A systematic review and pooled prevalence of burnout in pharmacists.

BACKGROUND: Burnout is an occupational phenomenon caused by ineffectively managed work-related stress. Burnout is common among healthcare professionals and has the capacity to compromise patient care, but is not well characterised in pharmacists. AIM: This systematic review aimed to establish the prevalence of burnout among pharmacists, and its associated risk factors. METHOD: A systematic search of Embase, PubMed, CINAHL and PsychInfo was carried out. Studies were included using the following eligibility criteria; original research investigating burnout prevalence in pharmacists in patient-facing roles in any jurisdiction, using any validated burnout measurement instrument. No language or date barriers were set. Data were extracted by the first author and accuracy checked by co-authors. A pooled prevalence was estimated, and narrative synthesis provided. RESULTS: Burnout prevalence data were extracted from 19 articles involving 11,306 pharmacist participants across eight countries. More than half (51%) of pharmacists were experiencing burnout. Associated risk factors included longer working hours, less professional experience, high patient and prescription volumes, excessive workload and poor work/life balance. The COVID-19 pandemic has negatively impacted pharmacist burnout and resilience. Involvement in education and training and access to burnout management resources were associated with lower rates of burnout, but burnout intervention effectiveness is unknown. CONCLUSION: Burnout remains high among pharmacists and may negatively affect the quality of patient care. There is significant heterogeneity pertaining to the definition and assessment of burnout and there remains a need to identify and evaluate effective individual and organisational burnout interventions.

A systematic review of interventions to enhance adherence and persistence with ADHD pharmacotherapy.

Although high rates of poor adherence/persistence have been documented in ADHD, there is limited research targeting the problem. This systematic review evaluated interventions to address poor adherence/persistence to ADHD pharmacotherapy, with the aim of guiding the development of future interventions. An extensive search was conducted from January 1980 until January 2021. Thirteen studies were identified involving interventions based on psychoeducation, behavioural therapy, combined psychoeducation/behavioural therapy, technology-based interventions, written informed consent and a nursing support line. All 13 studies (including five RCTs) reported improvement in adherence/persistence and five studies (including four RCTs) also reported improvement in ADHD symptomatology. Almost all studies involved interventions utilising some form of education. Three RCTs of psychoeducation alone were included, with two of the three studies reporting adherence benefits at three and 12 months respectively. The third RCT was terminated early due to poor recruitment. A behavioural intervention RCT reported improved adherence six months post intervention (but not at 12 months), although a substantial drop-out rate was observed. A final included RCT used a Smartphone Application and reported a short term increase in adherence. The authors of the studies in this review make salient attempts at improving adherence and provide insight for future intervention development. We believe future interventions should involve combinations of strategies, have a theoretical framework and target the most common reasons for non-adherence. Interventions should also be integratable into routine care and include patient input to maximise sustainability.

A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15). Methods: Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1ß, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints. Findings: Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1ß, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients. Conclusions: In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic. Funding: ECSA-2020-009; Elaine Galwey Research Bursary.

Educating pharmacy students through a pandemic: Reflecting on our COVID-19 experience.

The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.

A Systematic Review and Pooled Prevalence of Delirium in Critically Ill Children.

OBJECTIVES: Pediatric delirium is a neuropsychiatric disorder with disrupted cerebral functioning due to underlying disease and/or critical care treatment. Pediatric delirium can be classified as hypoactive, hyperactive, and mixed. This systematic review was conducted to estimate the pooled prevalence of pediatric delirium using validated assessment tools in children (Cornell Assessment of Pediatric Delirium, Pediatric Confusion Assessment Method for the ICU, PreSchool Confusion Assessment Method for the ICU, Pediatric Confusion Assessment Method for the ICU Severity Scale, and Sophia Observation Withdrawal Symptoms Pediatric Delirium scale), identify modifiable and nonmodifiable risk factors, and explore the association of pediatric delirium with clinical outcomes. DATA SOURCES: A systematic search of PubMed, EMBASE, and CINAHL databases was undertaken for full articles pertaining to pediatric delirium prevalence. STUDY SELECTION: No language or date barriers were set. Studies were included where the following eligibility criteria were met: study design aimed to estimate pediatric delirium prevalence arising from treatment in the intensive care setting, using a validated tool. Only randomized controlled trials, cross-sectional studies, or cohort studies allowing an estimate of the prevalence of pediatric delirium were included. DATA EXTRACTION: Data were extracted by the primary researcher (D.S.) and accuracy checked by coauthors. DATA SYNTHESIS: A narrative synthesis and pooled prevalence meta-analysis were undertaken. CONCLUSIONS: Pediatric delirium, as determined by the Cornell Assessment of Pediatric Delirium score, is estimated to occur in 34% of critical care admissions. Eight of 11 studies reporting on subtype identified hypoactive delirium as most prevalent (46-81%) with each of the three remaining reporting either hyperactive (44%), mixed (57%), or equal percentages of hypoactive and mixed delirium (43%) as most prevalent. The development of pediatric delirium is associated with cumulative doses of benzodiazepines, opioids, the number of sedative classes used, deep sedation, and cardiothoracic surgery. Increased time mechanically ventilated, length of stay, mortality, healthcare costs, and associations with decreased quality of life after discharge were also found. Multi-institutional and longitudinal studies are required to better determine the natural history, true prevalence, long-term outcomes, management strategies, and financial implications of pediatric delirium.

Tenofovir Treatment Has Lower Risk of Hepatocellular Carcinoma than Entecavir Treatment in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis.

PURPOSE: Tenofovir (TDF) and entecavir (ETV) are both equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). They have comparable efficacy in virologic response, but their effect on the development of hepatocellular carcinoma (HCC) in CHB is controversial. Therefore, we aimed to compare TDF and ETV evaluating the risk of HCC development in CHB patients. METHODS: A systematic literature search was conducted up to November 2019 in MEDLINE/PubMed, SCOPUS, and Web of Science databases without language and time restrictions. DerSimonian and Laird random-effects models were used to estimate combined hazard ratios (HRs) and 95% CIs. RESULTS: Seven studies containing 35,785 participants were included in this systematic review and meta-analysis. The pooled HR (95% CI) of HCC in the patients who used TDF versus patients who used ETV was 0.75 (0.56-0.96). There was no significant heterogeneity detected among the included studies results (I2 = 47.5%). There was no significant publication bias detected among the included studies (Begg's p = 0.88 and Egger's regression test p = 0.96). CONCLUSIONS: Evidence to date suggests that TDF treatment is associated with significantly fewer cases of HCC when compared to ETV.

A clinician's guide to self-poisoning with paracetamol in youth: The what, when and why?

AIM: Deliberate self-poisoning or overdose is a common presentation to the paediatric emergency departments (ED) due to a lack of emergency access to child and adolescent mental health services. We overview medical and psychiatric assessment of overdoses in youth with the most commonly implicated drug, paracetamol, as a case study. METHODS: A what, when and why framework is adopted to guide clinicians on what information should be ascertained, when overdose treatment should be initiated and how to explore why the overdose occurred. RESULTS: Presentations are often asymptomatic while gastrointestinal symptoms offer an alarm signal for severe hepatotoxicity. A worst-case exposure amount and time elapsed since ingestion should be calculated to determine whether N-acetylcysteine treatment is indicated. Establishing reasons why the young person took the overdose, along with assessing the degree of remorse or regret, is crucial for discharge planning. CONCLUSION: Given the importance of timely assessment and treatment, paediatric emergency staff need to be familiar with the protocol for care. Attention needs to be focused on both the medical and psychological risk, and staff need to consider the reasons behind the overdose and following a biopsychosocial assessment, ensure that the young person and family are adequately signposted for future mental health care if needed.

The challenges of COVID-19 for community pharmacists and opportunities for the future.

Pharmacists, like psychiatrists, have modified their practices amidst COVID-19 in order to guarantee care and support to their patients. Designated an essential frontline service, community pharmacists are facing a spectrum of challenges to surmount to ensure patient care continues. These include assisting in the prevention of infection, managing supply chains, preventing stockpiling and provision of evidence-based medical information. However, disasters like COVID-19 disproportionately affect poor and vulnerable populations, and patients with mental health conditions may be among the hardest hit. Pharmacist-level, system-level and regulatory responses have sought to minimise this impact, although there is likely to be a lasting impression on the profession, both good and bad. This article reviews the pandemic-related challenges and responses by pharmacists, as well as forming recommendation for areas of professional support and role expansion, particularly in the case of mental health.

'Both useful in their own way': Video podcasts and typed solutions as feedback on undergraduate pharmaceutical calculations skills assessment.

INTRODUCTION: Accurately completing pharmaceutical calculations is a core professional skill for pharmacists. To date, few studies have focused on to providing feedback on calculations, or the role of technology in feedback provision. This study aimed to develop a theory-informed video podcast-based method of providing formative feedback and evaluate student perceptions. METHODS: First-year pharmacy students (n = 53) completed a formative pharmaceutical calculations assessment. Two forms of feedback were designed and evaluated; typed solutions (traditional format commonly used/seen in textbooks) and video podcasts informed by instructional design theory (novel format). RESULTS: A survey was completed by 70% (37/53) of students. Specific features of video podcasts reported useful included hearing reasoning, and the ability to pause and rewind. Most (76%) reported positive attitudes towards video podcasts, considered them useful (75%) and helpful for learning (79%). A comparable number (76% and 71% respectively) felt positively about typed solutions. The majority (51%) preferred to receive both types rather than podcasts alone (24%), or typed solutions alone (8%). Free-text responses indicated both were used in different ways; typed solutions for quick verification and video podcasts for clarification. CONCLUSIONS: Video podcasts appear to be a potentially helpful additional method of delivering feedback that afford specific advantages. They can be readily developed by faculty with minimal expense/difficulty. However, as respondents indicated that they used both kinds of feedback in different ways to support their learning, and indicated a preference to receive both types, they should be considered an addition rather than replacement for typed solutions.

Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta-analysis.

The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study was to evaluate the efficacy of roxadustat for the treatment of anemia in patients who are dialysis dependent (DD) or dialysis independent (NDD) CKD. We performed a systematic review of randomised controlled trials (RCTs) comparing treatment with roxadustat versus placebo or epoetin alfa up to November 2019. We investigated the efficacy of roxadustat in the levels of hemoglobin and other clinical parameters in renal anemia in patients with NDD and DD-CKD. We estimated weighted-mean difference (WMD) using random effect models. We included six RCTs comprising 1001 patients of whom 70.6 % were treated with roxadustat and 294 controls. The control group for studies of NDD-CKD patients was placebo whereas an active control of epoetin-alfa was used in studies of DD-CKD patients. Median follow-up time was 8 weeks. All trials were industry-sponsored. Overall, roxadustat increased hemoglobin levels by 1.20 g/dl (95 % CI:0.66, 1.75,P < 0.0001,I2 = 99.3 %). Hemoglobin levels increased by 1.99 g/dl in NDD-CKD patients versus placebo and 0.52 g/dl in DD-CKD patients versus epoetin-alfa. Roxadustat was associated with a decrease the levels of hepcidin by -49.3 ng/dl (-38.5 ng/dl in NDD patients versus placebo and -27.7 ng/dl in DD patients versus epoetin alfa), a decrease in ferritin of -49.7 µmol/l (-52.2 µmol/l in NDD patients versus placebo and -7.3 µmol/l in DD patients versus epoetin alfa), and increase in total iron-binding capacity of 32.2 µmol/l (14.1 µmol/l in NDD patients versus placebo and 13.6 µmol/l in DD patients versus epoetin alfa). The percentage change in the transferrin saturation levels was -2.07 % (-6%, NDD patients versus placebo, and +3.7 % in DD patients versus epoetin alfa) in anemia associated CKD patients. This review found roxadustast increases the levels of hemoglobin, serum transferrin, intestinal iron absorption, and reduces hepcidin in both NDD and DD-CKD patients. Safety data is still emerging.

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study.

BACKGROUND: Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing. AIMS: This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies. METHODS: A literature search was undertaken to identify a clonidine pharmaockinetic-pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed. RESULTS: A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates. CONCLUSION: The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady-state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study.

OBJECTIVES: There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation. DESIGN: A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11-16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined. SETTING: Two tertiary PICUs. PATIENTS: Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72-75%) of the study time compared with the unexposed group at 70% (95% CI, 67-72%) giving a ratio of 1.06 (95% CI, 1.02-1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3-11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 µg/kg/hr (95% CI, -0.68 to 1.18 µg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher. CONCLUSIONS: Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use.

A qualitative study exploring the decision of parents to use medication in attention-deficit hyperactivity disorder.

BACKGROUND: Reported prevalence of ADHD in children varies greatly from country to country. There is a similar disparity between rates of medication prescriptions for ADHD, with significant variation existing between rates in USA and Europe. North American studies report that parents have concerns about starting and continuing ADHD medication in children, though little is known about experiences in other geographies and healthcare systems. These studies may inform supports required, and help understand if these concerns may result in different treatment patterns, in other geographies. OBJECTIVE: To explore experiences of parents of children who used ADHD medication in Ireland. METHODS: A qualitative methodology was employed. Data were gathered through in-depth semi-structured interviews with ten parents who had a child with ADHD and had commenced medication. Analysis was performed using a phenomenographic approach. RESULTS: Four descriptive categories relating to parents' experiences of decision-making emerged. Symptom severity prior to diagnosis, duration of ADHD symptoms and parental struggle to make an informed risk/benefit decision influenced decision-making. The child's immediate response to medication was identified as an important factor facilitating persistence and adherence. Over time, parents sought to regain some control over and gain confidence in medication management and decision-making. CONCLUSIONS: The decision to use medication in ADHD is difficult and dynamic for parents in Ireland. It is driven by a sense of urgency and powerlessness, mobilizing feelings of doubt, anxiety and guilt before concluding with a sense of autonomy and increased confidence. Lack of awareness of ADHD and treatments, alongside access to care issues, add to parental anxiety in Ireland. This is in contrast to previous North American studies. Current provisions of support and information at the time of ADHD diagnosis are insufficient. Initial reaction to medication options should be explored by clinicians and support continued over time.

Effect of Overencapsulation on the Disintegration and Dissolution of Licensed Formulations for Blinding in Randomized Controlled Trials.

Overencapsulation is a technique used to conceal tablet products for blinding in randomized controlled trials. A tablet is inserted in an opaque capsule shell with backfill excipient to prevent rattling. Regulatory authorities require evidence that such modification does not materially alter drug release to approve their use in trials. The objective of this study was to assess impact of overencapsulation on disintegration and dissolution of 4 immediate-release drug products (penicillin V, gemfibrozil, ciprofloxacin, and furosemide). Each unmodified tablet was compared to 3 overencapsulated tablets with differing backfill excipient (colloidal silica, lactose monohydrate, or microcrystalline cellulose). All 12 overencapsulated tablets met disintegration and dissolution acceptance criteria. Dissolution acceptance was dependent on apparatus as only 4/12 formulations met specifications using the rotating basket compared to 12/12 using the rotating paddle. Significant differences in release were observed at early time points (T5-T15). No correlation was observed between aqueous solubility and release, although dissolution of the lipophilic drug gemfibrozil was least impacted by overencapsulation. There was evidence that type/quantity of backfill delays release at early time points. These findings indicate that under the specified conditions, overencapsulated formulations of 4 drugs, 1 from each class of the Biopharmaceutics Classification System, met compendial requirements for release testing.

Effectiveness of α2agonists for sedation in paediatric critical care: study protocol for a retrospective cohort observational study.

INTRODUCTION: Mechanically ventilated children in paediatric intensive care units are commonly administered analgesics and sedative agents to minimise pain and distress and facilitate cooperation with medical interventions. Opioids and benzodiazepines are the most common analgesic and sedative agents but have safety concerns. The α2 agonists clonidine and dexmedetomidine are alternative sedatives in use despite neither having robust evidence to support their use. Studies evaluating effectiveness of α2 agonists to date have not focused on sedation-based outcomes instead focusing on opioid-sparing properties and ventilation outcomes. The aim of this study is to evaluate if an opioid-based sedation regimen, with an α2 agonist adjunct (clonidine or dexmedetomidine), produces a non-inferior proportion of time adequately sedated compared with a control group without an α2 agonist adjunct, while conferring potential additional benefits such as reduced opioid administration and less exposure to potential additional agents such as benzodiazepines. METHODS AND ANALYSIS: We will conduct a retrospective cohort study in two Irish paediatric intensive care units using clinical information on patient characteristics, sedation scores and drug use. Eligible children admitted between January 2014 and June 2016 who were mechanically ventilated and received an opioid infusion will be included. Patients will be categorised into two exposure categories (received an α2 agonist or did not receive an α2 agonist) and the time adequately sedated (measured using the COMFORT Behaviour Score) will be calculated using interpolation of nursing sedation scores at each recorded time point. At least 150 per group is planned for inclusion to ensure adequate study power. Propensity score matching will be used in analysis to account for potential confounding by indication. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of both hospitals. Dissemination will occur via local, national and international presentations for academic and healthcare audiences as well as through peer reviewed publications.

Design and Evaluation of Video Podcasts for Providing Online Feedback on Formative Pharmaceutical Calculations Assessments.

Objective. To evaluate worked example video podcasts as a method of providing feedback to pharmacy interns for an online and formative pharmaceutical calculations assessment. Methods. A theory-informed approach based on multimedia learning theory was used to design video podcasts as feedback on a calculations examination. A mixed-methods evaluation completed by pharmacy interns enrolled in Ireland's National Pharmacy Internship Programme was used to establish cognitive and affective attitudes toward video podcasts compared with conventional written solutions. Results. The majority of students found video podcasts were clear, helpful for learning, easy to understand, and useful as a method of feedback. Majority reported that they felt positively about standard written solutions. The evaluation suggested distinct benefits for each kind of feedback, something that has not been previously reported. Thematic analysis of qualitative data indicated useful features of video podcasts, including clear explanation, step-by-step approach, and synchronization of audio and visual information. Conclusion. Respondents reported positive cognitive and affective attitudes toward video podcasts as online feedback. Video podcasts are a helpful and novel way of providing feedback on pharmaceutical calculations. A similar opinion of traditional written solutions suggests that students may benefit from both forms of feedback. Further study is required to identify the particular benefits associated with both kinds.

Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review.

OBJECTIVE: Children in PICUs normally require analgesics and sedatives to maintain comfort, safety, and cooperation with interventions. α2-agonists (clonidine and dexmedetomidine) have been described as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. This systematic review aimed to determine whether α2-agonists were effective in maintaining patients at a target sedation score over time compared with a comparator group. We also aimed to determine whether concurrent use of α2-agonists provided opioid-sparing effects. DATA SOURCES: A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS. STUDY SELECTION: We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation. DATA EXTRACTION: Two authors independently screened articles for inclusion. DATA SYNTHESIS: Six randomized controlled trials with sufficient data were identified and critically appraised. Three clonidine trials (two vs placebo and one vs midazolam) and three dexmedetomidine trials (two vs fentanyl, one vs midazolam) were included. Due to study heterogeneity it was not possible to pool studies. A narrative synthesis is provided. CONCLUSIONS: Reporting of study results using the outcome "time maintained at target sedation score' for clonidine or dexmedetomidine was poor. Only one trial compared clonidine with midazolam using a sedation score outcome. This study was underpowered to demonstrate equivalence to midazolam as a sedative. The adjunctive use of clonidine demonstrated significant decreases in opioid use in neonates but not in older groups. Clonidine dose was inconsistent between studies. Dexmedetomidine demonstrated an opioid-sparing effect in two small trials. Further studies, including dose-finding studies and studies with sedation score-based outcomes, are needed.