Variation in clinical practice guideline recommendations for medication use in pregnancy in Australia: A systematic review.

BACKGROUND: Medication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent. AIMS: This systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: We identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first-line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed. CONCLUSION: Multiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes.

The Australian evidence-based clinical practice guideline for attention deficit hyperactivity disorder.

OBJECTIVE: The objective of this article was to provide an overview of the development and recommendations from the Australian evidence-based clinical practice guideline for attention deficit hyperactivity disorder (ADHD). The guideline aims to promote accurate and timely identification and diagnosis, and optimal and consistent treatment of ADHD. METHODS: Development integrated the best available evidence with multidisciplinary clinical expertise and the preferences of those with lived experience, underpinned by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. The 23 guideline development group members included psychiatrists, paediatricians, general practitioners, psychologists, speech pathologists, occupational therapists, educators, Indigenous psychologists, and people with a lived experience; with two independent chairs and a methodologist. Where appropriate, evidence reviews from the National Institute for Health and Care Excellence (NICE) 2018 'Attention Deficit Hyperactivity Disorder: Diagnosis and Management' guideline were updated. Fifty prioritised clinical questions were addressed in 14 systematic reviews (new and updated from NICE 2018) and 28 narrative reviews. RESULTS: The 113 clinical recommendations apply to young children (5 years and under), children, adolescents and adults. They provide guidance for clinicians on identification, screening, diagnosis, multimodal treatment and support, including pharmacological and non-pharmacological interventions. The guideline and supporting information are available online: https://adhdguideline.aadpa.com.au/. CONCLUSIONS: The guideline was approved by the National Health and Medical Research Council (NHMRC) of Australia and relevant medical and allied health professional associations. It is anticipated that successful implementation and uptake of the guideline by organisations, health care providers and other professionals will increase delivery of evidence-based treatment and improve health outcomes for the more than 800,000 Australians with ADHD.

Impact of antibiotic allergy labels on patient outcomes in a tertiary paediatric hospital.

AIMS: Antibiotic allergies are reported in 5-15% of children. This study aimed to evaluate the impact of common ß-lactam antibiotic allergy labels (AALs) on hospital treatment, focusing on length of stay and appropriateness of antibiotic prescribing. METHODS: This was a retrospective cohort study over 21 months at the Royal Children's Hospital Melbourne, Australia. A subset of children with the most common ß-lactam allergies, and who required admission for intravenous antibiotics over a 12-month period, was analysed for appropriateness of prescribing. Non-allergic patients were matched to evaluate associations between AALs and hospital treatment. RESULTS: There were 98 912 children admitted over the study period, of whom 938 (1%) had at least one AAL on first admission. Of all encounters, 5145 (2.5%) were for children with AALs. The most common AALs were to amoxicillin and amoxicillin-clavulanic acid combinations (40.8%), cefalexin (14.4%) and trimethoprim-sulfamethoxazole (9.7%). For the subset, there were 66 admissions for children who required intravenous antibiotics. Documentation was adequate for 27% of AALs. Inappropriate prescribing occurred in almost half (47%). Hospital stay was longer for children with AALs (median 4.7 days; IQR 2.3-9.2) compared to non-allergic controls (median 3.9 days; IQR 1.9-6.8; P = .02). Children with AALs were more likely to receive restricted antibiotics (aOR 3.03; 95% CI, 1.45-6.30; P = .003). CONCLUSION: This is the first study to demonstrate high rates of inappropriate prescribing in children with AALs. Children with AALs were significantly more likely to receive restricted antibiotics and had a longer length of stay compared with non-allergic controls.

A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability.

AIMS: Severe behavioural problems (SBP) are a major contributor to morbidity in children with intellectual disability (ID). Medications used to treat SBP in ID are associated with a high risk of side effects. Cannabidiol has potential therapeutic effects in SBP. This pilot study aimed to investigate the feasibility of conducting a randomised placebo-controlled trial of cannabidiol to reduce SBP in children with ID. METHODS: This is a double-blind, placebo-controlled, two-armed, parallel-design, randomised controlled trial of cannabidiol in children aged 8-16 years with ID and SBP. Participants were randomised 1:1 to receive either 98% cannabidiol in oil (Tilray, Canada) or placebo orally for 8 weeks. The dose was up-titrated over 9 days to 20 mg/kg/day in two divided doses, with a maximum dose of 500 mg twice/day. The feasibility and acceptability of all study components were assessed. RESULTS: Eight children were randomised, and all completed the full study protocol. There were no serious adverse events or drop-outs. Protocol adherence for key study components was excellent: study visits 100%, medication adherence 100%, blood tests 92% and questionnaire completion 88%. Parents reported a high degree of acceptability with the study design. All parents reported they would recommend the study to other families with children with similar problems. There was an efficacy signal in favour of active drug. CONCLUSIONS: The findings suggest that the study protocol is feasible and acceptable to patients with ID and SBP and their families.

A nationwide parent survey of antibiotic use in Australian children.

BACKGROUND: Antimicrobial resistance is increasing globally, largely due to high rates of antibiotic use and misuse. Factors that influence frequent antibiotic use in children are poorly understood. OBJECTIVES: This study describes rates of antibiotic use in Australian children and investigates parental factors including knowledge, attitudes and behaviours that influence antibiotic use. METHODS: An online questionnaire relating to antibiotic use was administered as part of the Royal Children's Hospital National Child Health Poll to a randomly recruited nationwide sample of parents or guardians of children aged 0-17 years in Australia. Data on antibiotic use in children and parental knowledge of appropriate indications for antibiotics and behaviours were collected. Standard binary logistic regression was used to assess associations between parent demographics and behaviour with antibiotic administration. RESULTS: The survey was completed by 2157 parents (64% completion rate), of which 1131 (52%) reported having given oral antibiotics to one or more of their children in the preceding 12 months. Of the 3971 children represented overall, 1719 (43%) had received at least one course of antibiotics. The average number of courses per child was 0.86 overall and 1.96 courses per child among those with reported antibiotic use. Notably, 194/1131 (17%) parents reported giving antibiotics to their child without a prescription. Poor parental knowledge of antibiotic indications was associated with antibiotic use. CONCLUSIONS: Reducing excessive use of antibiotics in children is necessary in the global strategy for preventing antimicrobial resistance. This study identified areas for public health interventions to educate parents and increase regulation of access to antibiotics.

Protocol for a single patient therapy plan: A randomised, double-blind, placebo-controlled N-of-1 trial to assess the efficacy of cannabidiol in patients with intractable epilepsy.

AIM: This paper describes the use of the single patient therapy plan (SPTP). The SPTP has been designed to assess the efficacy at an individual level of a commercially available cannabinoid product, cannabidiol, in reducing seizure frequency in paediatric patients with intractable epilepsy. METHODS: The SPTP is a randomised, double-blind, placebo-controlled N-of-1 trial designed to assess the efficacy of treatment in a neurology outpatient setting. The primary objective of the SPTP is to assess the efficacy of cannabidiol in reducing seizure frequency in each patient with intractable epilepsy, with change in seizure frequency being the primary outcome of interest. The analysis adopts a Bayesian approach, which provides results in the form of posterior probabilities that various levels of benefit (based on the primary outcome measure, seizure frequency) have been achieved under active treatment compared to placebo, accompanied by decision rules that provide thresholds for deciding whether treatment has been successful in the individual patient. The SPTP arrangement is most accurately considered part of clinical practice rather than research, since it is aimed at making clinical treatment decisions for individual patients and is not testing a hypothesis or collecting aggregate data. Therefore, Human Research Ethics Committee approval was considered not to be required, although it is recommended that hospital Clinical Ethics Committees provide ethical oversight. CONCLUSION: These SPTP resources are made available so that they may inform clinical practice in the treatment of severe epilepsy or adapted for use in other conditions.

Vancomycin is commonly under-dosed in critically ill children and neonates.

AIMS: Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients. METHODS: We reviewed the medical records of all patients receiving intravenous vancomycin in a tertiary paediatric and neonatal intensive care unit over a 10-month period. Demographic, vancomycin dosing, TDM and drug-related adverse effects data were collected. RESULTS: In total, 115 children received 126 courses of vancomycin and had at least 1 TDM blood sample taken at steady state. In only 38/126 (30%) courses was the target concentration (10-20 mg/L) achieved at the initial steady state trough sample. Of the 88 courses that had initial trough concentrations outside the target range, the dose was adjusted in only 49 (56%). Overall, minimum doses of 30 mg/kg/day in neonates with a corrected gestational age of <35 weeks, and 50 mg/kg/day in older children, were required to achieve target vancomycin concentrations. Vancomycin-attributable nephrotoxicity occurred in 10/126 (8%) courses and there were no episodes of red man syndrome. CONCLUSION: In critically ill children, individualised dosing is needed. In the absence of Bayesian model-based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered.

Medication error trends and effects of person-related, environment-related and communication-related factors on medication errors in a paediatric hospital.

AIM: This study aimed to examine reported medication error trends in an Australian paediatric hospital over a 5-year period and to determine the effects of person-related, environment-related and communication-related factors on the severity of medication outcomes. In particular, the focus was on the influence of changes to a hospital site and structure on the severity of medication errors. METHODS: A retrospective clinical audit was undertaken over a 5-year period of paediatric medication errors submitted to an online voluntary reporting system of an Australian, tertiary, public teaching paediatric hospital. All medication errors submitted to the online system between 1 July 2010 and 30 June 2015 were included. RESULTS: A total of 3340 medication errors was reported, which corresponded to 0.56% medication errors per combined admissions and presentations or 5.73 medication errors per 1000 bed days. The most common patient outcomes related to errors requiring monitoring or an intervention to ensure no harm occurred (n = 1631, 48.8%). A new hospital site and structure had 0.354 reduced odds of producing medication errors causing possible or probable harm (95% confidence interval 0.298-0.421, P < 0.0001). Patient and family involvement had 1.270 increased odds of identifying medication errors associated with possible or probable harm compared with those causing no harm (95% confidence interval 1.028-1.568, P = 0.027). Interrupted time series analyses showed that moving to a new hospital site and structure was associated with a reduction in reported medication errors. CONCLUSION: Encouraging child and family involvement, facilitating hospital redesign and improving communication could help to reduce the harm associated with medication errors.

Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations.

AIMS: Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children. METHODS: Children admitted to the Royal Children's Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin-related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity. RESULTS: Seventy-six children received c-amB and 39 received l-amB. Standard drug administration (recommended dose and infusion time) occurred in 74% (56/76) of patients on c-amB and 85% (33/39) on l-amB. In these 89 children, infusion-related reactions were similar for both c-amB and l-amB (23% (13/56) vs. 9% (3/33); P = 0.15); none occurred in children aged <90 days. There was no difference in amphotericin-associated glomerulotoxicity (c-amB 14% (8/56) vs. l-amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c-amB 3.1 vs. l-amB 2.3 mmol kg-1  d-1 ; P = 0.29). Hepatotoxicity occurred more frequently with l-amB than c-amB (83% (24/29) vs. 56% (20/36); P = 0.032). CONCLUSIONS: When appropriately administered, l-amB was associated with more hepatotoxicity than c-amB, with no difference in infusion-related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.

Medication prescribed by Australian paediatricians: Psychotropics predominate.

AIM: The aims of this study were to examine: (i) medications prescribed by Australian general and community paediatricians, (ii) predictors of prescribing (child age, gender) and (iii) changes in medication prescription between 2008 and 2013. METHODS: Two patient-level practice national audits were conducted by the Australian Paediatric Research Network in 2008 and 2013. General and community paediatricians in outpatient clinics and private practices recorded demographic data, diagnoses and medications prescribed for all patients seen over a 2-week period. RESULTS: In 2008, 199 paediatricians submitted data on 8345 consultations, and in 2013, 180 paediatricians submitted data on 7102 consultations. The most frequently prescribed drug class was psychotropics, prescribed for 46.8% of patients with developmental-behavioural/mental health (DB/MH) diagnoses in 2008 and 49.8% in 2013 (P = 0.015). Within this class, in 2013, the stimulants were prescribed in 35.3% of DB/MH consultations, antidepressants in 7.8% and antipsychotics in 5.6%. The next most frequently prescribed drug classes were laxatives (4.6% of all consultations in 2013), asthma preventers (4.1%), melatonin (3.7%), asthma relievers (2.6%) and proton-pump inhibitors (2.2%), topical corticosteroids (1.8%) and antihistamines (1.4%). Medication prescription was predicted by patient age (P < 0.001, both audits) and male gender (P < 0.01, both audits) but not by measured prescriber variables. The rates of prescribing of psychotropics, melatonin, laxatives and enuresis medications increased between 2008 and 2013. CONCLUSIONS: Australian paediatricians prescribe mostly psychotropic medications, and the amount prescribed appears to be increasing. Paediatricians need good training and professional development in mental health diagnosis and management and the rational prescribing of psychotropic medications.

Medication communication between nurses and doctors for paediatric acute care: An ethnographic study.

AIMS AND OBJECTIVES: To examine how communication between nurses and doctors occurred for managing medications in inpatient paediatric settings. BACKGROUND: Communication between health professionals influences medication incidents' occurrence and safe care. DESIGN: An ethnographic study was undertaken. METHODS: Semi-structured interviews, observations and focus groups were conducted in three clinical areas of an Australian tertiary paediatric hospital. Data were transcribed verbatim and thematically analysed using the Medication Communication Model. RESULTS: The actual communication act revealed health professionals' commitment to effective medication management and the influence of professional identities on medication communication. Nurses and doctors were dedicated to providing safe, effective medication therapy for children, within their scope of practice and perceived role responsibilities. Most nurses and junior doctors used tentative language in their communication while senior doctors tended to use direct language. Irrespective of language style, nurses actively engaged with doctors to promote patients' needs. Yet, the medical hierarchical structure, staffing and attendant expectations influenced communication for medication management, causing frustration among nurses and doctors. Doctors' lack of verbal communication of documented changes to medication orders particularly troubled nurses. Nurses persisted in their efforts to acquire appropriate orders for safe medication administration to paediatric patients. CONCLUSIONS: Collaborative practice between nurses and doctors involved complex, symbiotic relationships. Their dedication to providing safe medication therapy to paediatric patients facilitated effective medication management. At times, shortcomings in interdisciplinary communication impacted on potential and actual medication incidents. RELEVANCE TO CLINICAL PRACTICE: Understanding of the complexities affecting medication communication between nurses and doctors helps to ensure interprofessional respect for each other's roles and inherent demands. Interdisciplinary education delivered in healthcare organisations would facilitate greater clarity in communication related to medications. Encouraging the use of concise, clear words in communication would help to promote improved understanding between parties, and accuracy and efficacy of medication management.

Voriconazole dosing and therapeutic drug monitoring in children: experience from a paediatric tertiary care centre.

OBJECTIVES: Therapeutic drug monitoring (TDM) of voriconazole is recommended to achieve trough concentrations of 1-5 mg/L. In children, this is challenging due to age-related variability in voriconazole pharmacokinetics. This study describes our experience with voriconazole, focusing on dosing regimens, dose adjustment and TDM. METHODS: We reviewed the medical records of immunocompromised children who received voriconazole from July 2009 to January 2015 and had TDM. Demographic, clinical and voriconazole dosing and monitoring data were collected. RESULTS: Fifty-five children received 62 courses of voriconazole and had TDM, with a total of 256 samples taken. Only 71.0% of courses (44/62) had TDM at the correct time, and at least one therapeutic level was achieved in only 52.3% (23/44) of these. Twenty-six courses had at least one sub-therapeutic level and in only 61.5% was the dose adjusted. Patients aged <6, 6-12 and >12 years required median intravenous doses of 8.8, 7.5 and 4.0 mg/kg twice daily, respectively (P < 0.001). With oral administration, patients aged 6-12 and >12 years required median doses of 4.7 and 4.3 mg/kg twice daily, respectively (P = 0.307). Levels within the target range were observed to fall below 1 mg/L in 36.4% of unchanged dosing regimens. Photosensitive skin reactions (20.0%) and hepatotoxicity (12.7%) were the most frequent adverse events and occurred in children with voriconazole levels <5 mg/L. CONCLUSIONS: There is significant intra- and inter-individual variability in voriconazole concentrations in children, particularly in children <6 years of age. This warrants repeated TDM throughout treatment. Standardized guidelines for TDM and dose adjustment are required in children.

Development of a population pharmacokinetic-pharmacodynamic model of a single bolus dose of unfractionated heparin in paediatric patients.

BACKGROUND: Unfractionated heparin (UFH) is the anticoagulant of choice in paediatric patients undergoing a variety of cardiac procedures. There are currently no population pharmacokinetic-pharmacodynamic (PKPD) models for UFH in paediatrics. OBJECTIVE: The aim of the present study was to develop and evaluate a PKPD model of UFH in paediatrics. METHODS: Data from 64 children who received 75-100 IU kg(-1) of UFH during cardiac angiography were analysed. Five blood samples were collected at baseline and at 15, 30, 45 and 120 min postdose. The UFH concentration was quantified using a protamine titration assay. The UFH effect was quantified using activated partial thromboplastin time (aPTT). A PKPD model was fitted using nonlinear mixed-effects modelling. Patient covariates such as gender, weight (WT) and fat-free mass (FFM) were tested. The final model was evaluated using the likelihood ratio test and visual predictive checks (VPCs). RESULTS: A one-compartment model with linear elimination provided the best fit for the dose-concentration data. FFM was a significant covariate on clearance. A linear model provided the best fit for the concentration-effect data using aPTT as a biomarker for effect. The models performed well using VPCs. However, when used to simulate UFH infusion (at a much lower dose), the model overpredicted target aPTT responses. CONCLUSIONS: A PKPD model to describe the time course of the UFH effect was developed in a paediatric population. FFM was shown to describe drug disposition well. However, when applied to smaller UFH infusion doses, the model overpredicted target aPTT responses. This unsuccessful extrapolation may be attributed to a possible nonlinear relationship for heparin PKPD.

High-resolution twin-ion metabolite extraction (HiTIME) mass spectrometry: nontargeted detection of unknown drug metabolites by isotope labeling, liquid chromatography mass spectrometry, and automated high-performance computing.

The metabolic fate of a compound can often determine the success of a new drug lead. Thus, significant effort is directed toward identifying the metabolites formed from a given molecule. Here, an automated and nontargeted procedure is introduced for detecting drug metabolites without authentic metabolite standards via the use of stable isotope labeling, liquid chromatography mass spectrometry (LC/MS), and high-performance computing. LC/MS of blood plasma extracts from rats that were administered a 1:1 mixture of acetaminophen (APAP) and (13)C6-APAP resulted in mass spectra that contained "twin" ions for drug metabolites that were not detected in control spectra (i.e., no APAP administered). Because of the development of a program (high-resolution twin-ion metabolite extraction; HiTIME) that can identify twin-ions in high-resolution mass spectra without centroiding (i.e., reduction of mass spectral peaks to single data points), 9 doublets corresponding to APAP metabolites were identified. This is nearly twice that obtained by use of existing programs that make use of centroiding to reduce computational cost under these conditions with a quadrupole time-of-flight mass spectrometer. By a manual search for all reported APAP metabolite ions, no additional twin-ion signals were assigned. These data indicate that all the major metabolites of APAP and multiple low-abundance metabolites (e.g., acetaminophen hydroxy- and methoxysulfate) that are rarely reported were detected. This methodology can be used to detect drug metabolites without prior knowledge of their identity. HiTIME is freely available from https://github.com/bjpop/HiTIME .

Anti-infective use in children and pregnancy: current deficiencies and future challenges.

There are a number of challenges to using anti-infective agents in children and pregnant women. There is limited understanding of the altered pharmacokinetics of anti-infectives in these populations and as a result, optimized dosing regimens are yet to be established. The potential adverse effects of the drug on pregnancy outcome and the developing foetus is a major consideration, and the long term implications of drug side effects must be taken into account when drug exposure occurs early in life. These factors hinder research and licensing of new anti-infective drugs in these populations. We describe the current deficiencies and future challenges of anti-infective use in children and pregnant women, providing specific examples.

Pristinamycin: old drug, new tricks?

Osteoarticular infections with Gram positive bacteria present an increasing challenge in an era of multidrug-resistant organisms. Prolonged intravenous antibiotic treatment is often required, with associated risks, costs and difficulties with administration; a safe, effective oral option would be ideal for this indication. Pristinamycin, an oral streptogramin antibiotic with bactericidal activity against Gram positive organisms including methicillin-resistant Staphylococcus aureus, has been used for over 50 years in Europe for the treatment of osteoarticular infections. We review the published evidence for the treatment of native bone and prosthesis-related osteoarticular infections with pristinamycin.

Interventions to reduce medication errors in pediatric intensive care.

OBJECTIVE: To systematically examine the research literature to identify which interventions reduce medication errors in pediatric intensive care units. DATA SOURCES: Databases were searched from inception to April 2014. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they involved the conduct of an intervention with the intent of reducing medication errors. DATA SYNTHESIS: In all, 34 relevant articles were identified. Apart from 1 study, all involved single-arm, before-and-after designs without a comparative, concurrent control group. A total of 6 types of interventions were utilized: computerized physician order entry (CPOE), intravenous systems (ISs), modes of education (MEs), protocols and guidelines (PGs), pharmacist involvement (PI), and support systems for clinical decision making (SSCDs). Statistically significant reductions in medication errors were achieved in 7/8 studies for CPOE, 2/5 studies for ISs, 9/11 studies for MEs, 1/2 studies for PGs, 2/3 studies for PI, and 3/5 studies for SSCDs. The test for subgroup differences showed that there was no statistically significant difference among the 6 subgroups of interventions, χ(2)(5) = 1.88, P = 0.87. The following risk ratio results for meta-analysis were obtained: CPOE: 0.47 (95% CI = 0.28, 0.79); IS: 0.37 (95% CI = 0.19, 0.73); ME: 0.36 (95% CI = 0.22, 0.58); PG: 0.82 (95% CI = 0.21, 3.25); PI: 0.39 (95% CI = 0.10, 1.51), and SSCD: 0.49 (95% CI = 0.23, 1.03). CONCLUSIONS: Available evidence suggests some aspects of CPOE with decision support, ME, and IS may help in reducing medication errors. Good quality, prospective, observational studies are needed for institutions to determine the most effective interventions.