bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contraindicated NSAIDs are frequently prescribed to elderly patients with peptic ulcer disease
Authors: Visser Loes E. , Graatsma Hayo H. , Stricker Bruno H. Ch. 
Published: March 2003

Aims  To establish the frequency with which NSAIDs were prescribed to elderly patients after admission to hospital for serious gastrointestinal complications and to study which factors are determinants of the prescription of these contraindicated drugs.Methods  A retrospective cohort study of patients from The Rotterdam Elderly Study, a prospective population‐based cohort study of people older than 55 years of age was carried out. Elderly patients with a hospital admission for serious gastrointestinal complications were followed until prescription of an NSAID, death, removal to another area or end of the study period, whichever came first. The following baseline determinants for receiving a contraindicated prescription were studied: gender, age, presence of rheumatoid arthritis or osteoarthritis, presence of cardiovascular risk factors, number of GP visits, number of visits to a medical specialist, cognitive function and the prescriber being a GP or a medical specialist.Results  Prescriptions of an NSAID after discharge from hospital, were identified in 73 patients (73%). Fifty‐one percent were prescribed aspirin of whom the large majority used it as an antithrombotic agent, and 49% were prescribed a nonaspirin NSAID after discharge from hospital. Twenty percent of the patients used more than one NSAID on one or more occasions after discharge. For patients who were prescribed NSAIDs before admission as well as after discharge, the proportion of contraindicated prescriptions with concomitant use of antiulcer drugs rose significantly from 0.19 before discharge to 0.60 after discharge for aspirin and from 0.11 to 0.61 for nonaspirin NSAIDs. In the multivariate analysis the only remaining factor with prognostic influence on prescription of NSAIDs was a history of NSAID use before cohort enrolment. A history of rheumatoid arthritis or osteoarthritis was not associated with NSAID prescription after discharge.Conclusions  Contraindicated NSAIDs are prescribed to a great extent in elderly patients, despite their greater vulnerability for life‐threatening gastrointestinal blood loss. It is remarkable that a history of rheumatoid arthritis or osteoarthritis is no significant determinant for receiving a contraindicated prescription, which suggests that these drugs are mainly prescribed for uncomplicated arthralgia.
Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic data
Authors: De Hoon, J. N. J. M. , Poppe K. A. , Thijssen H. H. W. , Struijker‐Boudier H. A. J. , Van Bortel L. M. A. B. 
Published: March 2003

Aims  To investigate the peripheral vascular effects and pharmacokinetics of dihydroergotamine (DHE) 0.5 mg after a single subcutaneous administration in humans.Methods  A double‐blind, placebo‐controlled cross‐over study was performed in 10 healthy male subjects. A wash‐out period of 2 weeks separated the two study periods. During each period, just before and at regular intervals after drug administration, vascular measurements were performed and venous blood samples were drawn. Vessel wall properties were assessed at the brachial artery, by ultrasound and applanation tonometry. Blood pressure and heart rate were recorded with an oscillometric device. Forearm blood flow was measured with venous occlusion plethysmography. For all parameter‐time curves the area under the curve (AUC) was calculated. Differences in AUC after placebo and DHE (ΔAUC) were analysed and the time‐course of the difference assessed. DHE pharmacokinetics were analysed according to a two‐compartment open model with an absorption phase.Results  AUC for blood pressure, heart rate and forearm vascular resistance did not change after DHE. Brachial artery diameter and compliance decreased (P < 0.01); ΔAUC (95% confidence interval) equalled −8.81 mm h (−12.97/−4.65) and −0.98 mm2 kPa−1 h (−1.61/−0.34), respectively. Diameter decreased (P < 0.05) from 1 until 24 h after DHE (peak decrease 9.7% at 10 h); compliance from 2 until 32 h (24.8% at 2 h). Time to reach maximum plasma concentration of DHE averaged 0.33 ± 0.08 h (± s.e.mean); terminal half‐life was 5.63 ± 1.15 h.Conclusions  DHE decreased diameter and compliance of the brachial artery whereas forearm vascular resistance remained unchanged. Thus, DHE acts on conduit arteries without affecting resistance arteries. Furthermore, a discrepancy was demonstrated between the plasma concentrations of DHE which rapidly reach peak levels and quickly decline, and its long lasting vasoconstrictor activity.
Risk of suicide in users of β‐adrenoceptor blockers, calcium channel blockers and angiotensin converting enzyme inhibitors
Authors: Sørensen Henrik Toft , Mellemkjær Lene , Olsen Jørgen H. 
Published: March 2003

Aims  To examine the risk of suicide in users of β‐adrenoceptor blockers, calcium channel blockers, and angiotensin converting enzyme inhibitors.Methods  We conducted a cohort study based on linkage of a population‐based prescription registry in North Jutland County, Denmark, and the nationwide Death Registry. From 1989 to 1995 there were 58 529 users of β‐adrenoceptor blockers, calcium channel blockers, and angiotensin converting enzyme inhibitors. The mortality rates from suicides in the cohort members were compared with the rates in the general population.
Results
One hundred and four suicides occurred in the cohorts. The standardized mortality ratio for suicide in users of β‐adrenoceptor blockers was 1.6 (95% confidence interval: 1.2–2.1), in users of calcium channel blockers 1.2 (95% confidence interval: 0.8–1.7), and in users of angiotensin converting enzyme inhibitors 1.2 (95% confidence interval: 0.7–1.8). In users of β‐adrenoceptor blockers, the risk of suicide was increased during the first 12 months after the start of therapy, standardized mortality ratio 2.1 (95% confidence interval: 1.2–3.5). There was a trend in the standardized mortality ratio of suicide from 0.9 (95% confidence interval: 0.4–1.9) in users of β‐adrenoceptor blockers with low lipid solubility, to 1.6 (0.8–2.8) and 2.7 (1.7–4.1) in users of β‐adrenoceptor blockers with medium and high lipid solubility, respectively.
Conclusions
Users of medium and high lipid soluble β‐adrenoceptor blockers may have an increased risk of suicide. Users of calcium channel blockers and angiotensin converting enzyme inhibitors do not seem to have a significantly increased risk of suicide.
Adverse drug reactions in patients admitted to hospital identified by discharge ICD‐10 codes and by spontaneous reports
Authors: Cox A. R. , Anton C. , Goh C. H. F. , Easter M. , Langford N. J. , Ferner R. E. 
Published: March 2003

Aims  We studied the international classification of disease (ICD) hospital discharge codes to find unreported adverse drug reactions (ADRs), and asked doctors about their attitudes to reporting some of these cases.Methods  We examined the ICD codes assigned on discharge to identify ADRs and compared these with spontaneous reports made to the Committee on Safety of Medicines (CSM). Doctors involved were sent brief résumés of cases and asked if they would report them.Results  49 of 21 365 patient episodes were coded on discharge as ADRs, of which 33 were ‘reportable’. Fourteen spontaneous reports were received by the CSM during the same period. The two groups did not overlap. 25 of 60 doctors responded to our questionnaire, and would have reported only 8 of 75 cases outlined.Conclusions  The ICD coding allowed us to identify important ADRs which most doctors would not report spontaneously.
Herb–drug interactions: Review and assessment of report reliability
Authors: Fugh‐Berman Adriane , Ernst E. 
Published: March 2003

Aims  The aim of this systematic review was to assess the published clinical evidence on interactions between herbal and conventional drugs.Methods  Four electronic databases were searched for case reports, case series or clinical trials of such interactions. The data were extracted and validated using a scoring system for interaction probability.Results  One hundred and eight cases of suspected interactions were found. 68.5% were classified as ‘unable to be evaluated’, 13% as ‘well‐documented’ and 18.5% as ‘possible’ interactions. Warfarin was the most common drug (18 cases) and St John's wort the most common herb (54 cases) involved.Conclusion  Herb–drug interactions undoubtedly do occur and may put individuals at risk. However our present knowledge is incomplete and more research is urgently needed.
Variability of cytochrome P450 1A2 activity over time in young and elderly healthy volunteers
Authors: Simon T. , Becquemont L. , Hamon B. , Nouyrigat E. , Chodjania Y. , Poirier J. M. , Funck‐Brentano C. , Jaillon P. 
Published: March 2003

Aims  To assess the age‐associated changes over time of plasma paraxanthine/caffeine (PAX/CAF) ratios used as a probe for CYP1A2 activity.Methods  Intraindividual and interindividual variabilities in PAX/CAF ratio were compared by phenotyping with caffeine, 16 young and 16 elderly healthy subjects on five occasions.
Results
PAX/CAF ratio variability was comparable regardless of age (intraindividual CV: 17.6 ± 6% and 16.2 ± 5.9%, interindividual CV: 48.1 ± 2.9% and 42.7 ± 3.6% in young and elderly, respectively). The PAX/CAF ratio was lower in elderly than in young subjects (95% CI for the difference: 0.004, 0.32) but the difference was not significant in nonsmokers compared separately.Conclusions  The variability over time of the PAX/CAF ratio is not influenced by age.
What benefit do patients expect from adding second and third antihypertensive drugs?
Authors: Leaman Hannah , Jackson Peter R. 
Published: March 2003

Aims  To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment.Methods  This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected.Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously.Conclusions  People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.
Effect of aspirin on vasodilation to bradykinin and substance P in patients with heart failure treated with ACE inhibitor
Authors: Davie Andrew P. , McMurray John J. V. 
Published: March 2003

Aims  We wanted to examine some of the mechanisms by which aspirin might be responsible for counteraction of the effects of ACE inhibitors. Aspirin has been reported to counteract the effects of ACE inhibitors in patients with heart failure. Despite this, there is little evidence on what the mediator of such an effect might be, although there is some evidence to implicate bradykinin and, perhaps, substance P.Methods  Twelve patients with congestive heart failure treated with an ACE inhibitor were studied on two occasions, after abstaining from aspirin for 14 days, and after 14 days of aspirin 150 mg once daily. Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of bradykinin and substance P, before and after intrabrachial aspirin.Results  Bradykinin caused profound vasodilation (peak 390%, 95% confidence intervals (CI) 300, 480%; P < 0.01), substance P slightly less (peak 222%, 95% CI 162, 283%; P < 0.01). Intra‐brachial aspirin had no effect on its own. The response to bradykinin was unchanged by intrabrachial aspirin (peak 404%, 95% CI 304, 504%) or oral aspirin (peak 320%, 95% CI 209, 431%; P = 0.2). The response to substance P was unchanged by intrabrachial aspirin (peak 226%, 95% CI 171, 281%) or oral aspirin (peak 220%, 95% CI 142, 297%; P = 0.86).Conclusions  Aspirin has no effect on the vasodilator response to bradykinin and substance P in patients with heart failure treated with an ACE inhibitor. Neither bradykinin nor substance P is likely to contribute to the reported interaction between aspirin and ACE inhibitors.
Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions
Authors: Ogutu B. R. , Newton C. R. J. C. , Crawley J. , Muchohi S. N. , Otieno G. O. , Edwards G. , Marsh K. , Kokwaro G. O. 
Published: March 2003

Aims  Convulsions are a common complication of severe malaria in children and are associated with poor outcome. Diazepam is used to terminate convulsions but its pharmacokinetics and pharmacodynamics have not been studied in this group. Accordingly, we carried out a comparative study of the pharmacokinetics of intravenous (i.v.) and rectal (p.r.) diazepam.Methods  Twenty‐five children with severe malaria and a convulsion lasting >5 min were studied. Sixteen children received diazepam intravenously (i.v.; 0.3 mg kg−1) and nine rectally (p.r.; 0.5 mg kg−1). Plasma diazepam concentrations were measured by reversed phase high‐performance liquid chromatography. The duration of convulsions, depth of coma, respiratory and cardiovascular parameters were monitored.Results  Median maximum plasma diazepam concentrations of 634 (range 402–1507) ng ml−1 and 423 (range 112–1953) ng ml−1 were achieved at 5 and 25 min following i.v. and p.r. administration, respectively. All patients except three (one i.v. and two p.r.) achieved plasma diazepam concentration >200 ng ml−1 within 5 min. Following p.r. administration, plasma diazepam concentrations were more variable than i.v. administration. A single dose of i.v. diazepam terminated convulsions in all children but in only 6/9 after p.r. administration. However, nine children treated with i.v. and all those treated with p.r. diazepam had a recurrence of convulsions occurring at median plasma diazepam concentrations of 157 (range: 67–169) and 172 (range: 74–393) ng ml−1, respectively. All the children in the i.v. and four in the PR diazepam group who had recurrence of convulsions required treatment. None of the children developed respiratory depression or hypotension.Conclusions  Administration of diazepam i.v. or p.r. resulted in achievement of therapeutic concentrations of diazepam rapidly, without significant cardio‐respiratory adverse effects. However, following p.r. administration, diazepam did not terminate all convulsions and plasma drug concentrations were more variable.
Management ofHelicobacter pylorieradication – the influence of structured counselling and follow‐up
Authors: Al‐Eidan F. A. , McElnay J. C. , Scott M. G. , McConnell J. B. 
Published: March 2003

Aims Helicobacter pylori(H. pylori) eradication rate varies according to the treatment regimen used and other factors, e.g. antimicrobial resistance and patient compliance. The aim of the present study was to evaluate the influence of patient counselling and follow‐up onH. pylorieradication rates and to document the effectiveness of a 1 week eradication regimen consisting of lansoprazole (30 mg once daily), amoxicillin (1 g twice daily) and clarithromycin (500 mg twice daily).Methods Seventy‐six dyspeptic patients, who at endoscopy were found to have gastritis, duodenitis or ulceration, and a positiveH. pyloriurease test, were recruited. Patients were randomly assigned to an intervention group (n = 38) or a control group (n = 38). Intervention patients received their medicines via the hospital pharmacy and were counselled (and followed up) by a hospital pharmacist. Control patients were given a standard advice sheet and referred to their GP who prescribed the same therapy.Results Intervention patients exhibited a statistically significant improvement in theH. pylorieradication rate (94.7%vs73.7%;P = 0.02) and compliance (92.1%vs23.7;P < 0.001). Of the 64H. pylorieradicated patients, 62 were able to eliminate their antisecretory medication compared with only 12 of theH. pyloripersistent patients (P < 0.001). A pharmacoeconomic evaluation indicated that counselling and follow‐up reduced the direct costs of eradication by approximately £30 per patient.Conclusions Structured patient counselling and follow‐up can have a significant effect onH. pylorieradication rates and should be a routine part of therapy.
Frequency of adverse drug reactions in children: A prospective study
Authors: Jonville‐Béra Annie Pierre , Giraudeau Bruno , Blanc Pascal , Beau‐Salinas Frèdèrique , Autret‐Leca Elisabeth 
Published: March 2003

Aims  To assess the frequency of adverse drug reactions (ADRs) in children in France.Methods  In a prospective study over a period of 1 week, we evaluated the incidence of ADRs (1) as a cause of admission to a regional children's hospital; (2) occurring during hospitalization in a regional children's hospital; and (3) as a cause of consultation with private paediatricians.Results  Four out of 260 children were admitted to the regional children's hospital for ADRs (1.53% [0.42, 3.89]) and six developed ADRs during hospitalization (2.64% [0.97, 5.66]), 4/428 attended the Accident and Emergency Department for ADRs (0.93% [0.25, 2.37]) and 8/1192 consulted a private paediatrician for ADRs (0.67% [0.29, 1.31]).Conclusions  Our results are in agreement with the incidence of ADRs in children found in others countries.
Evaluating a putative mimetic relationship between two butterflies, Adelpha bredowii and Limenitis lorquini
Authors: Prudic Kathleen L. , Shapiro Arthur M. , Clayton Nicola S. 
Published: March 2003

Abstract 1. A laboratory bioassay experiment was performed in order to investigate a long‐standing putative mimetic relationship between two butterflies, the Lorquin's admiral Limenitis lorquini and the California sister Adelpha bredowii (Lepidoptera, Nymphalidae). These butterfly species are commonly sympatric in their broad distribution on the west coast of the United States. The wing colour pattern of L. lorquini differs from the patterns exhibited by its North American congeners, resembling A. bredowii instead.2. The feeding responses of California scrub jays Aphelocoma californica (Passeriformes, Corvidae) to these prey types and a known palatable control, the buckeye butterfly Junonia coenia (Lepidoptera, Nymphalidae), were examined quantitatively. The birds usually demonstrated long handling times of A. bredowii before consumption, while L. lorquini was manipulated and consumed at the same rate as the control butterfly. The birds also exhibited feather ruffling and bill wiping after consuming A. bredowii while they did not exhibit such behaviours after consuming L. lorquini and J. coenia.3. The birds did not discriminate between the dorsal colour patterns of the two species in a choice experiment.4. Because A. bredowii was moderately unpalatable to the captive scrub jays and the birds were not discriminating in their choice, this suggests a Batesian mimetic relationship between L. lorquini and A. bredowii.
Factors associated with plasma lipids and lipoproteins in Type 1 diabetes mellitus: the EURODIAB IDDM Complications Study
Authors: Idzior‐Walus B. , Mattock M. B. , Solnica B. , Stevens L. , Fuller J. H. ,   the EURODIAB IDDM Complications Study Group
Published: March 2003

AbstractAim  To assess the determinants and prevalence of hyperlipidaemia in Type 1 diabetic patients in the EURODIAB IDDM Complications Study.Methods  Standardized questionnaire data were obtained and anthropometric and biochemical measurements performed on 3159 Type 1 diabetic patients, randomly selected from 31 diabetes clinics. Plasma lipid levels were determined centrally, using enzymatic methodsResults  Plasma total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), and HDL subfractions were higher in women than in men, while plasma triglycerides were higher in men (P < 0.001). Total cholesterol, low‐density lipoprotein cholesterol (LDL‐C) and HDL‐C and HDL‐C subfractions were, as expected, significantly associated with age and HbA1c in both sexes. Age and HbA1c adjusted values of triglyceride, total cholesterol, LDL‐C, HDL‐C and HDL3‐C in men and triglyceride and HDL2‐C in women showed significant associations with central obesity, measured as the waist to hip ratio (WHR). Current smokers had lipid profiles characteristic of insulin resistance in comparison to nonsmokers. Significant positive associations were observed between hypertension and plasma triglycerides, total cholesterol and LDL‐C in men and women. In men, degree of physical activity was negatively associated with triglyceride and positively related to HDL‐C and HDL3‐C. The prevalence of LDL‐hypercholesterolaemia (LDL‐C > 3.35 mmol/L) was 45% in men and in women, while plasma triglyceride levels > 1.7 mmol/L were observed in 12% of men and 8% of women.Conclusion  The results of this study indicate that lipid levels in Type 1 diabetic patients are strongly influenced by smoking habit and central obesity in a way that is characteristic of the insulin resistance syndrome.Diabet. Med. 18, 786–796 (2001)