Does nonsteroidal anti-inflammatory drug use modify the effect of a low-fat, high-fiber diet on recurrence of colorectal adenomas?

The Polyp Prevention Trial was designed to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), low-fat (20% energy) diet on recurrence of adenomatous polyps. Participants > or =35 years of age, with histologically confirmed colorectal adenoma(s) removed in the prior 6 months, were randomized to the intervention or control group. Demographic, dietary, and clinical information, including use of nonsteroidal anti-inflammatory drugs (NSAID), was collected at baseline and four annual visits. Adenoma recurrence was found in 754 of 1,905 participants and was not significantly different between groups. NSAID use was associated with a significant reduction in recurrence [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.63-0.95]. In this analysis, NSAIDs modified the association between the intervention and recurrence at baseline (P = 0.02) and throughout the trial (P = 0.008). Among participants who did not use NSAIDs, the intervention was in the protective direction but did not achieve statistical significance (OR, 0.87; 95% CI, 0.69-1.09). The intervention was protective among males who did not use NSAIDs at baseline (OR, 0.71; 95% CI, 0.54-0.94), but not among NSAIDs users (OR, 1.09; 95% CI, 0.74-1.62). For females, corresponding OR estimates were 1.28 (95% CI, 0.86-1.90) and 2.30 (95% CI, 1.24-4.27), respectively. The protective association observed for NSAID use was stronger among control (OR, 0.63; 95% CI, 0.47-0.84) than for intervention group participants (OR, 0.97; 95% CI, 0.74-1.28). These results should be interpreted cautiously given that they may have arisen by chance in the course of examining multiple associations and Polyp Prevention Trial study participants were not randomly assigned to both dietary intervention and NSAID use. Nevertheless, our results suggest that adopting a low-fat, high-fiber diet rich in fruits and vegetables may lower the risk of colorectal adenoma recurrence among individuals who do not regularly use NSAIDs.     

Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites

To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network’s variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination.     

Managing the Impact of Immunogenicity in an Era of Immunotherapy: From Bench to Bedside

Biotherapeutics have revolutionized our ability to treat life-threatening diseases. Despite clinical success, the use of biotherapeutics has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs). The multifactorial nature of immunogenicity has prevented a standardized approach for assessing this and each of the assessment methods developed so far does not exhibit high enough reliability to be used alone, due to limited predictiveness. This prompted the Roche Pharma Research and Early Development (pRED) Immunogenicity Working Group to establish an internal preclinical immunogenicity toolbox of in vitro/in vivo approaches and accompanying guidelines for a harmonized assessment and management of immunogenicity in early development. In this article, the complex factors influencing immunogenicity and their associated clinical ramifications are discussed to highlight the importance of an end-to-end approach conducted from lead optimization to clinical candidate selection. We then examine the impact of the resulting lead candidate categorization on the design and implementation of a multi-tiered ADA/immunogenicity assay strategy prior to phase I (entry into human) through early clinical development. Ultimately, the Immunogenicity Toolbox ensures that Roche pRED teams are equipped to address immunogenicity in a standardized manner, paving the way for lifesaving products with improved safety and efficacy.     

Birth Weight and Risk Factors for Cardiovascular Disease and Type 2 Diabetes in US Children and Adolescents: 10 Year Results from NHANES

Previous studies have shown that birth weight and other birth characteristics may be associated with risk for type 2 diabetes and cardiovascular disease (CVD) later in life; however, results using large US national survey data are limited. Our goal was to determine the aforementioned associations using nationally representative data. We studied children and adolescents 6–15 years using data from the National Health and Nutrition Examination Survey cycles 2001–2010. Survey and examination data included demographic and early childhood characteristics, current health status, physical activity information, anthropometric measurements, dietary data (total energy, saturated fat, sodium, and sugar intakes), biomarkers related to selected risk factors of CVD [systolic blood pressure (SBP), plasma C-reactive protein (CRP) and lipid profiles], and type 2 diabetes [fasting glucose, insulin, and homeostasis model assessment (HOMA)]. Birth weight (proxy-reported) was inversely associated with SBP among girls; SBP levels increased 1.4 mmHg for each 1,000 g decrease in birth weight (p = 0.003) after controlling for potential confounders. Birth weight was not associated with levels of CRP or lipid profiles across the three racial groups. In addition, birth weight was inversely related to levels of fasting insulin and HOMA among non-Hispanic Whites; for each 1,000 g decrease in birth weight, fasting insulin levels increased 9.1 % (p = 0.007) and HOMA scores increased 9.8 % (p = 0.007). Birth weight was inversely associated with the levels of SBP, fasting insulin, and HOMA. These results support a role for birth weight, independent of the strong effects of current body weight status, in increasing risk for CVD and type 2 diabetes.     

Effect of underlying disease and age on pneumococcal serotype distribution

The hospital records of 264 patients with 277 episodes of pneumococcal bacteremia occurring at New York Hospital-Cornell Medical Center over the period 1970 to 1980 were examined to determine whether serotype distribution varied with the underlying disease or age of the patient. The patients were placed into three groups according to their underlying disease. Group A consisted of all patients with significant impairment of their immune system. Group B included those patients with underlying conditions that were not associated with immune deficiency. Group C comprised those patients considered to be normal hosts. Overall, 84 percent of blood isolates were serotypes included in the vaccine. In Group A, only 73 percent of these isolates were vaccine types, compared with 85 percent in Group B and 97 percent in Group C (differences significant at p < 0.001). Vaccine serotypes were more common in children than adults (92 versus 81 percent), but in analysis that controlled for underlying disease, the elderly did not differ from younger adults in serotype distribution. The apparent predilection of nonvaccine serotypes to cause bacteremia in immunocompromised patients may be one factor limiting vaccine efficacy in this high-risk population.