Effects of the tumor necrosis factor-α antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis: results of a randomized controlled trial.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown. METHODS AND RESULTS: This randomized, controlled trial included 30 patients with moderate to severe psoriasis and a history, or multiple risk factors, of coronary atherosclerosis. Patients were randomized (2:1) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment (topical therapies or phototherapy). Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15, by (18)F-fluorodeoxyglucose uptake on positron emission tomography. The change in target: BACKGROUND: =0.004) but not for the control group (-0.10 [95% CI, -0.32 to 0.12]; P=0.35). The difference between study arms for this primary end point did not reach statistical significance (-0.13 [95% CI, -0.01 to 0.14]; P=0.32). The change in target: BACKGROUND: =0.021) and in carotid arteries (-0.32±0.15, P=0.037) when analyzed separately (secondary end points). Changes in other positron emission tomography indices also improved significantly with adalimumab compared with controls in the ascending aorta and carotids. High-sensitivity C-reactive protein decreased by 51% at week 16 with adalimumab compared with 5% in controls (P=0·002). CONCLUSIONS: The study did not meet its primary end point because the change in target:background ratio in patients randomized to adalimumab was not different from controls. Although adalimumab may reduce vascular inflammation in patients with moderate to severe psoriasis, this effect is not large enough to be demonstrated in a study with a small sample size. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00940862.

Costs associated with resource utilization during the palliative phase of care: a Canadian perspective.

OBJECTIVE: This study aimed to evaluate prospectively the resource utilization and related costs during the palliative phase of care in five regions across Canada. SUBJECTS: A cohort of 248 patients registered in a palliative care program and their main informal caregivers were consecutively recruited. RESEARCH DESIGN: A prospective research design with repeated measures was adopted. Interviews were conducted at two-week intervals until the patient s passing or up to a maximum of 6 months. MEASURES: The survey questions prompted participants to provide information on the types and number of goods and services they used, and who paid for these goods and services. RESULTS: The largest cost component for study participants was inpatient hospital care stays, followed by home care and informal caregiving time. In regard to cost sharing, the public health care system (PHCS), the family, and not-for-profit organizations (NFPO) sustained respectively 71.3%, 26.6%, and 1.6% of the mean total cost per patient. CONCLUSION: Such results provide a comprehensive picture of costs related to palliative care in Canada, by specifying the cost sharing between the PHCS, the family, and NFPO.

Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients.

PURPOSE: Many cancer patients take antioxidant vitamin supplements with the hope of improving the outcome of conventional therapies and of reducing the adverse effects of these treatments. A randomized trial was conducted to determine whether supplementation with antioxidant vitamins could reduce the occurrence and severity of acute adverse effects of radiation therapy and improve quality of life without compromising treatment efficacy. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial among 540 head and neck cancer patients treated with radiation therapy. Patients were randomly assigned into two arms. The supplementation with alpha-tocopherol (400 IU/d) and beta-carotene (30 mg/d) or placebos was administered during radiation therapy and for 3 years thereafter. During the course of the trial, supplementation with beta-carotene was discontinued because of ethical concerns. RESULTS: Patients randomly assigned in the supplement arm tended to have less severe acute adverse effects during radiation therapy (odds ratio [OR], 0.72; 95% CI, 0.52 to 1.02). The reduction was statistically significant when the supplementation combined alpha-tocopherol and beta-carotene for adverse effects to the larynx (OR, 0.38; 95% CI, 0.21 to 0.71) and overall at any site (OR, 0.38; 95% CI, 0.20 to 0.74). Quality of life was not improved by the supplementation. The rate of local recurrence of the head and neck tumor tended to be higher in the supplement arm of the trial (hazard ratio, 1.37; 95% CI, 0.93 to 2.02). CONCLUSION: Supplementation with high doses of alpha-tocopherol and beta-carotene during radiation therapy could reduce the severity of treatment adverse effects. However, this trial suggests that use of high doses of antioxidants as adjuvant therapy might compromise radiation treatment efficacy.

A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients.

BACKGROUND: Although low dietary intakes of antioxidant vitamins and minerals have been associated with higher risks of cancer, results of trials testing antioxidant supplementation for cancer chemoprevention have been equivocal. We assessed whether supplementation with antioxidant vitamins could reduce the incidence of second primary cancers among patients with head and neck cancer. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized chemoprevention trial among 540 patients with stage I or II head and neck cancer treated by radiation therapy between October 1, 1994, and June 6, 2000. Supplementation with alpha-tocopherol (400 IU/day) and beta-carotene (30 mg/day) or placebo began on the first day of radiation therapy and continued for 3 years after the end of radiation therapy. In the course of the trial, beta-carotene supplementation was discontinued after 156 patients had enrolled because of ethical concerns. The remaining patients received alpha-tocopherol or placebo only. Survival was evaluated by Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: After a median follow-up of 52 months, second primary cancers and recurrences of the first tumor were diagnosed in 113 and 119 participants, respectively. The effect of supplementation on the incidence of second primary cancers varied over time. Compared with patients receiving placebo, patients receiving alpha-tocopherol supplements had a higher rate of second primary cancers during the supplementation period (HR = 2.88, 95% CI = 1.56 to 5.31) but a lower rate after supplementation was discontinued (HR = 0.41, 95% CI = 0.16 to 1.03). Similarly, the rate of having a recurrence or second primary cancer was higher during (HR = 1.86, 95% CI = 1.27 to 2.72) but lower after (HR = 0.71, 95% CI = 0.33 to 1.53) supplementation with alpha-tocopherol. The proportion of participants free of second primary cancer overall after 8 years of follow-up was similar in both arms. CONCLUSIONS: alpha-Tocopherol supplementation produced unexpected adverse effects on the occurrence of second primary cancers and on cancer-free survival.