Hanne Madsen

Use of complementary/alternative medicine among paediatric patients

The use of complementary/alternative medicine (CAM) is increasing. The aim was to characterise the use of CAM among patients in a paediatric department. All patients (aged 0-18 years), out-patients or hospitalised, in contact with the Department of Paediatrics, Odense University Hospital during a 2 week period in the autumn of 2001 were asked to participate. In total, 622 (92%) patients participated. The data were collected in an interviewer administered questionnaire during a short structured interview with the patient and parents. CAM was divided into herbal medicine (herbal drugs or dietary supplements) (HM), alternative therapy (AT) (i.e. acupuncture) or chiropractic (CHI). Of all patients, 53% had tried CAM at least once and 23% had tried CAM within the last month (15% HM, 7% AT and 2% CHI). There was no correlation between use of CAM and gender, age or if the patient was out-patient or hospitalised. The users were pre-school children. HM (Bio-Strath and Echinacea) was especially used to strengthen the immune system. Among AT, reflexological treatment was the most popular treatment. The most frequent users of CAM were patients with asthma, eczema or allergy plus patients suffering from gastrointestinal diseases or hospitalised for observation. More than 50% of the users experienced positive effects and 6% had side-effects from AM. Of the CAM users, 11% or 2% of the total paediatric population used CAM instead of conventional medicines. Conclusion: Of the paediatric patients, 53% had tried complementary/alternative medicine, which was used as a supplement to conventional medicine although we did not know how long it was used. Paediatric patients should be interviewed about their use of complementary/alternative medicine with regard to side-effects, interactions or lack of compliance with conventional medicine.

Nurse tele-consultations with discharged COPD patients reduce early readmissions--an interventional study.

Introduction:  Exacerbations of chronic obstructive pulmonary disease (ECOPD) are the most common cause for admissions and readmissions to medical wards worldwide.

Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide.

Our objective was to examine the interaction between fluvoxamine and tolbutamide to confirm that fluvoxamine inhibits CYP2C9.

The effect of real-time teleconsultations between hospital-based nurses and patients with severe COPD discharged after an exacerbation

Summary We investigated the effect of daily real-time teleconsultations for one week between hospital-based nurses specialised in respiratory diseases and patients with severe COPD discharged after acute exacerbation. Patients admitted with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) at two hospitals were recruited at hospital discharge. They were randomly assigned to intervention or control. The telemedicine equipment consisted of a briefcase with built-in computer including a web camera, microphone and measurement equipment. The primary outcome was the mean number of total hospital readmissions within 26 weeks of discharge. A total of 266 patients (mean age 72 years) were allocated to either intervention (n = 132) or control (n = 134). There was no significant difference in the unconditional total mean number of hospital readmissions after 26 weeks: mean 1.4 (SD 2.1) in the intervention group and 1.6 (SD 2.4) in the control group. In a secondary analysis, there was no significant difference between the two groups in mortality, time to readmission, mean number of total hospital readmissions, mean number of readmissions with AECOPD, mean number of total hospital readmission days or mean number of readmission days with AECOPD calculated at 4, 8, 12 and 26 weeks. Thus the addition of one week of teleconsultations between hospital-based nurses and patients with severe COPD discharged after hospitalisation did not significantly reduce readmissions or affect mortality.

Serum vitamin D in patients with chronic obstructive lung disease does not correlate with mortality--results from a 10-year prospective cohort study.

Background Recent studies have found vitamin D (25-OHD) deficiency and insufficiency to be common among patients with COPD. Serum level of 25-OHD seems to correlate to pulmonary function, COPD disease staging, and increased susceptibility to respiratory infections. We wanted to investigate whether vitamin D deficiency or insufficiency was associated with mortality rate in patients suffering from advanced COPD. Methods 25-OHD serum levels were measured in 462 patients suffering from moderate to very severe COPD. Patients were stratified into three groups according to serum levels of 25-OHD. Outcome measure was mortality in a 10 year follow-up period. Kaplan-Meier curves (KM) were plotted and mortality hazard ratios (HR) were calculated using Cox Proportional Hazard regression (Cox PH). Results Serum 25-OHD deficiency and insufficiency were prevalent. We were unable to demonstrate any association between baseline serum levels of 25-OHD and mortality rate. We found an association between mortality and age [HR 1.05 (CI 95%: 1.03–1.06)], Charlson score [HR 1.49 (CI 95%: 1.06–2.09)], increasing neutrophil count [HR 1.05 (CI 95%: 1.02–1.09)], severe [HR 1.41 (CI 95%: 1.06–1.86)]/very severe COPD [HR 2.19 (CI 95%: 1.58–3.02)] and a smoking history of more than 40 pack years [HR 1.27 (CI 95%: 1.02–1.70)]. Conclusions Serum level of 25-OHD does not seem to be associated with mortality rate, suggesting no or only a minor role of 25-OHD in disease progression in patients with moderate to very severe COPD.

Interaction between tramadol and phenprocoumon

We report an interaction between phenprocoumon (Marcoumar) and tramadol which led to an increase in International Normalised Ratio (INR) in two patients. A 54-year-old woman, otherwise healthy, with a suspected deep venous thrombosis in the left lower leg, was begun on heparin (10 000 IU twice daily) and phenprocoumon monitored by INR (therapeutic target range 2–3). Treatment was stopped after 2 days, because the diagnosis of deep venous thrombosis was not confirmed by ultrasonography. Tramadol (Nobligan, Grunenthal, Grunenthal GmbH, Aachen, Germany) 50–100 mg four times daily was given from day 3 for low back pain (figure). Her only other medication was paracetamol 1 g four times daily. As the INR kept rising despite withdrawal of phenprocoumon, phytomenadione (vitamin K1) 2 mg (day 5) and 5 mg (days 9–11) was given orally and the INR gradually fell to 0·9 (figure). On day 6, she had a nosebleed (INR 4·0). A 66-year-old woman with idiopathic lung fibrosis was admitted after a fall that resulted in fracture of a lumbar vertebra. Tramadol (Dolol, Nocomed Christianes, Chausee de Gand, Brussels, Belgium) 100 mg four times daily was prescribed for pain. Her other medication included estazolam 250 mg four times daily, diflunisal 50 mg three times daily, oxazepam 30 mg daily, calcium (400 mg) and vitamin D (5 g) twice daily, and paracetamol 1 g four times daily. 1 month later, she had a pulmonary embolism after an endoscopic retrograde cholangiopancreaticography, and treatment with heparin (12 500 IU twice daily) and phenprocoumon was begun. A rise in INR was seen and on day 6 phytomenadione 2 mg was given intramuscularly. Tramadol was stopped on day 8 and 3 days later, INR was stable at about 2 (figure). Albumin concentration, prothrombin time, and plasma transaminases were normal in both patients. Apart from tramadol, none of the prescribed drugs was suspected of affecting the anticoagulant effect of phenprocoumon. A pharmacodynamic interaction in which tramadol potentiated the action of phenprocoumon on vitamin K epoxide reductase may have caused the prolonged rise in INR. Several pharmacokinetic mechanisms are also possible. Increased absorption of phenprocoumon is unlikely because phenprocoumon is almost completely absorbed. An interaction caused by protein displacement of phenprocoumon (plasma protein binding 98–99%) and tramadol (plasma protein binding 20%) is unlikely because of the low protein binding of tramadol. A change in apparent volume of distribution is unlikely too, as none of the patients were oedematous at any time and both had normal serum creatinine. Tramadol is metabolised by CYP2D6, and phenprocoumon is probably metabolised by CYP2C9 but even so, we think the most likely mechanism for this interaction is inhibition of phenprocoumon metabolism in the liver by tramadol or one of its metabolites, as described for the drug interaction between warfarin and phenylbutazone. If tramadol is widely prescribed to older people taking anticoagulants this interaction should be monitored by frequent INR measurements. This advice also applies to warfarin, because adverse reports to the Danish Medicines Agency’s Committee on Adverse Drug Reactions suggest that tramadol increases the effect of both warfarin (three reports) and phenprocoumon (two reports).

Screening, prevention and treatment of osteoporosis in patients with chronic obstructive pulmonary disease - a population-based database study

Introduction:  A common extrapulmonary effect to chronic obstructive pulmonary disease (COPD) is osteoporosis.

Concurrent use of tramadol and oral vitamin K antagonists and the risk of excessive anticoagulation: a register-based nested case–control study

ObjectivesThe objective was to assess whether the concurrent use of tramadol and vitamin K antagonists (VKAs) leads to an increased risk of excessive anticoagulation.DesignThe study was designed as a case–control study, nested within users of VKA and with tramadol use as our main exposure. We used conditional logistic regression to control for potential confounders.SettingPrescription data from primary care were obtained from Odense Pharmacoepidemiological Database (OPED). Information about hospital admissions was obtained from the patient administrative system of Funen County (FPAS).SubjectsBoth cases and controls were selected from users of VKA. Cases were defined by being hospitalised with a main diagnosis indicating excessive anticoagulation. For each case, we selected 15 controls among VKA users, matched by age and sex.Main outcome measureOdds ratio for experiencing excessive anticoagulation attributable to the use of tramadol.ResultsA total of 178 patients were included, 30 of which were exposed to tramadol, along with 2643 controls, 114 of which were exposed to tramadol. The adjusted odds-ratio for experiencing excessive anticoagulation during use of tramadol was 3.1 (1.9–5.2). This corresponds to, on average, one excess case per 250 treatment years (CI 125–584). The result is potentially confounded by concomitant paracetamol use and the presence of acute illness.ConclusionCaution is advised when using tramadol in patients using VKA, and if possible, an alternative pain-medication should be used.

Calprotectin--a marker of mortality in COPD? Results from a prospective cohort study.

Abstract Calprotectin comprises more than 45% of the cytosolic content of neutrophil granulocytes. Because pathogenesis, disease activity and disease progression in COPD are believed to be partly dependent of neutrophil driven inflammation we decided to investigate whether plasma level of calprotectin (p-calprotectin) was associated with all-cause mortality in patients with COPD. We measured p-calprotectin in blood samples from 460 patients with moderate to very severe COPD in stable phase. Patients were stratified into three groups according to p-calprotectin level. Outcome measure was all-cause mortality. Analyses were adjusted for factors known to influence mortality using a Cox regression analysis. We found a time dependent correlation between p-calprotectin levels and mortality during the first 5 years of follow-up. Increasing levels of p-calprotectin were associated with concomitant increases in mortality from HR 1.56 (CI 95%: 1.03 –2.38) at calprotectin between 100 –200 ng/ml to HR 2.02 (CI 95%: 1.27-3.19) at calprotectin >200 ng/ml. P-calprotectin could be a useful marker of all-cause mortality in patients suffering from moderate to very severe COPD.

Appropriate selection for omalizumab treatment in patients with severe asthma

ABSTRACT Background: Omalizumab improves asthma control in patients with uncontrolled severe allergic asthma; however, appropriate patient selection is crucial. Information in this field is sparse. Objective: We aimed to estimate whether potential omalizumab candidates were appropriately selected according to guidelines, and the clinical effect of omalizumab treatment over time. Design: We performed a retrospective observational study on adult patients with asthma treated with omalizumab during 2006–2015 at the Department of Respiratory Medicine at Odense University Hospital (OUH), Denmark. Data were obtained from the Electronic Patient Journal of OUH and Odense Pharmaco-Epidemiological Database. Guideline criteria for omalizumab treatment were used to evaluate the appropriateness of omalizumab candidate selection, and the Asthma Control Test (ACT) to assess the clinical effects of omalizumab at weeks 16 and 52 from treatment initiation. Results: During the observation period, 24 patients received omalizumab, but only 10 patients (42%) fulfilled criteria recommended by international guidelines. The main reasons for not fulfilling the criteria were inadequately reduced lung function, insufficient number of exacerbations, and asthma standard therapy below Global Initiative for Asthma (GINA) step 4–5. Seventeen and 11 patients completed treatment at weeks 16 and 52, with a statistically significant increase in ACT score of 5.1 points [95% confidence interval (CI) 3.1–7.2, p = 0.0001] and 7.7 points (95% CI 4.3–11.1, p = 0.0005), respectively. Conclusion: Only 42% of the omalizumab-treated patients were appropriately selected according to current guidelines. Still, as omalizumab showed significant improvement in asthma control over time, it is important to keep this drug in mind as an add-on to asthma therapy in well-selected patients.