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Purpose To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects. Results Eighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N  = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha 2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21–0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08–0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06–0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10–0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09–0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64–0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61–0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care. Conclusion Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain.

Antipsychotic medications are commonly prescribed to critically ill adult patients and initiation of new antipsychotic prescriptions in the intensive care unit (ICU) increases the proportion of patients discharged home on antipsychotics. Critically ill adult patients are also frequently exposed to multiple psychoactive medications during ICU admission and hospitalization including benzodiazepines and opioid medications which may increase the risk of psychoactive polypharmacy following hospital discharge. The associated impact on health resource utilization and risk of new benzodiazepine and opioid prescriptions is unknown. What is the burden of health resource utilization and odds of new prescriptions of benzodiazepines and opioids up to 1-year post-hospital discharge in critically ill patients with new antipsychotic prescriptions at hospital discharge? We completed a multi-center, propensity-score matched retrospective cohort study of critically ill adult patients. The primary exposure was administration of ≥1 dose of an antipsychotic while the patient was admitted in the ICU and ward with continuation at hospital discharge and a filled outpatient prescription within 1-year following hospital discharge. The control group was defined as no doses of antipsychotics administered in the ICU and hospital ward and no filled outpatient prescriptions for antipsychotics within 1-year following hospital discharge. The primary outcome was health resource utilization (72-hour ICU readmission, 30-day hospital readmission, 30-day emergency room visitation, 30-day mortality). Secondary outcomes were administration of benzodiazepines and/or opioids in-hospital and following hospital discharge in patients receiving antipsychotics. 1,388 propensity-score matched patients were included who did and did not receive antipsychotics in ICU and survived to hospital discharge. New antipsychotic prescriptions were not associated with increased health resource utilization or 30-day mortality following hospital discharge. There was increased odds of new prescriptions of benzodiazepines (adjusted odds ratio [aOR] 1.61 [95%CI 1.19-2.19]) and opioids (aOR 1.82 [95%CI 1.38-2.40]) up to 1-year following hospital discharge in patients continuing antipsychotics at hospital discharge. New antipsychotic prescriptions at hospital discharge are significantly associated with additional prescriptions of benzodiazepines and opioids in-hospital and up to 1-year following hospital discharge.

CBT has been found to be as effective as prescription medications for short-term treatment of chronic insomnia. [...]there are indications that the beneficial effects of CBT may last well beyond the termination of active treatment.” Canadian Pharmacists Association—“Don’t prescribe or dispense benzodiazepines without building a discontinuation strategy into the patient’s treatment plan (except for patients who have a valid indication for long-term use)” Box 3 Components of cognitive behavioural therapy for insomnia Stimulus control—Associate the bed and bedroom with sleep: participants should avoid screen time in bed and get out of bed at night if they are having trouble sleeping Sleep restriction—Increase the homeostatic drive to sleep. A second systematic review and meta-analysis of 87 RCTs of 6303 patients in 2017 reported a number needed to treat (NNT) of 1.95 to improve insomnia severity index and an NNT of 11.1 to increase total sleep time.16 These effects are similar to those of benzodiazepines as seen in meta-analyses.910 The risk of adverse events such as daytime drowsiness, dizziness, fatigue, and adverse cognitive and psychomotor events was 2-5 times higher with sedatives compared with placebo.910 A systematic review (5 RCTs, 657 participants) found limited and low quality evidence that CBT-i is at least as effective as sedatives for insomnia and that its effects may be more durable.17 A well conducted randomised controlled trial (160 participants) found that the addition of sedatives to CBT-i achieved larger increase in sleep time and greater remission rate at six months, but long term outcomes were optimised with discontinuation of medication during maintenance CBT-i.18 An overview of systematic reviews (64 systematic reviews, 35 with meta-analysis) confirmed effectiveness across multiple outcomes (including sleep onset latency, total sleep time, wake after sleep onset, sleep quality, sleep satisfaction, sleep efficiency, insomnia severity index scores, fatigue severity, and health related quality of life) based on more than one high or moderate quality review with meta-analysis for zolpidem, suvorexant, doxepin, melatonin, and CBT-i. [...]very little data on harms were available (including hangover/morning sedation, accidental injuries, additional healthcare use related to harms of the intervention, delirium related to the intervention, sleep disordered breathing related to the intervention, all-cause mortality related to the intervention, and addiction, dependence, or diversion of medications).19 Finally, a high quality systematic review (37 RCTs, 2189 participants) on the efficacy of CBT-i for patients with insomnia comorbid with psychiatric and/or medical conditions found 36.0% who received CBT-i were in remission from insomnia compared with 16.9% of those in control or comparison conditions (pooled odds ratio 3.28 (95% CI 2.30 to 4.68); P<0.001) with the longest reported follow-up period of eight months.20 Individual components of CBT-i are effective, but greater and more sustained benefit is likely when these components are combined.212223 A meta-analyses published in 2017 (87 RCTs, 6303 participants) reported improvements in sleep measures with interventions having at least one component of CBT-i compared with placebo.16 Patients with limited access to in-person CBT-i may consider computerised,24 digital,25 internet-based,262728 group,3425 and telehealth-mediated CBT-i,29 all of which have demonstrated efficacy for treating insomnia.252628 Barriers to change System, patient, and clinician factors are known barriers to implementation of CBT-i and lead to early initiation of sedatives.

This proposed scoping review aims to examine studies assessing the impact of drug shortages on population-level drug utilization trends. The objectives of this review are to a) assess which drugs have been studied and describe associated drug characteristics, b) determine jurisdictions and healthcare settings that have conducted these studies, and c) describe how changes in drug use and the extent of shortage impacts are reported in literature. Drug shortages continue to impair drug access and delivery of quality care across the world. However, the impact of drug supply disruptions on availability and drug use are understudied in current literature. This proposed scoping review will identify this gap and inform future research initiatives aimed at determining the real-world impacts of drug shortages. Published and unpublished observational studies reporting on the effects of drug supply chain disruptions (shortages, discontinuations, and safety-based withdrawals) on consequent utilization trends faced by pharmaceutical products (i.e. prescription drugs, over-the-counter drugs, vaccines, therapy products, pharmaceutical solutions). Literature reviews, meta-analyses, randomized control trials, case series, case reports, and opinion pieces will be excluded. The search strategy will combine two key search concepts: drug shortages and drug utilization. The search will be conducted in MEDLINE and EMBASE. This will be followed by an extensive grey literature search in grey literature databases, targeted websites and Google. Furthermore, reference lists of included articles will be searched. Articles will be independently screened, selected and extracted by two reviewers. Data will be descriptively analyzed and presented in tables. Review registration number: Open Science Framework, https://osf.io/2p6e5.

Purpose Oral chlorhexidine is used widely for mechanically ventilated patients to prevent pneumonia, but recent studies show an association with excess mortality. We examined whether de-adoption of chlorhexidine and parallel implementation of a standardized oral care bundle reduces intensive care unit (ICU) mortality in mechanically ventilated patients. Methods A stepped wedge cluster-randomized controlled trial with concurrent process evaluation in 6 ICUs in Toronto, Canada. Clusters were randomized to de-adopt chlorhexidine and implement a standardized oral care bundle at 2-month intervals. The primary outcome was ICU mortality. Secondary outcomes were time to infection-related ventilator-associated complications (IVACs), oral procedural pain and oral health dysfunction. An exploratory post hoc analysis examined time to extubation in survivors. Results A total of 3260 patients were enrolled; 1560 control, 1700 intervention. ICU mortality for the intervention and control periods were 399 (23.5%) and 330 (21.2%), respectively (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI] 0.82 to 1.54; P  = 0.46). Time to IVACs (adjusted hazard ratio [aHR], 1.06; 95% CI 0.44 to 2.57; P  = 0.90), time to extubation (aHR 1.03; 95% CI 0.85 to 1.23; P  = 0.79) (survivors) and oral procedural pain (aOR, 0.62; 95% CI 0.34 to 1.10; P  = 0.10) were similar between control and intervention periods. However, oral health dysfunction scores (− 0.96; 95% CI − 1.75 to − 0.17; P  = 0.02) improved in the intervention period. Conclusion Among mechanically ventilated ICU patients, no benefit was observed for de-adoption of chlorhexidine and implementation of an oral care bundle on ICU mortality, IVACs, oral procedural pain, or time to extubation. The intervention may improve oral health.

Background Antipsychotic medications do not alter the incidence or duration of delirium, but these medications are frequently prescribed and continued at transitions of care in critically ill patients when they may no longer be necessary or appropriate. Objective The purpose of this study was to identify and describe relevant domains and constructs that influence antipsychotic medication prescribing and deprescribing practices among physicians, nurses, and pharmacists that care for critically ill adult patients during and following critical illness. Design We conducted qualitative semi-structured interviews with critical care and ward healthcare professionals including physicians, nurses, and pharmacists to understand antipsychotic prescribing and deprescribing practices for critically ill adult patients during and following critical illness. Participants Twenty-one interviews were conducted with 11 physicians, five nurses, and five pharmacists from predominantly academic centres in Alberta, Canada, between July 6 and October 29, 2021. Main Measures We used deductive thematic analysis using the Theoretical Domains Framework (TDF) to identify and describe constructs within relevant domains. Key Results Seven TDF domains were identified as relevant from the analysis: Social/Professional role and identity; Beliefs about capabilities; Reinforcement; Motivations and goals; Memory, attention, and decision processes; Environmental context and resources; and Beliefs about consequences . Participants reported antipsychotic prescribing for multiple indications beyond delirium and agitation including patient and staff safety, sleep management, and environmental factors such as staff availability and workload. Participants identified potential antipsychotic deprescribing strategies to reduce ongoing antipsychotic medication prescriptions for critically ill patients including direct communication tools between prescribers at transitions of care. Conclusions Critical care and ward healthcare professionals report several factors influencing established antipsychotic medication prescribing practices. These factors aim to maintain patient and staff safety to facilitate the provision of care to patients with delirium and agitation limiting adherence to current guideline recommendations.

ObjectiveThe aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).MethodsWe performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.ResultsAmong the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.ConclusionsPropranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.PROSPERO registration numberCRD42016033140

Background. We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB). Methods. A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge. Results. Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P < .0001) in hospital. Blood cultures were repeated within 2–4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52–.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06–1.56; P = .0109) for being discharged alive. Conclusions. ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.

Background Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing − 3 to − 8 cm H 2 O; dynamic transpulmonary driving pressure ≤ 15 cm H 2 O) during AHRF. Methods In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort. Results Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets. Conclusion Respiratory effort is frequently absent  under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy. Trial registration : This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).