Advanced Glycation End Products Induce PeroxisomeProliferator-Activated Receptor c Down-Regulation-Related Inflammatory Signals in Human Chondrocytesvia Toll-Like Receptor-4 and Receptor for AdvancedGlycation End Products

Accumulation of advanced glycation end products (AGEs) in joints is important in the development of cartilage destruction and damage in age-related osteoarthritis (OA). The aim of this study was to investigate the roles of peroxisome proliferator-activated receptor γ (PPARγ), toll-like receptor 4 (TLR4), and receptor for AGEs (RAGE) in AGEs-induced inflammatory signalings in human OA chondrocytes. Human articular chondrocytes were isolated and cultured. The productions of metalloproteinase-13 and interleukin-6 were quantified using the specific ELISA kits. The expressions of related signaling proteins were determined by Western blotting. Our results showed that AGEs enhanced the productions of interleukin-6 and metalloproteinase-13 and the expressions of cyclooxygenase-2 and high-mobility group protein B1 and resulted in the reduction of collagen II expression in human OA chondrocytes. AGEs could also activate nuclear factor (NF)-κB activation. Stimulation of human OA chondrocytes with AGEs significantly induced the up-regulation of TLR4 and RAGE expressions and the down-regulation of PPARγ expression in a time- and concentration-dependent manner. Neutralizing antibodies of TLR4 and RAGE effectively reversed the AGEs-induced inflammatory signalings and PPARγ down-regulation. PPARγ agonist pioglitazone could also reverse the AGEs-increased inflammatory signalings. Specific inhibitors for p38 mitogen-activated protein kinases, c-Jun N-terminal kinase and NF-κB suppressed AGEs-induced PPARγ down-regulation and reduction of collagen II expression. Taken together, these findings suggest that AGEs induce PPARγ down-regulation-mediated inflammatory signalings and reduction of collagen II expression in human OA chondrocytes via TLR4 and RAGE, which may play a crucial role in the development of osteoarthritis pathogenesis induced by AGEs accumulation

Effectiveness and Limitations of Hand Hygiene Promotion on Decreasing Healthcare–Associated Infections

BACKGROUND: Limited data describe the sustained impact of hand hygiene programs (HHPs) implemented in teaching hospitals, where the burden of healthcare-associated infections (HAIs) is high. We use a quasi-experimental, before and after, study design with prospective hospital-wide surveillance of HAIs to assess the cost effectiveness of HHPs. METHODS AND FINDINGS: A 4-year hospital-wide HHP, with particular emphasis on using an alcohol-based hand rub, was implemented in April 2004 at a 2,200-bed teaching hospital in Taiwan. Compliance was measured by direct observation and the use of hand rub products. Poisson regression analyses were employed to evaluate the densities and trends of HAIs during the preintervention (January 1999 to March 2004) and intervention (April 2004 to December 2007) periods. The economic impact was estimated based on a case-control study in Taiwan. We observed 8,420 opportunities for hand hygiene during the study period. Compliance improved from 43.3% in April 2004 to 95.6% in 2007 (p<.001), and was closely correlated with increased consumption of the alcohol-based hand rub (r = 0.9399). The disease severity score (Charlson comorbidity index) increased (p = .002) during the intervention period. Nevertheless, we observed an 8.9% decrease in HAIs and a decline in the occurrence of bloodstream, methicillin-resistant Staphylococcus aureus, extensively drug-resistant Acinetobacter baumannii, and intensive care unit infections. The intervention had no discernable impact on HAI rates in the hematology/oncology wards. The net benefit of the HHP was US$5,289,364, and the benefit-cost ratio was 23.7 with a 3% discount rate. CONCLUSIONS: Implementation of a HHP reduces preventable HAIs and is cost effective

Establishing and evaluating FRAX® probability thresholds in Taiwan

Background/purpose: The Taiwanese FRAX® calculator was launched in 2010. However, cost-effectiveness thresholds for the prescription of antiosteoporosis medications were not established. This study aims to establish and evaluate FRAX®-based probability thresholds in Taiwan. Methods: Using previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement. Results: With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%). Conclusion: Three FRAX®-based models of alendronate use were established in Taiwan to help optimize treatment strategies. The government is encouraged to incorporate FRAX®-based approaches into the reimbursement policy for antiosteoporosis medicines

Effect of Bone Area on Spine Density in Chinese Men and Women in Taiwan

Areal bone mineral density (BMD), the quotient of bone mineral content ( BMC) divided by the projectional bone area( BA), measured with dual-energy X-ray absorptiometers (DXA), is the most common parameter used today to evaluate spinal osteoporosis. To evaluate whether gender, age, weight, and height can determine spinal BA, and to compare BA and analyze its effects on spinal density in the two genders, we measured BA and BMC, and calculated areal BMD, and the bone mineral apparent density (BMAD = BMD/ the square root of BA) of the L-2 to L-4 vertebrae of 604 female and 223 male Chinese volunteers from 20 to 70 years of age using a Norland XR-26 DXA. Standardized for height and weight, BA showed a relatively large variation and a significant increase with increasing age in both genders. On the other hand, BMC stayed unchanged in men > 50 years of age and decreased with aging in postmenopausal women. Younger men (< 51 years) had a much larger mean BA (by 15.5%) and larger mean BMC(only 10%) than that of age-matched women. As a result, younger men had a slightly and significantly lower areal BMD (by 7.1%) and a much lower BMAD (by 16%) (p < 0. 0001 for both) than premenopausal women of similar age. Men had higher areal BMD and BMAD values than age-matched women only after age 50 years. Although taller body height, heavier weight, and increasing age were associated with a larger BA, these factors could not explain most of theinterindividual variations in BA in both genders. Thus anteroposterior BA of lumbar vertebrae measured with DXA seems to affect the areal BMD and BMAD readings in the two genders. The larger BA caused a low BMAD and probably underestimated the true volumetric spine density in men

Bone Densitometry of Proximal Femur in Chinese Subjects: Gender Differences in Bone Mass and Bone Area

　Bone mineral content (BMC), bone areas (BA) and bone mineral density ( BMD) of the proximal femur in healthy Chinese men (N=202) and women (N=507 ) 21-70 years old were measured to investigate sexual differences in densitometry of the femur. Densitometric values at the femoral neck, trochanter and Ward's triangle were generally greater in men than women of the same age. While BMD decreased with aging with similar slope of 0.2-1% per year, the actual readings were 10-15% lower than that of Caucasian people of same age and gender for Chinese men and women. Furthermore, with increasing age, trochanteric BA increased in women but not in men, and femoral neck BA increased in men but not in women. These different trends of change in bone dimensions were independent of weight or height and may reflect structural difference at the proximal femur and imply differences in mechanical strength between both genders