Anne B. Taegtmeyer

Physicians' Ability to Predict Patients' Adherence to Antihypertensive Medication in Primary Care

Addressing adherence to medication is essential and notoriously difficult. The purpose of this study was to determine physicians ability to predict patients adherence to antihypertensive therapy. Primary care physicians were asked to predict the adherence to medication of their hypertensive patients (n=42) by using a visual analogue scale (VAS) at the beginning of the study period. The patients were asked to report their adherence to medication using a VAS. The adherence was then monitored by using a Medical Event Monitoring System (MEMS) for 42±14 d. The means±SD (range) of MEMS measures for timing adherence, correct dosing, and adherence to medication were 82±27% (0 to 100%), 87±24percnt; (4 to 100%), and 94± 18% (4 to 108%), respectively. The physicians prediction of their patients adherence was 92± 15% The Spearman rank correlations between the physicians prediction and the MEMS measures of timing adherence, correct dosing, and adherence to medication was 0.42 (p=0.006), 0.47 (p=0.002), and –0.02 (p=0.888), respectively. The patients reported their own adherence to medication at 98±2% (range 83 to 100%). The Spearman correlations between the reported and actual behaviours were 0.27 (p=0.08) for timing adherence, 0.25 (p=0.12) for correct dosing, and 0.11 (p=0.51) for adherence to medication. The physicians ability to predict patients adherence to antihypertensive medication is limited and not accurate for identifying non-adherent patients in clinical practice. Even patients themselves are unable to give accurate reports of their own adherence to medication.

Electronic prescribing increases uptake of clinical pharmacologists' recommendations in the hospital setting

AIMSnTo determine whether electronic prescribing facilitates the uptake of clinical pharmacologists recommendations for improving drug safety in medical inpatients.nnnMETHODSnElectronic case records and prescription charts (either electronic or paper) of 502 patients hospitalized on medical wards in a large Swiss teaching hospital between January 2009 and January 2010 were studied by four junior and four senior clinical pharmacologists. Drug-related problems were identified and interventions proposed. The implementation and time delays of these proposed interventions were compared between the patients for whom paper drug charts were used and the patients for whom electronic drug charts were used.nnnRESULTSnOne hundred and fifty-eight drug-related problems in 109 hospital admissions were identified and 145 recommendations were made, of which 51% were implemented. Admissions with an electronic prescription chart (n= 90) were found to have 2.74 times higher odds for implementation of the change than those with a paper prescription chart (n= 53) (95% confidence interval 1.2, 6.3, P= 0.018, adjusted for any dependency introduced by patient, ward or clinical team; follow-up for two cases missing). The time delay between recommendations being made and their implementation (if any) was minimal (median 1 day) and did not differ between the two groups.nnnCONCLUSIONSnElectronic prescribing in this hospital setting was associated with increased implementation of clinical pharmacologists recommendations for improving drug safety when compared with handwritten prescribing on paper.

Effect of ABCB1 Genotype on Pre- and Post-Cardiac Transplantation Plasma Lipid Concentrations

Genetic variation of ATP-binding cassette subfamily B member 1 (ABCB1) which encodes P-glycoprotein (P-gp) has been associated with lipid levels and response to statins. Here, we studied these associations in patients with advanced heart failure who subsequently underwent transplantation. Fasting total cholesterol (TC), low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) concentrations in 268 adult heart transplant recipients were analysed retrospectively before and at 1xa0year after transplantation (nu2009=u2009176). ABCB1 genotyping and haplotyping for C1236T, G2677T/A and C3435T was performed using polymerase chain reaction. Pre-transplant LDL cholesterol was found to be associated with the C3435T genotype and the G2677T/A-C3435T and C1236T-G2677T/A-C3435T haplotypes. T-allele carriers at all loci (nu2009=u200977) had higher LDL levels than non-T-allele carriers (nu2009=u200924, 3.5u2009±u20091.2 vs. 2.8u2009±u20091.2xa0mmol/L, respectively, pu2009=u20090.025). This association remained after adjustment for age, sex, body mass index, statin use and underlying ischaemic heart disease. ABCB1 genotype was not associated with post-transplant lipid parameters. Hypercholesterolaemia (TC >5.7xa0mmol/L) was more prevalent post-transplant than pre-transplant (51% vs. 30%, respectively) and was likely related to steroid and calcineurin inhibitor use. Muscle-related statin effects were only seen in patients possessing the T-haplotype. In conclusion, an association between ABCB1 haplotype and plasma fasting LDL cholesterol concentration was found in patients with advanced heart failure. This association was not seen 1xa0year after cardiac transplantation.

Clinical Usefulness of Electronic Drug-Drug Interaction Checking in the Care of Cardiovascular Surgery Inpatients

Objectives: Drug-related problems (DRPs) are events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. This study tested the applicability of clinical decision support software in identifying and managing DRPs among cardiovascular surgery inpatients. Methods: Two clinical pharmacologists attended ward rounds on a low-dependency cardiovascular surgery ward every 2 weeks over a 7-month period. Three hundred and three patients were assessed. On average, patients received 17 scheduled and ‘as required’ medicines. DRPs were identified ‘manually’ via assessment of electronic prescription charts and patient records and ‘electronically’ using clinical decision support software (Pharmavista®). The numbers of alerts for optimizing medication safety generated by the two methods were compared. Results: Manual checking identified 346 DRPs leading to 346 alerts in 201 patients (overall 1.1 alerts/patient). Relevant interactions accounted for 44% of DRPs detected by clinical pharmacologists. Clinical decision support software, which could only report interactions, however, generated 1,370 alerts (average 4.5 alerts/patient). Only 147 (11%) drug-drug interaction alerts were identical to those identified by manual checking; the remaining 89% were considered not clinically relevant. Conclusions: Compared to identification of DRPs by clinical pharmacologists, the clinical decision support software performed poorly due to over-alerting and inability to assess for problems not caused by drug-drug interactions.

Acute thiopurine overdose : analysis of reports to a National Poison Centre 1995-2013

Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995–2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, nu200a=u200a35; 6-mercaptopurine, nu200a=u200a5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.

Roflumilast--a phosphodiesterase-4 inhibitor licensed for add-on therapy in severe COPD.

Roflumilast is a selective phosphodiesterase 4 inhibitor which has been licensed in the European Union since 2010 and in Switzerland since November 2011 as an add-on treatment for patients with chronic obstructive pulmonary disease (COPD) in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages 3 and 4 (FEV(1) <50% predicted after bronchodilatation) and frequent exacerbations despite correctly-dosed therapy with a long-acting bronchodilator. Roflumilast is designed to target both the systemic and pulmonary inflammation associated with COPD. In this review roflumilasts chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability and the current ongoing clinical trials involving roflumilast are outlined. Information has been sourced from the Swiss and US product information monographs, peer-reviewed published literature (identified from a PubMed MEDLINE search 1966 - March 2012 using the term roflumilast), the COPD GOLD international guidelines for the management of COPD (Revised 2011) and an independent analysis of phase 3 clinical trial data by FDA staff physicians. Clinical efficacy in terms of a modest gain in FEV(1)% and a reduction in exacerbation rate has been demonstrated in phase 3 clinical trials and roflumilast has been recently incorporated into international treatment guidelines. However data examining roflumilast as add-on therapy to long-acting bronchodilators and ICS (standard therapy) is currently awaited and phase 4 post-marketing studies are required to determine the incidence and severity of adverse events and the long-term beneficial effects of roflumilast as a maintenance therapy for COPD in every-day clinical practice.

Drug-related problems and factors influencing acceptance of clinical pharmacologists' alerts in a large cohort of neurology inpatients

QUESTIONS UNDER STUDY/PRINCIPLESnData regarding the prevalence and types of drug-related problems (DRPs) among neurology inpatients is sparse. The objective of this study was to characterise the types of DRPs seen among neurology inpatients and furthermore to study factors affecting the acceptance of clinical pharmacologists and pharmacists recommendations for improving drug safety.nnnMETHODSn1,263 consecutive inpatient cases in a Swiss university hospital neurology unit were assessed for the presence of DRPs over 12 months. Treating neurologists acceptance of the resulting recommendations was also recorded. Primary outcome measures were types of DRP, recommendations made by clinical pharmacologists and number of recommendations accepted. Factors potentially associated with acceptance were studied using univariate and multivariate generalised estimating equation modelling.nnnRESULTSnTwenty-nine percent of cases demonstrated one or more DRPs. DRPs were the cause of admission in 10 cases (0.8%). Inxa0total 494 DRPs were identified and 467 recommendations given, of which 62% were accepted. Factors associated with an increased likelihood of acceptance were prescriptions involving regularly administered drugs (odds ratio [OR] 2.57 95% confidence interval [CI] 1.73-3.80), adverse drug events (OR 2.5; 95% CI 1.29-5.06), known drug side-effect (OR 1.85; 95% CI 1.06-3.22), high-risk drug-drug interactions (OR 3.22; 95% CI 1.07-9.69) and interventions involving changing a drug (OR 2.71; 95% CI 1.17-6.25).nnnCONCLUSIONnClinical pharmacologists and pharmacists can play an important role in identifying DRPs among neurology inpatients. Their recommendations for optimising medication-safety are most likely to be accepted for regular prescriptions, prescriptions associated with an adverse drug event and high-risk drug combinations.

Breakthrough Pain Associated with a Reduction in Serum Buprenorphine Concentration during Dialysis.

PURPOSEnTo describe a case of breakthrough pain associated with a reduction in serum buprenorphine concentration during dialysis.nnnMETHODSnPharmacokinetic sampling of total and free buprenorphine and norbuprenorphine in an 80 year old male undergoing haemodialysis three times per week who received 5760 µg oral and transdermal buprenorphine daily was performed. The patients serum albumin concentration was 23g/l (reference range: 35-52 g/l).nnnFINDINGSnPharmacokinetic sampling revealed a free buprenorphine fraction of 32% (consistent with the hypoalbuminaemia), which was markedly reduced at the end of dialysis (free buprenorphine concentration 2.4 µg/l before vs. <0.1 µg/l after dialysis).nnnIMPLICATIONSnClinicians should be aware that some patients may require extra buprenorphine doses during dialysis to prevent significant falls in the concentration of active drug.

Acute mycophenolate overdose : case series and systematic literature analysis

Background: Literature regarding acute human toxicity of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) is limited. Objectives: Our objectives were to describe all cases of overdose with MMF or EC-MPS reported to the Swiss Toxicological Information Centre (STIC) or in the literature between 1995 and 2013. Therefore, we performed an observational case-series and systematic literature search to determine circumstances, magnitude, management and outcome of overdose with MMF or EC-MPS. Results: Of 152,762 reports to STIC, 15 (7 pediatric) involved overdose with MMF (n = 13) or EC-MPS (n = 2). Three cases from other centers were identified from a systematic literature search. The magnitude of overdose ranged from 1.2 to 16.7 (median 2.9) times usual dose. Six (33%) MMF overdoses had attributable symptoms, which included abdominal pain, vomiting, headache and dizziness. The majority of findings were minor, although a 9-fold MMF overdose caused hypotension 8 h after ingestion and a 12.5-fold overdose caused leukopenia after 5 days. Symptoms did not occur in patients who took 2.5 times or less of their usual MMF dose. Gastrointestinal decontamination measures with activated charcoal were undertaken in one-third of cases. Conclusions: Acute MMF and EC-MPS overdoses had a favorable outcome in all cases reported to STIC and in the literature.

Bronchial hyperresponsiveness testing in athletes of the Swiss Paralympic team

BackgroundThe aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury.MethodsForty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of ≥10% in either challenge test was deemed positive for exercise-induced bronchoconstriction.ResultsFourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (pu2009=u20090.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively.ConclusionEVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes.