To evaluate the responsiveness of quality of life (QoL) metrics to ocular and systemic events in patients with noninfectious uveitis.
Cohort study using randomized controlled trial data.
Patients ...with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.
Data on the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), EuroQol Questionnaire (EQ-5D), and Short Form Survey Instrument (SF-36) were evaluated semiannually during the first 3 years after randomization. The impact of ocular (e.g., changes in visual acuity VA, activity status, cataract surgery) and systemic events (e.g., infections requiring treatment) on the 6-month changes in QoL was assessed for each metric using generalized estimating equations.
The primary outcomes were the 6-month changes in vision-related (NEI-VFQ-25) and general health-related (EQ-5D index, SF-36 physical component summary PCS) QoL.
Changes in VA (adjusted change aΔ: 2.70 units per 5 letter change, P < 0.001), implant placement in at least 1 eye (aΔ: 5.50, P < 0.001), cataract surgery (aΔ: 3.01, P = 0.017), and quieting of all eyes active at the beginning of the interval (aΔ: 2.20, P < 0.010) were associated with improvements in the NEI-VFQ-25. Reductions in VA (aΔ: -0.014 per 5 letter decline, P = 0.003), infections requiring a prescription (aΔ: -0.024, P = 0.021), and incident uveitis activity in at least 1 eye (aΔ: -0.023, P = 0.031) were associated with declines in the EQ-5D index. Hospitalization (aΔ: -2.24, P = 0.019), infections requiring a prescription (aΔ: -1.00, P = 0.024), and vitreous hemorrhage in at least 1 eye (aΔ: -1.92, P = 0.021) were associated with declines in the SF-36 PCS. Declines in VA, initiation in IOP medication, and age were associated with changes in SF-36 PCS; however, the magnitude of the change was less than a single point.
The NEI-VFQ-25 was more sensitive to ocular changes than the general QoL metrics but less sensitive to acute systemic events. When performing QoL or cost-effectiveness analyses, it is important to consider the expected outcomes (e.g., ocular vs. systemic) to ensure that the selected measurement is sensitive enough to detect clinically important changes in disease status or effects of treatment.
To evaluate the long-term outcomes of uveitic macular edema (ME).
Longitudinal follow-up of a cohort of participants in a randomized clinical trial.
A total of 248 eyes of 177 participants with ...uveitic ME enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.
OCT measurements, taken at baseline and annually, were graded by reading center graders masked to clinical data. Macular edema was defined as a center macular thickness (CMT) ≥240 μm on time-domain OCT or time-domain OCT equivalent. Resolution of ME was defined as normalization of macular thickness on OCT. Relapse of ME was defined as increase in macular thickness to ≥240 μm in an eye that previously had resolution. Visual acuity was measured at each visit with logarithmic visual acuity charts.
Resolution and relapse of ME. Visual acuity.
Among 227 eyes with ME followed ≥1 year, the cumulative percent of eyes with ME resolving at any point during 7 years was 94% (95% confidence interval CI, 89-97). Epiretinal membranes on OCT were associated with a lower likelihood of ME resolution (hazard ratio HR, 0.74; 95% CI, 0.55-1.01; P = 0.05). Among 177 eyes with resolved ME, the cumulative percent with relapse within 7 years was 43% (95% CI, 32-51). Eyes in which ME resolved gained a mean of 6.24 letters (95% CI, 4.40-8.09; P < 0.001) compared with eyes that remained free from ME during the 1-year follow-up intervals, whereas eyes in which ME did not resolve experienced no gain in vision (mean change -1.30 letters; 95% CI, -2.70 to 0.09; P = 0.065), and eyes that developed ME during the year (incident or relapsed) experienced a mean loss of -8.65 letters (95% CI, -11.5 to -5.84, P < 0.001).
Given sufficient time and treatment, nearly all uveitic ME resolves, but episodes of relapse were common. Visual acuity results were better among eyes with resolved ME, suggesting that control of inflammation and resolution of ME might be visually relevant treatment targets.
To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression.
...Cohort study of participants from a randomized clinical trial.
A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery.
The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio HR 2.86, 95% CI 1.52, 5.42; P = .001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P = .005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P = .004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P = .07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data.
Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.
To evaluate the 3-year incremental cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for the treatment of noninfectious intermediate, posterior, and panuveitis.
Randomized, ...controlled, clinical trial.
Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment Trial.
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.
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.
The ICER at 3 years was $297,800/QALY for bilateral disease, driven by the high cost of implant therapy (difference implant - systemic Δ: $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 $50,000/QALY and $100,000/QALY was 0.003 and 0.04, respectively. The ICER for unilateral disease was more favorable, namely, $41,200/QALY at 3 years, because of a smaller difference in cost between the 2 therapies (Δ = $5300; P = 0.44) and a larger benefit in QALYs with the implant (Δ = 0.130; P = 0.12). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.53 and 0.74, respectively.
Fluocinolone acetonide implant therapy was reasonably cost-effective compared with systemic therapy for individuals with unilateral intermediate, posterior, or panuveitis but not for those with bilateral disease. These results do not apply to the use of implant therapy when systemic therapy has failed or is contraindicated. Should the duration of implant effect prove to be substantially >3 years or should large changes in therapy pricing occur, the cost-effectiveness of implant versus systemic therapy would need to be reevaluated.
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.
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.
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.
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.
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.
The objective of this study was to examine the association between active cigarette smoking, household passive smoke exposure, and pancreatic cancer risk using a prospective cohort design.
Two ...cohorts were established in Washington County, Maryland in 1963 (n = 45,749) and 1975 (n = 48,172). The Washington County Cancer Registry was used to ascertain the occurrence of pancreatic cancer in the 1963 cohort from 1963–1978 and in the 1975 cohort from 1975–1994. Poisson regression was used to analyze the associations between active smoking and household passive smoke exposure and pancreatic cancer risk.
Current active smoking was associated with a two-fold increased risk of pancreatic cancer in both cohorts. Among never-smokers in each cohort, exposure to household passive smoke was not associated with an increased risk of pancreatic cancer, although the confidence limits were wide due to a small number of cases.
This study further documents the approximate doubling of pancreatic cancer risk in current active smokers. Our results also indicate that household passive smoke exposure is not associated with pancreatic cancer risk, although our risk estimates lacked precision.
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.
In a study, three cycles of freezing and thawing had almost no effect on concentrations of cholesterol, micro-nutrients, and most of the hormones investigated (data not shown). For estrone, ...estradiol, testosterone, and SHBG, there was appreciable variation within the first three cycles, but the degree of variability was considerably less than the respective CVs. Although there were greater losses after 6 or 10 cycles for a few other analytes, these were too small to have a meaningful effect on results.
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