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The Cochrane Database of Systematic... Sep 2015Nausea and vomiting is a common and distressing presenting complaint in emergency departments (ED). The aetiology of nausea and vomiting in EDs is diverse and drugs are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea and vomiting is a common and distressing presenting complaint in emergency departments (ED). The aetiology of nausea and vomiting in EDs is diverse and drugs are commonly prescribed. There is currently no consensus as to the optimum drug treatment of nausea and vomiting in the adult ED setting.
OBJECTIVES
To provide evidence of the efficacy and safety of antiemetic medications in the management of nausea and vomiting in the adult ED setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8), MEDLINE (OvidSP) (January 1966 to August 2014), EMBASE (OvidSP) (January 1980 to August 2014) and ISI Web of Science (January 1955 to August 2014). We also searched relevant clinical trial registries and conference proceedings.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of any drug in the treatment of nausea and vomiting in the treatment of adults in the ED. Study eligibility was not restricted by language or publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We contacted authors of studies to obtain missing information if required.
MAIN RESULTS
We included eight trials, involving 952 participants, of which 64% were women. Included trials were generally of adequate quality, with six trials at low risk of bias, and two trials at high risk of bias. Three trials with 518 participants compared five different drugs with placebo; all reported the primary outcome as mean change in visual analogue scale (VAS) (0 to 100) for nausea severity from baseline to 30 minutes. Trials did not routinely report other primary outcomes of the change in nausea VAS at 60 minutes or number of vomiting episodes. Differences in mean VAS change from baseline to 30 minutes between placebo and the drugs evaluated were: metoclopramide (three trials, 301 participants; mean difference (MD) -5.27, 95% confidence interval (CI) -11.33 to 0.80), ondansetron (two trials, 250 participants; MD -4.32, 95% CI -11.20 to 2.56), prochlorperazine (one trial, 50 participants; MD -1.80, 95% CI -14.40 to 10.80), promethazine (one trial, 82 participants; MD -8.47, 95% CI -19.79 to 2.85) and droperidol (one trial, 48 participants; MD -15.8, 95% CI -26.98 to -4.62). The only statistically significant change in baseline VAS to 30 minutes was for droperidol, in a single trial of 48 participants. No other drug was statistically significantly superior to placebo. Other included trials evaluated a drug compared to "active controls" (alternative antiemetic). There was no convincing evidence of superiority of any particular drug compared to active control. All trials included in this review reported adverse events, but they were variably reported precluding meaningful pooling of results. Adverse events were generally mild, there were no reported serious adverse events. Overall, the quality of the evidence was low, mainly because there were not enough data.
AUTHORS' CONCLUSIONS
In an ED population, there is no definite evidence to support the superiority of any one drug over any other drug, or the superiority of any drug over placebo. Participants receiving placebo often reported clinically significant improvement in nausea, implying general supportive treatment such as intravenous fluids may be sufficient for the majority of people. If a drug is considered necessary, choice of drug may be dictated by other considerations such as a person's preference, adverse-effect profile and cost. The review was limited by the paucity of clinical trials in this setting. Future research should include the use of placebo and consider focusing on specific diagnostic groups and controlling for factors such as intravenous fluid administered.
Topics: Adult; Antiemetics; Droperidol; Emergency Service, Hospital; Female; Humans; Male; Metoclopramide; Nausea; Ondansetron; Prochlorperazine; Promethazine; Randomized Controlled Trials as Topic; Visual Analog Scale; Vomiting
PubMed: 26411330
DOI: 10.1002/14651858.CD010106.pub2 -
The Cochrane Database of Systematic... Jul 2016Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years.
OBJECTIVES
To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia.
SEARCH METHODS
We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics.
DATA COLLECTION AND ANALYSIS
Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence.
MAIN RESULTS
Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness.
AUTHORS' CONCLUSIONS
Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.
Topics: Administration, Oral; Amisulpride; Antipsychotic Agents; Benzodiazepines; Fluphenazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Treatment Outcome
PubMed: 27370402
DOI: 10.1002/14651858.CD010832.pub2 -
The Cochrane Database of Systematic... Feb 2015Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long-acting preparations, however, may be offset by a higher incidence of adverse effects.
OBJECTIVES
To assess the effects of fluphenazine decanoate and enanthate versus oral anti-psychotics and other depot neuroleptic preparations for individuals with schizophrenia in terms of clinical, social and economic outcomes.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (February 2011 and October 16, 2013), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials.
SELECTION CRITERIA
We considered all relevant randomised controlled trials (RCTs) focusing on people with schizophrenia comparing fluphenazine decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations.
DATA COLLECTION AND ANALYSIS
We reliably selected, assessed the quality, and extracted data of the included studies. For dichotomous data, we estimated risk ratio (RR) with 95% confidence intervals (CI). Analysis was by intention-to-treat. We used the mean difference (MD) for normal continuous data. We excluded continuous data if loss to follow-up was greater than 50%. Tests of heterogeneity and for publication bias were undertaken. We used a fixed-effect model for all analyses unless there was high heterogeneity. For this update. we assessed risk of bias of included studies and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table.
MAIN RESULTS
This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low.Compared with placebo, use of fluphenazine decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine decanoate with placebo reported clinically significant changes in global state or hospital admissions.Fluphenazine decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine decanoate with oral neuroleptics reported death or hospital admissions.No significant difference in relapse rates in the medium term between fluphenazine decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine decanoate and fluphenazine enanthate. No study comparing fluphenazine decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions.
AUTHORS' CONCLUSIONS
There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.
Topics: Administration, Oral; Antipsychotic Agents; Delayed-Action Preparations; Fluphenazine; Humans; Injections, Intramuscular; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25654768
DOI: 10.1002/14651858.CD000307.pub2 -
Brazilian Journal of Otorhinolaryngology 2022Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive diagnostic screening method improves diagnostic accuracy.
OBJECTIVE
This systematic review and meta-analysis was performed to assess the accuracy of chemiluminescence for diagnosis of oral cancer and precancerous lesions.
METHODS
Sixteen prospective and retrospective studies from PubMed, Cochrane database, SCOPUS, Web of Science, Embase, and Google Scholar were reviewed. Oral mucosal disorder, as detected by chemiluminescence, was compared with oral mucosal disorder detected by toluidine blue or visual examination. True-positive, true-negative, false-positive, and false-negative rates were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool (ver. 2).
RESULTS
Sensitivity, specificity, negative predictive value, and diagnostic odds ratio (DOR) of the use of toluidine blue were 0.832 (95% confidence interval [CI] 0.692-0.917), 0.429 (95% CI 0.217-0.672), 0.747 (95% CI 0.607-0.849), and 4.061 (95% CI 1.528-10.796; I=9.128%), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.743. Compared with toluidine blue, as used in 12 studies, chemiluminescence had a higher sensitivity (0.831 vs. 0.694); it had a lower specificity (0.415 vs. 0.734), negative predictive value (0.674 vs. 0.729), and DOR (3.891 vs. 7.705). Compared with clinical examination, as used in three studies, chemiluminescence had lower DOR (4.576 vs. 5.499) and area under the curve (0.818 vs. 0.91).
CONCLUSION
Although chemiluminescence itself has good sensitivity for diagnostic work-up of oral cancer and precancer, the diagnostic accuracy of chemiluminescence is comparable to or worse than toluidine blue and clinical examination. Diagnostic accuracy was therefore insufficient for reliable use of chemiluminescence alone.
Topics: Early Detection of Cancer; Humans; Luminescence; Mouth Diseases; Mouth Neoplasms; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Tolonium Chloride
PubMed: 32847738
DOI: 10.1016/j.bjorl.2020.06.011 -
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 -
The Cochrane Database of Systematic... Apr 2016Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a 'gold standard' to compare the efficacy of older and newer antipsychotic drugs. Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia, but this may not be the case and an unnecessary drain on very limited resources.
OBJECTIVES
To compare the effects of chlorpromazine with atypical or second generation antipsychotic drugs, for the treatment of people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register up to 23 September 2013.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared chlorpromazine with any other atypical antipsychotic drugs for treating people with schizophrenia. Adults (as defined in each trial) diagnosed with schizophrenia, including schizophreniform, schizoaffective and delusional disorders were included in this review.
DATA COLLECTION AND ANALYSIS
At least two review authors independently screened the articles identified in the literature search against the inclusion criteria and extracted data from included trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and the 95% confidence intervals (CIs). For continuous data, we determined the mean difference (MD) values and 95% CIs. We assessed the risk of bias in included studies and rated the quality of the evidence using the GRADE approach.
MAIN RESULTS
This review includes 71 studies comparing chlorpromazine to olanzapine, risperidone or quetiapine. None of the included trials reported any data on economic costs. 1. Chlorpromazine versus olanzapineIn the short term, there appeared to be a significantly greater clinical response (as defined in each study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to 3.99, low quality evidence). There was no difference between drugs for relapse (1 RCT, N = 70; RR 1.5, 95% CI 0.46 to 4.86, very low quality evidence), nor in average endpoint score using the Brief Psychiatric Rating Scale (BPRS) for mental state (4 RCTs, N = 245; MD 3.21, 95% CI -0.62 to 7.05,very low quality evidence). There were significantly more extrapyramidal symptoms experienced amongst people receiving chlorpromazine (2 RCTs, N = 298; RR 34.47, 95% CI 4.79 to 248.30,very low quality evidence). Quality of life ratings using the general quality of life interview (GQOLI) - physical health subscale were more favourable with people receiving olanzapine (1 RCT, N = 61; MD -10.10, 95% CI -13.93 to -6.27, very low quality evidence). There was no difference between groups for people leaving the studies early (3 RCTs, N = 139; RR 1.69, 95% CI 0.45 to 6.40, very low quality evidence). 2. Chlorpromazine versus risperidoneIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or risperidone (7 RCTs, N = 475; RR 0.84, 95% CI 0.53 to 1.34, low quality of evidence), nor in average endpoint score using the BPRS for mental state 4 RCTs, N = 247; MD 0.90, 95% CI -3.49 to 5.28, very low quality evidence), or any observed extrapyramidal adverse effects (3 RCTs, N = 235; RR 1.7, 95% CI 0.85 to 3.40,very low quality evidence). Quality of life ratings using the QOL scale were significantly more favourable with people receiving risperidone (1 RCT, N = 100; MD -14.2, 95% CI -20.50 to -7.90, very low quality evidence). There was no difference between groups for people leaving the studies early (one RCT, N = 41; RR 0.21, 95% CI 0.01 to 4.11, very low quality evidence). 3. Chlorpromazine versus quetiapineIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or quetiapine (28 RCTs, N = 3241; RR 0.93, 95% CI 0.81 to 1.06, moderate quality evidence) nor in average endpoint score using the BPRS for mental state (6 RCTs, N = 548; MD -0.18, 95% CI -1.23 to 0.88, very low quality evidence). Quality of life ratings using the GQOL1-74 scale were significantly more favourable with people receiving quetiapine (1 RCT, N = 59; MD -6.49, 95% CI -11.30 to -1.68, very low quality evidence). Significantly more people receiving chlorpromazine experienced extrapyramidal adverse effects (8 RCTs, N = 644; RR 8.03, 95% CI 4.78 to 13.51, low quality of evidence). There was no difference between groups for people leaving the studies early in the short term (12 RCTs, N = 1223; RR 1.04, 95% CI 0.77 to 1.41,moderate quality evidence).
AUTHORS' CONCLUSIONS
Most included trials included inpatients from hospitals in China. Therefore the results of this Cochrane review are more applicable to the Chinese population. Mostincluded trials were short term studies, therefore we cannot comment on the medium and long term use of chlorpromazine compared to atypical antipsychotics. Low qualityy evidence suggests chlorpromazine causes more extrapyramidal adverse effects. However, all studiesused varying dose ranges, and higher doses would be expected to be associated with more adverse events.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 27045703
DOI: 10.1002/14651858.CD010631.pub2 -
The Cochrane Database of Systematic... Oct 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between the various first-generation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between the various first-generation antipsychotics, however, low-potency first-generation antipsychotic drugs are sometimes perceived as less efficacious than high-potency first-generation compounds by clinicians, and they also seem to differ in their side effects.
OBJECTIVES
To review the effects of high-potency, first-generation perphenazine compared with low-potency, first-generation antipsychotic drugs for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (October 2010).
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing perphenazine with first-generation, low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis and using a random-effects model.
MAIN RESULTS
The review currently includes four relevant randomised trials with 365 participants. The size of the included studies was between 42 and 158 participants with a study length between one and four months. Overall, the methods of sequence generation and allocation concealment were poorly reported. Most studies were rated as low risk of bias in terms of blinding. Overall, attrition bias in the studies was high.The effects of perphenazine and low-potency antipsychotic drugs seemed to be similar in terms of the primary outcome - response to treatment (perphenazine 58%, low-potency antipsychotics 59%, 2 RCTs, n = 138, RR 0.97 CI 0.74 to 1.26 - moderate quality of evidence). There was also no clear evidence of a difference in acceptability of treatment with the number of participants leaving the studies early due to any reason, however results were imprecise (perphenazine 30%, low-potency antipsychotics 28%, 3 RCTs, n = 323, RR 0.78 CI 0.35 to 1.76, very low quality of evidence).There were low numbers of studies available for the outcomes experiencing at least one adverse effect (perphenazine 33%, low-potency antipsychotics 47%, 2 RCTs, n = 165, RR 0.83 CI 0.36 to 1.95, low quality evidence) and experiencing at least one movement disorder (perphenazine 22%, low-potency first-generation antipsychotics 0%, 1 RCT, n = 69, RR 15.62 CI 0.94 to 260.49, low quality evidence), and the confidence intervals for the estimated effects did not exclude important differences. Akathisia was more frequent in the perphenazine group (perphenazine 25%, low-potency antipsychotics 22%, 2 RCTs, n = 227, RR 9.45 CI 1.69 to 52.88), whereas severe toxicity was less so (perphenazine 42%, low-potency antipsychotics 69%, 1 RCT, n = 96, RR 0.61 CI 0.41 to 0.89).There were three deaths in the low-potency group by four months but the difference between groups was not significant (perphenazine 0%, low-potency antipsychotics 2%, 1 RCT, n = 96, RR 0.14 CI 0.01 to 2.69, moderate quality evidence). No data were available for our prespecified outcomes of interest sedation or quality of life. Data were not available for other outcomes such as relapse, service use, costs and satisfaction with care.The event rates reported quote simple aggregates and are not based on the RRs.
AUTHORS' CONCLUSIONS
The results do not show a superiority in efficacy of high-potency perphenazine compared with low-potency first-generation antipsychotics. There is some evidence that perphenazine is more likely to cause akathisia and less likely to cause severe toxicity, but most adverse effect results were equivocal. The number of studies as well as the quality of studies is low, with quality of evidence for the main outcomes ranging from moderate to very low, so more randomised evidence would be needed for conclusions to be made.
Topics: Adult; Antipsychotic Agents; Humans; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25290157
DOI: 10.1002/14651858.CD009369.pub2 -
Frontiers in Pharmacology 2023Methylene blue has a long history of clinical application. Thanks to phenothiazine chromophore, it has potential in photodynamic anticancer therapy. In spite of the...
Methylene blue has a long history of clinical application. Thanks to phenothiazine chromophore, it has potential in photodynamic anticancer therapy. In spite of the growing body of literature that has evaluated the action of this dye on different types of cancer, the systematic understanding of this problem is still lacking. Therefore, this systematic review was performed to study the efficacy of methylene blue in photodynamic anticancer therapy. This systematic review was carried out in accordance with the PRISMA guidelines, and the study protocol was registered in PROSPERO (CRD42022368738). Articles for the systematic review were identified through the PubMed database. SYRCLE's risk of bias tool was used to assess the studies. The results of systematic analysis are presented as narrative synthesis. Ten studies met the inclusion criteria and these full texts were reviewed. In the selected articles, the dosage of dye infusion ranged from 0.04 to 24.12 mg/kg. The effectiveness of photodynamic therapy with methylene blue against different types of cancer was confirmed by a decrease in tumor sizes in seven articles. The results of the systematic review support the suggestions that photodynamic therapy with methylene blue helps against different types of cancer, including colorectal tumor, carcinoma, and melanoma. In cases of nanopharmaceutics use, a considerable increase of anticancer therapy effectiveness was observed. The further research into methylene blue in photodynamic anticancer therapy is needed. (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368738), identifier (CRD42022368738).
PubMed: 37841915
DOI: 10.3389/fphar.2023.1264961 -
The Cochrane Database of Systematic... May 2021Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems.
OBJECTIVES
To assess the effectiveness and safety of using a sedative versus control (placebo, usual treatment or non-pharmacological treatment) for NAS due to withdrawal from opioids and determine which type of sedative is most effective and safe for NAS due to withdrawal from opioids.
SEARCH METHODS
We ran an updated search on 17 September 2020 in CENTRAL via CRS Web and MEDLINE via Ovid. We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
We included trials enrolling infants with NAS born to mothers with an opioid dependence with more than 80% follow-up and using randomised, quasi-randomised and cluster-randomised allocation to sedative or control.
DATA COLLECTION AND ANALYSIS
Three review authors assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS
We included 10 trials (581 infants) with NAS secondary to maternal opioid use in pregnancy. There were multiple comparisons of different sedatives and regimens. There were limited data available for use in sensitivity analysis of studies at low risk of bias. Phenobarbital versus supportive care: one study reported there may be little or no difference in treatment failure with phenobarbital and supportive care versus supportive care alone (risk ratio (RR) 2.73, 95% confidence interval (CI) 0.94 to 7.94; 62 participants; very low-certainty evidence). No infant had a clinical seizure. The study did not report mortality, neurodevelopmental disability and adverse events. There may be an increase in days' hospitalisation and treatment from use of phenobarbital (hospitalisation: mean difference (MD) 20.80, 95% CI 13.64 to 27.96; treatment: MD 17.90, 95% CI 11.98 to 23.82; both 62 participants; very low-certainty evidence). Phenobarbital versus diazepam: there may be a reduction in treatment failure with phenobarbital versus diazepam (RR 0.39, 95% CI 0.24 to 0.62; 139 participants; 2 studies; low-certainty evidence). The studies did not report mortality, neurodevelopmental disability and adverse events. One study reported there may be little or no difference in days' hospitalisation and treatment (hospitalisation: MD 3.89, 95% CI -1.20 to 8.98; 32 participants; treatment: MD 4.30, 95% CI -0.73 to 9.33; 31 participants; both low-certainty evidence). Phenobarbital versus chlorpromazine: there may be a reduction in treatment failure with phenobarbital versus chlorpromazine (RR 0.55, 95% CI 0.33 to 0.92; 138 participants; 2 studies; very low-certainty evidence), and no infant had a seizure. The studies did not report mortality and neurodevelopmental disability. One study reported there may be little or no difference in days' hospitalisation (MD 7.00, 95% CI -3.51 to 17.51; 87 participants; low-certainty evidence) and 0/100 infants had an adverse event. Phenobarbital and opioid versus opioid alone: one study reported no infants with treatment failure and no clinical seizures in either group (low-certainty evidence). The study did not report mortality, neurodevelopmental disability and adverse events. One study reported there may be a reduction in days' hospitalisation for infants treated with phenobarbital and opioid (MD -43.50, 95% CI -59.18 to -27.82; 20 participants; low-certainty evidence). Clonidine and opioid versus opioid alone: one study reported there may be little or no difference in treatment failure with clonidine and dilute tincture of opium (DTO) versus DTO alone (RR 0.09, 95% CI 0.01 to 1.59; 80 participants; very low-certainty evidence). All five infants with treatment failure were in the DTO group. There may be little or no difference in seizures (RR 0.14, 95% CI 0.01 to 2.68; 80 participants; very low-certainty evidence). All three infants with seizures were in the DTO group. There may be little or no difference in mortality after discharge (RR 7.00, 95% CI 0.37 to 131.28; 80 participants; very low-certainty evidence). All three deaths were in the clonidine and DTO group. The study did not report neurodevelopmental disability. There may be little or no difference in days' treatment (MD -4.00, 95% CI -8.33 to 0.33; 80 participants; very low-certainty evidence). One adverse event occurred in the clonidine and DTO group. There may be little or no difference in rebound NAS after stopping treatment, although all seven cases were in the clonidine and DTO group. Clonidine and opioid versus phenobarbital and opioid: there may be little or no difference in treatment failure (RR 2.27, 95% CI 0.98 to 5.25; 2 studies, 93 participants; very low-certainty evidence). One study reported one infant in the clonidine and morphine group had a seizure, and there were no infant mortalities. The studies did not report neurodevelopmental disability. There may be an increase in days' hospitalisation and days' treatment with clonidine and opioid versus phenobarbital and opioid(hospitalisation: MD 7.13, 95% CI 6.38 to 7.88; treatment: MD 7.57, 95% CI 3.97 to 11.17; both 2 studies, 91 participants; low-certainty evidence). There may be little or no difference in adverse events (RR 1.55, 95% CI 0.44 to 5.40; 2 studies, 93 participants; very low-certainty evidence). However, there was oversedation only in the phenobarbital and morphine group; and hypotension, rebound hypertension and rebound NAS only in the clonidine and morphine group.
AUTHORS' CONCLUSIONS
There is very low-certainty evidence that phenobarbital increases duration of hospitalisation and treatment, but reduces days to regain birthweight and duration of supportive care each day compared to supportive care alone. There is low-certainty evidence that phenobarbital reduces treatment failure compared to diazepam and very low-certainty evidence that phenobarbital reduces treatment failure compared to chlorpromazine. There is low-certainty evidence of an increase in days' hospitalisation and days' treatment with clonidine and opioid compared to phenobarbital and opioid. There are insufficient data to determine the safety and incidence of adverse events for infants treated with combinations of opioids and sedatives including phenobarbital and clonidine.
Topics: Bias; Chlorpromazine; Clonidine; Diazepam; Humans; Hypnotics and Sedatives; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Phenobarbital; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34002380
DOI: 10.1002/14651858.CD002053.pub4 -
Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110