Hepatitis C management: the challenge of dropout associated with male sex and injection drug use.

BACKGROUND: Anecdotal reports of poor patient compliance with hepatitis C disease management exist yet little data are available on the true rates of dropout. AIMS: To examine all referrals made to an urban tertiary care liver centre for hepatitis C virus (HCV) management, track subsequent progress and identify dropout trends. METHODS: A cross-sectional retrospective review was conducted to examine the HCV referrals received on 2000 through 2007. The demographic, clinical and treatment data were derived from medical charts and the hospital information system. RESULTS: A total of 588 individuals were referred for HCV disease management. The repeated referrals yielded 742 cases for analysis. Of the 742 referrals received, 141 (19%) failed to attend their initial appointment, 180 dropped out from early outpatient management, 29 failed to attend liver biopsy and 81 defected from subsequent outpatient follow-up. In total, 451 (61%) dropouts occurred. In those treated, a sustained viral response rate of 74% was observed (18/30 genotype 1; 4/5 genotype 2; 40/49 genotype 3). Statistically significant associations between history of injection drug use and dropout immediately after the referral (P<0.001), dropout from early outpatient management (P<0.001) and dropout over entire span of disease management (P<0.001) were observed. Male sex was also associated with dropout from disease management (P<0.05). CONCLUSIONS: An exceptionally high rate of dropout exists within the HCV disease management framework, particularly in the early stages of service delivery. Dropout was associated with sex and positive history of injection drug use. The study findings have led to the development of innovative approaches helping to optimize the disease management in this population. These developments are discussed

Additive effects of estrogen and mechanical stress on nitric oxide and prostaglandin E2 production by bone cells from osteoporotic donors.

Contains fulltext : 48714.pdf (publisher's version ) (Closed access)Mechanical loading is thought to provoke a cellular response via loading-induced flow of interstitial fluid through the lacuno-canalicular network of osteocytes. This response supposedly leads to an adaptation of local bone mass and architecture. It has been suggested that loss of estrogen during menopause alters the sensitivity of bone tissue to mechanical load, thereby contributing to the rapid loss of bone. The present study aimed to determine whether estrogen modulates the mechanoresponsiveness of bone cells from osteoporotic women. Bone cell cultures from nine osteoporotic women (aged 62-90 years) were pre-cultured for 24 h with 10(-11) mol/l 17beta-estradiol (E2) or vehicle, and subjected to 1 h of pulsating fluid flow (PFF) or static culture. E2 alone enhanced prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production by 2.8-fold and 2.0-fold, respectively, and stimulated endothelial nitric oxide synthase protein expression by 2.5-fold. PFF, in the absence of E2, stimulated PGE(2) production by 3.1-fold and NO production by 3.9-fold. Combined treatment with E2 and PFF increased PGE(2) and NO production in an additive manner. When expressed as PFF-treatment-over-control ratio, the response to fluid shear stress was similar in the absence or presence of E2. These results suggest that E2 does not affect the early response to stress in bone cells. Rather, E2 and shear stress both promote the production of paracrine factors such as NO and PGE(2) in an additive manner

Deep Impact: observations from a worldwide Earth-based campaign

peer reviewedOn 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics