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The Cochrane Database of Systematic... Jan 2020Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the course of the day. It is commonly experienced during inpatient admission in the terminal phase of illness. It can cause symptoms such as agitation and hallucinations and is distressing for terminally ill people, their families and staff. Delirium may arise from any number of causes and treatment should aim to address these causes. When this is not possible, or treatment is unsuccessful, drug therapy to manage the symptoms may become necessary. This is the second update of the review first published in 2004.
OBJECTIVES
To evaluate the effectiveness and safety of drug therapies to manage delirium symptoms in terminally ill adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO from inception to July 2019, reference lists of retrieved papers, and online trial registries.
SELECTION CRITERIA
We included randomised controlled trials of drug therapies in any dose by any route, compared to another drug therapy, a non-pharmacological approach, placebo, standard care or wait-list control, for the management of delirium symptoms in terminally ill adults (18 years or older).
DATA COLLECTION AND ANALYSIS
We independently screened citations, extracted data and assessed risk of bias. Primary outcomes were delirium symptoms; agitation score; adverse events. Secondary outcomes were: use of rescue medication; cognitive status; survival. We applied the GRADE approach to assess the overall quality of the evidence for each outcome and we include eight 'Summary of findings' tables.
MAIN RESULTS
We included four studies (three new to this update), with 399 participants. Most participants had advanced cancer or advanced AIDS, and mild- to moderate-severity delirium. Meta-analysis was not possible because no two studies examined the same comparison. Each study was at high risk of bias for at least one criterion. Most evidence was low to very low quality, downgraded due to very serious study limitations, imprecision or because there were so few data. Most studies reported delirium symptoms; two reported agitation scores; three reported adverse events with data on extrapyramidal effects; and none reported serious adverse events. 1. Haloperidol versus placebo There may be little to no difference between placebo and haloperidol in delirium symptoms within 24 hours (mean difference (MD) 0.34, 95% confidence interval (CI) -0.07 to 0.75; 133 participants). Haloperidol may slightly worsen delirium symptoms compared with placebo at 48 hours (MD 0.49, 95% CI 0.10 to 0.88; 123 participants with mild- to moderate-severity delirium). Haloperidol may reduce agitation slightly compared with placebo between 24 and 48 hours (MD -0.14, 95% -0.28 to -0.00; 123 participants with mild- to moderate-severity delirium). Haloperidol probably increases extrapyramidal adverse effects compared with placebo (MD 0.79, 95% CI 0.17 to 1.41; 123 participants with mild- to moderate-severity delirium). 2. Haloperidol versus risperidone There may be little to no difference in delirium symptoms with haloperidol compared with risperidone within 24 hours (MD -0.42, 95% CI -0.90 to 0.06; 126 participants) or 48 hours (MD -0.36, 95% CI -0.92 to 0.20; 106 participants with mild- to moderate-severity delirium). Agitation scores and adverse events were not reported for this comparison. 3. Haloperidol versus olanzapine We are uncertain whether haloperidol reduces delirium symptoms compared with olanzapine within 24 hours (MD 2.36, 95% CI -0.75 to 5.47; 28 participants) or 48 hours (MD 1.90, 95% CI -1.50 to 5.30, 24 participants). Agitation scores and adverse events were not reported for this comparison. 4. Risperidone versus placebo Risperidone may slightly worsen delirium symptoms compared with placebo within 24 hours (MD 0.76, 95% CI 0.30 to 1.22; 129 participants); and at 48 hours (MD 0.85, 95% CI 0.32 to 1.38; 111 participants with mild- to moderate-severity delirium). There may be little to no difference in agitation with risperidone compared with placebo between 24 and 48 hours (MD -0.05, 95% CI -0.19 to 0.09; 111 participants with mild- to moderate-severity delirium). Risperidone may increase extrapyramidal adverse effects compared with placebo (MD 0.73 95% CI 0.09 to 1.37; 111 participants with mild- to moderate-severity delirium). 5. Lorazepam plus haloperidol versus placebo plus haloperidol We are uncertain whether lorazepam plus haloperidol compared with placebo plus haloperidol improves delirium symptoms within 24 hours (MD 2.10, 95% CI -1.00 to 5.20; 50 participants with moderate to severe delirium), reduces agitation within 24 hours (MD 1.90, 95% CI 0.90 to 2.80; 52 participants), or increases adverse events (RR 0.70, 95% CI -0.19 to 2.63; 31 participants with moderate to severe delirium). 6. Haloperidol versus chlorpromazine We are uncertain whether haloperidol reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 0.37, 95% CI -4.58 to 5.32; 24 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with chlorpromazine (MD 0.46, 95% CI -4.22 to 5.14; 24 participants). 7. Haloperidol versus lorazepam We are uncertain whether haloperidol reduces delirium symptoms compared with lorazepam at 48 hours (MD -4.88, 95% CI -9.70 to 0.06; 17 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with lorazepam (MD -6.66, 95% CI -14.85 to 1.53; 17 participants). 8. Lorazepam versus chlorpromazine We are uncertain whether lorazepam reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 5.25, 95% CI 0.38 to 10.12; 19 participants), or increases adverse events (MD 7.12, 95% CI 1.08 to 15.32; 18 participants). Agitation scores were not reported.
SECONDARY OUTCOMES
use of rescue medication, cognitive impairment, survival There were insufficient data to draw conclusions or assess GRADE.
AUTHORS' CONCLUSIONS
We found no high-quality evidence to support or refute the use of drug therapy for delirium symptoms in terminally ill adults. We found low-quality evidence that risperidone or haloperidol may slightly worsen delirium symptoms of mild to moderate severity for terminally ill people compared with placebo. We found moderate- to low-quality evidence that haloperidol and risperidone may slightly increase extrapyramidal adverse events for people with mild- to moderate-severity delirium. Given the small number of studies and participants on which current evidence is based, further research is essential.
Topics: Adult; Antipsychotic Agents; Chlorpromazine; Delirium; Haloperidol; Humans; Lorazepam; Randomized Controlled Trials as Topic; Terminally Ill
PubMed: 31960954
DOI: 10.1002/14651858.CD004770.pub3 -
Psychological Medicine Nov 2020Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.
METHODS
Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).
RESULTS
Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a 'good' response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36-3.41; I2 = 48.9) and 'any' response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35-3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on 'any' response (74.7% v. 65%; RR 1.15; 95% CI 0.82-1.62).
CONCLUSIONS
Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.
Topics: Antipsychotic Agents; Barbiturates; Benzodiazepines; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 31625485
DOI: 10.1017/S003329171900285X -
The Journal of Pediatrics Nov 2019To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the...
OBJECTIVES
To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the acute care setting.
STUDY DESIGN
Using keywords, 799 studies published up from December 1954 to February 2018 were extracted from MEDLINE via Pubmed, Embase via OVID, CINAHL via EBSCO, and Cochrane Controlled Trials Registry. Studies were evaluated for inclusion and exclusion by 2 independent reviewers using predetermined inclusion and exclusion criteria.
RESULTS
The search yielded 84 studies for full review, of which 54 were included in the systematic review. Studies were subsequently separated into 1 group of 6 case series studies containing quantitative data on sumatriptan, ondansetron, phenothiazines, prokinetic agents, carbohydrate, isometheptene, and aprepitant; 1 one group consisting only of qualitative studies containing expert recommendations.
CONCLUSIONS
Ondansetron has the most quantitative and qualitative evidence to support its inclusion in pediatric emergency department protocols as a rescue therapy. Sumatriptan and aprepitant are potential candidates for inclusion as abortive therapies. Qualitative data from retrospective studies and case reports are not applicable to a larger patient population. This report informs a need for controlled, prospective cohort studies and randomized, controlled trials to optimize current management protocols and to develop new medical interventions.
Topics: Child; Critical Care; Disease Management; Humans; Vomiting
PubMed: 31540764
DOI: 10.1016/j.jpeds.2019.06.057 -
International Journal of Molecular... Jul 2019The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries.
Topics: Bacteroidaceae Infections; Biofilms; Candida; Candidiasis; Curcumin; Dental Caries; Humans; Methylene Blue; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Rosaniline Dyes; Streptococcal Infections; Streptococcus; Tolonium Chloride; Treatment Outcome
PubMed: 31340425
DOI: 10.3390/ijms20143585