Evaluating automated machine learning platforms for use in healthcare.

Objective: To describe development and application of a checklist of criteria for selecting an automated machine learning (Auto ML) platform for use in creating clinical ML models. Materials and Methods: Evaluation criteria for selecting an Auto ML platform suited to ML needs of a local health district were developed in 3 steps: (1) identification of key requirements, (2) a market scan, and (3) an assessment process with desired outcomes. Results: The final checklist comprising 21 functional and 6 non-functional criteria was applied to vendor submissions in selecting a platform for creating a ML heparin dosing model as a use case. Discussion: A team of clinicians, data scientists, and key stakeholders developed a checklist which can be adapted to ML needs of healthcare organizations, the use case providing a relevant example. Conclusion: An evaluative checklist was developed for selecting Auto ML platforms which requires validation in larger multi-site studies.

Measuring the impact of pharmaceutical care bundle delivery on patient outcomes: an observational study.

BACKGROUND: Clinical pharmacists perform activities to optimise medicines use and prevent patient harm. Historically, clinical pharmacy quality indicators have measured individual activities not linked to patient outcomes. AIM: To determine the proportion of patients who receive a pharmaceutical care bundle (PCB) (consisting of a medication history, medication review, discharge medication list and medicines information on the discharge summary) as well as investigate the relationship between delivery of this PCB and patient outcomes. METHOD: Pharmaceutical care bundle activities were defined within state-wide (Queensland, Australia) clinical information systems and datasets were linked. An observational study using routinely recorded data was performed at ten participating sites for adult patients who had a non-same day hospital stay. The association between extent of PCB delivery and three patient outcomes were investigated: length of stay (LOS), unplanned readmission, and mortality. RESULTS: In total 283,813 patient hospital stays were evaluated. The delivery of the PCB occurred in 26.9% of patients at the ten participating hospital sites, ranging from 0.6 to 61.2% across sites. Patients with a longer LOS were more likely to receive delivery of the complete PCB (P < 0.001). There was no correlation between PCB and hospital standardised mortality ratio (r = 0.03, p = 0.93). Higher rates of delivery of the PCB were associated with lower rates of unplanned readmission within 30 days (r = - 0.993, p < 0.001). CONCLUSION: A complete PCB was delivered to 26.9% of patients and was associated with a significantly lower rate of unplanned readmission within 30 days.

Overcoming clozapine's adverse events: a narrative review of systematic reviews and meta-analyses.

INTRODUCTION: Clozapine is the gold standard treatment for treatment-resistant schizophrenia, however adverse events remain a clinical challenge. AREAS COVERED: This review presents a narrative synthesis of systematic reviews and meta-analyses that have reported the onset, incidence, prevalence, and management of clozapine's adverse events. We conducted a systematic literature search using PubMed, Embase, PsycINFO, OvidMEDLINE, CINAHL, and the Cochrane Database of Systematic Reviews from inception to April 2024. EXPERT OPINION: Effective management of clozapine's adverse events necessitates multi-faceted, individualized, and shared-decision strategies. Despite a lack of high-quality systematic evidence, expert inter-disciplinary solutions are provided to help address a critical need for clinical guidance. This 35-year update offers an evidence-based framework to assist clinicians, patients, and caregivers navigate the adverse events associated with clozapine therapy.

Clozapine is an important medication for people with schizophrenia who do not respond to other treatments. It has been used for over 30 years and provides relief from symptoms and improves quality of life. However, it has side effects that can be daunting for both healthcare workers and people taking clozapine. This article summarizes the latest research on clozapine's side effects into an easy-to-use guide to help understand the side effects better. With the right knowledge and a team approach involving healthcare workers, patients, their families and carers, the risks of clozapine's side effects can be managed. Proactive and careful monitoring for side effects, education on what to do if they occur, open conversations, and regular health checkups can significantly reduce the risk that side effects become a problem.

Prevalence of risk factors for venous thromboembolism and aspirin resistance in Australian patients undergoing total hip and knee arthroplasty.

INTRODUCTION: Aspirin is used for venous thromboembolism (VTE) prophylaxis after total hip and knee arthroplasty (THA/TKA). However, its efficacy is unclear in patients with multiple VTE risk factors and at risk of aspirin resistance (AR). BACKGROUND AND AIMS: To determine the prevalence of risk factors for VTE and AR in patients after THA/TKA and to determine the relationship between risk factors and drugs prescribed for thromboprophylaxis. METHODS: A retrospective cohort study of elective-THA/TKA in six Australian hospitals over a 1-year period. Medical records were manually reviewed to determine demographics, thromboprophylaxis regimen and presence of risk factors. The relationship between individual and cumulative risk factors with the thromboprophylaxis regimen was determined. RESULTS: In total, 1011 patients were included with a mean (SD) age of 65.9 (±11.0) years, and 56.4% were female. The five most prevalent risk factors were obesity (59.1%), age ≥65 years (58.2%), hypertension (45.3%), dyslipidaemia (35.9%) and diabetes (19.7%). Most patients had ≥1 risk factor for VTE (93.6%) and AR (93.6%), with 49.0% and 35.0% having ≥3 concurrent VTE and AR risk factors, respectively. The only significant relationship between risk factors and drugs was diabetes (P < 0.01). Rivaroxaban was more commonly used as the number of concurrent VTE risk factors increased (P < 0.05). CONCLUSION: Patients had a high prevalence of VTE and AR risk factors, suggesting aspirin may not be beneficial in many patients. Only diabetes was linked to the selection of thromboprophylaxis. Patients who received rivaroxaban had a greater average number of VTE risk factors. Guidelines should promote individualised prescribing in higher-risk patients.

The adverse inpatient medication event and frailty (AIME-frail) risk prediction model.

BACKGROUND: Medication harm affects between 5 and 15% of hospitalised patients, with approximately half of the harm events considered preventable through timely intervention. The Adverse Inpatient Medication Event (AIME) risk prediction model was previously developed to guide a systematic approach to patient prioritisation for targeted clinician review, but frailty was not tested as a candidate predictor variable. AIM: To evaluate the predictive performance of an updated AIME model, incorporating a measure of frailty, when applied to a new multisite cohort of hospitalised adult inpatients. METHODS: A retrospective cohort study was conducted at two tertiary Australian hospitals on patients discharged between 1st January and April 31, 2020. Data were extracted from electronic medical records (EMRs) and clinical coding databases. Medication harm was identified using ICD-10 Y-codes and confirmed by senior pharmacist review of medical records. The Hospital Frailty Risk Score (HFRS) was calculated for each patient. Logistic regression analysis was used to construct a modified AIME model. Candidate variables of the original AIME model, together with new variables including HFRS were tested. Performance of the final model was reported using area under the curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 4089 patient admissions were included, with a mean age ± standard deviation (SD) of 64 years (±19 years), 2050 patients (50%) were males, and mean HFRS was 6.2 (±5.9). 184 patients (4.5%) experienced one or more medication harm events during hospitalisation. The new AIME-Frail risk model incorporated 5 of the original variables: length of stay (LOS), anti-psychotics, antiarrhythmics, immunosuppressants, and INR greater than 3, as well as 5 new variables: HFRS, anticoagulants, antibiotics, insulin, and opioid use. The AUC was 0.79 (95% CI: 0.76-0.83) which was superior to the original model (AUC = 0.70, 95% CI: 0.65-0.74) with a sensitivity of 69%, specificity of 81%, positive predictive value of 0.14 (95% CI: 0.10-0.17) and negative predictive value of 0.98 (95% CI: 0.97-0.99). The DCA identified the model as having potential clinical utility between the probability thresholds of 0.05-0.4. CONCLUSION: The inclusion of a frailty measure improved the predictive performance of the AIME model. Screening inpatients using the AIME-Frail tool could identify more patients at high-risk of medication harm who warrant timely clinician review.

Unplanned Rehospitalisation due to Medication Harm following an Acute Myocardial Infarction.

INTRODUCTION: The contribution of medication harm to rehospitalisation and adverse patient outcomes after an acute myocardial infarction (AMI) needs exploration. Rehospitalisation is costly to both patients and the healthcare facility. Following an AMI, patients are at risk of medication harm as they are often older and have multiple comorbidities and polypharmacy. This study aimed to quantify and evaluate medication harm causing unplanned rehospitalisation after an AMI. METHODS: This was a retrospective cohort study of patients discharged from a quaternary hospital post-AMI. All rehospitalisations within 18 months were identified using medical record review and coding data. The primary outcome measure was medication harm rehospitalisation. Preventability, causality, and severity assessments of medication harm were conducted. RESULTS: A total of 1,564 patients experienced an AMI, and 415 (26.5%) were rehospitalised. Eighty-nine patients (5.7% of total population; 6.0% of those discharged) experienced a total of 101 medication harm events. Those with medication harm were older (p = 0.007) and had higher rates of heart failure (p = 0.005), chronic kidney disease (p = 0.046), chronic obstructive pulmonary disease (p = 0.037), and a prior history of ischaemic heart disease (p = 0.005). Gastrointestinal bleeding, acute kidney injury, and hypotension were the most common medication harm events. Forty percent of events were avoidable, and 84% were classed as "serious." Furosemide, antiplatelets, and angiotensin-converting enzyme inhibitors were the most commonly implicated medications. The median time to medication harm rehospitalisation was 79 days (interquartile range: 16-200 days). CONCLUSION: Medication harm causes unplanned rehospitalisation in 5.7% of all AMI patients (1 in 17 patients; 6.0% of those discharged). The majority of harm was serious and occurred within the first 200 days of discharge. This study highlights that measures to attenuate the risk of medication harm rehospitalisation are essential, including post-discharge medication management.

Defining quality indicators, pharmaceutical care bundles and outcomes of clinical pharmacy service delivery using a Delphi consensus approach.

BACKGROUND: Clinical pharmacy quality indicators are often non-uniform and measure individual activities not linked to outcomes. AIM: To define a consensus agreed pharmaceutical care bundle and patient outcome measures across an entire state health service. METHOD: A four-round modified-Delphi approach with state Directors of Pharmacy was performed (n = 25). They were asked to rate on a 5-point Likert scale the relevance and measurability of 32 inpatient clinical pharmacy quality indicators and outcome measures. They also ranked clinical pharmacy activities in order from perceived most to least beneficial. Based upon these results, pharmaceutical care bundles consisting of multiple clinical pharmacy activities were formed, and relevance and measurability assessed. RESULTS: Response rate ranged from 40 to 60%. Twenty-six individual clinical pharmacy quality indicators reached consensus. The top ranked clinical pharmacy quality indicator was 'proportion of patients where a pharmacist documents an accurate list of medicines during admission'. There were nine pharmaceutical care bundles formed consisting between 3 and 7 activities. Only one pharmaceutical care bundle reached consensus: medication history, adverse drug reaction/allergy documentation, admission and discharge medication reconciliation, medication review, provision of medicines education and provision of a medication list on discharge. Sixteen outcome measures reached consensus. The top ranked were hospital acquired complications, readmission due to medication misadventure and unplanned readmission within 10 days. CONCLUSION: Consensus has been reached on one pharmaceutical care bundle and sixteen outcomes to monitor clinical pharmacy service delivery. The next step is to measure the extent of pharmaceutical care bundle delivery and the link to patient outcomes.

Advanced-scope pharmacist roles in medical outpatient clinics: a cost-consequence analysis.

BACKGROUND: There is a growing body of evidence that supports the clinical effectiveness of pharmacist roles in outpatient settings. However, limited studies have investigated the economic efficiency of advanced-scope outpatient pharmacist roles, particularly in the Australian setting. Assessing the overall costs and benefits of these outpatient pharmacist roles is needed to ensure service sustainability. AIMS: To use a cost-consequence approach to evaluate the advanced-scope outpatient pharmacist roles across multiple clinic disciplines from the hospital perspective. METHODS: A cost-consequence analysis was undertaken using data from a previous clinical-effectiveness study. All outpatient pharmacist consults conducted from 1 June 2019 to 31 May 2020 across 18 clinic disciplines were evaluated. Consequences from the pharmacist services included number of consults conducted, number of medication-related activities and number of resolved recommendations. RESULTS: The overall cost to the hospital for the outpatient pharmacist service across all clinics was AU$1 991 122, with a potential remuneration of AU$3 895 247. There were 10 059 pharmacist consults undertaken for the 12-month period. Medication-related activities performed by pharmacists primarily included 6438 counselling and education activities and 4307 medication list activities. When the specialist pharmacist roles were added to the outpatient clinics, several health service benefits were also realised. CONCLUSIONS: The addition of pharmacist roles to outpatient clinics can increase the cost of services; however, they also can increase medication optimisation activities. Future research should examine a societal perspective that includes broader cost and effectiveness outcomes. This study could justify the implementation of advanced-scope outpatient pharmacist roles in other Australian hospitals.

Impact of pharmacists during in-hospital resuscitation or medical emergency response events: A systematic review.

BACKGROUND: We sought to determine the impact of the presence of a pharmacist on medication and patient related outcomes during the emergency management of critically ill patients requiring resuscitation or medical emergency response team care in a hospital setting. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of databases from January 1995 to April 2023 was conducted to identify studies of contemporary pharmacist practice. Results were extracted and analysed for included studies, those evaluating the impact of the presence of a pharmacist on medication and patient related outcomes during the emergency management of critically ill hospitalised patients requiring resuscitation or medical emergency response team care. To determine risk of bias, the Newcastle-Ottowa Quality Assessment scale was used for non-randomised studies and the Revised Cochrane risk-of-bias tool for randomised trials. RESULTS: Of 1345 studies identified, 54 were selected for full text review, and 30 were included in the final analysis. There were 29 cohort studies and one randomised controlled trial. The studies reported the impact of a pharmacist for a variety of patient presentations. The study team assigned each study to one of eight patient cohorts: acute stroke, cardiac arrest, rapid response calls, S-T segment elevation myocardial infarction, acute haemorrhage, major trauma resuscitation, sepsis and status epilepticus. The most frequently reported outcome, associated with a statistically significant benefit in 23 studies, was time to medication administration. Few studies reported a significant difference in patient outcome measures such as mortality. Only 8 of the 30 studies were assessed to have a low risk of bias. CONCLUSIONS: The results of this systematic review provide support for a beneficial impact of a pharmacist presence and intervention during resuscitation or medical emergency response team care, with significant improvements in outcomes such as time to initiation of time-critical medications, medication appropriateness and guideline compliance. However, studies were predominantly small and retrospective and were not powered to detect differences in patient related measures such as length of stay and mortality. Future research should investigate the clinical impacts of the pharmacist in ED resuscitation settings in controlled, prospective studies with robust sampling methods.

The impact of hospital-based post-discharge pharmacist medication review on patient clinical outcomes: A systematic review.

Background: Clinical pharmacists have been shown to identify and resolve medication related problems post-discharge, however the impact on patient clinical outcomes is unclear. Aims: To undertake a systematic review to identify, critically appraise and present the evidence on post-discharge hospital clinics that provide clinical pharmacist medication review; report the patient clinical outcomes measured; and describe the activities of the clinical pharmacist. Methods: Published studies evaluating a patient clinical outcome following a post-discharge hospital clinic pharmacy service were included. All studies needed a comparative design (intervention vs control or comparator). Pubmed, Embase, CINAHL, PsycnINFO, Web of Science, IPA and APAIS-Health databases were searched to identify studies. The type of clinic and the clinical pharmacist activities were linked to patient clinical outcomes. Results: Fifty-seven studies were included in the final analysis, 14 randomised controlled trials and 43 non-randomised studies. Three key clinic types were identified: post-discharge pharmacist review alone, inpatient care plus post-discharge review and post-discharge collaborative clinics. The three main outcome metrics identified were hospital readmission and/or representation, adverse events and improved disease state metrics. There was often a mix of these outcomes reported as primary and secondary outcomes. High heterogeneity of interventions and clinical pharmacist activities reported meant it was difficult to link clinical pharmacist activities with the outcomes reported. Conclusions: A post-discharge clinic pharmacist may improve patient clinical outcomes such as hospital readmission and representation rates. Future research needs to provide a clearer description of the clinical pharmacist activities provided in both arms of comparative studies.

Experiences and learnings of pharmacists, students, and clinical assistants working collaboratively in a COVID-19 vaccination clinic: a qualitative study.

Background: The involvement of pharmacists and pharmacy clinical assistants (CAs) in hospital clinics has demonstrated benefits for improving medication safety and care delivery. Internationally, pharmacy staff played a crucial role in the safe storage, provision and administration of vaccines, as well as reinforcement of pharmacovigilance efforts during the COVID-19 pandemic. In Australia, healthcare providers collaborated to rapidly facilitate a phased COVID-19 vaccination program. The perspectives of the pharmacy team, including pharmacy students, involved in implementing novel health services are underexplored in the literature. Objective: To describe the key learnings in how a team of pharmacists, CAs and pharmacy students contributed to the COVID-19 vaccine service, and to explore their preparedness and experiences working at a vaccination clinic within a quaternary hospital. Method: This study involved semi-structured interviews with pharmacy students, CAs and pharmacists. All pharmacy staff who worked in the clinic were invited to participate in the study and a snowball strategy was used to maximise recruitment. The interviews were audio-recorded, transcribed, and analysed using inductive thematic techniques to identify major themes. Results: A total of 11 participants were interviewed including: four pharmacists, four CAs and three undergraduate students. Using thematic analysis, five main themes were identified: (1) Potential for student value and experiential learning; (2) Adaptive procedures and work practices in a rapidly changing environment; (3) Clear leadership, with role clarity, role expansion and interchangeability; (4) Supportive learning environment and (5) Stakeholder drivers for service delivery and to optimise societal benefit. These five themes often interacted with each other, highlighting the complexities of implementing and operating the service. Conclusions: The vaccine clinic service provided a novel and valuable opportunity for students, CAs, and pharmacists to work collaboratively, extending their scope of practice to contribute to better national health outcomes. Participants expressed their support for future initiatives involving pharmacy students and healthcare staff collaborating in hospital settings.

Pharmacists reducing medication risk in medical outpatient clinics: a retrospective study of 18 clinics.

BACKGROUND: The role of pharmacists in hospital inpatient settings is well recognised; however, pharmacists are relatively new to outpatient clinic settings in Australia. Evidence to justify the clinical effectiveness of pharmacists, in terms of identifying and resolving medication-related problems in an outpatient setting in Australia is limited. AIMS: To investigate the clinical effectiveness of outpatient clinic pharmacists across multiple medical disciplines. METHODS: A retrospective observational study was conducted by auditing medical records for patients who had an outpatient clinic pharmacist consult between June 2019 and February 2020 in a large quaternary hospital. All pharmacist recommendations targeting a medication-related problem were audited. Recommendations were considered 'resolved' if accepted and actioned by the patient and/or a clinician. The resolved recommendations were risk rated using a validated tool for medication-related patient harm. RESULTS: There were 18 clinic pharmacist roles across multiple medical disciplines, of which 46 pharmacists conducted outpatient consults. A total of 7599 consults was conducted and a purposeful random sample of 572 (8%) consults was audited for 552 unique patients. There were 399 recommendations recorded in the notes by clinic pharmacists, a mean (standard deviation) of 0.95 (0.97) per patient. Of these, 328 (82%) were resolved; 269 (82%) were classified as low or moderate risk and 59 (18%) were classified as high-risk recommendations. CONCLUSIONS: Clinic pharmacists in multidisciplinary outpatient clinics are effective at identifying and resolving medication-related problems. Our research demonstrated that 18% of these resolved recommendations prevented a high-risk medication-related harm event.

Obesity and the Risk of Venous Thromboembolism after Major Lower Limb Orthopaedic Surgery: A Literature Review.

The risk of venous thromboembolism following total joint arthroplasty is significantly greater than those of other types of elective orthopaedic procedures. This risk is increased in obesity due to the associated prothrombotic physiological and hematological changes that predispose to embolic events. The prevalence of obesity is increasing in the aging population, which contributes to a further increase in the risk of postoperative thrombosis in the older patients. There is a lack of clear evidence regarding dosing information for thromboprophylaxis medications in patients with obesity. As a result, the currently available thromboprophylaxis guidelines do not provide specific recommendations for this group. Suboptimal dosing regimens for these medications can place these patients at a risk of bleeding or clotting complications postsurgery. Hence any increase in dosage may require intensive surveillance for the residual anticoagulant effects and careful balancing of risks and benefits on an individual basis. Our review discusses the basis for increased thrombotic risk in obesity, the evidence supporting dosage recommendations, and the implications of the current guidelines for pharmacological thromboprophylaxis in patients with obesity undergoing lower limb arthroplasty.

Predicting Therapeutic Response to Unfractionated Heparin Therapy: Machine Learning Approach.

BACKGROUND: Unfractionated heparin (UFH) is an anticoagulant drug that is considered a high-risk medication because an excessive dose can cause bleeding, whereas an insufficient dose can lead to a recurrent embolic event. Therapeutic response to the initiation of intravenous UFH is monitored using activated partial thromboplastin time (aPTT) as a measure of blood clotting time. Clinicians iteratively adjust the dose of UFH toward a target, indication-defined therapeutic aPTT range using nomograms, but this process can be imprecise and can take ≥36 hours to achieve the target range. Thus, a more efficient approach is required. OBJECTIVE: In this study, we aimed to develop and validate a machine learning (ML) algorithm to predict aPTT within 12 hours after a specified bolus and maintenance dose of UFH. METHODS: This was a retrospective cohort study of 3019 patient episodes of care from January 2017 to August 2020 using data collected from electronic health records of 5 hospitals in Queensland, Australia. Data from 4 hospitals were used to build and test ensemble models using cross-validation, whereas data from the fifth hospital were used for external validation. We built 2 ML models: a regression model to predict the aPTT value after a UFH bolus dose and a multiclass model to predict the aPTT, classified as subtherapeutic (aPTT <70 seconds), therapeutic (aPTT 70-100 seconds), or supratherapeutic (aPTT >100 seconds). Modeling was performed using Driverless AI (H2O), an automated ML tool, and 17 different experiments were iteratively conducted to optimize model accuracy. RESULTS: In predicting aPTT, the best performing model was an ensemble with 4x LightGBM models with a root mean square error of 31.35 (SD 1.37). In predicting the aPTT class using a repurposed data set, the best performing ensemble model achieved an accuracy of 0.599 (SD 0.0289) and an area under the receiver operating characteristic curve of 0.735. External validation yielded similar results: root mean square error of 30.52 (SD 1.29) for the aPTT prediction model, and accuracy of 0.568 (SD 0.0315) and area under the receiver operating characteristic curve of 0.724 for the aPTT multiclassification model. CONCLUSIONS: To the best of our knowledge, this is the first ML model applied to intravenous UFH dosing that has been developed and externally validated in a multisite adult general medical and surgical inpatient setting. We present the processes of data collection, preparation, and feature engineering for replication.

The Effect of Digitization on the Safe Management of Anticoagulants.

BACKGROUND: Anticoagulants are high-risk medications and are a common cause of adverse events of hospitalized inpatients. The incidence of adverse events involving anticoagulants has remained relatively unchanged over the past two decades, suggesting that novel approaches are required to address this persistent issue. Electronic medication management systems (eMMSs) offer strategies to help reduce medication incidents and adverse drug events, yet poor system design can introduce new error types. OBJECTIVE: Our objective was to evaluate the effect of the introduction of an electronic medical record (EMR) on the quality and safety of therapeutic anticoagulation management. METHODS: A retrospective, observational pre-/poststudy was conducted, analyzing real-world data across five hospital sites in a single health service. Four metrics were compared 1-year pre- and 1-year post-EMR implementation. They included clinician-reported medication incidents, toxic pathology results, hospital-acquired bleeding complications (HACs), and rate of heparin-induced thrombocytopenia. Further subanalyses of patients experiencing HACs in the post-EMR period identified key opportunities for intervention to maximize safety and quality of anticoagulation within an eMMS. RESULTS: A significant reduction in HACs was observed in the post-EMR implementation period (mean [standard deviation [SD]] =12.1 [4.4]/month vs. mean [SD] = 7.8 [3.5]/month; p = 0.01). The categorization of potential EMR design enhancements found that new automated clinical decision support or improved pathology result integration would be suitable to mitigate future HACs in an eMMS. There was no significant difference in the mean monthly clinician-reported incident rates for anticoagulants or the rate of toxic pathology results in the pre- versus post-EMR implementation period. A 62.5% reduction in the cases of heparin-induced thrombocytopenia was observed in the post-EMR implementation period. CONCLUSION: The implementation of an EMR improves clinical care outcomes for patients receiving anticoagulation. System design plays a significant role in mitigating the risks associated with anticoagulants and consideration must be given to optimizing eMMSs.

Treatment strategies for clozapine-induced hypotension: a systematic review.

Background: Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant. Objectives: Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers. Design: We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence. Data Sources and Methods: PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention. Results: We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril® combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use. Conclusion: Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided. Registration: PROSPERO (Registration No. CRD42020191530).

Scoping Review of Studies Evaluating Frailty and Its Association with Medication Harm.

INTRODUCTION: Frailty is associated with an increased risk of death and morbid events. Frail individuals are known to have multiple comorbidities which are often associated with polypharmacy. Whilst a relationship between polypharmacy and frailty has been demonstrated, it is not clear if there is an independent relationship between frailty and medication harm. AIMS: This scoping review aimed to identify and critically appraise studies evaluating medication harm in patients with frailty. METHODS: PubMed, EMBASE, CINAHL and Cochrane databases were searched from inception until 1 February 2021 using key search terms that are synonymous with frailty (such as frail and frail elderly) and medication harm (such as adverse drug events and adverse drug reactions). To be included, studies must have identified medication harm as a primary or secondary outcome measure, and used a frailty assessment tool to determine frailty, or clearly defined how frailty was assessed. Data were narratively synthesised and presented in tables. The checklist from the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Heart, Lung, and Blood Institute was used to assess the quality and risk of bias of studies that met the inclusion criteria. RESULTS: Of 2685 retrieved abstracts, 24 underwent full-text review and nine studies met the inclusion criteria. Three studies were retrospective cohort studies, and six were prospective observational studies. Six studies comprised two distinct groups of frail and non-frail individuals, and the remaining three studies evaluated medication harm in an entirely frail population. Seven studies used validated frailty tools such as the Clinical Frailty Scale, Fried Frailty Index, and Fried Frailty Phenotype. Two studies measured frailty using self-defined criteria. Overall, frail individuals were at risk of medication harm with rates ranging between 18.7 and 77% across the nine studies. However, whether frailty is an independent predictor of medication harm remains uncertain, as this was only evaluated in one study. The risk of bias assessment identified limitations in methods and reporting with all nine studies. CONCLUSION: This scoping review identified nine studies evaluating medication harm in frail patients. However, all were limited by the methodological quality and inadequate reporting of study factors. There are few high-quality studies that described a relationship between medication harm and frailty. More robust studies are required that examine the independent relationship between frailty and medication harm, after adjusting for all possible confounders and in particular polypharmacy.

Benefits, challenges and contributors to the introduction of new hospital-based outpatient clinic pharmacist positions.

Background: Pharmacists working within interprofessional teams in the outpatient setting are well placed to address medication-related problems before and after hospital admission. Therefore, exploration of these roles is warranted. Objectives: To explore pharmacists' and other health professionals' perspectives of the impact of pharmacists working within interprofessional teams in outpatient clinics. Furthermore, we endeavoured to identify both the challenges and contributors to success with the introduction of pharmacists into these settings. Methods: This qualitative study involved semi-structured interviews with both hospital outpatient clinic pharmacists and other clinic health professionals to gain an in-depth understanding of how the introduction of pharmacists into clinics impacted clinic processes, patient care, and relationships with other health professionals. Participants were recruited from the outpatient clinics who had recently added a pharmacist to their service. Participants involved in setting up the roles were invited to participate in a voluntary interview, the transcripts from which were analysed into themes and sub-themes using an inductive and deductive approach. Results: A total of 34 staff were interviewed of which 68% were female and 74% were aged between 31 and 50 years. The cohort included 16 outpatient pharmacists, nine pharmacist team leaders, five clinic nurses and four clinic doctors (specialist consultant or registrar). Three overall themes were identified: the benefits, the contributors, and the challenges of introducing clinical pharmacy services to outpatient clinics. When establishing a clinic role, pharmacists' awareness, adaptability, and strong communication were shown to be key traits to building rapport and trustworthiness with the established clinic team. Conclusions: When pharmacists are integrated into multidisciplinary outpatient clinics they and their colleagues believe that they provide benefits to the patients and the clinics. Decision makers need to be cognizant of factors that contribute to, as well as those that impede, the successful implementation of outpatient pharmacist roles.