Statins and the progression of age-related macular degeneration in the United States.

PURPOSE: To study the effect of statin exposure on the progression from non-exudative to exudative age-related macular degeneration (AMD). METHODS: Retrospective cohort study of commercially insured patients diagnosed with non-exudative AMD (n = 231,888) from 2007 to 2015. Time-to-event analysis of the association between exposure to lipid-lowering medications and time from non-exudative AMD to exudative AMD diagnosis was conducted. Outcome measures included progression to exudative AMD, indicated by diagnosis codes for exudative AMD or procedural codes for intravitreal injections. RESULTS: In the year before and after first AMD diagnosis, 11,330 patients were continuously prescribed lipid-lowering medications and 31,627 patients did not take any lipid-lowering medication. Of those taking statins, 21 (1.6%) patients were on very-high-dose lipophilic statins, 644 (47.6%) on high-dose lipophilic statins, and 689 (50.9%) on low-dose lipophilic statins. We found no statistically significant relationship between exposure to low (HR 0.89, 95% CI 0.83 to 1.38) or high-dose lipophilic statins (HR 1.12, 95% CI 0.86 to 1.45) and progression to exudative AMD. No patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD, though this difference was not statistically significant due to the subgroup size (p = .23, log-rank test). CONCLUSIONS: No statistically significant relationship was found between statin exposure and risk of AMD progression. Interestingly, no patients taking very-high-dose lipophilic statins progressed to exudative AMD, a finding that warrants further exploration.

Evaluation of Racial, Ethnic, and Socioeconomic Associations With Treatment and Survival in Uveal Melanoma, 2004-2014.

Importance: Identifying disparities in uveal melanoma (UM) treatment patterns and survival across racial, ethnic, and socioeconomic (SES) groups reveals possible inequities in ophthalmologic health care. Objective: To examine the association of race, ethnicity, and SES with UM treatment and survival. Design, Setting, and Participants: A retrospective cohort analysis of 28% of the US population using the Surveillance, Epidemiology, and End Results (SEER) 18 registries from January 1, 2004, to December 31, 2014, was conducted. Data analysis was performed from April to July 2018. SEER identified 4475 individuals using International Classification of Diseases for Oncology, Third Edition site and morphology codes. Exposures: Race, ethnicity, and SES estimated by tertile using Yost Index composite scores. Main Outcomes and Measures: Treatment odds ratios (ORs), 1-year and 5-year survival estimates, mortality hazard ratios (HRs), and Kaplan-Meier survival curves. Hypothesis was formulated before data collection. Results: Multivariate analyses of 4475 individuals (2315 [51.7%] men; non-Hispanic white, 4130 [92.3%]; nonwhite, 345 [7.7%]) showed that patients who were nonwhite (OR, 1.45; 95% CI, 1.12-1.88) and socioeconomically disadvantaged (lower SES: OR, 2.21; 95% CI, 1.82-2.68; middle SES: OR, 1.86; 95% CI, 1.56-2.21) were more likely to receive primary enucleation. No interactions were observed between race/ethnicity, SES, and stage at diagnosis. From 2004 to 2014, rates of primary enucleation decreased across all racial/ethnic and SES groups, but disparities persisted. Socioeconomically disadvantaged patients had lower 5-year all-cause survival rates (lower SES: 69.2%; middle SES: 68.1%; and upper SES: 73.8%), although disease-specific survival did not vary significantly by racial/ethnic or SES strata. Mortality risk was associated with older age at diagnosis (56-68 years: HR, 1.70; 95% CI, 1.44-2.01; ≥69 years: HR, 3.32; 95% CI, 2.85-3.86), advanced stage of UM (stage 2: HR, 1.40; 95% CI, 1.19-1.65; stage 3: HR, 2.26; 95% CI, 1.87-2.73; and stage 4: HR, 10.09; 95% CI, 7.39-13.77), and treatment with primary enucleation (HR, 2.14; 95% CI, 1.88-2.44) with no racial/ethnic or SES variation. Conclusions and Relevance: In this study, SEER data from 2004 to 2014 suggest that nonwhite and socioeconomically disadvantaged patients with UM are more likely to be treated with primary enucleation, although no such variation appears to exist in disease-specific survival. These differences reveal opportunities to address issues regarding treatment choice in UM.

Characteristics of Ophthalmology Trials Registered in ClinicalTrials.gov, 2007-2018.

PURPOSE: To perform a comprehensive analysis of characteristics of ophthalmology trials registered in ClinicalTrials.gov. DESIGN: Cross-sectional study. METHODS: All 4,203 ophthalmologic clinical trials registered on ClinicalTrials.gov between October 1, 2007, and April 30, 2018, were identified by using medical subject headings (MeSH). Disease condition terms were verified by manual review. Trial characteristics were assessed through frequency calculations. Hazard ratios and 95% confidence intervals were determined for characteristics associated with early discontinuation. RESULTS: The majority of trials were multiarmed (73.6%), single-site (69.4%), randomized (64.8%), and had <100 enrollees (66.3%). A total of 33% used a data-monitoring committee (DMC), and 50.6% incorporated blinding. Other groups (51.6%) were funded by industry, whereas 2.6% were funded by the US National Institutes of Health (NIH). NIH trials were significantly more likely to address oncologic (NIH = 15.5%, Other = 3%, Industry = 1.5%; P < 0.001) or pediatric disease (NIH = 20.9%, Other = 5.9%, Industry = 1.4%; P < 0.001). Industry-sponsored trials (69.6% of phase 3 trials) were significantly more likely to be randomized (Industry = 68.7%, NIH = 58.9%, Other = 60.8%; P < 0.001) and blinded (Industry = 57.2%, NIH = 42.7%, Other = 43.5%; P < 0.001). A total of 359 trials (8.5%) were discontinued early, and 530 trials (12.6%) had unknown status. Trials were less likely to be discontinued if funded by sources other than industry (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55-0.95; P = 0.021) and/or had a DMC (HR, 0.71; 95% CI, 0.55-0.92; P = 0.010). CONCLUSIONS: Ophthalmology trials in the past decade reveal heterogeneity across study funding sources. NIH trials were more likely to support historically underfunded subspecialties, whereas Industry trials were more likely to face early discontinuation. These trends emphasize the importance of carefully monitored and methodologically sound trials with deliberate funding allocation.

Racial, Ethnic, and Socioeconomic Disparities in Retinoblastoma Enucleation: A Population-Based Study, SEER 18 2000-2014.

PURPOSE: To determine the effect of race, ethnicity, and census tract-level composite socioeconomic status (SES) on retinoblastoma enucleation. This study augments Truong and associates, providing multivariate analyses combining sociodemographic and clinical characteristics with more accurate SES measures. We hypothesized that children from nonwhite, Hispanic, and lower socioeconomic backgrounds would have increased adjusted odds of enucleation. DESIGN: Retrospective cohort analysis. SETTING: Multicenter population-based study using the Surveillance, Epidemiology, and End Results (SEER) 18 Registries. STUDY POPULATION: Children aged 18 years and younger diagnosed with retinoblastoma between 2000 and 2014. Subjects were identified using International Classification of Diseases-Oncology (ICD-O) site and morphology codes. MAIN OUTCOME MEASURES: Enucleation odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Analysis of 959 retinoblastoma patients revealed that 70.8% were enucleated. Adjusted analyses showed associations between enucleation and Asian (OR 2.00, CI 1.08-3.71) or black (2.42, 1.41-4.16) race, Hispanic ethnicity (1.69, 1.16-2.46), and low SES (1.68, 1.09-2.58). Significantly increased enucleation risk was associated with older age at diagnosis (age 1-2 years 2.55, 1.80-3.61; >2 years 4.88, 2.57-9.25), unilateral disease (5.00, 3.45-7.14), and advanced stage (regional 4.71, 2.51-8.84; distant 3.15, 1.63-6.08). No interactions were observed between race, ethnicity, SES, and stage at diagnosis. Enucleation rates decreased over time across all racial, ethnic, and socioeconomic groups. CONCLUSIONS: Children from nonwhite, Hispanic, and lower socioeconomic backgrounds are more likely to receive enucleation. These associations are independent of stage of diagnosis, suggesting larger systemic disparities in retinoblastoma care. The origin of these differences requires further study and attention by clinicians and policy makers.

Disparities in location of death of adolescents and young adults with cancer: A longitudinal, population study in California.

BACKGROUND: Patients with a terminal illness should have access to their chosen location of death. Cancer is the leading cause of non-accidental death among adolescents and young adults (AYAs; those aged 15-39 years). Although surveys have suggested that a majority of these patients prefer a home death, to the authors' knowledge, little is known regarding their barriers to accessing their preferred location of death. As a first step, the authors sought to determine, across a large population, 20-year trends in the location of death among AYA patients with cancer. METHODS: Using the Vital Statistics Death Certificate Database of the California Office of Statewide Health Planning and Development, the authors performed a retrospective, population-based analysis of California patients with cancer aged 15 to 39 years who died between 1989 and 2011. Sociodemographic and clinical factors associated with hospital death were examined using multivariable logistic regression. RESULTS: Of 30,573 AYA oncology decedents, 57% died in a hospital, 33% died at home, and 10% died in other locations (eg, hospice facility or nursing facility). Between 1989 and 1994, hospital death rates decreased from 68.3% to 53.6% and at-home death rates increased from 16.8% to 35.5%. Between 1995 and 2011, these rates were stable. Those individuals who were more likely to die in a hospital were those aged <30 years, of minority race, of Hispanic ethnicity, who lived ≤10 miles from a specialty center, and who had a diagnosis of leukemia or lymphoma. CONCLUSIONS: Overall, the majority of AYA cancer deaths occurred in a hospital, with a 5-year shift to more in-home deaths that abated after 1995. In-hospital deaths were more common among younger patients, patients of minority race/ethnicities, and those with a leukemia or lymphoma diagnosis. Further study is needed to determine whether these rates and disparities are consistent with patient preferences. Cancer 2017;123:4178-4184. © 2017 American Cancer Society.

Radiation history affects continence outcomes after advance transobturator sling placement in patients with post-prostatectomy incontinence.

OBJECTIVE: To evaluate the effects of preoperative external radiation therapy (XRT) on a cohort of patients who underwent AdVance transobturator urethral sling (ATUS) placement for post-prostatectomy incontinence. METHODS: Thirty-seven patients underwent placement of an ATUS from 2008 to 2010. Patients with and without a history of preoperative XRT were retrospectively compared in regard to their demographical, preoperative, perioperative, and postoperative details. RESULTS: The median follow-up was 17.3 months. Preoperative pad usage was significantly higher in the XRT patient group (P = .03). Overall, 19 patients (51.4%) used no pads, 10 patients (27.0%) were improved, 4 patients (10.8%) had no change, and 4 patients (10.8%) experienced worsening incontinence after the surgery. In patients with and without a history of XRT, 0 (0%) and 19 (63.3%) used no pads, 2 (28.6%) and 8 (26.7%) were improved, 2 (28.6%) and 2 (6.7%) showed no change, and 3 (42.9%) and 1 (3.3%) were worse, respectively. In comparing patients with more severe incontinence preoperatively (>1 pad/day), those with and without radiation, 0 (0%) and 7 (46.7%) used no pads, 2 (28.6%) and 7 (46.7%) were improved, 2 (28.6%) and 0 (0%) had no change, and 3 (42.9%) and 1 (6.7%) were worse, respectively, after ATUS placement. Thus, patients without XRT had an advantage in postoperative pad usage (P = .001), and, furthermore, had improved quality of life (86.2% vs 28.6%, P = .006). CONCLUSION: The ATUS provides excellent continence outcomes in patients suffering from post-prostatectomy urinary incontinence. However, previous pelvic irradiation seems to severely compromise the effectiveness of the ATUS.

Asthma discordance in twins is linked to epigenetic modifications of T cells.

T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures. Our study was conducted in a monozygotic twin cohort of adult twin pairs (n = 21) all discordant for asthma. Regulatory T cell (Treg) and effector T cell (Teff) subsets were assessed for levels of cellular function, protein expression, gene expression and CpG methylation within Forkhead box P3 (FOXP3) and interferon gamma-γ (IFNγ) loci. Comparisons by asthma and current report of exposure to second hand smoke were made. Treg from asthmatic discordant twins demonstrated decreased FOXP3 protein expression and impaired Treg function that was associated with increased levels of CpG methylation within the FOXP3 locus when compared to their non-asthmatic twin partner. In parallel, Teff from discordant asthmatic twins demonstrated increased methylation of the IFNγ locus, decreased IFNγ expression and reduced Teff function when compared to Teff from the non-asthmatic twin. Finally, report of current exposure to second hand smoke was associated with modifications in both Treg and Teff at the transcriptional level among asthmatics. The results of the current study provide evidence for differential function of T cell subsets in monozygotic twins discordant for asthma that are regulated by changes in DNA methylation. Our preliminary data suggest exposure to second hand smoke may augment the modified T cell responses associated with asthma.