The impact of a summative national prescribing assessment and curriculum type on the development of the prescribing competence of junior doctors.

PURPOSE: The primary aim of this study was to investigate the effect of including the Dutch National Pharmacotherapy Assessment (DNPA) in the medical curriculum on the level and development of prescribing knowledge and skills of junior doctors. The secondary aim was to evaluate the relationship between the curriculum type and the prescribing competence of junior doctors. METHODS: We re-analysed the data of a longitudinal study conducted in 2016 involving recently graduated junior doctors from 11 medical schools across the Netherlands and Belgium. Participants completed three assessments during the first year after graduation (around graduation (+ / - 4 weeks), and 6 months, and 1 year after graduation), each of which contained 35 multiple choice questions (MCQs) assessing knowledge and three clinical case scenarios assessing skills. Only one medical school used the DNPA in its medical curriculum; the other medical schools used conventional means to assess prescribing knowledge and skills. Five medical schools were classified as providing solely theoretical clinical pharmacology and therapeutics (CPT) education; the others provided both theoretical and practical CPT education (mixed curriculum). RESULTS: Of the 1584 invited junior doctors, 556 (35.1%) participated, 326 (58.6%) completed the MCQs and 325 (58.5%) the clinical case scenarios in all three assessments. Junior doctors whose medical curriculum included the DNPA had higher knowledge scores than other junior doctors (76.7% [SD 12.5] vs. 67.8% [SD 12.6], 81.8% [SD 11.1] vs. 76.1% [SD 11.1], 77.0% [12.1] vs. 70.6% [SD 14.0], p < 0.05 for all three assessments, respectively). There was no difference in skills scores at the moment of graduation (p = 0.110), but after 6 and 12 months junior doctors whose medical curriculum included the DNPA had higher skills scores (both p < 0.001). Junior doctors educated with a mixed curriculum had significantly higher scores for both knowledge and skills than did junior doctors educated with a theoretical curriculum (p < 0.05 in all assessments). CONCLUSION: Our findings suggest that the inclusion of the knowledge focused DNPA in the medical curriculum improves the prescribing knowledge, but not the skills, of junior doctors at the moment of graduation. However, after 6 and 12 months, both the knowledge and skills were higher in the junior doctors whose medical curriculum included the DNPA. A curriculum that provides both theoretical and practical education seems to improve both prescribing knowledge and skills relative to a solely theoretical curriculum.

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

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

Do we become better prescribers after graduation: A 1-year international follow-up study among junior doctors.

AIM: The aim of this study was to investigate how the prescribing knowledge and skills of junior doctors in the Netherlands and Belgium develop in the year after graduation. We also analysed differences in knowledge and skills between surgical and nonsurgical junior doctors. METHODS: This international, multicentre (n = 11), longitudinal study analysed the learning curves of junior doctors working in various specialties via three validated assessments at about the time of graduation, and 6 months and 1 year after graduation. Each assessment contained 35 multiple choice questions (MCQs) on medication safety (passing grade ≥85%) and three clinical scenarios. RESULTS: In total, 556 junior doctors participated, 326 (58.6%) of whom completed the MCQs and 325 (58.5%) the clinical case scenarios of all three assessments. Mean prescribing knowledge was stable in the year after graduation, with 69% (SD 13) correctly answering questions at assessment 1 and 71% (SD 14) at assessment 3, whereas prescribing skills decreased: 63% of treatment plans were considered adequate at assessment 1 but only 40% at assessment 3 (P < .001). While nonsurgical doctors had similar learning curves for knowledge and skills as surgical doctors (P = .53 and P = .56 respectively), their overall level was higher at all three assessments (all P < .05). CONCLUSION: These results show that junior doctors' prescribing knowledge and skills did not improve while they were working in clinical practice. Moreover, their level was under the predefined passing grade. As this might adversely affect patient safety, educational interventions should be introduced to improve the prescribing competence of junior doctors.

Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics.

AIM: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. METHODS: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. RESULTS: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. CONCLUSION: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.

EurOP2E - the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers.

PURPOSE: Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. METHODS: CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. RESULTS: Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. CONCLUSION: Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system.

Different antibiotic treatments for group A streptococcal pharyngitis.

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications.  AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.

Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults.

BACKGROUND: Depression and anxiety are the most frequent indication for which antidepressants are prescribed. Long-term antidepressant use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that 30% to 50% of long-term antidepressant prescriptions had no evidence-based indication. Unnecessary use of antidepressants puts people at risk of adverse events. However, high-certainty evidence is lacking regarding the effectiveness and safety of approaches to discontinuing long-term antidepressants. OBJECTIVES: To assess the effectiveness and safety of approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. SEARCH METHODS: We searched all databases for randomised controlled trials (RCTs) until January 2020. SELECTION CRITERIA: We included RCTs comparing approaches to discontinuation with continuation of antidepressants (or usual care) for people with depression or anxiety who are prescribed antidepressants for at least six months. Interventions included discontinuation alone (abrupt or taper), discontinuation with psychological therapy support, and discontinuation with minimal intervention. Primary outcomes were successful discontinuation rate, relapse (as defined by authors of the original study), withdrawal symptoms, and adverse events. Secondary outcomes were depressive symptoms, anxiety symptoms, quality of life, social and occupational functioning, and severity of illness. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 33 studies involving 4995 participants. Nearly all studies were conducted in a specialist mental healthcare service and included participants with recurrent depression (i.e. two or more episodes of depression prior to discontinuation). All included trials were at high risk of bias. The main limitation of the review is bias due to confounding withdrawal symptoms with symptoms of relapse of depression. Withdrawal symptoms (such as low mood, dizziness) may have an effect on almost every outcome including adverse events, quality of life, social functioning, and severity of illness. Abrupt discontinuation Thirteen studies reported abrupt discontinuation of antidepressant. Very low-certainty evidence suggests that abrupt discontinuation without psychological support may increase risk of relapse (hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.59 to 2.74; 1373 participants, 10 studies) and there is insufficient evidence of its effect on adverse events (odds ratio (OR) 1.11, 95% CI 0.62 to 1.99; 1012 participants, 7 studies; I² = 37%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of abrupt discontinuation on withdrawal symptoms (1 study) is very uncertain. None of these studies included successful discontinuation rate as a primary endpoint. Discontinuation by "taper" Eighteen studies examined discontinuation by "tapering" (one week or longer). Most tapering regimens lasted four weeks or less. Very low-certainty evidence suggests that "tapered" discontinuation may lead to higher risk of relapse (HR 2.97, 95% CI 2.24 to 3.93; 1546 participants, 13 studies) with no or little difference in adverse events (OR 1.06, 95% CI 0.82 to 1.38; 1479 participants, 7 studies; I² = 0%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of discontinuation on withdrawal symptoms (1 study) is very uncertain. Discontinuation with psychological support Four studies reported discontinuation with psychological support. Very low-certainty evidence suggests that initiation of preventive cognitive therapy (PCT), or MBCT, combined with "tapering" may result in successful discontinuation rates of 40% to 75% in the discontinuation group (690 participants, 3 studies). Data from control groups in these studies were requested but are not yet available. Low-certainty evidence suggests that discontinuation combined with psychological intervention may result in no or little effect on relapse (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies) compared to continuation of antidepressants. Withdrawal symptoms were not measured. Pooling data on adverse events was not possible due to insufficient information (3 studies). Discontinuation with minimal intervention Low-certainty evidence from one study suggests that a letter to the general practitioner (GP) to review antidepressant treatment may result in no or little effect on successful discontinuation rate compared to usual care (6% versus 8%; 146 participants, 1 study) or on relapse (relapse rate 26% vs 13%; 146 participants, 1 study). No data on withdrawal symptoms nor adverse events were provided. None of the studies used low-intensity psychological interventions such as online support or a changed pharmaceutical formulation that allows tapering with low doses over several months. Insufficient data were available for the majority of people taking antidepressants in the community (i.e. those with only one or no prior episode of depression), for people aged 65 years and older, and for people taking antidepressants for anxiety. AUTHORS' CONCLUSIONS: Currently, relatively few studies have focused on approaches to discontinuation of long-term antidepressants. We cannot make any firm conclusions about effects and safety of the approaches studied to date. The true effect and safety are likely to be substantially different from the data presented due to assessment of relapse of depression that is confounded by withdrawal symptoms. All other outcomes are confounded with withdrawal symptoms. Most tapering regimens were limited to four weeks or less. In the studies with rapid tapering schemes the risk of withdrawal symptoms may be similar to studies using abrupt discontinuation which may influence the effectiveness of the interventions. Nearly all data come from people with recurrent depression.   There is an urgent need for trials that adequately address withdrawal confounding bias, and carefully distinguish relapse from withdrawal symptoms. Future studies should report key outcomes such as successful discontinuation rate and should include populations with one or no prior depression episodes in primary care, older people, and people taking antidepressants for anxiety and use tapering schemes longer than 4 weeks.

'Never change a winning team': GPs' perspectives on discontinuation of long-term antidepressants.

BACKGROUND: Long-term antidepressant use, much longer than recommended by guidelines, can harm patients and generate unnecessary costs. Most antidepressants are prescribed by general practitioners (GPs) but it remains unclear why they do not discontinue long-term use. AIM: To explore GPs' views and experiences of discontinuing long-term antidepressants, barriers and facilitators of discontinuation and required support. DESIGN AND SETTING: Qualitative study in Belgian GPs. METHOD: 20 semi-structured face-to-face interviews with GPs. Interviews were analysed thematically. RESULTS: The first theme, 'Success stories' describes three strong motivators to discontinue antidepressants: patient health issues, patient requests and a new positive life event. Second, not all GPs consider long-term antidepressant use a 'problem' as they perceive antidepressants as effective and safe. GPs' main concern is the risk of relapse. Third, GPs foresee that discontinuation of antidepressants is not an easy and straightforward process. GPs weigh up whether they have the necessary skills and whether it is worth the effort to start this process. CONCLUSION: Discontinuation of long-term antidepressants is a difficult and uncertain process for GPs, especially in the absence of a facilitating life-event or patient demand. The absence of a compelling need for discontinuation and fear of relapse of symptoms in a stable patient are important barriers for GPs when considering discontinuation. In order to increase GPs' motivation to discontinue long-term antidepressants, more emphasis on the futility of the actual effect and on potential harms related to long-term use is needed.KEY POINTSCurrent awareness:Long-term antidepressant use, much longer than recommended by guidelines, can harm patients and generate unnecessary costs.Main statements: • Discontinuation of long-term antidepressants is a difficult and uncertain process for GPs. • More emphasis on the futility of the actual effect of antidepressants and on potential harms related to long-term use is needed.

Regulatory reliance to approve new medicinal products in Latin American and Caribbean countries.

OBJECTIVE: To describe the current status of regulatory reliance in Latin America and the Caribbean (LAC) by assessing the countries' regulatory frameworks to approve new medicines, and to ascertain, for each country, which foreign regulators are considered as trusted regulatory authorities to rely on. METHODS: Websites from LAC regulators were searched to identify the official regulations to approve new drugs. Data collection was carried out in December 2019 and completed in June 2020 for the Caribbean countries. Two independent teams collected information regarding direct recognition or abbreviated processes to approve new drugs and the reference (trusted) regulators defined as such by the corresponding national legislation. RESULTS: Regulatory documents regarding marketing authorization were found in 20 LAC regulators' websites, covering 34 countries. Seven countries do not accept reliance on foreign regulators. Thirteen regulatory authorities (Argentina, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Mexico, Panama, Paraguay, Peru, Uruguay, and the unique Caribbean Regulatory System for 15 Caribbean States) explicitly accept relying on marketing authorizations issued by the European Medicines Agency, United States Food and Drug Administration, and Health Canada. Ten countries rely also on marketing authorizations from Australia, Japan, and Switzerland. Argentina, Brazil, Chile, and Mexico are reference authorities for eight LAC regulators. CONCLUSIONS: Regulatory reliance has become a common practice in the LAC region. Thirteen out of 20 regulators directly recognize or abbreviate the marketing authorization process in case of earlier approval by a regulator from another jurisdiction. The regulators most relied upon are the European Medicines Agency, United States Food and Drug Administration, and Health Canada.

Discontinuation of medications at the end of life: A population study in Belgium, based on linked administrative databases.

AIMS: The aim of this study was to examine the use of potentially inappropriate medication (PIM) in relation to time before death, to explore whether PIMs are discontinued at the end of life, and the factors associated with this discontinuation. METHODS: We conducted a retrospective register-based mortality cohort study of all deceased in 2012 in Belgium, aged at least 75 years at time of death (n = 74 368), using linked administrative databases. We used STOPPFrail to identify PIMs received during the period from 12 to 6 months before death (P1) and the last 4 months (P2) of life. RESULTS: Median age was 86 (IQR 81-90) at time of death, 57% were female, 38% were living in a nursing home, and 16% were admitted to hospital between 2 years and 4 months before death. Overall, PIM use was high, and increased towards death for all PIMs. At least one PIM was discontinued during P2 for one in five (20%) of the population, and 49% had no discontinuation. Being hospitalized in the period before the last 4 months of life, living in a nursing home, female gender and a higher number of medications used during P1 were associated with discontinuation of PIMs (respective aOR [95% CI]: 2.89 [2.73-3.06], 1.29 [1.23-1.36], 1.26 [1.20-1.32], 1.17 [1.16-1.17]). CONCLUSION: Initial PIM use was high and increased towards death. Discontinuation was observed in only one in five PIM users. More guidance for discontinuation of PIMs is needed: practical, evidence-based deprescribing guidelines and implementation plans, training for prescribers and a better consensus on what inappropriate medication is.

Balancing medication use in nursing home residents with life-limiting disease.

PURPOSE: Balancing medications that are needed and beneficial and avoiding medications that may be harmful is important to prevent drug-related problems, and improve quality of life. The aim of this study is to describe medication use, the prevalence of deprescribing of medications suitable for deprescribing, and the prevalence of new initiation of potentially inappropriate medications (PIMs) in nursing home (NH) residents with life-limiting disease in Flanders. METHODS: NH residents aged ≥ 65, suffering from end stage organ failure, advanced cancer, and/or dementia (n = 296), were included in this cross-sectional study with retrospective analyses of medication use at the time of data collection (t2) and 3 to 6 months before (t1). The appraisal of appropriateness of medications was done using a list of medications documented as suitable for deprescribing, and STOPPFrail criteria. RESULTS: Residents' (mean age 86 years, 74% female) mean number of chronic medications increased from 7.4 (t1) to 7.9 (t2). In 31% of those using medications suitable for deprescribing, at least one medication was actually deprescribed. In 30% at least one PIM from the group of selected PIMs was newly initiated. In the subgroup (n = 76) for whom deprescribing was observed, deprescribing was associated with less new initiations of PIMs (r = - 0.234, p = 0.042). CONCLUSION: Medication use remained high at the end of life for NH residents with life-limiting disease, and deprescribing was limited. However, in the subgroup of 76 residents for whom deprescribing was observed, less new PIMs were initiated.

Barriers and enablers to deprescribing in people with a life-limiting disease: A systematic review.

BACKGROUND:: Knowing the barriers/enablers to deprescribing in people with a life-limiting disease is crucial for the development of successful deprescribing interventions. These barriers/enablers have been studied, but the available evidence has not been summarized in a systematic review. AIM:: To identify the barriers/enablers to deprescribing of medications in people with a life-limiting disease. DESIGN:: Systematic review, registered in PROSPERO (CRD42017073693). DATA SOURCES:: A systematic search of MEDLINE, Embase, Web of Science and CENTRAL was conducted and extended with a hand search. Peer-reviewed, primary studies reporting on barriers/enablers to deprescribing in the context of explicit life-limiting disease were included in this review. RESULTS:: A total of 1026 references were checked. Five studies met the criteria and were included in this review. Three types of barriers/enablers were found: organizational, professional and patient (family)-related barriers/enablers. The most prominent enablers were organizational support (e.g. for standardized medication review), involvement of multidisciplinary teams in medication review and the perception of the importance of coming to a joint decision regarding deprescribing, which highlighted the need for interdisciplinary collaboration and involving the patient and his family in the decision-making process. The most important barriers were shortages in staff and the perceived difficulty or resistance of the nursing home resident's family - or the resident himself. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS:: The scarcity of findings in the literature highlights the importance of filling this gap. Further research should focus on deepening the knowledge on these barriers/enablers in order to develop sustainable multifaceted deprescribing interventions in palliative care.

A tailored e-learning gives long-term changes in determinants of GPs' benzodiazepines prescribing: a pretest-posttest study with self-report assessments.

Objective: Despite guidelines and campaigns, general practitioners (GPs) continue to overprescribe benzodiazepines (BZDs). New approaches to improve prescribing are needed. Using behavior change techniques and tailoring interventions to user characteristics are vital to promote behavior change. This study evaluated the impact of a tailored e-learning module on factors known to determine BZD prescribing within GPs.Design: A pretest-posttest study design with three self-report assessments concerning determinants of BZD prescribing: at baseline, immediately after the module (short term) and six months after completion (long term).Setting: Flanders (Belgium)Intervention: A tailored e-module that focuses on avoiding initial BZD prescriptions and using psychological interventions as an alternative.Subjects: 244 GPsMain outcome measures: Assessed determinants include GPs' attitudes concerning treatment options, perceptions of the patient and self-efficacy beliefs. Readiness to adhere to prescribing guidelines was evaluated through assessing motivation, self-efficacy and implementability of non-pharmacological interventions.Results: A significant and durable impact on determinants of BZD prescribing was observed. GPs underwent desirable changes in attitudes, perceptions and self-efficacy beliefs and these changes remained significant six months later.Conclusion: Tailoring an e-intervention to target group characteristics appears to be successful in promoting behavioral change in experienced GPs. Significant and lasting changes were observed in determinants of prescribing BZDs.Key PointsA tailored e-intervention resulted in significant and long term changes in previously identified determinants of prescribing BZDs. The e-module resulted in a positive impact on GPs' readiness to adhere to BZD prescribing guidance and the way they experience psychosocial consultations. Tailoring an e-intervention to target group characteristics appears to be successful in promoting behavioral change in experienced GPs.

Changes in medication use in a cohort of patients with advanced cancer: The international multicentre prospective European Palliative Care Cancer Symptom study.

BACKGROUND: Information on medication use in the last months of life is limited. AIM: To describe which medications are prescribed and deprescribed in advanced cancer patients receiving palliative care in relation to time before death and to explore associations with demographic variables. DESIGN: Prospective study, using case report forms for monthly data collection. Medication included cancer treatment and 19 therapeutic groups, grouped into four categories for: (1) cancer therapy, (2) specific cancer-related symptom relief, (3) other symptom relief and (4) long-term prevention. Data were analysed retrospectively using death as the index date. We compared medication use at 5, 4, 3, 2 and 1 month(s) before death by constructing five cross-sectional subsamples with medication use during that month. Paired analyses were done on a subsample of patients with at least two assessments before death. SETTING/PARTICIPANTS: We studied the medication use of 720 patients (mean age 67, 56% male) in 30 cancer centres representing 12 countries. RESULTS: From 5 to 1 month(s) before death, cancer therapy decreased (55%-24%), most medications for symptom relief increased, for example, opioids (62%-81%) and sedatives (35%-46%), but medication for long-term prevention decreased (38%-27%). The prevalence of chemotherapy was 15.5% in the last month of life, with 9% of new courses started in the last 2 months. With higher age, chemotherapy and opioid use decreased. CONCLUSION: Medications for symptom relief increased in almost all medication groups. Deprescribing was found in heart medication/anti-hypertensives and cancer therapy, although use of the latter remained relatively high.

Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia.

BACKGROUND: Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in people with dementia although there is uncertainty about the effectiveness of their long-term use for this indication and concern that they may cause harm, including higher mortality. When behavioural strategies have failed and treatment with antipsychotic drugs is instituted, regular attempts to withdraw them have been recommended in guidelines. Physicians, nurses and families of older people with dementia may be reluctant to stop antipsychotics, fearing deterioration of NPS.This is an update of a Cochrane Review published in 2013. OBJECTIVES: To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia and NPS in primary care or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older participants with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on participants' behaviour and assess safety. SEARCH METHODS: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), theCochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources up to 11 January 2018. SELECTION CRITERIA: We included all randomised, controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia who had been treated with an antipsychotic drug for at least three months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 10 studies involving 632 participants. One new trial (19 participants) was added for this update.One trial was conducted in a community setting, eight in nursing homes and one in both settings. Different types of antipsychotics at varying doses were discontinued in the studies. Both abrupt and gradual withdrawal schedules were used. Reported data were predominantly from studies at low or unclear risk of bias.We included nine trials with 575 randomised participants that used a proxy outcome for overall success of antipsychotic withdrawal. Pooling data was not possible due to heterogeneity of outcome measures used. Based on assessment of seven studies, discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence).Two trials included only participants with psychosis, agitation or aggression who had responded to antipsychotic treatment. In these two trials, stopping antipsychotics was associated with a higher risk of leaving the study early due to symptomatic relapse or a shorter time to symptomatic relapse.We found low-quality evidence that discontinuation may make little or no difference to overall NPS, measured using various scales (7 trials, 519 participants). There was some evidence from subgroup analyses in two trials that discontinuation may reduce agitation for participants with less severe NPS at baseline, but may be associated with a worsening of NPS in participants with more severe NPS at baseline.None of the studies assessed withdrawal symptoms. Adverse effects of antipsychotics (such as falls) were not systematically assessed. Low-quality evidence showed that discontinuation may have little or no effect on adverse events (5 trials, 381 participants), quality of life (2 trials, 119 participants), or cognitive function (5 trials, 365 participants).There were insufficient data to determine whether discontinuation of antipsychotics has any effect on mortality (very low-quality evidence). AUTHORS' CONCLUSIONS: There is low-quality evidence that antipsychotics may be successfully discontinued in older people with dementia and NPS who have been taking antipsychotics for at least three months, and that discontinuation may have little or no important effect on behavioural and psychological symptoms. This is consistent with the observation that most behavioural complications of dementia are intermittent and often do not persist for longer than three months. Discontinuation may have little or no effect on overall cognitive function. Discontinuation may make no difference to adverse events and quality of life. Based on the trials in this review, we are uncertain whether discontinuation of antipsychotics leads to a decrease in mortality.People with psychosis, aggression or agitation who responded well to long-term antipsychotic drug use, or those with more severe NPS at baseline, may benefit behaviourally from continuation of antipsychotics. Discontinuation may reduce agitation for people with mild NPS at baseline. However, these conclusions are based on few studies or small subgroups and further evidence of benefits and harms associated with withdrawal of antipsychotic is required in people with dementia and mild and severe NPS.The overall conclusions of the review have not changed since 2013 and the number of available trials remains low.

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

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

Teaching young GPs to cope with psychosocial consultations without prescribing: a durable impact of an e-module on determinants of benzodiazepines prescribing.

BACKGROUND: Despite guidelines and campaigns to change prescribing behavior, General Practitioners (GPs) continue to overprescribe benzodiazepines (BZDs). New approaches to improve prescribing are needed. Using behavior change techniques and tailoring interventions to user characteristics are vital to promote behavior change. This study evaluated the impact of an e-module on factors known to determine BZD prescribing practice. METHODS: A tailored e-module that focuses on avoiding initial BZD prescriptions (and using psychological interventions as an alternative) was developed and offered to GPs in vocational training. Three self-report assessments took place: at baseline, immediately after the module (short term) and at least six months after completion (long term). Assessed determinants include GPs' attitudes concerning treatment options, perceptions of the patient and self-efficacy beliefs. Readiness to adhere to prescribing guidelines was evaluated through assessing motivation, self-efficacy and implementability of non-pharmacological interventions. Changes in determinants were analyzed using the Wilcoxon signed-rank test. Changes in readiness to adhere to guidelines was analyzed using the nonparametric McNemar Bowker test. RESULTS: A desirable, significant and durable impact on determinants of BZD prescribing was observed. GPs (n = 121) underwent desirable changes in their attitudes, perceptions and self-efficacy beliefs and these changes remained significant months after the intervention. Barriers to using a non-pharmacological approach often cited in literature remained absent and were not highlighted by the intervention. Furthermore a significant impact on GPs' readiness to adhere to guidelines was observed. Participants reported change in their ability to cope with psychosocial consultations and to have tried using non-pharmacological interventions. CONCLUSIONS: Tailoring an e-intervention to target group (GPs) characteristics appears to be successful in promoting behavioral change in GPs undertaking vocational training. Significant and lasting changes were observed in determinants of prescribing BZDs. The e-intervention resulted in a positive impact on participants' readiness to adhere to BZD prescribing guidance and their coping with psychosocial consultations. Investigating which mechanisms of change are responsible for the observed effectiveness could help to refine and improve future interventions.

Too many, too few, or too unsafe? Impact of inappropriate prescribing on mortality, and hospitalization in a cohort of community-dwelling oldest old.

AIMS: Little is known about the impact of inappropriate prescribing (IP) in community-dwelling adults, aged 80 years and older. The prevalence at baseline (November 2008September 2009) and impact of IP (misuse and underuse) after 18 months on mortality and hospitalization in a cohort of community-dwelling adults, aged 80 years and older (n = 503) was studied. METHODS: Screening Tool of Older People's Prescriptions (STOPP-2, misuse) and Screening Tool to Alert to Right Treatment (START-2, underuse) criteria were cross-referenced and linked to the medication use (in Anatomical Therapeutic Chemical coding) and clinical problems. Survival analysis until death or first hospitalization was performed at 18 months after inclusion using Kaplan-Meier, with Cox regression to control for covariates. RESULTS: Mean age was 84.4 (range 80-102) years. Mean number of medications prescribed was 5 (range 0-16). Polypharmacy (≥5 medications, 58%), underuse (67%) and misuse (56%) were high. Underuse and misuse coexisted in 40% and were absent in 17% of the population. A higher number of prescribed medications was correlated with more misused medications (rs  = .51, P < 0.001) and underused medications (rs  = .26, P < 0.001). Mortality and hospitalization rate were 8.9%, and 31.0%, respectively. After adjustment for number of medications and misused medications, there was an increased risk of mortality (HR 1.39, 95% CI 1.10, 1.76) and hospitalization (HR 1.26, 95% CI 1.10, 1.45) for every additional underused medication. Associations with misuse were less clear. CONCLUSION: IP (polypharmacy, underuse and misuse) was highly prevalent in adults, aged 80 years and older. Surprisingly, underuse and not misuse had strong associations with mortality and hospitalization.

Systematic review of cross-national drug utilization studies in Latin America: methods and comparability.

PURPOSE: We systematically review the cross-national drug utilization studies performed in Latin America (LA) in order to analyze the methods applied and assess the validity of the data to ensure the comparability. METHODS: A systematic search in Medline, Embase, and BIREME was performed. Drug utilization studies including LA countries and comparing drug exposure data on volume were included. The data validity was judged independently by two authors as having low, medium, high, or unclear risk of bias. RESULTS: Out of 1191 articles, 25 were kept for full text reading. Finally, five studies were selected. Eight different Latin American countries were involved in the comparisons. The selected studies analyzed wholesale data from a private research company collecting information from the private healthcare sector. In three studies, a high risk of bias in the extrapolation method applied was identified. In one study, a risk of data collection bias was detected. The most frequent limitation detected by the original authors was related to the unavailability of information from the public sector in LA. CONCLUSION: Drug utilization studies comparing data cross-nationally are scarce in LA. In general, validity of the comparisons is hampered by a potential risk of extrapolation bias given the lack of available data on drug consumption from the public healthcare sector. Setting up systems to remediate this situation is a future challenge for researchers and (supra)national authorities in the region.