Synthesis of Antimonene on Germanium.

The lack of large-area synthesis processes on substrates compatible with industry requirements has been one of the major hurdles facing the integration of 2D materials in mainstream technologies. This is particularly the case for the recently discovered monoelemental group V 2D materials which can only be produced by exfoliation or growth on exotic substrates. Herein, to overcome this limitation, we demonstrate a scalable method to synthesize antimonene on germanium substrates using solid-source molecular beam epitaxy. This emerging 2D material has been attracting a great deal of attention due to its high environmental stability and its outstanding optical and electronic properties. In situ low energy electron microscopy allowed the real time investigation and optimization of the 2D growth. Theoretical calculations combined with atomic-scale microscopic and spectroscopic measurements demonstrated that the grown antimonene sheets are of high crystalline quality, interact weakly with germanium, exhibit semimetallic characteristics, and remain stable under ambient conditions. This achievement paves the way for the integration of antimonene in innovative nanoscale and quantum technologies compatible with the current semiconductor manufacturing.

Effects of exercise training on neuromuscular junction morphology and pre- to post-synaptic coupling in young and aged rats.

The objective of this study was to determine whether pre- to post-synaptic coupling of the neuromuscular junction (NMJ) could be maintained in the face of significant morphological remodeling brought about by exercise training, and whether aging altered this capacity. Eighteen young adult (8 mo) and eighteen aged (24 mo) Fischer 344 rats were randomly assigned to either endurance trained (treadmill running) or untrained control conditions resulting in four groups (N=9/group). After the 10-week intervention rats were euthanized and hindlimb muscles were surgically removed, quickly frozen at approximate resting length and stored at -85°C. The plantaris and EDL muscles were selected for study as they have different functions (ankle extensor and ankle flexor, respectively) but both are similarly and overwhelmingly comprised of fast-twitch myofibers. NMJs were stained with immunofluorescent procedures and images were collected with confocal microscopy. Each variable of interest was analyzed with a 2-way ANOVA with main effects of age and endurance training; in all cases significance was set at P⩽0.05. Results showed that no main effects of aging were detected in NMJs of either the plantaris or the EDL. Similarly, endurance training failed to alter any synaptic parameters of EDL muscles. The same exercise stimulus in the plantaris however, resulted in significant pre- and post-synaptic remodeling, but without altering pre- to post-synaptic coupling of the NMJs. Myofiber profiles of the same plantaris and EDL muscles were also analyzed. Unlike NMJs, myofibers displayed significant age-related atrophy in both the plantaris and EDL muscles. Overall, these results confirm that despite significant training-induced reconfiguration of NMJs, pre- to post-synaptic coupling remains intact underscoring the importance of maintaining proper apposition of neurotransmitter release and binding sites so that effective nerve to muscle communication is assured.

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy. METHODS: In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child-Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt. RESULTS: Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8-8.5 cm), which decreased with tace to 5.0 cm (range: 3.3-7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival. CONCLUSIONS: The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.

Aging influences adaptations of the neuromuscular junction to endurance training.

This investigation sought to determine if aging affected adaptations of the neuromuscular junction (NMJ) to exercise training. Twenty young adult (8 months) and 20 aged (24 months) rats were assigned to either a program of treadmill exercise, or sedentary conditions. Following the 10-week experimental period, rats were euthanized, and soleus and plantaris muscles were removed and frozen. Longitudinal sections of the muscles were fluorescently stained to visualize pre-synaptic nerve terminals and post-synaptic endplates on both slow- and fast-twitch fibers. Images were collected with confocal microscopy and quantified. Muscle cross-sections were histochemically stained to assess muscle fiber profiles (size and fiber type). Our analysis of NMJs revealed a high degree of specificity and sensitivity to aging, exercise training, and their interaction. In the soleus, slow-twitch NMJs demonstrated significant (P ≤ 0.05) training-induced adaptations in young adult, but not aged rats. In the fast-twitch NMJs of the soleus, aging, but not training, was associated with remodeling. In the plantaris, aging, but not training, remodeled the predominant fast-twitch NMJs, but only pre-synaptically. In contrast, the slow-twitch NMJs of the plantaris displayed morphologic adaptations to both aging and exercise in pre- and post-synaptic components. Muscle fiber profiles indicated that changes in NMJ size were unrelated to adaptations of their fibers. Our data show that aging interferes with the ability of NMJs to adapt to exercise training. Results also reveal complexity in the coordination of synaptic responses among different muscles, and different fiber types within muscles, in their adaptation to aging and exercise training.

'Access arrangements' for biobanks: a fine line between facilitating and hindering collaboration.

This decade is witnessing the proliferation of large-scale population-based biobanks. Many biobanks have reached the stage of offering access to their collection of data and samples to the scientific community. This, however, requires that access arrangements be established to govern the relationship between biobanks and users. Access arrangements capture the convergence of all normative elements in the life cycle of a biobank: policies, laws, common practices, commitments made by the biobank to participants, the expectations of funders, and the needs of the scientific community. Furthermore, access arrangements shape new legal agreements between 'biobankers' and researchers to ensure appropriate, regulated and efficient use of biobank materials. This paper begins by examining the particularities of access arrangements, identifying the key elements of these new regulatory instruments. Second, the paper looks at various strategies used by biobanks to regulate access and surveys the underlying motivations of these strategies and the impact they can have on potential international collaboration. Third, an example of the challenges encountered in creating access policy is illustrated using the case of CARTaGENE, a biobank based in Montreal, Canada. Last, the paper presents how Public Population Project in Genomics (P(3)G) facilitates the work of biobankers and improves collaboration throughout the international human genomics research community.

A European survey on biobanks: trends and issues.

Biobanks have recently gained great significance for research and personalised medicine, being recognised as a crucial infrastructure. At the same time, the widely varied practices in biobanking may also pose a barrier to cross-border research and collaboration by limiting access to samples and data. Nevertheless, the extent of the actual activities and the impact of the level of networking and harmonisation have not been fully assessed. To address these issues and to obtain missing knowledge on the extent of biobanking in Europe, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre, in collaboration with the European Science and Technology Observatory (ESTO), conducted a survey among European biobanks. In total, 126 biobanks from 23 countries responded to the survey. Most of them are small or medium-sized public collections set up either for population-based or disease-specific research purposes. The survey indicated a limited networking among the infrastructures. The large majority of them are stand-alone collections and only about half indicated to have a policy for cross-border sharing of samples. Yet, scientific collaborations based on the use of each biobank appear to be prominent. Significant variability was found in terms of consent requirements and related procedures as well as for privacy and data protection issues among the biobanks surveyed. To help promote networking of biobanks and thus maximise public health benefits, at least some degree of harmonisation should be achieved.

Re-treatment with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy.

BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.

Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alpha-2a plus ribavirin.

BACKGROUND: The impact of reduced drug exposure on outcomes in patients with chronic hepatitis C has not been determined in routine clinical practice. AIM: To examine the impact of exposure to peginterferon alpha-2a and ribavirin on early virological response (EVR) and sustained virological response (SVR) in treatment-naive patients with HCV genotype 1 infection enrolled in a large expanded access programme. METHODS: Eight hundred and ninety-one patients treated for 48 weeks with an initial ribavirin dose of 800 or 1000/1200 mg/day were evaluated. Ribavirin 1000 mg/day (<75 kg) or 1200 mg/day (>or=75 kg) and peginterferon alpha-2a 180 microg/week were considered optimal. The impact of reduced drug exposure (expressed as a percentage of optimal) on EVR and SVR was evaluated. RESULTS: Mean ribavirin exposure in week 0-12 was 70% and 96% in patients assigned to ribavirin 800 and 1000/1200 mg/day, respectively. EVR and SVR rates were lower in patients assigned to ribavirin 800 than 1000/1200 mg/day (EVR, 75% vs. 84%, respectively, P < 0.001; SVR, 45% vs. 54%, respectively, P = 0.011). Furthermore, there was a strong correlation between achievement of EVR and SVR and ribavirin dose over the first 12 weeks expressed either as absolute dose or proportion of optimal dose received (P < 0.001 for both). CONCLUSIONS: Ribavirin exposure to week 12 is significantly associated with EVR and SVR in genotype 1 patients. Maintenance of an optimal ribavirin dose is the most important modifiable factor during combination therapy for chronic hepatitis C.

Caregivers attitudes for very premature infants: what if they knew?

BACKGROUND: Decisions about resuscitation of extremely premature babies are controversial. Such decisions may reflect poor understanding of outcomes. OBJECTIVE: To compare caregivers' attitudes towards the resuscitation of a premature infant if they are only told the infant's gestational age or if they are only given prognostic information for infants at that gestational age. DESIGN/METHODS: Residents and nurses involved in perinatal care were asked whether they would resuscitate a depressed AGA 24-week gestation infant at birth. In another question they were asked whether they would resuscitate a depressed preterm infant with a 50% chance of survival, knowing that of those who survived, 50% would have a development 'within normal limits', 20-25% a serious handicap and 40% with behavioural and/or learning disability. RESULTS: Two hundred and seventy-nine caregivers responded (91% response rate). In the scenario that only presented gestational age, 21% of respondents would resuscitate. In the scenario that only presented prognostic statistics, 51% of respondents would resuscitate (p<0.05). CONCLUSIONS: Providers of perinatal health care respond to vignettes differently depending upon the format in which information is provided. The relative unwillingness to resuscitate a baby of 24-week gestation is surprising since outcomes for such babies are the same or better than those we described in the scenario that provided only outcome data without specifying gestational age. Two explanations are possible: (1) respondents have irrational negative associations with low gestational ages or (2) respondents are unaware of actual outcomes.

Survival after liver transplantation for hepatitis C is unchanged over two decades in Canada.

Allograft failure secondary to recurrence of hepatitis C virus (HCV) infection is the most common cause of death and retransplantation among recipients with HCV infection. It has been suggested that patients transplanted for HCV have had worse outcomes in more recent years than in previous years (the 'era effect'). A Canadian transplantation registry database was analyzed to determine the outcomes of patients transplanted over the years for HCV. The results of the present analysis of 1002 patients show that the 'era effect' was not seen in liver transplantation recipients with HCV in Canada, because no survival difference was noted based on the year of transplantation. All groups had overall two-year and five-year survival rates of 76% to 83% and 69% to 72%, respectively. The present study's national results prove continued benefit to transplantation of HCV patients.

Does a rapid decline in the hematological and biochemical parameters induced by interferon and ribavirin combination therapy for the hepatitis C virus predict a sustained viral response?

BACKGROUND AND OBJECTIVES: To analyze whether rapid myelosuppression and a decrease in alanine aminotransferase (ALT) induced by standard interferon (IFN) and ribavirin (RBV) combination therapy predict a sustained viral response (SVR) in hepatitis C virus patients. PATIENTS AND METHODS: Data from 111 patients (mean age 48.1 years) with chronic hepatitis C virus were retrospectively analyzed. All patients were treated with the same initial doses of IFN and RBV combination therapy. The following laboratory values were measured at baseline, and then at weeks 2, 4, 8, 12 and 24 of treatment: hemoglobin, white blood cells (WBCs), neutrophils, platelets and ALT. A delta value was then calculated for each interval from baseline (baseline values minus two weeks, etc). The delta value of each variable was then compared between the responders and nonresponders using Wilcoxon's signed rank test. RESULTS: Sixty patients (54%) achieved an SVR. There were no significant differences between the responder and nonresponder groups for baseline variables. The delta value of ALT was the only significant marker in the prediction of an SVR. The mean +/- SD delta values for the ALT at week 2 of treatment were 71+/-92 U/L and 44+/-85 U/L for the responders and nonresponders, respectively (P<0.0046). At week 4, the values were 101+/-96 U/L and 84+/-100 U/L for the responders and nonresponders, respectively (P<0.0154). The decline was then calculated for the ALT as a percentage decrease from baseline: at weeks 2 and 4, the decreases were 64% and 66%, respectively, for the responders, and 43% and 41%, respectively, for the nonresponders. At week 2, the delta values for WBC count were found to be significant in predicting failure to achieve an SVR, with mean +/- SD delta values of 0.85 x 10(9)/L+/-1.48 x 10(9)/L and 1.53 x 10(9)/L+/-2.16 x 10(9)/L for the responders and nonresponders, respectively (P<0.0173). The same trend emerged at two weeks for neutrophils: 0.72 x 10(9)/L+/-1.33 x 10(9)/L for the responders and 1.02 x 10(9)/L+/-1.20 x 10(9)/L for the nonresponders (P<0.0150). The delta values were insignificant for hemoglobin, lowest hemoglobin values and platelets. CONCLUSIONS: The decline rates of ALT from baseline to week 2 and 4 of IFN and RBV combination therapy are good predictors of an SVR. A significant drop in WBC and neutrophil values is a predictor of failure to achieve an SVR. The hemoglobin, platelets and lowest hemoglobin values failed to predict an SVR.

Sudden infant deaths in sitting devices.

BACKGROUND: As episodes of decreased oxygenation levels have been recorded in premature infants placed in car seats, it is believed that these infants are at risk of life-threatening events and death. No data on the prevalence of such infant deaths are available. The aim of our study was to determine the incidence of sudden deaths in infants occurring in sitting devices in a whole population and to determine whether premature infants account for a disproportionate number of these deaths. DESIGN: Retrospective population-based cohort study reviewing all cases of sudden unexpected death in infants between birth and 1 year of age that occurred in the province of Quebec between January 1991 and December 2000. RESULTS: Of the 508 deaths reviewed, 409 were unexplained and 99 were explained after investigation. Seventeen deaths occurred in a sitting device, of which 10 were unexplained. There was no excess of premature infants dying. However, there was an excess of infants of less than 1 month of age found to have died in a sitting position in the unexplained death group. In addition, three infants who died in a sitting position had an increased risk of upper airway obstruction. CONCLUSION: Although very few deaths occurred in car seats, our results suggest that caution should be used when placing younger infants in car seats and similar sitting devices, whether the infants have been born prematurely or not. We also recommend that more attention be given to infants at increased risk of upper airway obstruction.

Exploring differences in response to treatment with peginterferon alpha 2a (40kD) and ribavirin in chronic hepatitis C between genotypes 2 and 3.

Chronic hepatitis C virus (HCV) infections with genotype 2 or 3 are associated with favourable sustained virologic response (SVR) rates. However, genotype 3 may respond less well. We reassessed all treatment-naive patients with genotype 2 and 3 participating in a large expanded-access, non-randomized, open-label trial, evaluating 180microg pegylated interferon (peg-IFN) alpha-2a (40kD) once weekly and 800 mg/day ribavirin for 24-48 weeks. Factors measured prior to initiation of antiviral therapy were considered in the multiple logistic regression model for predicting SVR. In total, 180 patients were analysed of which 72 (40%) were infected by genotype 2 and 108 (60%) genotype 3. The baseline characteristics between patients infected by genotype 2 or 3 were no different including the distribution of hepatic fibrosis stages by METAVIR score. Overall SVR was lower in those patients infected with genotype 3. The significant multivariate predictors of lack of SVR were hepatic fibrosis (P = 0.014) and genotype 3 (P = 0.030). The negative impact of cirrhosis (METAVIR score F4) on treatment response was more evident among subjects with genotype 3 than those with genotype 2 (P = 0.027). There is significant interaction between cirrhosis and genotype 3 leading to a poor antiviral response in such patients requiring an alternate management strategy. This finding should be confirmed in a larger population.

Mode of transmission, rather than the hepatitis C virus, as a major determinant of poor interpersonal relationships in patients with chronic hepatitis C.

BACKGROUND: Recent studies have demonstrated that patients with the hepatitis C virus (HCV) have significant neurocognitive impairment. OBJECTIVE: To assess whether chronic HCV infection impacts on patient marital status, living arrangement and employment. METHODS: The charts of patients with chronic hepatitis C and hepatitis B were reviewed. RESULTS: The mean (+/- SD) age of the 129 patients with the hepatitis B virus (HBV) was 46+/-15 years and that of the 428 patients with HCV was 48+/-15 years. Sixty-seven per cent of HBV patients were men, compared with 68% of HCV patients. Eighty per cent of HCV patients were Caucasian, compared with 44% of patients with HBV. The main modes of transmission were intravenous drug use (37%) and transfusion of blood products (37%) for HCV, compared with country of origin (76%) for HBV. There were no differences in marital status rates between HBV- and HCV-infected patients (HBV - married (73%), single (21%) and divorced (6%); and HCV - married (66%), single (23%) and divorced (10%); P=0.20). HCV patients lived alone more often than HBV patients (HBV - 13%, HCV - 22%; P=0.03). There was no difference in overall employment rate between HCV and HBV patients (81% versus 87%; P=0.15). Though there may not have been overall differences between HCV and HBV marital status and employment status, there were differences in the HCV subgroups. These subgroup differences were discovered in the multivariate analysis; mode of transmission was identified as the only predictor of the patients' marital status and employment status. CONCLUSIONS: The most important determinant of interpersonal relationships was the mode of transmission of the viral hepatitis rather than the type of viral infection: past intravenous drug users had lower level relationships.

Moderate aging does not modulate morphological responsiveness of the neuromuscular system to chronic overload in Fischer 344 rats.

The purpose of this investigation was to determine the effect of aging on neuromuscular adaptations to chronic overload. Eight young adult (8 months old) and eight aged (22 months old) Fischer 344 rats underwent unilateral synergist ablation to overload the plantaris and soleus muscles of that hindlimb and to provide control muscles from the contralateral hindlimb. Cytofluorescent staining and confocal microscopy were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs). Histochemical staining and light microscopy were used to assess adaptations of myofibers to chronic overload. Results demonstrate that NMJs of young adult and aged muscles did not undergo morphological remodeling as a result of 4 weeks of chronic overload. In contrast, myofibers of young and aged rats displayed significant (P<0.05), but similar hypertrophy ( approximately 18%) following that 4 week intervention. In both age groups, however, this hypertrophy was detected in the plantaris, but not the soleus. These data indicate that moderate aging (the equivalent of 65 years in human lifetime) does not modify the sensitivity of the neuromuscular system to chronic overload.

Moral distress in the neonatal intensive care unit: caregiver's experience.

BACKGROUND: The Neonatal Intensive Care Unit (NICU) can be ethically charged, which can create challenges for health-care workers. OBJECTIVE: To determine the frequency with which nurses and residents have experienced ethical confrontations and what factors are associated with increased frequency. DESIGN/METHODS: An anonymous questionnaire was distributed to nurses in a university center, a high-risk obstetric service, a maternity hospital NICU with 85% in-born patients and an outborn NICU, most of whose preterm admissions are those with surgical complications. Obstetric and pediatric residents in the four universities of the province also received the questionnaire, which included demographics, opinions regarding the gestational age threshold at which resuscitation of a premature infant with bradycardia was appropriate, knowledge of cerebral palsy (CP) outcomes (as an indicator of knowledge about long-term sequelae of prematurity) and questions about ethical confrontation in the NICU. RESULTS: Two hundred and seventy-nine caregivers participated (115 full time nurses and 164 residents). All the distributed questionnaires were completed. Frequent ethical confrontation was reported by 35% of the nurses and 19% of the residents. Among the nurses, moral distress differed significantly between work environments. Nurses working in an out-born NICU and obstetric nurses were more likely to overestimate CP prevalence (P<0.05). Nurses who overestimated CP rates had higher thresholds for resuscitation and were more likely to experience ethical confrontations. Of the residents, 60% were pediatric and 40% obstetric. All groups of residents frequently overestimated the prevalence of CP, and knowledge differed significantly by residency program (P<0.05). The residents who overestimated CP rates had higher thresholds for resuscitation, had more incorrect answers regarding prematurity outcomes and were less likely to have ethical confrontations. CONCLUSIONS: A large proportion of nurses and residents report frequent ethical confrontations. Many residents and nurses have limited knowledge of outcomes and high threshold for resuscitation. Ethical confrontation is more common among nurses with poor knowledge about outcomes, and less common in residents with poor knowledge about outcomes.

Elderly patients are at greater risk of cytopenia during antiviral therapy for hepatitis C.

UNLABELLED: The results of antiviral therapy for hepatitis C virus (HCV) have improved recently with the use of pegylated interferon (PEG-IFN)/ribavirin (RBV) combination therapy. At this point, most patients with chronic HCV remain untreated. Thus, it is anticipated that therapy will be more appealing and prescribed more broadly than in the past, including in patients considered marginal. AIM: To examine the effects of PEG-IFN-based antiviral therapy in elderly patients with chronic HCV. METHODS: The charts of patients treated with chronic HCV were reviewed. Patients were defined as elderly if they were 60 years of age or older. The control group consisted of patients younger than 60 years of age who were matched to the treated elderly patients based on sex, treating physician, prescribed treatment and intended prescribed treatment duration. The data recorded included end of treatment response, sustained virological response (SVR), adverse events, dose modification and withdrawal of therapy. RESULTS: Thirty of 147 (20.4%) elderly patients attending a hepatitis C clinic were treated. The average age of the elderly patients was 65+/-4 years. Forty-three per cent were men and 57% were women. Ten per cent received IFN monotherapy, 70% received a combination of IFN/RBV therapy and 20% received a combination of PEG-IFN/RBV therapy. The overall response rates in the elderly patients compared with the younger patients was 46.7% versus 65.8% (P=0.11) for end of treatment response and 33.3% versus 51.2% (P=0.13) for SVR. The rate of dose modification was 50% in the elderly patients compared with 29% in the control group (P=0.08). Therapy was discontinued in 53% of the elderly compared with 34% of younger patients (P=0.17). The younger patients reported more side effects than elderly patients; although, there were more laboratory abnormalities (anemia, thrombocytopenia and neutropenia) in the elderly patients during therapy than in the younger group (0.93 per patient versus 0.49 per patient, P=0.01). CONCLUSION: Elderly patients with chronic HCV can be treated successfully. However, they are more at risk to develop cytopenias while on treatment. In such patients, the close monitoring of blood counts is necessary. Larger studies are needed to confirm these findings and to determine whether SVR differs in this population.

Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy.

BACKGROUND: The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. AIMS: We evaluated the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. PATIENTS: Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. METHODS: Patients were retreated with peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (<50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. RESULTS: A total of 312 patients (212 non-responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non-responders and relapsers were similar although more non-responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non-responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. CONCLUSIONS: These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non-responders and relapsers by retreating with peginterferon alfa-2a (40KD) plus ribavirin.

Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and ribavirin in clinical practice.

BACKGROUND: Pegylated interferon alfa-2a (40 KD) plus ribavirin therapy induces sustained virological response rates up to 63% in randomized-controlled trials. AIM: To conduct a prospective open-label programme to examine the efficacy and safety of this therapy in routine clinical practice. METHODS: Treatment-naive patients with chronic hepatitis C received, at the discretion of the investigator, pegylated interferon alfa-2a 180 microg/week + ribavirin 800 mg/day for 24 or 48 weeks. In total, 508 patients were enrolled [334 non-cirrhotic; 174 cirrhotic (defined as stage F3 and F4)]. RESULTS: In genotype 1 patients treated for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and 34% in cirrhotics. Sustained virological response rates in genotype 2 or 3 non-cirrhotics were 79% (24 weeks) and 72% (48 weeks). Corresponding values for cirrhotic genotype 2/3 were 66% and 44%. The negative predictive value of an early virological response at week 12 was 94%. Predictive factors for sustained virological response on multivariate analysis were genotype (2/3 vs. 1), low viral load and degree of fibrosis. Rates of serious adverse events (

Increased and decreased activity elicits specific morphological adaptations of the neuromuscular junction.

The objective of this investigation was to compare the effects of decreased vs. increased activity on the neuromuscular system. Twenty-four young adult (7 weeks old) Sprague-Dawley rats were randomly assigned to three treatment groups (N=8/group). Increased activity was achieved by treadmill running for up to 1 h/day. Decreased activity was induced by muscle unloading via the hindlimb suspension model. Control animals engaged in normal weight bearing and ambulatory activity. At the end of the 10 week intervention period, animals were killed and soleus muscles were removed, quickly frozen, and examined using cytofluorescent (neuromuscular junctions) and histochemical (myofibers) procedures. Pre-synaptic morphology was quantified by measuring nerve terminal branching, and post-synaptic assessment was conducted by staining acetylcholine receptors at the endplate. Myofiber profiles of solei were compiled by determining fiber size (cross-sectional area) and fiber type composition. Results show that exercise training significantly (P