic

Dissolution (or in vitro release) studies constitute an important aspect of pharmaceutical drug development. One important use of such studies is for justifying a biowaiver for post-approval changes which requires establishing equivalence between the new and old product. We propose a statistically rigorous modeling approach for this purpose based on the estimation of what we refer to as the F₂ parameter, an extension of the commonly used f₂ statistic. A Bayesian test procedure is proposed in relation to a set of composite hypotheses that capture the similarity requirement on the absolute mean differences between test and reference dissolution profiles. Several examples are provided to illustrate the application. Results of our simulation study comparing the performance of f₂ and the proposed method show that our Bayesian approach is comparable to or in many cases superior to the f₂ statistic as a decision rule. Further useful extensions of the method, such as the use of continuous-time dissolution modeling, are considered.     

Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child

Purpose

To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165.

Methods

A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF.

Results

Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection.

Conclusions

These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.     

Longitudinal Commercial Claims–Based Cost Analysis of Diabetic Retinopathy Screening Patterns

Background

Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service.

Objective

To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes.

Methods

Truven Health MarketScan commercial databases (2000–2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001–2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001–2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1–4, 5–7, and 8–10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables.

Results

In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts’ mean incremental cost increase was $185 between the 0- and 1–4–year cohorts (P <.003) and $202 between the 0- and 5–7–year cohorts (P <.023). The cost differences between the other cohorts, including $217 between the 0- and 8–10–year cohorts (P <.066), were not statistically significant.

Conclusions

Based on our analysis, the annual retinopathy screening rate for patients with diabetes has remained low since 2001, and has been well below the guideline-recommended screening levels. For patients with type 2 diabetes, the mean increase in healthcare expenditures over a 10-year period after diagnosis is not statistically different among those with various retinopathy screening rates, although the increase in healthcare spending is lower for patients with diabetes who were not screened for retinopathy compared with patients who did get screened.     

New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives Dave Singh

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β₂-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV₁), although the FEV₁ improvement was limited to approximately 80–90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV₁ and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.     

Chronic Recurrent Spontaneous Bacterial Peritonitis

The mortality rate in spontaneous bacterial peritonitis is reportedly high. Patients rarely survive the initial infection. Most patients die either because of infection or end-stage liver disease. A patient with alcoholic cirrhosis and portal hypertension with five distinct episodes of spontaneous bacterial peritonitis over a 2 1/2-year period is described.     

Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.