Cataract Surgery in Patients With Uveitis Treated With Systemic Therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study: Risk Factors and Outcomes.

PURPOSE: 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. DESIGN: Cohort study of participants from a randomized clinical trial. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results.

PURPOSE: To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab. DESIGN: Single-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes. METHODS: Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes. MAIN OUTCOME MEASURES: The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP). RESULTS: One hundred ninety-four participants (225 eligible eyes) were randomized to dexamethasone (n = 65 participants and 77 eyes), methotrexate (n = 65 participants and 79 eyes), or ranibizumab (n = 64 participants and 69 eyes). All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35%, 11%, and 22% for dexamethasone, methotrexate, and ranibizumab, respectively. Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P < 0.01) or ranibizumab (P = 0.018). Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001). Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME. CONCLUSIONS: At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results.

PURPOSE: To evaluate the long-term outcomes of uveitic macular edema (ME). DESIGN: Longitudinal follow-up of a cohort of participants in a randomized clinical trial. PARTICIPANTS: A total of 248 eyes of 177 participants with uveitic ME enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. METHODS: 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. MAIN OUTCOME MEASURES: Resolution and relapse of ME. Visual acuity. RESULTS: 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). CONCLUSIONS: 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.

Responsiveness of Vision-Specific and General Quality of Life Metrics to Ocular and Systemic Events in Patients with Uveitis.

PURPOSE: To evaluate the responsiveness of quality of life (QoL) metrics to ocular and systemic events in patients with noninfectious uveitis. DESIGN: Cohort study using randomized controlled trial data. PARTICIPANTS: Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. METHODS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues. METHODS: We compared the expression of Nrf2 and six of its target genes in alveolar macrophages, nasal, and bronchial epithelium and peripheral blood mononuclear cells (PBMCs) in current and former smokers with COPD. We compared cell-type specific of Nrf2 and its target genes as well as markers of oxidative and inflammatory stress. RESULTS: We enrolled 89 patients; expression all Nrf2 target gene measured were significantly higher in the bronchial epithelium from smokers compared to non-smokers. None were elevated in alveolar macrophages and only one was elevated in each of the other compartments. CONCLUSION: Bronchial epithelium is the most responsive tissue for transcriptional activation of Nrf2 target genes in active smokers compared to former-smokers with COPD that correlated with oxidative stress and inflammatory markers. There were no consistent trends in gene expression in other cell types tested. TRIAL REGISTRATION: Clinicaltrials.gov : NCT01335971.

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.

PURPOSE: To evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI). DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: Patients with uveitic ME. METHODS: Patients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes. MAIN OUTCOME MEASURES: The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, 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, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 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, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in 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 (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups. CONCLUSIONS: Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.

Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.

PURPOSE: To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial. DESIGN: Randomized clinical trial with extended follow-up. METHODS: Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically related. RESULTS: A total of 250 eyes (146 patients) had at least 1 implant placed. Median follow-up time after implant placement was 6 years (range 0.5-9.2 years). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval [CI]: 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. Thirty-nine implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%-48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, P < .001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or its treatment. CONCLUSION: There is an increasing risk of dissociation of Retisert implants during follow-up; the risk is greater with removal/exchange surgeries, but the risk of both spontaneous and surgically related events increases with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected.

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.

Hypotony in patients with uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial.

PURPOSE: To assess the prevalence of hypotony in patients with severe forms of uveitis. METHODS: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified. RESULTS: Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01). CONCLUSIONS: Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment.

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

OBJECTIVES: The public has long been encouraged to engage in sun-safe practices to minimize exposure to sunlight, the major cause of nonmelanoma skin cancer. More recently, some have advocated unprotected sun exposure to increase cutaneous synthesis of vitamin D as a way to promote health. We assessed the net result of these conflicting messages. METHODS: In a cross-sectional survey in 2007, questionnaires were mailed to participants of an ongoing cohort study in Washington County, Maryland. The study population consisted of 8,027 adults (55% response rate). RESULTS: Thirty percent of respondents were aware that unprotected sun exposure increased endogenous vitamin D levels. Among those who were aware of this benefit, 42% reported going out into the sun to increase vitamin D levels. Sun-seeking to increase vitamin D production did not significantly differ according to self-reported personal history of skin cancer, but was significantly higher among women, older age groups, those with less education, and vitamin D supplement users. CONCLUSION: A substantial proportion of respondents reported sun-seeking behavior expressly to increase endogenous vitamin D levels. The message about sun exposure and vitamin D is reaching the general public; however, this finding poses challenges to skin cancer prevention efforts.

The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acids, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.

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.

Smoking and risk of fatal prostate cancer in a prospective U.S. study.

OBJECTIVES: To examine the association of cigarette smoking with subsequent fatal prostate cancer. METHODS: Two private censuses were conducted in Washington County, Maryland, in which 26,810 adult men in 1963 and 28,292 in 1975 provided smoking information. Prostate cancer deaths through 2000 (1963 cohort, 240 deaths; and 1975 cohort, 184 deaths) were ascertained by review of the death certificates. Poisson regression analysis was used to estimate the rate ratio of prostate cancer death adjusted for age. RESULTS: Overall, cigarette smokers in the 1963 census cohort were not more likely to die of prostate cancer than those who had never smoked cigarettes, pipes, or cigars when considering the total follow-up period. However, current smokers of 20 or more cigarettes per day (rate ratio 2.38; 95% confidence interval 0.94 to 5.99) and former smokers (rate ratio 2.75; 95% confidence interval 1.13 to 6.74) had a greater risk of death from prostate cancer during the first 10 years of follow-up. Weaker positive associations of prostate cancer death with current and former cigarette smoking were seen during the first 10 years of follow-up in the 1975 census cohort. Current cigarette smoking at baseline was not associated with the prostate cancer incidence. CONCLUSIONS: The lack of an association between cigarette smoking and prostate cancer incidence, but the tendency of greater prostate cancer mortality in former and current cigarette smokers earlier in the follow-up period is consistent with other studies in which smoking was assessed once at baseline.

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.

A prospective cohort study of bladder cancer risk in relation to active cigarette smoking and household exposure to secondhand cigarette smoke.

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.

Active cigarette smoking, household passive smoke exposure, and the risk of developing pancreatic cancer.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

The influence of offering free transdermal nicotine patches on quit rates in a local health department's smoking cessation program.

Nicotine replacement therapy (NRT) has added to the menu of options available to assist cigarette smokers in quit attempts, but cost remains a barrier to access. A quasi-experimental study was carried out to compare quit rates and continuous abstinence from smoking before (n=601) and after (n=311) free nicotine patches were offered to smokers who participated in the Washington County (Maryland) Health Department's "Stop Smoking for Life" group behavioral cessation program. After free NRT was offered, the quit rates upon completion of the program increased from 38% to 65% [difference 27%; 95% confidence limits (CL) 21%, 34%]. The difference in continuos abstinence from smoking between the two groups was no longer statistically significant after 6 months of follow-up, reflecting the more rapid rate of reversion to smoking that occurred during the 18-month follow-up period among the free NRT group who had quit [adjusted rate ratio (RR) 1.35; 95% CL 1.03, 1.78]. Enrollment during the first 18 months after free NRT was 37% greater than the program's first 18 months (P=.08). In conclusion, adding free nicotine patches to a smoking cessation program was associated with increased program enrollment and significantly increased short-term-but not long-term-quit rates. The rapid reversion to smoking in the group who received free nicotine patches could potentially be obviated if participants extend their use of nicotine patches after the free 6-week supply is exhausted.