Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

/pdf/sipuleucel-t-immunotherapy-for-castration-resistant-prostate-31dll2jbjc.pdf

Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

2016 Alzheimer's disease facts and figures

Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases With Time, Based on Systematic Review

Objective The aim of this study was to quantify the global burden of osteoporotic fracture worldwide. Methods The incidence of hip fractures was identified by systematic review and the incidence of osteoporotic fractures was imputed from the incidence of hip fractures in different regions of the world. Excess mortality and disability weights used age- and sex-specific data from Sweden to calculate the Disability Adjusted Life Years (DALYs) lost due to osteoporotic fracture. Results In the year 2000 there were an estimated 9.0 million osteoporotic fractures of which 1.6 million were at the hip, 1.7 million at the forearm and 1.4 million were clinical vertebral fractures. The greatest number of osteoporotic fractures occurred in Europe (34.8%). The total DALYs lost was 5.8 million of which 51% were accounted for by fractures that occurred in Europe and the Americas. World-wide, osteoporotic fractures accounted for 0.83% of the global burden of non-communicable disease and was 1.75% of the global burden in Europe. In Europe, osteoporotic fractures accounted for more DALYs lost than common cancers with the exception of lung cancer. For chronic musculo-skeletal disorders the DALYs lost in Europe due to osteoporosis (2.0 million) were less than for osteoarthrosis (3.1 million) but greater than for rheumatoid arthritis (1.0 million). Conclusion We conclude that osteoporotic fractures are a significant cause of morbidity and mortality, particularly in the developed countries.

An estimate of the worldwide prevalence and disability associated with osteoporotic fractures.

This study predicts the burden of incident osteoporosis-related fractures and costs in the United States, by sex, age group, race/ethnicity, and fracture type, from 2005 to 2025. Total fractures were >2 million, costing nearly $17 billion in 2005. Men account for >25% of the burden. Rapid growth in the disease burden is projected among nonwhite populations.

Introduction: The aging of the U.S. population will likely lead to greater prevalence of osteoporosis. Policy makers require precise projections of the disease burden by demographic subgroups and skeletal sites to effectively target osteoporosis intervention and treatment programs.

Materials and Methods: A state transition Markov decision model was used to estimate total incident fractures and costs by age, sex, race/ethnicity, and skeletal site for the U.S. population ≥50 years of age for 2005–2025.

Results: More than 2 million incident fractures at a cost of $17 billion are predicted for 2005. Total costs including prevalent fractures are more than $19 billion. Men account for 29% of fractures and 25% of costs. Total incident fractures by skeletal site were vertebral (27%), wrist (19%), hip (14%), pelvic (7%), and other (33%). Total costs by fracture type were vertebral (6%), hip (72%), wrist (3%), pelvic (5%), and other (14%). By 2025, annual fractures and costs are projected to rise by almost 50%. The most rapid growth is estimated for people 65–74 years of age, with an increase >87%. An increase of nearly 175% is projected for Hispanic and other subpopulations.

Conclusions: Osteoporosis prevention, treatment, and education efforts should address all skeletal sites, not just hip and vertebral, and appropriate attention is warranted for men and diverse race/ethnicity subgroups.

Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025.

Assessment of fracture risk and its application to screening for postmenopausal osteoporos

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis

https://www.gastrojournal.org/article/S0016-5085(97)70025-8/pdf

Prevalence and clinical spectrum of gastroesophageal reflux : a population-based study in Olmsted County, Minnesota

Low body mass index (BMI) is a well-documented risk factor for future fracture. The aim of this study was to quantify this effect and to explore the association of BMI with fracture risk in relation to age, gender and bone mineral density (BMD) from an international perspective using worldwide data. We studied individual participant data from almost 60,000 men and women from 12 prospective population-based cohorts comprising Rotterdam, EVOS/EPOS, CaMos, Rochester, Sheffield, Dubbo, EPIDOS, OFELY, Kuopio, Hiroshima, and two cohorts from Gothenburg, with a total follow-up of over 250,000 person years. The effects of BMI, BMD, age and gender on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson regression model in each cohort separately. The results of the different studies were then merged. Without information on BMD, the age-adjusted risk for any type of fracture increased significantly with lower BMI. Overall, the risk ratio (RR) per unit higher BMI was 0.98 (95% confidence interval [CI], 0.97–0.99) for any fracture, 0.97 (95% CI, 0.96–0.98) for osteoporotic fracture and 0.93 (95% CI, 0.91–0.94) for hip fracture (all p 0.30). After adjusting for BMD, these RR became 1 for any fracture or osteoporotic fracture and 0.98 for hip fracture (significant in women). The gradient of fracture risk without adjustment for BMD was not linearly distributed across values for BMI. Instead, the contribution to fracture risk was much more marked at low values of BMI than at values above the median. This nonlinear relation of risk with BMI was most evident for hip fracture risk. When compared with a BMI of 25 kg/m2, a BMI of 20 kg/m2 was associated with a nearly twofold increase in risk ratio (RR=1.95; 95% CI, 1.71–2.22) for hip fracture. In contrast, a BMI of 30 kg/m2, when compared with a BMI of 25 kg/m2, was associated with only a 17% reduction in hip fracture risk (RR=0.83; 95% CI, 0.69–0.99). We conclude that low BMI confers a risk of substantial importance for all fractures that is largely independent of age and sex, but dependent on BMD. The significance of BMI as a risk factor varies according to the level of BMI. Its validation on an international basis permits the use of this risk factor in case-finding strategies.

Lee J. Melton

Papers

Assessment of fracture risk and its application to screening for postmenopausal osteoporos

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis

Prevalence and clinical spectrum of gastroesophageal reflux : a population-based study in Olmsted County, Minnesota

Body mass index as a predictor of fracture risk: A meta-analysis

The worldwide problem of osteoporosis: insights afforded by epidemiology.