Background: Patients with multiple sclerosis (MS) may have a higher risk of cardiovascular diseases (CVD) than the general population, but data are limited. Methods: We conducted a population-based cohort study involving Danish citizens diagnosed with MS (n = 13,963) from 1977 to 2006 and an age- and sex-matched population cohort (n = 66,407) using data on MS, arterial CVD and comorbidity from the Danish National Registry of Patients. We calculated the risk of arterial CVD for all subjects and computed adjusted incidence rate ratios (IRRs). Results: During the first year of follow-up, the risk of myocardial infarction (MI) was 0.2% among patients with MS (adjusted IRR = 1.84; 95% confidence interval, CI: 1.28–2.65, compared with population cohort members), whereas the 1-year risk of overall stroke was 0.3% (adjusted IRR = 1.96; 95% CI: 1.42–2.71). IRRs were 1.92 (95% CI: 1.27–2.90) for heart failure and 0.77 (95% CI: 0.42–1.39) for atrial fibrillation/flutter. During the subsequent 2–30 years of follow-up, IRRs remained elevated for overall stroke (1.23; 95% CI: 1.10–1.38) and heart failure (1.53; 95% CI: 1.37–1.71) but decreased for acute MI (1.10; 95% CI: 0.97–1.24). Conclusion: In this Danish cohort, the risk of CVD among MS patients was low, but greater than that in the general population, particularly in the short term.

The risk of developing a cardiovascular outcome was not materially elevated for patients with early psoriasis overall. In subanalyses, however, there was a suggestion of an increased (but low absolute) MI risk for patients with psoriasis aged < 60 years, mainly with severe disease.

Psoriasis has been associated with lymphohematopoietic and solid cancers; however, reports have been inconsistent. Cancer incidence was compared between psoriasis and psoriasis-free patients, and the roles of psoriasis duration and treatment were explored in this observational study using the UK General Practice Research Database. Among 67,761 patients, 1,703 patients had incident cancer; of whom 54% had a history of psoriasis. Incidence rate ratios for lymphohematopoietic and pancreatic cancers were 1.81 (95% confidence interval (CI) 1.35-2.42) and 2.20 (95% CI 1.18-4.09), respectively. In a nested case-control analysis, adjusted odds ratios (ORs) for cancer overall were 1.50 (95% CI 1.30-1.74) for psoriasis of >or=4 years duration and 1.53 (95% CI 0.97-2.43) for patients receiving systemic treatment (marker of disease severity). Lymphohematopoietic malignancy risk was highest in patients with systemic treatment. The OR for patients without systemic treatment was 1.59 (95% CI 1.01-2.50) for psoriasis of <2 years and 2.12 (95% CI 1.45-3.10) for that of >or=2 years duration. Risks of bladder/kidney and colorectal cancers were increased with longer-duration psoriasis. Psoriasis patients may have an increased overall risk of incident cancer (mainly lymphohematopoietic and pancreatic). Longer-term psoriasis and more severe disease may increase the risk of some cancers. These observations need further confirmation, particularly because of the potential of findings by chance in observational studies with subgroup analyses.

OBJECTIVE—Although postchallenge hyperglycemia is a well-established feature of type 2 diabetes, its association with risk of mortality is uncertain. Therefore, the aim of this study was to assess the independent association of fasting and 2-h glucose levels with all-cause and cardiovascular disease (CVD) mortality. RESEARCH DESIGN AND METHODS—We analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study, a prospective cohort study of U.S. adults examined in the NHANES II, and focused on the 3,092 adults aged 30–74 years who underwent an oral glucose tolerance test at baseline (1976–1980). Deaths were identified from U.S. national mortality files from 1976 to 1992. To account for the complex survey design, we used SUDAAN statistical software for weighted analysis. RESULTS—Compared with their normoglycemic counterparts (fasting glucose [FG] &lt;7.0 and 2-h glucose &lt;7.8 mmol/l), adults with fasting and postchallenge hyperglycemia (FG ≥7.0 and 2-h glucose ≥11.1 mmol/l) had a twofold higher risk of death after 16 years of follow-up (age- and sex-adjusted relative hazard [RH] 2.1, 95% CI 1.4–3.2). However, adults with isolated postchallenge hyperglycemia (FG &lt;7.0 and 2-h glucose ≥11.1 mmol/l) were also at higher risk of death (1.6, 1.0–2.6). In proportional hazards analysis, FG (fully adjusted RH 1.10 per 1 SD; 95% CI 1.01, 1.22) and 2-h glucose (1.14, 1.00–1.29) showed nearly identical predictive value for mortality. Similar trends were observed for CVD mortality. CONCLUSIONS—These results suggest that postchallenge hyperglycemia is associated with increased risk of all-cause and CVD mortality independently of other CVD risk factors.

Background: Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. Objective: To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS. Methods: A total of 1,326 patients were randomized 1 : 1 : 1 to two short-course regimens of cladribine tablets (3.5 or 5.25 mg/kg cumulative dose over 96 weeks) or placebo. Safety assessments included monitoring for adverse events (AEs), routine physical and neurologic examinations and frequent laboratory parameter assessments. Results: Of the randomized patients, 88.6% completed treatment with cladribine tablets versus 86.3% with placebo. Lymphopenia was the most commonly reported AE in patients treated with cladribine tablets and was anticipated based on the mechanism of action. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators. Herpes zoster infections developed in 20 (2.3%) cladribinetreated patients; all cases were dermatomal. There were no herpes zoster infections in the placebo group. Nine (1.0%) patients experienced events related to uterine leiomyomas in the cladribine tablets groups versus one (0.2%) with placebo. Three isolated cases of malignancy were reported in cladribine-treated patients during the study; a fourth was reported during post-study surveillance. A pre-malignant cervical carcinoma in situ was also reported. The incidence of malignancies during the study did not exceed the expected rate in a population standardized for country, gender and age. Conclusion: The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.