Background & Aims:
Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus (HBV). This randomized, dose-ranging, phase 2 study compared the ...efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients.
Methods:
Hepatitis B e antigen (HBeAg)-positive and -negative patients (n = 182), viremic despite lamivudine treatment for ≥24 weeks or having documented lamivudine resistance substitutions, were switched directly to entecavir (1.0, 0.5, or 0.1 mg daily) or continued on lamivudine (100 mg daily) for up to 76 weeks.
Results:
At week 24, significantly more patients receiving entecavir 1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine (13%;
P < .0001). Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point (
P < .01). After 48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46, and 2.85 log
10 copies/mL on entecavir 1.0, 0.5, and 0.1 mg, respectively, significantly higher than 1.37 log
10 copies/mL on lamivudine. Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0, 0.5, and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%). One virologic rebound due to resistance occurred (in the 0.5-mg group).
Conclusions:
In HBeAg-positive and HBeAg-negative lamivudine-refractory patients, treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels. One milligram of entecavir was more effective than 0.5 mg in this population.
Peginterferon alfa-2a plus ribavirin improves sustained virological responses compared with interferon alfa-2b and ribavirin, or peginterferon alfa-2a alone in chronic hepatitis C. We examined the ...impact of these treatments on health related quality of life (HRQOL).
Patients (
n=1121) were randomized to peginterferon alfa-2a weekly plus ribavirin or placebo, or interferon alfa-2b thrice weekly plus ribavirin. HRQOL was assessed with the SF-36 Health Survey and Fatigue Severity Scale (FSS).
Patients receiving peginterferon alfa-2a plus ribavirin reported better HRQOL than those receiving interferon alfa-2b plus ribavirin. These differences were statistically significant for three SF-36 domains and both FSS scores (
p<=0.05). Patients receiving peginterferon alfa-2a plus placebo had the least impairment; adding ribavirin significantly decreased five domains of the SF-36 and both FSS scores. Sustained virological response was associated with improvement at follow-up on all SF-36 and FSS scores.
The effects of combination therapy on HRQOL and fatigue are less with peginterferon alfa-2a plus ribavirin than interferon alfa-2b plus ribavirin. Each medication in combination therapy with interferon and ribavirin, affects patients' quality of life differently. Understanding the relationship of specific therapeutic options to HRQOL may help physicians minimize the impact of therapy on HRQOL.
The study of nuclear cluster states bound by valence neutrons is a field of recent large interest. In particular, it is important to study the pre-formation of α-clusters in α-conjugate nuclei and ...the dynamical condensation of clusters during nuclear reactions 1–5. The NUCL–EX collaboration has recently initiated an experimental campaign of exclusive measurements of fusion–evaporation reactions with light nuclei as interacting partners. In collisions involving light systems, the low expected multiplicity of fragments increases the probability of achieving a quasi-complete reconstruction of the event. In particular the formation and decay modes of an excited 24Mg system have been studied through two different reactions, 12C (95 MeV)+ 12C and 14N (80.7 MeV)+ 10B, which have been used to produce fused systems with nearly the same mass and excitation energy (~60 MeV). In particular, even the de-excitation of the Hoyle state in 12C have been studied, both in peripheral (projectiles de-excitation) and in central collisions (six α-particles channel). Moreover, a research campaign studying pre-equilibrium emission of light charged particles and cluster properties of light and medium-mass nuclei has been carried out. For this purpose, a comparative study of the three nuclear systems 18O+28Si, 16O+30Si and 19F+27Al has been recently studied using the GARFIELD+RCo 4π setup 6. The experimental data are compared with the predictions of simulated events generated with the statistical models (GEMINI++ and HFl) and through dynamical models like Stochastic Mean Field (SMF) and Antisymmetrized Molecular Dynamics (AMD) and filtered with a software replica of our apparatus in order to take into account the experimental conditions.
To investigate the impact of pregnancy on human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus type 1 (HIV-1)-infected women, the HHV-8 DNA presence and load were analyzed in ...peripheral blood mononuclear cells (PBMCs) and cervicovaginal secretions (CVSs) from 15 pregnant women coinfected with HIV-1 and HHV-8. HHV-8 detection was analyzed in relation to anti-HHV-8 antibodies and HIV-1-related parameters. Nucleotide sequence analysis of an ORFK1 hypervariable region of the HHV-8 strains was performed. HHV-8 was detected in maternal PBMCs (5/15 women) from the second trimester and in CVSs (5/15 women) mainly from the third trimester. The HHV-8 load significantly increased late in pregnancy in both maternal compartments and was associated with a significant increase in HIV-1 shedding in the genital tract. Antilytic antibodies were significantly more common in HHV-8 DNA-positive women. An elevated HHV-8 load was found in the PBMCs of an infant born to a mother with large amounts of HHV-8 in both compartments at delivery. Different ORFK1 subtypes were found in maternal samples, whereas the same subtype was identified in the mother-child pair. These data suggest that pregnancy may induce HHV-8 replication in HIV-1-infected women. An augmented HHV-8 load may, in turn, influence mother-to-child transmission, since one of the HIV-1-infected mothers with HHV-8 reactivation transmitted her ORFK1 subtype to the infant, who showed a high level of HHV-8 viremia indicative of a primary infection. This finding documents for the first time the perinatal transmission of a specific HHV-8 subtype. Vertical transmission may thus play a role in HHV-8 spread also in areas of subendemicity among HIV-1-infected women.
The consent process is complex and somewhat of an artform for procedural specialties. Readability of consent forms was objectively examined. The objective readability of the texts exceeds local and ...international recommendations.
Background
The aim of this study was to conduct a readability analysis on both patient take‐home information and consent forms for common foot and ankle procedures. Our hypothesis was that the objective reading skills required to read and comprehend the documentation currently in use would exceed the recommendations in place by both national and international bodies.
Methods
The current Queensland Health consent forms are divided into specific subsections. The readability of consent form subsections C and G (sections containing detailed information on risks of the procedure and pertaining to informed patient consent specifically) and patient take‐home information (provided as take‐home leaflet from the consent form which is procedure specific) was assessed by an online readability software program using five validated methods calculated by application of the algorithms for (i) Flesch–Kincaid grade level, (ii) the SMOG (Simple Measure of Gobbledygook), (iii) Coleman–Liau index, (iv) automated readability index and the (v) Linsear Wriste formula.
Results
The mean ± standard deviation reading grade level of risk (section C), grade level of patient consent (section G) and grade level for procedure‐specific take‐home patient information were 8.7 ± 0.9, 11.6 ± 1.2 and 7.5 ± 0.2, respectively.
Conclusion
The readability of sections C and G of the Queensland Health consent form exceeds the recommendations by national and international bodies, but the patient take‐home information appears suitable. Consideration should be given to lower the reading grade level of patient consent forms to better reflect the reading grade of the Australian population.
Several reports have indicated that patients with low CD4+ cell count could be at a higher risk for arterial lesions or cardiovascular disease (CVD). Recently, current use of abacavir has been ...associated with an excess risk of CVD. High sensitivity-C-reactive protein and interleukin-6 levels were high for patients receiving the drug. These data lead to the hypothesis that alternative mechanisms may be at work other that those linked to lipid changes and "classic" risk factors for atheroma. Consequently, we investigated the ultrasound characteristics of carotid plaques in HIV-positive patients comparing the results with those obtained from patients affected by atherosclerosis and patients with arteritis. The study population included 110 HIV-positive patients and 91 HIV-negative patients (61 atherosclerotic patients and 30 with arteritis). All patients were subjected to ultrasonography of the epi-aortic vessels. When compared to atherosclerotic patients, there was a significantly higher proportion of HIV-positive patients with hypoechogenic and homogeneous lesions, uniform in their parietal and endoluminal portions with a smooth or slightly irregular surface. No significant differences were found between HIV-positive and arteritis patients. This ultrasonographic study confirms that inflammatory mechanisms could play a major role in the onset of vascular damage in HIV-1 positive patients.
The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside ...reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed.
Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade > or =III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity.
Incidence of grade > or =III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade > or =III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome.
Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine amino-transferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought ...to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study.
Methods
Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up.
Results
Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%,
p
< 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (
p
< 0.001).
Conclusions
Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.
Background
SGLT2 inhibitors have been shown to reduce hospitalisation in patients with chronic heart failure (CHF). The cardioprotective mechanisms of gliflozins however have not been fully ...elucidated. The aim of this study was therefore to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in patients with diabetes and HF.
Methods
Seventy‐eight patients with diabetes and CHF were enroled in the study and followed up; 38 started treatment with SGLT2i, while the remaining 40 continued their previous antidiabetic therapy. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2i.
Results
After 3 months of therapy with SGLT2i, echocardiographic parameters assessing both left and right ventricular dimensions and function were found as significantly improved in patients switching to SGLT2i than control group: LVEF (45 ± 9% vs. 40 ± 8%, p < 0.001), LVEDD (54 ± 6.5 vs. 56 ± 6.5 mm, p < 0.01), GLS (−13 ± 4% vs. −10 ± 3%, p < 0.001), TAPSE (21 ± 3 vs. 19 ± 3 mm, p < 0.001), RV S' (12.9 ± 2.5 vs 11.0 ± 1.9 cm/sec, p < 0.001) and PAsP (24 ± 8 vs. 31 ± 9 mmHg, p < 0.001). Also mitral (1.0 ± 0.5 vs. 1.3 ± 0.5, p < 0.01) and tricuspid regurgitation (1.0 ± 0.5 vs. 1.3 ± 0.5, p < 0.01) improved after SGLT2i therapy. Changes were not statistically significant in patients not treated with SGLT2i (p n.s. in all cases).
Conclusions
In a real‐world scenario, treatment with SGLT2i in patients with CHF and diabetes is associated with an improvement in both left and right ventricular function assessed at echocardiography. These data may explain potential anti‐remodelling effects of gliflozins.
Chronic heart failure (CHF) is characterized by higher rates of atrial fibrillation (AF) and endothelial dysfunction (ED). First line anticoagulant therapy in AF is represented by direct oral ...anticoagulants (DOACs); several patients, however, are still treated with vitamin-K inhibitors. The use of DOACs is associated in previous studies with an improved vascular function.
We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with CHF and AF shifting from warfarin to DOACs.
Forty-three consecutive outpatients were enrolled in the study. FMD was assessed at baseline and after 4 months. Patients were compared according to AC therapy.
After the first measurement of FMD, 18 patients “switched” to DOACs because of poor compliance to warfarin therapy or time in therapeutic range, 19 patients continued to use DOACs, 6 warfarin.
“Switched” patients to DOACs therapy showed an improved FMD (19.0 ± 6.6% vs 3.8 ± 1.3%, p < 0.0001); C-reactive protein (CRP) levels decreased in “switched” patients from 1.4 ± 0.5 to 1.0 ± 0.7 mg/dl (p < 0.05). FMD and CRP changes were not significant in patients who did not changed anticoagulant therapy. In switched patients, changes in CRP levels were proportional to FMD changes (r = −0.50, p < 0.05). Shifting from warfarin to DOACs was significantly correlated to improved FMD levels even at multivariable analysis (p < 0.05).
Switch from warfarin to DOACs in patents with CHF and AF was associated in an observational non randomized study with an improved endothelial function. Changes in FMD values were related to changes in CRP levels.
•Switch from warfarin to DOACs in patients with CHF and AF was associated in an observational non randomized study with an improved endothelial function.•Changes in FMD values were related to changes in CRP levels.•Anticoagulation with DOACs may be preferable over warfain in patients with CHF and AF.
PDF
