Showing papers in "European Journal of Clinical Pharmacology in 2013"

Systematic review of anticholinergic risk scales in older adults

Abstract: Background Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults. Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden. However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load. This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency.

NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: A randomized controlled trial for pharmacogenetics-based therapy

Abstract: Objective This study is a pharmacogenetic clinical trial designed to clarify whether the N-acetyltransferase 2 gene (NAT2) genotype-guided dosing of isoniazid improves the tolerability and efficacy of the 6-month four-drug standard regimen for newly diagnosed pulmonary tuberculosis.

Medication errors in the Middle East countries: A systematic review of the literature

Abstract: Background Medication errors are a significant global concern and can cause serious medical consequences for patients. Little is known about medication errors in Middle Eastern countries. The objectives of this systematic review were to review studies of the incidence and types of medication errors in Middle Eastern countries and to identify the main contributory factors involved.

Medication prescribing in frail older people

Abstract: Purpose While some people remain fit and active as they grow older, others experience complex problems: disease, dependency and disability. Frailty is a term used to describe this latter group, capturing differences in health status among older people. Many frail older people have multiple chronic co-morbidities and functional impairments and, according to guidelines for the management of individual conditions, should be prescribed long lists of medications. However, older people (particularly those who are frail) are often excluded from drug trials, and treatment decisions are therefore based on evidence extrapolated from more robust patient groups with fewer physiological deficits. The risk of adverse drug reactions (ADRs) increases with increasing patient frailty, and polypharmacy has negative consequences above and beyond the risks of individual drugs. Increasing numbers of medications are associated with a higher likelihood of non-adherence and a significantly greater risk of ADRs. Older people taking five or more medications are at higher risk of delirium and falls, independent of medication indications.

Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms

Abstract: We assessed the prevalence of difficulties in swallowing solid oral dosage forms in a general practice population. Reasons, nature, and characteristics of tablets and capsules causing such difficulties were investigated as well as general practitioners’ (GP) awareness of these difficulties. A questionnaire survey was conducted in 11 general practices and consecutive patients taking at least one solid oral dosage form for ≥4 weeks were invited to respond to a questionnaire at the practices and one at home. Physicians completed a short questionnaire for each included patient. Of all participants (N = 1,051), 37.4 % reported having had difficulties in swallowing tablets and capsules. The majority (70.4 %) of these patients was not identified by their GP. The occurrence of swallowing difficulties was related to gender (f>m), age (young>old), dysphagia [adjusted odds ratio (adOR): 7.9; p < 0.0001] and mental illness (adOR: 1.8; p < 0.05). By asking “Do you choke while eating or drinking?”, affected patients could be identified with a sensitivity of 62.6 % and a specificity of 78.1 %. Because of these difficulties, 58.8 % of the affected patients had already modified their drugs in a way that may alter safety and efficacy and 9.4 % indicated to be non-adherent. One in 11 primary care patients had frequent difficulties in swallowing tablets and capsules while GPs grossly underestimated these problems. Therefore, physicians should rule out swallowing difficulties regularly to avoid non-adherence and inappropriate drug modifications. Special attention should be paid to specific patient groups (e.g. women and patients with dysphagia, dysphagia indicators, or mental illness).

Contamination and adulteration of herbal medicinal products (HMPs): an overview of systematic reviews.

Abstract: The aim of this overview of systematic reviews is to summarise and critically evaluate the evidence from systematic reviews of the adulteration and contamination of herbal medicinal products (HMPs). Five electronic databases were searched to identify all relevant systematic reviews. Twenty-six systematic reviews met our inclusion criteria. The most commonly HMPs were adulterated or contaminated with dust, pollens, insects, rodents, parasites, microbes, fungi, mould, toxins, pesticides, toxic heavy metals and/or prescription drugs. The most severe adverse effects caused by these adulterations were agranulocytosis, meningitis, multi-organ failure, perinatal stroke, arsenic, lead or mercury poisoning, malignancies or carcinomas, hepatic encephalopathy, hepatorenal syndrome, nephrotoxicity, rhabdomyolysis, metabolic acidosis, renal or liver failure, cerebral edema, coma, intracerebral haemorrhage, and death. Adulteration and contamination of HMPs were most commonly noted for traditional Indian and Chinese remedies, respectively. Collectively these data suggest that there are reasons for concerns with regards to the quality of HMPs. Adulteration and contamination of HMPs can cause serious adverse effects. More stringent quality control and its enforcement seem to be necessary to avoid health risks.

Pregabalin abuse among opiate addicted patients.

Abstract: Pregabalin is a novel GABA-analogue approved for the treatment of partial onset seizures, neuropathic pain, and general anxiety disorder. Pregabalin has been classified as a Schedule V drug with a low risk of inflicting abuse or addiction. However, some publications have indicated that pregabalin may have a potential for abuse among patients with past or current opiate addiction. Thus, we hypothesized that pregabalin might be abused by patients who were undergoing an opiate replacement therapy and never had an indication for taking pregabalin on medical grounds. Urine specimens from 124 patients with opiate dependency syndrome and from 111 patients with other addiction disorders (alcohol, benzodiazepines, cannabis, amphetamines) were screened for pregabalin by means of a mass spectrometer analysis. We found 12.1 % of all urine specimens from patients with opiate addiction to be positive for pregabalin. None of the patients concerned had a medical indication for using pregabalin. In the control group, 2.7 % of the patients were tested positively for pregabalin, due to their taking it regularly for chronic pain or general anxiety. Our data suggest that pregabalin is liable to be abused among individuals with opiate dependency syndrome Thus, vigilance and caution are called for when patients with a past or current opiate dependency are exposed to treatment with pregabalin.

Evaluation of coagulation assays versus LC-MS/MS for determinations of dabigatran concentrations in plasma

Abstract: Background Dabigatran is an oral direct thrombin inhibitor for which routine laboratory monitoring is currently not recommended. However, there are situations in which measurements of the drug and its effect are desirable. We therefore compared and validated different coagulation methods for assessments of dabigatran in clinical samples in relation to measurements of plasma dabigatran, without the purpose of establishing effective and safe concentrations of dabigatran in plasma.

Pregabalin abuse and dependence in Germany: results from a database query

Abstract: Purpose Pregabalin (PRG) is approved for the treatment of neuropathic pain, partial seizures and generalised anxiety disorder in many countries and currently under study for other indications. Supported by case reports and the results of a limited number of studies there is an ongoing debate on the potential of PRG to cause addictive behaviours. However, currently available evidence on this issue is sparse, and any definitive assessment of PRG’s potential for abuse and dependence is not yet in sight. The aim of our study was to identify the number of cases of PRG abuse or dependence reported to the database of a German medical regulatory body and to obtain insights into further usage-specific parameters.

Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU

Abstract: To assess the methodological quality of Orphan Medicinal Product (OMP) dossiers and discuss possible reasons for the small number of products licensed. Information about orphan drug designation, approval, refusal or withdrawal was obtained from the website of the European Medicines Agency and from the European Public Assessment Reports. From 2000 up to 2010, 80.9 % of the 845 candidate orphan drug designations received a positive opinion from the European Medicines Agency (EMA)’s Committee on Orphan Medicinal Products. Of the 108 OMP marketing authorizations applied for, 63 were granted. Randomised clinical trials were done for 38 OMPs and placebo was used as comparator for nearly half the licensed drugs. One third of the OMPs were tested in trials involving fewer than 100 patients and more than half in trials with 100–200 cases. The clinical trials lasted less than one year for 42.9 % of the approved OMPs. Although there may have been some small improvements over time in the methods for developing OMPs, in our opinion, the number of patients studied, the use of placebo as control, the type of outcome measure and the follow-up have often been inadequate. The present system should be changed to find better ways of fostering the development of effective and sustainable treatments for patients with orphan diseases. Public funds supporting independent clinical research on OMPs could bridge the gap between designation and approval. More stringent criteria to assess OMPs’ efficacy and cost/effectiveness would improve the clinical value and the affordability of products allowed onto the market.

Underreporting in pharmacovigilance: an intervention for Italian GPs (Emilia-Romagna region).

Abstract: Underreporting is a major limitation of spontaneous reporting systems for suspected adverse drug reactions (ADRs). Several interventions to increase the ADR reporting rate have been proposed, but their efficacy remains poorly investigated. This was a questionnaire study aimed at assessing the knowledge, attitudes, and behavior of general practitioners (GPs) regarding ADR reporting and at evaluating whether a monthly e-mail-based newsletter on drug safety could affect the rate and the quality of the ADR reports submitted by these GPs. Three local health authorities (LHAs) of the Emilia–Romagna region were chosen on the basis of their ADR reporting rate during the period preceding the study: Rimini (high), Ferrara (average), and Piacenza (low reporting rate). All GPs (n = 737) associated with these three LHAs were recruited. The pooled number of ADR reports sent by GPs in the remaining seven LHAs of the region was used as controls. The study covered a period of 3 years and was divided into: (1) identification of the reasons leading to underreporting through a questionnaire (Phase I); (2) the intervention, i.e., sending a newsletter for a 10-month period (Phase II); (3) evaluation of the intervention outcomes during the 10 months following the period in which the newsletter had been received (Phase III). Among GPs involved, 22.8 % returned the questionnaire. Over 94 % of the respondents considered the spontaneous reporting of suspected ADRs to be part of their professional obligations, but only 6.5 % had submitted at least one report in the previous 6 months. Following the completion of Phase II, the overall number of reports coming from the LHAs subjected to the intervention rose by 49.2 % compared to 2009, while the number of reports coming from the control LHAs increased by 8.8 %. Rimini and Piacenza showed a 200 % increase in the number of ADR reports submitted by GPs, while the number of ADR reported submitted by the control group decreased by 25.5 %. In 2011, the number of overall ADRs reports from the LHAs subjected to the intervention decreased by 6.8 %; this decrease reached 50.0 % of the GPs. Control HLAs showed an overall decline of 4.3 %, while the total number of ADRs from GPs increased by 63.3 %. Ferrara was excluded from the analysis due to confounding factors. The periodic e-mail update on the safety of drugs represents an effective and inexpensive way to raise the awareness of GPs on the importance of spontaneous ADR reporting. Since the outcome of the intervention seemed to disappear after the intervention was stopped, there appears to be a need to adopt a policy of regular updates and educational strategies for health professionals.

Influence of polymorphisms and TNF and IL1β serum concentration on the infliximab response in Crohn's disease and ulcerative colitis.

Abstract: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are partially attributable to an increased secretion of proinflamatory cytokines, such as tumour necrosis factor (TNF) and interleukin-1β (IL1β), which play essential roles in the disease pathogenesis and are target molecules for specific therapy. Given the inter-individual variability in the response to the anti-TNF monoclonal antibody infliximab, the aim of our study was to explore the predictive value of TNF and/or IL1β as surrogate markers of infliximab response. Serial serum concentrations of TNF and IL1β and TNF promoter region and IL1B polymorphisms were determined in 47 patients (29 CD and 18 UC) receiving infliximab and correlated with treatment response. Baseline serum concentrations of TNF and IL1β were higher in UC patients than in CD patients (p = 0.0097 and 0.0024, respectively). CD patients showing <0.64 pg/ml IL1β at baseline were more frequently responders than non-responders (p = 0.036), and the C allele of the IL1B polymorphism was associated with higher IL1β serum concentrations (p = 0.026) and with poorer clinical remission after 14 weeks of infliximab treatment. No significant association was found between serum TNF concentration or TNF polymorphism and patient response to infliximab. This is the first study evaluating the pharmacogenetic role of the rs1143634 polymorphism of IL1B and TNF polymorphisms in infliximab-treated IBD patients. We found an association between the rs1143634 C allele and higher serum IL1β concentrations and a lower response to infliximab treatment in CD patients that warrants the interest of future studies in larger and independent series.

The prevalence and incidence of medicinal cannabis on prescription in The Netherlands.

Abstract: Background A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients. However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor’s prescription. This study describes a retrospective database study of The Netherlands.

Novel oral anticoagulants: clinical pharmacology, indications and practical considerations.

Abstract: Novel oral anticoagulants are approved in several indications: rivaroxaban, apixaban, and dabigatran for the prevention of venous thromboembolism after elective hip or knee replacement surgery, and edoxaban for hip or knee replacement surgery and hip fracture surgery (in Japan only); rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE; and rivaroxaban, apixaban, and dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. These agents overcome some limitations of traditional anticoagulants, are suggested to have no requirement for routine coagulation monitoring, and are administered orally. Rivaroxaban, apixaban, and dabigatran have different pharmacological characteristics, and guidance is needed on optimum doses and dosing intervals and the effects of renal or hepatic impairment, age, food, and other drugs. Dabigatran has stricter prescribing advice than rivaroxaban or apixaban for patients with moderate-to-severe renal impairment. All three drugs have restrictions on use in patients with hepatic impairment. Apixaban requires twice-daily dosing in all indications, whereas rivaroxaban and dabigatran are dosed once- or twice-daily depending on indication. Although head-to-head comparisons are lacking, the novel oral anticoagulants may show favorable cost–benefit relations compared with traditional vitamin K antagonists or no therapy. This review summarizes the pharmacology of rivaroxaban, apixaban, edoxaban, and dabigatran, and the indications for which they are approved. Issues regarding the optimization of the use of these anticoagulants for the management of thromboembolic disorders will also be discussed.

Interface management of pharmacotherapy : joint hospital and primary care drug recommendations

Abstract: Purpose In September 2012 an interactive course on the “Interface Management of Pharmacotherapy” was organized by the Stockholm Drug and Therapeutics Committee in cooperation with Department of Clinical Pharmacology at Karolinska Institutet and at Karolinska University Hospital in Stockholm, Sweden, in collaboration with the WHO. The basis for the course was the “Stockholm model” for the rational use of medicines but also contained presentations about successful models in interface management of pharmacotherapy in other European countries.

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray

Abstract: Purpose A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects.

Potentially inappropriate medication use among patients with Alzheimer disease in the REAL.FR cohort: be aware of atropinic and benzodiazepine drugs!

Abstract: Objective Few studies have investigated potentially inappropriate medication (PIM) use in patients with Alzheimer’s disease (AD). The aim of our study was to assess the prevalence of PIM in community-dwelling patients diagnosed with mild-to-moderate AD and identify the clinical factors associated with PIM prescriptions.

First European case of convulsions related to analytically confirmed use of the synthetic cannabinoid receptor agonist AM-2201

Abstract: Purpose There is increasing reported use of synthetic cannabinoid receptor agonists (SCRA) across Europe. To date, there is limited information on the acute toxicity (harm) related to the use of these products. We describe here a case in which an individual developed convulsions related to the use of the SCRA AM-2201.

Drug-induced anaphylaxis: a decade review of reporting to the Portuguese Pharmacovigilance Authority

Abstract: Purpose Anaphylaxis is a potentially fatal systemic adverse drug reaction (ADR). It is an unpredictable and mostly dose-independent event that occurs suddenly following exposure to the causative drug. Our objective was to characterize a case series of anaphylactic reactions reported to the Portuguese Pharmacovigilance authority during the past decade. Patients’ demographic data and implicated drugs were analyzed as well as the severity of the ADR and time trends.

Prediction of the tacrolimus population pharmacokinetic parameters according to CYP3A5 genotype and clinical factors using NONMEM in adult kidney transplant recipients

Abstract: Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of clinical covariates, including the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene encoding P-glycoprotein (ABCB1), on the PK parameters in adult Korean kidney transplant recipients. Clinical data were collected retrospectively for 400 days after the initiation of a tacrolimus-based immunosuppression therapy. Data from 2,788 trough blood samples obtained from 80 subjects were used to perform a population PK analysis with a nonlinear mixed-effect model (NONMEM). The estimated population mean values of clearance (CL/F) and volume of distribution (V/F) were 22.9 L/h and 716 L, respectively, and the k a was fixed to 4.5 h-1. The CYP3A5 genotype, hematocrit level, and post-operative days were identified as the main covariates that influence CL/F, and body weight was found to have a significant effect on V/F. Other covariates, including ABCB1 genotype, corticosteroid dosage, sex, and other clinical data, did not contribute to the pharmacokinetics of tacrolimus. This tacrolimus population PK model will be a valuable tool in developing rational guidelines and provides a basis for individualized therapy after kidney transplantation in clinical settings of Korea.

Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain

Abstract: Purpose To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms.

Nilotinib population pharmacokinetics and exposure-response analysis in patients with imatinib-resistant or -intolerant chronic myeloid leukemia

Abstract: Purpose We evaluated the population pharmacokinetics (PK) and exposure-response relationship of nilotinib in patients with imatinib-resistant or -intolerant chronic myeloid leukemia (CML).

Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case–control study in a new general practice database

Abstract: To test the ability a new Spanish primary care research database (BIFAP) to capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs and other drugs and compare the results with previous studies We performed a nested case–control study in persons aged 40–90 years old included in the period 2001–2005 Potential cases were selected through a computer search followed by an individual blinded review Controls matched for age, sex and calendar year were randomly selected The exposure window was defined as 0–30 days before the index date Adjusted odds ratios were obtained through unconditional logistic regression models In a study cohort of 669,115 subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases Increased risks were found with current use of NSAIDs (RR = 172; 95 %CI: 141–209), metamizole (152; 109–213), low-dose aspirin (174; 137–221), other antiplatelet drugs (173; 127–236), and oral anticoagulants (200; 144–277) We did not find an increased risk with current use of oral corticosteroids (111; 066–186), SSRIs (105; 077–142), or paracetamol (100; 082–123) Acid-suppressing drugs reduced the risk among users of NSAIDs (058; 039–085), particularly in users with antecedents of peptic ulcer (016; 005–058) We detected a decreasing time-trend in the relative risk and the population attributable proportion associated with NSAIDs over the study period The increased risk of UGIB associated with NSAIDs was lower than previously reported, which could partly be explained by methodological differences, but a decreasing burden over time of this drug safety problem is suggested BIFAP has shown to be a valuable tool for pharmacoepidemiological research

Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: A placebo-controlled, ex vivo, serial placebo-controlled serial crossover study

Abstract: Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA’s cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function. Methods: Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA’s antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation. Results: Ibuprofen and naproxen inhibit ASA’s antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold. Conclusions: COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA’s antithrombocyte effect.

Comparative epidemiology of hospital-acquired adverse drug reactions in adults and children and their impact on cost and hospital stay – a systematic review

Abstract: Purpose To study and analyze the comparative impact of hospital-acquired adverse drug reactions (ADRs) in adult and pediatric patients in terms of the economic implications, (length of) hospital stay, and salient features in relation to the incidence rate, severity, morbidity, mortality, and preventability of the ADRs.

Therapeutic drug monitoring for tomorrow.

Abstract: Therapeutic drug monitoring (TDM) represents an early approach to personalised medicine. It helps the clinician to individualise drug treatment and guide dosage to reach systemic drug concentrations associated with therapeutic efficacy and/or to reduce the risk of concentration-dependent adverse effects. Well into the fifth decade of TDM as a service to healthcare, this concept is still expanding, and new areas for clinical implementation continue to emerge. The aim of this overview is to discuss promising new therapeutic areas in future TDM services, how to improve the clinical interpretation of single drug measurements and how recent technology development opens the doors to research and new applications.

Safety of ginger use in pregnancy: results from a large population-based cohort study

Abstract: The objective of the study was to examine the safety of ginger use during pregnancy on congenital malformations and selected pregnancy outcomes. The Norwegian Mother and Child Cohort study, a large population-based cohort, provided the data used in this study. Our study population consisted of 68,522 women. Data on ginger use and socio-demographic factors were retrieved from three self-administered questionnaires completed by the women during weeks 17 and 30 of the pregnancy and when their child was 6 months old. Data on pregnancy outcomes were provided by the Medical Birth Registry of Norway. Among the 68,522 women in the study, 1,020 (1.5 %) women reported using ginger during pregnancy. The use of ginger during pregnancy was not associated with any increased risk of congenital malformations. No increased risk for stillbirth/perinatal death, preterm birth, low birth weight, or low Apgar score was detected for the women exposed to ginger during pregnancy compared to women who had not been exposed. Use of ginger during pregnancy does not seem to increase the risk of congenital malformations, stillbirth/perinatal death, preterm birth, low birth weight, or low Apgar score. This finding is clinically important for health care professionals giving advice to pregnant women with NPV.

Adherence to preventive statin therapy according to socioeconomic position

Abstract: To explore whether long-term adherence to preventive statin therapy depends on socioeconomic position (SEP). A cohort of individuals without established cardiovascular disease (CVD) or diabetes initiating preventive statin therapy during 2002–2005 was followed in the individual-level Danish registries for 4 years or until censoring events (death, emigration, CVD or diabetes). Only individuals aged 40–84 years for whom information was available on the SEP indicators, education and income were included (N = 76,038). Two different aspects of poor adherence were applied as outcome measures: (1) Proportion of days covered (PDC) with medication below 80 %, assuming a daily dose of one tablet (continuity); (2) Discontinuation defined as a gap between two consecutive prescriptions exceeding 365 days (persistence). Stratum-specific logistic regression analyses were applied to estimate the odds ratio (OR) for PDC <80 % across SEP, adjusting for age and hypertension. Hazard ratio (HR) for discontinuation was estimated by Cox regression analyses. Adjusting mutually for income and education, the OR for PDC <80 % decreased with increasing income. Comparing the highest income quintile with the lowest, the OR were 0.64 (95 % Confidence Interval 0.64–0.65) and 0.73 (0.73–0.74) in men aged 40–64 and 65–84 years, respectively; in women, the figures were 0.79 (0.79–0.79) and 0.95 (0.94–0.95), respectively. While observed increases in adherence with longer education in unadjusted analyses were attenuated after adjustment for income among men, the potential inverse relationship between length of education and adherence was enhanced among women. Applying discontinuation as outcome, analogous differences were demonstrated. Adherence to preventive statin therapy in Denmark decreases with decreasing income—especially in men aged 40–64 years.

Nurse-led interventions to enhance adherence to chronic medication: systematic review and meta-analysis of randomised controlled trials

Abstract: Non-adherence to chronic medication remains an important problem with vast consequences and without solutions to date. Nurses are well positioned to provide adherence care, yet currently represent an underutilised force in improving adherence and outcomes. This review aims to synthesise the effect of nurse-led interventions on adherence to chronic medication. Using Review Manager software, a meta-analysis was conducted. The search term medication adherence was combined with random* and nurse in PubMed and ISI Web of Knowledge. Retrieved articles’ reference lists were hand searched. Included were randomised controlled trials on nurse-led interventions, aiming to improve chronic medication adherence. Articles were to be in English and published from 2006 to 2011. Quality was assessed using an adapted version of the CONSORT tool. Ten studies met the selection criteria, seven of which were on HIV-positive patients. Their quality was acceptable to high. Counselling was the intervention most frequently assessed, mostly given face-to-face, but also in groups and via electronic messages. All interventions enhanced adherence. Of the five studies reporting adherence as mean percentage of adherence, pooled mean differences were +5.39 (1.70–9.07) (short term) and +9.49 (4.68–14.30) (long term), favouring the intervention groups. Of the studies reporting adherence dichotomously, odd's ratios were 1.55 (1.04–2.29) (short term) and 1.87 (1.35–2.61) (long term). The longer counselling was effectuated, the better the results. Counselling appears to be an effective approach that nurses can use to supplement other methods, building a multifaceted strategy to enhance adherence. Tackling non-adherence seems to demand continuous efforts and follow-up.

Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

Abstract: Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5–1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.