A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment

<p>Abstract</p> <p>Background</p> <p>About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX.</p> <p>Methods/design</p> <p>The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life.</p> <p>Conclusion</p> <p>The HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier NCT00394992</p

Rapid increases in obesity in Jamaica, compared to Nigeria and the United States

<p>Abstract</p> <p>Background</p> <p>Weight gain in adulthood is now common in many populations, ranging from modest gains in developing countries to a substantial percentage of body weight in some Western societies. To examine the rate of change across the spectrum of low to high-income countries we compared rates of weight change in samples drawn from three countries, Nigeria, Jamaica and the United States.</p> <p>Methods</p> <p>Population samples from Nigeria (n = 1,242), Jamaica (n = 1,409), and the US (n = 809) were selected during the period 1995–1999 in adults over the age of 19; participation rates in the original survey were 96%, 60%, and 60%, respectively. Weight in (kg) was measured on 3 different occasions, ending in 2005. Multi-level regression models were used to estimate weight change over time and pattern-mixture models were applied to assess the potential effect of missing data on estimates of the model parameters.</p> <p>Results</p> <p>The unadjusted weight gain rate (standard error) was 0.34(0.06), 1.26(0.12), 0.34(0.19) kg/year among men and 0.43(0.06), 1.28(0.10), 0.40(0.15) kg/year among women in Nigeria, Jamaica, US, respectively. Regression-adjusted weight change rates were significantly different across country, sex, and baseline BMI. Adjusted weight gain in Nigeria, Jamaica and US was 0.31(0.05), 1.37(.04), and 0.52(0.05) kg/year respectively. Women in Nigeria and the US had higher weight gains than men, with the converse observed among Jamaicans. The obese experienced weight loss across all three samples, whereas the normal weight (BMI < 25) had significant weight gains. Missing data patterns had an effect on the rates of weight change.</p> <p>Conclusion</p> <p>Weight change in sample cohorts from a middle-income country was greater than in cohorts from either of the low- or high-income countries. The steep trajectory of weight gain in Jamaica, relative to Nigeria and the US, is most likely attributable to the accelerating effects of the cultural and behavioral shifts which have come to bear on transitional societies.</p

Age and Sex Ratios in a High-Density Wild Red-Legged Partridge Population

The dynamics of a wild red-legged partridge population were examined over a 14-year period in Spain to identify patterns in age and sex ratios in relation to weather parameters, and to assess the importance of these parameters in population dynamics and management. The results gave age ratios of 1.07 (but 2.13 in July counts), juvenile sex ratios of 1.01 and adult sex ratios of 1.47. Overall, 12% more females were hatched and female juvenile mortality was 7.3% higher than in males. Sex differential mortality explains the 19.2% deficit in adult females, which are more heavily predated than males during the breeding period. Accordingly, age ratios are dependent on sex ratios and both are density dependent. Over time, ratios and density changes appear to be influenced by weather and management. When the habitat is well conserved, partridge population dynamics can be explained by a causal chain: weather operates on net primary production, thereby affecting partridge reproduction and predation and, as a result, age and sex ratios in the October population. A reduction in the impact of predation (i.e. the effects of ground predators on eggs, chicks and breeding females) is the key factor to improve the conservation of partridge populations and associated biological processes