Publications by authors named "Martina Teichert"

59 Publications

Survey on general practitioners' and pharmacists' opinions regarding patient-initiated treatment of recurring urinary tract infections.

Int J Clin Pharm 2021 Jun 10. Epub 2021 Jun 10.

Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Background The Dutch general practitioners (GP) guideline for urinary tract infections (UTI) recommends patient-initiated treatment for women with recurring UTI. In countries other than the Netherlands, community pharmacists play a role in dispensing antibiotics for recurring UTI without preceding GP consultation. Objective To study GP and pharmacist opinions regarding the desirability of patient-initiated treatment, including potential pharmacist support for, and consequences of, facilitated access to antibiotics. Setting Dutch community pharmacies that cooperate with at least two GPs in their regional primary care network. Method Pharmacists in a postgraduate education program invited their residency pharmacist and 2-3 GPs to anonymously complete an online questionnaire. Questions related to diagnosis, treatment and potential role of the pharmacist. Answers were formulated as multiple-choice or ratings on a 5-point Likert scale. Data were analysed per professional group using descriptive statistics. Answers of pharmacists and GP to corresponding questions were analysed using a Chi-square test (p < 0.05). Main outcome measure Desirability of patient-initiated treatment and supporting role of the pharmacist. Results A total of 170 GPs and 76 pharmacists completed the questionnaires. Of the GPs, 35.1% supported patient-initiated treatment. Of the pharmacists, 69.7% were willing to dispense an antibiotic to a patient without preceding GP consultation after performing a probability check. In total, 65.7% of GPs and 44.7% of pharmacists thought that facilitated access to antibiotics would increase use of antibiotics (p < 0.05). Conclusion Support of GPs for facilitated access to antibiotic treatment by patient-initiated UTI treatment was limited, even with pharmacist support. The majority of pharmacists were willing to dispense an antibiotic after a probability check of an episode of recurring UTI, but both pharmacists and GPs were concerned about overuse of antibiotics.
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http://dx.doi.org/10.1007/s11096-021-01295-2DOI Listing
June 2021

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

Int J Clin Pract 2021 Aug 13;75(8):e14289. Epub 2021 May 13.

Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1111/ijcp.14289DOI Listing
August 2021

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

Pharmacoepidemiol Drug Saf 2021 Aug 4;30(8):1027-1036. Epub 2021 May 4.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1002/pds.5242DOI Listing
August 2021

Adherence to guideline recommendations for urinary tract infections in adult women: a cross-sectional study.

Prim Health Care Res Dev 2021 04 5;22:e11. Epub 2021 Apr 5.

Department of Clinial Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands.

Aim: To study whether changes in drug preferences in the Dutch guideline for the treatment of Urinary Tract Infection (UTI) for General Practitioners (GPs) in 2013, resulted in corresponding changes in antibiotic dispensing.

Background: For the treatment of uncomplicated UTI, nitrofurantoin remained the first choice, while fosfomycin became the second choice and changed ranks with trimethoprim. For a subsequent febrile UTI, ciprofloxacin became the first choice and changed ranks with amoxicillin/clavulanic acid, co-trimoxazole remained the third choice.

Methods: In this observational cross-sectional study, routinely collected dispensing data from the Dutch Foundation of Pharmaceutical Statistics from 2012 to 2017 were used. The number of women 18 years and older, treated with one of the guideline antibiotics for uncomplicated UTI and subsequent febrile UTI were analysed annually. Proportions were calculated. Data were stratified for age categories. Failure of uncomplicated UTI treatment was defined as the dispensing of an antibiotic for febrile UTI within 14 days after the dispensing of an antibiotic for uncomplicated UTI.

Findings: Data were available from 81% of all pharmacies in 2012 to 89% in 2017. Percentages of women dispensed nitrofurantoin were relatively stable with 87.4% in 2012 and 84.4% in 2017. Percentages of women dispensed fosfomycin increased from 5.4% in 2012 to 21.8% in 2017, whereas percentages of women dispensed trimethoprim decreased from 17.8% to 8.0%. Within age categories, the percentage of women dispensed fosfomycin increased from 12.4% in women 18-30 years old to 36.7% in women above 80 years old. Percentages of women dispensed antibiotics for febrile UTI remained stable at 5% annually. Percentages of women receiving ciprofloxacin increased from 1.9% in 2012 to 3.3% in 2017, while those receiving amoxicillin/clavulanic acid decreased from 2.9% to 1.8%. New guideline recommendations resulted in corresponding changes in dispensed antibiotics for uncomplicated UTI and subsequent febrile UTI. Drug choices differed for age categories.
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http://dx.doi.org/10.1017/S1463423621000116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101080PMC
April 2021

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

Fam Pract 2021 06;38(3):292-298

Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1093/fampra/cmaa116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211144PMC
June 2021

Pragmatic trial on inhaled corticosteroid withdrawal in patients with COPD in general practice.

NPJ Prim Care Respir Med 2020 10 9;30(1):43. Epub 2020 Oct 9.

Department of Primary and Community Care, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

The therapeutic value of inhaled corticosteroids (ICSs) for COPD is limited. In published RCTs, ICS could be withdrawn in COPD patients without increasing exacerbation risk when bronchodilator treatment is optimized. Here we report on the feasibility and risks of ICS withdrawal in Dutch general practice for COPD patients without an indication for ICSs. In our pragmatic trial, general practitioners decided autonomously which of their COPD patients on ICS treatment could stop this, how this was done, and whether additional bronchodilator therapy was needed. We recruited 62 COPD patients (58 analysed) who were eligible for ICS withdrawal in 79 practices. In 32 patients (55.2%, 95% CI: 42.5-67.3%) ICS was withdrawn successfully, 19 (32.8%, 95% CI: 22.1-45.6%) restarted ICS treatment within six months, 12 patients (20.7%, 95% CI: 12.3-32.8%) had a moderate exacerbation, and one patient had a severe exacerbation. ICS withdrawal was successful in just over half of the patients with COPD without an indication for ICS.
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http://dx.doi.org/10.1038/s41533-020-00198-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547069PMC
October 2020

The General Practice and Residential Aged Care Facility Concordance of Medication (GRACEMED) study.

Int J Med Inform 2020 11 29;143:104264. Epub 2020 Aug 29.

Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Macquarie Park, NSW, Australia.

Background: The lack of interoperable IT systems between residential aged care facilities (RACF) and general practitioners (GP) in primary care settings in Australia introduces the potential for medication discrepancies and other medication errors. The aim of the GRACEMED study is to determine the extent and potential severity of medication discrepancies between general practice and RACFs, and identify factors associated with medication discrepancies.

Methods: A cross sectional study of medication discrepancies between RACF medication orders and GP medication lists was conducted in the Sydney North Health Network, Australia. A random sample of RACF residents was included from practice lists provided by the general practices. RACF medication orders and GP medication lists for the included residents were compared, and medication discrepancies between the two sources were identified and characterised in terms of discrepancy type, potential for harm and associated factors.

Results: 31 GPs and 203 residents were included in the study. A total of 1777 discrepancies were identified giving an overall discrepancy rate of 72.6 discrepancies for every 100 medications. Omissions were the most common discrepancy type (35.2%,) followed by dose discrepancies (34.4%) and additions (30.4%). 48.5% of residents had a discrepancy with the potential to result in moderate harm and 9.8% had a discrepancy with the potential for severe harm. Number of medications prescribed was the only factor associated with medication discrepancies.

Conclusion: Increased use of systems that allow information sharing and improved interoperability of clinical information is urgently needed to address medication safety issues experienced by RACF residents.
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http://dx.doi.org/10.1016/j.ijmedinf.2020.104264DOI Listing
November 2020

Drug Burden Index and Cognitive and Physical Function in Aged Care Residents: A Longitudinal Study.

J Am Med Dir Assoc 2020 08;21(8):1086-1092.e1

Department of PharmacoTherapy, PharmacoEpidemiology & PharmacoEconomics, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, the Netherlands.

Objectives: Anticholinergic/antimuscarinic and sedative medications (eg, benzodiazepines) have been found to be associated with poorer cognitive and physical function and mobility impairment in older age. However, previous studies were mostly conducted among community-dwelling older individuals and had often a cross-sectional design. Accordingly, our aim was to examine longitudinal associations between cumulative exposure to anticholinergic and sedative medications and cognitive and physical function among residents from aged care homes.

Design: Longitudinal study.

Setting And Participants: A total of 4624 residents of Dutch aged care homes of whom data were collected between June 2005 and April 2014.

Methods: Outcome measures were collected with the Long-Term Care Facilities assessment from the international Residential Assessment Instrument (interRAI-LTCF) and included the Cognitive Performance Scale, the Activities of Daily Living (ADL) Hierarchy scale, a timed 4-meter walk test, distance walked, hours of physical activity, and days being outside. Cumulative exposure to anticholinergic and sedative medications was calculated with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Associations were examined with linear mixed models to take the potential dependence of observations into account (ie, data were collected at repeated assessment occasions of residents who were clustered in aged care homes). Analyses were adjusted for sex, age, dementia, comorbidity (neurological, psychiatric, cardiovascular, oncological, and pulmonary), fractures, depressive symptoms, and medications excluded from the DBI.

Results: We observed significant longitudinal associations between a higher DBI and poorer ADLs, fewer hours of physical activity, and fewer days being outside. We found no significant longitudinal association between a higher DBI and poorer cognitive function.

Conclusions And Implications: Over time, cumulative exposure to anticholinergic and sedative medications is associated with poorer physical but not cognitive function in aged care residents. Careful monitoring of aged care residents with high cumulative anticholinergic and sedative medication exposure is needed.
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http://dx.doi.org/10.1016/j.jamda.2020.05.037DOI Listing
August 2020

Assessing the Implementation of Pharmacogenomic Panel-Testing in Primary Care in the Netherlands Utilizing a Theoretical Framework.

J Clin Med 2020 Mar 17;9(3). Epub 2020 Mar 17.

Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Despite overcoming many implementation barriers, pharmacogenomic (PGx) panel-testing is not routine practice in the Netherlands. Therefore, we aim to study pharmacists' perceived enablers and barriers for PGx panel-testing among pharmacists participating in a PGx implementation study. Here, pharmacists identify primary care patients, initiating one of 39 drugs with a Dutch Pharmacogenetic Working Group (DPWG) recommendation and subsequently utilizing the results of a 12 gene PGx panel test to guide dose and drug selection. Pharmacists were invited for a general survey and a semi-structured interview based on the Tailored Implementation for Chronic Diseases (TICD) framework, aiming to identify implementation enablers and barriers, if they had managed at least two patients with actionable PGx results. In total, 15 semi-structured interviews were performed before saturation point was reached. Of these, five barrier themes emerged: (1) unclear procedures, (2) undetermined reimbursement for PGx test and consult, (3) insufficient evidence of clinical utility for PGx panel-testing, (4) infrastructure inefficiencies, and (5) HCP PGx knowledge and awareness; and two enabler themes: (1) pharmacist perceived role in delivering PGx, and (2) believed clinical utility of PGx. Despite a strong belief in the beneficial effects of PGx, pharmacists' barriers remain, an these hinder implementation in primary care.
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http://dx.doi.org/10.3390/jcm9030814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141350PMC
March 2020

Exploring Patient's Perspectives and Experiences After Start with Inhalation Maintenance Therapy: A Qualitative Theory-Based Study.

Patient Prefer Adherence 2020 29;14:203-212. Epub 2020 Jan 29.

Leiden University Medical Centre, Department of Clinical Pharmacy and Toxicology, Leiden, The Netherlands.

Background: Treatment of obstructive lung disease with inhalation therapy needs changes in patient behavior. Shortly after the start with inhaled corticosteroids (ICS) maintenance therapy, patients might be in need of additional pharmaceutical care, tailored to their individual needs. This study aimed to provide insight into patient behavior, goals and perceptions regarding their medical treatment at start with ICS therapy, by telephone interviews with ICS starters. Besides, this study investigated pharmacists' and patients' experiences with these interviews and opinions on the utility of this type of consultation for daily practice.

Methods: Semi-structured telephone interviews were conducted by pharmacists with adult patients 2-3 weeks after starting ICS. The Theoretical Domain Framework (TDF) was used for data analysis and coding. Afterward, the patients and pharmacists were questioned about their experiences with the interview.

Results: Five pharmacists conducted interviews with 23 ICS starters. Except the domains "environmental context and resources", "optimism", and "reinforcement", the remaining 11 domains in the TDF were addressed in the interviews. The majority of patients defined personal goals, which mainly addressed disease or symptom control (clinical goals). Some patients showed a lack of knowledge regarding the clinical indication or therapy duration. Views on beneficial medication effects differed between patients. Some patients specifically mentioned concerns or anxiety about side effects. The interviewees described different perceptions on the necessity of a personalized routine for regular medication use. Patients and pharmacists both felt positive about an added value of these interviews for daily practice.

Conclusion: Patient interviews shortly after start with ICS therapy revealed various perceptions and beliefs that might influence medication use and achievement of individual treatment goals. The patients appreciated the opportunity to ask questions and share their perspectives and needs with their pharmacist, and the pharmacists experienced that the interviews had added value.
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http://dx.doi.org/10.2147/PPA.S234094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996208PMC
January 2020

Persistence of oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study.

Res Pract Thromb Haemost 2020 Jan 24;4(1):141-153. Epub 2019 Oct 24.

Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands.

Background: In contrast to vitamin K antagonists (VKA), direct oral anticoagulants (DOAC's) are not strictly monitored and dose titrated by anticoagulation clinics in the Netherlands. This may affect drug persistence of atrial fibrillation (AF) patients, whom often require lifelong treatment.

Objectives: To assess persistence of DOACs and of VKAs in patients with AF.

Methods: Dispensing data from the Dutch Foundation of Pharmaceutical Statistics were used to monitor persistence of AF patients to DOAC from 1 January 2012-1 April 2016. In addition, we estimated the persistence of AF patients to VKA between 1 January 2004 and 1 January 2012 in data from the Anticoagulation Clinic Leiden. Non-persistence was defined as the cumulative incidence of patients who completely stopped DOAC, switched to another oral anticoagulant or stopped their VKA.

Results: DOAC users (n = 77 333) were younger than VKA users (n = 10 079; 70 vs 73 years). Non-Persistence to DOAC (ie stopping with any oral anticoagulant) was 34% at 1 and 64% at 4 years, compared to 22% at one and 36% at 4 years for VKA. Approximately a Twenty-five percent of those who had stopped their initial DOAC switched to another anticoagulant (VKA or another DOAC). Multivariable analyses revealed that young age, female sex, no concomitant drug use and non-adherence were predictors for non-persistence of DOAC.

Conclusions: Persistence to DOAC was low and in line with other observational studies, and higher for VKA. Our results show a clear correlation between age <60 years and worse persistence, as well as with female and non-adherence to DOAC.
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http://dx.doi.org/10.1002/rth2.12261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971315PMC
January 2020

Correction to: Cost-Utility and Budget Impact Analysis for Stopping the Inappropriate Use of Proton Pump Inhibitors After Cessation of NSAID or Low‑Dose Acetylsalicylic Acid Treatment.

Drugs Aging 2020 Jan;37(1):75

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.

Errors were subsequently identified in the article, and the following corrections should be noted.
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http://dx.doi.org/10.1007/s40266-019-00719-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965039PMC
January 2020

SERIES: eHealth in primary care. Part 2: Exploring the ethical implications of its application in primary care practice.

Eur J Gen Pract 2020 Dec 30;26(1):26-32. Epub 2019 Oct 30.

Department of Public Health and Primary Care, Leiden University Medical Centre, Leiden, the Netherlands.

eHealth promises to increase self-management and personalised medicine and improve cost-effectiveness in primary care. Paired with these promises are ethical implications, as eHealth will affect patients' and primary care professionals' (PCPs) experiences, values, norms, and relationships. We argue what ethical implications related to the impact of eHealth on four vital aspects of primary care could (and should) be anticipated. (1) EHealth influences dealing with predictive and diagnostic uncertainty. Machine-learning based clinical decision support systems offer (seemingly) objective, quantified, and personalised outcomes. However, they also introduce new loci of uncertainty and subjectivity. The decision-making process becomes opaque, and algorithms can be invalid, biased, or even discriminatory. This has implications for professional responsibilities and judgments, justice, autonomy, and trust. (2) EHealth affects the roles and responsibilities of patients because it can stimulate self-management and autonomy. However, autonomy can also be compromised, e.g. in cases of persuasive technologies and eHealth can increase existing health disparities. (3) The delegation of tasks to a network of technologies and stakeholders requires attention for responsibility gaps and new responsibilities. (4) The triangulate relationship: patient-eHealth-PCP requires a reconsideration of the role of human interaction and 'humanness' in primary care as well as of shaping Shared Decision Making. Our analysis is an essential first step towards setting up a dedicated ethics research agenda that should be examined in parallel to the development and implementation of eHealth. The ultimate goal is to inspire the development of practice-specific ethical recommendations.
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http://dx.doi.org/10.1080/13814788.2019.1678958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034078PMC
December 2020

Cost-Utility and Budget Impact Analysis for Stopping the Inappropriate Use of Proton Pump Inhibitors After Cessation of NSAID or Low-Dose Acetylsalicylic Acid Treatment.

Drugs Aging 2020 01;37(1):67-74

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.

Background: In accordance with current guidelines, proton pump inhibitors (PPIs) are now generally prescribed as a protective co-medication in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose acetylsalicylic acid (LDASA). However, less attention is paid to the corresponding discontinuation of a PPI after cessation of NSAID or LDASA treatment.

Objective: The aim of this study was to assess the extent of inappropriate PPI use, as the proportion of patients who started a PPI as a protective co-medication but continued using these drugs after cessation of NSAID and LDASA treatment. We also sought to estimate the potential cost savings and effect gains of discontinuing inappropriate PPI use and the resulting decrease in adverse effects and their detrimental consequences.

Methods: Pharmacy dispensing data were used to map inappropriate PPI use in 2014 for community-dwelling patients. Strategies with or without PPI continuation were compared in the cost-utility analysis for a time horizon of 5 years from a healthcare perspective. Subsequently, incremental costs and effects (quality-adjusted life-years) were estimated with a Markov model.

Results: Related to NSAID and LDASA treatment, 11.0% and 5%, respectively, of the PPI users were found to inappropriately continue PPI co-treatment. Discontinuation in 71- to 80-year-old patients suggested cost savings of €170.46 (95% confidence interval 75-282) at a 0.003 (95% confidence interval 0.001-0.005) quality-adjusted life-year increase. The total budget impact of stopping inappropriate PPI use related to NSAID/LDASA treatment in the Netherlands would amount to almost €1,050,000 after 1 year. Correspondingly, successful interventions to stop a patient's inappropriate use would cost up to €29 and probably would pay for themselves in the following years.

Conclusions: A substantial number of patients inappropriately continue to use a PPI after cessation of NSAID or LDASA treatment. Because adverse effects and their detrimental consequences are avoided, interventions to stop inappropriate PPI use, particularly in older patients, are likely to pay for themselves.
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http://dx.doi.org/10.1007/s40266-019-00713-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965335PMC
January 2020

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

Cardiovasc Drugs Ther 2019 10;33(5):615-623

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.

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.
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http://dx.doi.org/10.1007/s10557-019-06907-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904377PMC
October 2019

Adherence to guideline recommendations for asthma care in community pharmacies: actual and needed performance.

NPJ Prim Care Respir Med 2019 07 11;29(1):26. Epub 2019 Jul 11.

Department of Clinical Pharmacy & Toxicology, Leiden University Medical Centre, Leiden, The Netherlands.

Pharmaceutical care guidelines aim to provide recommendations for pharmaceutical care, reduce unwanted pharmacy practice variation and ultimately improve the quality of healthcare. This study evaluated community pharmacists' adherence to recommendations for the provision of care to asthma patients with first dispensing and follow-up refill encounters in The Netherlands. Data were pharmacists' self-assessment of adherence to guideline recommendations, independent observations of dispensing encounters and a nationwide questionnaire on pharmacists' views on the desirable (clinical) necessity of applying guideline recommendations to their patient population. The 21 pharmacists who performed self-assessment judged their adherence concerning inhalation instructions as high. The lowest scores were reported for recommendations to collect additional information on the type of lung disease and for asking patients' expectations, wishes and concerns. Sixty-eight dispensing encounters were observed. In 83% of the 35 first dispensing observations, inhalation instruction was provided. This percentage was lower (62%) at refill dispensings. During all encounters, pharmacy staff seldom explored patients' perceptions or responded to patients' expectations, wishes and concerns. One hundred and four pharmacists completed the feasibility questionnaire. Pharmacists judged that all patients should receive inhalation instruction at first dispensing. They regarded it necessary to check on patients' expectations, wishes and concerns regarding the treatment for only up to 70% of the patients. More efforts on guideline implementation are needed, especially on follow-up dispensings and on gaining relevant information from patients and other healthcare professionals. Pharmacists still have opportunities to grow in applying a patient-tailored approach and exploring patients' individual needs, rather than providing practical information.
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http://dx.doi.org/10.1038/s41533-019-0139-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624277PMC
July 2019

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

J Med Internet Res 2019 05 30;21(5):e13551. Epub 2019 May 30.

Department of Clinical Pharmacy & Toxicology, Leiden University Medical Centre, Leiden, Netherlands.

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.
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http://dx.doi.org/10.2196/13551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658221PMC
May 2019

Feasibility, acceptability and potential effectiveness of an information technology-based, pharmacist-led intervention to prevent an increase in anticholinergic and sedative load among older community-dwelling individuals.

Ther Adv Drug Saf 2019 30;10:2042098618805881. Epub 2018 Oct 30.

University of Groningen, Groningen, The Netherlands.

Background: Anticholinergic/sedative medications are frequently used by older people, despite their negative impacts on cognitive and physical function. We explore the feasibility, acceptability and potential effectiveness of an innovative information technology (IT)-based intervention to prevent an increase in anticholinergic/sedative load in older people.

Methods: This was a prospective study in 51 Dutch community pharmacies. Pharmacists used an IT-based tool to identify patients aged ⩾65 years, with existing high anticholinergic/sedative loads (drug burden index ⩾2) and a newly initiated anticholinergic/sedative medication. We determined the following. Feasibility: number of eligible patients identified. Acceptability: pharmacists' satisfaction with the intervention, pharmacists' time investment and patients' willingness to reduce medication use. Potential effectiveness: number of recommendations, rate of agreement of general practitioners (GPs) with proposed recommendations and factors associated with agreement. To evaluate the latter, pharmacists conducted medication reviews and proposed recommendations to GPs for 5-10 patients selected by the IT-based tool.

Results: We included 305 patients from 47 pharmacies. Feasibility: a mean of 17.0 (standard deviation, 8.8) patients were identified per pharmacy. Acceptability: 43 pharmacists (91.5%) were satisfied with the intervention. The median time investment per patient was 33 min (range 6.5-210). Of 35 patients, 30 (85.7%) were willing to reduce medication use. Potential effectiveness: pharmacists proposed 351 recommendations for 212 patients (69.5%). GPs agreed with recommendations for 108 patients (35.4%). Agreement to stop a medication was reached in 19.8% of recommendations for newly initiated medications (37 of 187) and for 15.2% of recommendations for existing medications (25 of 164). Agreement was more likely for recommendations on codeine [odds ratio (OR) 3.30; 95% confidence interval (CI) 1.14-9.57] or medications initiated by a specialist (OR 2.85; 95% CI 1.19-6.84) and less likely for pharmacies with lower level of collaboration with GPs (OR 0.15; 95% CI 0.02-0.97).

Conclusion: This innovative IT-based intervention was feasible, acceptable and potentially effective. In one-third of patients an increase in anticholinergic/sedative load was prevented within reasonable time investment.
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http://dx.doi.org/10.1177/2042098618805881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463339PMC
October 2018

Development and Piloting of an Algorithm to Select Older Patients for Different Types of Medication Review.

Front Pharmacol 2019 19;10:217. Epub 2019 Mar 19.

Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

To develop and pilot an algorithm to select older people for different types of medication review based on their case complexity. Experts rated complexity of patient cases through a Delphi-consensus method. The case characteristics were included in a regression model predicting complexity to develop a criteria-based algorithm. The algorithm was piloted in four community pharmacies with 38 patients of high and low complexity. Pharmacists conducted medication reviews according to their personal judgment and rated the patients' complexity. Time needed for reviewing and number of interventions (proposed and implemented) were assessed. Feasibility was evaluated with in-depth interviews. We developed the algorithm with 75 cases proceeding from patients in average 79 years old and using 10 prescribed medications. The regression model (adjusted = 0.726, < 0.0001) resulted in the following criteria for the algorithm: "number of medications" × 1 + "number of prescribers" × 3 + "recent fall incident" × 7 + "does not collect own medication" × 4. The pharmacists performed advanced medication reviews with all patients. The time needed to perform the medication review did not differ significantly according to case complexity (76.9 min for high complexity; 66.1 min for low complexity). Agreement between the algorithm scores and the pharmacists' ratings on complexity degree was slight to moderate (Kappa 0.16-0.42). The pharmacists had mixed opinions about the feasibility of applying the algorithm, particularly regarding the criterion "fall incidents." We developed an algorithm with four criteria that distinguished between high and low complexity patients as rated by experts. Additional validation steps are needed before implementation.
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http://dx.doi.org/10.3389/fphar.2019.00217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433968PMC
March 2019

Barriers and facilitators for community pharmacists' participation in pharmacy practice research: a survey.

Int J Pharm Pract 2019 Aug 19;27(4):399-402. Epub 2019 Feb 19.

Department of IQ Healthcare, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.

Objectives: The aim of this study was to explore pharmacists' barriers and facilitators regarding participation in pharmacy practice research.

Methods: We conducted an online cross-sectional survey in 1974 community pharmacies in the Netherlands.

Key Findings: A total of 252 pharmacists completed the questionnaire. The majority agreed that participation in research should be part of daily practice. Efficient time investment and a clear benefit for general professional knowledge, patient care and pharmacy organisation were the most important facilitating factors.

Conclusions: To encourage pharmacists' participation, researchers should offer clear instructions, possibilities for flexible time management, simple patient inclusion, task delegation and no additional contacts with healthcare professionals due to the research.
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http://dx.doi.org/10.1111/ijpp.12522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767426PMC
August 2019

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

Pharmacoepidemiol Drug Saf 2019 03 12;28(3):315-321. Epub 2019 Feb 12.

PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, 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.
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http://dx.doi.org/10.1002/pds.4698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593836PMC
March 2019

Adverse drug reactions on sexual functioning: a systematic overview.

Drug Discov Today 2019 03 25;24(3):890-897. Epub 2019 Jan 25.

Leiden University Medical Center, Department of Clinical Pharmacy & Toxicology, Leiden, The Netherlands.

Adverse drug reactions (ADRs) that diminish sexual functioning can seriously affect a person's quality of life and can also affect drug adherence. However, no comprehensive overview on the subject is available and a lack of knowledge among healthcare professionals might be present. This systematic review of Summary of Products Characteristics identified 346 drugs registered with at least one sexual ADR. The drug class 'nervous system' (N) was represented most frequently with 105 drugs, followed by 'cardiovascular system' (C) with 89 drugs. For 16 drugs an incidence rate for sexual ADR of >10% was reported and for 98 drugs there was an incidence rate >1%. Because sexual ADRs occur in frequently used drugs, they should be considered in clinical practice to optimize drug treatment.
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http://dx.doi.org/10.1016/j.drudis.2019.01.012DOI Listing
March 2019

Long-Term Exposure to Anticholinergic and Sedative Medications and Cognitive and Physical Function in Later Life.

J Gerontol A Biol Sci Med Sci 2020 01;75(2):357-365

Department of PharmacoTherapy, -Epidemiology & -Economics, Faculty of Science and Engineering, University of Groningen, The Netherlands.

Background: Anticholinergic and sedative medications are frequently prescribed to older individuals. These medications are associated with short-term cognitive and physical impairment, but less is known about long-term associations. We therefore examined whether over 20 years cumulative exposure to these medications was related to poorer cognitive and physical functioning.

Methods: Older adult participants of the Longitudinal Aging Study Amsterdam (LASA) were followed from 1992 to 2012. On seven measurement occasions, cumulative exposure to anticholinergic and sedative medications was quantified with the drug burden index (DBI), a linear additive pharmacological dose-response model. Cognitive functioning was assessed with the Mini-Mental State Examination (MMSE), Alphabet Coding Task (ACT, three trials), Auditory Verbal Learning Test (AVLT, learning and retention condition), and Raven Colored Progressive Matrices (RCPM, two trials). Physical functioning was assessed with the Walking Test (WT), Cardigan Test (CT), Chair Stands Test (CST), Balance Test (BT), and self-reported Functional Independence (FI). Data were analyzed with linear mixed models adjusted for age, education, sex, living with a partner, BMI, depressive symptoms, comorbidities (cardiovascular disease, diabetes, cancer, COPD, osteoarthritis, CNS diseases), and prescribed medications.

Results: Longitudinal associations were found of the DBI with poorer cognitive functioning (less items correct on the three ACT trials, AVLT learning condition, and the two RCPM trials) and with poorer physical functioning (longer completion time on the CT, CST, and lower self-reported FI).

Conclusions: This longitudinal analysis of data collected over 20 years, showed that higher long-term cumulative exposure to anticholinergic and sedative medications was associated with poorer cognitive and physical functioning.
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http://dx.doi.org/10.1093/gerona/glz019DOI Listing
January 2020

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

Pharmacogenomics J 2019 10 16;19(5):480-489. Epub 2019 Jan 16.

Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1038/s41397-019-0070-8DOI Listing
October 2019

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

Pharmacoepidemiol Drug Saf 2018 12 15;27(12):1371-1378. Epub 2018 Nov 15.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1002/pds.4684DOI Listing
December 2018

Cost-Effectiveness Analysis of Genotype-Guided Treatment Allocation in Patients with Alcohol Use Disorders Using Naltrexone or Acamprosate, Using a Modeling Approach.

Eur Addict Res 2018 1;24(5):245-254. Epub 2018 Nov 1.

Department of Psychiatry, Donders Centre for Neuroscience, Radboud University Medical Centre, Nijmegen Institute for Scientist Practitioners in Addiction, Nijmegen, The Netherlands.

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.
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http://dx.doi.org/10.1159/000494127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492516PMC
March 2019

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

Pharmacoepidemiol Drug Saf 2018 12 28;27(12):1344-1355. Epub 2018 Sep 28.

German Institute for Drug Use Evaluation (DAPI), Berlin, DE, Germany.

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.
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http://dx.doi.org/10.1002/pds.4643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585743PMC
December 2018

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

J Oncol Pharm Pract 2019 Oct 27;25(7):1613-1621. Epub 2018 Sep 27.

3 Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

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.
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http://dx.doi.org/10.1177/1078155218801066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716205PMC
October 2019

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.

Int J Clin Pharmacol Ther 2018 Nov;56(11):518-530

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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http://dx.doi.org/10.5414/CP203264DOI Listing
November 2018

Persistence to direct oral anticoagulants for acute venous thromboembolism.

Thromb Res 2018 07 19;167:135-141. Epub 2018 May 19.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

Background: Currently, direct oral anticoagulants (DOACs) are the treatment of choice for venous thromboembolism (VTE) in the Netherlands. The main advantages of DOACs over vitamin K antagonists (VKAs) are that they are safer than VKA and that neither monitoring nor dose titrations are needed. A main drawback is a potential risk of lower drug persistence, as compared with VKA treatment, which is strictly controlled by anticoagulation clinics in the Netherlands.

Objectives: The primary aim of this study was to audit the persistence to DOAC treatment for acute VTE during the first 2 months in daily clinical practice.

Methods: Dispensing data from the Dutch Foundation of Pharmaceutical Statistics were used to monitor persistence to DOAC for treatment of VTE from 1 January 2012-1 April 2016. Non-persistence was defined as the cumulative incidence of patients who completely stopped DOAC or VKA treatment. In addition, we estimated the persistence to VKA treatment for VTE in data from the Anticoagulation Clinic Leiden.

Results: 1834 patients were selected as DOAC users for the indication VTE. The 2-month cumulative incidence of completely stopping DOAC was 20% (95% confidence interval [CI] 18-24). In the population of 4910 VKA users, 9.1% (95%CI 8.3-9.9) stopped prematurely with VKA.

Conclusion: The stopping rate of 20% we found is in line with other cardiovascular treatments. Further research into the reasons and consequences of prematurely stopping DOAC treatment for acute VTE is urgently needed.
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http://dx.doi.org/10.1016/j.thromres.2018.05.013DOI Listing
July 2018