The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium.

To evaluate the comparative effectiveness of three regional corticosteroid injections for uveitic macular edema: periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI). Design: Multicenter randomized clinical trialParticipants: Patients with uveitic macular edema Methods: Patients were randomized 1:1:1 to receive one of the three therapies. Patients with bilateral macular edema were assigned the same treatment for both eyes.Main Outcomes Measures: The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at BL) assessed with optical coherence tomography (OCT) by masked readers. Secondary outcomes included ≥20% improvement and resolution of macular edema, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks.Results: All treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, 99.87% Confidence Interval [CI]: 0.79, 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, 99.87% CI: 0.69, 0.56-0.86) had larger reductions in CST than PTA (p <0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, 99.87%CI: 0.88, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic macular edema. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than the PTA group at 8 weeks (p <0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (Hazard ratio [HR], 95% CI: 1.83, 0.91-3.65 and 2.52, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the two intravitreal treatment groups.Conclusions: Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic macular edema with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.

BackgroundCOPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).MethodsThis parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.ResultsBetween July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels.ConclusionSulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.Trial RegistrationClinicaltrials.gov: NCT01335971.

The associations were in the direction of increased risk for both passive smoking and current active smoking in both the 1963 and 1975 cohorts, but were stronger in the 1963 cohort. The results of this long-term, prospective cohort study corroborate the association between active cigarette smoking and cervical neoplasia and provide evidence that passive smoking is a risk factor for cervical neoplasia.

Objective To report the two-year incidence of raised intraocular pressure (IOP) and glaucomatous optic nerve damage in patients with uveitis randomized to either fluocinolone acetonide (FA) implants or systemic therapy. Secondarily, to explore patient and eye characteristics associated with IOP elevation or nerve damage. Design A randomized, partially masked trial in which patients were randomized to either FA implants or systemic therapy. Participants Patients age 13 years or older with non-infectious intermediate, posterior or panuveitis active within the prior 60 days for which systemic corticosteroids were indicated were eligible. Methods Visual fields were obtained at baseline and every 12 months using the Humphrey 24-2 SITA-fast protocol. Stereoscopic optic nerve photos were taken at baseline and at 3, 6, 12 and 24-month follow-up visits. IOP was measured by masked examiners at every study visit. Main Outcome Measures Glaucoma was diagnosed based on an increase in optic nerve cup-to-disc ratio with visual field worsening or increased cup-to-disc ratio alone, when visual fields were not available for cases where visual field change was not evaluable, due to missing data or severe visual field loss at baseline. Results Most patients were treated as assigned, among those evaluated for glaucoma 97% and 10% of patients assigned to implant and systemic treatment, respectively, received implants. More patients (65%) assigned to implants experienced an IOP elevation of at least 10 mmHg versus 24% assigned to systemic treatment (P<0.001). Similarly, 69% of patients assigned to the implant required IOP lowering therapy versus 26% in the systemic group (P<0.001). Glaucomatous optic nerve damage developed in 23% versus 6% (P<0.001) of implant and systemic patients, respectively. In addition to treatment assignment, black race, use of IOP-lowering medications and uveitis activity at baseline were associated with incident glaucoma (P < 0.05). Conclusion Implant-assigned eyes had about a four-fold risk of developing IOP elevation ≥ 10 mmHg and of incident glaucomatous optic neuropathy over the first two years compared to those assigned to systemic therapy. Central visual acuity was unaffected. Aggressive IOP monitoring with early treatment (often including early filtration surgery) are needed to avoid glaucoma when vision-threatening inflammation requires implant therapy.

Active cigarette smoking is a major risk factor for bladder cancer. Secondhand exposure to cigarette smoke may also contribute to bladder carcinogenesis. The authors conducted a prospective cohort study to examine the influence of both active smoking and household exposure to secondhand smoke (SHS) on subsequent bladder cancer risk. The study population included persons from two cohorts established from private censuses conducted in Washington County, Maryland, in 1963 (n = 45,749; 93 cases) and 1975 (n = 48,172; 172 cases). Poisson regression models were fitted to estimate the relative risk of bladder cancer associated with active and passive smoke exposure in the two cohorts (referent category: never smokers who did not live with any smokers). Current smokers had an elevated risk of bladder cancer in both the 1963 cohort (relative risk (RR) = 2.7, 95% confidence limits (CL): 1.6, 4.7) and the 1975 cohort (RR = 2.6, 95% CL: 1.7, 3.9) after adjustment for age, education, and marital status. Among nonsmoking women, current household SHS exposure was associated with bladder cancer risk in the 1963 cohort (RR = 2.3, 95% CL: 1.0, 5.4) but not in the 1975 cohort (RR = 0.9, 95% CL: 0.4, 2.3). This study further solidifies the evidence that active smoking is causally associated with bladder cancer. Additional studies are needed to determine whether passive smoking is a risk factor for bladder cancer.

Objectives-Because oxidative damage has been implicated in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, this study was designed to see if serum concentrations of tocopherol, carotene, and retinol, substances believed to be involved in the prevention or repair of oxidative damage, might be lower among persons who develop rheumatoid arthritis or systemic lupus erythematosus than among those who do not. Methods-For this prospective casecontrol study, persons with rheumatoid arthritis and systemic lupus erythematosus that developed two to 15 years after donating blood for a serum bank in 1974 were designated as cases. For each case, four controls were selected from the serum bank donors, matched for race, sex, and age. Stored serum samples from cases and controls were assayed for tocopherol, carotene, and retinol. Results-Cases of both diseases had lower serum concentrations of tocopherol, carotene, and retinol in 1974 than their matched controls. For rheumatoid arthritis, the diVerence for carotene (−29%) was statistically significant. Conclusions-These findings support those of a previous study that low antioxidant status is a risk factor for rheumatoid arthritis. They suggest a similar association for systemic lupus erythematosus.

Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.