bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Australian rise of esomeprazole—was expenditure on samples a contributor?
Authors: Kyle Gregory J. , Nissen Lisa M. , Tett Susan E. 
Published: December 2008

AbstractBackgroundAdministrative data from the Australian Pharmaceutical Benefits Scheme (PBS) showed rapid growth of esomeprazole dispensing when it was launched. Australia has universal prescription medicine coverage (the PBS), which included esomeprazole from August 2002. Free samples of new medicines are commonly provided to doctors.ObjectivesTo determine if a relationship exists between marketing expenditure on samples and the dispensing rate for esomeprazole in Australia between June 2002 and September 2006.MethodsQuarterly sample expenditures at product/brand level for proton pump inhibitors (PPIs) for Australian general practitioners were obtained for July 2002 to September 2006. Corresponding PBS dispensing data were obtained for all PPIs and converted to defined daily dose (DDD)/1000 population/day. Spending on samples was calculated as dollars per dispensed prescription and plotted against time on the Australian market.ResultsTotal PPI usage increased from 34.2 to 50.8 DDD/1000 population/day over the study period. Expenditure on samples per dispensed prescription was higher when a PPI was new on the market and diminished over 5–6 years to a relatively constant level. The rapid decline in this ratio was demonstrated by a case study following esomeprazole from launch in Australia for almost 5 years clearly demonstrating the initial investment to drive sales.ConclusionA relationship appears to exist between expenditure on esomeprazole samples and its usage in Australia. A high initial investment was followed by a rapid reduction in cost per prescription dispensed, predominantly due to growth in market share. This trend was consistent with other PPIs. Copyright © 2008 John Wiley & Sons, Ltd.
Medication adherence, first episode duration, overall duration and time without therapy: the example of bisphosphonates
Authors: Roughead Elizabeth E. , Ramsay Emmae , Priess Kym , Barratt John , Ryan Philip , Gilbert Andrew L. 
Published: December 2008

AbstractPurposeWe aimed to determine the duration of first episode of therapy and overall therapy as well as time without treatment for bisphosphonates.MethodsData were extracted from Department of Veterans' Affairs (DVA) dataset for those with at least one dispensing for a bisphosphonate between April 2001 and April 2007. Episodes of use were determined as the number of treatment days between the first and last prescription plus 35 days once a dispensing gap of 105 days had been reached, or where no treatment gaps were recorded, the study end date. Kaplan–Meier analyses were undertaken for the first episode of use, overall duration and time without treatment.ResultsWhen considering only the duration of first episode, median bisphosphonate use was 1.19 years. The median duration extended to 3.27 years when all episodes of use were considered. Overall, 52.0% of subjects reached at least 3 years of treatment and 66.5% of existing users had a duration of at least 3 years. Median time without treatment was 1.65 years. Overall, 81% of the cohort had enough medicine dispensed to be considered adherent throughout their duration of use.ConclusionOver 50% of subjects and 66% of existing users had duration consistent with the minimum recommended. Adherence within an episode was high. The focus for improving duration of bisphosphonate use should be on reducing the time without treatment, rather than adherence at the time of use. Studies assessing only the first episode of use in new users of medicines may underestimate duration. Copyright © 2008 John Wiley & Sons, Ltd.
Frequency of ill‐founded off‐label prescribing in Dutch general practice
Authors: Gijsen Ronald , Jochemsen Hadassa , van Dijk Liset , Caspers Peter 
Published: December 2008

AbstractPurposeThe aim of this study is to quantify the extent of ill‐founded off‐label drug prescriptions in Dutch general practice. The study is based upon information on both the prescription itself and the patient's medical history.MethodsIn total, 48 combinations of drugs and off‐label indications were selected from a list of 477 known off‐label combinations. These 48 combinations were considered as ill‐founded since pharmacotherapeutic handbooks or clinical practice guidelines did not provide evidence for their efficacy and safety. They were considered to be relevant for investigation in general practice. We used a nationally representative information network of 85 general practices in the Netherlands. By using information on the patients' diagnoses and medication in the period before and after the prescription, we were able to exclude non‐conclusively off‐label prescriptions.ResultsTwenty‐one of the selected 48 off‐label combinations did not occur in Dutch general practice. The drugs with the highest proportion of ill‐founded off‐label prescriptions were betahistine (26.7%), celecoxib (16.3%) and etoricoxib (12.5%). In total, 18.2% of the prescriptions, which were initially assessed as ill‐founded off‐label, were re‐evaluated as on‐label, after considering the patient's medical history.ConclusionsIll‐founded off‐label prescribing in Dutch general practice is limited for 48 relevant combinations of drugs and off‐label indications. In order to overcome limitations in registration databases, it is useful to look at as much information as possible—for example, co‐medication and co‐morbidity—when determining off‐label prescribing. Studying ill‐founded off‐label prescribing should be performed on a day‐to‐day basis, especially for recently introduced drugs. Copyright © 2008 John Wiley & Sons, Ltd.
Hemorrhagic stroke associated with antidepressant use in patients with depression: does degree of serotonin reuptake inhibition matter?
Authors: Chen Yan , Guo Jeff J. , Patel Nick C. 
Published: December 2008

AbstractObjectiveThis study aimed to determine whether the degree of serotonin (5‐HT) reuptake inhibition affects risk of hemorrhagic stroke associated with antidepressant use in patients with depression.MethodA population‐based, nested case‐control study was performed using a managed care medical claims database. Ninety two depressed patients with a diagnosis of hemorrhagic stroke were identified and matched with 552 controls by age, sex, and year of index date of depression (IDD). Diagnoses of depression, hemorrhagic stroke, and other medical comorbidities were identified using ICD‐9 codes. Antidepressants were classified as high, medium, or low reuptake inhibition based on their affinities for the 5‐HT reuptake transporter, determined using their respective equilibrium dissociation constants (KD; high: KD < 1 nM; medium: 1 ≤ KD < 10 nM; low: KD ≥ 10 nM). Conditional logistic regression analysis was performed to estimate the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of the risk of hemorrhagic stroke.ResultsCompared to non‐users of antidepressants, risk of hemorrhagic stroke did not significantly differ between patients who had ever used antidepressants with high (OR = 0.82; 95% CI = 0.44–1.55), medium (OR = 0.93; 95% CI = 0.37–2.31), or low (OR = 0.38; 95% CI = 0.11–1.41) 5‐HTT inhibition.ConclusionRisk of hemorrhagic stroke associated with antidepressant use may not be related to an antidepressant's degree of 5‐HT reuptake inhibition. Given the limitations of this study, additional studies are needed to confirm these findings. Copyright © 2009 John Wiley & Sons, Ltd.
Miscibility, morphology and thermal properties of poly(para‐dioxanone)/poly(D,L‐lactide) blends
Authors: Bai Wei , Zhang Zhi‐ping , Li Qing , Chen Dong‐Liang , Chen He‐Chun , Zhao Na , Xiong Cheng‐Dong 
Published: December 2008

AbstractBACKGROUND: Poly(para‐dioxanone) (PPDO) is a biodegradable polyester with excellent biodegradability, bioabsorbability, biocompatibility and mechanical flexibility. However, its high cost and relatively fast degradation rate have hindered the development of commercial applications. Blending with other polymers is a simple and convenient way of modifying the properties of aliphatic polyesters. Poly(D,L‐lactide) (PDLLA) is another polyester that has been extensively studied for biomedical applications due to its biocompatibility and suitable degradation rate. However, to our knowledge, blends of PPDO/PDLLA have not been reported in the literature.RESULTS: A series of biodegradable polymers were blended by solution co‐precipitation of PPDO and PDLLA in various blend ratios. The miscibility, morphology and thermal properties of the materials were investigated. DSC curves for all blends revealed two discrete glass transition temperatures which matched the values for pure PPDO and PDLLA. SEM images of fracture surfaces displayed evidence of phase separation consistent with the DSC results. The contact angles increased with the addition of PDLLA.CONCLUSION: PPDO/PDLLA blends exhibit two distinct glass transition temperatures that remain nearly constant and correspond to the glass transition temperatures of the homopolymers for all blend compositions, indicating that blends of PPDO and PDLLA are immiscible. Images of the surface obtained using SEM were also suggestive of a two‐phase material. The crystallinity of the PPDO phase in the blends was affected by the PDLLA content. The mechanical properties of the blends changed dramatically with composition. Adding PDLLA makes the blends less hydrophilic than PPDO. Copyright © 2008 Society of Chemical Industry
Morphology of nylon 1212 toughened with a maleated EPDM rubber
Authors: Wang Yudong , Wang Wanjie , Peng Fu , Liu Minying , Zhao Qingxiang , Fu Peng‐Fei 
Published: December 2008

AbstractBACKGROUND: Polyamides, or nylons, are an attractive class of engineering polymers due to their excellent strength and stiffness, low friction and chemical and wear resistance. However, they are highly notch‐sensitive, i.e. they are often ductile in the un‐notched state, but fail in a brittle manner when notched. A super‐tough nylon 1212 was prepared by blending nylon 1212 with ethylene propylene diene monomer (EPDM) grafted with maleic anhydride (MA). The morphologies of Izod impact fracture surfaces as well as xylene‐etched surfaces of the nylon were thoroughly investigated using scanning electron microscopy (SEM).RESULTS: The fracture morphology and the impact strength of the nylon 1212 blends are very well correlated. The impact fracture surface of the blends exhibits certain characteristic features, such as the observation of fiber‐like sticks when etched with boiling xylene, formed during the impact fracture process. SEM images of xylene‐etched surfaces as well as the results of X‐ray energy dispersive spectroscopy suggest that the successful toughening of nylon 1212 with EPDM‐graft‐MA is due to the reaction between the anhydride of EPDM‐graft‐MA and the amine end‐groups of nylon 1212, leading to the formation of a homogenous graft copolymer system.CONCLUSION: The copolymer system, acting as a surfactant, reduces the interfacial tension between nylon 1212 and EPDM‐graft‐MA and produces a highly compatible super‐tough nylon 1212. Copyright © 2008 Society of Chemical Industry
Lower critical solution temperatures of thermo‐responsive poly(N‐isopropylacrylamide) copolymers with racemate or single enantiomer groups
Authors: Li Peng‐Fei , Wang Wei , Xie Rui , Yang Mei , Ju Xiao‐Jie , Chu Liang‐Yin 
Published: December 2008

AbstractBACKGROUND: Thermo‐responsive copolymers with racemate or single enantiomer groups are attracting increasing attention due to their fascinating functional properties and potential applications. However, there is a lack of systematic information about the lower critical solution temperature (LCST) of poly(N‐isopropylacrylamide)‐based thermo‐responsive chiral recognition systems. In this study, a series of thermo‐responsive chiral recognition copolymers, poly[(N‐isopropylacrylamide)‐co‐(N‐(S)‐sec‐butylacrylamide)] (PN‐S‐B) and poly[(N‐isopropylacrylamide)‐co‐(N‐(R,S)‐sec‐butylacrylamide)] (PN‐R,S‐B), with different molar compositions, were prepared. The effects of heating and cooling processes, optical activity and amount of chiral recognition groups in the copolymers on the LCSTs of the prepared copolymers were systematically studied.RESULTS: LCST hysteresis phenomena are found in the phase transition processes of PN‐S‐B and PN‐R,S‐B copolymers in a heating and cooling cycle. The LCSTs of PN‐S‐B and PN‐R,S‐B during the heating process are higher than those during the cooling process. With similar molar ratios of N‐isopropylacrylamide groups in the copolymers, the LCST of the copolymer containing a single enantiomer (PN‐S‐B) is lower than that of the copolymer containing racemate (PN‐R,S‐B) due to the steric structural difference. The LCSTs of PN‐R,S‐B copolymers are in inverse proportion to the molar contents of the hydrophobic R,S‐B moieties in these copolymers.CONCLUSION: The results provide valuable guidance for designing and fabricating thermo‐responsive chiral recognition systems with desired LCSTs. Copyright © 2008 Society of Chemical Industry
Effect of hydrophobic monomer on the synthesis and swelling behaviour of a collagen‐graft‐poly[(acrylic acid)‐co‐(sodium acrylate)] hydrogel
Authors: Marandi Gholam Bagheri , Hariri Safoura , Mahdavinia Gholam Reza 
Published: December 2008

AbstractBACKGROUND: Graft polymerization of vinylic monomers onto natural backbones is an efficient approach for the synthesis of natural‐based superabsorbents. The nature of the monomers will affect the swelling behaviour of the superabsorbents. Here, a novel superabsorbent was synthesized through grafting of acrylic acid onto collagen in the presence of hydrophobic styrene as co‐monomer. Subsequently, the effect of styrene on the swelling behaviour of the superabsorbent was studied.RESULTS: The highly swelling superabsorbent was prepared by introducing styrene into a collagen‐graft‐poly(acrylic acid) hydrogel. By inclusion of styrene monomer, the swelling capacity of the hydrogel was increased; this is discussed according to the network composition. The effect of swelling media (salt solutions and various pH values) was investigated. The results of absorbency under load showed that hydrogels containing phenyl groups exhibit better behaviour; however, by introducing styrene, the rate of water uptake and resistance to water holding under heating was reduced. Scanning electron micrographs of hydrogels revealed a decrease in porosity on using styrene.CONCLUSION: Inclusion of styrene monomer in the ionic superabsorbent caused high swelling capacity with better absorbency under load. This can be used to prepare highly swelling superabsorbents with good mechanical properties. The pH reversibility of the synthesized superabsorbent makes it a candidate for use in the controlled release of drugs and in agrochemicals. Copyright © 2008 Society of Chemical Industry
Substituent effects in the Baeyer–Villiger reaction of acetophenones: a theoretical study
Authors: Reyes Lino , Alvarez‐Idaboy J. Raul , Mora‐Diez Nelaine 
Published: December 2008

AbstractThis paper reports the first complete theoretical study of substituent effects on the mechanism of the Baeyer– Villiger (BV) reaction in non‐polar solvents taking into account the lowest‐energy mechanism that has been proposed for this rearrangement which is non‐ionic and fully concerted. The BV reaction of p‐substituted acetophenones, p‐XC6H4COCH3 (X = NO2, CN, H, CH3, OCH3), with performic (PFA) and trifluoroperacetic (TFPAA) acids, catalyzed by formic (FA) and trifluoroacetic (TFAA) acids, respectively, using the MPWB1K functional and the 6‐311G(d,p) and 6‐311++G(d,p) basis sets, are studied. Solvent effects are taken into account by means of the PCM continuum model using dichloromethane as solvent. Electron‐donating substituents on the aryl group have a relatively small activation effect on the first step, but a pronounced activation effect on the second to the point of being able to change the rate‐determining step (RDS) of the reaction, as observed in the case of p‐methoxyacetophenone with TFPAA acids. After analyzing the changes in Gibbs free energy of activation, geometrical parameters, and charge distributions of the transition states (TSs), explanations are provided for the two distinct effects that substituents on the ketone have on the kinetics of the addition and migration steps of the BV oxidation. The effect of the acid/peracid pair used is also discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Nucleophilic and acid catalyst behavior of a protic ionic liquid in a molecular reaction media. Part 1
Authors: Adam Claudia G. , Fortunato Graciela G. , Mancini Pedro M. 
Published: December 2008

AbstractThis work presents a new approach using ionic liquids, namely ethylammonium nitrate. The aim was to analyze how the addition of small amounts of a protic ionic liquid to a pure molecular solvent, modifies the microscopic characteristics of a reaction medium. In order to achieve this, a kinetic study of nucleophilic aromatic substitution reactions between 1‐fluoro‐2,4‐dinitrobenzene and 1‐butylamine or piperidine was developed in this type of binary mixtures. We have detected nucleophiles competition originated by the presence of the ionic solvent at very low concentrations, observing the ethylamine derivative as the main substitution product. Moreover, in the light of previous results we have confirmed that the protic ionic liquid can act as both Brönsted acid and/or nucleophile. In this connection, we have selected the nucleophilic addition of amines to carbonyl compounds as reaction model. The protic ionic liquid in the presence of aromatic aldehydes substituted by electron‐donating groups makes possible the formation of the corresponding imines with good yields. The results demonstrated that the influence of the protic ionic liquid is very important in the course of both reaction systems. Copyright © 2008 John Wiley & Sons, Ltd.
Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer
Authors: Wiklund Fredrik , Zheng S. Lilly , Sun Jielin , Adami Hans‐Olov , Lilja Hans , Hsu Fang‐Chi , Stattin Pär , Adolfsson Jan , Cramer Scott D. , Duggan David , Carpten John D. , Chang Bao‐Li , Isaacs William B. , Grönberg Henrik , Xu Jianfeng 
Published: December 2008

AbstractBACKGROUNDProstate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer‐related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels.METHODSWe evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome‐wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer.RESULTSOf the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P ≤ 0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P‐trend = 3.4 × 10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients.CONCLUSIONSResults from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic‐specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk‐associated SNPs may be confounded by the prevalent use of PSA screening. Prostate 69:419–427, 2009. © 2008 Wiley‐Liss, Inc.
The discovery of HNPC‐A3066: a novel strobilurin acaricide
Authors: Liu Aiping , Wang Xiaoguang , Chen Can , Pei Hui , Mao Chunhui , Wang Yongjiang , He Haijun , Huang Lu , Liu Xinping , Hu Zhibin , Ou Xiaoming , Huang Mingzhi , Yao Jianren 
Published: December 2008

AbstractBACKGROUND: Although more than ten strobilurin analogues have been commercialized since 1996 as fungicides, only one was available as an acaricide as of 2003. To search for novel strobilurin analogues with unique biological activities, a synthetic screening programme was carried out.RESULTS: Syntheses of compounds analogous to the commercialized fungicide metominostrobin and the acaricide fluacrypyrim led to the discovery of a lead compound, (E)‐2‐{2‐[[3,5‐bis(trifluoromethyl)phenoxy]methyl]phenyl}‐2‐(methoxyimino)‐N‐methylacetamide (3b), that showed moderate acaricidal activity against Tetranychus urticae Koch. Compound 3b has a 3,5‐(CF3)2‐phenoxymethyl group instead of the unsubstituted phenoxy substituent in metominostrobin. Optimization of compound 3b was achieved by introducing an oxime ether bridge along with an alkylthio(alkyl) branch in place of the oxymethylene chain between two aromatic moieties, as well as by replacing the methoxyiminoacetamide group with a methoxyacrylate structure, leading to (E)‐ methyl 2‐{2‐[[[(Z)[1‐(3,5‐bis(trifluoromethyl)phenyl)‐2‐methylthioethylidene]amino]oxy] methyl]phenyl}‐3‐methoxyacrylate (6c) and (E)‐ methyl 2‐{2‐[[[(Z)[1‐(3,5‐bis(trifluoromethyl)phenyl)‐1‐methylthiomethylidene]amino]oxy]methyl]phenyl}‐3‐methoxyacrylate (9a, HNPC‐A3066).CONCLUSION: The above two compounds (6c, 9a) were shown to exhibit potent acaricidal and fungicidal activity. Compound 9a (HNPC‐A3066) also exhibits larvicidal and ovicidal activities against various acarids. The acaricidal potency is comparable with those of commercial acaricides such as fluacrypyrim, tebufenpyrad and chlorfenapyr. Copyright © 2008 Society of Chemical Industry
Current status of insecticide resistance in Q biotype Bemisia tabaci populations from Crete
Authors: Roditakis Emmanouil , Grispou Maria , Morou Evangelia , Kristoffersen Jon Bent , Roditakis Nikos , Nauen Ralf , Vontas John , Tsagkarakou Anastasia 
Published: December 2008

AbstractBACKGROUND: A major problem of crop protection in Crete, Greece, is the control of Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) with chemical insecticides owing to the rapid development of resistance. The aim of this study was to investigate the establishment of resistance and the underlying mechanisms to major insecticide classes with classical bioassays and known biochemical resistance markers.RESULTS: During a 2005–2007 survey, 53 Q biotype populations were collected. Application history records showed extensive use of neonicotinoids, organophosphates, carbamates and pyrethroids. High resistance levels were identified in the majority of populations (>80%) for imidacloprid (RF: 38–1958×) and α‐cypermethrin (RF: 30–600×). Low resistance levels (RF < 12) were observed for pirimiphos‐methyl. A strong correlation between resistance to imidacloprid and the number of applications with neonicotinoids was observed. Significant correlations were observed between COE and P450‐dependent monoxygenase activity with resistance to α‐cypermethrin and imidacloprid respectively. A propoxur‐based AChE diagnostic test indicated that iAChE was widespread in most populations. Resistance levels for α‐cypermethrin were increased when compared with a previous survey (2002–2003). Differentiation of LC50 values between localities was observed for imidacloprid only.CONCLUSION: Bemisia tabaci resistance evolved differently in each of the three insecticides studied. Imidacloprid resistance seems less established and less persistent than α‐cypermethrin resistance. The low resistance levels for pirimiphos‐methyl suggest absence of cross‐resistance with other organophosphates or carbamates used. Copyright © 2008 Society of Chemical Industry