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.

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.

Community pharmacist counseling improves adherence and asthma control: a nationwide study.

BACKGROUND: Pharmaceutical counseling (PC) interventions have been shown to improve adherence to controller medication and asthma control. However, the real-life impact of these PC interventions in difficult-to-control asthma patients remains unclear. We aimed to assess the effectiveness of PC interventions in real life using nationwide claims data. METHODS: Demographics and drugs use of patients who received ICS in 2017 with or without pharmaceutical counseling were retrieved from a Belgian claims database. Asthma-related drug use from 1 year before first ICS dispensing in 2017 (reference period) was compared with 1 year after. Outcomes were usage of inhaled corticosteroids (ICS) in defined daily doses (DDD), proportion of users of short-acting beta-agonist (SABA), antibiotics, oral corticosteroids (OCS), asthma biologicals and controller-to-total (CTT) ratio. RESULTS: The study population consisted of difficult-to-control asthma patients aged 5-40 years with at least the first interview within 90 days after first ICS dispensing (n = 1350). ICS usage increased significantly in the year after PC intervention compared with the reference period (+ 43.3 DDD/patient, p < 0.05). A nominal decrease was observed in the proportion of SABA (48.0 to 46.2%) and antibiotics (54.5 to 52.7%) after PC intervention compared with the reference period. CTT ratio significantly increased from 0.671 to 0.749 (p < 0.05). The proportion of biological users was nominally lower in the intervention group compared with a control group (n = 50,477) in the post-intervention time period (0.22% versus 0.30%). CONCLUSIONS: This first nationwide study among difficult-to-control asthma patients suggests that community pharmacist counseling is effective in real life to improve controller adherence and asthma control.

Effective Interventions for Diabetes Patients by Community Pharmacists: A Meta-analysis of Pharmaceutical Care Components.

OBJECTIVE: To evaluate randomized controlled trials (RCTs) that included interventions provided by community pharmacists for patients with type 1 and 2 diabetes, the analysis of each component of the intervention(s), and the description of the training that the pharmacists received. DATA SOURCES: The literature research was conducted in PubMed and in the Cochrane Central Register of Controlled Trials (January 2000 to April 2016) for RCTs with interventions provided by community pharmacists for patients with diabetes. Corresponding authors were contacted about missing data and intervention and training design. STUDY SELECTION AND DATA EXTRACTION: RCTs published in English or German were included if pharmaceutical care or medication therapy management was conducted by community pharmacists with diabetes patients. Basic information, intervention and training design data were extracted. DATA SYNTHESIS: The literature research resulted in 11 eligible studies for further analysis. The corresponding authors of 6 studies responded to our request and sent their raw data. The calculated meta-analytical effect of 640 analyzed patients was a hemoglobin A1C (A1C) difference of -0.66%, with a 95% CI of -0.86% to -0.45%. The analysis revealed that most intervention elements had a significant positive meta-analytical effect on the A1C values. CONCLUSIONS: Our meta-analysis suggests that community pharmacist-led interventions can improve glycemic control in patients with type 1 and 2 diabetes. The most effective intervention components were patient centered and interdisciplinary. Pharmaceutical care interventions should, therefore, include the following components: sending feedback to the physician, setting individual goals, reviewing medication, and assessing patients' health beliefs and medication knowledge.

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.

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.

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.

Improving inhaler adherence in patients with chronic obstructive pulmonary disease: a cost-effectiveness analysis.

BACKGROUND: The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness. METHODS: An economic analysis was performed from the Belgian healthcare payer's perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty. RESULTS: In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses. CONCLUSIONS: Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.

Effectiveness of pharmaceutical care for patients with chronic obstructive pulmonary disease (PHARMACOP): a randomized controlled trial.

AIMS: Few well-designed randomized controlled trials have been conducted regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of a pharmaceutical care programme for patients with COPD. METHODS: The pharmaceutical care for patients with COPD (PHARMACOP) trial is a single-blind 3 month randomized controlled trial, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged ≥ 50 years and with a smoking history of ≥ 10 pack-years. A computer-generated randomization sequence allocated patients to an intervention group (n = 371), receiving protocol-defined pharmacist care, or a control group (n = 363), receiving usual pharmacist care (1:1 ratio, stratified by centre). Interventions focusing on inhalation technique and adherence to maintenance therapy were carried out at start of the trial and at 1 month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnoea, COPD-specific and generic health status and smoking behaviour. RESULTS: From December 2010 to April 2011, 734 patients were enrolled. Forty-two patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score [mean estimated difference (Δ),13.5%; 95% confidence interval (CI), 10.8-16.1; P < 0.0001] and medication adherence (Δ, 8.51%; 95% CI, 4.63-12.4; P < 0.0001) were significantly higher in the intervention group compared with the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs. 35; rate ratio, 0.28; 95% CI, 0.12-0.64; P = 0.003). No other significant between-group differences were observed. CONCLUSIONS: Pragmatic pharmacist care programmes improve the pharmacotherapeutic regimen in patients with COPD and could reduce hospitalization rates.

Accuracy of the Medication Adherence Report Scale (MARS-5) as a quantitative measure of adherence to inhalation medication in patients with COPD.

BACKGROUND: Self-report is considered most suitable to measure medication adherence in routine clinical practice. However, accuracy of self-report as a quantitative measure of adherence is not well documented. OBJECTIVE: To assess the accuracy of a self-report measure of adherence (Medication Adherence Report Scale [MARS-5]) for identifying nonadherent users of inhalation medication among patients with chronic obstructive pulmonary disease (COPD), compared with medication refill adherence (MRA) as reference. METHODS: We used baseline data from the Pharmaceutical Care for Patients with COPD (PHARMACOP)-trial (n = 734). Patients with incomplete MARS-5 and/or incomplete pharmacy refill records were excluded (n = 121). Internal consistency of MARS-5 (Crohnbach α) and Spearman rank correlation (ρ) with MRA were calculated. Different thresholds for nonadherence were used to calculate sensitivity, specificity, and positive predictive value (PPV), compared with dichotomized MRA (MRA ≥80% = adherent). A receiver operating characteristic (ROC) curve was plotted to determine the goodness of test. RESULTS: 613 patients were included in the analysis. The mean adherence score by MARS-5 (range = 5-25) was 23.5 (SD = 2.6); mean adherence by MRA was 83.4% (SD = 23.8%). Internal consistency of MARS-5 was high (α = 0.77). Continuous MARS-5 scores correlated poorly with continuous MRA scores (ρ = 0.10; P = 0.011). When lowering the nonadherence threshold stepwise from 25 to 20, MARS-5 did not reach sufficient sensitivity (53% to 13%), specificity (57% to 94%), and PPV (42% to 57%) to detect nonadherers compared with dichotomized MRA. ROC curve plotting resulted in an area under the curve value of 0.56 (95% CI = 0.521-0.616; P = 0.005). CONCLUSION: Self-reported adherence measured by MARS-5 is inaccurate in identifying nonadherence to inhalation medication in patients with COPD.

Pharmacists' views on discontinuing long-term use of antidepressants and supporting patients during the discontinuation process: a qualitative study.

BACKGROUND: Long-term antidepressant (AD) use, much longer than recommended by guidelines, may cause harms and generate unnecessary costs. Community pharmacists have frequent contact with AD users and advise them on appropriate and safe medication use. GPs recognised pharmacists as potential sources of additional support for the AD discontinuation process, but there is a lack of knowledge about pharmacists' views. AIM: To explore pharmacists' perspectives on discontinuing long-term use of ADs and supporting patients during the discontinuation process and their barriers and facilitators. METHOD: Qualitative study in Belgian pharmacists. The authors conducted 14 semi-structured face-to-face interviews. Interviews were analysed thematically. RESULTS: The first theme 'Antidepressants at the pharmacy: a persistent taboo' described the challenges pharmacists encounter in initiating discussions with patients about their ADs and mental health, and the persistent taboo around ADs at pharmacies. Second, pharmacists were concerned about the risks associated with AD discontinuation but recognise that harm from continuing ADs may outweigh concerns. Third, although pharmacists can be a starting point for discontinuation, they hesitate to do this and question if this is their role. They prefer that GPs have this responsibility. CONCLUSION: Deprescribing long-term ADs is a challenging concept for pharmacists, especially when there is no patient request. The taboo around ADs and the fear of relapse of symptoms in a stable patient are important barriers for pharmacists when considering discontinuation. Pharmacist education and confidence-building is essential to involve the pharmacist in the discontinuation process. Findings also highlight a strong need for multidisciplinary collaboration and agreements with GPs to reduce unnecessary antidepressant treatment.

Rhinitis Control and Medication Use in a Real-World Sample of Patients With Persistent Rhinitis or Rhinosinusitis: A Community Pharmacy Study.

BACKGROUND: Little is known about rhinitis control in real-life, nor about the contribution of treatment-related and patient-related factors. OBJECTIVE: This study aimed to examine the level of rhinitis control and rhinitis medication utilization in patients with persistent rhinitis and to identify predictors of rhinitis control. METHODS: A cross-sectional observational study was conducted in patients with persistent rhinitis recruited in community pharmacies. Participants completed the Rhinitis Control Assessment Test, a questionnaire on patient/rhinitis characteristics, and rhinitis medication use. A visual analog scale for nasal symptoms was also completed. Pharmacy dispensing data were used to calculate adherence to intranasal glucocorticoids. Nasal spray technique was evaluated using a standardized checklist. Predictors of rhinitis control were explored using a linear regression model. RESULTS: A total of 1,514 patients, recruited in 215 pharmacies, participated in the study (mean age 48.7 y, 62% female). Almost 60% exhibited suboptimal rhinitis control (Rhinitis Control Assessment Test ≤ 21 of 30). A 50-mm cut-off on the visual analog scale yielded 78.1% sensitivity to identify suboptimal rhinitis control. Participants most frequently used intranasal glucocorticoids (55.6%) and intranasal decongestants (47.4%). Only 10.3% of current nasal spray users demonstrated perfect technique. More than half (54.8%) of glucocorticoid users were identified as underadherent. Female sex, self-reported nasal hyperreactivity, active asthma, and use of oral/intranasal decongestants or nasal saline were identified as predictors of worse rhinitis control. CONCLUSIONS: Suboptimal rhinitis control was common in this real-life sample of persistent rhinitis patients. Improving use of rhinitis medication may be key to increase disease control.

Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants: an intervention study in community pharmacies.

INTRODUCTION: Direct oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. METHODS: We conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. RESULTS: In total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. CONCLUSIONS: This study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations.

Vaginal distribution and retention of tablets comprising starch-based multiparticulates: evaluation by colposcopy.

We have developed fast-disintegrating tablets comprising starch-based pellets and excipient granules for intravaginal drug delivery. The purpose of this study was to evaluate the intravaginal disintegration, distribution and retention behavior of these tablets in sheep and women using colposcopy as visualization technique. One tablet was administered to each study subject (n = 6) and repeated colposcopy examination was performed over a 48 h and 24 h period in sheep and women, respectively. Colposcopy in sheep indicated that in vivo tablet disintegration was initiated within 30 min of vaginal administration and that due to disintegration of the pellets themselves, the formulation was transformed into a gel-like mass which distributed throughout the entire vaginal cavity within 2-4 h. In vivo tablet disintegration after intravaginal administration to women was complete within 4 h, whereby the formulation gradually spread throughout the vaginal cavity as complete covering was observed after 12 and 24 h. The persistent retention (up to 24 and 48 h in women and sheep, respectively) confirmed the long retention time of this vaginal formulation.