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Background Cancer cells rely on angiogenesis for growth and dissemination, and small cell lung cancer (SCLC) is a highly angiogenic tumor. We evaluated thalidomide, an anti-angiogenic agent, when combined with chemotherapy and as maintenance treatment. Methods A total of 724 patients (51% with limited and 49% with extensive disease) were randomly assigned to receive placebo or thalidomide capsules, 100-200 mg daily for up to 2 years. All patients received etoposide and carboplatin every 3 weeks for up to six cycles. Endpoints were overall survival, progression-free survival, tumor response rate, toxicity, and quality of life (Q0L). Hazard ratios (HRs) for comparing thalidomide against placebo were estimated using Cox regression modeling. Statistical tests were two-sided. Results The median overall survival was 10.5 months (placebo) and 10.1 months (thalidomide) (HR for death = 1.09, 95% confidence interval [Cl] = 0.93 to 1.27; P= .28). Among patients with limited-stage disease, there was no evidence of a survival difference (HR for death = 0.91, 95% Cl = 0.73 to 1.15), but among patients with extensive disease, survival was worse in the thalidomide group (HR for death = 1.36, 95% Cl = 1.10 to 1.68). Progression-free survival rates were also similar in the two groups (HR = 1.07, 95% Cl = 0.92 to 1.24). Thalidomide was associated with an increased risk of having a thrombotic event, mainly pulmonary embolus and deep vein thrombosis (19% thalidomide vs 10% placebo; HR = 2.13, 95% Cl = 1.41 to 3.20; P< .001). There were no statistically significant differences between treatments in hematological and nonhematological toxic effects, except more patients in the thalidomide group had rash, constipation, or neuropathy. Overall, QoL scores were similar in the two treatment groups, but thalidomide was associated with less insomnia and diarrhea and more constipation and peripheral neuropathy. Conclusions In this large randomized trial, thalidomide in combination with chemotherapy did not improve survival of patients with SCLC but was associated with an increased risk of thrombotic events. [ABSTRACT FROM AUTHOR]

Background: The influence of ethnicity and socioeconomic status on dementia risk, and the extent to which this is mediated by known risk factors remain incompletely understood. We addressed this issue using health records data from the diverse and deprived population of East London (<50% White and >50% in the most deprived quintile of the UK). Method: We performed a nested case‐control study in over 1,000,000 East London inhabitants. We identified 4137 cases of all cause dementia, and matched on age and gender to controls with ratio 1:4. Logistic regression was used to calculated odds ratios (ORs) for exposures of ethnicity and UK Index of Multiple Deprivation (IMD), before and after inclusion in the model of established modifiable risk factors (type II diabetes, hypertension, smoking, body mass index, depression and hearing loss). In order to reflect the relative importance of known modifiable risk factors in this deprived multiracial population, we calculated weighted population attributable fractions (PAF) for each factor. Result: Risk of dementia was higher in the Black and South Asian groups relative to White (ORs (95%CI) Black 1.43 (1.31, 1.56), South Asian 1.17 (1.06, 1.29)). Risk of dementia was reduced in all IMD quintiles relative to the most deprived (ORs (95%CI) 2nd 0.71 (0.66, 0.77), 3rd 0.52 (0.44, 0.60), 4th 0.71 (0.53, 0.94), 5th 0.59 (0.38, 0.87)). The effects of ethnicity and deprivation persisted after adjusting for known risk factors. Weighted PAFs for modifiable risk factors were notably higher in this population for depression (9.2%) and diabetes (6.2%) than those estimated in the Lancet Commission meta‐analyses (4% and 1.2% respectively). Conclusion: Membership of non‐White ethnic groups and socioeconomic deprivation are important determinants of dementia risk, with effects larger than many of the more established risk factors. These effects cannot be completely accounted for by known modifiable risk factors and further work is required to establish the responsible mechanisms. Depression and diabetes are of greater relative importance, and should be prioritised as targets for dementia prevention in more diverse and deprived populations. [ABSTRACT FROM AUTHOR]