Developments of the incidence of osteoporosis in The Netherlands: a PHARMO study.

PURPOSE: To assess recent and to predict future time trends in the incidence of osteoporosis using routine databases in The Netherlands in the period 1993-2015 and to compare estimations based on hip fractures versus a proxy based on pharmacy and hospitalisation data. METHODS: The incidence of hip fractures was estimated over the period 1986-2002 using information from the Dutch Medical Registry, covering more than 99% of all Dutch hospitalisations. Additionally, a proxy (hospitalisation for osteoporosis or osteoporotic fractures, treatment with glucocorticosteroids or treatment with anti-osteoporosis drugs) was constructed in order to identify osteoporotic patients in the PHARMO database. Age and gender specific incidences of hip fractures and osteoporosis were calculated and extrapolated to The Netherlands. Results of both studies were extrapolated till 2015 using a power function. RESULTS: The incidence of hip fractures decreased slightly (270 per 100,000 in 1993, 260 per 100,000 in 2002). The incidence of osteoporosis using the constructed proxy decreased from 870 per 100,000 in 1993 to 700 per 100,000 in 2002. The incidence of hip fractures and osteoporosis remained fairly constant when modelled till 2015. Both studies showed the same time trends. CONCLUSION: Both the estimations based on the hospitalisations for hip fracture and on our proxy for osteoporosis showed that the increase in the incidence of osteoporosis as observed in the 1990s is levelling off. Due to ageing of the population the absolute number of hip fractures will however increase. Our definition of osteoporosis resulted in a higher estimation of the incidence of osteoporosis and may be used in future studies to follow developments in osteoporosis prevalence and incidence.

Inappropriate initial treatment of secondary intra-abdominal infections leads to increased risk of clinical failure and costs.

AIMS: The objective of this population-based, retrospective cohort study was to investigate the incidence and initial antibiotic treatment of secondary intra-abdominal infections (sIAI) and to assess whether inappropriate initial antibiotic therapy affects patient outcomes. METHODS: All patients hospitalized for sIAI (1995-1998) were identified in the PHARMO Record Linkage System, a patient-centric database including pharmacy dispensing records from community pharmacies linked to hospitalization records in the Netherlands. Complementary in-hospital antibiotic drug use was obtained from the computerized inpatient pharmacy files. The patient outcomes considered were switch to second-line antibiotic treatment, re-operation, and death. In addition, a composite variable clinical failure was constructed based on the above-mentioned outcomes. Furthermore, the effect of clinical failure on length of hospital stay and costs of hospitalization was assessed. Associations between appropriateness of initial antibiotic treatment and outcomes were estimated using multivariate logistic and linear regression models. RESULTS: In the source population of 228,000 persons, 175 cases were classified as sIAI (mean age 49.3 +/- 24.5, 50.9% male) resulting in an incidence of 2.3/10,000 person-years [95% confidence interval (CI) 2.0, 2.7]. Initial antibiotic treatment was appropriate for 84% of the cases. The risk of clinical failure was 17.1%. Inappropriate initial antibiotic treatment increased the risk of clinical failure 3.4-fold (95% CI 1.3, 9.1). Length of hospital stay and costs of hospitalization were significantly increased for patients with clinical failure. CONCLUSIONS: Inappropriate choice of initial antibiotic therapy in sIAI patients leads to more clinical failure resulting in a longer hospital stay and higher costs of hospitalization compared with appropriate initial antibiotic therapy.

Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers.

In this study, an extract of Pterocarpus marsupium Roxb. containing pterostilbene has been evaluated for its PGE2-inhibitory activity in LPS-stimulated PBMC. In addition, the COX-1/2 selective inhibitory activity of P. marsupium (PM) extract was investigated. Biological activity, as well as safety of PM extract was evaluated in healthy human volunteers. PM extract, pterostilbene and resveratrol inhibited PGE2 production from LPS-stimulated human peripheral blood mononuclear cells (PBMC) with IC50 values of 3.2 +/- 1.3 microg/mL, 1.0 +/- 0.6 microM and 3.2 +/- 1.4 microM, respectively. When pterostilbene content of PM extract is calculated, PGE2 production inhibition of PM extract is comparable to PGE2 production inhibition of purified pterostilbene. Furthermore, in a COX-1 whole blood assay (WBA) PM extract was not effective while in a COX-2 WBA, PM extract decreased PGE2 production indicating COX-2 specific inhibition. In healthy human volunteers, the oral use of 450 mg PM extract did not decrease PGE2 production ex vivo in a WBA. Pterostilbene levels in serum were increased, but were 5-fold lower than the observed IC50 for PGE2 inhibition in LPS-stimulated PBMC. No changes from base-line of the safety parameters were observed and no extract-related adverse events occurred during the study. In conclusion, this is the first study to describe the selective COX-2 inhibitory activity of a Pterocarpus marsupium extract. Moreover, the PGE2 inhibitory activity of PM extract was related to its pterostilbene content. In humans, 450 mg PM extract resulted in elevated pterostilbene levels in serum, which were below the active concentration observed in vitro. In addition, short-term supplementation of 450 mg PM extract is considered to be a safe dose based on the long history of use, the absence of abnormal blood cell counts and blood chemistry values and the absence of extract-related adverse events. This strongly argues for a dose-finding study of PM extract in humans to corroborate the in vitro observed inhibitory activity on PGE2 production in order to resolve the potential use of PM extract in inflammatory disorders and/or inflammatory pain.