bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micturin (Terodiline Hydrochloride), Torsades de Pointe and other Arrhythmias — A Study using the VAMP Database
Authors: Hall G. C. , Chukwujindu J. , Richardson J. , Lis Y. , Wild R. N. 
Published: October 2006

AbstractIn a preliminary open study using the VAMP database only one confirmed case of torsades de pointe was identified from 9176 terodiline‐treated patients. The risk of torsades de pointe with terodiline is therefore 1.1 per 10,000.This preliminary study was followed by a retrospective cohort study which compared the risk of a patient treated with terodiline developing torsades de pointe, or other arrhythmias, with the risk in a matched reference population. In this study the follow‐up period of the patients treated with terodiline averaged 5 months (range 2 weeks to 41 months) and that of the controls averaged 6 months (range 2 weeks to 40 months).This comparative study showed that there was no significant difference in the risk of developing a cardiac arrhythmia between the cohort treated with terodiline and their reference patients. The incidence rate was 3.68 per 1000 in the group treated with terodiline and 3.33 per 1000 in the reference group. There was no significant difference in the risk of developing an arrhythmia in the terodiline‐treated patients compared with the controls (relative risk 1.1, 95% confidence intervals 0.64–1–90).
Completing the triangle — relationships between practice demography, general practitioner workload and prescribing
Authors: McGavock H. , Wilson‐Davis K. , Milligan Officer E. Administrative 
Published: October 2006

AbstractThe objective was to survey general practitioners' consulting workload and correlate workload with practice demography and prescribing. Two hundred and sixteen of the 345 Northern Irish practices completed a retrospective questionnaire of office consultations and home visits, November 1990. These data were amalgamated with the regional general practitioner prescribing database and statistical analyses were performed to reveal the frequency distribution of workload and to correlate workload with the number of partners, practice demography and prescribing. The consulting workload per doctor varied from 249 office consultations per month to 683. The commonest workload was 373 consultations per month. Single‐handed doctors had the largest workloads. The average length of consultation was 7.5 min a.m., 8.8 min p.m. Consulting workload correlated strongly with the number of patients over 60 (R = 0.72), mature adults 30–44 (R = 0.84) and children under 5 (R = 0.86), but weakly with the number of ‘officially‐deprived’ patients (R = 0.28). Workload could most precisely be predicted from practice demography using the equation:No. of consultations per month (for a given practice) = 1.31 (children 0–4) + 0.63 (children 10–14) + 0.004 (persons 15–59) + 0.1 (persons > 60) − 0.06 (deprived persons) + κR = 0.9006 (R2 = 0.811, i.e. 81.1% of variability in workload is determined by differences in practice demography)Where k is a categorical variable of number of partners in a practice.Similarly practice demography can explain 90.0% of the total variation in monthly total prescriptions per practice and 91.3% of the variation in total monthly prescription costs.Surgery workload correlated significantly with the number and cost of prescriptions (R = 0.35 to 0.50). This was true of specific prescribing (for proven pathology), for symptomatic prescribing and for prescribing of drugs often used less precisely than they should be (for presumptive diagnoses). On average, doctors issued 3.7 prescription items per consultation, with a net ingredient cost of £5.93 per prescription item. This study shows that general practitioner consulting workload is determined principally by the demography of the practice list and is itself a determinant of prescribing frequency and cost.
The systems for monitoring adverse drug reactions in Hong Kong
Authors: Chan Thomas Y. K. , Critchley Julian A. J. H. 
Published: October 2006

AbstractPost‐marketing surveillance is essential for providing additional safety information on drugs. In Hong Kong, a scheme to monitor ADRs was introduced in October 1986. It relies on voluntary reporting by hospital doctors and general practitioners of suspected ADRs. There appeared to be gross under‐reporting as only 68 reports were received between 1986 to 1991. Although hospital‐based studies have provided us with information on the pattern of and the risk factors for ADRs, spontaneous reporting on a national scale remains the only feasible and inexpensive method for monitoring ADRs. In order to increase reporting, we hope to convince the medical profession in Hong Kong of the importance in reporting ADRs and to make it easier for them to report.
Towards an adverse drug reactions dictionary. Should existing terminologies be harmonized?
Authors: Benichou C. 
Published: October 2006

AbstractDue to the worldwide marketing of drugs, centralization of information is mandatory. Several Adverse Drug Reactions (ADR) terminologies have been proposed. The most widely used are WHO‐ART and COSTART. However, because of cultural differences, all terms do not exist or do not have the same meaning in different languages or countries. Equivalence between terms of different terminologies are difficult to establish, since terms are proposed without definitions or precise guidelines for their use. Definitions given by medical dictionaries do not resolve this difficulty, since they are neither always concordant nor adapted to the level of information contained in spontaneous notifications. Therefore, it seems necessary to create a dictionary specific for ADR, listing all drug‐induced abnormalities and giving for each of them a definition adapted to the information usually available in pharmacovigilance. As most drug reactions are indistinguishable from non‐drug‐induced diseases, this dictionary must be created in concertation with experts in drug toxicity in each medical field, coming from different countries. An example of such an attempt is given; it was possible to draw a dictionary for liver and biliary disorders from an international consensus meeting of experts on definitions and criteria assessment of drug‐induced liver reactions. This approach could make unnecessary the harmonization of the various terminologies, since each of them would have to make a bridge towards a worldwide accepted ADR dictionary.
Delay and completeness of cancer registration in a post‐marketing surveillance study of cimetidine
Authors: Lucas T. , Beresford J. , Vessey M. 
Published: October 2006

AbstractData collected in a large multicentre post‐marketing surveillance study of cimetidine have been used to assess delay and completeness of cancer registration. With regard to delay, 44% of registrations in Nottingham were received within 2 years of the diagnosis of cancer but only 14% in Oxford and 6% in Portsmouth. By the end of the third year, these figures had become 82%, 62% and 62% respectively. With regard to completeness, in the period 3 to 10 years before the assessment date 9% of Nottingham, 36% of Oxford and 17% of Portsmouth neoplasms were still unregistered. Investigators using National Cancer Registry data for interpretation of their studies should be acquainted with the performance of the individual registries concerned.
PEM report number 3. Fluconazole
Authors: Inman William , Kubota Kiyoshi , Pearceb Gillian , Wilton Lynda 
Published: October 2006

AbstractThree groups of patients who were prescribed the oral anti‐fungal drug fluconazole between September 1988 and January 1989 were studied by Prescription‐Event Monitoring (PEM). The largest group of 13,440 patients, including 560 men, had been treated with a single 150 mg capsule. A smaller group of 798, including 55 men, had received more than one 150 mg capsule and a third small group of 777 patients, including 261 men, had received a course of treatment with 50 mg capsules. The first group was studied between February and June 1989 and the second and third groups in January 1990.In the two groups who had received single or multiple doses of 150 mg, the mean age of women was 34 and 35 years respectively and of men in both groups, 41 years. In the small group receiving 50 mg capsules the patients were considerably older, the males averaging 49 years and the females 46 years. While an overwhelming majority of females were treated for vaginal candidiasis, a significant number of men in the 150 mg groups and almost half the men in the 50 mg group had been treated for oral candidiasis. It was believed that a considerable number of men had been treated prophylactically while their partners were receiving treatment for vaginal candidiasis.General practitioners reported that the single 150 mg capsule had been effective in 85%. As expected, there were many cases of re‐infection or recurrences during the three‐month period of observation.The pattern of events was compared with data obtained from PEM studies of itraconazole and 31 other drugs. Upper respiratory tract and genito‐urinary infections were reported more frequently than with other drugs but the relationship was with the disease being treated rather than with the drug itself.There were four cases of angioneurotic oedema, only two of which were considered to have been possibly related to the use of fluconazole. There were also four reports of liver dysfunction, none of which was considered to be drug related.Although pregnancy is a contra‐indication, a total of 289 were reported. Thirty‐nine had terminated in spontaneous abortion and 38 were terminated therapeutically. Among women who used fluconazole prior to conception there were six abnormal pregnancies including four live births, one stillborn foetus with trisomy‐18 (Edwards' syndrome) and one anencephalic foetus. One mother had used fluconazole a week before conception. The baby had three short fingers on one hand. No abnormalities occurred in babies exposed during their mother's pregnancy.One hundred and twenty‐five deaths were investigated. Eighty of the deaths were due to cancer, 26 to neurological, cardiac or respiratory disease and seven to AIDS. Other or undetermined causes accounted for a further 12 deaths. No death was attributed to treatment.The overall conclusion reached after this study of more than 15,000 patients was that, while many events that had been recorded were attributable to the candidial infection, fluconazole was virtually free from recognizable side‐effects.
PEM report number 4. Ciprofloxacin
Authors: Inman William , Kubota Kiyoshi , Pearce Gillian , Wilton Lynda 
Published: October 2006

AbstractThe fluoroquinolone antibiotic ciprofloxacin has been studied by Prescription‐Event Monitoring (PEM) in 11,477 patients who had received prescriptions from general practitioners in England between November 1988 and January 1989. There were about 50% more females in the series than males and the average ages were 53.2 and 55.5 years respectively. Chest and urinary infections were the most common indications. Forty‐five per cent of the patients used 500 mg daily and 42% 1000 mg daily. Ciprofloxacin was said to have been effective in 90.3% of patients.The events were compared with those reported in 25 other studies in order to obtain some impression of the background rates in a population of more than a quarter of a million patients monitored by PEM. The events most frequently reported were related to the infections that were being treated and the most common side‐effects were those affecting the gastrointestinal system. There were three definite and one doubtful case of photosensitivy. Among the psychiatric events, only depression and malaise or lassitude occurred at a rate which exceeded one per 1000 patients during the first 13 weeks of follow‐up. Fourteen patients suffered convulsions but only two cases were considered to be possibly related either to treatment or to pyrexia associated with urinary tract infection. No cases of pseudomem‐branous colitis were identified although diarrhoea was the most common gastrointestinal event. Following the withdrawal of temafloxacin, the ciprofloxacin data were searched for evidence of hepatic or renal damage or hypoglycaemia, but no evidence was found with ciprofloxacin, or in, as yet uncompleted, studies of enoxacin, ofloxacin or norfloxacin. No serious adverse reactions (ADRs) or deaths attributable to ciprofloxacin were recorded and no previously unrecognized hazards were identified.The PEM data were compared with selected results from clinical trials. For the most part the incidence of events encountered during a three‐month period resembled those in clinical trials very closely.It was concluded that ciprofloxacin is a safe and effective antibiotic prescribed in general practice.
PEM report number 8. Cisapride
Authors: Inman William , Kubota Kiyoshi , Pearce Gillian , Wilton Lynda 
Published: October 2006

AbstractThe gastrointestinal prokinetic agent cisapride has been studied by Prescription‐Event Monitoring (PEM) in 13,234 patients who had received prescriptions from general practitioners in England between October 1990 and April 1991. There were 58% female and 41% male; the average age was 56 years. The most common indications were oesophageal reflux, dyspepsia and hiatus hernia.The events were compared with pooled data from a population of 332,402 patients in 33 PEM studies including those of omeprazole, nizatidine and famotidine which were used to provide estimates of background rates. The events most frequently reported were related to the conditions that were being treated, mainly those affecting the gastrointestinal tract. Diarrhoea was the most noteworthy among events identified as adverse reactions to cisapride. Dermatalogical, hepatic, cardiovascular and other sub‐groups of events were examined with particular care and no unacceptable hazards were detected.The PEM data were also compared with those from clinical trials involving treatment periods from four weeks to one year in similar patients. The pattern of events revealed by the PEM study closely matched the findings of clinical trials.It was concluded that cisapride is a safe and effective prokinetic agent causing few serious side‐effects when prescribed in general practice.
PEM report number 10. Zopiclone
Authors: Inman William , Kubota Kiyoshi , Pearce Gillian , Welton Lynda 
Published: October 2006

AbstractThe short‐acting, non‐benzodiazepine hypnotic, zopiclone, first marketed as ‘Zimovane’ in the United Kingdom in 1989, has been studied by Prescription‐Event Monitoring (PEM) in 13,177 patients. Of more than 24,000 forms that had been posted to general practitioners 55% were returned, the response ranging from 68% by doctors who had been sent only a single form to 19% from those who had been sent more than 30 forms. The mean ages of the patients were 53 and 54 or males and females respectively; 22% were aged over 70 years.Eighty‐five per cent of the patients were prescribed a dose of one tablet (7·5 mg). A large number of patients were using other psychotropic drugs concurrently — antidepressants, 12%; other hypnotics and sedatives, 8%.A subjective opinion of efficacy was favourable to the drug in 86% of patients.The pattern of events was compared with those encountered in a similar study of flunitrazepam, conducted eight years earlier, and with data from 31 other PEM studies. A large number of psychiatric events were noted, mostly attributable to concurrent disorders, some of which were clearly the reason for the patient's insomnia.There were only seven cases of possible dependence including three reported to the Committee on Safety of Medicines (CSM), for which no details were supplied to the Drug Safety Research Unit (DSRU). In this study there were no confirmed cases of dependence on zopiclone.Twenty patients overdosed deliberately with zopiclone alone, suffering no more than transient drowsiness. A further 16 took simultaneous overdoses of zopiclone and other drugs including one patient who took 28 tablets of zopiclone and 100 of co‐proxamol and died. Thirty‐seven patients overdosed with other drugs, with three deaths.PEM confirms that zopiclone has a very low risk of dependence and is safe in overdose.
Estimation of the signal generating value of spontaneous reports of adverse reactions
Authors: Biron Pierre , Balency Dominique 
Published: October 2006

AbstractThe main function of drug adverse reaction spontaneous reporting systems is the generation of early signals of previously undocumented serious reactions to recently marketed products. To quantify the signal generating value of case reports we first score them on a 6‐level causality/completeness scale combining the French and the European community assessment methods; prior documentation is scored on a 5‐level scale inspired from the French method. Then the prior documentation value is subtracted from the imputability value and the resulting difference is considered as a signal generating value. The result is a scale of ranks ranging from 1 to 10, averaging 4.8 in the database of our regional program. It may serve to compare the usefulness of spontaneous reports originating from different sources and it may encourage clinicans to submit more informative case reports.
Adverse drug reactions in HIV seropositive patients
Authors: Benichou C. , Eliaszewicz M. , Flahault A. 
Published: October 2006

AbstractPatients infected with the human immunodeficiency virus (HIV) will receive a number of drugs intended to fight the HIV infection itself or to avoid and treat its complications. In these patients, adverse drug reactions (ADRs) are unusual in their frequency, not in their type. They may involve all the systems and reduce the already limited therapeutic possibilities. The frequent absence of therapeutic alternatives may require, for certain reactions, the continuation of the suspected drug.The study of these patients may provide better comprehension of the mechanisms responsible for ADRs occurring in immuno‐competent patients, since the association of certain diseases with certain drugs increases the risk of drug reactions. The search for an enhancing, synergistic or at least a non‐neutralizing mechanism may improve the study or the prevention of all ADRs.The spread of HIV infection and the attempt to maintain the infected patient at home means that any physician is likely to be confronted with the diagnosis and treatment of a drug‐related toxicity in an HIV‐positive patient.In May 1993, a certain number of physicians who had specialized in the treatment of HIV‐infection and/or in management of ADRs, met to discuss the different toxicities observed with the drugs most often employed in this illness. The description, the incidences and the recommendations which are presented in this report reflect the opinion of a large majority — and often the unanimity — of the participants.
The impact and treatment of arthritis in general practice
Authors: Blackburn S. C. F. , Ellis R. , George C. F. , Kirwan J. R. 
Published: October 2006

AbstractFifty‐two general practitioners from a variety of practice settings recorded clinical information on 1964 patients with arthritis who independently completed questionnaires about their treatment, joints affected and disability. Of 1871 analysed, 79.4 per cent had osteoarthritis (OA) and 15.3 per cent rheumatoid arthritis (RA). Half of those with OA were under 65 years old, 60 per cent were obese and two‐thirds were women. The knee was the site most commonly affected. Mean disability scores (HAQ) were greater in RA than OA (1.28 versus 0.87) but 34 per cent of patients with OA were moderately disabled (score > 1) and 6 per cent severely disabled (score > 2), even after allowing for comorbid conditions. Disability increased markedly in patients over 75 years. Although these older OA patients were treated increasingly with simple analgesics alone, 69 per cent were taking non steroidal anti‐inflammatory drugs often in combination. Physiotherapy was not used frequently.These results illustrate the huge burden of disability caused by OA in the community and the opportunities to improve treatment.
Communication in pharmacovigilance
Authors: Moore N. , Montero D. , Coulson R. , De Abajo F. , Kreft‐Jais C. , Biron A. , Palop R. 
Published: October 2006

AbstractPharmacovigilance is a field where communication is paramount. Information, such as single case reports, is transferred from health professionals to National Regulatory Administrations and between administrations and industry. The cumulation of reports may be used for information purposes, and to assist in the identification of possible signals. These are then assessed by the analysis of individual and aggregate cases, the latter being exchanged between administrations for multinational analysis at the European level. Once a decision has been made on a possible alert, the decisions and the reasons thereof must be transmitted to administrations and to other correspondents, such as health professionals, the pharmaceutical industry and WHO.Within the CARE project of the DGXIII European Nervous System telematics research programme, the Pharmacovigilance Pilot, consisting of representatives of the French, Spanish, and UK pharmacovigilance systems, set out to identify and describe the messages corresponding to these communication needs, and the methods best suited to effective telematic transmission.The messages identified concern: the transmission of individual case reports, the transmission of cumulative and aggregate case reports, and of regulatory decisions.Each of these information messages have been structured for future inclusion into a network for electronic data interchange between administrations in pharmacovigilance. In time they should provide a common electronic vocabulary enabling all parties involved in pharmacovigilance to communicate telematically. Transmission options have been considered also. In view of the large number of existing and potential partners involved in the communication processes in pharmacovigilance, EDI (electronic data interchange) seems the most appropriate method to exchange these messages. Two of these, concerning the single case and the aggregate cases (rapid alerts) have been submitted to the Western European EDIFACT Board MD9 for integration into EDIFACT (as MEDADR and MEDPHV).
Electronic transmission of rapid alerts in pharmacovigilance: A pilot EC experiment
Authors: Montero D. , Moore N. , Coulson R. , Zabala J. L. , De Abajo F. , Kreft‐Jais C. , Wigglesworth K. , Biron A. , Monteagudo J. L. 
Published: October 2006

AbstractThough electronic communication and transfer of data is becoming commonplace, it is still rare between administrations. This is why CEC DGXIII started the European Nervous System (ENS) programme, to promote the use of telematics to facilitate the work of administrations. Pharmacovigilance is one of the pilots of CARE, an ENS project in health care. This pilot involves Instituto de Salud Carlos III (Spain), Medicines Control Agency (UK), and the French Pharmacovigilance System (France) along with Norsistemas Consultores (Spain). Its objective is to explore the possibilities of telematic transmission of Pharmacovigilance data between national administrations.The technical approach has tested the transmission of urgent drug alerts, information equivalent to that of the existing Rapid Alert scheme, up to now transmitted by fax. The network using international standards (Unix, X400, and EDI, based on X25 networks) has been set up between the three participating countries. The data structure for the drug alerts has been described and submitted to future European users. The message structure itself has been entered into the registration and validation process for EDIFACT certification. The application for message transmission has been written and is being tested and re‐evaluated. The information contained in these messages will be initially entered manually, but could be generated from national databases. Though this network at the present only concerns three countries, it is expected that most EC countries will be linked in the near future.