Self-management support with the Respiratory Adherence Care Enhancer instrument in asthma and chronic obstructive pulmonary disease: An implementation trial.

AIM: Suboptimal self-management with controller inhalation therapy in asthma and COPD is frequently observed with poor treatment outcomes. The developed 'Respiratory Adherence Care Enhancer' (RACE) instrument identifies and addresses individual barriers to self-management with a theoretical underpinning. This study investigates the feasibility of pharmaceutical support with this instrument. METHODS: An implementation trial was conducted with asthma and COPD patients in 5 community pharmacies in the Netherlands. Patients were allocated to standard care or add-on support with the RACE instrument. Patients were invited to complete the RACE questionnaire at baseline, 5-week and 10-week follow-up. Barrier profiles were accessible for the intervention group with subsequent consultations at baseline and 5-weeks. Experiences were collected from patients and consultants with a questionnaire and reported findings. Primary endpoints focused on the acceptability, practicality and implementation process. Secondary endpoints included between-group differences in barrier and disease control outcomes from baseline at 10-weeks follow-up. RESULTS: In total, 84 patients were included; 48 were assigned to intervention and 36 to standard care. Patient satisfaction of support with the RACE instrument was high (71%). Patients felt motivated, reassured and more confident about their disease management. Consultants reported an increase in awareness of patient barriers. Patient recognition of barrier profiles was 83.9% (±12.9%). The barrier inhaler techniques decreased significantly for the intervention group at follow-up with odds ratio 0.30 (95% confidence interval, 0.10-0.91). No significant differences were observed for changes in number of barriers and disease control. CONCLUSION: Self-management support with the RACE instrument is feasible and appreciated, facilitating behaviour change with patient-centred pharmaceutical care in asthma and COPD.

Availability and accessibility of HIV self-tests and self-sample kits at community pharmacies in the Netherlands.

BACKGROUND: In 2016 the WHO declared HIV self-testing and self-sampling an effective and safe test option that can reduce testing barriers. HIV self-tests and self-sampling kits (HIVST/HIVSS) are available for purchase at Dutch community pharmacies since 2019. We investigated the availability and accessibility of HIVST/HIVSS in community pharmacies, and factors associated with test availability. METHODS: An online survey among all Dutch community pharmacies (n = 1,987) was conducted between April and June 2021. Availability of HIVST/HIVSS and experiences of pharmacists with the test offer were analyzed with descriptive statistics. The association of pharmacy and pharmacists' characteristics with HIVST/HIVSS availability was explored by logistic regression analysis. RESULTS: In total, 465 pharmacists completed the questionnaire. Of the responding pharmacists, 6.2% (n = 29) offered HIVST/HIVSS. The majority (82.8%) sold between 0 and 20 tests per year. In total, pharmacies sold an estimated 370 HIVST/HIVSS per year. Pharmacies having HIVST/HIVSS available were less often located in moderately-urbanized to rural neighborhoods (OR 0.35, 95%CI 0.16-0.77 versus highly-urbanized), and were less often located in moderate-to-low SES neighborhoods (OR 0.40, 95%CI 0.18-0.88 versus high-SES). Reasons for not offering HIVST/HIVSS by pharmacists were no or little demand (69.3%), and not being familiar with these tests (17.4%). 52% of the pharmacists provided information about testing to test buyers. Reported options to improve the test offer were giving advice about (performing) the test to test buyers (72.4%), placing tests visible on the counter (51.7%), and advertisement (37.9%). CONCLUSION: HIVST/HIVSS have a limited practical availability in Dutch community pharmacies since their introduction in 2019, especially in lower-urbanized and lower-SES areas. Further research is needed to explore how to expand access to HIVST/HIVSS through community pharmacies in the Netherlands, and how to tailor it to the needs of pharmacy clients.

Patient reporting of sexual adverse events on an online platform for medication experiences.

AIMS: For >300 drugs, sexual side effects are included in the drug information leaflet. As sexual adverse events (sAEs) may be more easily shared at online medication platforms, patient-reported drug experiences may add to the current knowledge on sAE experiences. This study evaluated patient reports from the online platform mijnmedicijn.nl for the frequency of sAE reporting, sex differences concerning sAEs and to assess drugs with disproportional sAE reporting. METHODS: On the online platform, terms for sAEs as used by patients were collected with a poll. Subsequently, drug reports posted between 2008 and 2020 were searched for sAEs with the identified terms. From the retrieved reports, the sAE frequencies and complaints and reporting odds ratios (ROR) were calculated, stratified for sex and drug (class). sAE reporting was considered disproportional frequent if the lower 95% confidence interval bound of the ROR >2.0. RESULTS: For 189 drugs, sAEs were identified in 2408 reports (3.9%). Women posted 1383 reports (3.5% of all female reports) and men 1025 (4.7%). Almost half of the sAE reports addressed antidepressants: 586 reports of women (ROR 4.2; 95%CI 3.8-4.7) and 510 reports of men (ROR 7.5; 95%CI 6.6-8.5). Disproportional high numbers of sAE reports were found for 27 drugs, mostly antidepressants, hormonal contraceptives and drugs used in benign prostatic hyperplasia. Of these drugs with frequent sAEs, 7 had low sAE risks in their professional drug information. CONCLUSION: One in 25 drug reports on mijnmedicijn.nl included sAEs. The sAEs were reported frequently for antidepressants, contraceptives and drugs used in benign prostatic hyperplasia.

Effectiveness of a Pharmacist-Led Web-Based Medication Adherence Tool With Patient-Centered Communication: Results of a Clustered Randomized Controlled Trial.

BACKGROUND: Growing numbers of people use medication for chronic conditions; nonadherence is common, leading to poor disease control. A web-based tool to identify an increased risk for nonadherence with related potential individual barriers might facilitate tailored interventions and improve adherence. OBJECTIVE: This study aims to assess the effectiveness of a newly developed tool aimed at improving medication adherence. METHODS: We performed a cluster randomized controlled trial in patients initiating cardiovascular or oral blood glucose-lowering medication. Participants were recruited from community pharmacies. They completed an online questionnaire comprising assessments of their risk for medication nonadherence and subsequently of barriers to adherence. In pharmacies belonging to the intervention group, individual barriers displayed in a graphical profile on a tablet were discussed by pharmacists and patients with high nonadherence risk in face-to-face meetings and shared with their general practitioners and practice nurses. Tailored interventions were initiated by pharmacists. Barriers of control patients were not presented nor discussed and these patients received usual care. The primary outcome was the effectiveness of the intervention on medication adherence at 8 months' follow-up between patients with an increased nonadherence risk from the intervention and control groups, calculated from dispensing data. RESULTS: Data from 492 participants in 15 community pharmacies were available for analyses (intervention 253, 7 pharmacies; control 239, 8 pharmacies). The intervention had no effect on medication adherence (B=-0.01; 95% CI -0.59 to 0.57; P=.96), nor in the post hoc per-protocol analysis (B=0.19; 95% CI -0.50 to 0.89; P=.58). CONCLUSIONS: This study showed no effectiveness of a risk stratification and tailored intervention addressing personal barriers for medication adherence. Various potential explanations for lack of effectiveness were identified. These explanations relate, for instance, to high medication adherence in the control group, study power, and fidelity. Process evaluation should elicit possible improvements and inform the redesign of intervention and implementation. TRIAL REGISTRATION: The Netherlands National Trial Register NTR5186; https://tinyurl.com/5d8w99hk.

A Pharmacy-Based eHealth Intervention Promoting Correct Use of Medication in Patients With Asthma and COPD: Nonrandomized Pre-Post Study.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) affect millions of people worldwide. While medication can control and improve disease symptoms, incorrect use of medication is a common problem. The eHealth intervention SARA (Service Apothecary Respiratory Advice) aims to improve participants' correct use of inhalation medication by providing information and as-needed tailored follow-up support by a pharmacist. OBJECTIVE: The primary aim of this study was to investigate the effect of SARA on exacerbation rates in participants with asthma and COPD. Secondary aims were to investigate its effects in terms of adherence to maintenance medication and antimycotic treatment. METHODS: In this nonrandomized pre-post study, medication dispensing data from 382 Dutch community pharmacies were included. Exacerbation rates were assessed with dispensed short-course oral corticosteroids. Medication adherence between new and chronic users was assessed by calculating the proportion of days covered from dispensed inhalation maintenance medication. Antimycotic treatment was investigated from dispensed oral antimycotics in participants who were also dispensed inhaled corticosteroids (ICS). Outcomes were assessed 1 year before and 1 year after implementation of SARA and were compared between SARA participants and control participants. More specifically, for exacerbation rates and medication adherence, a difference score was calculated (ie, 1 year after SARA minus 1 year before SARA) and was subsequently compared between the study groups with independent-samples t tests. For antimycotics, the relative number of participants who were dispensed antimycotics was calculated and subsequently analyzed with a mixed-effects logistic regression. RESULTS: The study population comprised 9452 participants, of whom 2400 (25.39%) were SARA participants. The mean age of the population was 60.8 (15.0) years, and approximately two-thirds (n=5677, 60.06%) were female. The results showed an increase in mean exacerbation rates over time for both study groups (SARA: 0.05; control: 0.15). However, this increase in exacerbation rates was significantly lower for SARA participants (t9450=3.10, 95% CI 0.04-0.16; P=.002; Cohen d=0.06). Chronic users of inhalation medication in both study groups showed an increase in mean medication adherence over time (SARA: 6.73; control: 4.48); however, this increase was significantly higher for SARA participants (t5886=-2.74, 95% CI -3.86 to -0.84; P=.01; Cohen d=-0.07). Among new users of inhalation medication, results showed no significant difference in medication adherence between SARA and control participants in the year after implementation of SARA (t1434=-1.85, 95% CI -5.60 to 0.16; P=.06; Cohen d=-0.10). Among ICS users, no significant differences between the study groups were found over time in terms of the proportion of participants who were dispensed antimycotics (t5654=0.29, 95% CI -0.40 to 0.54; P=.76; Cohen d=0). CONCLUSIONS: This study provides preliminary evidence that the SARA eHealth intervention might have the potential to decrease exacerbation rates and improve medication adherence among patients with asthma and COPD.

Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study.

BACKGROUND: Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials. AIMS: To assess adherence to DOACs in atrial fibrillation patients in every day practice and identify predictors for non-adherence. METHODS: Individual linked dispensing data of atrial fibrillation patients who used DOACs were obtained from the Foundation for Pharmaceutical Statistics covering the Netherlands between 2012 and 2016. One year adherence to DOAC was calculated for initial DOAC as proportion of days covered (PDC) ≥80% and the association between clinical variables and adherence was assessed using logistic regression. In addition, we measured non-persistence, that is, patients who completely stopped their initial DOAC within 1 year follow-up. RESULTS: A total of 4797 apixaban-, 20 454 rivaroxaban- and 18 477 dabigatran users were included. The mean age was 69 years (n = 43 910), which was similar for the DOAC types. The overall proportion of patients with PDC ≥80% was 76%, which was highest for apixaban- (87%), followed by dabigatran- (80%) and rivaroxaban (69%) users. Multivariable analyses revealed that age ≤60 years, no concomitant drug use were predictors for non-adherence. Of atrial fibrillation patients who continued treatment, 97% had a PDC ≥80%, compared with only 56% for those who discontinued their DOAC treatment within 1 year. CONCLUSIONS: Non-adherence to DOACs was associated with age ≤60 years and no concomitant drugs use. Non-adherence was higher in patients who later discontinued DOAC treatment. Results of our study support research into interventions to improve adherence.

An estimation of patients at potential risk for drug-induced sexual dysfunction using pharmacy dispensing data.

BACKGROUND AND OBJECTIVES: Adverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. A multitude of diseases and drugs are known risk factors for sexual dysfunction. To inform patients better about these potential effects, more insight is needed on the estimated number of patients at high risk for sADRs and their characteristics. METHODS: This cross-sectional study estimated the number of patients in the Netherlands who were dispensed drugs with a potential very high risk (>10%) or high risk (1-10%) for sADRs as registered in the Summary of Product Characteristics, the official drug information text in Europe. RESULTS: In April 2019, 2.06% of the inhabitants of the Netherlands received drugs with >10% risk for sADRs and 7.76% with 1-10% risk. The majority of these patients had at least one additional risk factor for decreased sexual function such as high age or depression. Almost half of the patients were identified with two or more morbidities influencing sexual functioning. Paroxetine, sertraline and spironolactone were the most dispensed drugs with a potential >10% risk for sADRs. One-third of their first dispenses were not followed by a second dispense, with a higher risk of discontinuation for a decreasing number of morbidities. CONCLUSION: About 1 in 11 inhabitants of the Netherlands was dispensed a drug with a potential high risk for sADRs, often with other risk factors for sexual complaints. Further research is needed whether these users actually experience sADRs, to understand its impact on multimorbid patients and to provide alternatives if needed.

Womens' self-management skills for prevention and treatment of recurring urinary tract infection.

BACKGROUND: The guideline on urinary tract infections (UTI) of the Dutch College of General Practitioners provides recommendations on patient-initiated treatment and prevention of recurring UTI. AIM: To study familiarity with self-management skills for prevention of recurring UTI amongst adult women. DESIGN AND SETTINGS: An online questionnaire was developed, based on the UTI guideline and interviews with women having recurring UTI. Pharmacists in a postgraduate education programme (N = 76) aimed to invite 10 adult women with a recurring UTI prescription to complete the questionnaire. Women were asked for informed consent to link medication record data to questionnaire data. METHOD: We calculated proportions of the scores for self-management skills and analysed differences between age groups with chi-square test. RESULTS: Complete questionnaires were available for 719 women (mean age 55.1 ± 18.5 years). The proportions of women 18-50 years and women 51 years or older were 36.4% and 63.6%, respectively. Education levels of women 18-50 years were significantly higher than those of women 51 years and older. Before consulting a general practitioner (GP) for symptoms, 32.1% of all women increased fluid intake; additionally, 15.0% used analgesics and increased fluid intake. Of all women, 33.9% searched internet for information on self-management and 18% occasionally received a prescription for patient-initiated treatment, half of these prescriptions for use during vacation. Cranberry was used by 47%, d-mannose by 5% and vitamin C by 29% of all women. Awareness of different preventive behavioural measures (eg, fluid intake, washing without soap and emptying bladder after sexual intercourse) varied between 20% and 90%. CONCLUSION: Almost half of all women applied self-management (increased fluid intake, analgesics) before consulting a GP for recurring UTI. Awareness of preventive behavioural measures for recurring UTI varied considerably. Thus, education of women about the use of analgesics and behavioural measures deserves attention.

An economic model of the cost-utility of pre-emptive genetic testing to support pharmacotherapy in patients with major depression in primary care.

The pharmacokinetics of many antidepressants (tricyclic antidepressants (TCA) or selective serotonin re-uptake inhibitors (SSRI)) are influenced by the highly polymorphic CYP2D6 enzyme. Therefore, pharmacogenetics could play an important role in the treatment of depressive patients. The potential cost-utility of screening patients is however still unknown. Therefore, a Markov model was developed to compare the strategy of screening for CYP2D6 and subsequently adjust antidepressant treatment according to a patient's metabolizer profile of poor, extensive, or ultra metabolizer, with the strategy of no screening ('one size fits all' principle). Each week a patient had a probability of side effects, which was followed by dosage titration or treatment switching. After 6 weeks treatment effect was evaluated followed by treatment adjustments if necessary, with a total time horizon of the model of 12 weeks. The analysis was performed from a societal perspective. The strategy of screening compared with no screening resulted in incremental costs of €91 (95 percentiles: €39; €152) more expensive but also more effect with 0.001 quality adjusted life years (QALYs) (95 percentiles: 0.001; 0.002) gain. The incremental cost-effectiveness ratio (ICER) was therefore €77,406 per QALY gained, but varied between €22,500 and €377,500 depending on the price of screening and productivity losses. According to our model, we cannot unequivocally conclude that screening for CYP2D6 in primary care patients using antidepressants is be cost-effective, as the results are surrounded by large uncertainty. Therefore, information from ongoing studies should be used to reduce these uncertainties.

Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation.

PURPOSE: To study whether polypharmacy or drug-drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin. METHODS: We performed a systematic review and meta-analysis of studies that randomized patients with atrial fibrillation to DOACs or warfarin stratified by the number of concomitant drugs. Outcomes included stroke or systemic embolism (SE), all-cause mortality, major bleeding, and intracranial hemorrhage. Risk ratios (RR) were calculated and Mantel-Haenszel random effects were applied. RESULTS: Two high-quality studies were eligible, including 32,465 participants who received apixaban, rivaroxaban, or warfarin, with a median follow-up of 1.9 years. Of participants, 29% used < 5 drugs, 55% used 5-9 drugs, and 16% used ≥ 10 drugs. Drugs interacting with DOACs (P-glycoprotein/CYP3A4) were used by 6460 (20%) of patients. Patients with higher number of drugs (0-4 vs 5-9 vs ≥ 10) had higher rates of mortality (5.8%, 7.9%, 10.0%) and major bleeding (3.4%, 4.8%, 7.7%). Comparative efficacy or safety of DOACs versus warfarin was not affected by polypharmacy status or P-glycoprotein/CYP3A4 inhibitor use. However, the presence of polypharmacy (p = 0.001) or glycoprotein/CYP3A4-modulating drugs (p = 0.03) was correlated with increased risk of major bleeding when compared with warfarin. Overall, DOAC use was associated with a lower risk of stroke/SE (RR, 0.84; 95%CI, 0.74-0.94), all-cause mortality (RR, 0.91; 95%CI, 0.84-0.98), and intracranial hemorrhage (RR, 0.51; 95%CI, 0.38-0.70) compared with warfarin. CONCLUSIONS: DOACs were more effective than warfarin, and at least as safe. Polypharmacy was associated with adverse outcomes and attenuated the advantage in risk of major bleeding among rivaroxaban users, particularly in the presence of P-glycoprotein/CYP3A4-modulating drugs.

Anticholinergic and sedative medication use in older community-dwelling people: A national population study in the Netherlands.

PURPOSE: To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)-active medication used. METHODS: A cross-sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS-active medications used were identified with latent class analysis. RESULTS: Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS-active medications used: "combined psycholeptic/psychoanaleptic medication" (class 1, 57.9%), "analgesics" (class 2, 17.9%), "antiepileptic medication" (class 3, 17.8%), and "anti-Parkinson medication" (class 4, 6.3%). CONCLUSIONS: A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS-active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.

Laxative co-medication and changes in defecation patterns during opioid use.

INTRODUCTION: Opioid-induced constipation is a clinically relevant side effect and a cause of potentially avoidable drug-related hospital admissions. OBJECTIVES: To describe the presence of laxative co-medication, the reasons for not starting laxatives and to evaluate changes in stool patterns of opioid initiators. METHODS: In this observational study community pharmacists evaluated the availability of laxative co-medication in starting opioid users and registered reasons for non-use. Two opioid initiators per pharmacy were invited to complete questionnaires ('Bristol stool form scale' and 'Rome III Diagnostic Questionnaire for the Adult Functional Gastrointestinal Disorders') on their defecation prior to and during opioid use. Descriptive statistics and Chi square tests were used to analyse reasons for non-use of laxatives and changes in defecation patterns. RESULTS: Eighty-one pharmacists collected data from 460 opioid initiators. Of those, 344 (74.8%) used laxatives concomitantly. Main reason not to use laxatives was that either prescribers or patients did not consider them necessary. Sixty-seven (89.3%) of the 75 opioid starters with two questionnaires completed were not constipated at opioid start. Eleven of them (16%) developed constipation during opioid use (Chi square p=0.003). At follow-up within laxative users 10.6% were constipated compared to 20.7% in subjects without laxatives. CONCLUSION: One in four opioid starters did not dispose of laxative co-medication, mainly because they were not considered necessary by either the prescriber or the patient. The prevalence of constipation doubled during opioid use. A watchful waiting strategy for the use of laxative co-medication might include a monitoring of defecation patterns with validated questionnaires.

Self-Management Maintenance Inhalation Therapy With eHealth (SELFIE): Observational Study on the Use of an Electronic Monitoring Device in Respiratory Patient Care and Research.

BACKGROUND: Electronic inhalation monitoring devices (EIMDs) are available to remind patients with respiratory diseases to take their medication and register inhalations for feedback to patients and health care providers as well as for data collection in research settings. OBJECTIVE: This study aimed to assess the validity as well as the patient-reported usability and acceptability of an EIMD. METHODS: This observational study planned to include 21 community pharmacies in the Netherlands. Patient-reported inhalations were collected and compared to EIMD registrations to evaluate the positive predictive value of these registrations as actual patient inhalations. Patients received questionnaires on their experiences and acceptance. RESULTS: A convenience sample of 32 patients was included from across 18 pharmacies, and 932 medication doses were validated. Of these, 796 registrations matched with patient-reported use (true-positive, 85.4%), and 33 inhalation registrations did not match with patient-reported use (false-positive, 3.5%). The positive predictive value was 96.0%, and 103 patient-reported inhalations were not recorded in the database (false-negative, 11.1%). Overall, patients considered the EIMD to be acceptable and easy to use, but many hesitated to continue its use. Reminders and motivational messages were not appreciated by all users, and more user-tailored features in the app were desired. CONCLUSIONS: Patients' interaction with the device in real-world settings is critical for objective measurement of medication adherence. The positive predictive value of this EIMD was found to be acceptable. However, patients reported false-negative registrations and a desire to include more user-tailored features to increase the usability and acceptability of the EIMD.

No Evidence for an Association Between Renal Function and Serious Bleeding Events in Patients Treated With Coumarins: A Population-Based Study.

BACKGROUND: Although anticoagulation therapy is closely monitored in the Netherlands, coumarin-induced serious bleeding events are still observed. Current literature suggests that renal impairment may contribute to this. OBJECTIVE: To explore the association between renal function and bleeding events during coumarin treatment. METHODS: A nested case-control study was conducted using data from the PHARMO Database Network. Patients hospitalized for a bleeding event during coumarin treatment were selected as cases and matched on sex, birth year, and geographic region to up to 2 controls using coumarins without hospitalization for bleeding. All values of estimated glomerular filtration rates (eGFRs) were selected in the year before index date (case hospitalization date) and compared between cases and controls using logistic regression analyses. RESULTS: In total, 2224 cases were matched to 4398 controls (61% male; mean ± SD age 75 ± 11 and 78 ± 11 years among cases and controls, respectively). Availability of eGFR values was higher among cases compared with controls (mean ± SD eGFR values 4.5 ± 7.1 vs 3.2 ± 5.5), reflected in the significantly shorter time since last eGFR value (at index date, mean ± SD = 2.7 ± 3.0 vs 3.8 ± 3.1 months; odds ratio [OR] = 0.91, 95%CI = 0.89-0.92). No statistically significant difference was found for the mean eGFR value in the year before index date (mean ± SD 65.7 ± 22.8 vs 64.6 ± 20.9 mL/min/1.73 m2; OR per 10 units [95%CI] = 0.99 [0.96-1.02]). CONCLUSIONS: No association between renal function and serious bleeding events during coumarin treatment was observed.

Comparing outpatient oral antibiotic use in Germany and the Netherlands from 2012 to 2016.

PURPOSE: Overuse of antibiotics is of concern, but may differ between European countries. This study compares outpatient use of oral antibiotics between Germany (DE) and the Netherlands (NL). METHODS: For DE, we used the DAPI database with information on dispensings at the expense of the Statutory Health Insurance Funds from > 80% of community pharmacies. For NL, data were obtained from the Dutch Foundation for Pharmaceutical Statistics. Use of oral antibiotics was estimated as defined daily doses per 1000 inhabitants per day (DID), except for age comparisons as packages per 1000 inhabitants annually. National time trends were assessed with linear regression, stratified for the major antibiotic classes, and individual substances. RESULTS: From 2012 to 2016, outpatient antibiotic use was lower in NL than in DE (9.64 vs 14.14 DID in 2016) and non-significantly decreased slightly over time in both countries. In DE, dispensings of oral antibiotics to children were higher compared with NL for the age groups 2 to 5 (2.0-fold in 2016) and 6 to 14 years (2.7-fold in 2016). Use of cephalosporins was very low in NL (0.02 DID in 2016), but the second most frequently dispensed class in DE (2.95 DID in 2016). CONCLUSION: From 2012 to 2016, outpatient use of oral antibiotics was lower in NL than in DE. Differences were primarily observed in the age groups 2 to 5 and 6 to 14 years, although the recommendations of evidence-based guidelines in both countries were in agreement.

Direct oral anticoagulant use and subsequent start of proton pump inhibitors as proxy for gastric complaints.

PURPOSE: Dabigatran use has been linked to gastrointestinal complaints, but it is unknown if this leads to more use of proton pump inhibitors (PPI). Furthermore, it is unknown whether gastrointestinal complaints occur more frequently in dabigatran users compared with other direct oral anticoagulant (DOACs) users. We investigated the association between DOAC use (dabigatran, rivaroxaban, or apixaban) and subsequent PPI initiation as a proxy for gastrointestinal complaints. METHODS: In this population-based observational study with an active-comparator new user study design, anonymised dispensing data from Community Pharmacies in the Netherlands from 2012 to 2016 were used. Patients initiating DOAC for the treatment of atrial fibrillation without any PPI use before or at time of DOAC initiation were included. The outcome measure, subsequent PPI initiation, was determined in 28553 DOAC users. RESULTS: The patients initiating dabigatran (10 942), apixaban (4897), or rivaroxaban (12714) were comparable for age (mean 69 years), sex (62% men), socioeconomic class, and concomitant medication use. The risk of PPI initiation in apixaban versus rivaroxaban users was similar (adjusted hazard ratio 1.06; 95% confidence interval 0.96-1.31) The adjusted hazard ratio of initiating PPI for dabigatran users was 1.21 (95% confidence interval 1.14-1.29) compared with rivaroxaban/apixaban users. The cumulative incidence of PPI initiation at 6 months of follow-up for patients using dabigatran was 13.0%, and 10.0% for those using rivaroxaban/apixaban, yielding a number needing treatment of 33. CONCLUSIONS: Proton pump inhibitor initiation occurred frequently in incident DOAC users but more often in patients treated with dabigatran than in those treated with rivaroxaban or apixaban.

Development of clinical pharmacy services in Australia, Austria, Belgium, Bosnia-Herzegovina, Canada, Germany, Japan, Kosovo, Switzerland, the Netherlands, Thailand, USA and correlation with educational standards, level of research, and implemen.

OBJECTIVE: This study aimed to compare determinants of professional development between different countries to identify barriers and facilitators of development towards clinical pharmacy services and stimulate discussion of under-used potential and opportunities. MATERIALS: The study was conceived as a survey. The questionnaire was administered to a group of experts. METHODS: The survey was conducted as a cross-sectional study with descriptive and correlation analysis. A questionnaire was developed and adjusted to the study focus, covering aspects on general regulations for community pharmacies, professional education, implementation of clinical pharmacy services, and research in patient care. Results were compared for analyses. RESULTS: A total of twelve countries were included in this survey. Pharmacy studies took between 4 and 6 years plus residency in most countries. Curricula remained drug-oriented only in Austria, Bosnia-Herzegovina, and Germany; these three countries had the least pharmacotherapy content in their curricula. Canada, the USA, and Australia have established clinical pharmacy services in almost all fields of practice. Most other countries have implemented at least some clinical services, with the exception of Bosnia-Herzegovina, Germany, and Kosovo. The correlation coefficient between education, research, and implementation was 0.91. CONCLUSION: The results of the survey show that clinical pharmacy services are established to very different extents among the participating countries. The strong correlation suggests that achieving a successful transition in professional practice needs to address several aspects of education and research to reach progress. The collected data might help to identify potential areas of improvement to foster implementation of clinical pharmacy services.
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Cost-Effectiveness Analysis of Genotype-Guided Treatment Allocation in Patients with Alcohol Use Disorders Using Naltrexone or Acamprosate, Using a Modeling Approach.

Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI -28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000-0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping.

Use of pharmacy dispensing data to measure adherence and identify nonadherence with oral hypoglycemic agents.

PURPOSE: A framework for calculation of adherence for oral hypoglycemic agents (OHAs) based on data from health-insurance claims is available. Pharmacy dispensing data aid identification of nonadherent patients in pharmacy practices. However, use of these data for calculation of OHA adherence requires additional methodological categories. We examined the impact of different methodological choices on estimation of OHA adherence using pharmacy dispensing data. METHODS: Four methodological categories were added to the framework available to be used for adherence calculation with pharmacy dispensing data. Three adherence measures were defined to supply pharmacists with significant information on OHA use of their patients: (i) percentage of days covered by use periods of dispensed medication (PDC), (ii) mean rate of adherent patients with a PDC ≥80 % (MRAP80), and (iii) mean number of nonadherent patients (MNNP80) per pharmacy with a PDC <80 %. A basic scenario was developed from 16 methodological categories. Consequences of choices for different parameters within these categories on the scores of the three adherence measures were calculated from dispensing data between July 2013 and July 2014. RESULTS: Data were available for 604,500 OHA users in 1737 community pharmacies in the Netherlands. For the basic scenario, mean PDC for OHA was 88.3 %. MRAP80 was 80.3 %, which corresponded to an average of 69 nonadherent patients per pharmacy. Different choices for parameter values resulted in score variations for PDC of 85.0-91.8 %, for MRAP80 of 75.3-86.1 %, and between 49 and 92 MNNP80 per pharmacy. CONCLUSION: Sixteen methodological categories specified calculation of OHA adherence based on pharmacy dispensing data. Adherence scores expressed as percentages were relatively robust to variation in parameter values, but differed substantially for the absolute numbers of nonadherent patients per pharmacy.

A genome-wide association study for venous thromboembolism: the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.

Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community-based studies. Genotypes for genome-wide single-nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study-design appropriate regression methods. Meta-analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P ≤ 0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case-control studies. In the combined data from these two stages, additional genome-wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG; P < 5.0 × 10(-13) for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (P < 5.0 × 10(-6) ) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations.