BACKGROUND: Polypharmacy is common among individuals with multimorbidity, often leading to inappropriate medication use and is associated with an increased risk of frailty, hospitalisation and mortality. Structured medication reviews (SMRs) have emerged as a promising method for optimising medication use. However, research examining their efficacy is limited. This review aims to evaluate the impact of SMRs on improving outcomes for adults with multimorbidity and polypharmacy in primary care settings. Additionally, this review seeks to identify prevailing patterns and trends in the mode of delivery of SMRs.
METHODS: A systematic review will be conducted using Ovid MEDLINE, Ovid EMBASE, Web of Science and CINAHL (1997-present). Primary outcomes will include medication-related measures such as dose, frequency and dosage form. Secondary outcomes under investigation will include physical, mental, functional and health service outcomes, as reported. Two independent reviewers will conduct the screening and data extraction, resolving disagreements through discussion. Once eligible studies are identified, the extracted data will be summarised in tabular format. The risk of bias in the articles will be assessed using either the Cochrane Risk of Bias 2 tool or the Newcastle-Ottawa scale, depending on the design of the studies retrieved. Subgroup analysis will be performed using demographic variables and modes of delivery where the data supports. If appropriate, a meta-analysis of the data extracted will be conducted to determine the impact of the SMRs on reported outcomes. If a meta-analysis is not possible due to heterogeneity, a narrative synthesis approach will be adopted.
BACKGROUND: This proposed review is exempt from ethical approval as it aims to collate and summarise peer-reviewed, published evidence. This protocol and the subsequent review will be disseminated in peer-reviewed journals, conferences and patient-led lay summaries.
UNASSIGNED: CRD42023454965.

BACKGROUND: Deprescribing (medication dose reduction or cessation) is an integral component of appropriate prescribing. The extent to which deprescribing recommendations are included in clinical practice guidelines is unclear. This scoping review aimed to identify guidelines that contain deprescribing recommendations, qualitatively explore the content and format of deprescribing recommendations and estimate the proportion of guidelines that contain deprescribing recommendations.
METHODS: Bibliographic databases and Google were searched for guidelines published in English from January 2012 to November 2022. Guideline registries were searched from January 2017 to February 2023. Two reviewers independently screened records from databases and Google for guidelines containing one or more deprescribing recommendations. A 10% sample of the guideline registries was screened to identify eligible guidelines and estimate the proportion of guidelines containing a deprescribing recommendation. Guideline and recommendation characteristics were extracted and language features of deprescribing recommendations including content, form, complexity and readability were examined using a conventional content analysis and the SHeLL Health Literacy Editor tool.
RESULTS: 80 guidelines containing 316 deprescribing recommendations were included. Deprescribing recommendations had substantial variability in their format and terminology. Most guidelines contained recommendations regarding for who (75%, n=60), what (99%, n=89) and when or why (91%, n=73) to deprescribe, however, fewer guidelines (58%, n=46) contained detailed guidance on how to deprescribe. Approximately 29% of guidelines identified from the registries sample (n=14/49) contained one or more deprescribing recommendations.
CONCLUSIONS: Deprescribing recommendations are increasingly being incorporated into guidelines, however, many guidelines do not contain clear and actionable recommendations on how to deprescribe which may limit effective implementation in clinical practice. A co-designed template or best practice guide, containing information on aspects of deprescribing recommendations that are essential or preferred by end-users should be developed and employed.
BACKGROUND: osf.io/fbex4.

OBJECTIVE: Pharmacovigilance databases play a critical role in monitoring drug safety. The duplication of reports in pharmacovigilance databases, however, undermines their data integrity. This scoping review sought to provide a comprehensive understanding of duplication in pharmacovigilance databases worldwide.
METHODS: A scoping review.
METHODS: Reviewers comprehensively searched the literature in PubMed, Web of Science, Wiley Online Library, EBSCOhost, Google Scholar and other relevant websites.
METHODS: Peer-reviewed publications and grey literature, without language restriction, describing duplication and/or methods relevant to duplication in pharmacovigilance databases from inception to 1 September 2023.
METHODS: We used the Joanna Briggs Institute guidelines for scoping reviews and conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Two reviewers independently screened titles, abstracts and full texts. One reviewer extracted the data and performed descriptive analysis, which the second reviewer assessed. Disagreements were resolved by discussion and consensus or in consultation with a third reviewer.
RESULTS: We screened 22 745 unique titles and 156 were eligible for full-text review. Of the 156 titles, 58 (47 peer-reviewed; 11 grey literature) fulfilled the inclusion criteria for the scoping review. Included titles addressed the extent (5 papers), prevention strategies (15 papers), causes (32 papers), detection methods (25 papers), management strategies (24 papers) and implications (14 papers) of duplication in pharmacovigilance databases. The papers overlapped, discussing more than one field. Advances in artificial intelligence, particularly natural language processing, hold promise in enhancing the efficiency and precision of deduplication of large and complex pharmacovigilance databases.
CONCLUSIONS: Duplication in pharmacovigilance databases compromises risk assessment and decision-making, potentially threatening patient safety. Therefore, efficient duplicate prevention, detection and management are essential for more reliable pharmacovigilance data. To minimise duplication, consistent use of worldwide unique identifiers as the key case identifiers is recommended alongside recent advances in artificial intelligence.

OBJECTIVE: We conducted an updated systematic review and meta-analysis to investigate the effect of colchicine treatment on clinical outcomes in patients with COVID-19.
METHODS: Systematic review and meta-analysis.
METHODS: We searched PubMed, Embase, the Cochrane Library, medRxiv and ClinicalTrials.gov from inception to January 2023.
METHODS: All randomised controlled trials (RCTs) that investigated the efficacy of colchicine treatment in patients with COVID-19 as compared with placebo or standard of care were included. There were no language restrictions. Studies that used colchicine prophylactically were excluded.
METHODS: We extracted all information relating to the study characteristics, such as author names, location, study population, details of intervention and comparator groups, and our outcomes of interest. We conducted our meta-analysis by using RevMan V.5.4 with risk ratio (RR) and mean difference as the effect measures.
RESULTS: We included 23 RCTs (28 249 participants) in this systematic review. Colchicine did not decrease the risk of mortality (RR 0.99; 95% CI 0.93 to 1.05; I2=0%; 20 RCTs, 25 824 participants), with the results being consistent among both hospitalised and non-hospitalised patients. There were no significant differences between the colchicine and control groups in other relevant clinical outcomes, including the incidence of mechanical ventilation (RR 0.75; 95% CI 0.48 to 1.18; p=0.22; I2=40%; 8 RCTs, 13 262 participants), intensive care unit admission (RR 0.77; 95% CI 0.49 to 1.22; p=0.27; I2=0%; 6 RCTs, 961 participants) and hospital admission (RR 0.74; 95% CI 0.48 to 1.16; p=0.19; I2=70%; 3 RCTs, 8572 participants).
CONCLUSIONS: The results of this meta-analysis do not support the use of colchicine as a treatment for reducing the risk of mortality or improving other relevant clinical outcomes in patients with COVID-19. However, RCTs investigating early treatment with colchicine (within 5 days of symptom onset or in patients with early-stage disease) are needed to fully elucidate the potential benefits of colchicine in this patient population.
UNASSIGNED: CRD42022369850.

The landscape of medical treatments is undergoing a transformative shift. Precision medicine has ushered in a revolutionary era in healthcare by individualizing diagnostics and treatments according to each patient\'s uniquely evolving health status. This groundbreaking method of tailoring disease prevention and treatment considers individual variations in genes, environments, and lifestyles. The goal of precision medicine is to target the \"five rights\": the right patient, the right drug, the right time, the right dose, and the right route. In this pursuit, in silico techniques have emerged as an anchor, driving precision medicine forward and making this a realistic and promising avenue for personalized therapies. With the advancements in high-throughput DNA sequencing technologies, genomic data, including genetic variants and their interactions with each other and the environment, can be incorporated into clinical decision-making. Pharmacometrics, gathering pharmacokinetic (PK) and pharmacodynamic (PD) data, and mathematical models further contribute to drug optimization, drug behavior prediction, and drug-drug interaction identification. Digital health, wearables, and computational tools offer continuous monitoring and real-time data collection, enabling treatment adjustments. Furthermore, the incorporation of extensive datasets in computational tools, such as electronic health records (EHRs) and omics data, is also another pathway to acquire meaningful information in this field. Although they are fairly new, machine learning (ML) algorithms and artificial intelligence (AI) techniques are also resources researchers use to analyze big data and develop predictive models. This review explores the interplay of these multiple in silico approaches in advancing precision medicine and fostering individual healthcare. Despite intrinsic challenges, such as ethical considerations, data protection, and the need for more comprehensive research, this marks a new era of patient-centered healthcare. Innovative in silico techniques hold the potential to reshape the future of medicine for generations to come.

BACKGROUND: Pharmacists provide a spectrum of services and comprehensive medication management for patients with substance use disorders (SUDs) with many providing timely and increased access to care for patients. Prior studies have evaluated other healthcare professionals\' attitudes, knowledge and practice in regard to SUD treatment and harm reduction services. However, no reviews to date summarise the available literature on the attitudes, knowledge and practice in regard to SUD treatment and harm reduction services from the pharmacist perspective. This scoping review aims to systematically map the extent, range and nature of available evidence and identify and describe gaps in knowledge, practice and attitudes towards SUD treatment among pharmacists with the goal of providing information for meaningful integration of pharmacists into SUD care.
METHODS: We will use the framework proposed by Arksey and O\'Malley (2005) updated with recommendations by Levac et al (2010) and the Joanna Briggs Institute (2020). The protocol is registered via Open Science Framework (https://osf.io/92dek). We will search for peer-reviewed literature containing empirical evidence investigating SUD treatment or harm reduction with outcomes pertaining to the knowledge, practice or attitudes of pharmacists. Findings will be guided and assessed by research objectives and summarised using descriptive statistics and thematically for quantitative and qualitative findings, respectively. This review will be conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews.
BACKGROUND: Our findings will provide crucial information and support for future interventions and programmes which aim to meaningfully integrate pharmacists into SUD care. We will disseminate findings at conferences and publish in a peer-reviewed journal. In addition, we will integrate feedback on search strategy, data extraction and our dissemination approach from multidisciplinary collaborators including those within our team\'s institution and outside experts with clinical or administrative knowledge in SUD care.

BACKGROUND: Up to 15% of adult patients in the clinical setting report to be allergic to penicillin. However, in most cases, penicillin allergy is not confirmed. Due to the negative aspects associated with erroneous penicillin allergy, the implementation of active delabelling processes for penicillin allergy is an important part of antibiotic stewardship programmes. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabelling interventions and summarises components and structures that facilitate, support or constrain structured penicillin allergy delabelling.
METHODS: This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases MEDLINE (via PubMed), EMBASE and Cochrane Library were searched for studies reporting on any intervention to identify, assess or rule out uncertain penicillin allergy. To improve completeness, two further databases are also searched for grey literature. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting and associated regulatory factors will be extracted and analysed. In addition, exclusion criteria for participation in the delabelling intervention and criteria for not delabelling penicillin allergy will be summarised. In case of failed protocols, these are highlighted and quantitatively analysed if possible. Two independent reviewers will perform the screening process and data extraction. Discordant decisions will be resolved through review by a third reviewer. Bias assessment of the individual studies will be performed using the Newcastle Ottawa Scale.
BACKGROUND: Because individual patient-related data are not analysed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient\'s experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies.
METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers.
RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number.
CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias.
BACKGROUND: OSF - https://osf.io/7kea3.

BACKGROUND: Dexmedetomidine is a promising pharmaceutical strategy to minimise opioid use during surgery. Despite its growing use, it is uncertain whether dexmedetomidine can improve patient-centred outcomes such as quality of recovery and pain.
METHODS: We will conduct a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL approximately in October 2023. We will include randomised controlled trials evaluating the impact of systemic intraoperative dexmedetomidine on patient-centred outcomes. Patient-centred outcome definition will be based on the consensus definition established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC). Our primary outcome will be the quality of recovery after surgery. Our secondary outcomes will be patient well-being, function, health-related quality of life, life impact, multidimensional assessment of postoperative acute pain, chronic pain, persistent postoperative opioid use, opioid-related adverse events, hospital length of stay and adverse events. Two reviewers will independently screen and identify trials and extract data. We will evaluate the risk of bias of trials using the Cochrane Risk of Bias Tool (RoB 2.0). We will synthesise data using a random effects Bayesian model framework, estimating the probability of achieving a benefit and its clinical significance. We will assess statistical heterogeneity with the tau-squared and explore sources of heterogeneity with meta-regression. We have involved patient partners, clinicians, methodologists, and key partner organisations in the development of this protocol, and we plan to continue this collaboration throughout all phases of this systematic review.
BACKGROUND: Our systematic review does not require research ethics approval. It will help inform current clinical practice guidelines and guide development of future randomised controlled trials. The results will be disseminated in open-access peer-reviewed journals, presented at conferences and shared among collaborators and networks.
UNASSIGNED: CRD42023439896.

We sought to better understand the utility and role of animal models of infection for Food and Drug Administration (FDA)-approved antibiotics for the indications of community-, hospital-acquired-, and ventilator-associated bacterial pneumonia (CABP, HABP, VABP), complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), and acute bacterial skin and structural infections (ABSSSIs). We reviewed relevant documents from new drug applications (NDA) of FDA-approved antibiotics from 2014-2019 for the above indications. Murine neutropenic thigh infection models supported the choice of a pharmacokinetic-pharmacodynamic (PKPD) target in 11/12 NDAs reviewed. PKPD targets associated with at least a 1-log bacterial decrease were commonly considered ideal (10/12 NDAs) to support breakpoints. Plasma PK, as opposed to organ specific PK, was generally considered most reliable for PKPD correlation. Breakpoint determination was multi-disciplinary, accounting at minimum for epidemiologic cutoffs, non-clinical PKPD, clinical exposure-response and clinical efficacy. Non-clinical PKPD targets in combination with probability of target attainment (PTA) analyses generated breakpoints that were consistent with epidemiologic cutoffs and clinically derived breakpoints. In 6/12 NDAs, there was limited data to support clinically derived breakpoints, and hence the non-clinical PKPD targets in combination with PTA analyses played a heightened role in the final breakpoint determination. Sponsor and FDA breakpoint decisions were in general agreement. Disagreement may have arisen from differences in the definition of the optimal PKPD index or the ability to extrapolate protein binding from animals to humans. Overall, murine neutropenic thigh infection models supported the reviewed NDAs by providing evidence of pre-clinical efficacy and PKPD target determination, and played, in combination with PTA analysis, a significant role in breakpoint determination for labeling purposes.