bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of once‐daily single generic fixed‐drug combination tablet of tenofovir, lamivudine and efavirenz among HIV‐infected Thais
Authors: Maek‐a‐Nantawat W , Avihingsanon A , Thainsanguankul W , Wongsabut J , Gorowara M , Ramautarsing R , Clarke A , Hsu D , Ruxrungtham K 
Published: November 2012

BackgroundGeneric fixed dose combinations (FDCs) of nucleoside reverse transcriptase inhibitors (NRTIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs) is commonly used in resource‐limited settings to increase adherence to lifelong treatment. However, the cumulative evidence of the long‐term complications, particularly mitochondrial toxicity of NRTIs, especially stavudine (or zidovudine), brings about widespread use of tenofovir (TDF). This study was aimed to assess the efficacy and safety of a FDC comprising 300 mg tenofovir (TDF), 300 mg LAM and 600 mg efavirenz (EFV).MethodsA Phase II open‐label clinical trial was conducted at HIV‐NAT, Thai AIDS Research Center, Thai Red Cross from April 2010 to December 2011. Patients were eligible to enroll if they were either: 1) on TDF, LAM and EFV as separate tablets, for at least 6 months with an undetectable viral load (= switch arm) or 2) treatment‐naïve. Safety profiles, including liver and renal functions, were assessed at baseline, weeks 4, 12, 24 and 48. In switch group, mid‐dose TDF plasma concentrations were measured by HPLC at baseline and week 4 after a switch to single FDC tablet.ResultsA total of 100 patients were enrolled (51 naïve). Median age was 34 years and 30% were female. The median baseline CD4 cell count (IQR) was 512 (395–620) cells/L and 232 (164–284) cells/L for the switch arm and ARV‐naïve group, respectively. The median (IQR) log10 HIV‐1 RNA for ARV‐naïve group was 4.9 (4.2–5.3) copies/mL. By ITT analysis, the proportion of cases with HIV RNA<50 copies/mL was 93% and 92% at week 24 and 48, respectively. Only 1 confirmed virological failure at week 12 with NNRTI‐resistant mutations (A98G, K103N, V118I, E138Q, Y181C). The reported 3 SAEs (severe headache, infective endocarditis, cervical dysplasia) were found and one was possibly related to the study drug. There were 49 mild to moderate efavirenz‐related central nervous system events, occurring in first few days‐weeks. There were no statistically significant changes on renal function and liver enzymes. Mean plasma concentrations of all three drugs in FDC met the acceptable target levels.ConclusionThe generic FDC of TDF/3TC/EFV was well tolerated and efficacious. Our findings lend support to the use of this generic FDC as first‐line antiretroviral therapy in resource limited settings.
HIV2 late presenters in an infectious disease ward: six years’ experience
Authors: Pires D , Zagalo A , Antunes F 
Published: November 2012

Purpose of the studyAbout a third of HIV‐infected patients in Europe present for care late in their disease. In 2010 a consensus was reached for a definition of late presentation, providing a new tool for research and acting. With regard to HIV2 infection this population has never been characterized.MethodsRetrospective analysis of the clinical records of all the HIV2‐infected patients who meet the inclusion criteria (those defined by the European Late Presenter Consensus working group: Late presentation of HIV infection: a consensus definition 1) admitted to our ward between January 2006 and December 2011. The patients were characterized according to epidemiological, clinical and immunologic status and outcome.Summary of resultsDuring the period analyzed, 15 HIV2 patients were late presenters. The mean age of the patients was 48 years old (although 53% were older than 50 years); 8 (53%) were men; 11 (73%) were of African origin. Heterosexual transmission was reported in three of the patients, in the remainder the transmission mode was not available. The mean TCD4 cell was 188 (range 27–339), with 8 (53%) with a CD4 count below 200 cells. Twelve (80%) of the patients fulfilled AIDS criteria. There were 3 deaths, corresponding to a mortality rate of 20%. The cause of death was disseminated tuberculosis in two cases and non‐Hodgkin's lymphoma in the third case.ConclusionsMost late presenters with HIV2 infection are of African origin, there is an even distribution between genders, their mean age is around 50 years old, more than half had a CD4 cell count below 200 and there was a 20% mortality rate. These patients pose challenges at various levels: their mortality rate is much higher than in the general HIV‐infected population and they are diagnosed very late, leading to a disproportionate increase in risk of transmission, morbidity and mortality.
TRANxITION 144‐week results: switching virologically stable HIV patients from immediate‐release nevirapine (NVP IR) to extended‐release NVP (XR)
Authors: Arastéh K , Drulak M , Guo J , Livrozet J , Orkin C , Quinson A , Ward D 
Published: November 2012

Purpose of the studyTRANxITION compared the efficacy and safety of switching virologically suppressed patients from NVP IR (200 mg BID) to NVP XR (400 mg QD) and demonstrated the non‐inferior efficacy of NVP XR in virologically suppressed patients. Here, post‐48‐week safety and efficacy results of patients initially randomized to NVP IR and allowed to switch to NVP XR after 48 weeks, were compared to patients on NVP XR throughout the study.MethodsTRANxITION was an open‐label, parallel‐group, non‐inferiority clinical trial where adult HIV‐1 patients receiving NVP IR plus a fixed‐dose NRTI combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV), with undetectable viral loads (VL) were initially randomized (2:1) to NVP XR or NVP IR. After week 48, patients initially randomized to NVP IR were allowed to switch to NVP XR. Primary endpoint was continued virologic suppression (VL<50 copies/mL) at week 24. Secondary endpoints included long‐term follow‐up at 48 and 144 weeks.Summary of resultsAt week 48, proportions of patients with virologic response (LLOQ = 50 copies/mL TaqMan, FAS) were 88.5% (131/148) NVP IR BID arm, and 88.8% (262/295) NVP XR QD, with an observed difference of 0.3% (95% CI −6.1, 6.7). Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups at week 48, 6.4% (19/295) vs. 6.1% (9/148) respectively, although serious AEs were slightly higher in the NVP XR group (10.2%, 30/295, vs. 8.1%, 12/148 for the NVP‐IR group). After week 48, all but 13 patients in the NVP IR arm switched to NVP XR. At week 144, proportions of patients with virologic response were 115/121 (95.0%, patients switching from IR to XR after week 48 [IRpost48XR]), and 238/250 (95.2%, patients on XR throughout [XRpost48]). DAIDS grade 3 and 4 events were similar for both post‐week‐48 XR groups at week 144, with (10/130, 7.7%, [IRpost48XR] vs. (31/276, 11.2% [XRpost48]), while serious AEs were higher in the XRpost48 patients (54/276, 19.6% vs. 17/130, 13.1% for the IRpost48XR group).ConclusionsNVP XR QD resulted in continued virologic suppression at weeks 48 and 144. While fewer patients remained in the study post‐week 48, both XR groups had high virologic response rates. Rates of serious AEs were modestly higher than seen at week 24 in both post‐week‐48 XR arms up to week 144, most likely due to the open‐label design of the study.
Reasons for antiretroviral treatment changes in Spanish HIV 1 patients in 2011: SWITCH AUDIT study
Authors: Tasias M , Viciana P , Deig E , Arranz J , Pasquau J , Vera F , Pujol E , Vergas J , Bernardino J , Pedrol E 
Published: November 2012

BackgroundUntil the past decade, immune/viral failure was the main reason for antiretroviral treatment changes. After HAART generalization the management of antiretroviral treatment toxicities was the most prevalent reason for treatment modification. Today, with the advent of new more potent and less toxic drugs as well as more convenient combinations may have changed the situation. We aim to describe the main reasons that today leads to ART changes in HIV+ patients in Spain in the current clinical practice.MethodsMulticentre, national, cross‐sectional epidemiological study. Eligible patients had to be HIV+, >18 years old and under current ART that was going to be changed by any reason. Patients did sign inform consent. The study consisted in a single visit (change of treatment) in which data on social and demographic characteristics, HIV disease and ARV treatment were collected.Results349 patients were included; mean age: 43.7±8.9 y, 70.5% male and 89.1% Caucasian. Main transmission categories were IVDU (36.4%) and heterosexual (36.4%). Mean time from HIV diagnosis was 11.3±7.6 y. 59.5% were CDC C category. Median CD4 nadir was: 155 cells/mm3 and median CD4 at the time of switching was 467 cells/mm3. 64.1% had undetectable viral load (<50 copies/ml); 40.1% had HCV or HBV co‐infection. Main reasons for treatment change were simplification (40.2%), treatment toxicities (29.2%) and immune/viral failure (20.1%). No significant correlations were found between reason for changing treatment and age, gender, race, nationality and level of education. Simplification was significantly the main reason both in employed and unemployed patients (p<0.01).ConclusionsCurrently, treatment simplification was the most prevalent reason for a change of treatment even in advanced lines of treatment. This is so probably because of the advent of ARV drugs that are more potent and effective, with less toxicity and more convenient. Treatment simplification was significantly the first cause of treatment change in those patients who are currently working or seeking for a job. This highlights the need for simpler regimens that can adapt to an active life.
Switch from efavirenz to nevirapine, with full dose after one week: efficacy, safety and pharmacokinetics
Authors: Curran A , Crespo M , van den Eynde E , Perez M , Burgos J , Navarro J , Falcó V , Villar del Saz S , Ocaña I , Ribera E 
Published: November 2012

Purpose of the studyIn a prior study in patients switching from efavirenz (EFV) due to neurologic side effects, we compared nevirapine (NVP) full dose (200 mg twice‐daily) from the beginning to the standard dosage (200 mg once‐daily for two weeks and then increase to 200 mg twice‐daily) [1]. Adequate concentrations were seen with the experimental arm but with a trend towards higher toxicity, with 25% of patients having to stop NVP due to rash or hepatitis. Our hypothesis is that NVP 200 mg daily for 1 week and then increasing it to 200 mg twice‐daily will achieve adequate plasmatic concentrations with better tolerability.MethodsPatients taking an EFV‐based regimen were offered to switch to NVP without changing the backbone. Patients received NVP 200 mg once‐daily for 1 week and 200 mg twice‐daily thereafter. EFV and NVP plasma trough levels were determined at days 0, 3, 7, 14, 30 and 90. Blood tests were performed at each visit and AE recorded. Chi‐squared and Fisher exact test were used for qualitative variables and Mann‐Whitney U and Wilcoxon signed rank tests for quantitative variables.Summary of results22 patients were included, 73% male, median age 48 years, median CD4 569 cell/mm3, all with CV <25 copies/mL and 41% had HCV co‐infection. Reasons for switch were CNS symptoms in 50%, dyslipidemia in 46% and pregnancy desire in 4%. Backbone was TDF+FTC in 73% and ABC+3TC in 27%. Median NVP trough concentrations were 2.2, 2.7, 4.3, 4.5 and 5.5 µg/mL at 3, 7, 14, 30 and 90 days, respectively. 35% of patients had NVP plasma trough levels >3 µg/mL at day 7 and 88% at day 14. EFV concentrations were subtherapeutic (<1 µg/mL) at day 7 and undetectable in all but one patient at day 14. There was a significant increase in GGT (+22 mg/dL, p=.013) and significant decreases in total cholesterol (−16 mg/dL, p=.035) and triglycerides (−50 mg/dL, p=.005) after 3 months. In the first month, two patients had to stop NVP due to rash and one due to rash and hepatitis. There was no correlation between plasma concentrations and rash or hepatitis. There were no virologic failures.ConclusionsNevirapine concentrations were adequate when dose was increased to 200 mg twice daily after one week, maintaining virologic efficacy and with good tolerability.
Nanostructured Crystalline Comb Polymer of Perylenebisimide by Directed Self‐Assembly: Poly(4‐vinylpyridine)‐pentadecylphenol Perylenebisimide
Authors: Narayan Rekha , Kumar Prashant , Narayan K. S. , Asha S. K. 
Published: November 2012

AbstractWell defined nanostructured polymeric supramolecular assemblies are formed when an asymmetric perylenebisimide substituted with ethylhexyl chains on one end and functionalized with 3‐pentadecylphenol at the other termini (PDP‐UPBI) is complexed with poly(4‐vinylpyridine) (P4VP) via a non‐covalent specific interaction such as hydrogen‐bonding. The resulting P4VP(PDP‐UPBI)n complexes are fully solution processable. The bulk structure and morphologies of the supramolecular film studied using small angle and wide angle X‐ray scattering reveals highly crystalline nature of the complex. Thin film morphology of the 1:1 complex analyzed using transmission electron microscopy shows uniform lamellar structures in the domain range of 5–10 nm. A clear trend of improved electrical parameters in P4VP(PDP‐UPBI) system compared to pristine (PDP‐UPBI) is observed from space charge limited current measurements. In short, a simple and facile method to obtain spatially defined organization of n‐type semiconductor perylenebisimide molecules using hydrogen bonding interactions with P4VP as the structural motif is showcased herein.
Metal Nanocrystal‐Embedded Hollow Mesoporous TiO2 and ZrO2 Microspheres Prepared with Polystyrene Nanospheres as Carriers and Templates
Authors: Jin Zhao , Wang Feng , Wang Feng , Wang Junxin , Yu Jimmy C. , Wang Jianfang 
Published: November 2012

AbstractNoble metal nanocrystals with different shapes and compositions are embedded in hollow mesoporous metal oxide microspheres through an ultrasonic aerosol spray. Polystyrene (PS) nanospheres are employed simultaneously as a hard template to create hollow interiors inside the oxide microspheres and as the carrier to bring pregrown metal nanocrystals, including Pd nanocubes, Au nanorods, and Au core/Pd shell nanorods, into the oxide microspheres. Calcination removes the PS template and causes the metal nanocrystals to adsorb on the inner surface of the hollow oxide microspheres. The catalytic performances of the Pd nanocube‐embedded TiO2 and ZrO2 microspheres are investigated using the reduction of 4‐nitrophenol as a model reaction. The presence of the mesopores in the oxide microspheres allows the reactant molecules to diffuse into the hollow interiors and subsequently interact with the Pd nanocubes. The embedding of the metal nanocrystals in the hollow oxide microspheres prevents the aggregation of the metal nanocrystals and reduces the loss of the catalyst during recycling. The Pd nanocube‐embedded ZrO2 microspheres are found to exhibit a much higher catalytic activity, a much larger catalytic reaction rate, and a superior recyclability in comparison with a commercial Pd/C catalyst. This preparation approach could potentially be utilized to incorporate various types of mono‐ and multimetallic nanocrystals with different sizes, shapes, and compositions into hollow mesoporous oxide microspheres. Such a capability can facilitate the studies of the catalytic properties of various combinations of metal nanocrystals and metal oxide supports and therefore guide the design and creation of high‐performance catalysts.
Membrane‐Directed High Bactericidal Activity of (Gold Nanoparticle)–Polythiophene Composite for Niche Applications Against Pathogenic Bacteria
Authors: Adhikari Manab Deb , Goswami Sudeep , Panda Biswa Ranjan , Chattopadhyay Arun , Ramesh Aiyagari 
Published: November 2012

AbstractThe use of nanoscale materials as bactericidal agents represents a novel paradigm in the development of therapeutics against drug‐resistant pathogenic bacteria. In this paper the antimicrobial activity of a water soluble (gold nanoparticle)–polythiophene (AuNP‐PTh) composite against common bacterial pathogens is reported. The nanocomposite is broad‐spectrum in its bactericidal activity and exhibits a membrane‐directed mode of action on target pathogens. The therapeutic potency of AuNP‐PTh is demonstrated by experiments which reveal that the nanocomposite can breach the outer membrane defense barrier of Gram‐negative pathogens for subsequent killing by a hydrophobic antibiotic, inhibit the growth of model gastrointestinal pathogens in simulated gastric fluid, and significantly eradicate bacterial biofilms. The high bacterial selectivity and lack of cytotoxicity on human cells augers well for future therapeutic application of the nanocomposite against clinically relevant pathogenic bacteria.
A Frontier Molecular Orbital Theory Approach to Understanding the Mayr Equation and to Quantifying Nucleophilicity and Electrophilicity by Using HOMO and LUMO Energies
Authors: Zhuo Lian‐Gang , Liao Wei , Yu Zhi‐Xiang 
Published: November 2012

AbstractObtaining the reactivities (such as nucleophilicities and electrophilicities) of molecules is of fundamental importance in chemistry. Mayr and co‐workers have developed the Mayr equation, which has been widely used to quantify nucleophilicity and electrophilicity. Herein we propose a theoretical understanding of the Mayr equation based on frontier molecular orbital (FMO) theory and the Eyring equation of the transition state theory, showing that the nucleophilicity of a molecule is related to the energy of this molecule’s highest occupied molecular orbital (HOMO), while the electrophilicity is related to the energy of the lowest unoccupied molecular orbital (LUMO) of the electrophile. Consequently, we propose a new approach by combining the FMO theory and the Mayr equation to predict the reactivities of new molecules. Ab initio calculation results support these linear relationships between LUMO energies and the Mayr electrophilicities (E) and the HOMO energies and the Mayr nucleophilicities (N) for sets of electrophiles and nucleophiles, respectively. For each set of nucleophiles or electrophiles, their different reactivities are mainly controlled by the electronic effects of the substituents. If other effects, such as sterics, affect reactivity for a set of electrophiles or nucleophiles, the linear relationships between HOMO levels and N values and LUMO levels and E values cannot be secured. The present approach through combining Mayr equation and the quantitative FMO theory suggests that the Mayr nucleophilicity or electrophilicity of a new molecule, which could be an intermediate of a reaction, unstable reactant, or a hypothetical reactive species, can be obtained through ab initio calculations of the frontier molecular orbital energies, and this will greatly expand the data sets of Mayr nucleophilicities and electrophilicities.
Performance of surface‐modified poly(etherimide) hollow‐fiber membranes in a membrane gasLiquid contacting process with response surface methodology
Authors: Bakeri G. , Rana D. , Ismail A. F. , Matsuura T. , Ghaee A. 
Published: November 2012

AbstractA surface‐modifying macromolecule (SMM) was used to enhance the surface hydrophobicity of poly(ether imide) (PEI) hollow‐fiber membranes. The membranes were used for a membrane contactor to absorb CO2 with water. The effects of three hollow‐fiber fabrication parameters, that is, the PEI concentration in the casting dope, the SMM concentration in the casting dope, and the air gap, on the liquid entry pressure of water (LEPw) and the absorption rate (AR) of CO2 were investigated with response surface methodology. The model developed for LEPw satisfied the criterion for regression but had a low goodness of fit. The model predicted that LEPw would increase with PEI (weight percentage) but decrease with air gap. Furthermore, it showed a minimum value with a change in SMM (weight percentage). The model developed for the AR of CO2 had meaningful statistical parameters and was accurate; this indicated that interactions existed between the fabrication parameters on the AR of CO2. The performance of one of the fabricated membranes was compared with in‐house and commercially made hydrophobic membranes in terms of the AR of CO2 with distilled water as an absorbent on the lumen side and pure CO2 on the shell side. The comparison showed a superior CO2 flux in the surface‐modified membrane; for example, at a liquid velocity of 0.4 m/s, the surface‐modified membrane exhibited a 416% higher AR than the commercial membrane contactor (Celgard MiniModule 0.75X5) made of polypropylene. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Preparation and characterization of ethyl menthane carboxamide microcapsules using PLA
Authors: Jincheng Wang , Xinyu Dong 
Published: November 2012

AbstractUsing polylactic acid (PLA) as wall and ethyl menthane carboxamide (EMC) as core substance, microencapsulated EMC (MEMC) agents were prepared based on solvent evaporation method. The structure and morphology of MEMC were analyzed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and laser particle size analyzer. The MEMC agents had a mean diameter of about 10–20 μm. Moreover, the thermal properties of the MEMC agents were measured by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The melting point and thermal stability were improved due to the encapsulation of PLA resin. In addition, polyvinyl alcohol (PVA) and PLA concentration, stirring rate, and oil/water ratio were investigated for their effects on the particle size. As demonstrated by experimental results, the diameters of the microcapsules decreased with increasing stirring rate and oil/water ratio, and increased with increasing PLA concentration. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Hydrolysis and thermal degradation of poly(L‐lactide) in the presence of talc and modified talc
Authors: Jo Mi‐Yeong , Ryu Yeon Jong , Ko Jun Hee , Yoon Jin‐San 
Published: November 2012

AbstractTalc and talc modified with trimethoxy(octadecyl)silane (O‐talc) were melt compounded with poly (L‐lactide) (PLA). The crystallization behavior, tensile properties, and impact strength of the PLA composites were examined before and after the incorporation of talc and O‐talc. The molecular weight of PLA in the PLA composites was measured as a function of the hydrolysis time and temperature. The effect of talc and O‐talc on the thermal stability of PLA was examined and quantified by the activation energy of thermal degradation and the integral procedural decomposition temperature value determined from the corresponding thermo‐gravimetric analysis weight loss profiles. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013