Association between critical care admission and chronic medication discontinuation post-hospital discharge: A retrospective cohort study.

Background: Discontinuation of important chronic medication after hospitalisation is common. This study aimed to investigate the association between critical care (vs non-critical care) admission and discontinuation of chronic medications post-hospital discharge, along with factors associated with discontinuation among critical care survivors. Methods: This was a retrospective cohort study in Lothian, Scotland of adults who were admitted to hospital between 01/01/2012 and 31/12/2019 and survived to hospital discharge. Medication classes investigated were statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs), beta-blockers, oral anticoagulants, and thyroid hormones. The risk of medication discontinuation for each class was estimated by odds ratios (OR), with 95% confidence intervals (95%CI), using multivariable logistic regression adjusted for patient demographics, main clinical condition, and index comorbidity. A secondary analysis assessed factors associated with discontinuation in critical care survivors. Results: There were 22,340 critical care and 367,185 non-critical care survivors included. Critical care admission had the highest association with ACEi/ARBs discontinuation (adjusted OR 2.41, 95%CI: 2.26-2.58), followed by oral anticoagulants (adjusted OR 1.33, 95%CI: 1.15-1.53), and beta blockers (adjusted OR 1.18, 95%CI: 1.07-1.29). There was no significant association with thyroid hormones or statin discontinuation. Among critical care survivors, hospital length of stay of 14 days or more was associated with increased discontinuation across all medication classes. Conclusion: Critical care admission was associated with discontinuation of three out of five medication classes studied (ACEi/ARBs, beta-blockers, and oral anticoagulants). Further research is needed to understand the reason for increased medication discontinuation in critical care survivors and how these risks can be mitigated to improve patient outcomes.

Qualitative Insights Into Patients' and Family Members' Experiences of In-Hospital Medication Management After a Critical Care Episode.

Background: Patient recovery after a critical illness can be protracted, requiring a care continuum that extends along a patient pathway from the critical care unit, hospital ward, and into the community care setting. High-quality care on patient transfer from critical care, including medication safety, is facilitated by education for patients and families, family engagement, support systems, and health care professional (HCP)-patient communication. Currently, uncertainty exists regarding how HCPs can and should engage with critical care patients and family members about their medication. Research Question: What are the views and experiences of critical care patients and family members about their involvement in, communication about, understanding of, and decision-making related to their medication after transfer from critical care to the hospital ward? Study Design and Methods: This qualitative study used semistructured interviews, conducted with critical care patients and family members after transfer from critical care to a hospital ward in a large National Health Service hospital trust. Anonymized transcripts of interviews were analyzed thematically using a coding framework developed from understandings of patient and family engagement in medication administration. Results: Twenty-seven participants (15 patients and 12 family members of patients) completed the interviews. We identified five themes and 15 subthemes, providing an overview of patients' and family members' views on medication management during acute illness and ongoing recovery. Themes identified were: impact of acute illness and treatment burden on preexisting illness, preexisting knowledge and capability, beliefs about persons roles and expectations, care continuity and individualized information exchange, and engagement in practice. Interpretation: This study demonstrated that critical care patients and family members want to engage with HCPs about medication administration. HCPs must take an individualized approach to communication and timing, acknowledging the dynamic interplay between patients and family members, using multimodal forms of communication.

Psychotropic prescribing after hospital discharge in survivors of critical illness, a retrospective cohort study (2012-2019).

Background: Many people survive critical illness with the burden of new or worsened mental health issues and sleep disturbances. We examined the frequency of psychotropic prescribing after critical illness, comparing critical care to non-critical care hospitalised survivors, and whether this varied in important subgroups. Methods: This retrospective cohort study included 23,340 critical care and 367,185 non-critical care hospitalised adults from 2012 through 2019 in Lothian, Scotland, who survived to discharge. Results: One-third of critical care survivors (32%; 7527/23,340) received a psychotropic prescription within 90 days after hospital discharge (25% antidepressants; 14% anxiolytics/hypnotics; 4% antipsychotics/mania medicines). In contrast, 15% (54,589/367,185) of non-critical care survivors received a psychotropic prescription (12% antidepressants; 5% anxiolytics/hypnotics; 2% antipsychotics/mania medicines). Among patients without psychotropic prescriptions within 180 days prior to hospitalisation, after hospital discharge, the critical care group had a higher incidence of psychotropic prescription (10.3%; 1610/15,609) compared with the non-critical care group (3.2%; 9743/307,429); unadjusted hazard ratio (HR) 3.39, 95% CI: 3.22-3.57. After adjustment for potential confounders, the risk remained elevated (adjusted HR 2.03, 95% CI: 1.91-2.16), persisted later in follow-up (90-365 days; adjusted HR 1.38, 95% CI: 1.30-1.46), and was more pronounced in those without recorded comorbidities (adjusted HR 3.49, 95% CI: 3.22-3.78). Conclusions: Critical care survivors have a higher risk of receiving psychotropic prescriptions than hospitalised patients, with a significant proportion receiving benzodiazepines and other hypnotics. Future research should focus on the requirement for and safety of psychotropic medicines in survivors of critical illness, to help guide policy for clinical practice.

Deciphering complexity in Pd-catalyzed cross-couplings.

Understanding complex reaction systems is critical in chemistry. While synthetic methods for selective formation of products are sought after, oftentimes it is the full reaction signature, i.e., complete profile of products/side-products, that informs mechanistic rationale and accelerates discovery chemistry. Here, we report a methodology using high-throughput experimentation and multivariate data analysis to examine the full signature of one of the most complicated chemical reactions catalyzed by palladium known in the chemical literature. A model Pd-catalyzed reaction was selected involving functionalization of 2-bromo-N-phenylbenzamide and multiple bond activation pathways. Principal component analysis, correspondence analysis and heatmaps with hierarchical clustering reveal the factors contributing to the variance in product distributions and show associations between solvents and reaction products. Using robust data from experiments performed with eight solvents, for four different reaction times at five different temperatures, we correlate side-products to a major dominant N-phenyl phenanthridinone product, and many other side products.

MOF-based heterogeneous catalysis in continuous flow via incorporation onto polymer-based spherical activated carbon supports.

We present an approach to harnessing the tuneable catalytic properties of complex nanomaterials for continuous flow heterogeneous catalysis by combining them with the scalable and industrially implementable properties of carbon pelleted supports. This approach, in turn, will enable these catalytic materials, which largely currently exist in forms unsuitable for this application (e.g. powders), to be fully integrated into large scale, chemical processes. A composite heterogeneous catalyst consisting of a metal-organic framework-based Lewis acid, MIL-100(Sc), immobilised onto polymer-based spherical activated carbon (PBSAC) support has been developed. The material was characterised by focused ion beam-scanning electron microscopy-energy dispersive X-ray analysis, powder X-ray diffraction, N2 adsorption, thermogravimetric analysis, atomic absorption spectroscopy, light scattering and crush testing with the catalytic activity studied in continuous flow. The mechanically robust spherical geometry makes the composite material ideal for application in packed-bed reactors. The catalyst was observed to operate without any loss in activity at steady state for 9 hours when utilised as a Lewis acid catalyst for the intramolecular cyclisation of (±)-citronellal as a model reaction. This work paves the way for further development into the exploitation of MOF-based continuous flow heterogeneous catalysis.

Amine-modified polyionic liquid supports enhance the efficacy of PdNPs for the catalytic hydrogenation of CO2 to formate.

Palladium nanoparticles stabilised by aniline modified polymer immobilised ionic liquid is a remarkably active catalyst for the hydrogenation of CO2 to formate; the initial TOF of 500 h-1 is markedly higher than either unmodified catalyst or its benzylamine and N,N-dimethylaniline modified counterparts and is among the highest to be reported for a PdNP-based catalyst.

Economic evaluations of adult critical care pharmacy services: a scoping review.

OBJECTIVES: To summarise the extent and type of evidence available regarding economic evaluations of adult critical care pharmacy services in the context of UK practice. METHODS: A literature search was conducted in eight electronic databases and hand searching of full-text reference lists. Of 2409 journal articles initially identified, 38 were included in the final review. Independent literature review was undertaken by two investigators in a two-step process against the inclusion and exclusion criteria; title and abstract screening were followed by full-text screening. Included studies were taken from high-income economy countries that contained economic data evaluating any key aspect of adult critical care pharmacy services. Grey literature and studies that could not be translated into the English language were excluded. RESULTS: The majority were before-and-after studies (18, 47%) or other observational studies (17, 45%), and conducted in North America (25, 66%). None of the included studies were undertaken in the UK. Seven studies (18%) included cost-benefit analysis; all demonstrated positive cost-benefit values for clinical pharmacist activities. CONCLUSIONS: Further high-quality primary research focussing on the economic evaluation of UK adult critical care pharmacy services is needed, before undertaking a future systematic review. There is an indication of a cost-benefit value for critical care pharmacist activities. The lack of UK-based economic evaluations is a limitation to further development and standardisation of critical care pharmacy services nationally.

Understanding medication safety involving patient transfer from intensive care to hospital ward: a qualitative sociotechnical factor study.

OBJECTIVE: To understand the sociotechnical factors affecting medication safety when intensive care patients are transferred to a hospital ward. Consideration of these medication safety factors would provide a theoretical basis, on which future interventions can be developed and evaluated to improve patient care. DESIGN: Qualitative study using semistructured interviews of intensive care and hospital ward-based healthcare professionals. Transcripts were anonymised prior to thematic analysis using the London Protocol and Systems Engineering in Patient Safety V.3.0 model frameworks. SETTING: Four north of England National Health Service hospitals. All hospitals used electronic prescribing in intensive care and hospital ward settings. PARTICIPANTS: Intensive care and hospital ward healthcare professionals (intensive care medical staff, advanced practitioners, pharmacists and outreach team members; ward-based medical staff and clinical pharmacists). RESULTS: Twenty-two healthcare professionals were interviewed. We identified 13 factors within five broad themes, describing the interactions that most strongly influenced the performance of the intensive care to hospital ward system interface. The themes were: Complexity of process performance and interactions; Time pressures and considerations; Communication processes and challenges; Technology and systems and Beliefs about consequences for the patient and organisation. CONCLUSIONS: The complexity of the interactions on the system performance and time dependency was clear. We make several recommendations for policy change and further research based on improving: availability of hospital-wide integrated and functional electronic prescribing systems, patient flow systems, sufficient multiprofessional critical care staffing, knowledge and skills of staff, team performance, communication and collaboration and patient and family engagement.

Analysis of Adsorbed Polyphosphate Changes on Milled Titanium Dioxide, Using Low-Field Relaxation NMR and Photoelectron Spectroscopy.

In this study, changes in the adsorbed amount and surface structure of sodium hexametaphosphate (SHMP) were investigated for aluminum-doped TiO2 pigment undergoing milling. Relaxation NMR was utilized as a potential at-line technique to monitor the effect of milling on surface area and surface chemistry, while XPS was used primarily to consider the dispersant structure. Results showed that considerable amounts of weakly adsorbed SHMP could be removed with washing, and the level of dispersant removal increased with time, highlighting destructive effects of sustained high-energy milling. Nonetheless, there were no significant chemical changes to the dispersant, although increases to the bridging oxygen (BO) peak full width at half-maximum (FWHM) suggested some chemical degradation was occurring with excess milling. Relaxation NMR revealed a number of important features. Results with unmilled material indicated that dispersant adsorption could be tracked with pseudo-isotherms using the relative enhancement rate (Rsp), where the Rsp decreased with dispersant coverage, owing to partial blocking of the quadrupolar surface aluminum. Milled samples were also tracked, with very accurate calibrations of surface area possible from either T1 or T2 relaxation data for systems without dispersant. Behavior was considerably more complicated with SHMP, as there appeared to be an interplay between the dispersant surface coverage and relaxation enhancement from the surface aluminum. Nevertheless, findings highlight that relaxation NMR could be used as a real-time technique to monitor the extent of milling processes, so long as appropriate industrial calibrations can be achieved.

Critical care pharmacy workforce: a 2020 re-evaluation of the UK deployment and characteristics.

INTRODUCTION: Critical care pharmacists improve the quality and efficiency of medication therapy whilst reducing treatment costs where they are available. UK critical care pharmacist deployment was described in 2015, highlighting a deficit in numbers, experience level, and critical care access to pharmacy services over the 7-day week. Since then, national workforce standards have been emphasised, quality indicators published, and service commissioning documents produced, reinforced by care quality assessments. Whether these initiatives have resulted in further development of the UK critical care pharmacy workforce is unknown. This evaluation provides a 2020 status update. METHODS: The 2015 electronic data entry tool was updated and circulated for completion by UK critical care pharmacists. The tool captured workforce data disposition as it was just prior to the COVID-19 pandemic, at critical care unit level. MAIN FINDINGS: Data were received for 334 critical care units from 203 organisations (96% of UK critical care units). Overall, 98.2% of UK critical care units had specific clinical pharmacist time dedicated to the unit. The median weekday pharmacist input to each level 3 equivalent bed was 0.066 (0.043-0.088) whole time equivalents, a significant increase from the median position in 2015 (+ 0.021, p < 0.0001). Despite this progress, pharmacist availability remains below national minimum standards (0.1/level 3 equivalent bed). Most units (71.9%) had access to prescribing pharmacists. Geographical variation in pharmacist staffing levels were evident, and weekend services remain extremely limited. CONCLUSIONS: Availability of clinical pharmacists in UK adult critical care units is improving. However, national standards are not routinely met despite widely publicised quality indicators, commissioning specifications, and assessments. Additional measures are needed to address persistent deficits and realise gains in organisational and patient-level outcomes. These measures must include promotion of cross-professional collaborative working, adjusted funding models, and a nationally recognised training pathway for critical care pharmacists.

Development and Experimental Validation of a Dispersity Model for In Silico RAFT Polymerization.

The exploitation of computational techniques to predict the outcome of chemical reactions is becoming commonplace, enabling a reduction in the number of physical experiments required to optimize a reaction. Here, we adapt and combine models for polymerization kinetics and molar mass dispersity as a function of conversion for reversible addition fragmentation chain transfer (RAFT) solution polymerization, including the introduction of a novel expression accounting for termination. A flow reactor operating under isothermal conditions was used to experimentally validate the models for the RAFT polymerization of dimethyl acrylamide with an additional term to accommodate the effect of residence time distribution. Further validation is conducted in a batch reactor, where a previously recorded in situ temperature monitoring provides the ability to model the system under more representative batch conditions, accounting for slow heat transfer and the observed exotherm. The model also shows agreement with several literature examples of the RAFT polymerization of acrylamide and acrylate monomers in batch reactors. In principle, the model not only provides a tool for polymer chemists to estimate ideal conditions for a polymerization, but it can also automatically define the initial parameter space for exploration by computationally controlled reactor platforms provided a reliable estimation of rate constants is available. The model is compiled into an easily accessible application to enable simulation of RAFT polymerization of several monomers.

Critical care pharmacist research activity, experience and interests: a 2021 United Kingdom survey.

BACKGROUND: Research and innovation are essential for effective healthcare service delivery, leading to improvements in patient health and wellbeing. National policy dictates that research delivery is embedded into daily practice of United Kingdom (UK) healthcare professionals, including pharmacists. There is a limited understanding of critical care pharmacist research activities, experiences and interests. It is, therefore, important to describe current practice including barriers and facilitators to enable increased engagement. OBJECTIVES: To describe UK critical care pharmacist research activity, experiences, interests and barriers to better engagement. METHOD: An electronic survey was developed, piloted and distributed (June to October 2021) to all critical care pharmacists via UK professional organisations. KEY FINDINGS: The survey was completed by 126 pharmacists, providing a 54% response rate. Few pharmacists reported research capability (postgraduate qualification with a research component, 31% (39/126)) and opportunity (dedicated research time, 28.6% (36/126)), only 12.7% (16/126) have both these influencers. Those that did, produced significantly more research outputs (median 4 (0,9) versus 0 (0,1), P = 0.023) and undertook grant funding applications (X2 (1, n = 126) = 25.8, P < 0.001), compared to those without. The most frequently reported barrier to research was the time (opportunity), (71.4%, 90/126). Few pharmacists reported having a research mentor (13.3%, 16/120). Most pharmacists reported an interest in collaborating on research projects across a broad range of areas. CONCLUSIONS: Critical care pharmacists are motivated to participate in the evaluation continuum including research, although most report capability and opportunity barriers to delivery. We suggest policy recommendations to address limitations and increase pharmacist research involvement.

A Brief Introduction to Chemical Reaction Optimization.

From the start of a synthetic chemist's training, experiments are conducted based on recipes from textbooks and manuscripts that achieve clean reaction outcomes, allowing the scientist to develop practical skills and some chemical intuition. This procedure is often kept long into a researcher's career, as new recipes are developed based on similar reaction protocols, and intuition-guided deviations are conducted through learning from failed experiments. However, when attempting to understand chemical systems of interest, it has been shown that model-based, algorithm-based, and miniaturized high-throughput techniques outperform human chemical intuition and achieve reaction optimization in a much more time- and material-efficient manner; this is covered in detail in this paper. As many synthetic chemists are not exposed to these techniques in undergraduate teaching, this leads to a disproportionate number of scientists that wish to optimize their reactions but are unable to use these methodologies or are simply unaware of their existence. This review highlights the basics, and the cutting-edge, of modern chemical reaction optimization as well as its relation to process scale-up and can thereby serve as a reference for inspired scientists for each of these techniques, detailing several of their respective applications.

Clinical frailty and polypharmacy in older emergency critical care patients: a single-centre retrospective case series.

BACKGROUND AND OBJECTIVES: Admission of complex and frail patients to critical care units is common. Little is known about the relationship between clinical frailty and polypharmacy measures in critical care patients or how a critical care admission affects polypharmacy.We sought to: (1) Describe the extent and relationship between clinical frailty and polypharmacy in a cohort of older emergency general critical care patients, and to (2) Describe the effect of the critical care pathway on patient polypharmacy measures. METHODS: A retrospective evaluation was undertaken in all patients ≥70 years of age, admitted as emergencies to the general critical care units of a single large UK academic hospital, over a 2-year period (March 2016 to February 2018) (n=762). Patient Clinical Frailty Scale (CFS) and polypharmacy measures on admission were described and association was tested. Medication changes and documentation on care transitions were analysed in a randomly selected convenience cohort of critical care survivors (n=77). RESULTS: On admission patients had a median of 9 (5;12) medicines, of which a median of 3 (2;5) were high-risk medicines. Polypharmacy (5-9 medicines) and hyperpolypharmacy (≥10 medicines) occurred in 80.7% (615/762) and 43.2% (329/762) of patients, respectively. A degree of frailty was the standard (median CFS 4 (3;5)) with 45.7% (348/762) CFS 4-5 and 20% (153/762) CFS ≥6. The patient median CFS increased by 1 with polypharmacy classification increments (p<0.001). In the survivor cohort, a median of 6 (4;8) and 5 (4;8) medication changes occurred on critical care and hospital discharges, respectively. A minority of patients had detailed medication continuity plans on care transitions. CONCLUSIONS: Polypharmacy and frailty were very common in this UK single-centre cohort of older emergency critical care patients. There was a significant association between the degree of polypharmacy and frailty score. The critical care pathway created extensive changes in patient medication therapy. Medication changes on care transitions often lacked detailed documentation.

Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis.

The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions. Our approach is applied to a Heck cyclization-deprotection reaction sequence, used in the synthesis of a precursor for 1-methyltetrahydroisoquinoline C5 functionalization. A simple method for multipoint sampling with a single online HPLC instrument was designed, enabling accurate quantification of each reaction, and an in-depth understanding of the reaction pathways. Notably, integration of Bayesian optimization techniques identified an 81 % overall yield in just 14 h, and revealed a favorable competing pathway for formation of the desired product.

Automated stopped-flow library synthesis for rapid optimisation and machine learning directed experimentation.

For the discovery of new candidate molecules in the pharmaceutical industry, library synthesis is a critical step, in which library size, diversity, and time to synthesise are fundamental. In this work we propose stopped-flow synthesis as an intermediate alternative to traditional batch and flow chemistry approaches, suited for small molecule pharmaceutical discovery. This method exploits the advantages of both techniques enabling automated experimentation with access to high pressures and temperatures; flexibility of reaction times, with minimal use of reagents (µmol scale per reaction). In this study, we integrate a stopped-flow reactor into a high-throughput continuous platform designed for the synthesis of combinatory libraries with at-line reaction analysis. This approach allowed ∼900 reactions to be conducted in an accelerated timeframe (192 hours). The stopped flow approach used ∼10% of the reactants and solvents compared to a fully continuous approach. This methodology demonstrates a significantly improved synthesis success rate of smaller libraries by simplifying the implementation of cross-reaction optimisation strategies. The experimental datasets were used to train a feed-forward neural network (FFNN) model providing a framework to guide further experiments, which showed good model predictability and success when tested against an external set with fewer experiments. As a result, this work demonstrates that combining experimental automation with machine learning strategies can deliver optimised analyses and enhanced predictions, enabling more efficient drug discovery investigations across the design, make, test and analysis (DMTA) cycle.

A Delphi consensus study to identify priorities for improving and measuring medication safety for intensive care patients on transfer to a hospital ward.

BACKGROUND: Intensive care patients surviving to transfer to a lower-acuity hospital ward experience ongoing challenges to their recovery and lack a well-defined and developed care pathway. The transfer process to a hospital ward exposes intensive care patients to high rates of medication errors, which increase their risk of adverse drug events. OBJECTIVE: The aims of this study were to identify priorities for medication-related intervention components and outcome measures for improving medication safety for intensive care patients transferring to a hospital ward. METHODS: Three panels involving 129 participants covering (i) intensive care, (ii) hospital ward health-care professionals and (iii) public representatives completed an electronic Delphi survey conducted over three phases. The Delphi process comprised three sections (medication-related intervention components, medication outcomes and patient outcomes). Items were graded in their level of importance, with predefined important criteria. Item agreement required consensus across all three panels. Intervention barriers and facilitators identified in participant comments were categorized according to a socio-technical systems approach to the patient journey and patient safety (Systems Engineering Initiative for Patient Safety 3.0 model). RESULTS: Of the 129 (84.5%) participants, 109 completed all three Delphi phases. Consensus was achieved for 48 intervention components, 13 medication outcome measures and 11 patient outcome measures. Phase 1 provided 158 comments comprising >200 individual barriers and facilitators to intervention delivery. Frequently cited facilitators included clearly specified roles and responsibilities (10.7% (organizational conditions)), patient and family as agents (8.8% (care team)), medicines-related information easily accessible (7.8% (tools and technologies)) and clear medication plan and communication (7.3% (tasks)). CONCLUSIONS: Our findings provide identification of priorities for medication-related intervention components to improve medication safety for intensive care patients transferring to a hospital ward. Prioritization is complemented by the identification and socio-technical categorization of barriers and facilitators to intervention delivery. The identified important medication and patient outcomes to measure will inform the design of a future patient medication safety intervention study.

Medication-related interventions to improve medication safety and patient outcomes on transition from adult intensive care settings: a systematic review and meta-analysis.

BACKGROUND: Patients recovering from an episode in an intensive care unit (ICU) frequently experience medication errors on transition to the hospital ward. Structured handover recommendations often underestimate the challenges and complexity of ICU patient transitions. For adult ICU patients transitioning to a hospital ward, it is currently unclear what interventions reduce the risks of medication errors.The aims were to examine the impact of medication-related interventions on medication and patient outcomes on transition from adult ICU settings and identify barriers and facilitators to implementation. METHODS: The systematic review protocol was preregistered on PROSPERO. Six electronic databases were searched until October 2020 for controlled and uncontrolled study designs that reported medication-related (ie, de-prescribing; medication errors) or patient-related outcomes (ie, mortality; length of stay). Risk of bias (RoB) assessment used V.2.0 and ROBINS-I Cochrane tools. Where feasible, random-effects meta-analysis was used for pooling the OR across studies. The quality of evidence was assessed by Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Seventeen studies were eligible, 15 (88%) were uncontrolled before-after studies. The intervention components included education of staff (n=8 studies), medication review (n=7), guidelines (n=6), electronic transfer/handover tool or letter (n=4) and medicines reconciliation (n=4). Overall, pooled analysis of all interventions reduced risk of inappropriate medication continuation at ICU discharge (OR=0.45 (95% CI 0.31 to 0.63), I2=55%, n=9) and hospital discharge (OR=0.39 (95% CI 0.2 to 0.76), I2=75%, n=9). Multicomponent interventions, based on education of staff and guidelines, demonstrated no significant difference in inappropriate medication continuation at the ICU discharge point (OR 0.5 (95% CI 0.22 to 1.11), I2=62%, n=4), but were very effective in increasing de-prescribing outcomes on hospital discharge (OR 0.26 (95% CI 0.13 to 0.55), I2=67%, n=6)). Facilitators to intervention delivery included ICU clinical pharmacist availability and participation in multiprofessional ward rounds, while barriers included increased workload associated with the discharge intervention process. CONCLUSIONS: Multicomponent interventions based on education of staff and guidelines were effective at achieving almost four times more de-prescribing of inappropriate medication by the time of patient hospital discharge. Based on the findings, practice and policy recommendations are made and guidance is provided on the need for, and design of theory informed interventions in this area, including the requirement for process and economic evaluations.