[Summary text]
Study design: Randomized controlled trial
Study grouping: Parallel group
Baseline Characteristics
Intervention
Control
Intervention 2
Included criteria: Participants included adult patients receiving hospice or pal-liative care with advanced, progressive disease that was no lon-ger curable who required inpatient care by a specialist pallia-tive care team. Participants needed to meet the following3 criteria: delirium diagnosed via criteria from theDiagnosticand Statistical Manual of Mental Disorders(Fourth Edition, TextRevision), Memorial Delirium Assessment Scale (MDAS) scoreof 7 or more, and presence of the target symptoms of de-lirium associated with distress, defined as a delirium symp-toms score of 1 or more (sum of the scores from items 2 [inap-propriate behavior], 3 [inappropriate communication], and4 [illusions and hallucinations] on the Nursing Delirium Screen-ing Scale [NuDESC] [severity range, 0-6])
Excluded criteria: Exclusion criteria included delirium due to substance with-drawal, history of neuroleptic malignant syndrome, regular useof antipsychotic drugs within 48 hours (a single as-needed dosewas allowed if administered more than 24 hours before thestudy for a nondelirium indication), previous adverse reac-tion to antipsychotic drugs, extrapyramidal disorders, pro-longed QT interval, clinician-predicted survival of 7 days or fewer, cerebrovascular accident or seizure in the prior 30 days,and pregnancy or breastfeeding. Participants were required tospeak English and be able to swallow liquids
Pretreatment: The study reached its preplanned sample size, withcomparable clinicodemographic baseline data between arms
Intervention Characteristics
Intervention
Control
Intervention 2
SAE (under indlæggelse)
Delirium varighed (Mean CI)
Delirium varighed (Mean SD)
Kritisk Uro
Indlæggelsestid
Genindlæggelser Op til 3 mdr. efter udskrivelse
Fald
Angst
Ekstrapyramidale bivirkninger
Ekstrapyramidale bivirkninger
Kognitiv funktion
Død
Delirium severity
Sponsorship source: This study was funded by the Australian Government’s Department of Health under the National Palliative Care Strategy.Individual site funding was supplemented by grant NHMRC 480476 from the National Health and Medical Research Council, Australia
Country: Australia
Setting: inpatient hospice or hospital palliative care
Comments: http://www.anzctr.org.au/trial_view.aspx?ACTRN=ACTRN12607000562471
Authors name: Meera R. Agar
Institution: Centre for Cardiovascular and Chronic Care, Faculty of Health,University of Technology Sydney
Email: meera.agar@uts.edu.au
Address: Centre for Cardiovascular and Chronic Care, Faculty of Health,University of Technology Sydney, Level 3, 235 Jones St (PO Box 123),Ultimo, New South Wales, Australia
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Kontrol
Included criteria: April 2006-august 2008 adult patients admitted to the medical and surgical ICU at each institution with delirium diagnosed with the ICDSC, had an order for as-needed haloperidol and were tolerating enteral nutrition.
Excluded criteria: History of irreversible cognitive dysfunctionAdmitted with a primary neurological condition or injuryHistory of hepatic encephalopathy or end-stage liver failure (Childs Pugh B or worse)Actively withdrawing from alcoholTreatment with an antipsychotic agent in the 30 days before ICU-admissionCurrent treatment with dexmedetomidine or neuromuscular blockerCurrent treatment with an agent having either the potential to affect the quetipine concentration or increase the risk of QTc prolongation.Baseline QTc > 500 msPregnancyNon-english speakingPresence of a condition preventing delirium assessmentPrognosis considered hopelessInformed consent could not be obtained from the legally authourized representative.
Pretreatment: Væsentlig flere intuberede ved start i placebo gruppe og flere udsat for fentanyl og benzo i de sidste 24 timer. Flere kom hjemmefra i interventionsgruppe.
Intervention Characteristics
Intervention
Kontrol
Død/mortality (Ved udskrivelse)
Genindlæggelser/readmissions (3 mdr FU)
Fald/falls (Ved udskrivelse)
Funktionsevne/physical function (ved udskrivelse)
Angst/anxiety (Ved udskrivelse)
Ekstrapyramidale bivirkninger/extrapyramidal symptoms (Ved udskrivelse)
Uro/restlessness (ved udskrivelse)
SAE (Ved udskrivelse)
Død/mortality (3 mdr FU)
Delirium severity (ved udskrivelse)
Sponsorship source: Society of Critical Care Medicines; Critical Care Pharmacy research Award; Astra Zeneca Pharmaceuticals; Author grant support from Hospira
Country: US
Setting: Intensive care unit /critically ill
Comments:
Authors name: J.Devlin
Institution: Northeastern University School of Pharmacy, Boston MA
Email: j.devlin@neu.edu
Address: Northeastern University School of Pharmacy, Boston MA
Susanne Stabel Gren on 07/06/2016 07:59
Select
Placebokontrolleret RCT på ITA-ptt. Selvom det er en lille gruppe 36 skal det med
Jakob Carlsen on 07/06/2016 18:51
Select
Quetiapin med "ad-on" serenase. Lille, men relevant?!
Nkr 42 Delir on 14/06/2016 22:42
Outcomes
Indlæggelsestid (Ved udskrivelse) opgjort i median (interquartile range)Intervention: 24 (11-33)Kontrol: 26 (17-49)Delirvarighed (Ved udskrivelse) opgjort i median (interquartile range)Intervention: 36 (12-87) timerKontrol: 120 (60-195)
Henning Keinke Andersen on 16/06/2016 22:09
Outcomes
I assume the notified mortality rates (2 resp. 3) are at discharge from the hospital unit!
Study design: Randomized controlled trial
Study grouping: Parallel group
Baseline Characteristics
Intervention
Control
Intervention 2
Overall
Included criteria: Patients who had been admitted to the par-ticipating hospitals were eligible for inclusion if they were 18 years of age or older and were re-ceiving treatment in a medical or surgical ICU with invasive or noninvasive positive pressure ventilation, vasopressors, or an intraaortic balloon pump, and they were eligible for random assign-ment to a trial group if they had delirium.
Excluded criteria: We excluded patients who, at baseline, had severe cognitive impairment, as determined by medical record review and the short form of the Infor-mant Questionnaire on Cognitive Decline in the Elderly (IQCODE; scores range from 1.0 to 5.0, with higher scores indicating more severe cogni-tive impairment [a score of ≥4.5 resulted in exclu-sion because of severe dementia])22; were at high risk for medication side effects because of preg-nancy, breast-feeding, a history of torsades de pointes, QT prolongation, a history of neurolep-tic malignant syndrome, or allergy to haloperidol or ziprasidone; were receiving ongoing treatment with an antipsychotic medication; were in a mori-bund state; had rapidly resolving organ failure; were blind, deaf, or unable to speak or under-stand English; were incarcerated; or were en-rolled in another study or trial that prohibited coenrollment. Details of the inclusion and exclu-sion criteria are provided in the Supplementary Appendix. Noncomatose patients were excluded if informed consent could not be obtained within 72 hours after inclusion criteria had been met, and comatose patients were excluded if informed consent could not be obtained within 120 hours after inclusion criteria had been met.
Pretreatment: There were no significant differences in baseline characteristics between the trial groups (Table1)
Intervention Characteristics
Intervention
Control
Intervention 2
SAE (under indlæggelse)
Delirium varighed (Mean CI)
Delirium varighed (Mean SD)
Kritisk Uro
Indlæggelsestid
Genindlæggelser Op til 3 mdr. efter udskrivelse
Fald
Angst
Ekstrapyramidale bivirkninger
Ekstrapyramidale bivirkninger
Kognitiv funktion
Død
Delirium severity
Sponsorship source:
Country: USA
Setting:
Comments: The trial was registered at ClinicalTrials.gov on September 29, 2010, before the first patient was enrolled. The statistical analysis plan was regis-tered at Open Science Framework (https://osf.io/mq38r)on March 22, 2018
Authors name: T.D. Girard
Institution:
Email: wes.ely@vumc.org.
Address: Dr. Ely at the Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center at Vanderbilt University, 2525 West End Ave., Suite 450, Nashville, TN 37203
NKR 42 Delir on 19/08/2020 02:54
Screen
3 arme
Helle Svenningsen on 19/08/2020 22:58
Select
patienterne er både < og > 65 år, og der skelnes ikke i resultaterne
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Kontrol
Included criteria: Screening for delirium was conducted by daily contactwith medical, surgical and orthopedic wards at the UniversityHospital of Wales by a research assistant. An attempt wasmade to recruit those who met theDSM-IVcriteria fordelirium on the same day if they had a DRS-R-98 total scoreof 15 or more.
Excluded criteria: Individuals with major pre-existing cognitivedeficits, alcohol withdrawal, pre-existing psychosis, sub-stance dependence, inability to comply with the constraints ofthe trial, or who were on medication that interacted withquetiapine were excluded from the study. The nature anddegree of any pre-existing cognitive deficits were determinedby reviewing clinical notes and by obtaining informationfrom a reliable informant. Informed consent was obtainedfrom participants with mental capacity.
Pretreatment: none stated
Intervention Characteristics
Intervention
Kontrol
Død/mortality (3 mdr FU)
Genindlæggelser/readmissions (3 mdr FU)
Fald/falls (Ved udskrivelse)
Funktionsevne/physical function (ved udskrivelse)
Angst/anxiety (Ved udskrivelse)
Ekstrapyramidale bivirkninger/extrapyramidal symptoms (Ved udskrivelse)
Uro/restlessness (ved udskrivelse)
SAE (Ved udskrivelse)
Delirium severity (ved udskrivelse)
Sponsorship source: AstraZeneca UKsponsored the study and provided funding for a researchassistant, trial medication,and the randomization codes
Country: UK
Setting: Medical , surgical og orthopedic wards
Comments:
Authors name: Tayyeb A. Tahir
Institution: Department of Liaison Psychiatry, University Hospital of Wales, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
Email: tayyeb.tahir@wales.nhs.uk
Address: Corresponding author. Department of Liaison Psychiatry, Room 124,1st Floor, Monmouth House, University Hospital of Wales, CF14 4XNCardiff, UK
Jakob Carlsen on 08/06/2016 05:15
Select
Seroquel vs. placebo.
Susanne Stabel Gren on 11/06/2016 18:30
Included
DB.blindet RCT skal med
Henning Keinke Andersen on 16/06/2016 23:10
Outcomes
NB! Død er efter 30 dage og ikke 3 mdrExtrapyramidal symptoms reported as 'abnormal involuntary movements' (tolerability) p 488Why not death at discharge, reported in fig 1 (3 IV; 1 Placebo)?Går udfra ITT analyser
Wrong intervention
Wrong comparator
Wrong intervention
Wrong comparator
Wrong study design
Wrong study design
Wrong patient population
Wrong study design
Wrong outcomes
Wrong patient population
Wrong study design
Wrong intervention
Wrong study design
Wrong patient population
Wrong study design
Wrong study design
Wrong study design
Wrong study design
Wrong study design
Wrong study design
Wrong intervention
Wrong intervention
Wrong intervention
Wrong intervention
Wrong comparator
Wrong patient population
Wrong patient population
Wrong comparator
Wrong study design
Wrong comparator
Wrong study design
Wrong study design
Wrong study design
Wrong intervention
Wrong study design
Wrong setting
Wrong intervention
Wrong outcomes
Wrong comparator
Wrong study design
Wrong study design
Wrong study design
Wrong patient population
Wrong study design
Wrong study design
Wrong study design
Wrong study design
Wrong study design
Wrong patient population
Wrong outcomes
Wrong study design
Wrong study design
Wrong study design
Wrong intervention
Wrong intervention
Wrong study design
Wrong study design
Wrong patient population
Wrong patient population
Wrong comparator
dublicate
Wrong comparator
Wrong comparator
Wrong intervention
Wrong comparator
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Detection bias due to knowledge of the allocated interventions by outcome assessors
Attrition bias due to amount, nature or handling of incomplete outcome data
Reporting bias due to selective outcome reporting
Bias due to problems not covered elsewhere in the table
Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.
rights reserved. Randomization and Masking <b>Site randomization schedules were generated using random number tables at an independent blinded central registry. Par- ticipants were randomized in blocks of 6 by site in a 1:1:1 ratio by arm. Allocation concealment was by sealed opaque enve- lopes. Site</b> clinical trial pharmacists who opened
Judgement Comment: Computergenerated random number table
randomized, double-blind, placebo-con- trolled, phasewe randomly assigned the patients, in a 1:1:1 ratio, to receive placebo, haloperidol, or ziprasidone using a computer-generated, permuted- block randomization scheme, with stratification according to trial site.
Quote: "Computer-generated randomization codes"
Describe the method used to conceal the allocation sequence in sufficient detail to determine wether intervention allocations could have been foreseen in advance of, during, enrolement.
Allocation concealment was by sealed opaque enve- lopes.clinical trial pharmacists who opened the treat- ment schedules to prepare the intervention were not other- wise involved in patient care.
Judgement Comment: Not enough details. 'Known to the investigator at each site'
The research personnel, managing clinicians, patients, and their families were not aware of the trial-group assignments.
Quote: "Computer-generated randomization codes were kept in sealed envelopes at the University Hospital of Wales' Pharmacy. In addition, a set of individual treatment codes was kept by the Scottish Poisons Information Bureau, Royal Infirmary Edin- burgh, for emergency out-of-hours use only."
Describe all measures used, if any to blind study participants and personnel from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.
Site clinical trial pharmacists who opened the treat- ment schedules to prepare the intervention were not other- wise involved in patient care. Study medication was dispensed in opaque screw-top bottles, which were identical in terms of volume, color, and smell and taste of the contents. Treat- ment assignment was double-blinded: both participants and investigators were masked to treatment group for the dura- tion of the study.Study medication was dispensed in opaque screw-top bottles, which were identical in terms of volume, color, and smell and taste of the contents.
Judgement Comment: Patients blinded, no info on personnel
patients, and their families were not aware of the trial-group assignments.The research personnel, managing clinicians, patients, and their families were not aware of the trial-group assignments. The trial drugs or placebo were administered intravenously with the use of colorless prepara- tions delivered in identical bags. s
Judgement Comment: De beskriver ikke selve blindingsprocessen
Describe all measures used, if any to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.
covariate. Second- ary outcomes included daily MDAS score, lowest delirium symptoms score, daily use of midazolam use, extrapyramidal symptoms assessed by the Extrapyramidal Symptom Rating Scale, sedation assessed by the Richmond Agitation- Sedation Scale, National Cancer Institute Common Terminol- ogy Criteria for Adverse Events, and survival.ment assignment was double-blinded: both participants and investigators were masked to treatment group for the dura- tion of the study.
Judgement Comment: Ej beskrevet hvem der vurderer. Desuden databehandling ej beskrevet om blinding.
Objective measures of relevant outcomes
Judgement Comment: Ej beskrevet
Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.
Present results from ITT analyses
Judgement Comment: 36 pts randomised. Data were obtained from all 18 allocated pts in each group.
A total of 300 of 6100 (5%) potential assessments for delirium or coma were missing; we imputed these individual assessments using polytomous logistic regression that included multiple co- variates. After calculating days alive without delirium or coma, we then used complete case analysis for all outcomes (see the Supplementary Appendix).COMMENTSafraporterer på alle der er randomiseret
Quote: "To account for the noncompleters, due to various reasons given below, it was important to take into account missing data and the improvement in delirium with or without medication; we used non-linear, mixed-effects model to estimate differences in recovery trajectories between treatment groups. Initially, we considered models that allowed different starting and long-term mean values in the two treatment groups; however, no significant evidence of such differences was found."
Judgement Comment: There is a substantial drop-out rate for each group (5/21 for IV - and 7/21 for placebo). And it is notified that the trial stopped at an early stage (p 489)
State how the possibility of selective outcome reporting was examined by the review authors and what was found.
TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12607000562471.
Judgement Comment: No study protocol available, but the outlined endpoints in the RCT are all reported.
ClinicalTrials.gov number, NCT01211522.)The trial was registered at ClinicalTrials.gov on September 29, 2010, before the first patient was enrolled. The statistical analysis plan was regis- tered at Open Science Framework (https://osf. io/ mq38r) onWe analyzed all data using an intention-to- treat approach and compared the effects of halo- peridol, ziprasidone, and placebo with respect to the primary end point using the Kruskal–Wallis test in unadjusted analyses and proportional-odds logistic regression in adjusted analyse
Judgement Comment: The outlined outcomes are reported fully of partial. Primary outcome (DRS-R-98) is reported
State any important concerns about bias not addressed in the other domains in the tool. If particular questions/entries were re-specified in the review's protocol, responses should be provided for each question/entry.
Interest Disclosures: None reported. Funding/Support: <b>This study was funded by the Australian Government’s Department of Health under the National Palliative Care Strategy. Individual site funding was supplemented by grant NHMRC 480476 from the National Health and Medical Research Council, Australia. Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; preparation review, or approval of the manuscript; and decision to submit the manuscript for publication.</b> Additional Contributions: Debbie Marriott, Flinders
Judgement Comment: Study seems to be free of other sources of bias
it is not stated weather or not the patients had delirium before randomization. And the how do they obtain consent. Also they treat for he full 14 days, but what is the patients did not have delirium throughout the trail period.
Judgement Comment: Not quite sure whether the clinicians decision on dosage changes will affect the outcome. Probbably - therefore the 'unclear'