bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a short postgraduate course in rational pharmacotherapy for general practitioners
Authors: Akici Ahmet , Kalaça Sibel , Ugurlu M. Ümit , Karaalp Atila , Çali Şanda , Oktay Şule 
Published: December 2004

Aims  The impact of a short postgraduate course on rational pharmacotherapy planning behaviour of general practitioners (GP) was investigated via a face‐to‐face interview with 25 GPs working at health centres in Istanbul.Methods  GPs were randomly allocated to control and intervention groups. Intervention group attended a 3‐day‐training program preceded and followed by a written exam to plan treatment for simulated cases with a selected indication. The participants’ therapeutic competence was also tested at the post‐test for an unexposed indication to show the transfer effect of the course. In addition, patients treated by these GP's were interviewed and the prescriptions were analysed regarding rational use of drugs (RUD) principles at the baseline, 2 weeks and 4 months after the course.Results  At the baseline there was not any significant difference between the control and intervention groups in terms of irrational prescribing habits. The questionnaires revealed that the GPs were not applying RUD rules in making their treatment plans and they were not educating their patients efficiently. Training produced a significant improvement in prescribing habits of the intervention group, which was preserved for 4 months after the course. However, very low scores of the pretest indicate the urgent necessity for solutions.Conclusions  Training medical doctors on RUD not only at the under‐ but also at the postgraduate level deserves attention and should be considered by all sides of the problem including academia, health authorities and medical associations.
The effect of hypertension and hypercholesterolemia screening with subsequent intervention letter on the use of blood pressure and lipid lowering drugs
Authors: Atthobari Jarir , Monster Taco BM , De Jong Paul E , De Jong‐van den Berg Lolkje TW ,   Prevend Study Group
Published: December 2004

Aim  To evaluate the effect of a letter intervention that was send to both the participants of a population screening and their general practitioners. We also tested what predicting variables influenced the GP to actually prescribe blood pressure lowering drugs (BPLD) or lipid lowering drugs (LLD).Method  The study design was cross sectional, in the PREVEND outpatient clinic in Groningen University Hospital, the Netherlands. We used the clinical data of the 8592 subjects that participated in the first screening of the PREVEND study. Data on drug use was collected from community pharmacies. Drug use was measured the year before and after the screening with the subsequent intervention letter. As control population without intervention, we used the data from the InterAction DataBase (IADB) standardized for the population characteristics of the intervention group. The letter intervention was sent to participants who had shown after screening to have either an elevated blood pressure or plasma cholesterol, and the letter contained the advice to use a BPLD or LLD. Main outcome measures were proportion of patients prescribed BPLD and/or LLD in the year before and after the intervention, and variables that influence the GP to prescribe BPLD and LLD.Results  Data from the community pharmacy were available from 7567 (88%) subjects. 397 participants (5.2%) received a letter with advice to start a BPLD, and 326 participants (4.3%) received a letter with advice to start a LLD. The prevalence of patients who were using BPLD and LLD before the intervention was not significantly different between the intervention and control group, 16.6 (CI 95% 15.8 –17.5) vs 16.0 and 4.8 (4.4–5.3) vs 4.6, respectively. After the letter intervention, the prevalence of BPLD use was higher in the intervention group compared with the control group (19.4 [18, 5–20, 3]vs 17.0%), as was the prevalence of LLD use (7.1[6.5–7.7) vs 5.4%). The same held true for the incidence of BPLD (3.4[3.0–3.8]vs 2.5%) and LLD use (2.1 [1, 6–2, 4]vs 1.0%), respectively, in the year after the intervention. Univariate and multivariate analysis showed that a higher blood pressure and cholesterol level, but not the presence of other cardiovascular risk factors, were associated to with a greater percentage use of a BPLD and a LLD.Conclusion  A population survey followed by a letter of intervention to both the patient and GP are effective to improve the use of blood pressure and lipid lowering drugs as a primary prevention in patients with hypertension and hyperlipidemia. Our therapeutic advice however, was followed only in about one of the three subjects with hypertension and one of the four subjects with hyperlipidemia. The levels of blood pressure and plasma total cholesterol are important variables influencing the GP to prescribe a BPLD and/or LLD.
Have COX‐2 inhibitors influenced the co‐prescription of anti‐ulcer drugs with NSAIDs?
Authors: Teeling Mary , Bennett Kathleen , Feely John 
Published: December 2004

Aims  To quantify usage of COX‐2 inhibitors compared with nonselective NSAIDs and to determine their impact (including financial) on the co‐prescription of antipeptic ulcer (anti‐PU) drugs.Methods  The Irish General Medical Services prescription database (covering 1.2 million people) was examined for NSAID prescriptions during December 1999‐November 2001. NSAID users were excluded during the first 6 months. During the next 12 months (study period) patients on NSAIDs (≥ 3 prescriptions) were identified. The study period and final 6 months provided data on co‐prescription of anti‐PU drugs. Age, gender, number of concomitant prescriptions, co‐prescribing of anti‐PU drugs and monthly cost were evaluated for 8 NSAIDs (n= 4 non‐selective NSAIDs and n= 4 COX‐2 inhibitors) and odds ratios (OR) calculated using logistic regression.Results  COX‐2 inhibitors were prescribed more frequently in older, female patients and those receiving multiple medications. After adjustment for age, gender and polypharmacy, anti‐PU drugs were prescribed more frequently with COX‐2 inhibitors (OR = 1.31 (1.23,1.40)). COX‐2 inhibitors were up to 10‐fold more expensive, median monthly costs (including anti‐PU drugs) ranging from €34.61 (COX‐2 inhibitors) to €3.26 (nonselective NSAIDs).Conclusions  Since COX‐2 inhibitors are associated with increased rates of co‐prescription of anti‐PU drugs and are more expensive than non‐selective NSAIDs, these results suggest that the expected cost‐savings with COX‐2 inhibitors may not be occurring in practice.
Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol
Authors: Malonne H. , Sonet B. , Streel B. , Lebrun S. , De Niet S. , Sereno A. , Vanderbist F. 
Published: December 2004

Aims To compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche‐en‐Famenne, Belgium) with that of an immediate release capsule (Topalgic® 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability.Methods The first study had an open, single‐dose, three‐treatment, three‐period, six‐sequence, randomised, crossover design with at least a five‐day wash‐out. The second study had an open, steady‐state, two‐treatment, two‐period, two‐sequence, randomised crossover design with at least a seven‐day wash‐out. Both studies contained 30 healthy subjects. Both enantiomers of tramadol and O‐demethyl‐tramadol (the only active metabolite of tramadol) were assayed in the plasma using an LC‐MS/MS method. AUC∞, AUCt, Cmax, Tmax, and T1/2 were estimated. Statistical analysis was performed using univariate anova, the Wilcoxon nonparametric method or Friedman's nonparametric anova where appropriate.Results Tramadol had a significantly lower Cmax and longer Tmax than the conventional formulation. Thus, the mean (± sd) Cmax of tramadol were 646 ± 192 and 300 ± 94 ng ml−1 for Topalgic® 4 × 50mg and Tramadol LP 200 mg, respectively (95% confidence interval on the difference expressed as a percentage 42–51). AUC of tramadol from both formulations was comparable (similar AUC∞ and AUCt). Thus, the mean AUC∞ of (+/–)tramadol obtained after multiple dosing were 4611 ± 1944 and 5105 ± 2101 ngh ml−1 after Topalgic® 4 × 50mg and Tramadol LP 200 mg, respectively (95%CI 102–123%). We also demonstrate that the pharmacokinetics of the drug are not influenced by the intake of food. Thus, the mean AUC∞ of (+/–) tramadol were 5444 ± 1637 and 5169 ± 1580 ngh ml−1 after Tramadol LP 200 mg given in the fasting and fed states, respectively (95%CI = 88–103%).Conclusions The new sustained release form of tramadol exhibits adequate properties for once a day administration. Furthermore, its pharmacokinetic profile is not affected by the intake of food.
Trends in accessibility to medicines for children in New Zealand: 1998–2002
Authors: Chui Jocelyn , Tordoff June , Kennedy Julia , David Reith  
Published: December 2004

Background Reported rates of unlicensed and off‐label use of medicines in children raise concerns regarding overall access of children to medicinesObjective To assess changes in availability of proprietary formulations suitable for infants and young children; licensing of medicines; and subsidization of medicines for children in New Zealand.Methods Review of the New Ethicals Catalogue, New Ethicals Compendium, product data sheets and the New Zealand Pharmaceutical Schedule covering the years 1998–2002 inclusive.Results There was a decrease in the total number of medicines licensed in New Zealand from 2014 to 1840; but there was an increase in the number and percentage of suitable formulations that were licensed for paediatric use from 616[31%] to 642[35%]. The number of suitable paediatric formulations that were subsidized decreased from 281[13.9%] to 260[14.1%]. The number of orally available chemical entities with suitable formulations, licensed and subsidized for paediatric use declined from 101[5.0%] to 94[5.1%], but all of these chemical entities that were withdrawn had therapeutic alternatives that were licensed and subsidized. Only 36% of new medicines that had licensing for children were licensed for the 0–23 month age group.Conclusion There have been modest improvements in licensing of medicines for children in New Zealand from 1998 to 2002.
The presence of emphysema does not affect the systemic bioactivity of inhaled fluticasone in severe chronic obstructive pulmonary disease
Authors: Lee Daniel K. C. , Lipworth Brian J. 
Published: December 2004

AimsTo assess the systemic bioactivity of fluticasone proprionate (FP) 2000 µg daily on sensitive adrenal and bone markers in severe chronic obstructive pulmonary disease (COPD) patients with or without significant emphysema.MethodsTen patients without emphysema (COPD group: age 55 years, FEV1 51% predicted and DLCO 83% predicted) and 10 patients with emphysema (COPDE group: age 59 years, FEV1 43% predicted and DLCO 49% predicted) received FP 2000 µg daily via a spacer for 2 weeks. There was a 1‐week washout period prior to FP treatment where patients were given salmeterol and oxitropium, after stopping their usual inhaled corticosteroids for the duration of the study. Measurements including overnight 10 h urinary cortisol excretion corrected for creatinine (OUCC) and serum osteocalcin concentrations were performed at baseline following washout and after 2 weeks of FP.ResultsValues for OUCC and serum osteocalcin concentrations pre‐ and post‐FP were not significantly different between the COPD and COPDE groups. There was significant suppression of OUCC (nmol mmol−1) by FP treatment within the COPD group (P = 0.03): 7.86 vs 4.64 (95% CI on the difference 0.47, 5.98), and within the COPDE group (P = 0.006): 7.13 vs 4.27 (95% CI on the difference: 1.03, 4.69). Likewise, there was significant suppression of osteocalcin concentration (nmol l−1) by FP treatment within the COPD group (P = 0.04): 7.24 vs 6.34 (95% CI on the difference: 0.01, 1.78), and within the COPDE group (P = 0.03): 6.92 vs 5.72 (95% CI on the difference: 0.12, 2.29).ConclusionsSevere COPD patients who are receiving high dose FP are susceptible to the development of systemic adverse effects, irrespective of the presence of emphysema.
The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects
Authors: Niemi Mikko , Kajosaari Lauri I. , Neuvonen Mikko , Backman Janne T. , Neuvonen Pertti J. 
Published: December 2004

AimsOur aim was to investigate the effect of the CYP2C8 inhibitor trimethoprim on the pharmacokinetics and pharmacodynamics of the antidiabetic drug repaglinide, and to examine the influence of the former on the metabolism of the latter in vitro.MethodsIn a randomized, double‐blind, crossover study with two phases, nine healthy volunteers took 160 mg trimethoprim or placebo orally twice daily for 3 days. On day 3, 1 h after the last dose of trimethoprim or placebo, they ingested a single 0.25 mg dose of repaglinide. Plasma repaglinide and blood glucose concentrations were measured for up to 7 h post‐dose. In addition, the effect of trimethoprim on the metabolism of repaglinide by human liver microsomes was investigated.ResultsTrimethoprim raised the AUC(0,∞) and Cmax of repaglinide by 61% (range, 30–117%; P= 0.0008) and 41% (P = 0.005), respectively, and prolonged the t½ of repaglinide from 0.9 to 1.1 h (P = 0.001). Trimethoprim had no significant effect on the pharmacokinetics of its aromatic amine metabolite (M1), but decreased the M1 : repaglinide AUC(0,∞) ratio by 38% (P = 0.0005). No effect of trimethoprim on the blood glucose‐lowering effect of repaglinide was detectable. In vitro, trimethoprim inhibited the metabolism of (220 nm) repaglinide in a concentration‐dependent manner.ConclusionsTrimethoprim raised the plasma concentrations of repaglinide probably by inhibiting its CYP2C8‐mediated biotransformation. Although the interaction did not significantly enhance the effect of repaglinide on blood glucose concentration at the drug doses used, the possibility of an increased risk of hypoglycaemia should be considered during concomitant use of trimethoprim and repaglinide in patients with diabetes.
A prospective multicentre study of pharmacist initiated changes to drug therapy and patient management in acute care government funded hospitals
Authors: Dooley Michael J. , Allen Karen M. , Doecke Christopher J. , Galbraith Kirsten J. , Taylor George R. , Bright Jennifer , Carey Dianne L. 
Published: December 2004

AimsTo determine the cost savings of pharmacist initiated changes to hospitalized patients’ drug therapy or management in eight major acute care government funded teaching hospitals in Australia.MethodsThis was a prospective study performed in eight hospitals examining resource implications of pharmacists’ interventions assessed by an independent clinical panel. Pharmacists providing clinical services to inpatients recorded details of interventions, defined as any action that directly resulted in a change to patient management or therapy. An independent clinical review panel, convened at each participating centre, confirmed or rejected the clinical pharmacist's assessment of the impact on length of stay (LOS), readmission probability, medical procedures and laboratory monitoring and quantified the resultant changes, which were then costed.ResultsA total of 1399 interventions were documented. Eight hundred and thirty‐five interventions impacted on drug costs alone. Five hundred and eleven interventions were evaluated by the independent panels with three quarters of these confirmed as having an impact on one or more of: length of stay, readmission probability, medical procedures or laboratory monitoring. There were 96 interventions deemed by the independent panels to have reduced LOS and 156 reduced the potential for readmission. The calculated savings was $263 221 for the eight hospitals during the period of the study. This included $150 307 for length of stay reduction, $111 848 for readmission reduction.ConclusionsThe annualized cost savings relating to length of stay, readmission, drugs, medical procedures and laboratory monitoring as a result of clinical pharmacist initiated changes to hospitalized patient management or therapy was $4 444 794 for eight major acute care government funded teaching hospitals in Australia.
Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function
Authors: Kamerling Ingrid M. C. , Van Haarst Aernout D. , Burggraaf Jacobus , Schoemaker Rik C. , De Kam Marieke L. , Heinzerling Hartmut , Cohen Adam F. , Masclee Ad A. M. 
Published: December 2004

AimTo assess the effects of the motilin receptor antagonist RWJ‐68023 on basal and motilin‐stimulated proximal gastric volume.MethodsEighteen healthy male volunteers received RWJ‐68023 in two different doses or placebo for 135 min. After 45 min, subjects received a motilin infusion for 90 min. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored using visual analogue scales. Motilin and RWJ‐68023 concentrations were assessed by radioimmunoassay and liquid chromatography‐mass spectrometry, respectively.ResultsBoth dosages of RWJ‐68023 were safe and well tolerated. The most common adverse events were of gastrointestinal origin. RWJ‐68023 did not affect basal proximal gastric volume, but the high‐dose RWJ‐68023 reduced the contractile effect of motilin on the stomach. This antagonizing effect of RWJ‐68023 was only significant (P = 0.014) during the distension procedure.ConclusionsThe RWJ‐68023 doses used in this study were selected to accomplish plasma concentrations that would block the motilin effect entirely. However, the antagonizing effect of RWJ‐68023 was partial and only present when the tonic condition of the stomach was modulated by motilin.
Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine
Authors: Van Riemsdijk M. M. , Sturkenboom M. C. J. M. , Ditters J. M. , Tulen J. H. M. , Ligthelm R. J. , Overbosch D. , Stricker B. H. 
Published: December 2004

AimsWe performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas.MethodsWe enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine prophylaxis during the period between 1 May 1999 and 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after starting weekly intake of 250 mg mefloquine. We compared the intraindividual change in scores between baseline and follow‐up visit on the Dutch shortened Profile of Mood States, and on the Continuous Performance Test (CPT) which measures sustained attention.ResultsThe final cohort consisted of 151 subjects with a mean age of 38 years. In this population, a significant impairment of mood state was observed in those with a body mass index (BMI) ≤ 20 kg m−2. Stratification for gender showed that the total mood disturbance in females in the lowest BMI category significantly increased by 8.42 points [95% confidence interval (CI) 3.33, 13.50], whereas BMI did not affect the risk in males. Stratification for history of use of mefloquine showed that the risks were highest in first‐time users. Analyses of the CPT showed that reaction time in women with a BMI ≤ 20 kg m−2 increased significantly by 22.5 ms (95% CI 7.80, 37.20), whereas reaction time in men showed a slight and nonsignificant decrease.ConclusionRisk factors for mefloquine‐associated neuropsychiatric adverse events and concentration impairment are female gender, low BMI, and first‐time use. The frequency of neuropsychiatric effects is highest in women with a BMI ≤ 20 kg m−2.
Agranulocytosis, arthritis and systemic vasculitis in a patient receiving the oral iron chelator L1 (deferiprone)
Authors: CASTRIOTA‐SCANDERBEG ALESSANDRO , SACCO MICHELE 
Published: December 2004

A thalassaemic girl presented with agranulocytosis, arthritis of both ankles and clinical and laboratory features consistent with the diagnosis of systemic vasculitis, during oral iron chelator L1 (deferiprone) treatment. Changes in the humoral and cell‐mediated immune function, including antinuclear antibodies (ANA), anti‐DNA and extractable‐nuclear antigens (ENA) antibodies positivity, increased immunoglobulin values, decreased T suppressor and the presence of circulating immune complexes, suggest a cause‐and‐effect relationship with the observed clinical manifestations.A careful monitoring of the immune function is recommended in patients who are receiving the oral iron chelator L1.
Iron metabolism in transgenic mice with hypoplastic anaemia due to incomplete deficiency of erythropoietin
Authors: RAJA K. B. , MAXWELL P. H. , RATCLIFFE P. J. , SALISBURY J. R. , SIMPSON R. J. , PETERS T. J. 
Published: December 2004

Iron overload is a serious complication of many forms of anaemia, arising in part from mechanisms associated with compensatory increases in erythropoiesis. To investigate other mechanisms by which anaemia itself may perturb iron metabolism, without the confounding effects of compensatory erythropoiesis, we studied transgenic mice with a partially disabling insertion in the erythro‐poietin gene, which manifested as incomplete erythropoietin deficiency.Mice were studied aged 7–8 weeks. Haemoglobin concentrations were 6.6 ± 0.8 g/dl in mice homozygous for the modified erythropoietin gene, 12.9 ± 2.2 g/dl in heterozygous mice and 14.1 ± 1.0 g/dl in controls. Homozygous mice showed significant hepatic iron loading (2‐fold increase in liver non‐haem iron, compared with heterozygous mice and normal controls, with iron staining principally in the periportal hepatocytes). Absorption studies using 59Fe showed increased uptake from the lumen of an in vivo isolated duodenal segment in homozygous mice, although at this point in time overall transfer of radioiron to the circulation and other tissues (mucosal transfer) was not different from controls. These observations demonstrate that anaemia can lead to hepatic iron loading even in the absence of increased erythropoiesis, and are consistent with the possibility that anaemic hypoxia can enhance mucosal iron uptake by the duodenal enterocyte.
Expression of intercellular adhesion molecule 1 (ICAM‐1) in childhood acute lymphoblastic leukaemia: correlation with clinical features and outcome
Authors: MIELCAREK MARCO , SPERLING CHRISTIAN , SHRAPPE MARTIN , MEYER ULRIKE , RIEHM HANSJO¨RG , LUDWIG WOLF‐DIETER 
Published: December 2004

To investigate whether expression of intercellular adhesion molecule 1 (ICAM‐1, CD54) in childhood acute lymphoblastic leukaemia (ALL) has an impact on the biological behaviour of the disease, we evaluated 751 children of the ALL‐BFM 90 trial with B‐cell precursor‐ (n = 6777) or T‐cell‐ALL (n = 74) for CD54 expression within immunological subgroups, its correlation to certain clinical features, and therapy outcome.The highest percentage of patients expressing CD54 was found in common‐ and pre‐B‐ALL (76.1% and 61.4%, respectively). There was intermediate expression in pre‐pre‐B‐ALL (47.8%), and the lowest expression was detected in T‐ALL (12.2%).A significant positive correlation could be demonstrated between low CD54 expression (< 20% stained blasts) and high peripheral leucocyte counts, central nervous system (CNS) involvement, and splenomegaly at the time of diagnosis (P < 0.01). In addition, CD54 expression was a favourable but not independent prognostic factor. Event‐free survival estimate at 4.5 years was 86% for CD54+ patients (n = 463), compared with 78% for CD54− patients (n = 241) (P < 0.01). These findings demonstrate that CD54 expression has an impact on dissemination patterns and outcome of childhood ALL, and emphasizes the potential relevance of adhesion mechanisms in influencing clinical characteristics and prognosis of haematological malignancies.