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Background 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, patient's sex and physician's specialty may be present. Purpose To investigate the incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC on a full-population scale. Methods Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between January 1st, 2013 and December 31st, 2019 were identified. OAC use was investigated per half-year with a repeated cross-sectional design, based on medication prescription claims on a day-to-day basis. Incident use was defined as the first OAC use during the study period in OAC-naïve AF patients, whereas prevalent OAC use was defined as at least 1 OAC dispensing during a specific half-year. Factors influencing NOAC versus VKA initiation were identified by multivariable logistic regression models. Results Among 448,661 included OAC-treated AF patients (260,184 prevalent NOAC and 188,477 prevalent VKA users), 297,818 were newly-treated (232,739 incident NOAC and 65,079 incident VKA users). The mean age of incident NOAC and VKA users was 76±10 and 71±12 years, and 48% and 47% were female, respectively. Incident OAC use ranged from 45–49 to 42–44 users/10,000 persons between 2013–2019, 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% versus +33% between 2013–2019) and female subjects had a 5% significantly lower odds of NOAC versus VKA initiation than men after multivariable adjustment. Conclusions Prevalent anticoagulant use increased with 29% in Belgium between 2013 and 2019. However, potential (N)OAC underuse among female AF patients was observed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO)

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.

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.

Objectives Alcohol and medication use are increasingly prevalent in the older population. Concurrent use of alcohol and alcohol-interactive (AI) medication can lead to significant adverse consequences. Methods Three reference works were used to create an explicit list of drug substances for which information about the interaction with alcohol was available in at least one of them. Additional information was extracted from the Summary of Product Characteristics (SPC). The first aim was to generate a list of 256 substances with standardized advice regarding the concurrent use of each drug with alcohol. The second aim was to observe the prevalence of potential drug–alcohol-interactions. The list was applied to a database containing information about alcohol and medication use of 1,016 community-dwelling older patients (≥70 years) with polypharmacy. Results About half of the sample population reported to consume alcohol at least once a week. Around 22% were classified as frequent drinkers (5–7 days/week) and 11% as heavier drinkers (>7 units/week). Ninety-three percent alcohol consumers in our sample took at least one chronic drug that potentially interacts with alcohol and 42% used at least one chronic drug for which alcohol use is considered contraindicated. Conclusions We developed an explicit list of potentially drug–alcohol-interactions in older adults, with standardized handling advice. We observed that prevalence of potential drug–alcohol-interactions is substantial in community-dwelling older patients with polypharmacy.

Background The Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3S)-tool was developed in 2016 as a screening tool to detect drug-related problems (DRPs) and to help in performing medication reviews in older people (≥ 65 years). Objective This study aimed to revise and update the GheOP3S-tool. Methods Users’ comments were collected to improve the usability and appropriateness of the original GheOP3S-tool, followed by a two-round modified Delphi process according to the RAND/UCLA appropriateness method. This included a literature review, a round zero meeting, a first written round (with 15 international and multidisciplinary experts) and a second face-to-face round (with 11 experts) to change, delete or add GheOP3S-criteria. An additional third round with 14 community pharmacists was organised to preserve criteria applicable in the current community pharmacy practice. Results The updated GheOP3S-tool consists of five lists of DRPs and a new addendum containing medications that should be avoided or used with caution in older people with reduced renal function. During the first two rounds, related criteria were grouped, 14 criteria were added and 17 criteria were deleted from the original tool. All criteria were deemed applicable in round 3. This led to a final tool (version 2) with 64 GheOP3S-criteria. Conclusion GheOP3S-criteria were revised and updated according to experts’ agreement on their clinical relevance and recent scientific evidence. Future studies should investigate the impact of pharmacist-led medication reviews with GheOP3S-tool version 2 on clinical, humanistic and economic outcomes in primary care. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00862-6.

Although obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF-related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta-analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73-0.87]; RR 0.63, 95%CI [0.57-0.70]; and RR 0.42, 95%CI [0.31-0.57], respectively) and all-cause mortality (RR 0.73, 95%CI [0.64-0.83]; RR 0.61, 95%CI [0.52-0.71]; and RR 0.56, 95%CI [0.47-0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to = 30 and >= 40 kg/m(2), respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to

Background This study aimed to evaluate the prevalence of potential drug-drug interactions (DDIs) and the appropriateness of direct oral anticoagulant (DOAC) dosing according to both the Summary of Product Characteristics (SmPC) and the European Heart Rhythm Association (EHRA) Practical Guide in a ‘real-world’ sample of non-valvular atrial fibrillation (NVAF) patients. Methods and results Data of a cross-sectional observational study in a primary care sample of 654 long-term DOAC users were used for this sub-analysis. A total of 262 potential DDIs were identified in 220 patients (33.6%). Pharmacodynamic DDIs were present in 163 patients (24.9%) and pharmacokinetic DDIs in 82 patients (12.5%). One-third of patients (33.8%) received reduced DOAC dose. According to the dosing recommendations in the SmPC, 81.7% of DOACs were dosed appropriately. According to the EHRA recommendations, 76.6% of DOACs were dosed appropriately. Dosing recommendations were consistent for 90.7% of patients, with both the SmPC and EHRA Practical Guide considering DOACs dosed appropriately in 74.5% of patients, overdosed in 7.8%, underdosed in 7.6% and contraindicated in 0.8%. However, for the remaining 9.3% dosing recommendations differed between SmPC and EHRA. Conclusions This ‘real-world’ analysis of DOAC dosing demonstrated that in about one-third of NVAF patients potential DDIs were present. In 18.3% and 23.4% of patients, DOACs were dosed inappropriately according to the SmPC and EHRA Practical Guide respectively. In almost 10% of the study population dosing advice was inconsistent between both references. More research is needed to ensure appropriate DOAC dosing in this ‘grey zone’ population.

Resume Introduction Il existe un nombre croissant d’articles decrivant les roles et demontrant les impacts de l’activite du pharmacien et de ses collaborateurs en milieu communautaire et en etablissement de sante. Il n’y a toutefois pas de profil de cette litterature publiee par les pharmaciens exercant en Belgique. Methode Il s’agit d’une revue de litterature. L’objectif principal de cet article est de rassembler des preuves afin de decrire et de mettre en evidence les differentes caracteristiques du role des pharmaciens et l’impact de leurs activites en Belgique. La recherche documentaire a ete effectuee dans trois bases de donnees soit PubMed, Embase et CINAHL entre le 01/01/2006 et le 30/09/2019. Resultats Des 232 articles identifies, 65 ont ete retenus pour analyse. Les etudes comprenaient uniquement des donnees descriptives (73,9 %, 48/65) ou des donnees descriptives associees a des mesures de l’impact du pharmacien (26,1 %, 17/65). L’etude a mis en evidence la presence de pharmaciens exercant l’une ou l’autre des 21 activites pharmaceutiques avec, en ordre decroissant, les revues de medication, le conseil aux patients (i.e. processus ponctuel qui cible un medicament), l’education therapeutique des patients (i.e. processus continu, interdisciplinaire, qui vise non seulement a informer mais aussi former et evaluer le patient) et les activites de reconciliation medicamenteuse. Les etudes etaient menees uniquement dans des officines (53,8 %, 35/65), des hopitaux (29,2 %, 19/65), les deux a la fois (7,7 %, 5/65) et d’autres milieux de pratique (9,2 %, 6/65). Dix-sept des 65 etudes incluses comportaient une mesure de l’impact de la presence du pharmacien. Sur les 35 mesures d’impact associees aux interventions pharmaceutiques, 23 comprenaient des effets positifs, 12 des effets neutres et aucun des effets negatifs. Conclusion Il s’agit de la premiere revue de litterature sur les roles et les impacts du pharmacien en Belgique. Soixante-cinq articles ont ete retenus dont 17 comportant des mesures de l’impact de l’activite pharmaceutique. Sur les 35 mesures d’impact associees aux interventions pharmaceutiques, 23 comprenaient des effets positifs, 12 des effets neutres et aucun des effets negatifs. Ces donnees s’inscrivent dans le cadre du plan d’action pour le developpement de la pharmacie clinique dans les hopitaux belges pour la periode 2015–2020.

Rhinitis medicamentosa (RM) is a type of nonallergic rhinitis caused by prolonged use of nasal decongestants (NDs). Although it is a preventable phenotype of rhinitis, little is known about patients dealing with this condition.To gain a better understanding of patients' views and experiences of ND overuse, and potential facilitators and barriers to discontinue the overuse.We performed a qualitative study using in-depth semistructured interviews with 22 patients who have been using an ND on an almost daily basis for at least 6 months. The interviews were conducted face-to-face, audio-recorded, and transcribed verbatim. Data analysis followed the grounded theory approach.Interviewees described the large impact of nasal congestion on their daily lives. Despite efforts to try other treatment options, the ND was considered the only effective aid to resolve the troublesome symptom. Most participants were aware that the prolonged use was problematic, sometimes leading to hiding behavior in order to avoid criticism by others including their health professionals. Many participants expressed a strong will to discontinue. However, multiple barriers to withdrawal were identified including fear of surgery or the impact of withdrawal on sleep, lack of good alternatives, and negative experiences with past withdrawal attempts. Patients thus face a dilemma in which the barriers to withdrawal currently outweigh the possible benefits.The use of NDs is considered indispensable by many chronic users. The facilitators and barriers identified in this study provide opportunities to reduce the use of NDs and the prevalence of RM in the future.

Direct oral anticoagulants (DOACs) can be involved in clinical relevant drug-drug interactions (DDIs) which may compromise safe and effective use. However, assessing the clinical relevance of DDIs with DOACs and managing these interactions optimally, can be challenging in clinical practice.To develop a practice-oriented list of potentially clinically relevant DDIs with DOACs with corresponding management plans for which it is important to screen in ambulatory care.The RAND/UCLA appropriateness method was used to develop the DOACs DDI list. In a first step a preliminary list was compiled of potentially clinically relevant DDIs per DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) using five reference sources. Subsequently, a two-step modified Delphi process involving a multidisciplinary panel (n = 10) including both pharmacists and physicians with expertise in all decision-making disciplines involved in care for patients using DOACs and with diversity of practice setting, was used to reach expert agreement on a final list of DDIs with corresponding management plans.After a two-step consensus round, 71 DDIs for 20 different interacting drugs were included: five pharmacodynamic, nine pharmacokinetic inhibitor and six pharmacokinetic inducer interacting drugs. Considerations raised and discussed by the panellists were related to (1) the necessity of the interacting drug, (2) the manageability of the DDI (whether there are any alternatives), (3) the (clinical) evidence-base for the DDI and (4) the (potential) consequences of the DDI.We developed a consensus list with specific and straightforward management plans on potentially clinically relevant DDIs with DOACs, for use in ambulatory care.

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.

Introduction Both oral retinoid and valproate containing medicines are highly teratogenic. Their use by women of childbearing age is controlled by risk minimization measures (RMMs) introduced by the European Medicine Agency, including the pregnancy prevention programme (PPP). In 2018, the RMMs were revised as previous measures were insufficient to prevent the use of these medicines during pregnancies. Aim & Methods A cross-sectional survey was conducted among patients, physicians and pharmacists to evaluate the implementation of the revised RMMs in Belgium. The primary outcome was compliance with key aspects of the PPP. Differences in compliance between oral retinoid and valproate stakeholders were investigated. The relationship between potential determinants (population characteristics and RMM usage) and compliance was studied via multiple logistic regression. Results A total of 317 eligible patients, physicians and pharmacists participated. The majority of the studied patients fail to comply with the PPP, mainly driven by poor implementation of pregnancy testing. A large number of healthcare providers is unaware of the available educational materials. Conclusion It is likely that a substantial part of Belgian women of childbearing age using oral retinoids or valproate insufficiently meet the PPP requirements. We propose to better inform healthcare providers about the mandatory PPPs and available educational materials as well as to support them with the implementation of such programmes to improve the safe use of these teratogenic medicines.

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.

The Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3 S)-tool was recently developed as an explicit screening tool to detect drug-related problems (DRPs) and to help in performing medication reviews. In this study, we aimed (a) to describe the characteristics of the detected DRPs and the subsequent pharmacists' recommendations with their acceptance and implementation rate resulting from a pharmacist-led medication review using the GheOP3 S-tool and (b) to assess the potential impact of the intervention., info:eu-repo/semantics/published

Background and objective: The prevalence of potentially inappropriate prescribing (PIP) among nursing home (NH) residents is high. This study aimed to investigate the acceptance and implementation ...

BACKGROUND: The Association of Pharmacists in Belgium (APB) and local pharmacy associations launched a pilot project in collaboration with research teams from three Belgian universities to study the impact and implementation-related issues of a medication review (MR) service type 2a in Belgian community pharmacies. OBJECTIVE: The aim of this paper is to describe the implementation process of the MR service and to present the implementation evaluation of the pilot study (testing stage). METHODS: The pilot project was a prospective observational study using mixed methods. The implementation evaluation was based on the RE-AIM model and the framework for the implementation of services in pharmacy (FISpH). Collected implementation outcomes were classified into four dimensions: reach, adoption, implementation and intent of maintenance. RESULTS: During the testing stage, 80 pharmacies participated in the study, but 25 dropped out (31%), mainly because of a reported lack of time (adoption). The 55 remaining pharmacies included 457 patients. Recruiting patients into the service was challenging for pharmacists as 48.5% of patients refused the pharmacists' proposal (reach). Internal organizational factors were major barriers for pharmacists, followed by the lack of adoption by the pharmacy team. Large pharmacies in which pharmacy owner led the project were observed to be more proactive in implementing the MR service by integrating organizational strategies to assist the implementation process (implementation). Interviewed pharmacists perceived this new service as a professionally satisfying activity. Among participating pharmacists, 92.5% found this service feasible in practice, but believed it required adapted resources to reorganize the internal pharmacy workload, additional support, such as broad-based media campaigns to increase physicians' and patients' awareness and attitudes towards the service, and modified software (maintenance). CONCLUSIONS: The medication review service was implemented in 68% of participating pilot Belgian community pharmacies but would require adapted resources and supports for larger scale implementation. ispartof: RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY vol:15 issue:6 pages:710-723 ispartof: location:United States status: published

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 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.

Atrial fibrillation and non-vitamin K antagonist oral anticoagulants: from clinical trials to real-world clinical practice. For decades, vitamin K antagonists (VKAs) were the only oral anticoagulants available for the prevention of thromboembolism in patients with atrial fibrillation (AF). Since 2012, non-vitamin K antagonist oral anticoagulants (NOACs) are available for this indication, which have proven to be at least as effective and safe as VKAs in randomized controlled trials (RCTs). NOACs have additional benefits, such as a fast onset of action, a fixed-dose regimen without requiring regular monitoring, less interactions and less intracranial bleeding. Their emergence has caused a paradigm shift in anticoagulation therapy, with NOACs being the anticoagulant of choice compared to VKAs. Since strict in- and exclusion criteria were used in the pivotal RCTs, concerns have risen regarding the generalizability of these results to real-life clinical practice in patients with multiple comorbidities. In this manuscript, this extrapolation is discussed, focusing on 4 different topics regarding appropriate NOAC use: the management of AF patients with a single stroke risk factor, the importance of an optimal therapy adherence, potential drug-drug interactions with NOACs and addressing a geriatric AF patient after a fall. Hopefully, this manuscript will help guide clinicians in the optimal use of NOACs in their daily clinical practice.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fund for Scientific Research Flanders (FWO) Background 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. Moreover, VKAs are still recommended in morbidly obese patients (body mass index (BMI) ≥40 kg/m², body weight >120 kg) due to lack of data for NOACs in these patients. Purpose A critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum. Methods After searching the Medline database, phase III randomized controlled trials (RCTs) and longitudinal observational cohort studies on the effectiveness and safety of NOACs versus VKAs in obese (BMI ≥30 kg/m²), and class III obese (BMI ≥40 kg/m²) non-valvular AF patients, and in low body weight (≤60 kg) AF patients during a mean/median follow-up of ≥6 months were included. The meta-analyses were performed using a random effects model with the Mantel-Haenszel method. Results A meta-analysis based on 4 phase III RCTS and 3 longitudinal observational cohort studies demonstrated that NOAC use in obese and class III obese AF patients 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) as 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]), and similar mortality risks (RR 0.68, 95%CI [0.42-1.10]) were observed for NOAC- versus VKA-treated patients in a meta-analysis based on 4 phase III RCTs and 2 longitudinal observational cohort studies. Conclusions The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight of ≤60 kg. However, more data are needed in underweight AF patients (BMI

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.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/mThe 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/m

An amendment to this paper has been published and can be accessed via the original article.

The idea of patients self-administering their medication in hospital is not new; it was first cited in literature in 1959. Up to date, there is a growing body of literature that recognizes the importance of this approach. In this current state of the literature, self-administration of medication in hospital is positioned in the context of the definition of health as proposed by Huber et al. and Orem’s self-care deficit theory: first identify the concept of medication self-administration, as well as the prevalence, existing procedures, tools, and proven effects of interventions; then the findings should point the way forward for research, practice, and policy.

Background and objective: An accurate medication scheme may be a useful tool to improve medication safety in primary care. This study aimed to identify (1) pharmacists’ alterations to nurse...

BACKGROUND: Renal function progressively worsens with age. Potentially inappropriate prescribing (PIP) of renally excreted active drugs (READs) is common in older adults, leading to an increased rate of iatrogenic illness. The Ghent Older People's Prescription community Pharmacy Screening (GheOP3S-) tool is an effective, explicit instrument that was developed for community pharmacists (CPs) to detect PIP. So far, this tool does not assess PIP of the frequently used READs in older patients with renal impairment. OBJECTIVES: This study aimed to expand the GheOP3S-tool with the first addendum to screen for PIP of frequently used READs, and to perform a cross-sectional analysis using the addendum and the medication history of a group of older adults with polypharmacy. METHODS: The addendum was developed in three steps: (1) collection of individual and combined READs, (2) collection of dose-adjustment recommendations, and (3) expert panel evaluation. Consequently, the addendum was applied retrospectively on the medication list of 60 older adults with polypharmacy and with four renal function-estimating equations. RESULTS: The addendum includes 61 READs recommendations for dose/drug-adjustment alternatives, laboratory test follow-ups, and patients' referral to specialists' care. In the cross-sectional analysis, 35-78% of patients were diagnosed with renal impairment, depending on the equations used for renal function estimation. Among patients with renal impairment, 21-46% of the prescribed READs were deemed potentially inappropriate by the GheOP3S-tool addendum. CONCLUSION: The GheOP3S-tool was expanded with an addendum on PIP of READs in renal impairment for older patients. The cross-sectional analysis using the addendum suggests that PIP of READs is common in older patients with polypharmacy and renal impairment. Using this addendum, CPs might contribute to diminishing PIP of READs.

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 patientsinstead of healthcare professionalsprepare 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 patientswere 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.

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.

Zowel in Belgie als in Europa wordt het aantal personen ouder dan 65 jaar alsmaar groter. Recente cijfers geven aan dat ongeveer 20% van de totale populatie ouder is dan 65 jaar, wat in Belgie neerkomt op ruim twee miljoen oudere personen.1

ObjectiveThis study aimed to assess implementation adherence (how well the patient’s actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users.MethodsA cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ).ResultsA total of 766 patients (mean age 76.2±8.8 years, median CHA2DS2-VASc score 4 (IQR=3–4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8–99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score ConclusionsOur data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients’ thromboembolic risk and NOACs’ short half-lives, further optimisation of NOAC use seems warranted in this population.

Background: Reflux occurs in 50% of healthy infants at some point. This is most often a physiological condition and does not require drug treatment. Various studies have shown that the use of drugs affecting gastric acidity (DAGAs) in infants is increasing. This entails disadvantages such as unnecessary exposure of infants to medication and their side effects and a higher cost to society. Objective: To get an image of the current practice in Flanders regarding diagnosis and treatment of gastro-oesophageal reflux disease (GORD) in infants and the associated use of DAGAs. To this end, we determined both parents&rsquo, and health care providers&rsquo, experiences and perceptions about these treatments. Method: An observational cross-sectional study was conducted in April and May 2019. We developed a questionnaire for parents and three different questionnaires for health care providers (HCPs), including midwives, general practitioners, paediatricians and community pharmacists (CPs). The questionnaire for parents was only available through an online platform. HCPs were questioned face-to-face and through an online platform. Results: This study made clear that the counselling of children with GORD is multidisciplinary as the median number of counselling HCPs is 3 (interquartile range (IQR) = 2&ndash, 4). 63% of the included 251 parents also seek support through online forums and groups. 60% of parents report that no physical tests were performed before DAGAs were prescribed and 39% of parents additionally state they perceived no effect of the prescribed DAGAs. Although parents reported to understand HCPs well (average score 7.4/10), satisfaction with care and information provision was scored lower (between 4.8 and 6.1/10). On the other hand, 234 HCPs answered the questionnaire, of which 89 midwives, 78 community pharmacists and 67 physicians. Only 45 HCPs indicate that guidelines to diagnose or treat GORD are clear. Physicians confirm they perform very little physical testing before starting DAGAs. Provided nonmedical measures to patients are largely in line with the European guidelines, however perceived effectiveness is moderate. Conclusion: Parents are in need for more information about tests, nutrition and (non)medical measures. HCPs on the other hand are in need for clear guidelines on diagnosing and treating GORD.

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.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that-potentially severe-side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease. ispartof: CLINICAL AND TRANSLATIONAL ALLERGY vol:10 issue:1 ispartof: location:England status: published

OBJECTIVE: To assess eye drop technique and patient-reported problems with eye drop instillation in a primary care sample of eye drop users. METHODS: Cross-sectional observational study in 136 community pharmacies in Belgium. Patient inclusion criteria were being age ≥ 18 years and using eye drops for ≥ 1 month (to ensure that patients were already familiar with eye drop instillation). Participants demonstrated their eye drop technique and completed a self-administered questionnaire. RESULTS: Participants (n = 678) had a mean age of 68.9 ± 12.4 years. During the demonstration, almost everyone (98.0%) successfully instilled at least one drop in the eye, although 14% required multiple attempts to achieve this. Only 3% of the sample exhibited perfect drop technique, meaning that they performed correctly all the steps. Most common deviations were touching the bottle to the eye or eyelid (40.7% of patients), and failing to close the eye (67.8%) and perform nasolacrimal occlusion for at least 1 min (94.7%) after drop instillation. Importantly, we found that 20% of ophthalmic suspensions were not shaken before use. Forty percent of patients reported ≥ 1 problem with eye drop instillation. Most common problems were difficulties with getting a drop in the eye (18.3% of patients), too many drops coming out of the bottle (14.6%), and difficulty squeezing the bottle (12.2%). About half of the sample recalled having had education in eye drop instillation technique. CONCLUSION: This study showed suboptimal eye drop technique in real-world clinical practice. A proactive role of community pharmacists in detecting and resolving these problems could be helpful.

Background The emergence of non-vitamin K antagonist oral anticoagulants (NOAC) has caused a paradigm shift in anticoagulation therapy, with NOAC being increasingly used compared to vitamin K antagonists. Despite the numerous RCTs with NOAC, further follow-up on how this high risk new drug class is used in real-world clinical practice is warranted. Purpose This study aimed to describe NOAC use in a primary care sample of long-term NOAC users, and investigated (i) adherence, (ii) patients' perceptions, (iii) drug interactions and (iv) appropriateness of dosing. Methods A cross-sectional observational study was conducted in 158 community pharmacies. Participants were home-dwelling adults treated with a NOAC for at least one year. They completed a questionnaire collecting data on socio-demographics, clinical characteristics, current medication use, self-reported adherence to NOAC (via Medication Adherence Report Scale, MARS), and beliefs and perceptions about NOAC (via Beliefs about Medicines Questionnaire, BMQ). Adherence to NOAC (self-reported (MARS) and calculated using pharmacy dispensing data (Medication Possession Ratio (MPR)); patients' beliefs and perceptions about NOAC (BMQ); and prevalence of drug interactions and inappropriate dosing (using the recommendations in the summary of product characteristics (SmPC) and the 2018 European Heart Rhythm Association (EHRA) Practical Guide) were assessed. Results Participants (n=766) had a mean age of 76.2±8.8 years, several co-morbidities (median of 5 (IQR 4–6)) and high thromboembolic risk (median CHA2DS2-VASc score of 4 (IQR 3–4)). The majority (93.5%) used NOAC for non-valvular atrial fibrillation, while the other 6.5% used it for the prevention of recurrent deep vein thrombosis or pulmonary embolism. Forty point five percent of the study sample used rivaroxaban, 36.2% apixaban, 21.1% dabigatran and 2.2% edoxaban. About 85% was adherent according to MPR (MPR ≥80%) and self-reported adherence was also high (mean MARS score 24.6±1.0). Two-thirds reported at least one adverse event of the NOAC, with easy bruising/bleeding being most prevalent (40.2% of patients). BMQ showed that 91.3% of patients favoured the “necessity” over the “concerns” of NOAC use. Thirty-one percent of patients had ≥1 drug interaction(s) with NOAC; amiodarone (10.4% of patients), antiplatelet agents (9.7%) and NSAIDs (9.0%) were the most common interacting drugs. NOAC dosing was inappropriate in 15.9% of patients according to SmPC and in 23.1% according to EHRA. Intriguingly, underdosing was more common using the SmPC as reference, while overdosing was more common using the EHRA guideline. Conclusions This real-world analysis of NOAC use revealed high adherence and necessity beliefs, drug interactions in 30% of patients, and suboptimal dosing in about one fifth of patients. These findings can inform the design of targeted community pharmacist interventions to improve quality of NOAC use.

The Ghent Older People's Prescriptions community Pharmacy Screening (GheOPProspective observational study in community-dwelling older patients (70 years or older, using five or more medications). Community pharmacists performed medication reviews resulting in the documentation of “GheOPTwenty-one pharmacists detected 470 DRPs with a median (IQR) of 6 (4-8) per patient in 75 patients (about half “GheOPThis study demonstrates a relatively high acceptance of pharmacists' recommendations, although implementation could be improved. Pharmacist-led medication reviews with multidisciplinary meetings using the GheOP

Background: The Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3S-)tool was recently developed to screen for potentially inappropriate prescribing (PIP). Objective: We aimed (1) to determine PIP prevalence in older nursing home (NH) residents with polypharmacy using the GheOP3S-tool and (2) to identify those PIPs that are most frequently detected. Method: A cross-sectional study was carried out between February and June 2014 in 10 NHs in Belgium, supplied by a community pharmacy chain. For each NH, 40 residents (>70 years, using >5 chronic drugs) were included. PIP prevalence was determined using the GheOP3S-tool. Results: 400 NH residents were included [mean age (±SD) 86.2 (±6.3) years; median number of drugs (±IQR) 10 (7–12)]. A total of 1728 PIPs were detected in 387 (97 %) participants (Median 4; IQR 2–6). The most prevalent items can be assigned to three categories: long-term use of central nervous system drugs (i.e. benzodiazepines, antidepressants and antipsychotics), use of anticholinergic drugs (mutual combinations and with underlying constipation/dementia) and underuse of osteoporosis prophylaxis. Conclusion: Screening for PIP by means of the GheOP3S-tool revealed a high prevalence of PIP among older NH residents with polypharmacy. This finding urges for initiatives on the patient-level, but also on a broader, institutional level.

Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a 1. Overall, dogs were more sensitive than humans to QT-interval change, an a 1 of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.

Patients with headache often self-treat their condition with over-the-counter analgesics. However, overuse of analgesics can cause medication-overuse headache. The present study aimed to identify subgroups of individuals with headache who self-medicate, as this could be helpful to tailor intervention strategies for prevention of medication-overuse headache. Patients (n = 1021) were recruited from 202 community pharmacies and completed a self-administered questionnaire. A hierarchical cluster analysis was used to group patients as a function of sociodemographics, pain, disability, and medication use for pain. Three patient clusters were identified. Cluster 1 (n = 498, 48.8%) consisted of relatively young individuals, and most of them suffered from migraine. They reported the least number of other pain complaints and the lowest prevalence of medication overuse (MO; 16%). Cluster 2 (n = 301, 29.5%) included older persons with mainly non-migraine headache, a low disability, and on average pain in 2 other locations. Prevalence of MO was 40%. Cluster 3 (n = 222, 21.7%) mostly consisted of patients with migraine who also report pain in many other locations. These patients reported a high disability and a severe limitation of activities. They also showed the highest rates of MO (73%).

Background Guidelines for the safe administration of drugs through enteral feeding tube (EFT) are an important tool to minimise the risk of errors. This study aimed to investigate knowledge of these guidelines among staff of residential care facilities (RCF) for people with ID. Method Knowledge was assessed using a 13-item self-administered questionnaire. Questions reflected key aspects of guidelines on medication administration via EFT. All staff members that administer medication through EFT in Belgian RCFs were invited to participate (n = 553). Results Nine out of 10 RCFs participated, and 356 questionnaires were collected. Almost all participants were women (96%), and most (82%) had a non-nursing educational background. Mean self-perceived knowledge of medication administration via EFT was 6.7 (on a 0–10 scale). On average, 5.7 (SD 1.9) out of 13 questions were answered correctly. A nursing degree and previous education on medication administration via EFT were associated with significantly higher scores. Guideline recommendations regarding rinsing of used medicine cups (90% correct answers) and preparation of hard gelatin capsules (89%) were known best. Those regarding the use of protective equipment when crushing toxic substances (4% correct answers), crushing of sustained release and enteric-coated dosage forms (6%), elevation of the patient's backrest (14%) and flushing of the EFT (15%) were known the least. Conclusion This study identified a substantial lack of knowledge of guidelines for drug administration through EFT among staff of RCFs for people with ID. Our findings call for tailored educational programmes in order to increase knowledge on this subject.

Background: Pharmaceutical compounding of orphan active ingredients can offer cost-effective treatment to patients when no other drug product is available for a rare disease or during periods of drug product shortages. Additionally, it allows customized therapy for patients with rare diseases. However, standardized compounding formulas and procedures, and monographs are required to ensure the patients' safety. Results: Standardized formulas and compounding procedures were developed for seven orphan active ingredients (L-arginine, sodium benzoate, sodium phenylbutyrate, L-carnitine, chenodesoxycholic acid, primaquine phosphate, pyridoxal phosphate) and one non-orphan molecule (sodium perchlorate) regularly compounded by hospital pharmacists for extemporaneous use. The stability of these formulations was evaluated over 3months at refrigerated (5 degrees C) and standard storage conditions (25 degrees C/60%RH) using HPLC-based assays and a suitable shelf life was assigned to the formulations. Additionally, suitable analytical methods for quality control of formulations of pyridoxal phosphate and sodium perchlorate were developed as monographs for these components were not available in the European Pharmacopeia or United States Pharmacopeia. Conclusions: Availability of compounding formulas and protocols, as well as stability information, for orphan active ingredients can improve patients' access to treatment for rare diseases. Such data were collected for seven orphan active ingredients to treat patients with rare diseases when no other treatment is available. More efforts are needed to develop standardized formulas and compounding procedures for additional orphan active ingredients whose clinical efficacy is well-known but which are not available as products with a marketing authorization. Additionally, a legal framework at EU level is required to enable the full potential of pharmaceutical compounding for orphan active ingredients.