bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participation in a clinical trial influences the future management of patients with gastro‐oesophageal reflux disease in general practice
Authors: MEINECHE‐SCHMIDT V. , HVENEGAARD A. , JUHL H. H. 
Published: September 2006

SummaryBackground  The long‐term effects of participation in trials has not been reported. A randomized‐controlled trial (the ONE study) reported on the management of gastro‐oesophageal reflux disease with esomeprazole in primary care, testing on‐demand treatment vs. treatment courses.Aim  To evaluate the impact of participation in a trial on General Practitioners management and patient behaviour.Methods  Management of gastro‐oesophageal reflux disease was compared between General Practitioners who participated in ONE (ONE‐GPs) and a random sample of General Practitioners who did not participate in ONE (Other‐GPs). Symptom presentation and satisfaction with treatment was compared between patients who had participated in ONE (ONE‐patients) and patients who had not (Other‐patients).Results  ONE‐GPs prescribed on‐demand treatment with proton‐pump inhibitors to 47% of the patients, Other‐GPs to 27%. ONE‐patients consulted for significantly less symptoms compared with Other‐patients. ONE‐patients reported significantly higher patient satisfaction compared with Other‐patients. ONE‐patients used 98 doses during 6 months whereas Other‐patients used 76 doses.Conclusions  Participation in a clinical trial influenced both doctors and patients. Treatment modalities introduced by the trial were used in daily practice by the General Practitioners. Patients who had participated in the trial consulted for less symptoms and used more medication, compared with patients who did not participate.
Systematic review: lamivudine prophylaxis for chemotherapy‐induced reactivation of chronic hepatitis B virus infection
Authors: KOHRT H. E. , OUYANG D. L. , KEEFFE E. B. 
Published: September 2006

SummaryBackground  Reactivation of hepatitis B virus infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well‐documented and potentially fatal complication. Data supporting the use of lamivudine for primary prophylaxis have emerged, but its use remains controversial and is not standardized.Aim  To review current randomized‐controlled trials, randomized trials and prospective case series to provide a clinically applicable, evidence‐based recommendation.Methods  The published literature was identified using a MEDLINE/PubMed search with secondary review of cited publications, and inclusion of all prospective studies.Results  In nine prospective trials and one randomized‐controlled trial, the rate of hepatitis among subjects receiving lamivudine prophylaxis ranged from 0% to 20% (16 of 173, 9.2%), compared with 33–67% among controls. Of patients receiving prophylaxis, 0–24% (15 of 173, 8.7%) developed hepatitis B virus reactivation, compared with 29–56% of controls. Three reactivation‐related mortalities were reported (one receiving prophylaxis, two controls). No patients withdrew secondary to toxicity or development of lamivudine‐resistant mutations.Conclusions  The available data show a four‐ to sevenfold decrease in the rate of hepatitis and hepatitis B virus reactivation in patients who receive lamivudine prophylaxis. It is thus recommended that all hepatitis B surface antigen carriers receive lamivudine, or a comparable anti‐viral agent, as prophylaxis from the initiation of chemotherapy until at least 1 year following its completion.
The effects of tegaserod on oesophageal function and bolus transport in healthy volunteers: studies using concurrent high‐resolution manometry and videofluoroscopy
Authors: FOX M. , MENNE D. , STUTZ B. , FRIED M. , SCHWIZER W. 
Published: September 2006

SummaryBackground  Tegaserod is a partial 5‐hydroxytryptamine 4 receptor agonist with prokinetic effects on the gastrointestinal tract, its effects on oesophageal function are unknown.Aim  A randomized, placebo controlled, double‐blind trial assessed the effect of tegaserod on the oesophagus in healthy, asymptomatic subjects.Method  A 7‐day course of tegaserod 6 mg b.d. vs. placebo was prescribed (n = 17/21 completed both phases of study). High‐resolution manometry and pH measurements were performed before and after a test meal. Bolus transport of liquids and solids was studied by high‐resolution manometry and videofluoroscopy.Results  Tegaserod had no effect on lower oesophageal sphincter pressure compared with placebo, peristaltic velocity increased (P < 0.001) and distal contractile pressure decreased slightly (P < 0.05). Transient lower oesophageal sphincter relaxations and reflux were infrequent regardless of treatment. During the studies of bolus transport, high‐resolution manometry revealed that tegaserod promoted mid‐oesophageal contractility (P < 0.02) and shortened the ‘proximal transition zone’ (P < 0.05), the level where bolus escape occurred most frequently. These effects had no effect on liquid bolus transport; however a non‐significant trend to improved solid bolus transport was observed (66% vs. 31%;P = 0.07).Conclusion  Tegaserod did not alter lower oesophageal sphincter pressure, but had significant effects on peristaltic function. High‐resolution manometry promoted mid‐oesophageal contractility during bolus transport. This effect was associated with a non‐significant trend to improved solid bolus transit.
The effect of sildenafil on segmental oesophageal motility and gastro‐oesophageal reflux
Authors: KIM H. S. , CONKLIN J. L. , PARK H. 
Published: September 2006

SummaryBackground  Sildenafil is an inhibitor of type 5 phosphodiesterase. It relaxes or inhibits contraction of smooth muscle by increasing cellular concentrations of cyclic guanosine monophosphate. Multichannel intraluminal impedance manometry/pH allow the precise evaluation of oesophageal bolus transit and acid/non‐acid reflux.Aim  To investigate the effect of sildenafil on segmental oesophageal motor function and gastro‐oesophageal reflux.Methods  Eight healthy volunteers underwent multichannel intraluminal impedance manometry baseline, and 15, 30 and 45 min before and after a 50‐mg dose of sildenafil successively. The subjects underwent 2‐h multichannel intraluminal impedance/pH studies on two separate days after either water or sildenafil ingestion.Results  Sildenafil decreased the resting lower oesophageal sphincter pressure and prolonged the duration of lower oesophageal sphincter relaxation for the 45 min following its ingestion. At 15 min, distal onset velocity, total bolus transit time, bolus presence time and segmental transit time were delayed in the mid to distal oesophagus. At 30 min, distal onset velocity was restored but bolus presence time and bolus presence time were still delayed in distal smooth muscle segment. At 45 min, total bolus transit time and distal onset velocity were restored but bolus presence time and segmental transit time were delayed more in the transition zone. Sildenafil did not alter the reflux.Conclusion  Sildenafil alters lower oesophageal sphincter function and oesophageal bolus transit, but not induce gastro‐oesophageal reflux.
Adherence rates with infliximab therapy in Crohn's disease
Authors: KANE S. , DIXON L. 
Published: September 2006

SummaryBackground  Inflammatory bowel disease is associated with non‐adherence to treatment with oral medications.Aim  To assess the intravenous infliximab adherence rate and identify risk factors for non‐adherence to treatment.Methods  Infliximab infusion dates for 1 June 2002–30 October 2003 were obtained. Additional information was obtained from two other administrative and patient‐based databases. Non‐adherence was defined as a ‘No Show’ designation for a scheduled appointment. Non‐adherence rate, odds ratios for associations to ‘No Show’ appointments and analysis were performed to identify patient characteristics associated with non‐adherent behaviour.Results  One thousand hundred and eighty‐five infliximab infusions were scheduled for 274 patients. Forty‐eight (4%) of appointments were classified as ‘No Show’. Six patients accounted for 13/48 (27%) of failed appointments; another 35 patients missed one appointment. ‘No Show’ appointments were more likely to be for female patients, those on concomitant immunomodulators and those >18 weeks from initial infusion. Patients who missed >1 appointment were more likely to be female and have Medicaid vs. those with only one missed appointment (P < 0.05). Indication, patient area code and race were not significantly associated with single or repeated No Show behaviour.Conclusions  Overall, the non‐adherence rate for infliximab is low. Risk factors that may contribute to non‐adherence to treatment include female gender and maintenance dosing.
Influence of delaying gastric emptying on meal‐related symptoms in healthy subjects
Authors: TACK J. , COULIE B. , VERBEKE K. , JANSSENS J. 
Published: September 2006

SummaryBackground  Although delayed gastric emptying is often found in functional dyspepsia, a causal role for delayed emptying in inducing symptoms has not been demonstrated.Aim  To investigate the influence of delaying gastric emptying rate in healthy volunteers on the occurrence of meal‐related symptoms.Methods  Fourteen healthy subjects (six men, mean age 23 ± 1) underwent gastric emptying studies twice using the 14C octanoic acid and 13C glycin breath test after pre‐treatment with saline or sumatriptan 6 mg s.c. Breath samples were taken before meal and at 15‐min intervals for a period of 360 min postprandially. At each breath sampling, the subject was asked to grade the intensity (0–6) of four dyspeptic symptoms.Results  Sumatriptan pre‐treatment significantly delayed solid but not liquid gastric emptying (t1/2 respectively 159 ± 11 vs. 112 ± 9 min, P < 0.005 and 134 ± 11 vs. 116 ± 12 min, N.S.). Sumatriptan significantly decreased the mean cumulative symptom score (21.3 ± 5.5 vs. 8.0 ± 2.6, P = 0.01), as well as scores for each individual symptom.Conclusion  A moderate delay in gastric emptying in health is not associated with an increase of meal‐related symptoms. This observation argues against a causal role for delayed gastric emptying in the pathogenesis of dyspeptic symptoms.
Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study
Authors: FLOREANI A. , NIRO G. , ROSA RIZZOTTO E. , ANTONIAZZI S. , FERRARA F. , CARDERI I. , BALDO V. , PREMOLI A. , OLIVERO F. , MORELLO E. , DURAZZO M. 
Published: September 2006

SummaryBackground  Many reports of autoimmune hepatitis (AIH) were written in the ‘pre‐Hepatitis C era’ and data on the natural history are still incomplete.Aim  To evaluate the clinical presentation and the natural history of type I AIH.Methods  Seventy‐three consecutive patients with a regular follow‐up of at least 2 years were prospectively included in the study. The mean follow‐up was 91 ± 61 months.Results  Patients with ‘acute’ onset at presentation were significantly older than patients with ‘chronic’ onset (P < 0.05) and had significantly higher serum levels of transaminase, γ‐glutamyltransferase and bilirubin; Prothrombin time was significantly lower in the said group compared with AIH patients with ‘chronic’ onset. In 4 of 63 (6.3%) female patients, AIH had the onset during pregnancy; in all of them the outcome of pregnancy was favourable. The major events during the follow‐up included oesophageal varices (n = 9) and ascites (n = 4), and 60 patients remained in remission while receiving immunosuppression. None of the patients died during the follow‐up, but seven patients were transplanted. The cumulative transplant‐free probability of survival was 73.5% at 280 months.Conclusions  Elderly patients have more frequently an acute onset at presentation. Survival in AIH is apparently good; with early diagnosis, and improved medical therapy, liver transplantation for AIH will become a rare event in future.
Evaluation of a pharmacotherapy context‐learning programme for preclinical medical students
Authors: Vollebregt J. A. , Van Oldenrijk J. , Kox D. , Van Galen S. R. , Sturm B. , Metz J. C. M. , Richir M. C. , De Haan M. , Hugtenburg J. G. , De Vries T. P. G. M. 
Published: September 2006

What is already known about this subject• Context‐learning in medicine is mainly based on theories explaining how medical expertise is achieved, particularly with regard to diagnostic problem solving.• By frequently solving diagnostic clinical problems doctors generate so‐called networks of organized knowledge in their memory.• Preclinical medical students are well able to learn to choose and prescribe drugs.What this study adds• Preclinical pharmacotherapy context learning for medical students has a modest but positive effect on learning cognitive pharmacotherapeutic skills, i.e. choosing a drug treatment and determining patient information.• The effect can be obtained with role‐play sessions, a suboptimal form of context learning, with a minimal study load and a high appreciation by students.AimTo evaluate a context‐learning pharmacotherapy programme for approximately 750 2nd, 3rd and 4th year preclinical medical students with respect to mastering cognitive pharmacotherapeutic skills, i.e. choosing a (drug) treatment and determining patient information.MethodsThe context‐learning pharmacotherapy programme consists of weekly organized role play sessions in the form of consulting hours. Fourth year students sit for a therapeutic Objective Structured Clinical Examination (OSCE) in the form of consulting hours at the outpatient clinic. Sixty‐one 2nd, 74 3rd and 49 4th year medical students who attended the role play sessions and the OSCE were randomly selected. Their performances were assessed by clinical examiners and clinical experts and compared with a reference group of 6th year graduated students. Additionally, the scores of a questionnaire on study load and appreciation were collected.ResultsThe level of the pharmacotherapeutic skills of the 4th year students who followed the pharmacotherapy context‐learning programme was not far below that of 6th year graduates who had finished their clinical clerkships, but had not followed the pharmacotherapy programme. The time spent on the programme was about 1% of the total study load per year. The students appreciated the role play sessions and OSCE by around 80% and 99% of the maximum possible scores.ConclusionsPreclinical pharmacotherapy context learning has a modest but positive effect on learning cognitive pharmacotherapeutic skills, i.e. choosing a drug treatment and determining patient information. This effect has been obtained with role play sessions, a suboptimal form of context learning, with a minimal study load and a high appreciation by students.
Transfer of dexamphetamine into breast milk during treatment for attention deficit hyperactivity disorder
Authors: Ilett Kenneth F. , Hackett L. Peter , Kristensen Judith H. , Kohan Rolland 
Published: September 2006

What is already known about this subject• There are presently no published data on dexamphetamine transfer into breast milk or on its effects in the breast‐fed infant.What this study adds• We have provided quantitative data on the absolute and relative infant doses of dexamphetamine for the breast‐fed infant.• We have also documented a lack of overt adverse effects in breast‐fed infants despite measurable dexamphetamine concentrations in the infants’ plasma.• Hence we now make recommendations for infant safety and monitoring when mothers taking the drug wish to breastfeed.AimsTo investigate dexamphetamine transfer into milk, infant doses and effects in the breast‐fed infant.MethodsFour women taking dexamphetamine, and their infants were studied.ResultsThe median maternal dexamphetamine dose was 18 mg day−1 (range 15–45 mg day−1). Median (interquartile range) descriptors were 3.3 (2.2–4.8) for milk/plasma ratio, 21 µg kg−1 day−1 (11–39) for absolute infant dose and 5.7% (4–10.6%) for relative infant dose. No adverse effects were seen. In three infants tested, dexamphetamine in plasma was undetected in one (limit of detection 1 µg l−1) and present at 18 µg l−1 and 2 µg l−1 in the other two.ConclusionDexamphetamine readily transfers into milk. The relative infant dose was <10% and within a range that is generally accepted as being ‘safe’ in the short term.
Effectiveness of β‐blocker therapy in daily practice patients with advanced chronic heart failure; is there an effect‐modification by age?
Authors: Dobre Daniela , DeJongste Mike J. L. , Lucas Carolien , Cleuren Ger , Van Veldhuisen Dirk J. , Ranchor Adelita V. , Haaijer‐Ruskamp Flora 
Published: September 2006

AimsThe effects of β‐blockers in daily practice patients with advanced chronic heart failure (CHF) and a broad range of ejection fraction (EF) are not well established. We aimed to assess, first, the association between β‐blocker prescription at discharge and mortality in a cohort of patients with advanced CHF, and second, whether this association is modified by the age of the patient.MethodsPatients diagnosed with advanced CHF (n = 625) were prospectively followed after discharge from the Cardiology Department. The mean age was 76 years, 53% male, mean EF 42 ± 16%. Overall, 308 (49%) patients had a β‐blocker prescribed at discharge, 140 (22%) low‐dose and 168 (27%) high‐dose therapy. We used multivariate Cox analysis to assess the association between β‐blocker use at discharge and mortality.ResultsAfter a mean follow‐up of 22 months, 117 (27%) patients died. Prescription of a β‐blocker was associated with a 45% relative risk reduction (hazard ratio 0.55, 95% confidence interval 0.39, 0.78). The relative risk reduction was similar with low and high doses of β‐blockers (42% and 49%). However, the relative risk reduction was higher in younger than in older patients (P = 0.006). In patients ≤75 years old prescription of a β‐blocker was associated with 71% risk reduction, whereas in patients >75 years old it was associated with 21% risk reduction.ConclusionsIn this daily practice cohort of patients with advanced CHF, prescription of a β‐blocker was associated with significant mortality reduction. However, the beneficial effects of β‐blockers appear to be greater in younger patients.
Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infection
Authors: Kartikasari A. E. R. , Georgiou N. A. , De Geest M. , Van Kats‐Renaud J. H. , Bouwman J. J. M. , Van Asbeck B. S. , Marx J. J. M. , Visseren F. L. J. 
Published: September 2006

AbstractBackground  Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection‐mediated endothelial activation.Materials and methods  Endothelial intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and endothelial selectin (E‐selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells.Results  An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up‐regulated Cp‐induced VCAM‐1 expression, whereas synergistically potentiated Cp‐induced ICAM‐1 expression. Together with CMV, iron also enhanced ICAM‐1 and VCAM‐1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections.Conclusions  Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis.
Increased cardiac endothelial nitric oxide synthase expression in patients taking angiotensin‐converting enzyme inhibitor therapy
Authors: Morawietz H. , Rohrbach S. , Rueckschloss U. , Schellenberger E. , Hakim K. , Zerkowski H.‐R. , Kojda G. , Darmer D. , Holtz J. 
Published: September 2006

AbstractBackground  The efficacy of angiotensin‐converting enzyme (ACE) inhibitors has been demonstrated in large clinical trials, but knowledge of the underlying mechanisms remains incomplete. Therefore, this study investigated the impact of ACE inhibitor therapy on cardiac nitric oxide (NO) synthases in patients with coronary artery disease (CAD) or heart failure.Patients and methods  The mRNA expression was quantified by standard calibrated competitive RT‐PCR, protein expression by Western blotting and NOS activity by monitoring the conversion of [3H]arginine to [3H]citrulline during enzymatic formation of NO in tissue homogenates of myocardium of patients with, or without, ACE inhibitor treatment before elective coronary artery bypass grafting or heart transplantation.Results  The mRNA expression (amol µg−1 RNA) of endothelial NO synthase (eNOS) was higher (22·5 ± 4·8, n = 23) in the atrial myocardium of patients taking ACE inhibitor treatment, before elective coronary artery bypass grafting, compared with patients not taking this therapy (8·9 ± 0·7, n = 33, P < 0·0001). The ACE inhibitor therapy increased eNOS protein expression from [(9 ± 0·7) relative units (RUs) to (12 ± 0·9) RUs, P < 0·05, respectively] and cardiac NOS activity from 17·6 ± 1·3 to 23·7 ± 1·1 pmol mg protein−1 min−1 (P < 0·001, respectively). Inducible and neuronal NO synthase expression was not changed by the ACE inhibition. A similar up‐regulation of eNOS by ACE inhibition was found in the left ventricles of patients with heart failure. The augmented endothelial NOS expression and activity was not the result of differences in clinical characteristics and concomitant therapy between the patient groups.Conclusion  Increased eNOS expression and activity might contribute to the beneficial effects of ACE inhibitor therapy in the treatment of CAD and heart failure.