Quality indicators for appropriate in-hospital pharmacotherapeutic stewardship: An international modified Delphi study.

AIMS: In-hospital prescribing errors may result in patient harm, such as prolonged hospitalisation and hospital (re)admission, and may be an emotional burden for the prescribers and healthcare professionals involved. Despite efforts, in-hospital prescribing errors and related harm still occur, necessitating an innovative approach. We therefore propose a novel approach, in-hospital pharmacotherapeutic stewardship (IPS). The aim of this study was to reach consensus on a set of quality indicators (QIs) as a basis for IPS. METHODS: A three-round modified Delphi procedure was performed. Potential QIs were retrieved from two systematic searches of the literature, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. In two written questionnaires and a focus meeting (held between the written questionnaire rounds), potential QIs were appraised by an international, multidisciplinary expert panel composed of members of the European Association for Clinical Pharmacology and Therapeutics (EACPT). RESULTS: The expert panel rated 59 QIs and four general statements, of which 35 QIs were accepted with consensus rates ranging between 79% and 97%. These QIs describe the activities of an IPS programme, the team delivering IPS, the patients eligible for the programme and the outcome measures that should be used to evaluate the care delivered. CONCLUSIONS: A framework of 35 QIs for an IPS programme was systematically developed. These QIs can guide hospitals in setting up a pharmacotherapeutic stewardship programme to reduce in-hospital prescribing errors and improve in-hospital medication safety.

The European List of Key Medicines for Medical Education: A Modified Delphi Study.

Rational prescribing is essential for the quality of health care. However, many final-year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely accessible in Europe. For this, we used a modified Delphi study method consisting of three parts. In part one, we created an initial list based on a literature search. In part two, a group of 64 coordinators in CPT education, selected via the Network of Teachers in Pharmacotherapy of the European Association for Clinical Pharmacology and Therapeutics, evaluated the accessibility of each medicine in his or her country, and provided a diverse group of experts willing to participate in the Delphi part. In part three, 463 experts from 24 European countries were invited to participate in a 2-round Delphi study. In total, 187 experts (40%) from 24 countries completed both rounds and evaluated 416 medicines, 98 of which were included in the final list. The top three Anatomical Therapeutic Chemical code groups were (1) cardiovascular system (n = 23), (2) anti-infective (n = 21), and (3) musculoskeletal system (n = 11). This European List of Key Medicines for Medical Education could be a starting point for country-specific lists and could be used for the training and assessment of CPT.

Using artificial intelligence to create diverse and inclusive medical case vignettes for education.

AIMS: Medical case vignettes play a crucial role in medical education, yet they often fail to authentically represent diverse patients. Moreover, these vignettes tend to oversimplify the complex relationship between patient characteristics and medical conditions, leading to biased and potentially harmful perspectives among students. Displaying aspects of patient diversity, such as ethnicity, in written cases proves challenging. Additionally, creating these cases places a significant burden on teachers in terms of labour and time. Our objective is to explore the potential of artificial intelligence (AI)-assisted computer-generated clinical cases to expedite case creation and enhance diversity, along with AI-generated patient photographs for more lifelike portrayal. METHODS: In this study, we employed ChatGPT (OpenAI, GPT 3.5) to develop diverse and inclusive medical case vignettes. We evaluated various approaches and identified a set of eight consecutive prompts that can be readily customized to accommodate local contexts and specific assignments. To enhance visual representation, we utilized Adobe Firefly beta for image generation. RESULTS: Using the described prompts, we consistently generated cases for various assignments, producing sets of 30 cases at a time. We ensured the inclusion of mandatory checks and formatting, completing the process within approximately 60 min per set. CONCLUSIONS: Our approach significantly accelerated case creation and improved diversity, although prioritizing maximum diversity compromised representativeness to some extent. While the optimized prompts are easily reusable, the process itself demands computer skills not all educators possess. To address this, we aim to share all created patients as open educational resources, empowering educators to create cases independently.

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.

Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

A comparison of the clinical pharmacotherapy knowledge of medical and surgical residents and consultants.

PURPOSE: Knowledge of clinical pharmacotherapy is essential for all who prescribe medication. The aims of this study were to investigate differences in the pharmacotherapy and polypharmacy knowledge of medical and surgical residents and consultants and whether this knowledge can be improved by following an online course. METHODS: Design: A before-and-after-measurement. SETTING: An online course available for Dutch residents and consultants working in hospitals. STUDY POPULATION: Dutch residents and consultants from different disciplines who voluntarily followed an online course on geriatric care. INTERVENTION: An online 6-week course on geriatric care, with 1 week dedicated to clinical pharmacotherapy and polypharmacy. Variables, such as medical vs surgical specialty, consultant vs resident, age, and sex, that could predict the level of knowledge. The effects of the online course were studied using repeated measures ANOVA. The study was approved by the National Ethics Review Board of Medical Education (NERB dossier number 996). RESULTS: A total of 394 residents and 270 consultants, 220 from surgical and 444 from medical specialties, completed the online course in 2016 and 2017. Residents had higher test scores than consultants for pharmacotherapy (73% vs 70%, p < 0.02) and polypharmacy (75% vs 72%, p < 0.02). The learning effect did not differ. Medical residents/consultants had a better knowledge of pharmacotherapy (74% vs 68%, p < 0.001) and polypharmacy (77% vs 66%, p < 0.001) than surgical residents/consultants, but the learning effect was the same. CONCLUSIONS: Residents and consultants had a similar learning curve for acquiring knowledge, but residents outperformed consultants on all measures. In addition, surgical and medical residents/consultants had similar learning curves, but medical residents/consultants had higher test scores on all measures.

Factors influencing in-hospital prescribing errors: A systematic review.

AIM: In-hospital prescribing errors (PEs) may result in patient harm, prolonged hospitalization and hospital (re)admission. These events are associated with pressure on healthcare services and significant healthcare costs. To develop targeted interventions to prevent or reduce in-hospital PEs, identification and understanding of facilitating and protective factors influencing in-hospital PEs in current daily practice is necessary, adopting a Safety-II perspective. The aim of this systematic review was to create an overview of all factors reported in the literature, both protective and facilitating, as influencing in-hospital PEs. METHODS: PubMed, EMBASE.com and the Cochrane Library (via Wiley) were searched, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, for studies that identified factors influencing in-hospital PEs. Both qualitative and quantitative study designs were included. RESULTS: Overall, 19 articles (6 qualitative and 13 quantitative studies) were included and 40 unique factors influencing in-hospital PEs were identified. These factors were categorized into five domains according to the Eindhoven classification ('organization-related', 'prescriber-related', 'prescription-related', 'technology-related' and 'unclassified') and visualized in an Ishikawa (Fishbone) diagram. Most of the identified factors (87.5%; n = 40) facilitated in-hospital PEs. The most frequently identified facilitating factor (39.6%; n = 19) was 'insufficient (drug) knowledge, prescribing skills and/or experience of prescribers'. CONCLUSION: The findings of this review could be used to identify points of engagement for future intervention studies and help hospitals determine how to optimize prescribing. A multifaceted intervention, targeting multiple factors might help to circumvent the complex challenge of in-hospital PEs.

The Dutch list of essential drugs for undergraduate medical education: A modified Delphi study.

AIMS: Prescribing errors among junior doctors are common in clinical practice because many lack prescribing competence after graduation. This is in part due to inadequate education in clinical pharmacology and therapeutics (CP&T) in the undergraduate medical curriculum. To support CP&T education, it is important to determine which drugs medical undergraduates should be able to prescribe safely and effectively without direct supervision by the time they graduate. Currently, there is no such list with broad-based consensus. Therefore, the aim was to reach consensus on a list of essential drugs for undergraduate medical education in the Netherlands. METHODS: A two-round modified Delphi study was conducted among pharmacists, medical specialists, junior doctors and pharmacotherapy teachers from all eight Dutch academic hospitals. Participants were asked to indicate whether it was essential that medical graduates could prescribe specific drugs included on a preliminary list. Drugs for which ≥80% of all respondents agreed or strongly agreed were included in the final list. RESULTS: In all, 42 (65%) participants completed the two Delphi rounds. A total of 132 drugs (39%) from the preliminary list and two (3%) newly proposed drugs were included. CONCLUSIONS: This is the first Delphi consensus study to identify the drugs that Dutch junior doctors should be able to prescribe safely and effectively without direct supervision. This list can be used to harmonize and support the teaching and assessment of CP&T. Moreover, this study shows that a Delphi method is suitable to reach consensus on such a list, and could be used for a European list.

A Clinical Pharmacology and Therapeutics Teacher's Guide to Race-Based Medicine, Inclusivity, and Diversity.

The relationship between race and biology is complex. In contemporary medical science, race is a social construct that is measured via self-identification of study participants. But even though race has no biological essence, it is often used as variable in medical guidelines (e.g., treatment recommendations specific for Black people with hypertension). Such recommendations are based on clinical trials in which there was a significant correlation between self-identified race and actual, but often unmeasured, health-related factors such as (pharmaco)genetics, diet, sun exposure, etc. Many teachers are insufficiently aware of this complexity. In their classes, they (unintentionally) portray self-reported race as having a biological essence. This may cause students to see people of shared race as biologically or genetically homogeneous, and believe that race-based recommendations are true for all individuals (rather than reflecting the average of a heterogeneous group). This medicalizes race and reinforces already existing healthcare disparities. Moreover, students may fail to learn that the relation between race and health is easily biased by factors such as socioeconomic status, racism, ancestry, and environment and that this limits the generalizability of race-based recommendations. We observed that the clinical case vignettes that we use in our teaching contain many stereotypes and biases, and do not generally reflect the diversity of actual patients. This guide, written by clinical pharmacology and therapeutics teachers, aims to help our colleagues and teachers in other health professions to reflect on and improve our teaching on race-based medical guidelines and to make our clinical case vignettes more inclusive and diverse.

Improving Appropriate Prescribing For Geriatric Patients Using a Clinical Decision Support System.

Purpose: Polypharmacy is a known risk factor for potentially inappropriate prescribing. Recently there is an increasing interest in clinical decision support systems (CDSS) to improve prescribing. The objective of this study was to evaluate the impact of a CDSS, with the START-STOPP criteria as main content in the setting of a geriatric ward. Endpoints were 1) appropriateness of prescribing and 2) acceptance rate of recommendations. Methods: This prospective study comparing the use of a CDSS with usual care involved patients admitted to geriatric wards in two teaching hospitals in the Netherlands. Patients were included from January to May 2017. The medications of 64 patients in the first six weeks was assessed according to the current standard, whereas the medications of 61 patients in the second six weeks were also assessed by using a CDSS. Medication appropriateness was assessed with the Medication Appropriateness Index (MAI). Results: The medications of 125 patients (median age 83 years) were reviewed. In both the usual care group and the intervention group MAI scores decreased significantly from admission to discharge (within group analyses, p<0.001). This effect was significantly larger in the intervention group (p<0.05). MAI scores at discharge in the usual care group and the intervention group were respectively 9.95±6.70 and 7.26±5.07. The CDSS generated 193 recommendations, of which 71 concerned START criteria, 45 STOPP criteria, and 77 potential interactions. Overall, 31.6% of the recommendations were accepted. Conclusion: This study shows that a CDSS to improve prescribing has additional value in the setting of a geriatric ward. Almost one third of the software-generated recommendations were interpreted as clinically relevant and accepted, on average one per patient.

[Carbapenems: take it when needed but leave it if you can]. / Carbapenems: inzetten als het moet, vermijden als het kan.

Surveillance data and literature have shown a worldwide increase in infections with resistant bacteria, which has led to increased prescriptions of carbapenems, which in turn has led to increased carbapenem resistance. There is also an increasing use of carbapenems in the Netherlands, a county usually very conservative in antibiotic use. Carbapenem sparing strategies are essential in an attempt to prevent further rise of infections caused by carbapenem resistant bacteria. This article discusses carbapenem sparing strategies with old forgotten antibiotics and novel antibiotics from a Dutch perspective.

Teaching resources for the European Open Platform for Prescribing Education (EurOP2E)-a nominal group technique study.

The European Open Platform for Prescribing Education (EurOP2E) seeks to improve and harmonize European clinical pharmacology and therapeutics (CPT) education by facilitating international collaboration and sharing problem-based, online, open educational resources. The COVID-19 pandemic forced teachers to switch to virtual modalities, highlighting the need for high-quality online teaching materials. The goal of this study was to establish the online problem-based teaching resources needed to sustain prescribing education during the pandemic and thereafter. A nominal group technique study was conducted with prescribing teachers from 15 European countries. Results were analyzed through thematic analysis. In four meetings, 20 teachers from 15 countries proposed and ranked 35 teaching materials. According to the participants, the most necessary problem-based-online teaching materials related to three overarching themes. Related to learning outcomes for CPT, participants proposed creating prescription scenarios, including materials focusing on background knowledge and resources on personalized medicine and topical/ethical issues such as the prescription's impact on planetary health. Second, related to teaching, they proposed online case discussions, gamification and decision support systems. Finally, in relation to faculty development, they recommend teacher courses, a repository of reusable exam questions and harmonized formularies. Future work will aim to collaboratively produce such materials.

Neurofilament light increases over time in severe COVID-19 and is associated with delirium.

Neurological monitoring in sedated Intensive Care Unit patients is constrained by the lack of reliable blood-based biomarkers. Neurofilament light is a cross-disease biomarker for neuronal damage with potential clinical applicability for monitoring Intensive Care Unit patients. We studied the trajectory of neurofilament light over a month in Intensive Care Unit patients diagnosed with severe COVID-19 and explored its relation to clinical outcomes and pathophysiological predictors. Data were collected over a month in 31 Intensive Care Unit patients (166 plasma samples) diagnosed with severe COVID-19 at Amsterdam University Medical Centre, and in the first week after emergency department admission in 297 patients with COVID-19 (635 plasma samples) admitted to Massachusetts General hospital. We observed that Neurofilament light increased in a non-linear fashion in the first month of Intensive Care Unit admission and increases faster in the first week of Intensive Care Unit admission when compared with mild-moderate COVID-19 cases. We observed that baseline Neurofilament light did not predict mortality when corrected for age and renal function. Peak neurofilament light levels were associated with a longer duration of delirium after extubation in Intensive Care Unit patients. Disease severity, as measured by the sequential organ failure score, was associated to higher neurofilament light values, and tumour necrosis factor alpha levels at baseline were associated with higher levels of neurofilament light at baseline and a faster increase during admission. These data illustrate the dynamics of Neurofilament light in a critical care setting and show associations to delirium, disease severity and markers for inflammation. Our study contributes to determine the clinical utility and interpretation of neurofilament light levels in Intensive Care Unit patients.

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.

Estimation of glomerular filtration rate for drug dosing in patients with very high or low body mass index.

An accurate estimated glomerular filtration rate (eGFR) is essential in drug dosing. This study demonstrates the limitations of indexed (ml/min/1.73 m2 ) and de-indexed (ml/min) eGFR based drug dosing in patients with obesity or underweight. This systematic study aimed to determine the most appropriate approach to estimate the GFR for standardized eGFR based drug dosing in these patients. (Raw) data of 12 studies were selected to investigate the accuracy and bias of both the indexed and de-indexed estimations of the Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), and of the Cockcroft-Gault (CG) in patients with obesity or underweight. Accuracy was calculated as the proportion of eGFR values within 30% of the measured GFR (P30) using an inert tracer (e.g., iohexol, inulin, 51 Cr-EDTA, or iothalamate clearance). An accuracy of at least 80% was considered acceptable. GFR values estimated with the CG, MDRD, and CKD-EPI differ significantly within a patient with obesity or underweight regardless of whether it is indexed or de-indexed. All studies, with two exceptions, show that all three equations are inaccurate for patients with underweight or class II obesity (P30: 55%-94%). De-indexing eGFR improves not or modestly the accuracy, and mostly remains below the 80% (P30: 62%-100%). CG was highly inaccurate in obese and underweight patients (P30: 7%-82%). Although these results show that CG is obsolete, the accuracy of MDRD and CKD-EPI is low in patients with obesity or underweight and de-indexing is not the solution. Better education and more accurate methods for appropriate drug dosing (e.g., measured GFR with inert tracer, therapeutic drug monitoring, or 24-h creatinine clearance) are recommended.

Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial.

BACKGROUND: Early antibiotic discontinuation has been advocated in haematology patients with fever of unknown origin during chemotherapy-induced neutropenia, but its safety is unknown. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment. METHODS: This non-inferiority, open-label, multicentre, randomised trial was done in six hospitals in the Netherlands. Adult patients (≥18 years) who were treated with intensive chemotherapy or haematopoietic stem-cell transplantation (HSCT) for a haematological malignancy, and had fever of unknown origin during high-risk neutropenia (<0·5 × 109/L expected for ≥7 days) were eligible. After onset of fever, patients received either 500 mg intravenous imipenem-cilastatin four times a day or 1000 mg intravenous meropenem three times a day. Between 48 h and 72 h of treatment, participants were randomly assigned (1:1) by a computer-generated sequence to receive a short-term (72 h [60-84]; short treatment group) or extended (≥9 days until being afebrile for 5 days or neutrophil recovery; extended treatment group) carbapenem regimen. The composite primary endpoint was treatment failure, defined as recurrent fever or a carbapenem-sensitive infection between day 4 and day 9 and septic shock or respiratory failure or death from day 4 until neutrophil recovery. The study was designed to assess the non-inferiority of the short treatment compared with the extended treatment regimen, with a non-inferiority margin of 10%. The primary outcome was adjudicated by an independent outcome committee, who were masked to treatment allocation, and was analysed in the intention-to-treat and per-protocol populations. The trial is completed and registered with ClinicalTrials.gov, NCT02149329. FINDINGS: Between Dec 1, 2014, and July 1, 2019, 281 patients were included in the intention-to-treat analysis: 144 (51%) patients were assigned to the short treatment group and 137 (49%) to the extended treatment group. Median age was 59 years (IQR 52-65); 109 (39%) patients were women and 172 (61%) were men; 205 (73%) patients received HSCT. In the intention-to-treat analysis, 28 (19%) of 144 patients in the short treatment group versus 21 (15%) of 137 patients in the extended treatment group had treatment failure (adjusted risk difference [ARD] 4·0% [90% CI -1·7% to 9·7%]; p=0·25). In the per-protocol analysis (n=225), 24 (23%) of 104 patients in the short treatment group and 19 (16%) of 121 patients in the extended treatment group had treatment failure (ARD 7·3% [0·3% to 14·9%]; p=0·11). The most common grade 3-5 infection-related adverse events were mucositis (23 [20%] of 114 adverse events in the short treatment group vs 28 [29%] of 98 adverse events in the extended treatment group), fever of unknown origin (20 [18%] vs 16 [16%] events), and bacteraemia (15 [13%] vs 13 [13%] events). The number of serious adverse events were higher in the short treatment group (23 [16%] of 144 patients) than in the extended treatment group (14 [10%] of 137 patients), due to an increased rate of readmission (17 [12%] patients in the short treatment group vs ten [7%] in the extended treatment group). Death before 30 days after neutrophil recovery occurred in five (3%) participants in the short treatment group: two due to progressive leukaemia, two due to candidaemia, and one due to Enterococcus faecium bacteraemia and drug-induced pneumonitis. One (1%) patient died in the extended treatment group due to candidaemia. None of the deaths were related to carbapenem-sensitive infections. INTERPRETATION: Early discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. FUNDING: The Netherlands Organisation for Health Research and Development and Fonds NutsOhra.

An inter-professional student-run medication review programme. Reducing adverse drug reactions in a memory outpatient clinic: a controlled clinical trial.

BACKGROUND: We investigated if the addition of an inter-professional student-led medication review team (ISP-team) to standard care can increase the number of detected ADRs and reduce the number of ADRs 3 months after an outpatient visit. RESEARCH DESIGN AND METHODS: In this controlled clinical trial, patients were allocated to standard care (control group) or standard care plus the ISP team (intervention group). The ISP team consisted of medical and pharmacy students and student nurse practitioners. The team performed a structured medication review and adjusted medication to reduce the number of ADRs. Three months after the outpatient visit, a clinical pharmacologist who was blinded for allocation performed a follow-up telephone interview to determine whether patients experienced ADRs. RESULTS: During the outpatient clinic visit, significantly more (p < 0.001) ADRs were detected in the intervention group (n = 48) than in the control group (n = 10). In both groups, 60-63% of all detected ADRs were managed. Three months after the outpatient visit, significantly fewer (predominantly mild and moderately severe) ADRs related to benzodiazepine derivatives and antihypertensive causing dizziness were detected in the patients of the intervention group. CONCLUSIONS: An ISP team in addition to standard care increases the detection and management of ADRs in elderly patients resulting in fewer mild and moderately severe ADRs.

Prescribing errors in post - COVID-19 patients: prevalence, severity, and risk factors in patients visiting a post - COVID-19 outpatient clinic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has necessitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identified as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescribing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post-COVID-19 patients, hospitalized during the first wave of COVID-19 in the Netherlands, 3 months after discharge. METHODS: This prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3 months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs. RESULTS: Ninety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identified PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identified ICU admission (OR 6.08, 95% CI 2.16-17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34-21.5) as independent risk factors for PEs. CONCLUSIONS: PEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID-19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.