bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical pharmacovigilance analysis strategies
Authors: Lawrence Gould A. 
Published: September 2003

AbstractPurposeTo compare two recently proposed Bayesian methods for quantitative pharmacovigilance with respect to assumptions and results, and to describe some practical strategies for their use.MethodsThe two methods were expressed in common terms to simplify identifying similarities and differences, some extensions to both methods were provided, and the empirical Bayes method was applied to accumulated experience on a new antihypertensive drug to elucidate the pattern of adverse‐event reporting. Both methods use the logarithm of the proportional risk ratio as the basic metric for association.ResultsThe two methods provide similar numerical results for frequently reported events, but not necessarily when few events are reported. Using a lower 5% quantile of the posterior distribution gives some assurance that potential signals are unlikely to be noise. The calculations indicated that most potential adverse event–drug associations that were well‐recognized after 6 years of use could be identified within the first year, that most of the associations identified in the first year persisted over time. Other insights into the pattern of event reporting were also noted.ConclusionBoth methods can provide useful early signals of potential drug–event associations that subsequently can be the focus of detailed evaluation by skilled clinicians and epidemiologists. Copyright © 2002 John Wiley & Sons, Ltd.
Regional variation in the use of medications by older Canadians—a persistent and incompletely understood phenomena
Authors: Hogan D. B. , Maxwell C. J. , Fung T. S. , Ebly E. M. 
Published: September 2003

AbstractBackgroundWe have previously reported on regional variability in medication consumption by older Canadians. In this study, we used longitudinal data to determine whether regional differences in commonly consumed medications persisted and to explore potential explanatory factors for observed differences.MethodsWe utilized data from the second phase of the Canadian Study of Health and Aging to assess the number, types, and variability of medications used between regions. Linear and logistic regressions (LRs) were used to predict the number of medications and the use of specific agents where significant regional variability was found to exist.ResultsThere were significant regional differences in the number of medications consumed and in the prevalence of use of acetaminophen (p < 0.002), benzodiazepines (p < 0.020), nitrates (p = 0.040), and complementary and alternative medicines (CAMs; p < 0.020). The proportion of subjects using acetaminophen was highest in British Columbia (44.6%) and lowest in Quebec (27.3%). Benzodiazepine and nitrate consumption was highest in Quebec (35.9 and 19%, respectively) and lowest in the Praires (18.2%) and Atlantic Canada (6.6%). CAM use was highest in British Columbia (47.1%) and lowest in the Atlantic region (26.8%). Similar inter‐regional differences had been found 5 years previously. There were no significant regional differences in the prevalence of hypertension, myocardial infarction, diabetes, arthritis/rheumatism, or depression. Region remained a significant explanatory variable for the number of medications and nitrate, benzodiazepine, and CAM use in our multivariate models.ConclusionsRegional differences in medication use persisted over the course of this longitudinal study. Much of the variability remains unexplained. The reasons for regional differences in consumption of drugs and their clinical significance should be addressed. Copyright © 2003 John Wiley & Sons, Ltd.
Risk factors for adverse events in analgesic drug users: results from the PAIN study
Authors: Moore Nicholas , Charlesworth Andrew , Van Ganse Eric , LeParc Jean‐Marie , Jones Judith K. , Wall Richard , Schneid Hélène , Verrière François 
Published: September 2003

AbstractBackgroundThe relative influence of various risk factors for adverse events (AE) in analgesics users have never been precisely quantified. Advantage was taken of data generated in the paracetamol, aspirin and ibuprofen new tolerability (PAIN) study, a large randomized double‐blinded trial of paracetamol, aspirin or ibuprofen for common pain in general practice to attempt this.ObjectiveIdentify and quantify factors associated with the occurrence of AE in users of analgesic drugs.MethodMultivariate logistic regression analysis of potential risk factors for all AE, clinically significant AE (SAE) and clinically significant gastro‐intestinal AE (GI SAE).ResultsOf the 8677 patients included in the study, 8633 contributed data. The main risk factors for SAE were indication: compared to those treated for musculoskeletal pain, patients treated for menstrual pain had an odds ratio (95% Confidence Interval) of 0.4 (0.2–0.7), sore throat 0.6 (0.5–0.8), cold and flu 0.7 (0.6–0.8), headache 0.8 (0.7–1.0); concomitant use of medication contra‐indicated in the drugs' labeling (OR: 2.2; 1.6–2.9); increasing number of other concomitant medications: 1: OR 1.5 (1.3–1.8); 2–3: OR 1.9 (1.6–2.3); more than 3: OR (2.7; 2.1–3.5); treatment with aspirin: OR 1.4; (1.2–1.6) but not ibuprofen: OR 0.9; (0.8–1.1) compared to paracetamol; history of previous GI disorder OR 1.4 (1.0–1.8); female gender: OR 1.3 (1.1–1.4). Age was not significantly associated with AE in the multivariate analysis. Risk factors for all AE and GI SAE were mostly the same as for significant AE, but there were fewer GI SAE with ibuprofen than with paracetamol (OR 0.8; 0.6–0.9).ConclusionApart from the analgesic used and its indication, the main risk factors identified for AE in users of first‐line analgesics for common pain were the number and nature of concomitant medication. Copyright © 2003 John Wiley & Sons, Ltd.
Randomized controlled intervention in cardiovascular drug treatment in nursing homes
Authors: Ulfvarson Johanna , Adami Johanna , Ullman Bengt , Wredling Regina , Reilly Marie , von Bahr Christer 
Published: September 2003

AbstractObjectiveTo study drug treatment of patients with cardiovascular diseases (heart failure, post‐myocardial infarction, angina pectoris, hypertonia or cardiac valvular disease) in nursing homes and assess effect of medication advice.InterventionThe patients were randomized to an intervention or control group. Medication reviews were made by one specialist in clinical pharmacology and one in cardiology. Symptoms related to heart failure or adverse reactions to cardiovascular drugs were recorded using a questionnaire. Quality of life and activities of daily living (ADL) were assessed and follow‐ups performed after 2 weeks and 3 months. Outcome measures were changes of drug therapy and the global scores computed from symptoms scales.ResultsEighty patients were randomized. They had a mean age of 87 years and their average number of drugs was 9.6. Changed drug therapy was suggested in 40 patients and the advice was followed by the responsible physicians in 19 patients. The physicians mostly followed advice for changed furosemide therapy but not for introducing an ACE‐inhibitor, probably due to uncertain diagnosis and need for follow‐up after initiation of such therapy. No significant changes from baseline to later follow‐up were found in the mean total scores of any questionnaire.ConclusionIntervention did not affect cardiovascular symptoms. Drug revisions should involve more than one class of drugs in order to be cost‐effective. Copyright © 2003 John Wiley & Sons, Ltd.
Pattern of prescriptions issued by nursing home‐based physicians versus office‐based physicians for frail elderly patients in German nursing homes
Authors: Pittrow David , Krappweis J. , Rentsch A. , Schindler C. , Hach I. , Bramlage P. , Kirch W. 
Published: September 2003

AbstractPurposeThe purpose of this study was to describe the physician prescription pattern for frail elderly patients in German nursing homes and to identify differences, if any, between that of physicians based in the nursing homes (A) and those with office‐based practices (B).MethodsRetrospective, longitudinal study of medication prescriptions on the basis of the database of a health insurance (Betriebskrankenkasse) in Berlin, Germany. We assessed the medication prescriptions for all 996 unselected insured individuals aged ≥ 60 years who were insured throughout 1999 and lived in nursing homes. We analyzed selected patient characteristics and prescription data. Drugs were classified according to the WHO ATC code and were assigned a mean daily defined dose (DDD).Results816 individuals were women and 180 were men. A total of 78% of women and 43% of men were aged 80 years or older. Two hundred sixty three patients were seen by nursing home‐based physicians (A) and 733 by office‐based physicians (B). The median of prescriptions per patient and year was 31 (A) and 37 (B) (p between groups < 0.001). Patients in Group A also received a lower number of DDDs in comparison to Group B (1109 vs 1250; p < 0.01). Costs were substantially higher in group B, and in both groups higher in the 60–69 years old in comparison to the more senior patients. The prescription pattern suggested a considerable frequency of inappropriate drug use in both groups in the following classes: psychopharmacological agents (neuroleptics, antidepressants, hypnotics), pain medication, digitalis glycosides, laxants and loop diuretics. On an average, office‐based physicians (B) prescribed relatively more medications in all major classes with the exception of non‐opiate analgesics, laxants and anxiolytics.ConclusionsThese data are indicative of a considerable use of inappropriate medication for frail geriatric patients. Differences between the prescribing pattern among nursing home‐based and office‐based physicians were not substantial, however, the latter group prescribed relatively more drugs. Copyright © 2003 John Wiley & Sons, Ltd.
Approaches to combat with confounding by indication in observational studies of intended drug effects
Authors: McMahon Alex D. 
Published: September 2003

AbstractThere has been a resurgence of controversy about the usefulness of observational data to study the efficacy of drugs. Nearly every week a researcher makes some criticism of clinical trials or justifies observational research into intended effects, with other researchers offering a contradictory viewpoint. Literature reviews are not useful in this regard because the contradictory studies will not usually be carried out. Some methods are discussed which may have potential utility in the study of intended effects. There may be a marginal role for statistical techniques such as propensity scores and confounder scores. More promising techniques may include ecological analyses, restriction of subjects and blinded prospective review. Because it is currently unknown when the observational study of drug efficacy is possible, we should arguably always carry out a study of the determinants of prescribing first, and possibly consider using the various techniques that are outlined in this article. Copyright © 2003 John Wiley & Sons, Ltd.
Benefit‐risk analysis: a proposal using quantitative methods
Authors: Holden William L. , Juhaeri Juhaeri , Dai Wanju 
Published: September 2003

AbstractThis is the first part of a two‐article series which will introduce the theory and practice of a proposed set of quantitative methods for benefit‐risk analysis. Adjustments to number‐needed‐to‐treat (NNT) analysis and a new method, minimum clinical efficacy (MCE) analysis are presented and critically discussed. The goal of these methods is to condense into a summary metric the benefit‐risk profile of a product so that manufacturers, regulators, clinicians and patients can better understand and participate in risk management. A second article will present examples of these methods. Copyright © 2003 John Wiley & Sons, Ltd.
Initiator‐fragment incorporation radical polymerization of divinylbenzene in the presence of glyoxylic oxime ether: Formation of soluble hyperbranched polymer
Authors: Sato Tsuneyuki , Sato Nobuyuki , Seno Makiko , Hirano Tomohiro 
Published: September 2003

AbstractThe copolymerization of divinylbenzene (DVB) and ethylstyrene (EtSt) was carried out at 70 and 80 °C in benzene with dimethyl 2,2‐azobisisobutyrate (MAIB) at high concentrations as initiator in the presence of methyl benzyloxyiminoacetate (MBOIA), a glyoxylic oxime ether, as a retarder. The copolymerization system of DVB (0.25 mol/L), EtSt (0.25 mol/L), MBOIA (0.5 mol/L), and MAIB (0.5 mol/L) gave benzene‐soluble copolymers despite a considerably high concentration of DVB as an excellent crosslinker. The yield and molecular weight of the resulting copolymers increased with time both at 70 and 80 °C and then leveled off because of initiator consumption. The homogeneous polymerization system involved electron spin resonance (ESR), observable nitrogen‐centered polymer radicals (MBOIA·) under the actual polymerization conditions. The MBOIA· concentration increased with time despite a homogeneous polymerization system, suggesting the formation of rigid hyperbranched polymers. A benzene solution of isolated copolymer also showed an ESR signal. The copolymer was soluble in acetone, toluene, chloroform, ethyl acetate, tetrahydrofuran, and N,N‐dimethylformamide but insoluble in n‐hexane, methanol, and dimethyl sulfoxide. MAIB fragments as high as 30–40 mol % were incorporated into the copolymers through initiation and primary radical termination, on the basis of which this polymerization was named the initiator‐fragment incorporation radical polymerization. MBOIA (13–16 mol%) was also incorporated into the copolymers through an opening of the CN bond. The intrinsic viscosity of the copolymers was very low (0.08 dL/g), and the reduced viscosity was almost independent of the polymer concentration, supporting a hyperbranched structure of them. Gel permeation chromatography and multi‐angle laser light scattering and transmission electron microscopy revealed that the copolymer was formed as a hyperbranched nanoparticle. The thermal behavior of the copolymer was examined by dynamic thermogravimetry and differential scanning calorimetry. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3038–3047, 2003
Terpyridine‐modified poly(vinyl chloride): Possibilities for supramolecular grafting and crosslinking
Authors: Meier Michael A. R. , Schubert Ulrich S. 
Published: September 2003

AbstractCommercially available poly(vinyl chloride) (PVC) was covalently modified with terpyridine supramolecular binding units in a two‐step reaction. First, PVC was modified with aromatic thiols to introduce OH functionalities into the polymer backbone, which were subsequently reacted with an isocyanate‐functionalized terpyridine binding unit. The resulting functionalized material contained metal‐ion binding sites, which could be used for grafting and crosslinking reactions. A grafting experiment was performed with a small organic terpyridine ligand. The complexation of the modified PVC with several transition‐metal ions was studied with ultraviolet–visible spectroscopy and gel permeation chromatography. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2964–2973, 2003
Immiscible polymers in double spin‐coated electroluminescent devices containing phenyl‐substituted tris(8‐hydroxyquinoline)aluminum derivatives soluble in a host polymer
Authors: Shoji E. , Miyatake K. , Hlil A. R. , Hay A. S. , Maindron T. , Jousseaume V. , Dodelet J. P. , Tao Y. , D'Iorio M. 
Published: September 2003

AbstractThree new phenyl‐substituted tris(8‐hydroxyquinoline)aluminum (AlQ3) derivatives have been synthesized: tris(5‐phenyl‐8‐quinolinolate‐N1,O8)aluminum, tris(5,7‐diphenyl‐8‐quinolinolate‐N1,O8)aluminum, and tris[5,7‐bis(p‐fluorophenyl)‐8‐quinolinolate‐N1,O8]aluminum. These AlQ3 derivatives are easily soluble in common organic solvents and form solid‐phase solutions in a poly(aryl ether ketone) host polymer (A435). These interesting properties allow the use of soluble AlQ3 derivatives in double spin‐coated organic light‐emitting devices of the type ITO/NPB‐QP/A435 + 50 wt % soluble AlQ3 derivative/Mg, where NPB‐QP is a hole‐transporting polymer insoluble in toluene, the solvent for A435. Typical double spin‐coated organic layer devices are characterized by an emission at 530–539 nm, a threshold voltage of 6–9 V, and a maximum luminance of 1800–4000 cd/m2 at 21–25 V. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3006–3016, 2003
Use of germanium initiators in ring‐opening polymerization of L‐lactide
Authors: Finne Anna , Reema  , Albertsson Ann‐Christine 
Published: September 2003

AbstractThree different, new germanium initiators were used for ring‐opening polymerization of L‐lactide. Chlorobenzene and 120 °C was a usable polymerization system for solution polymerization, and the results from the polymerizations depended on the initiator structure and bulkiness around the insertion site. The average molecular weights as measured by size exclusion chromatography increased linearly with the monomer conversion, and the molecular weight dispersity was around 1.2 for initiators 1 and 2, whereas it was around 1.4 for initiator 3. The average molecular weight of poly(L‐lactide) could be controlled with all three initiators by adding different ratios of monomer and initiator. The reaction rate for the solution polymerization was, however, overall extremely slow. With an initial monomer concentration of 1 M and a monomer‐to‐initiator ratio of 50, the conversion was 93% after 161 h for the fastest initiator. In bulk polymerization, 160 °C, the conversion was 90% after 10 h. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3074–3082, 2003
Contribution of steric and electrostatic repulsion forces to the stability of styrene latices copolymerized with acrylic acid
Authors: Reynhout X. E. E. , Hoekstra L. , Meuldijk J. , Drinkenburg A. A. H. 
Published: September 2003

AbstractAcrylic acid (AA) is used in many emulsion polymerization formulations to improve the colloidal stability of the latex product. The improved stability originates from electrostatic repulsion complemented with steric repulsion. The strength of the electrostatic and steric repulsion forces in a styrene (S)/AA copolymer latex was investigated at different pH values, electrolyte concentrations, and temperatures. A comparison was made with an S homopolymer latex. Transmission electron microscopic pictures, combined with visual inspections, provided understanding of the mechanisms leading to coagulation in polystyrene (PS)/AA copolymer latices. Colloidal stability of the unswollen sodium dodecyl sulfate stabilized PS latex is based on electrostatic repulsion. Destabilization by sodium chloride resulted in aggregation. The acidic PS/AA latex remained stable against aggregation at high electrolyte concentrations because of steric repulsion. The acidic PS/AA latex showed a strong tendency to flocculate at increasing electrolyte concentrations. Flocculation was not observed for high‐pH PS/AA latices at high electrolyte concentrations. Steric repulsion of the acid PS/AA latex was lost at temperatures higher than the critical coagulation temperature (35 °C), and flocculation was followed by aggregation and coalescence. The high‐pH PS/AA latex was stable even at high electrolyte concentrations and temperatures up to 80 °C because of strong electrosteric stabilization. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2985–2995, 2003
Synthesis and cationic photopolymerization of epoxy‐functional siloxane monomers and oligomers
Authors: Jang Myoungsouk , Crivello James V. 
Published: September 2003

AbstractA series of difunctional silicon‐containing monomers were prepared with a novel method consisting of the monohydrosilation of an α,ω‐difunctional SiH‐terminated siloxane with a vinyl‐functional epoxide or oxetane followed by the dehydrodimerization of the resulting SiH‐functional intermediate. This method used simple, readily available starting materials and could be conducted as a streamlined one‐pot, two‐step synthesis. This novel method was also applied to the synthesis of several epoxy–silicone oligomers. The reactivities of these new monomers and oligomers were examined with Fourier transform real‐time infrared spectroscopy and optical pyrometry. Those monomers containing epoxycyclohexyl groups displayed excellent reactivity in cationic ring‐opening polymerization in the presence of lipophilic onium salt photoinitiators. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3056–3073, 2003
Development of new dyeing photoinitiators based on benzylideneimidazopyridine dyes
Authors: Pyszka Ilona , Kucybała Zdzisław , Pączkowski Jerzy 
Published: September 2003

AbstractSeveral dyes containing benzylideneimidazopyridine moiety (BIPDs) were synthesized and evaluated as photoinitiators for free‐radical polymerization induced with the visible emission of an argon‐ion laser. One method of dye structure change was applied in our study. The modification was based on the character of the substituent introduced into both the imidazopyridine skeleton and phenyl ring. Several different groups were tested including heavy atoms (CI, Br) as well as electron‐accepting (NO2), and electron‐donating groups [N(CH3)2, OCH3]. Analysis of the dye properties demonstrated that there is a significant heavy atom effect on the photoinitiation ability of the novel dyes in both cases, for example, when a heavy atom is introduced into the phenyl ring as well as into the imidazopyridine part of the molecule. The introduction of an electron‐acceptor or electron‐donor group into the phenyl part of the dye caused a dramatic decrease in its photosensitivity. The type of applied counterion had no effect on the overall sensitivity of a dye. BIPDs are not particularly good photoinitiators. Further modification of the dye structure involved the elimination of the motion of a CC bond by the coplanarization of the styrylium residue with other parts of the dye. This approach decreased the degree of branching of the dye, which stabilized the molecule in its excited state. The formed dye, quinoline[2,3‐b]‐2,3‐dihydro‐1H‐imidazo[1,2‐a]pyridinium bromide (QDIPB), exhibited dramatically enhanced sensitivity. QDIPB possessed broad structured spectra with a long‐wavelength part shifted to the blue as compared to other BIPD dyes. The change of the absorption spectra and its high photoinitiation ability makes QDIPB a good candidate for the photoinitiating system applied in dental restorative materials. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3048–3055, 2003