bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal therapy in hepatitis C virus genotypes 2 and 3 patients
Authors: Petta Salvatore , Craxì Antonio
Published: January 2011

Current guidelines recommend that patients with genotype 2 (G2) and 3 (G3) chronic hepatitis C be treated with pegylated interferon (PEG‐IFN) plus low doses of ribavirin (800 mg/day) for 24 weeks, resulting in a sustained virological response (SVR) rate of approximately 80%. Considering these high response rates, several recent randomized trials have assessed whether shorter treatment (12–16 weeks) could be cost‐effective in these patients. The results of these studies vary but suggest better responsiveness in G2 patients, and overall, do not strongly support reducing treatment to <24 weeks in all patients. On the other hand, the presence of a rapid virological response (RVR) (defined as an undetectable hepatitis C virus‐RNA at 4 weeks of treatment) was always reported to be the best positive predictor of achieving SVR in both G2 and G3 patients. These results suggest that in a subgroup of subjects with RVR (G2>G3, viral load <400 000 IU, low fibrosis, no metabolic cofactors), shorter treatment is as effective as standard regimens, and that it can be proposed mainly if problems of poor tolerance or adherence are foreseen. It is possible that the SVR rate in non‐RVR patients and non‐responder patients could also be improved by prolonging therapy, but this must be specifically investigated in other studies along with the role of IL28B polymorphisms.
Future hepatitis C virus treatment: interferon‐sparing combinations
Authors: Gane Edward
Published: January 2011

An estimated million people have chronic hepatitis C virus (HCV) infection. With current treatment success rates, by 2030, more than 40% will be cirrhotic and the number of cases with end‐stage liver disease is projected to treble. Current standard‐of‐care is the combination of pegylated interferon plus ribavirin for 24–48 weeks. Unfortunately this is associated with poor efficacy (45% in HCV GT1; 75% in GT2 and 65% in GT 3) and tolerability. Many patients are either unsuitable for or decline current treatment infection because of the significant side‐effects associated with this treatment, including those with decompensated cirrhosis or sever psychiatric illness. It is hoped that the development of direct acting antiviral agents (DAAs) will address this huge unmet medical need. The addition of a protease inhibitor to pegylated interferon plus ribavirin is associated with increase in efficacy and shortened duration of therapy in patients with HCV GT1 and is likely to become the new standard‐of‐care. However, triple therapy will not be suitable for patients with non‐1 HCV infection, or contraindications to interferon. It is hoped that the combination of multiple DAAs which target different steps of HCV replication should provide interferon‐free treatment regimen. Current and planned studies will determine which combination (protease, nonnucleoside polymerase, nucleoside polymerase, NS5A, cyclophyllin B inhibitors), how many DAAs and duration of therapy will be required to optimise cure. It will also be important to minimise the emergence of multi‐resistance, which would jeopardise future retreatment options
Chronic hepatitis B: peginterferon or nucleos(t)ide analogues?
Authors: Sonneveld Milan J. , Janssen Harry L. A.
Published: January 2011

Pegylated interferon‐α (PEG‐IFN) is still an important treatment option for both HBeAg‐positive and HBeAg‐negative chronic hepatitis B (CHB) patients even with the availability of potent nucleos(t)ide analogues (NUCs) with a low risk of resistance. The major advantages of PEG‐IFN‐based treatment include the limited duration of treatment and the good probability of achieving a sustained off‐treatment response. Responders to PEG‐IFN have an increased probability of HBsAg loss and survival. However, the limited number of patients who achieve a response and the high costs and side‐effects associated with PEG‐IFN limit its clinical use. The potent NUCs entecavir and tenofovir are therefore often used as a first‐line treatment option. Unfortunately, the off‐treatment durability of response to NUCs is generally low, requiring long‐term continuous therapy. Recent progress making it possible to select patients with a high probability of achieving a response to PEG‐IFN, and to adapt therapy early on in probable non‐responders, should help further optimize the utilization of PEG‐IFN in CHB.
Hepatitis C virus genotype 4 therapy: progress and challenges
Authors: Kamal Sanaa M.
Published: January 2011

The hepatitis C virus genotype 4 (HCV‐4) is prevalent in Egypt, the Middle East and Africa. Recently, the epidemiology of HCV‐4 has changed and this genotype has begun to cross borders and spread to several regions in Europe through immigration and injection drug use. HCV‐4 has been considered a difficult‐to‐treat genotype based on the low sustained virological response (SVR) rates obtained with conventional interferon (IFN)‐based regimens. Pegylated interferons (PEG‐IFN) plus ribavirin therapy for chronic HCV‐4 has been associated with increased SVR rates of more than 60%. Shorter treatment of chronic HCV‐4 patients with rapid and early virological responses has been associated with high SVR rates, better compliance, fewer adverse events and lower costs. Despite this progress, the treatment of HCV‐4 non‐responders, injection drug users, patients coinfected with human immunodeficiency virus, thalassaemic patients, patients on haemodialysis and patients with HCV‐4 recurrence after liver transplantation still represents a significant therapeutic challenge. Treatment of HCV‐4 has markedly improved, with higher sustained response rates and the possibility of shorter regimens. Despite the recent progress in the treatment of HCV‐4, more research is required to optimize current therapy and include genotype 4 patients in clinical trials on emerging therapies such as specifically targeted antiviral therapy for HCV with protease and/or polymerase inhibitors.
Treatment of HBeAg‐negative chronic hepatitis B with pegylated interferon
Authors: Lampertico Pietro , Viganò Mauro , Colombo Massimo
Published: January 2011

Serum HBeAg‐negative chronic hepatitis B, which is usually a late stage of chronic hepatitis B virus infection, is difficult to treat, because it is characterized by fluctuating alanine transaminase values resulting in hepatitis flares, accelerated progression to cirrhosis and liver cancer. Antiviral treatment, either long‐term nucleot(s)ide therapy or 1‐year administration of pegylated interferon (PEG‐IFN), is therefore necessary to limit the course of the disease. A sustained virological response to PEG‐IFN is achieved in approximately 1/4 of the patients, with significant rates of HBsAg seroclearance. While waiting for the results of several studies whose goal is to improve the long‐term efficacy of PEG‐IFN, the treatment strategy can be optimized by a careful selection of patients, discontinuation of PEG‐IFN as early as possible in primary non‐responders and extended therapy (up to 96 weeks) in responders.
Treatment of HBeAg‐positive chronic hepatitis B with nucleos(t)ide analogues
Authors: Leung Nancy
Published: January 2011

HBeAg seropositivity is a marker for active viral replication. In the natural history of chronic hepatitis B infection, HBeAg marks the first two of the four phases, namely the immune tolerant phase and the immune clearance phase, and is associated with highly replicative activity of the hepatitis B virus (HBV). Most HBV consensus reports and guidelines recommend antiviral therapy if the immune clearance phase is prolonged and if there is evidence of significant necroinflammation and fibrosis. Two main types of antiviral agents have been approved for treating patients in the immune clearance phase: interferon and nucleos(t)ide analogues (NUCs). The endpoints of therapy are viral suppression with HBeAg seroconversion, undetectable serum HBV DNA, normalization of serum alanine transaminase and improvement in the histological necroinflammatory and fibrosis scores. The ultimate goal of therapy is to obtain clinical benefit for the patient by reducing complications including hepatocellular carcinoma (HCC). The choice between interferon‐based immune modulators or NUCs that target the HBV DNA polymerase must be carefully weighed on an individual basis. Therapy with NUCs is often preferred by doctors and patients because it is easy to administer, with predictable efficacy and minimal side‐effects. In specific patient subgroups such as those with decompensated disease, poor predictors of response or lack of response to interferon‐based therapy and/or significant comorbidities that cannot tolerate interferon‐induced side effects, NUCs therapy is the obvious choice. Entecavir and tenofovir are the treatments of choice because their efficacy and safety profile are better than lamivudine, adefovir and telbivudine. More importantly, there is a minimal risk of drug resistance during long‐term therapy with these agents.
The role of genetic markers in hepatitis C virus therapy: a major step for individualized care
Authors: McHutchison John G.
Published: January 2011

It has been understood for some time that the treatment outcome of hepatitis C virus (HCV) infection is influenced by host genetic factors. Three independent genome‐wide association studies have recently identified that a genetic variation in theIL28Bgene [interferon‐λ3 (IFN‐λ3)] determines the outcome of IFN‐α‐based therapy in patients with genotype 1 chronic hepatitis C infection. This genetic polymorphism is also strongly associated with a higher likelihood of spontaneous clearance following acute hepatitis C infection. These results confirm the importance of specific host genetic markers in predicting outcome and treatment response. They also provide the framework and potential for a clinically relevant and meaningful pharmacogenomic approach to personalizing anti‐HCV treatment.
Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B
Authors: Moucari Rami , Marcellin Patrick
Published: January 2011

HBsAg is a very important clinical test that might not only indicate active hepatitis B virus (HBV) infection but might also be used to predict clinical and treatment outcome. Clearance of HBsAg in patients with chronic HBV infection is associated with a much better clinical outcome, although surveillance for early detection of hepatocellular carcinoma (HCC) should continue. HBV DNA quantification is currently used for selecting candidates for therapy, monitoring response to therapy and detecting the emergence of drug resistance. Assays for HBsAg quantification are less expensive than HBV DNA and fully automated with a high throughput capacity. HBsAg titering may be a useful tool to manage patients with chronic HBV, to more clearly define which patients may, and more importantly, may not, benefit from treatment. Baseline and on‐treatment HBsAg quantification may help to refine future treatment algorithms for both immune‐modulator therapy and nucleos(t)ide analogues. Both HBV markers provide complementary information on the status of HBV infection. However, the relevance of serum HBsAg levels and its use as a reliable replacement for both covalently closed circular DNA and HBV DNA remain unclear.
The role of triple therapy with protease inhibitors in hepatitis C virus genotype 1 naïve patients
Authors: Nelson David R.
Published: January 2011

With the introduction of direct‐acting oral antiviral agents we are on the verge of a new era that will transform the treatment landscape. This review discusses recent developments in drug discovery for hepatitis C protease inhibitors. First generation protease inhibitors will offer higher sustained viral response rates in naïve populations when combined with standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new challenges in viral resistance and increased adverse events.
Novel molecular therapies in hepatocellular carcinoma
Authors: Faivre Sandrine , Bouattour Mohamed , Raymond Eric
Published: January 2011

The approval of sorafenib as the standard of care (SOC) for advanced hepatocellular carcinoma (HCC) fostered interest to further evaluate several other targeted therapies and extend the positioning of sorafenib alone and in combination with other drugs and local therapies at earlier stages and in an adjuvant setting. This review highlights current research using targeted therapies in HCC. Information for this review was compiled by searching PubMed and MEDLINE databases for articles published until September 2010. Several small molecules and humanized antibodies with anti‐angiogenic and antiproliferative properties are currently being investigated in preclinical and/or clinical trials. Results are awaited from these clinical trials and offer promise for extending the current treatment options in HCC. Currently published data suggest that substantial progress may be achieved in the treatment of patients with HCC in the next 10 years.
The difficulties of managing severe hepatitis B virus reactivation
Authors: Roche Bruno , Samuel Didier
Published: January 2011

Reactivation of hepatitis B is characterized by a sudden increase in hepatitis B virus (HBV) replication in a patient with prior evidence of resolved or inactive HBV infection. Although HBV reactivation can occur spontaneously, it usually occurs after chemotherapy, immunosuppression (organ transplantation) or an alteration in immune function (therapy for autoimmune disease, human immunodeficiency virus infection). The clinical presentation cases can vary, ranging from a subclinical, asymptomatic course to severe acute hepatitis and even death. Although reactivation of HBV is mainly found in HBsAg‐positive patients, it can be observed in serologically recovered anti‐hepatitis B core antibody (HBc)‐positive, HBsAg‐negative patients. Serum HBV DNA typically increases during immune suppression, followed by a disease flare and HBV DNA clearance following immune restoration after immune suppression is stopped. In organ transplant recipients, without immune reconstitution, high HBV DNA levels can lead to fibrosing cholestatic hepatitis related to the direct cytopathic effect of HBV. Several randomized, controlled trials and meta‐analyses have shown that reactivation can be prevented by lamivudine prophylaxis. Screening for HBsAg and anti‐HBc should be performed before beginning immunosuppressive treatment and routine prophylaxis is recommended in HBsAg‐positive patients. The optimal duration of prophylaxis remains to be determined. In anti‐HBc‐positive patients with or without anti‐hepatitis B surface antigen, alanine transaminase and HBV DNA levels should be closely monitored and antiviral therapy should be started when HBV reactivation is confirmed. The use of new more potent nucleos(t)ides analogues with lower resistance rates would seem to be logical; however, experience with these drugs in the prophylaxis and treatment of severe HBV reactivation is limited.
Role of insulin resistance and hepatic steatosis in the progression of fibrosis and response to treatment in hepatitis C
Authors: Sanyal Arun J.
Published: January 2011

Hepatitis C is a common cause of chronic viral infection of the liver. It is associated with insulin resistance and the development of type 2 diabetes mellitus. It is also associated with the development of hepatic steatosis. The presence of hepatic steatosis is associated with an increased risk of having hepatic fibrosis. This is also associated with the severity of insulin resistance. These findings are specifically germane for those with genotype1 infection. Genotype 3 infection independently causes steatosis and successful treatment of the virus is followed by resolution of steatosis. In genotype 1 infection, the presence of hepatic steatosis is also a risk factor for failure to respond to pegylated interferon and ribavirin therapy. Unfortunately efforts to treat insulin resistance prior to antiviral therapy have not been very successful. Newer efforts focused on the role of specific micro RNAs in mediating the metabolic effects of hepatitis C virus infection may provide to ameliorate the metabolic risks of HCV infection.
How to use virological tools for the optimal management of chronic hepatitis C
Authors: de Leuw Philipp , Sarrazin Christoph , Zeuzem Stefan
Published: January 2011

Approximately 180 million individuals are chronically infected with hepatitis C, which is strongly associated with the development of cirrhosis, end‐stage liver disease and hepatocellular carcinoma. Several virological tools (anti‐HCV antibody assays, measurement of HCV‐RNA, HCV‐genotyping) are useful in management of hepatitis C infected patients. The primary goal of antiviral therapy in chronic hepatitis C is a sustained virological response (SVR). The HCV genotype should be determined in every patient considered for antiviral therapy because the currently recommended treatment duration and ribavirin doses differ among HCV genotypes. Exact subtyping might gain increased importance for future therapies with direct‐acting antiviral agents (DAA) because of differences of antiviral activities and barriers to resistance among HCV subtypes. Monitoring HCV RNA by a highly sensitive assay (LOD≤15 IU/ml) is the basis for management of response guided therapy of chronic hepatitis C with pegylated IFN plus ribavirin. Rules for early discontinuation of antiviral therapy in non‐responders and determination of optimal treatment durations in virologic responders have been developed for application of individualized treatment strategies.
Hepatitis B virus resistance to antiviral drugs: where are we going?
Authors: Zoulim Fabien
Published: January 2011

Chronic hepatitis B virus (HBV) infections remain a major public health problem worldwide. According to World Health Organization estimates, more than 300 million people are chronically infected and exposed to the risk of developing severe complications including cirrhosis and hepatocellular carcinoma (HCC). Major progress in the treatment of chronic hepatitis B (CHB) has been made during the last decade with the development of antivirals that inhibit viral polymerase activity. Antiviral drug resistance is an important factor in determining the success of long‐term therapy for CHB. The development of resistance to nucleoside analogues (NUCs) has been associated with exacerbations of liver disease. Sequential therapy increases the risk of the emergence of multidrug resistance. The selection of a potent antiviral with a high barrier to resistance as a first‐line therapy provides the best chance of achieving long‐term treatment goals and should be used whenever possible. This has led to a significant decrease in drug resistance in countries where this strategy is affordable. However, the barrier to resistance of a given antiviral agent is influenced by the genetic barrier, drug potency, patient adherence, pharmacological barrier, viral fitness, the drug mechanisms of action and cross resistance. Furthermore, because of specific viral kinetics, prolonged treatment with NUCs does not result in the clearance of the viral genome from the infected liver. It is therefore important to continue research to identify new viral and immune targets and develop novel antiviral strategies for controlling viral replication as well as preventing drug resistance and its complications in the long term.
Milestones and perspectives in viral hepatitis B
Authors: Hadziyannis Stephanos J.
Published: January 2011

There have been numerous research milestones since the discovery of the hepatitis B virus (HBV) in the 1960s. These mark major advances in the serology and epidemiology of HBV infection, in indentifying the wide clinical spectrum of acute and chronic hepatic diseases as well as the extrahepatic conditions induced by this virus, the molecular biology of the virus including its variants and mutants, its molecular diagnosis and monitoring, the host immune responses to the infecting virus, the pathogenesis and immunopathogenesis of liver disease as well as its natural course and outcome. These landmark discoveries are the firm background for current and future developments in treatment. There are three consecutive and partly overlapping chronological periods to treatment milestones beginning with recombinant standard interferon‐alpha (IFN‐α) in the 1980s, then oral antivirals from 1998 to the present and in 2005 pegylated IFN‐α (PEG‐IFN). The renewed interest in PEG‐IFN‐α treatment is now focused on both HBeAg‐positive and HBeAg‐negative chronic hepatitis B and it now also aims at HBsAg loss when associated with on‐treatment monitoring of serum HBV DNA and HBsAg levels, resulting in the closest thing to a cure of hepatitis B. The impressive progress made in all aspects of hepatitis B research suggests that curative therapy may be developed for all patients and for all phases of HBV infection in the foreseeable future. However for the moment, realistic efforts should be made to make treatment as widely available and affordable as possible and to apply current therapies to significantly reduce HBV morbidity and mortality.
Hepatitis D revival
Authors: Wedemeyer Heiner
Published: January 2011

More than 30 years after Mario Rizzetto and colleagues described a new antigen in livers of HBsAg‐positive patients called the “delta antigen”, a re‐emerging interest in hepatitis delta is currently observed. The state‐of‐the art on basic and clinical research on hepatitis delta was presented during a monothematic conference organized by the European Association for the Study of the Liver (EASL) in September 2010. Hepatitis delta is caused by infection with the hepatitis D virus (HDV) which requires presence of HBsAg for complete replication and transmission. Recent data confirmed the severe long‐term course of HDV infection with high rates of hepatic decompensation while controversial data on the risk for the development of hepatocellular carcinoma were reported. Pegylated interferon alpha can lead to sustained HDV RNA elimination in about one quarter of patients while HBV polymerase inhibitors are ineffective against HDV. Novel treatment options include prenylation inhibitors and HBV entry inhibitors which are currently in early clinical development.
New direct‐acting antivirals' combination for the treatment of chronic hepatitis C
Authors: Asselah Tarik , Marcellin Patrick
Published: January 2011

Chronic hepatitis C is one of the leading causes of chronic liver disease, with approximately 170 million people infected worldwide. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma (HCC). Sustained virological response (SVR) is long lasting, associated with a reduced risk of cirrhosis and HCC. In the near future, standard of care (SOC) treatment of hepatitis C virus (HCV) will include the addition of direct‐acting antivirals (DAAs) with a protease inhibitor to the pegylated interferon (PEG‐IFN) plus ribavirin (RBV). In HCV genotype 1 patients, promising results have been reported when the protease inhibitor telaprevir or boceprevir is added to the SOC, increasing SVR rates from less than 50% (PEG‐IFN plus RBV) to 70% (in patients treated with a triple combination of PEG‐IFN, RBV plus a protease inhibitor). The future management of patients with these new molecules will require good clinical practice, knowledge of indications, prediction of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet, requiring studies in special populations (human immunodeficiency virus–HCV‐coinfected patients, transplanted patients, etc.) in genotype non‐1 patients and in absolute non‐responders. Combinations of antivirals with additive potency that lack cross resistance and with a good safety profile may provide new regimens in the future to make HCV the first chronic viral infection eradicated worldwide with a finite duration of combination DAA therapy without IFN. There is ongoing development of new molecules such as HCV enzyme inhibitors. The aim of this review is to summarize the results obtained with DAAs: protease and polymerase inhibitors.
Interprofessional collaboration in the ICU: how to define?*
Authors: Rose Louise
Published: January 2011

The intensive care unit (ICU) is a dynamic, complex and, at times, highly stressful work environment that involves ongoing exposure to the complexities of interprofessional team functioning. Failures of communication, considered examples of poor collaboration among health care professionals, are the leading cause of inadvertent harm across all health care settings. Evidence suggests effective interprofessional collaboration results in improved outcomes for critically ill patients. One recent study demonstrated a link between low standardized mortality ratios and self‐identified levels of collaboration. The aim of this paper is to discuss determinants and complexities of interprofessional collaboration, the evidence supporting its impact on outcomes in the ICU, and interventions designed to foster better interprofessional team functioning. Elements of effective interprofessional collaboration include shared goals and partnerships including explicit, complementary and interdependent roles; mutual respect; and power sharing. In the ICU setting, teams continually alter due to large staff numbers, shift work and staff rotations through the institution. Therefore, the ideal ‘unified’ team working together to provide better care and improve patient outcomes may be difficult to sustain. Power sharing is one of the most complex aspects of interprofessional collaboration. Ownership of specialized knowledge, technical skills, clinical territory, or even the patient, may produce interprofessional conflict when ownership is not acknowledged. Collaboration by definition implies interdependency as opposed to autonomy. Yet, much nursing literature focuses on achievement of autonomy in clinical decision‐making, cited to improve job satisfaction, retention and patient outcomes. Autonomy of health care professionals may be an inappropriate goal when striving to foster interprofessional collaboration. Tools such as checklists, guidelines and protocols are advocated, by some, as ways for nurses to gain influence and autonomy in clinical decision‐making. Protocols to guide ICU practices such as sedation and weaning reduce the duration of mechanical ventilation in some studies, while others have failed to demonstrate this advantage. Existing organizational strategies that facilitate effective collaboration between health care professionals may contribute to this lack of effect.
Nursing leadership at the crossroads: evidence‐based practice ‘Matching Michigan‐minimizing catheter related blood stream infections’*
Authors: Goeschel Christine A
Published: January 2011

Aims and objectives: A highly successful intervention to reduce infections in intensive care units (ICUs) is now being widely replicated and involved significant nursing leadership. The objective of this manuscript is to describe briefly the intervention, and more explicitly the implications for nursing leadership as quality improvement and patient safety become global healthcare priorities.

Design: Collaborative cohort study in over 100 ICUs in the United States to implement and evaluate interventions to improve patients' safety.

Methods: Conceptual model aimed at improving clinicians' use of five evidence‐based recommendations to reduce rates of catheter‐related bloodstream infections rates, with measurement and feedback of infection rates.

Results: One hundred and three ICUs contributed 1981 ICU‐months of data representing 375,757 catheter‐days. The median rate of catheter‐related bloodstream infection per 1000 catheter‐days decreased from 2.7 infections at baseline to 0 at 3 months after implementation of the study intervention (P ≤ 0·002), and the mean rate per 1000 catheter‐days decreased from 7.7 at baseline to 1.4 at 16–18 months of follow‐up (P < 0·002). During the sustainability period, the mean bloodstream infection rate did not significantly change from the initial 18 month postimplementation period (−1%, 95% confidence interval −9% to 7%). Eighty seven percent of the original study participants had data available for the sustainability study.

Conclusions: Broad use of this intervention with achievement of similar results could substantially reduce the morbidity and costs associated with catheter‐related bloodstream infections.

Relevance to clinical practice: The initial Michigan study and the follow‐up analysis, that demonstrated sustained improvements, are leading to similar projects in other countries, include the Matching Michigan project in England. Discussing not only the technical components of the program, but also the nursing leadership aspects may assist nurses just embarking on this work.
Understanding the effects of oxygen administration in haemorrhagic shock
Authors: Knight Amanda R , Fry Lauren E , Clancy Richard L , Pierce Janet D
Published: January 2011

Aims and objectives: The aim of this article is to provide a review of the literature regarding oxygen administration and the use of oxygen in patients experiencing haemorrhagic shock (HS).

Results: Oxygen is administered to patients to assist them in maintaining oxygenation. The administration of oxygen is complex and varies significantly among patients. In order to optimize patient care, clinicians need to be aware of the potential effects, both beneficial and harmful, that oxygen can have on the body.

Inclusion and exclusion criteria: Literature inclusion criteria for this article was any article (1995 to present) pertaining to oxygen administration and HS. Also included were articles related to tissue injury caused by an overabundance of free radicals with the administration of oxygen. Articles related to oxygen and wound healing, pollution, aerospace, food and industrial uses were excluded.

Conclusions: This review of the literature provides an overview of the use of oxygen in clinical practice and HS. The harmful effects of oxygen are highlighted to alert the clinician to this potential when there is an overabundance of oxygen.

Relevance to clinical practice: Oxygen is one of the most common drugs used in the medical community; however, the effects of oxygen on the body are not well understood. The use of oxygen if not prescribed correctly can cause cellular damage and death. Clinicians need to be more aware of the effects of oxygen and the damage it may cause if not administered properly.
Liberal Silences and the Political Economy of Global Governance
Authors: Kirkup Alex
Published: January 2011

The books under review, though offering important advances in understanding their particular issue areas of global governance, together reproduce a number of liberal political-economic silences that obscure key power relations, a process made visible through resistance. These silences privilege the formal public–private sphere of civil society over both alternative expressions of social agency and the continuing importance of state sovereignty, leading to false claims of wider participation, partnership and empowerment in global politics and also unexpected social and environmental consequences.
Managing Ethnic Conflict: The Merits and Perils of Territorial Accommodation
Authors: Wolff Stefan
Published: January 2011

Territorial accommodation in the management of ethnic conflict, while widely practised, has also been the subject of much academic debate which has failed to reach a conclusive verdict on its utility to contribute to sustainable conflict settlements. Reviewing three recent volumes on the role of institutions in conflict management processes, I focus on their central argument in relation to the question of whether territorial accommodation is a viable strategy for conflict management. While none of the volumes offers a conclusion to the debate over the merits of territorial approaches, they all provide sophisticated answers to some of the key questions continuously raised in this debate and all have significant potential to inform its policy dimension and to shape future research.
The Triumph of Anti-liberalism? Reconciling Radicalism to Realism in International Relations Theory
Authors: Hall Ian
Published: January 2011

One of the most significant developments in international relations theory in the past decade has been the reconciliation of radical post-positivist theorists to realism. This article examines the causes and consequences of that reconciliation. It argues that while advances in the history of international thought have prompted substantive re-evaluations of the work of past realist thinkers, including that of Carl Schmitt and Hans J. Morgenthau, the reconciliation of radicalism and realism has occurred because of the radicals' realisation of their common antiliberalism. Drawing upon the work of Stephen Holmes, the article concludes with a discussion of the implications of the rise of anti-liberalism among international relations theorists.
Bringing the State Back into Cosmopolitanism: The Idea of Responsible Cosmopolitan States
Authors: Brown Garrett Wallace
Published: January 2011

When surveying the cosmopolitan literature one is often struck by the ease with which the state is rendered morally and empirically otiose and by resulting ambiguities about the role states could play in creating a cosmopolitan condition. In response to these ambiguities, the purpose of this article is to examine some recent cosmopolitan arguments and to see what answers, if any, they have for bridging the gap between cosmopolitan theory and state practice. By doing so, this article will map out the recent relationship between cosmopolitanism and the state while also suggesting that cosmopolitans should reconsider a research agenda based on the idea of responsible cosmopolitan states as a means to create stronger links between cosmopolitan theory and contemporary international practice.
Carbamazepine coadministration with an oral contraceptive: Effects on steroid pharmacokinetics, ovulation, and bleeding
Authors: Davis Anne R. , Westhoff Carolyn L. , Stanczyk Frank Z.
Published: January 2011

Purpose:  Antiepileptic drugs (AEDs) are widely used in reproductive‐age women. The AED carbamazepine (CBZ) induces the hepatic cytochrome P450 system, thereby accelerating hormone metabolism. We sought to assess the pharmacodynamic effects of CBZ on breakthrough bleeding and ovulation during oral contraceptive (OC) use.

Methods:  A double‐blind, randomized, crossover study of healthy women ages 18–35 years. Participants took an OC containing 20 μg ethinyl estradiol (EE) and 100 μg levonorgestrel (LNG) for 4 months. Concurrently, participants took 600 mg CBZ or a matching placebo for 2 months each, administered in random order. During the second month of CBZ or placebo, we measured EE and LNG levels 12 times over 24 h, ovarian follicular diameters with eight biweekly vaginal ultrasounds, weekly progesterone levels, and bleeding (using a diary).

Key Findings:  We enrolled 25 women; 10 completed the study. Five women discontinued because of reversible CBZ side effects. Mean area under the curve (AUC) measurements were lower during CBZ use compared to placebo for EE (1,778 vs. 986 pg*h/ml, p < 0.001) and LNG (24.8 vs. 13.8 pg*h/ml, p = 0.04). Ovulation occurred in 5 of 10 CBZ cycles compared to 1 of 10 placebo cycles (p = 0.06). Three or more days of breakthrough bleeding occurred during 8 of the 10 CBZ cycles compared to 2 of the 10 placebo cycles (p = 0.07).

Significance:  A commonly used dose of CBZ decreased levels of contraceptive steroids, increased breakthrough bleeding, and permitted ovulation during use of a low‐dose OC. Women treated with CBZ are not adequately protected from pregnancy by low‐dose OCs.
Core Decompression of the Equine Navicular Bone: An In Vitro Biomechanical Study
Authors: Jenner Florien , Kirker‐Head Carl
Published: January 2011

Objective:To determine the effect of core decompression surgery and bone mineral density (BMD) on the mechanical properties of equine navicular bones.

Study Design:Experimental, in vitro study.

Sample Population:Fore limb navicular bones (n=36 pairs) from sound 2–5‐year‐old horses with no radiographic abnormalities of the distal aspect of the forelimbs.

Methods:Navicular BMD was measured using dual energy X‐ray absorptiometry. One randomly assigned navicular bone from each pair served as control. The contralateral test specimen was allocated to 1 of 6 treatment groups defined by drill bit size (3.2 versus 2.5 mm diameter) and by the number of drill channels (1, 2, or 3) created in the proximal border of the bone. Bones were then tested until failure in 3‐point bending. Data were statistically analyzed using ANOVA and regression analysis.

Results:There were significant (P<.001) positive correlations between BMD and biomechanical data. A significant (P<.001) reduction in breaking strength was noted between intact and drilled bone pairs; however, the diameter and number of decompression channels did not significantly (P>.05) influence the extent of the reduction in mechanical strength.

Conclusion:In vitro core decompression significantly decreases the breaking strength of the equine navicular bone.
Treatment of Epiglottic Entrapment by Transnasal Axial Division in Standing Sedated Horses Using a Shielded Hook Bistoury
Authors: Lacourt Mathieu , Marcoux Marcel
Published: January 2011

Objectives:To report use of a shielded hook bistoury developed for correction of epiglottic fold entrapment in standing sedated horses.

Study Design:Prospective clinical study.

Animals:Standardbreds (n=8), 3–19 years of age.

Methods:Epiglottic fold entrapment was corrected during standing sedation using a shielded hook bistoury passed nasally into the pharynx. Owners, trainers, and referring veterinarians were contacted by telephone to establish outcome.

Results:Axial division of the entrapping epiglottic fold was successful in all horses. No short‐ or long‐term complications occurred. Axial transection of the entrapping fold was performed rapidly (mean, 83 seconds between advancing the bistoury into the pharynx and transection of the entrapping fold).

Conclusion:Transnasal axial division of the aryepiglottic fold can be accomplished safely using the shielded hook bistoury. The shield mechanism minimizes the risk of injury from the cutting blade to adjacent structures.
Translating the Insomnia Severity Index Into Arabic
Authors: Suleiman Khaled H. , Yates Bernice C.
Published: January 2011

Purpose: The purpose of this study was to translate the Insomnia Severity Index (ISI) into Arabic (Fusha dialect), and obtain preliminary reliability and validity estimates for the translated version.

Background: Arabic populations experience sleep problems that interfere with their vitality and quality of life. The ISI was established to screen for insomnia in both clinical and research situations.

Design: This study used a descriptive correlational design. The ISI was translated into Arabic using the back‐translation method and compared with three other sleep measures: the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, and the Vitality Subscale from the Medical Outcomes Study Short Form‐36. These measures were administered to 35 healthy Arabic bilingual participants from three community locations.

Findings: The mean ISI score was 9.2 (SD= 5.8; range 0–20). Internal consistency reliability was 0.84. The correlations between the total ISI score and the single items ranged from 0.49 to 0.92 (p < .01). In terms of convergent validity, the total ISI score showed a strong positive correlation with the Pittsburgh Sleep Quality Index global score (r= 0.76, p < .001) and a moderate, negative correlation with vitality (r= ‐0.38, p=.026).

Conclusions: The translated ISI demonstrated adequate reliability and validity. The translated ISI needs further testing in a larger sample of both clinical and healthy Arabic populations in their own countries.

Clinical Relevance: Preliminary psychometric estimates show that the translated ISI is reliable and valid in this community‐dwelling Arabic sample. The translated ISI allows for Arabic researchers to screen for insomnia and plan for future intervention studies.
Emerging Biobehavioral Factors of Fatigue in Sickle Cell Disease
Authors: Ameringer Suzanne , Smith Wally R.
Published: January 2011

Purpose: The symptom most frequently associated with sickle cell disease (SCD) is pain, but recent research is beginning to indicate that fatigue as an increasingly important symptom of this disease upon which to focus research efforts. This article explores biological and behavioral factors that can potentially contribute to fatigue in SCD.

Organizing Framework: A biobehavioral framework guides this discussion of factors that may contribute to SCD fatigue.

Findings: The pathophysiology of the disease process, such as the profound hemolytic anemia and unpredictable vasoocclusive crises, suggests that individuals with SCD are at risk for both acute and chronic fatigue. For example, hypoxemia can cause muscle weakness and produce oxidative stress, which, in turn, increases fatigue. Sickled erythrocytes disrupt the vascular endothelium and stimulate proinflammatory cytokines, which are linked to sleep disruptions. Pain, the most notorious symptom of SCD, has a complex and mechanistically poorly understood relationship with fatigue.

Conclusions: Little is known about the symptom of fatigue in SCD. Considering the biological and behavioral factors of SCD that could potentially contribute to fatigue, there is a great need for research on the nature and potential mechanisms of fatigue in SCD.

Clinical Relevance: Fatigue in SCD may negatively affect quality of life. Understanding factors that may contribute to fatigue aids the clinician in identifying causes and determining treatment.
Nurse Leader Mentor as a Mode of Being: Findings From an Australian Hermeneutic Phenomenological Study
Authors: McCloughen Andrea , O’ Brien Louise , Jackson Debra
Published: January 2011

Purpose: To develop an interpretation of Australian nurse leaders’ understandings and experiences of mentorship for nurse leadership. The study aimed to explore experiential meanings and understandings that Australian nurse leaders apply to their mentoring relationships; determine whether mentoring relationships contribute to nurse leader development in Australia; and identify how Australian nurse leaders conceptualize mentorship.

Design: Hermeneutic phenomenology provided the methodological framework for the study. A purposive sample of 13 Australian nurse leaders was interviewed so they could share subjective experiences of mentorship through conversational narrative. Interview transcripts were analyzed to uncover and isolate key aspects of the phenomenon in text. An adaptation of Radnitzky's hermeneutic circle was used to develop a hermeneutic meaning interpretation of the text.

Findings: The lived experience of mentorship for nurse leadership was understood and described through three existential motifs: imagination, journey, and mode of being. This article specifically addresses the finding that mentorship for leadership was sustained by the mentor's mode of being. These nurse leaders were not formally prepared to be mentors; rather, they grew into being mentors as a result of their life journeys.

Conclusions: The nurse leaders possessed a life attitude of mentorship that impacted how they perceived and interacted with their world. Mentorship was not formally learned, nor was it enacted as an adjunct role. Being a mentor was a fully integrated aspect of their person.

Clinical Relevance: Nurse‐leaders use mentorship to grow and develop leadership potential in other nurses. Formal preparation to be a mentor is not fundamental to all mentorship. Some nurse leaders who mentor others for leadership grow into being mentors as a result of lifelong subjective experiences.
PCOS – what matters in early pregnancy?– data from a cross‐sectional, multicenter study
Authors: VANKY ESZTER , STRIDSKLEV SOLHILD , SKOGØY KRISTIN , KLEGGETVEIT ODRUN , HJELLE SISSEL , BRANDIS PHILIP V. , EIKELAND TORUNN , FLO KARIN , BERG KRISTIN FLATEN , BUNFORD GABOR , LUND AGNETHE , BJERKE CECILIE , ALMÅS INGUNN , BERG ANN HILDE , DANIELSSON ANNA , LAHMAMI GULIM , CARLSEN SVEN M.
Published: January 2011

Objective. To describe patient characteristics according to different diagnostic criteria in early pregnancy, in women with polycystic ovary syndrome (PCOS). Design. Descriptive, cross‐sectional study of 257 women with PCOS in the first trimester of pregnancy. Setting. Data from a multicenter trial at the time of inclusion. Population. 257 PCOS women with singleton pregnancies. Methods. Investigator‐administrated questionnaires were filled out. Clinical examination was performed by the investigators. Fasting blood samples were collected. Main outcome measures. Biometric data, androgens, glucose and insulin levels. Results. Women who met the National Institutes of Health (NIH) criteria for PCOS had higher body mass index (BMI), testosterone, dehydroepiandrostenedione, free testosterone index (FTI) and insulin levels compared with those who only met the Rotterdam consensus criteria. Adjusted for age and BMI, only testosterone and FTI were higher in those who met the NIH criteria. BMI was a strong, independent predictor of both systolic and diastolic blood pressure in early PCOS pregnancy, while both FTI and fasting insulin were independent predictors of systolic blood pressure. Twenty‐two (9%) of the participants had gestational diabetes mellitus in the first trimester of pregnancy. Conclusions. In the first trimester, PCOS women diagnosed according to NIH criteria were more metabolically and endocrinologically abnormal compared with those who only met the Rotterdam consensus criteria. BMI and FTI were independent predictive factors for blood pressure. There was a high prevalence of gestational diabetes mellitus in early PCOS pregnancies.
Trends in live births in the past 20 years in Zhengzhou, China
Authors: HAN WEI , SONG JIANGANG , LIU AIQING , HUO KAIMING , XU FALIN , CUI SHIHONG , WANG XIAOYANG , ZHU CHANGLIAN
Published: January 2011

Objective. To evaluate changing trends in neonatal births and deaths in a provincial women's and children's hospital over the past 20 years. Design: Retrospective longitudinal study. Setting. Henan Provincial Women's and Children's Hospital, China. Population. Live births in Henan Provincial Women's and Children's Hospital from January 1987 to December 2006. Methods: Data was stratified by sex, birth weight, delivery type, maternal age, gestational age, and single or multiple births. The incidence of low Apgar scores and neonatal death was calculated for each fiscal year. Main outcome measures: Trends in the fundamental status of hospital‐born live births and risk factors for neonatal death. Results. 26 760 hospital live births were included. The ratio of males to females was 1.16:1. The mean gestational age decreased from 39.5±1.4 weeks to 38.4±2.5 weeks (p <0.001) and multiple births increased from 1.5 to 7.3% (p<0.001). The proportion of preterm births increased from 4.7 to 18.9% (p<0.001), maternal age increased from 25.9±3.7 years to 29.0±4.4 years (p<0.001), and cesarean deliveries increased from 23.7 to 65.5% (p<0.001). The incidence of low Apgar scores decreased from 12.9 to 1.1% (p<0.001). The incidence of neonatal death was 8.5/1 000 live births, with preterm births and low Apgar scores accounting for 72.8 and 16.2% of all neonatal deaths, respectively. Conclusion. Preterm births, multiple births, and cesarean deliveries increased dramatically. Preterm birth is the leading cause of neonatal death.