Optimizing anticoagulation therapy for in-hospital patients on direct oral anticoagulants: a single-centre modified Delphi study.

AIMS: The management of patients treated with direct oral anticoagulants (DOACs) during hospitalization is a common challenge in clinical practice. Although bridging is generally not recommended, too often DOACs are switched to parenteral therapy with low molecular weight heparins. Our objectives were to update a local guideline for perioperative DOAC management and to develop a guideline for the anticoagulation management in non-surgical patients regarding temporary DOAC discontinuation. METHODS: We executed a two-step modified Delphi study in a 1000-bed university hospital in Belgium. The Delphi questionnaires were developed based on a literature review and a telephone survey of prescribers. Two expert panels were established: one dedicated to perioperative DOAC management and the other to DOAC management in non-surgical patients. Both panels completed two rounds, commencing with an individual and online round, followed by a face-to-face group session. RESULTS: After the two-round Delphi process, the updated perioperative guideline on DOAC management included reasons for delaying the resumption of DOACs following surgery, such as oral intake not possible, the probability of re-intervention within 3 days, and insufficient haemostasis (e.g. active clinically significant haematoma, haemorrhagic drains or wounds). Furthermore, a guideline for non-surgical hospitalized patients was developed, outlining possible reasons for interrupting DOAC therapy. Both guidelines offer clear anticoagulation therapy strategies corresponding to the identified scenarios. CONCLUSIONS: We have updated and developed guidelines for DOAC management in surgical and non-surgical patients during hospitalization, which aim to support prescribers and to enhance targeted prescription review by hospital pharmacists.

Trends in oral anticoagulant use in patients with atrial fibrillation in Belgium from 2013 to 2019: A nationwide cohort study.

AIM: Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly preferred over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management. However, differences in oral anticoagulant (OAC) prescribing according to patient's age, sex and physician's specialty may be present. Therefore, incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC were investigated. METHODS: Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between 2013 and 2019 were identified. OAC use was investigated per half-year. Factors influencing NOAC vs. VKA initiation were identified by multivariable logistic regression. RESULTS: Among 448 661 included OAC-treated AF patients, 297 818 were newly treated. Incident OAC use ranged from 45-49 to 42-44 users/10 000 persons between 2013 and 2019, whereas prevalent OAC use increased from 337 to 435 users/10 000 persons. Incident and prevalent NOAC use exceeded VKA use since 2013 and 2015, respectively, and NOACs represented 92% of incident and 81% of prevalent OAC users in 2019. Apixaban was the most frequently used NOAC since 2016. NOACs were significantly more prescribed by cardiologists and to older patients, whereas VKAs were more initiated in patients with cardiovascular, renal and hepatic comorbidities. Prevalent OAC use increased less in women than men (25.3% vs. 33.0% between 2013 and 2019) and female subjects had 5% significantly lower odds of NOAC vs. VKA initiation than men. CONCLUSION: Since 2013, prevalent anticoagulant use increased almost one third in Belgium, while incident use was stable. Potential (N)OAC underuse in women requires further exploration.

Minimal Adherence Threshold to Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation to Reduce the Risk of Thromboembolism and Death: A Nationwide Cohort Study.

PURPOSE: Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks. METHODS: Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes. RESULTS: 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and < 80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90-94% versus 100% (aHR 1.09, 95%CI (1.01-1.17)). Findings were similar with once-daily and twice-daily dosed NOACs. CONCLUSION: Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be ≥ 90%, preferably even ≥ 95%.

Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study.

PURPOSE: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. METHODS: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified. RESULTS: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)). CONCLUSION: Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis.

AIMS: P-glycoprotein (P-gp) and CYP3A4-interacting drugs influence plasma levels of non-vitamin K antagonist oral anticoagulants (NOACs). However, the clinical relevance is questioned. Therefore, the impact of pharmacokinetically-interacting drugs on the effectiveness and safety of NOACs in patients with atrial fibrillation (AF) was investigated. METHODS: A meta-analysis was performed based on randomized controlled trials and observational studies retrieved from Pubmed and Embase that investigated the impact of concomitantly used P-gp/CYP3A4-interacting drugs on the risk-benefit profile of NOACs in AF patients. RESULTS: Fifteen studies were included, investigating 21 711 and 306 421 NOAC-treated AF patients with and without P-gp/CYP3A4 inhibitor use respectively, while only 1 study included P-gp/CYP3A4 inducers. In NOAC-treated AF patients, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding (relative risk [RR] 1.10, 95% confidence interval [CI; 1.01-1.19]) and all-cause mortality risks (RR 1.14, 95%CI [1.05-1.23]) compared to not using P-gp/CYP3A4 inhibitors, while the risks of stroke/systemic embolism (RR 0.88, 95%CI [0.77-1.01]), intracranial bleeding (RR 0.89, 95%CI [0.68-1.15]) and gastrointestinal bleeding (RR 1.09, 95%CI [0.91-1.30]) were not significantly different. Concomitant use of amiodarone with NOACs was associated with lower thromboembolic (RR 0.75, 95%CI [0.61-0.92]), similar major bleeding (RR 0.92, 95%CI [0.80-1.07]) but higher mortality risks (RR 1.21, 95%CI [1.05-1.39]). Coadministration of verapamil or diltiazem was associated with higher major bleeding risks (RR 1.64, 95%CI [1.31-2.06]), but comparable thromboembolic (RR 1.10, 95%CI [0.75-1.61]) and mortality risks (RR 1.01, 95%CI [0.77-1.33]). CONCLUSION: Given the higher bleeding and mortality risks in NOAC-treated AF patients concomitantly using P-gp/CYP3A4 inhibitors, close monitoring is warranted.

Physicians' and pharmacists' views and experiences regarding use of direct oral anticoagulants in clinical practice.

AIM: Direct oral anticoagulants (DOACs) are increasingly used compared to vitamin K antagonists (VKAs). Guidelines advocate a structured multidisciplinary approach in the management of patients treated with DOACs. The aim of this study was to assess the views and experiences of physicians and pharmacists regarding DOAC use in clinical practice. METHODS: An online questionnaire was sent to both primary (general practitioners [GPs], community pharmacists) and secondary healthcare professionals (cardiologists, residents in internal medicine and hospital pharmacists) between March and July 2020. The questionnaire covered four topics: (i) current practice, (ii) prescribing behaviour (only for physicians), (iii) self-perceived knowledge about DOACs and (iv) views and opinions about DOACs versus VKAs. RESULTS: In total, 110 physicians and 111 pharmacists completed the survey. Healthcare professionals in secondary care had more experience with DOACs and felt more confident with higher self-perceived knowledge about DOACs compared to their colleagues in primary care. Healthcare professionals' self-perceived knowledge was more or less complementary, for example physicians felt less confident in managing drug-drug interactions (DDIs) where pharmacists reported being more confident in this topic. Physicians reported uncertainties on the potential impact of risk factors - such as older age, lower body weight and DDIs - on appropriate DOAC dosing. CONCLUSION: Complementarity in physicians' and pharmacists' self-perceived knowledge levels of DOACs may facilitate and necessitate future multidisciplinary collaboration initiatives for the management and follow-up of DOAC patients.

Prevalence and management of drug interactions between nonsteroidal anti-inflammatory drugs and antithrombotics in ambulatory care.

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents is associated with increased risks of both bleeding and thromboembolism. In this prospective intervention study, community pharmacists screened for NSAID-antithrombotic interactions and contacted the prescribing physician to discuss interaction management. We included 782 interactions; these were found in an older, polymedicated patient population (mean age: 68 y, median of 5 other drugs). Ibuprofen (in 43.0% of cases) and low-dose aspirin (78.8%) were the most frequently involved NSAID and antithrombotic, respectively. Anticoagulants were involved in 16.1% of interaction cases. For 61% of cases, the interacting drugs were prescribed by the same physician. The pharmacist-physician discussion about how to manage the interaction mostly resulted in no change of pharmacotherapy (60.7%); the most frequent reason given by physicians was that the NSAID was for short-term use only. In 39.3% of cases the discussion resulted in a pharmacotherapy change; replacing the NSAID by paracetamol was the most common change.

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis.

PURPOSE: Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed. METHODS AND RESULTS: After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m2, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients. CONCLUSION: The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m2) and on differences between NOACs in these patients.

The perspectives of parents, general practitioners, and community pharmacists about treating an ill child in primary care: a comparative study.

As children are unable to make health-related decisions themselves, parents play a central role in consultations with healthcare providers. Parents' perspectives are therefore the focus of this study. Our first aim was to determine parents' expectations of a healthcare visit with a general practitioner and a community pharmacist. The second aim was to determine the general practitioners' and community pharmacists' perspectives about consultations with children. An observational cross-sectional study was conducted in April and May 2018. We developed three questionnaires: one for parents, one for general practitioners, and one for community pharmacists. The questionnaire for parents was only available through an online platform. The healthcare providers were questioned face-to-face and through an online platform. The study included 380 respondents. Parents considered prescribing or proposing medication the least important action by a general practitioner or community pharmacist, respectively. As well, parents expect information in most cases from both healthcare providers. The questionnaire for general practitioners and community pharmacists revealed that prescribing or proposing medication was regarded the least important action.Conclusion: Considering parents' expectations for a consultation with a general practitioner or community pharmacist, there is a substantial resemblance with the healthcare providers' perspective.What is Known:• The previous studies focusing on parents' perspectives were carried out in a hospital setting or focused on a specific disorder.• Parents consider reassurance and advice from their general practitioner to be very important; the treatment is considered less important.What is New:• Parents considered for both general practitioners' and community pharmacists' verbal information, answers to their questions, and reassurance as more important than receiving pharmacological treatment, while general practitioners and community pharmacists consider prescribing/proposing medication and providing written information as less important.• The expectations of the different groups (parents in relation to not only the healthcare providers but also the general practitioners and community pharmacists compared to each other) know a great resemblance.

Pharmacokinetic evaluation of linezolid administered intravenously in obese patients with pneumonia.

OBJECTIVES: Altered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obese patients with pneumonia. METHODS: Fifteen obese pneumonia patients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA. RESULTS: A two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumonia patients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patients <65 years old. CONCLUSIONS: Standard linezolid dosing is likely to provide insufficient target attainment against MRSA in obese patients. Body weight and especially age are important characteristics to be considered when administering linezolid to treat MRSA infections.

Self-management of medication during hospitalisation: Healthcare providers' and patients' perspectives.

AIMS AND OBJECTIVES: To explore healthcare providers' and patients' perspectives on self-management of medication during the patients' hospital stay. BACKGROUND: Self-administration of medications relates to the process in which hospitalised patients-instead of healthcare professionals-prepare and consume medications by themselves. Literature suggests possible advantages of medication self-management such as increased patient satisfaction, adherence to pharmacotherapy and self-care competence. DESIGN: A qualitative descriptive study design was adopted, using semistructured interviews and qualitative content analysis to examine data. METHODS: Six physicians, 11 nurses, six hospital pharmacists and seven patients were recruited from one regional hospital and two university hospitals, situated in Belgium. Interviews were conducted between October 2014-January 2015. RESULTS: Strengths of medication self-management were described by participants, relating to benefits of self-management for patients, time-saving benefits for nurses and benefits for better collaboration between patients and healthcare providers. Weaknesses were also apparent for patients as well as for nurses and physicians. Opportunities for self-management of medication were described, relating to the organisation, the patient and the process for implementing self-management. Threats for self-management of medication included obstacles related to implementation of self-managed medications and the actual process of providing medication self-management. A structured overview of conditions that should be fulfilled before allowing self-management of medication concerned patient-related conditions, the self-managed medication and the organisation of self-management of medication. CONCLUSIONS: This study provides new insights on the strengths, weaknesses, opportunities and threats from the perspectives of key stakeholders. Interpretation of these findings resulted in an overview of adaptations in the medication management process to facilitate implementation of self-management of medication. RELEVANCE TO CLINICAL PRACTICE: A medication management process for self-management of medication was proposed. Further interventional studies are needed to test and refine this process before implementing it in daily practice.

Community pharmacists' evaluation of potentially inappropriate prescribing in older community-dwelling patients with polypharmacy: observational research based on the GheOP³S tool.

Background: In this study, we aimed to (i) determine the prevalence of potentially inappropriate prescribing (PIP) in community-dwelling older polypharmacy patients using the Ghent Older People's Prescriptions community-Pharmacy Screening (GheOP³S) tool, (ii) identify the items that account for the highest proportion of PIP and (iii) identify the patient variables that may influence the occurrence of PIP. Additionally, pharmacist-physician contacts emerging from PIP screening with the GheOP³S tool and feasibility of the GheOP³S tool in daily practice were evaluated. Methods: A prospective observational study was carried out between December 2013 and July 2014 in 204 community pharmacies in Belgium. Patients were eligible if they were (i) ≥70 years, (ii) community-dwelling, (iii) using ≥5 chronic drugs, (iv) a regular visitor of the pharmacy and (v) understanding Dutch or French. Community pharmacists used a structured interview to obtain demographic data and medication use and subsequently screened for PIP using the GheOP³S tool. A Poisson regression was used to investigate the association between different covariates and the number of PIP. Results: In 987 (97%) of 1016 included patients, 3721 PIP items were detected (median of 3 per patient; inter quartile range: 2-5). Most frequently involved with PIP are drugs for the central nervous system such as hypnosedatives, antipsychotics and antidepressants. Risk factors for a higher PIP prevalence appeared to be a higher number of drugs (30% extra PIPs per 5 extra drugs), female gender (20% extra PIPs), higher body mass index (BMI, 20% extra PIPs per 10-unit increase in BMI) and poorer functional status (30% extra PIPs with 6-point increase). The feasibility of the GheOP³S tool was acceptable although digitalization of the tool would improve implementation. Despite detecting at least one PIP in 987 patients, only 39 physicians were contacted by the community pharmacists to discuss the items. Conclusion: A high prevalence of PIP in community-dwelling older polypharmacy patients in Belgium was detected which urges for interventions to reduce PIP.

SelfMED: Self-Administration of Medication in Hospital: A Prevalence Study in Flanders, Belgium.

BACKGROUND: Self-management is a key element in regaining and maintaining health. However, during hospitalization it becomes less obvious. Patient self-administration of medication during hospitalization is suggested to be beneficial to patient satisfaction, adherence to pharmacotherapy, and self-care competence. OBJECTIVES: This study aimed to examine the prevalence of self-administration of medication during hospitalization, and possible contributing factors. DESIGN AND SETTING: A cross-sectional observational study was conducted in 12 Belgian hospitals from February 2015 until June 2015. PARTICIPANTS: Data were collected on all hospitalized patients at 57 wards, based in 12 hospitals. DATA COLLECTION: A structured questionnaire at ward level and patient level on medication management, self-administration of medication, and rationale for prohibiting or allowing patients to self-administer their medication was conducted in consultation with the head nurse. RESULTS: Of the 1,269 patients participating in this study, 22% self-administered at least one medicine during hospitalization and 13.8% self-administered at least 50% of their total amount of medication. In the opinion of the head nurse, 40.9% of the hospitalized patients would have been able to self-administer their medication during hospitalization. Only a few wards had an available procedure and screening tool to assess the competence of the patients to self-administer their medication. This did not affect the prevalence of self-administration. Self-administration occurred significantly more at surgical short-stay wards, compared to other wards. The self-administering patients were on average younger and female and had a lower number of different medications per day before and during hospitalization. These patients had a good health status and were independent to mildly dependent on nurses on the ward. Related factors were used to provide a multivariate logistic regression model. CONCLUSIONS: Sometimes self-administration of medication was allowed. According to the surveyed nurses, however, more patients would be able to self-administer their medication during hospitalization. There seems to be a lack of procedures and screening tools to assess the competence or appropriateness of patients to self-administer their medication. CLINICAL RELEVANCE: This study provides new knowledge about the prevalence of self-administration of medication, contributing factors, the types of self-administered medications, and the organization of self-administration of medication on different wards.

Older patients' prescriptions screening in the community pharmacy: development of the Ghent Older People's Prescriptions community Pharmacy Screening (GheOP³S) tool.

BACKGROUND: Ageing of the population often leads to polypharmacy. Consequently, potentially inappropriate prescribing (PIP) becomes more frequent. Systematic screening for PIP in older patients in primary care could yield a large improvement in health outcomes, possibly an important task for community pharmacists. In this article, we develop an explicit screening tool to detect relevant PIP that can be used in the typical community pharmacy practice, adapted to the European market. METHODS: Eleven panellists participated in a two-round RAND/UCLA (Research and Development/University of California, Los Angeles) process, including a round zero meeting, a literature review, a first written evaluation round, a second face-to-face evaluation round and, finally, a selection of those items that are applicable in the contemporary community pharmacy. RESULTS: Eighteen published lists of PIP for older patients were retrieved from the literature, mentioning 398 different items. After the two-round RAND/UCLA process, 99 clinically relevant items were considered suitable to screen for in a community pharmacy practice. A panel of seven community pharmacists selected 83 items, feasible in the contemporary community pharmacy practice, defining the final GheOP³S tool. CONCLUSION: A novel explicit screening tool (GheOP³S) was developed to be used for PIP screening in the typical community pharmacy practice.

Drug administration via enteral feeding tube in residential care facilities for individuals with intellectual disability: A focus group study on guideline implementation.

People with profound intellectual disabilities often receive medication through enteral feeding tube (EFT). In a previous study, we found that current guidelines concerning medication preparation and administration through EFT are often not followed in residential care facilities (RCFs) for individuals with intellectual disabilities. The present qualitative study aimed to identify barriers and facilitators experienced by RCF staff members to following guidelines on medication administration via EFT, by conducting focus group interviews. Time constraints, lack of knowledge, lack of clear administration instructions, lack of necessary materials, and limited gastric fluid tolerance in certain residents were identified as barriers to following guidelines. Other influencing factors were the number of staff members, residents, and medications; habits; and the residents' comfort and well-being. To optimize care for this vulnerable patient population with EFT, an intervention can be set up focusing on improving staff members' medication-related knowledge and providing clear administration instructions and the necessary materials.

Physiology-based IVIVE predictions of tramadol from in vitro metabolism data.

PURPOSE: To predict the tramadol in vivo pharmacokinetics in adults by using in vitro metabolism data and an in vitro-in vivo extrapolation (IVIVE)-linked physiologically-based pharmacokinetic (PBPK) modeling and simulation approach (Simcyp®). METHODS: Tramadol metabolism data was gathered using metabolite formation in human liver microsomes (HLM) and recombinant enzyme systems (rCYP). Hepatic intrinsic clearance (CLintH) was (i) estimated from HLM corrected for specific CYP450 contributions from a chemical inhibition assay (model 1); (ii) obtained in rCYP and corrected for specific CYP450 contributions by study-specific intersystem extrapolation factor (ISEF) values (model 2); and (iii) scaled back from in vivo observed clearance values (model 3). The model-predicted clearances of these three models were evaluated against observed clearance values in terms of relative difference of their geometric means, the fold difference of their coefficients of variation, and relative CYP2D6 contribution. RESULTS: Model 1 underpredicted, while model 2 overpredicted the total tramadol clearance by -27 and +22%, respectively. The CYP2D6 contribution was underestimated in both models 1 and 2. Also, the variability on the clearance of those models was slightly underpredicted. Additionally, blood-to-plasma ratio and hepatic uptake factor were identified as most influential factors in the prediction of the hepatic clearance using a sensitivity analysis. CONCLUSION: IVIVE-PBPK proved to be a useful tool in combining tramadol's low turnover in vitro metabolism data with system-specific physiological information to come up with reliable PK predictions in adults.

Potentially inappropriate prescribing in community-dwelling older people across Europe: a systematic literature review.

BACKGROUND: Potentially inappropriate prescribing (PIP) is one of the main risk factors for adverse drug events (ADEs) in older people. PURPOSE: This systematic literature review aims to determine prevalence and type of PIP in community-dwelling older people across Europe, as well as identifying risk factors for PIP. METHODS: The PubMed and Web of Science database were searched systematically for relevant manuscripts (January 1, 2000-December 31, 2014). Manuscripts were included if the study design was observational, the study participants were community-dwelling older patients in Europe, and if a published screening method for PIP was used. Studies that focused on specific pathologies or that focused on merely one inappropriate prescribing issue were excluded. Data analysis was performed using R statistics. RESULTS: Fifty-two manuscripts were included, describing 82 different sample screenings with an estimated overall PIP prevalence of 22.6 % (CI 19.2-26.7 %; range 0.0-98.0 %). Ten of the sample screenings were based on the Beers 1997 criteria, 19 on the Beers 2003 criteria, 14 on STOPP criteria (2008 version), 8 on START-criteria (2008 version), and 7 on the PRISCUS list. The 24 remaining sample screenings were carried out using compilations of screening methods or used country-specific lists such as the Laroche criteria. It appears that only PIP prevalence calculated from insurance data significantly differs from the other data collection method categories. Furthermore, risk factors most often positively associated with PIP prevalence were polypharmacy, poor functional status, and depression. Drug groups most often involved in PIP were anxiolytics (ATC-code: N05B), antidepressants (N06A), and nonsteroidal anti-inflammatory and anti-rheumatic products (M01A). CONCLUSION: PIP prevalence in European community-dwelling older adults is high and depends partially on the data collection method used. Polypharmacy, poor functional status, and depression were identified as the most common risk factors for PIP.

Understanding medication adherence among patients of Turkish descent with type 2 diabetes: a qualitative study.

OBJECTIVES: To explore perspectives of Turkish migrants with type 2 diabetes mellitus (T2DM) on adherence to oral hypoglycaemic agents (OHA). DESIGN: In-depth interviews with 21 T2DM patients of Turkish descent recruited from primary care and community sources in Ghent, Belgium, using a theoretical sampling procedure. Analysis was guided by a grounded theory approach, using Nvivo 8. RESULTS: Respondents reported a multitude of barriers and facilitators of adherence to OHA. Some of these barriers are distinctive for T2DM patients of Turkish descent. Respondents' causal beliefs about stress and the Belgian climate often led to non-adherence during less stressful periods, like summer holidays in Turkey. Some respondents adjusted their medication use to food intake or during Ramadan fasting. Concerns about OHA were the main reason for the widespread use of herbal medicine in this sample. The religious framework used to interpret diabetes led, in combination with feelings of depression, to non-adherence in some respondents while it facilitated medication adherence in others. A potential gender effect with respect to the self-management of OHA was observed. Non-distinctive factors include: beliefs about OHA, polypharmacy, beliefs about the course of diabetes, forgetfulness, the perception of the doctor's medical expertise, feelings of depression and social support. CONCLUSION: Health care providers should explore in detail and regularly patients' perspectives on illness beliefs, medication beliefs and their trust in doctors' medical expertise as this will provide useful starting points for promoting medication adherence. Whenever possible health care workers should engage with their patients in therapeutic alliances.

Modelling of drug-induced QT-interval prolongation: estimation approaches and translational opportunities.

Safety pharmacology studies are performed to assess whether compounds may provoke severe arrhythmias (e.g. Torsades de Pointes, TdP) and sudden death in man. Although there is strong evidence that drugs inducing TdP in man prolong the QT interval in vivo and block the human ether-a-go-go-related gene (hERG) ion channel in vitro, not all drugs affecting the QT interval or the hERG will induce TdP. Nevertheless, QT-interval prolongation and hERG blockade currently represent the most accepted early risk biomarkers to deselect drugs. An extensive pharmacokinetic/pharmacodynamic (PK/PD) analysis is developed to understand moxifloxacin's-induced effects on the QT interval by comparing the relationship between results of an in vitro patch-clamp model to in vivo models. The frequentist and the fully Bayesian estimation procedures were compared and provided similar performances when the best model selected in NONMEM is subsequently implemented in WinBUGS, which guarantees a straightforward calculation of the probability of QT-interval prolongation greater than 2.5 % (10 ms). The use of the percent threshold to account for the intrinsic differences between species and a new calculation of the probability curve are introduced. The concentration providing the 50 % probability indicates that dogs are more sensitive than humans to QT-interval prolongation. However, based on the drug effect, a clear distinction between species cannot be made. An operational PK/PD model of agonism was used to investigate the relationship between effects on the hERG and QT-interval prolongation in dogs. The proposed analysis contributes to establish a translational relationship that could potentially reduce the need for thorough QT studies.

[Drug shortages in the hospital: management, causes and budget impact]. / Indisponibilité des medicaments dans les hôpitaux: gestation, causes et impact sur le budget.

INTRODUCTION: Drug shortages have become an issue of growing interest for pharmacists. Both number and type of shortages have increased over the past decade and it is challenging to provide drug continuity. Aim To describe management and impact of drug shortages for the hospital pharmacy. To gain insight into the causes of shortages. METHODS: The management process for drug shortages was analysed for the hospital pharmacies of the Ghent University Hospital (GUH) and the Acute Care Hospital Sint-Lucas Ghent. Insights in possible causes were obtained by semi-structured interview with the Federation for Belgian Pharmacists (Association Pharmaceutique beIge (APB)), the Belgian association of the pharmaceutical industry (pharma.bel and the Federal Agency for Medicines and Health Products (FAMHPI. A database of 1329 drug shortages (Jan 2001-Feb 2014 of the GUH was used to define drug classes affected by shortages (mean shortage days per year, standard deviation (SDI), type of shortage [urgent/ important] %, total number (n)), formulation (parenteral:oral and duration of the shortages (median, interquartile range (IQR)). The total cost impact for the GUH pharmacy was estimated by calculating average, minimum and maximum time investment by the pharmacy team (Delphi-techniquel and by calculating the cost difference between original and alternative drug acquisition costs. Impact is presented as base case scenario (minimum as best and maximum as worst case scenario). RESULTS: The different management phases for the pharmacist are problem identification, preparation of solution and implementation. Communication and extensive administration are essential components. Causes are production related, next to distribution inequivalences, quota and European market flows. Shortages with anti-infectious, cardiovascular and hormonal system drugs have the highest and constant proportion of drug shortage days, with recently appearance of other important drug classes such as anticancer therapy [2011 and further). The average number of drug shortage days in 2011-2013 is 8020 (SD 2142 compared to period 2001-2010 with on average 4633 days (SD 1731]. Fifty-four percent of the shortages is important for the direct hospital care and 22.9% needs urgent action. The proportion parenteral versus oral in the database is 3.3:1. Median duration of a shortage is 29 [IQR 11-65]1 days. The average excess cost of an equipotent dose of the alternative drug was 4.9 (SD 31.3) Euro. Total cost impact (gross salary and drug acquisition cost] for GUH pharmacy in 2013 is 117 281.4 Euro (best case: 88 345.06 and worst case: 151,208.2 Euro. CONCLUSION: The importance of the shortages and the diversification of the drug classes involved have an impact on the hospital pharmacy management. For the GUH this represents an important workload and an increased drug acquisition cost. Causes of shortages are production related but also distributional inequivalences and quota play an important role.