A novel biomathematical model that analyzes the combined alanine transaminase (ALT) and viral‐load kinetics during the first month of pegylated interferon (Peg‐IFN) plus ribavirin (RBV) therapy was ...successfully applied in 90 of 97 (93%) chronic hepatitis C patients in order to compute the number of infected cells at the end of therapy (Ieot). The Ieot indices were lower in sustained virological responders than in relapsers (RELs) and nonresponders (NRs) (median values: 31 vs. 2,190 vs. 1,090,000; P < 0.001), and were independently associated with treatment outcomes (P = 0.003). A threshold of 250 Ieot was shown to identify sustained virological response (SVR) with high positive predictive value (93%) and good diagnostic accuracy (81%). The time taken to attain 250 Ieot ranged from 3 to 11 months in patients with hepatitis C virus (HCV) genotypes 2 or 3 and from 3 to 18 months in those with HCV genotypes 1 or 4. Overall, the duration of therapy would have been 49 months less than that suggested by the most recent algorithms based on a rapid virological response (RVR) at week 4.
Clinical Pharmacology & Therapeutics (2008); 84, 2, 212–215 doi:10.1038/clpt.2008.21
In this work, a flow analysis system with hydride generation and Fourier transform infrared (FTIR) spectrometric detection has been developed for the determination of antimony in pharmaceuticals. The ...method is based on the on-line mineralization/oxidation of the organic antimonials present in the sample and pre-reduction of Sb(V) to Sb(III) with K
2S
2O
8 and KI, respectively; prior to the stibine generation. The gaseous SbH
3 is separated from the solution in a gas phase separator, and transported by means of a nitrogen carrier into a short pathway (10 cm) IR gas cell, where the corresponding FTIR spectrum is acquired by accumulating 3 scans in a continuous mode. The 1893 cm
−1 band was used for the quantification of the antimony. The procedure is carried out in a closed system, which reduces sample handling and makes possible the complete automation of the antimony determination. The figures of merit of the proposed method (linear range: 0–600 mg
l
−1, limit of detection (3
σ)=0.9 mg
l
−1, limit of quantification (10
σ)=3 mg Sb
l
−1, precision (R.S.D.) less than 1% and sample frequency=28 h
−1), are appropriate for the designed application. Furthermore, precise and accurate results were found for the analysis of different antimonial pharmaceutical samples, indicating that the methodology developed represents a valid alternative for the determination of antimony in pharmaceuticals, which could be suitable for the routine control analysis.
Purpose
– Effective engineering asset management is essential in delivering public services safely whilst avoiding breakdowns and accidents. The purpose of this paper is to ensure asset safety and ...sustainability, public sector firms have to adopt new processes and practices. It is the role of supervisors to implement the changes, and as part of the new public management (NPM) public sector reforms, public sector asset managers have more discretionary power to implement further changes related to increased accountability.
Design/methodology/approach
– The paper explores the impact of management practices on supervisor-employee relationships and employees’ perception of autonomy, employees’ attitudes towards change and their perceptions of organisational culture within Australian public sector engineering asset management organisations, and in the context of NPM reforms and consequent changes in supervisory discretionary power. Social exchange theory provided the theoretical framework and a self-report survey was administered to 149 employees.
Findings
– The findings from a structural equation model indicate positive and significant relationships between the variables in this study. A finding of significant interest was that public sector employees are on average slightly dissatisfied with their supervisors and feel they have a minimal amount of autonomy in the workplace. This may represent an unintended consequence of NPM reforms.
Research limitations/implications
– The implication of the findings is that an effective relationship between supervisors and employees is a necessary ingredient for achieving change, and ensuring asset safety and sustainability. Social exchange theorists argue that the low level of satisfaction with the supervisors evident in this study is one factor compromising asset safety and sustainability.
Originality/value
– The roadblocks to good supervisory relationships in the post NPM environment must be dismantled and the findings clearly indicate a need for targeted development of supervisors/management skills to ameliorate the negative effects of the NPM regime and enable effective change management.
Background/Aims
: We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, ...followed-up prospectively for a mean of 6 years (21 months–12 years).
Methods
: Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively.
Results
: Disease progression was associated with older age (
P<0.001), absence of previous HBeAg history (
P=0.017) and higher serum HBV-DNA levels (
P=0.009) (more frequently observed in unremitting disease profile,
P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations,
P=0.045) correlated with end stage complications in cirrhotics (
P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (
P=0.015): interferon slowed disease progression (
P<0.001).
Conclusions
: The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.
The morphology of graphene‐based foams can be engineered by reinforcing them with nanocrystalline zirconia, thus improving their oil‐adsorption capacity; This can be observed experimentally and ...explained theoretically. Low zirconia fractions yield flaky microstructures where zirconia nanoparticles arrest propagating cracks. Higher zirconia concentrations possess a mesh‐like interconnected structure where the degree of coiling is dependant on the local zirconia content.
The aim of antiviral therapy of chronic hepatitis B is to control Hepatitis B Virus (HBV) replication and to cure liver disease avoiding the progression of chronic hepatitis to cirrhosis and the end ...stage complications of cirrhosis. HBeAg/anti-HBe seroconversion is the hallmark of response in hepatitis B "e" antigen (HBeAg) positive patients. In the patients with antibody against HBeAg (anti-HBe positive) the combination of HBV DNA and anti-HBc IgM tests provides adequate diagnostic accuracy. Patients with biochemical and/or histological disease activity are eligible to therapy. The drug choice is based on age, disease severity, risk of complications, side effects and compliance, particularly in anti-HBe positive patients where prolonged treatment is needed. Interferon (5-6 MU daily or 9-10 MU thrice weekly for 4-6 months) is the first line therapy for HBeAg positive patients and (5-6 MU thrice weekly for 12-24 months) for anti-HBe positive patients. When IFN is contraindicated or ineffective, Lamivudine (100 mg) or Adefovir Dipivoxil (10 mg) are given as long as 4-6 months after HBeAg/anti-HBe seroconversion or for long-term treatments in HBeAg positive non-responders and anti-HBe positive patients. Patients with more advanced forms of cirrhosis and portal hypertension are to be treated within liver transplantation programs. Fifteen to 30% of treated patients achieve sustained response and more than 60% of them experience long-term disease remission during therapy. In perspectives, currently available molecular and immunologic tools and modelling of viral dynamics will help to address the therapy issue with more complex, efficacious and individually tailored treatment schedules.
Recent advances in therapy for patients with chronic hepatitis B (CHB) infection offer the potential for a more successful treatment outcome, but also raise a number of questions in clinical practice ...regarding diagnosis and staging of CHB to ensure such potential is realized. In patients without cirrhosis, some forms of antiviral therapy can switch patients from an active disease phase into an inactive hepatitis B surface antigen (HBsAg) carrier state, and eventually lead to HBsAg clearance and HBsAg antibody seroconversion, the closest to a cure in CHB; thus, one of the most important diagnostic questions that clinicians face is the identification of patients with early forms of CHB within a large cohort of asymptomatic HBsAg-positive individuals, most of whom are inactive HBsAg carriers. Two major categories of diagnostic markers are currently available: virus-specific markers and liver disease markers. Most markers involve the use of non-invasive serological testing, but invasive diagnostic procedures, such as liver biopsy, are also an option. In this article, we review current opinions on the appropriate use of diagnostic procedures, answering some important questions for the clinician, such as why, how, when and in whom they might best be used.
Objectives We studied the impact of hepatitis B virus (HBV) polymerase/reverse transcriptase (Pol/Rt) heterogeneity on adefovir rescue therapy in 34 consecutive chronic hepatitis B patients with ...viral breakthrough during lamivudine monotherapy. Methods The Pol/Rt A–F domains were directly sequenced in all patients at baseline, and 12 and 24 months. Response to therapy was evaluated at 3, 6, 12 and 24 months by quantitative HBV-DNA. Results Primary treatment failures did not occur. At 6 months 24/34 (70.6%) patients had viraemia < 104 copies/mL initial viral response (IVR); at 12 and 24 months 23 (71.9%) and 26 (81.3%) of 32 had HBV-DNA < 200 copies/mL complete viral response (CVR). IVR or CVR patients did not show viral breakthroughs, which occurred in one of the six remaining patients. All but three patients had baseline rtM204I/V substitutions associated with rtL180M in 23, rtL80I/V in 14, rtV173L in 4, rtT184S in 3, rtQ215S in 2 and rtA181S in 2 cases. rtA181S without rtM204I/V was found in one patient. Four of the six patients (67%) without 24 month CVR showed rtA181S or rtT184S substitutions either alone or with typical lamivudine resistance profiles. Baseline HBV-DNA levels were negatively associated with IVR (univariate analysis, P = 0.023). At least one of rtA181S and rtT184S substitutions correlated negatively with IVR and CVR (univariate analysis, P = 0.001) and was independently associated with absence of CVR (P = 0.016). Conclusions Lamivudine monotherapy favours the emergence of viral quasispecies that influence the response rate to adefovir rescue therapy independently from baseline viraemia and lower the susceptibility to other nucleos(t)ide analogues.
Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because ...of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of 42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P < 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wild-type HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus.
PDF
