Alyce Burke

Serum concentrations of α tocopherol, β carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus

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 α tocopherol, β 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 case-control 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 α tocopherol, β carotene, and retinol. RESULTS Cases of both diseases had lower serum concentrations of α tocopherol, β carotene, and retinol in 1974 than their matched controls. For rheumatoid arthritis, the difference for β 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.

Active and passive cigarette smoking and the risk of cervical neoplasia.

OBJECTIVE: Evidence links active cigarette smoking to cervical neoplasia, but much less is known about the role of passive smoking. Using a prospective cohort design, we examined personal cigarette smoking and household passive smoke exposure in relation to the risk of cervical neoplasia. METHODS: Cohorts were established based on data collected on the smoking status of all household members during private censuses of Washington County, Maryland in 1963 (n = 24,792) and 1975 (n = 26,381). Using the Washington County Cancer Registry, the occurrence of cervical neoplasia in the two cohorts was ascertained from 1963–1978 and from 1975–1994. Poisson regression models were fitted to estimate the relative risk of developing cervical neoplasia associated with active and passive smoking in both cohorts. The referent category for all comparisons was never smokers not exposed to passive smoking. RESULTS: The adjusted relative risk and 95% confidence limits for passive smoking was 2.1 (1.3, 3.3) in the 1963 cohort and 1.4 (0.8, 2.4) in the 1975 cohort. The adjusted relative risk and 95% confidence limits for current smoking were 2.6 (1.7, 4.1) and 1.7 (1.1, 2.6) in the 1963 and 1975 cohort, respectively. CONCLUSION: 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. LEVEL OF EVIDENCE: II-2

Risk of elevated intraocular pressure and glaucoma in patients with uveitis: results of the multicenter uveitis steroid treatment trial.

OBJECTIVE To report the 2-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, we sought 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 aged ≥ 13 years with noninfectious 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 Swedish interactive threshold algorithm (SITA) fast protocol. Stereoscopic optic nerve photos were taken at baseline and at 3-, 6-, 12-, and 24-month follow-up visits. Masked examiners measured IOP 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, for cases where visual field change was not evaluable, because of 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 ≥ 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). CONCLUSIONS Implant-assigned eyes had about a 4-fold risk of developing IOP elevation of ≥ 10 mmHg and incident glaucomatous optic neuropathy over the first 2 years compared with those assigned to systemic therapy. Central visual acuity was unaffected. Aggressive IOP monitoring with early treatment (often including early filtration surgery) is needed to avoid glaucoma when vision-threatening inflammation requires implant therapy. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Nonsteroidal anti-inflammatory drugs and the risk of developing breast cancer in a population-based prospective cohort study in Washington County, MD.

The objective of this study was to examine the association between nonsteroidal anti‐inflammatory drug (NSAID) use and the development of breast cancer, and to assess whether this association differed by estrogen receptor (ER) subtype. Data were analyzed from 15,651 women participating in CLUE II, a cohort study initiated in 1989 in Washington County, MD. Medication data were collected at baseline in 1989 and in 1996. Incident cases of invasive breast cancer occurring from baseline to March 27, 2006 were identified through linkage of cohort participants with the Washington County Cancer Registry and the Maryland State Cancer Registry. Cox proportional hazards modeling was used to calculate the risk ratios (RR) and 95% confidence intervals (95% CI) for breast cancer associated with medication use. Among women in the CLUE II cohort, 418 invasive breast cancer cases were identified during the follow‐up period. The results showed that self‐reported use of NSAIDs in both 1989 and in 1996 was associated with a 50% reduction in the risk of developing invasive breast cancer compared with no NSAID use in either 1989 or 1996 (RR = 0.50; 95% CI 0.28, 0.91). The protective association between NSAID use and the risk of developing breast cancer was consistent among ER‐positive and ER‐negative breast cancers, although only the RR for ER‐positive breast cancer was statistically significant. Overall, findings from this study indicate that NSAID use is associated with a decrease in breast cancer risk and that the reduction in risk is similar for ER‐positive and ER‐negative tumors.

Cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for noninfectious intermediate, posterior, and panuveitis.

OBJECTIVE To evaluate the 3-year incremental cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for the treatment of noninfectious intermediate, posterior, and panuveitis. DESIGN Randomized, controlled, clinical trial. PARTICIPANTS Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment Trial. METHODS Data on cost and health utility during 3 years after randomization were evaluated at 6-month intervals. Analyses were stratified by disease laterality at randomization (31 unilateral vs 224 bilateral) because of the large upfront cost of the implant. MAIN OUTCOME MEASURES The primary outcome was the incremental cost-effectiveness ratio (ICER) over 3 years: the ratio of the difference in cost (in United States dollars) to the difference in quality-adjusted life-years (QALYs). Costs of medications, surgeries, hospitalizations, and regular procedures (e.g., laboratory monitoring for systemic therapy) were included. We computed QALYs as a weighted average of EQ-5D scores over 3 years of follow-up. RESULTS The ICER at 3 years was

Hypotony in Patients with Uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

297,800/QALY for bilateral disease, driven by the high cost of implant therapy (difference implant - systemic [Δ]:

Sun-seeking behavior to increase cutaneous vitamin D synthesis: when prevention messages conflict.

16,900; P < 0.001) and the modest gains in QALYs (Δ = 0.057; P = 0.22). The probability of the ICER being cost-effective at thresholds of

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial

50,000/QALY and

Periocular Triamcinolone vs. Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) Trial.

100,000/QALY was 0.003 and 0.04, respectively. The ICER for unilateral disease was more favorable, namely,

Association Between α-Tocopherol, γ-Tocopherol, Selenium, and Subsequent Prostate Cancer

41,200/QALY at 3 years, because of a smaller difference in cost between the 2 therapies (Δ =