bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achilles tendinitis induced by pefloxacin and other fluoroquinolone derivatives
Authors: Meyboom R. H. B. , Olsson S. , Knol A. , Dekens‐Konter J. A. M. , De Koning G. H. P. 
Published: October 2006

AbstractFour cases have been reported to the Netherlands Pharmacovigilance Foundation LAREB of Achilles tendinitis, as a suspected adverse reaction to pefloxacin. More than 20 cases of tendinitis and tendon rupture have previously been described in the literature in association with pefloxacin and various other fluoroquinolone derivatives. The mechanism involved is still unknown. Tendon disorders as an adverse drug reaction are very rarely reported to the WHO Collaborating Centre for International Drug Monitoring. The exception is in association with fluoroquinolone derivatives. More information is needed with regard to the frequency of tendinopathy during the use of pefloxacin and the other drugs in this group. Patients using a fluoroquinolone derivative should be informed on the risk of developing tendinitis and tendon rupture.
Adverse drug reactions: Comparison of two report methods
Authors: Hanesse B. , Legras B. , Royer R. J. , Guillemin F. , Briancon S. 
Published: October 2006

AbstractIncreasing numbers of effective therapeutic agents changed the practice of medical care. One of the costs of the widespread use of new therapies is the occurrence of adverse drug reactions (ADR). We compared a routine procedure of spontaneous reporting to a systematic registration of medical informations including adverse drug reactions in a cluster‐randomized controlled trial. This study was carried out during the first semester of 1993 at the Centre Hospitalier et Universitaire de Nancy, France receiving about 100,000 patients a year. The 10 participating departments were paired‐matched. For the first eight weeks of the study, reporting methods were randomly assigned within each pair. For the second eight weeks of the study, the attribution of methods was reversed. All patients, who left a participating department within one of these two periods were included. Subsequent discharges after further readmissions for the same patient were not considered. Thus, the study was based on 5967 patients. We received 46 ADR reports. After adjustment for age and sex, using a logistic regression model, the probability for reporting ADR for a patient is twice as likely by systematic registration of medical information than by the routine procedure of spontaneous reporting. Generalization of this supplementary method for reporting adverse drug reactions appears interesting.
Drug risk assessment: A case for large trials with lean protocols
Authors: Hasford Joerg 
Published: October 2006

AbstractThe common tools of pharmacoepidemiology are: the spontaneous report registries, the case control study, and the cohort study. Since large sample sizes are usually needed, the classic randomized trial, which collects large amounts of data per patient, seems to be impracticable. Yusuf et al.6 have suggested using large trials with simple protocols and only minimal data collection to allow for recruitment of large sample sizes (> 1000). As the objectives of drug safety studies are not met by the large trial simple protocol design, the large trial, lean protocol design is suggested. Its characteristics are that it is: multicentric, randomized, with no efficacy assessment, recording only baseline, follow‐up and outcome data which are crucial to the primary objective of the trial; there is no ‘by tradition’ collection of data. The indications, the ethics and the biometry of randomized trials with safety variables as major endpoint are discussed.Large trials with a lean protocol are feasible. To illustrate the possible usefulness, a trial will be reported whose primary objective was to assess the rate of a specified adverse event. In general, randomized trials with safety measures as primary endpoints can play an important role in drug risk assessment and their use should be encouraged.
Evaluation of ACE‐inhibitor (ACE‐I) associated cough using modified prescription sequence analysis (PSA)
Authors: Bowman Lee , Carlstedt Bruce C. , Miller Michael E. , McDonald Clement J. 
Published: October 2006

AbstractObjective — Identify whether the prescription sequence of cough suppressant within one year following patients' first ACE‐I prescription can be used as an indicator for the occurrence of ACE‐I associated cough.Design — Observational retrospective controlled cohort design using all patients receiving ACE‐I as study cohort and patients having prescriptions for hydralazine, clonodine and prazosin as the control. Patient demographics and prescribing indications were controlled statistically using multivariate logistic regression.Setting — A large computerized clinical database encompassing the medical records of 450,000 patients seen over a 20‐year period at a county medical centre ambulatory clinic.Patients — 5373 patients exposed to any of captopril, enalapril, lisinopril, clonodine, hydralazine or prazosin.Main results — This study identified an odds ratio (OR) of 1.53 [95% confidence interal (CI) 1.17 to 2.01] for receipt of an antitussive following patients' first ACE‐I prescription. Other significant risk factors included female gender [OR = 1.52, CI 1.13 to 2.07] and diagnosis of congestive heart failure [OR = 1.47, CI 1.10 to 1.94].Conclusion — The receipt of an antitussive following ACE‐I prescription may be used to monitor for ACE‐I associated cough, although its utility is unknown.
Recall of medication during pregnancy: Validity and accuracy of an adjusted questionnaire
Authors: de Jong Pieternel C. M. Pasker , Berns Mary P. H. , van Duynhoven Yvonne T. H. P. , Nijdam Wies S. , Eskes Tom K. A. B. , Zielhuis Gerhard A. 
Published: October 2006

AbstractObjective — To study the validity and accuracy of an adjusted questionnaire on medical drug use during pregnancy eight years after the pregnancy.Methods — The ability of a questionnaire on medication during pregnancy to detect actual use (= sensitivity) was tested against information collected 8 years previously (in 1983–1984) from 473 women with high‐risk pregnancies who delivered at the University Hospital Nijmegen, the Netherlands.Results — For separate drug groups, the sensitivity varied between 5% and 91%. The timing of use was recalled moderately well. Although specific questions on drug groups did improve the sensitivity as compared to an earlier questionnaire, the improvement was not enough to make the questionnaire valid. High maternal education, low birth weight, low gestational age and a low 5‐min Apgar score were related to better recall. The sensitivity of the questionnaire depended on the behavioural score of the child, implying recall bias.Conclusion — Questionnaire data on drug use during pregnancy obtained eight years after delivery are not a valid source of information.
Relevance and limits of pharmacogenetics to detect patients at risk of adverse drug reactions
Authors: Bechtel Pierre R. 
Published: October 2006

AbstractFor more than 15 years genetic polymorphism of drug metabolism has been extensively studied. Poor Metabolizer (PM) and Extensive Metabolizer (EM) Slow Acetylators (SA) Rapid Acetylators (RA) phenotype and genotype can be defined for CYP2D6 (Debrisoquine) and N‐AT (acetylation). Lists of drugs whose metabolism is CYP2D6 or N‐AT dependent have been published. So it is theoretically possible to forecast an adverse drug reaction (ADR) for a specific patient who is given a drug affected by a polymorphism. However, not only PM are at risk of ADRs. When an active or reactive metabolite is produced, EM might be at risk whatever the enzyme involved. Drug interactions must also be taken into account. Competitive inhibition of the metabolism of a drug CYP2D6 dependent provokes not only a blurring effect on phenotyping, leading to a misclassification, but also increases the risk of ADRs. New drug metabolic polymorphism is under scrutiny. Determination of phenotypes and genotypes when possible, development of investigations of drug metabolic capacity at large, in patients exhibiting ADR's, might improve the efficiency of pharmacovigilance to forecast at‐risk subjects.
Pattern of treatment and metabolic control in orally treated diabetic patients in France and Sweden
Authors: Vauzelle‐Kervroëdan Françoise , Bergman Ulf , Forhan Anne , Stålhammar Jan , Papoz Laure 
Published: October 2006

AbstractThere are large differences in therapeutic habits in the treatment of diabetes in European countries. A cross‐sectional comparison was made of 654 French and 241 Swedish orally treated diabetic patients, aged 50–74 years. Good diabetic control was based on HbA1c (<7 per cent) and body mass index (<27 kg/m2 for men and <25 kg/m2 for women). The French patients were more often male, and about 3 years younger in both sexes. Duration of diabetes was similar in men but shorter in Swedish women, while obesity was more frequent among French men and similar in women. HbA1c was significantly lower in both sexes in the French sample. This difference was, however, no longer significant, when obesity was taken into account. Good diabetic control was found only in about a quarter of men and in one out of seven women. Differences in treatment were mainly due to prescription of metformin alone, which was very uncommon in Sweden. The average prescribed daily doses were generally lower in France. The differences between the two diabetic groups indicate different characteristics of the patients, in spite of the same inclusion criteria, together with different strategies for the oral treatment of diabetes in the two countries.
Determinants of drug utilization in an elderly population in North and West Belfast
Authors: Passmore A. P. , Crawford V. L. S. , Beringer T. R. O. , Gilmore D. H. , Montgomery A. 
Published: October 2006

AbstractThis study was designed to survey drug prescribing for all patients over 65 years in institutional and hospital care in North and West Belfast, together with a home‐based sample, and to determine the influence of age, sex, mental score, functional score and place of abode on prescribing habits. Multiple regression analysis was used to analyse the effects of the various parameters on number of drugs received. Drugs were categorized into therapeutic classes and for each class a separate logistic regression analysis was performed to identify the variables which independently predicted receipt of that class.A total of 1094 people were surveyed with an average of 3.26 medications per person. The most common classes of drugs received were diuretics (39.8 per cent), analgesics (31.7 per cent), hypnotics (25.3 per cent), phenothiazines (21.7 per cent) and laxatives (20.9 per cent). Number of drugs received was not predicted by age or sex but by institutional or hospital placement. Placement was also the most significant independent predictor of drug class. Age, sex, mental and functional scores were less significant.Drug utilization in this representative elderly population seemed appropriate with low prescribing rates for some drug classes considered hazardous or ineffective in this age group.
Disturbance of menstruation as a side‐effect of nonsteroidal anti‐inflammatory drugs (NSAIDs)
Authors: Meyboom R. H. B. , Heymeijer G. W. J. , van den Bemt P. M. L. A. , de Koning G. H. P. 
Published: October 2006

AbstractMenstrual disturbances are not a generally recognized side‐effect of non‐steroidal antiinflammatory drugs (NSAIDs). Five case reports to the Netherlands Pharmacovigilance Foundation LAREB concern menstrual disturbances in suspected connection with the use of an NSAID. In one patient at several occasions the use of naproxen for dysmenorrhoea was followed by interruption of menstruation. In four other women the use of diclofenac, indomethacin or naproxen was followed by hypo‐ or amenorrhoea of one cycle duration. Prostaglandins play a complex role in the physiology of menstruation. The effects of NSAIDs on cyclo‐oxygenase and prostaglandin metabolism may explain the observed disturbances of menstruation. Female patients of child‐bearing age using an NSAID — either to treat dysmenorrhea or for other reasons — should be aware of the possibility of interruption, delay, decrease or missing of a menstrual period.
Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): Evaluation for drug risk based on sale numbers in defined daily doses (DDD). Example of the H2‐antagonists
Authors: Rzany Berthold , Mockenhaupt Maja , Holländer Norbert , Stocker Ulrich , Mueller Judit , Baur Susan , Schöpf Erwin 
Published: October 2006

AbstractWe report on the results of the registration of SJS, SJS/TEN overlap and TEN with maculae in West‐Germany and Berlin from 01.04.90 to 31.12.92. The results are based on the ‘Dokumentationszentrum schwerer Hautreaktionen’, a registry on severe skin reactions, which regularly contacts more than 1500 hospitals (departments of dermatology, departments of pediatrics, burn units and internal medicine departments with intensive care facilities). With a response rate ranking from 77% to 95% over a period of 33 months 270 cases of SJS, SJS/TEN overlap and TEN have been included into the registry. More than 1690 single drugs had been taken two weeks prior to the skin reaction. Among those drugs ranitidine was found in 25 patients. Other H2‐antagonists were taken in 12 cases (famotidine in 11 cases and cimetidine in one case). Evaluation of drug risk incidences for these drugs were calculated based on prescription data in defined daily doses (DDD), which were obtained from the ‘Wissenschaftliches Institut der Ortskrankenkassen’ (WIDO), Heidelberg, Germany. For ranitidine incidences of 0.19, 0.14, 0.10 could be evaluated, compared to 0.11, 0.29 for famotidine and 0.06 for cimetidine for 1990, 1991 and 1992, respectively. Over the observation period the incidences for ranitidine were stable in contrast to famotidine. As probable confounding factors co‐medication with phenytoin, dexamethasone, heparin and, in addition, concomitant illnesses as brain‐tumours and cerebral metastasis could be found. The example of the H2‐antagonists shows that incidence data should be interpreted cautiously. To avoid misinterpretation incidences should be observed over a period of several years, and in every case confounding factors should be taken into account.
Utilization patterns of subsidized and nonsubsidized reimbursable peptic ulcer medication in Belgium
Authors: Stichele R. H. Vander , Petri H. 
Published: October 2006

AbstractStudy objective — To provide an exploratory description of a dynamic population of Belgian patients treated with reimbursable peptic ulcer medications (ATC Class A20B) and to estimate the annual number (prevalence) of patients treated with reimbursable peptic ulcer medications per 1000 inhabitants in Belgium in 1991.Setting — Community pharmacies in Belgium, a country with 107 inhabitants, where reimbursement of attack therapy (3 months) and maintenance therapy (9 months) is only possible after endoscopic or radiologic confirmation of ulcer or severe esophagitis.Design — Cross‐sectional two month registration study of consecutive recipients of reimbursable peptic ulcer medication in a convenience sample of 31 volunteer community pharmacists (a 0.5% sample of Belgian community pharmacies).Methods — Data from a simple, self‐administered (with assistance from the pharmacist) questionnaire of two pages were used to classify patients in one of four patterns of therapy (attack therapy, relapse therapy, maintenance therapy for 9 months, maintenance therapy longer than 9 months) and to determine the average consumption of medication packages within each pattern. The number of patients using reimbursable peptic ulcer medication over one year was estimated from these observational data and from the annual sales volume with a theoretical model.Results — The questionnaire was completed by 432 of 481 elegible patients (an 89.9% response rate) in 27 participating pharmacies. Ninety‐two per cent of the patients had requested or had obtained reimbursement; 74% had at least one EDG in the past 12 months (1/3 combined with at least one X‐ray). Only nine patients of the small subgroup of 34 patients without reimbursement had undergone diagnostic examinations.Discussion — The study of complex utilization patterns with a simplified model provides a rough estimation of the annual number of medication users.Conclusions — In Belgium, a country with strict reimbursement control, mainly based on EGD performed by medical specialists, the annual prevalence of patients using reimbursable peptic ulcer medication is estimated at 30.5 patients/1000 inhabitants/ year. In this country, there is a high utilization of EGD, a high rate of 9 months maintenance therapy and some evidence for channelling of omeprazole. Further longitudinal follow up and comparison with different reimbursement systems in other countries is needed to evaluate the cost‐effectiveness and the impact of different regulatory approaches to reimbursement regulation on medication utilization.
A study of the utilization of non‐steroidal anti‐inflammatory drugs using a pharmacy‐based approach
Authors: Sift Rosemary , van Staa Tjeerd‐Pieter , Abenhaim Lucien , Ebner Daniel 
Published: October 2006

AbstractThe extent of compliance and drug exposure characteristics among NSAID users has not been extensively studied. We measured drug compliance in patients who obtained a NSAID in one of four German pharmacies, by an interview four weeks later.The study population consisted of 526 persons with an average age of 57 years, and two‐thirds of the participants were women. We observed that only half of the patients had followed the recommended dosage regimen for the NSAID. Persons with complaints lasting three months or less were more likely to be compliant than chronically ill patients (OR = 5.0, 95 per cent CI: 3.0–8.2).We concluded that this heterogeneity in drug utilization must be considered in the design of observational studies.
Incidence of symptomatic liver function abnormalities in a cohort of NSAID users
Authors: Lanza Lee L. , Walker Alexander M. , Bortnichak Edward A. , Gause Douglas O. , Dreyer Nancy A. 
Published: October 2006

AbstractBackground — A small number of published reports have provided estimates of incidence rates of symptomatic liver dysfunction in NSAID users, and most information has pertained to cases admitted to the hospital.Methods — We studied members of a health maintenance organization who were age 20 to 64 years in 1989–1991. Beginning with health insurance claims data for over 68,000 users of NSAIDs, and obtaining abstracts of medical records of potential cases, we ascertained the frequency of liver function abnormalities, including only cases with documented symptoms treated either as outpatients or hospital inpatients.Results — Overall, symptomatic liver dysfunction was rare, with 25 cases confirmed in the cohort of 68,028 people (0.37 cases per 1000 users of NSAIDs). For people who received a prescription NSAID in the previous six months, the crude incidence rate was 24 cases in 46,636 person‐years, or 0.51 per 1000 person‐years. For people who did not have a prescription NSAID in the previous six months, the crude incidence rate was 1 case in 13,303 person‐years, or 0.075 per 1000 person‐years. Of the 25 confirmed cases, 19 (76%) had alanine aminotransferase and/or aspartate aminotransferase at least 1.5 times the upper limit of normal values; the remaining six had abnormal results but of lesser magnitude. In five cases (20%) physician's notes document that a diagnosis of drug‐induced hepatic dysfunction was considered. Only 3 (12%) of the 25 cases were admitted to the hospital.Conclusion — Although symptomatic liver dysfunction was relatively more frequent during the six months following NSAID use than at later times, the overall risk was low. Given the limitations of the available data, the apparent association with NSAID use may be confounded by other causes of liver dysfunction that could not be fully evaluated, such as other hepatotoxic medications, viral infections, or other medical conditions.
Absorption of Ionizable Drugs: Nonlinear Dependence on log P, pKa and pH ‐ Quantitative Relationships
Authors: Schaper Klaus‐Jürgen 
Published: October 2006

AbstractObserved rates of absorption of drugs by passive diffusion through lipid membranes depend on certain physicochemical properties of the drug being absorbed and of the lipid barrier to be penetrated. By combining the pH partition theory, the unstirred layer hypothesis, and LFE considerations several model equations were derived. Within congeneric series of acidic or basic compounds these equations allow one to quantitatively describe the nonlinear dependence of the rate of absorption on lipophilicity and degree of ionization as well as to explain the observation of pH shifts in pH absorption profiles of drugs. Generally an excellent fit of the equations to observed rate constants for several classes of compounds was obtained. Furthermore some indications are presented that absorption rates are influenced by aqueous as well as by lipid stagnant diffusion layers adjacent to the aqueous/lipid interface.
BC(DEF) Coordinates 3. Their Acquisition from Physical Property Data
Authors: Cramer Richard D. 
Published: October 2006

AbstractNewly derived property equations correlate BC(DEF) coordinates with calculated molar volume and refractivity and partitioning between water and six organic solvents. A new method is described for obtaining the BC(DEF) coordinates of a molecule from available physical property data. Its application to 500 compounds indicates that the BC(DEF) intercorrelation describes the properties of large and polar molecules, such as drugs, almost as well as those of simpler molecules. The effects of an erroneous physical property value on calculated BC(DEF) coordinates are described.
Relationship between Polarographic Adsorption Data and Hydrophobicity
Authors: Kühne Ronald , Franke Rainer , Dittrich Jürgen , Kretschmer Erhard 
Published: October 2006

AbstractGibbs free energies of adsorption of hydrophobic solutes at the dropping mercury electrode at zero potential and of partitioning in the system octanol/water are shown to be correlated for a number of compounds. It is suggested that polarographic adsorption data may serve as hydrophobicity parameters in QSAR work.
2n‐Factorial Schemes in Drug Design Extensions Increasing Versatility
Authors: Austel Voikhard 
Published: October 2006

AbstractSeveral extensions of 2n‐factorial series design are reported. These extensions comprise rotation of the factorial schemes as well as “axial” schemes. Thereby factorial series design becomes more flexible so that synthetic accessibility can be better accounted for. By combining 2n‐factorial schemes with axial schemes one can satisfy needs for larger numbers of samples which are required e.g. for deriving quantitative structure‐activity‐relationships or for deciding upon further examination of structural fields. The new schemes can be applied manually as well as in connection with pattern recognition techniques.
Some Critical Remarks Concerning the Inductive Parameter σI Part I: Aliphatic Amines
Authors: Bijloo Greetje J. , Rekker Roelof F. 
Published: October 2006

AbstractCorrelation analysis was applied to a series of pKa values of 135 primary, secondary and tertiary aliphatic amines and included 57 alkyl substituted and 78 nonalkyl substituted structures.It could be established that the σI data set in its latest version as proposed by Charton is very useful in practice, provided the small σI values for alkylgroups are replaced by zero throughout.