An evaluation of a strategy to improve the support of orthopaedic nurses through a team preceptorship programme

Transition to a new work area is often stressful for both experienced and new graduate nurses. It is essential that the new graduate be supported through this transition period to enable them to adjust to the environment itself, refine knowledge, and develop skills specific to their chosen clinical stream. In past years, several strategies have been designed with varying levels of success.This study evaluates an Australian transition support model, where the fundamental difference is that the management of the program is facilitated by a nurse possessing refined leadership, communication, clinical and organisational skills.The model has been evaluated on its effectiveness in meeting specific outcomes. The findings revealed that this coordinated team approach provided increased support for the new graduate, reduced the stress and workloads on the preceptors, whilst promoting confidence in the new starters and preventing conflict between preceptors and preceptees. The Coordinator’s role was shown to be an effective and crucial component in the Coordinated Team Preceptorship Model (CTPM) and findings illustrated that a team preceptorship model is not sustainable without a Coordinator.     

Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18–65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate-the equivalent of 900 mg aspirin- combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2-severe or moderate-to grade 1 or 0-mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.     

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA- seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.     

Simultaneous targeting of HCV replication and viral binding with a single lentiviral vector containing multiple RNA interference expression cassettes.

Chronic hepatitis C virus (HCV) infection has a major medical impact and current treatments are often unsuccessful. RNA interference represents a promising new approach to tackling this problem. The current study details the design and testing of self-inactivating lentiviral vectors (LV) delivering RNA interference to prevent HCV replication and infection. Vectors were constructed with single, double, and triple cassettes expressing short hairpin RNAs (shRNAs) simultaneously targeting two regions of the HCV 1b genome and the host cell receptor, CD81. The shRNAs directed against HCV IRES or NS5b regions were shown to be effective in inhibiting HCV replication in vitro (82 and 98%, respectively). No evidence of shRNA-related interferon production was observed. Vectors containing CD81 shRNA reduced cell surface expression up to 83% and reduced cell binding of HCV surface protein E2 up to 82% while not affecting levels of unrelated surface protein (Ber-EP4) or HCV replication. Double or triple shRNA vectors were independently effective in simultaneously reducing HCV replication, CD81 expression, and E2 binding. This study demonstrates lentiviral delivery of multiple shRNA, inhibiting HCV in a specific, IFN-independent, manner. The targeting of multiple viral and host cell elements simultaneously by RNAi could increase the potency of antiviral gene therapies.     

Persistent fatigue in liver transplant recipients: a two-year follow-up study

Background:  Fatigue after liver transplantation (LTx) is a major problem that is associated with lower daily functioning and health-related quality of life (HRQoL). This study aimed to assess changes over time in fatigue following LTx. We also examined daily functioning and HRQoL changes over time and assessed the influence of fatigue and changes in fatigue on daily functioning and HRQoL. We determined whether sleep quality, anxiety, and depression were associated with fatigue.
Methods:  We identified 70 LTx recipients who had previously participated in a cross-sectional study and reassessed them after two yr to determine changes in level of fatigue, daily functioning, and HRQoL. We also assessed sleep quality, anxiety, and depression after two yr.
Results:  Level of fatigue and level of daily functioning were unchanged at follow-up. HRQoL domains remained stable or worsened. Fatigue was a significant predictor of daily functioning and all HRQoL domains (p < 0.01). Change in fatigue was a significant predictor of daily functioning and the HRQoL domains of "physical functioning,""vitality," and "pain" (p < 0.05). Sleep quality, anxiety, and depression were associated with fatigue severity (r = 0.35 to r = 0.60, p < 0.05).
Conclusion:  This longitudinal study shows that fatigue is a chronic problem after LTx and that daily functioning and HRQoL do not improve over time. This study supports the need for intervention programs to address fatigue after LTx.     

New therapeutic opportunities for hepatitis C based on small RNA

Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, anti-sense oligonucleotides (ASO), or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA (miR-122) in viral replication and discuss its potential for HCV molecular therapy.     

An evaluation of prognostic factors and tumor staging of resected carcinoma of the esophagus

OBJECTIVE: To evaluate prognostic factors and tumor staging in patients after esophagectomy for cancer. SUMMARY BACKGROUND DATA: Several reports have questioned the appropriateness of the sixth edition of the International Union Against Cancer (UICC) TNM guidelines for staging esophageal cancer. Additional pathologic characteristics, besides the 3 basic facets of anatomic spread (tumor, node, metastases), might also have prognostic value. METHODS: All patients who underwent resection of the esophagus for carcinoma between January 1995 and March 2003 were extracted from a prospective database. Univariate and multivariate analysis was performed to identify prognostic factors for survival. The goodness of fit and accuracy of 3 staging models (UICC-TNM, Korst classification, Rice classification) predicting survival were assessed. RESULTS: A total of 292 patients (mean age, 63 years) underwent esophagectomy. The 5-year overall survival rate was 29% (median, 21 months). pT-, pN-, pm-stage, and radicality of the resection were independent prognostic factors. Subdivision of T1 tumors into mucosal and submucosal showed significant differences in 5-year survival between both groups: 90% versus 47%, respectively (P = 0.01). Subdivision of pN-stage into 3 groups based on the number of positive nodes (0, 1-2, and >3 nodes positive) or the lymph node ratio (0, 0.01-0.2, and >0.2) also refined staging (P = 0.001 and P < 0.001, respectively). The current subclassification of M1 (M1a and M1b) is not warranted (P = 0.41). The staging model of Rice was more accurate than the UICC-TNM classification in predicting survival. CONCLUSION: This study supports the view that the current (6th edition) UICC-TNM staging model for esophageal cancer needs to be revised.     

Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial

OBJECTIVE: To determine whether extended transthoracic esophagectomy for adenocarcinoma of the mid/distal esophagus improves long-term survival. BACKGROUND: A randomized trial was performed to compare surgical techniques. Complete 5-year survival data are now available. METHODS: A total of 220 patients with adenocarcinoma of the distal esophagus (type I) or gastric cardia involving the distal esophagus (type II) were randomly assigned to limited transhiatal esophagectomy or to extended transthoracic esophagectomy with en bloc lymphadenectomy. Patients with peroperatively irresectable/incurable cancer were excluded from this analysis (n = 15). A total of 95 patients underwent transhiatal esophagectomy and 110 patients underwent transthoracic esophagectomy. RESULTS: After transhiatal and transthoracic resection, 5-year survival was 34% and 36%, respectively (P = 0.71, per protocol analysis). In a subgroup analysis, based on the location of the primary tumor according to the resection specimen, no overall survival benefit for either surgical approach was seen in 115 patients with a type II tumor (P = 0.81). In 90 patients with a type I tumor, a survival benefit of 14% was seen with the transthoracic approach (51% vs. 37%, P = 0.33). There was evidence that the treatment effect differed depending on the number of positive lymph nodes in the resection specimen (test for interaction P = 0.06). In patients (n = 55) without positive nodes locoregional disease-free survival after transhiatal esophagectomy was comparable to that after transthoracic esophagectomy (86% and 89%, respectively). The same was true for patients (n = 46) with more than 8 positive nodes (0% in both groups). Patients (n = 104) with 1 to 8 positive lymph nodes in the resection specimen showed a 5-year locoregional disease-free survival advantage if operated via the transthoracic route (23% vs. 64%, P = 0.02). CONCLUSION: There is no significant overall survival benefit for either approach. However, compared with limited transhiatal resection extended transthoracic esophagectomy for type I esophageal adenocarcinoma shows an ongoing trend towards better 5-year survival. Moreover, patients with a limited number of positive lymph nodes in the resection specimen seem to benefit from an extended transthoracic esophagectomy.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.