Identifying characteristics of an effective fracture liaison service: systematic literature review.

Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.

Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer.

We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m(-2) 30-min intravenous infusion, and high-dose 5-FU 2600 mg m(-2) plus LV 300 mg m(-2) 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36-68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54-84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB-HDFL given (average: 7.9: range: 4-14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand-foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3-25.5 months), and the median overall survival was 25.0 months with a follow-up of 5.5 to 45+ months. This VNB-HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC.

Identification of oxidation products of (-)-epigallocatechin gallate and (-)-epigallocatechin with H(2)O(2).

(-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are two important antioxidants in tea. They also display some antitumor activities, and these activities are believed to be mainly due to their antioxidative effects. However, the specific mechanisms of antioxidant action of tea catechins remain unclear. In this study are isolated and identified two novel reaction products of EGCG and one product of EGC when they were reacted separately with H(2)O(2). These products are formed by the oxidation and decarboxylation of the A ring in the catechin molecule. This study provides unequivocal proof that the A ring of EGCG and EGC may also be an antioxidant site. This study also indicates an additional reaction pathway for the oxidation chemistry of tea catechins.

Real-time measurement of lysis of mural platelet deposits by fibrinolytic agents under arterial flow.

An in vitro whole blood reperfusion model was employed to quantify: (a) initial rates of lysis of mural platelet deposits from flowing blood onto fibrin-coated surfaces and (b) plasmin-mediated consumption of plasma plasminogen and fibrinogen, by recombinant tissue-type plasminogen activator (rt-PA) and two t-PA variants, KHRR 296-299 AAAA (K-tPA) and T103N, N117Q, KHRR 296-299 AAAA (TNK-tPA), at wall shear rates of either 500 or 1000 s(-1). K- and TNK-tPA are more fibrin-specific than rt-PA, and are also resistant to inactivation by plasminogen activator inhibitor-1 (PAI-1). At 500 s(-1), no agent showed significant lysis of mural platelet deposits on fibrin, even at concentrations as high as 10 microg/ml of blood. At 1000 s(-1), each agent demonstrated a dose-dependent lysis of mural platelet deposits, due to plasmin-mediated lysis of the fibrin substrate (fibrinolysis). The local concentration of thrombolytic agents close to the fibrin-coated surface is probably higher than the concentration of released PAI-1 from the adherent and activated platelets. Hence, the initial rates of lysis achieved by K- and TNK-tPA were not significantly different from that by rt-PA, when each agent was tested at either 1 or 10 microg/ml of blood. However, TNK-tPA, at 1 microg/ml, caused the most extensive lysis at the end of the 50 min reperfusion period (50% vs 29% and 17% by rt-PA and K-tPA, respectively). K- and TNK-tPA, at concentrations as high as 10 microg/ml of blood, caused plasminogen activation that was controlled by the natural plasmin inhibitors, and, thus, no proteolytic degradation of plasma fibrinogen (fibrinogenolysis). On the contrary, rt-PA at 1 microg/ml revealed slight fibrinogenolysis that became extensive at 10 microg/ml. This study demonstrates the potential use of an in vitro model, that mimics the in vivo hemodynamic environment, in evaluating the performance of thrombolytic agents. The data suggest that: (a) adequate flow must accompany fibrinolysis for successful embolization, and (b) the TNK variant may lyse annular thrombi after recanalization, at least as efficiently as rt-PA does, while causing lesser defect of systemic hemostasis.

A comparative study of the lipids of chylomicron membrane and fat core and of the lymph serum of dogs.

Thoracic lymph was collected from 13 dogs fed corn oil and butterfat. The chylomicrons were isolated by centrifugation. The lipid composition of the fat core and the membrane of the chylomicron was compared to that of the surrounding lymph serum. The fat cores contained 90-96% triglyceride, 0.7-1.9% free cholesterol, 0.2-0.5% steryl ester, 0.9-3.5% free fatty acid and 1.4-6.1% diglyceride, but no phospholipid. The lipids of the membranes contained 58-75% phospholipid, 20-35% triglyceride, 2-5% free cholesterol, 1-2% free fatty acid, and 2-3% diglyceride, but little or no steryl ester. The membrane phospholipids were made up of 70-90% lecithin, 5-20% phosphatidyl ethanolamine, and 1-3% each of lysolecithin and sphingomyelin. The lymph serum contained 24-47% of total lipid as phospholipid, of which 70-92% was lecithin; the phosphatidyl ethanolamine, lysolecithin and sphingomyelin also present contributed 1-10% each. The neutral lipids of the lymph serum contained 49-75% triglyceride, 2-15% free cholesterol, 6-23% esterified cholesterol, 10-33% free fatty acid and 1-6% diglyceride.Alterations in dietary fat, or plant sterol supplementation led to lesser changes in the lipids of the chylomicron membranes than in the lipids of any other lymph fraction. The least variation was seen in the phospholipids.