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Brazilian Journal of Otorhinolaryngology 2022Traditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Traditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a single method and a single alternative, while multiple diagnostic options and the ranking thereof were methodologically not possible.
OBJECTIVE
To evaluate the diagnostic values of various methods in patients with oral potential malignant disease by performing a network meta-analysis.
METHODS
Two authors independently searched the databases (MEDLINE, SCOPUS, the Cochrane Register of Controlled Trials, and Google scholar) up to June 2020 for studies comparing the diagnostic accuracy of various tools (autofluorescence, chemiluminescence, cytology, narrow band imaging, and toluidine blue) with visual examination or other tools. The outcomes of interest for this analysis were sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Both a standard pairwise meta-analysis and network meta-analysis were conducted.
RESULTS
Treatment networks consisting of six interventions were defined for the network meta-analysis. The results of traditional meta-analysis showed that, among six methods, narrow band imaging showed higher sensitivity, specificity, negative predictive value, positive predictive value, and accuracy compared to visual examination. The results of network meta-analysis showed that autofluorescence, chemiluminescence, and narrow band imaging had higher sensitivity compared with visual examination, and that chemiluminescence and narrow band imaging had higher negative predictive value compared with visual examination. However, autofluorescence and chemiluminescence had lower specificity compared with visual examination. There were no significant differences in positive predictive value and accuracy among the six interventions.
CONCLUSION
This study demonstrated that narrow banding imaging has superiority in terms of sensitivity and negative predictive value compared with the other five tested agents.
Topics: Humans; Sensitivity and Specificity; Early Detection of Cancer; Mouth Neoplasms; Tolonium Chloride; Narrow Band Imaging; Mouth Diseases
PubMed: 33642212
DOI: 10.1016/j.bjorl.2020.12.019 -
The Cochrane Database of Systematic... Jan 2015Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first-generation ("conventional", "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first-generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high-quality systematic review appeared highly necessary.
OBJECTIVES
To compare the efficacy, acceptability, and tolerability of haloperidol with other first-generation antipsychotics in schizophrenia and schizophrenia-like psychosis.
SEARCH METHODS
In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first-generation antipsychotic drug (with the exception of the low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse events), and specific adverse effects.
DATA COLLECTION AND ANALYSIS
At least two review authors independently extracted data from the included trials. The methodological quality of the included studies was assessed using The Cochrane Collaboration`s 'Risk of bias' tool.We analysed dichotomous outcomes with risk ratios (RR) and continuous outcomes with mean differences (MD), both with the associated 95% confidence intervals (CI). All analyses were based on a random-effects model and we preferably used data on an intention-to-treat basis where possible.
MAIN RESULTS
The systematic review currently includes 63 randomised trials with 3675 participants. Bromperidol (n = 9), loxapine (n = 7), and trifluoperazine (n = 6) were the most frequently administered antipsychotics comparator to haloperidol. The included studies were published between 1962 and 1993, were characterised by small sample sizes (mean: 58 participants, range from 18 to 206) and the predefined outcomes were often incompletely reported. All results for the main outcomes were based on very low or low quality data. In many trials the mechanism of randomisation, allocation, and blinding was frequently not reported. In short-term studies (up to 12 weeks), there was no clear evidence of a difference between haloperidol and the pooled group of the other first-generation antipsychotic agents in terms of the primary outcome "clinically important response to treatment" (40 RCTs, n = 2132, RR 0.93 CI 0.87 to 1.00). In the medium-term trials, haloperidol may be less effective than the other first-generation antipsychotic group but this evidence is based on only one trial (1 RCT, n = 80, RR 0.51 CI 0.37 to 0.69).Based on limited evidence, haloperidol alleviated more positive symptoms of schizophrenia than the other antipsychotic drugs. There were no statistically significant between-group differences in global state, other mental state outcomes, behaviour, leaving the study early due to any reason, due to inefficacy, as well as due to adverse effects. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term.
AUTHORS' CONCLUSIONS
The findings of the meta-analytic calculations support the statements of previous narrative, unsystematic reviews suggesting comparable efficacy of first-generation antipsychotics. In efficacy-related outcomes, there was no clear evidence of a difference between the prototypal drug haloperidol and other, mainly high-potency first-generation antipsychotics. Additionally, we demonstrated that haloperidol is characterised by a similar risk profile compared to the other first-generation antipsychotic compounds. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term. The results were limited by the low methodological quality in many of the included original studies. Data for the main results were low or very low quality. Therefore, future clinical trials with high methodological quality are required.
Topics: Administration, Oral; Antipsychotic Agents; Haloperidol; Humans; Loxapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Trifluoperazine
PubMed: 25592299
DOI: 10.1002/14651858.CD009831.pub2 -
Surgical Oncology Apr 2024In patients with colorectal cancer (CRC), the most important factor to decide the need of adjuvant chemotherapy is the histological lymph node (LN) evaluation. Our work... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
In patients with colorectal cancer (CRC), the most important factor to decide the need of adjuvant chemotherapy is the histological lymph node (LN) evaluation. Our work aimed to give a broad view over the use of methylene blue and its consequences in the number of lymph node harvest.
METHODS
PUBMED, WEB OF SCIENCE and EMBASE databases were consulted, retrieving clinical trials, which mentioned the used of intra-arterial methylene blue in patients with colorectal cancer.
RESULTS
Eighteen clinical trials analyzing the use of intra-arterial methylene blue in specimens of colorectal cancer were selected. The articles show a statistical difference between the use of methylene blue and the classical dissection in both variable at study. The results of the statistical analysis of the lymph node harvest variable demonstrate a significant statistical difference between the group that received methylene blue injection and the group that underwent conventional dissection. There is a significant statistical difference between the experimental and control groups for the ideal lymph node harvest (lymph node harvest count greater than 12).
CONCLUSION
The use of intra-arterial methylene blue revealed a high potential for the quantification of lymph nodes, considering the increase of lymph node harvest and the higher percentage of cases with more than 12 lymph nodes count, albeit the high heterogeneity between the studies in terms of reported results. Future investigations with controlled double blinded studies obtaining better categorized results should be conducted in order to better evaluate this technique and compare it to the current paradigm.
Topics: Humans; Lymph Node Excision; Methylene Blue; Lymph Nodes; Dissection; Colorectal Neoplasms; Sentinel Lymph Node Biopsy
PubMed: 38377643
DOI: 10.1016/j.suronc.2024.102046 -
Techniques in Coloproctology Apr 2019Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional...
BACKGROUND
Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional assessment of IUI includes visual inspection and palpation. This is especially challenging during laparoscopic procedures and has translated into an increased risk of IUI. The use of near-infrared fluorescent (NIRF) imaging is currently being considered as a novel method to identify the ureters intraoperatively. The aim of this review is to describe the currently available and experimental dyes for ureter visualization and to evaluate their feasibility of using them and their effectiveness.
METHODS
This article adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for systematic reviews. A systematic literature search was performed in the PubMed database. All included articles were screened for eligibility by two authors. Three clinical trial databases were consulted to identify ongoing or completed unpublished trials. Risk of bias was assessed for all articles.
RESULTS
The search yielded 20 articles on ureter visualization. Two clinically available dyes, indocyanine green (ICG) and methylene blue (MB), and eight experimental dyes were described and assessed for their feasibility to identify the ureter. Two ongoing clinical trials on CW800-BK and one trial on ZW800-1 for ureter visualization were identified.
CONCLUSIONS
Currently available dyes, ICG and MB, are safe, but suboptimal for ureter visualization based on the route of administration and optical properties, respectively. Currently, MB has potential to be routinely used for ureter visualization in most patients, but (cRGD-)ZW800-1 holds potential for this role in the future, owing to its exclusive renal clearance and the near absence of background. To assess the benefit of NIRF imaging for reducing the incidence of IUI, larger patient cohorts need to be examined.
Topics: Fluorescence; Fluorescent Dyes; Fluoroscopy; Humans; Indocyanine Green; Laparoscopy; Methylene Blue; Spectroscopy, Near-Infrared; Ureter
PubMed: 31030340
DOI: 10.1007/s10151-019-01973-4 -
The Cochrane Database of Systematic... Jan 2018Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI.
OBJECTIVES
To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse.
SEARCH METHODS
On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers).
SELECTION CRITERIA
We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data.
DATA COLLECTION AND ANALYSIS
We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach.
MAIN RESULTS
We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 294, RR 0.96, 95% CI 0.86 to 1.07, low-quality evidence).For risperidone versus ziprasidone, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 240, RR 0.96, 95% CI 0.85 to 1.10, low-quality evidence).For many comparisons, important outcomes were missing; and no data were reported in any study for metabolic disturbances, global impression of illness severity, quality of life or mortality.
AUTHORS' CONCLUSIONS
There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.
Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Diagnosis, Dual (Psychiatry); Humans; Mental Disorders; Olanzapine; Patient Dropouts; Perphenazine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Substance-Related Disorders; Thiazoles
PubMed: 29355909
DOI: 10.1002/14651858.CD011057.pub2 -
Asian Pacific Journal of Cancer... May 2020Either blue dye (BD) or radioisotope (RI) is mainly used for sentinel lymph node biopsy (SLNB) in breast cancer patients. Unlike the BD, RI has lower false-negative rate... (Meta-Analysis)
Meta-Analysis
Indocyanine Green Fluorescence Versus Blue Dye or Radioisotope Regarding Detection Rate of Sentinel Lymph Node Biopsy and Nodes Removed in Breast Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
Either blue dye (BD) or radioisotope (RI) is mainly used for sentinel lymph node biopsy (SLNB) in breast cancer patients. Unlike the BD, RI has lower false-negative rate of SLNB. However, its lymphoscintigraphy, difficulty in preoperative injection, and undetected sentinel lymph nodes in some cases cause surgeons to rely only on BD. Currently, indocyanine green (ICG) fluorescence method (ICG-SLNB) is increasingly used as an alternative to the conventional mapping methods in many centers. This systematic review compared ICG with the conventional method of BD or RI in terms of detection rate of SLNB and the number of sentinel lymph nodes (SLNs) removed in.
METHODS
We searched all relevant studies published between January 2000 and October 2019. All data on for evaluation of SLN detection rate, number of SLNs removed per patient, and tumor positive rate of SLNB were extracted.
RESULTS
A total of 30 studies, including 4,216 SLN procedures were retrieved. There was a statistically significant difference between ICG and BD method in terms of SLN detection rate (OR, 6.73; 95% CI, 4.20-10.78). However, there was no significant difference between ICG and RI in this regard (OR, 0.90; 95% CI, 0.40-2.03). The number of SLNs removed per patient were 2.35 (1.46-5.4), 1.92 (1.0-3.64), and 1.72 (1.35-2.08) for ICG, BD, and RI, respectively. Only in 8 studies, the tumor positive rates in SLNB could be analyzed (ICG, 8.5-20.7%; BD, 12.7-21.4%; RI, 11.3-16%).
CONCLUSION
ICG-SLNB could be an additional or an alternative method for axillary node mapping in breast cancer.
.Topics: Breast Neoplasms; Coloring Agents; Female; Fluorescence; Humans; Indocyanine Green; Methylene Blue; Prognosis; Radiopharmaceuticals; Sentinel Lymph Node
PubMed: 32458621
DOI: 10.31557/APJCP.2020.21.5.1187 -
The Cochrane Database of Systematic... Jul 2017Nausea is a common symptom in advanced cancer, with a prevalence of up to 70%. While nausea and vomiting can be related to cancer treatments, such as chemotherapy,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea is a common symptom in advanced cancer, with a prevalence of up to 70%. While nausea and vomiting can be related to cancer treatments, such as chemotherapy, radiotherapy, or surgery, a significant number of people with advanced cancer also suffer from nausea unrelated to such therapies. Nausea and vomiting may also cause psychological distress, and have a negative impact on the quality of life of cancer patients; similarly to pain, nausea is often under-treated. The exact mechanism of action of corticosteroids on nausea is unclear, however, they are used to manage a number of cancer-specific complications, including spinal cord compression, raised intracranial pressure, and lymphangitis carcinomatosis. They are also commonly used in palliative care for a wide variety of non-specific indications, such as pain, nausea, anorexia, fatigue, and low mood. However, there is little objective evidence of their efficacy in symptom control, and corticosteroids have a wide range of adverse effects that are dose and time dependent. In view of their widespread use, it is important to seek evidence of their effects on nausea and vomiting not related to cancer treatment.
OBJECTIVES
To assess the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients.
SEARCH METHODS
We searched CENTRAL, MEDLINE Ovid, Embase Ovid, CINAHL EBSCO, Science Citation Index Web of Science, Latin America and Caribbean Health Sciences (LILACS), Conference Proceedings Citation Index - Science Web of Science, and clinical trial registries, from inception to 23rd August 2016.
SELECTION CRITERIA
Any double-blind randomised or prospective controlled trial that included adults aged 18 years and over with advanced cancer with nausea and vomiting not related to chemotherapy, radiotherapy, or surgery were eligible for the review, when using corticosteroids as antiemetic treatment.
DATA COLLECTION AND ANALYSIS
All review authors independently assessed trial quality and extracted data. We used arithmetic means and standard deviations for each outcome to report the mean difference (MD) with 95% confidence interval (CI). We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
Three studies met the inclusion criteria, enrolling 451 participants. The trial size varied from 51 to 280 participants. Two studies compared dexamethasone to placebo, and the third study compared a number of additional interventions in various combinations, including metoclopramide, chlorpromazine, tropisetron, and dexamethasone. The duration of the studies ranged from seven to 14 days. We included two studies (127 participants) with data at eight days in the meta-analysis for nausea intensity; no data were available that incorporated the same outcome measures for the third study. Corticosteroid therapy with dexamethasone resulted in less nausea (measured on a scale of 0 to 10, with a lower score indicating less nausea) compared to placebo at eight days (MD 0.48 lower nausea, 95% CI 1.53 lower to 0.57 higher; very low-quality evidence), although this result was not statistically significant (P = 0.37). Frequency of adverse events was not significantly different between groups, and the interventions were well tolerated. Factors limiting statistical analysis included the lack of standardised measurements of nausea, and the use of different agents, dosages, and comparisons. Subgroup analysis according to type of cancer was not possible due to insufficient data. The quality of this evidence was downgraded by three levels, from high to very low due to imprecision, likely selection bias, attrition bias, and the small number of participants in the included studies.
AUTHORS' CONCLUSIONS
There are few studies assessing the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients. This review found very low-quality evidence which neither supported nor refuted corticosteroid use in this setting. Further high quality studies are needed to determine if corticosteroids are efficacious in this setting.
Topics: Adrenal Cortex Hormones; Adult; Chlorpromazine; Dexamethasone; Humans; Indoles; Metoclopramide; Nausea; Neoplasms; Time Factors; Tropisetron; Vomiting
PubMed: 28671265
DOI: 10.1002/14651858.CD012002.pub2 -
Photodiagnosis and Photodynamic Therapy Apr 2024The aim was to systematically review clinical studies that investigated the efficacy of antimicrobial photodynamic therapy (aPDT) in reducing oral yeasts growth (OYG) in... (Review)
Review
OBJECTIVE
The aim was to systematically review clinical studies that investigated the efficacy of antimicrobial photodynamic therapy (aPDT) in reducing oral yeasts growth (OYG) in individuals wearing implant overdentures (IO).
METHODS
The focused question was "Is aPDT effective in reducing OYG in patients wearing IO?" Literature search was performed in accordance with PRISMA guidelines. Indexed databases were searched without time and language restrictions up to and including January 2024. Clinical studies were included; and letters to the Editor, case-reports/case-series, perspectives/commentaries, in-vitro/ex-vivo studies, studies on animal models and expert opinions were excluded. The risk of bias was also assessed.
RESULTS
Two clinical studies were included and processed for data extraction. The study population comprised of 100 (mean age: 58.5 years) and 53 (mean age: 58.5 years) individuals. The numbers of males and females included in these studies ranged between 33 and 35 males and 18-67 females, respectively. In both studies, follow-up evaluations were performed after 60 days. In both studies, aPDT was performed using a 660 nm diode laser at a power of 100 mW and using methylene-blue as photosensitizer. Results from both studies showed that aPDT is effective in significantly reducing oral yeasts CFU/ml and improvement of OHRQoL of individuals using IO.
CONCLUSION
The aPDT is useful in reducing OYG on IO; however, further well-designed and power-adjusted studies are needed in this area of research.
Topics: Photochemotherapy; Humans; Photosensitizing Agents; Denture, Overlay; Methylene Blue; Lasers, Semiconductor; Yeasts; Clinical Trials as Topic
PubMed: 38548040
DOI: 10.1016/j.pdpdt.2024.104050 -
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 -
The Cochrane Database of Systematic... Dec 2018Early accurate detection of all skin cancer types is essential to guide appropriate management, reduce morbidity and improve survival. Basal cell carcinoma (BCC) is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early accurate detection of all skin cancer types is essential to guide appropriate management, reduce morbidity and improve survival. Basal cell carcinoma (BCC) is usually localised to the skin but has potential to infiltrate and damage surrounding tissue, while cutaneous squamous cell carcinoma (cSCC) and melanoma have a much higher potential to metastasise and ultimately lead to death. Exfoliative cytology is a non-invasive test that uses the Tzanck smear technique to identify disease by examining the structure of cells obtained from scraped samples. This simple procedure is a less invasive diagnostic test than a skin biopsy, and for BCC it has the potential to provide an immediate diagnosis that avoids an additional clinic visit to receive skin biopsy results. This may benefit patients scheduled for either Mohs micrographic surgery or non-surgical treatments such as radiotherapy. A cytology scrape can never give the same information as a skin biopsy, however, so it is important to better understand in which skin cancer situations it may be helpful.
OBJECTIVES
To determine the diagnostic accuracy of exfoliative cytology for detecting basal cell carcinoma (BCC) in adults, and to compare its accuracy with that of standard diagnostic practice (visual inspection with or without dermoscopy). Secondary objectives were: to determine the diagnostic accuracy of exfoliative cytology for detecting cSCC, invasive melanoma and atypical intraepidermal melanocytic variants, and any other skin cancer; and for each of these secondary conditions to compare the accuracy of exfoliative cytology with visual inspection with or without dermoscopy in direct test comparisons; and to determine the effect of observer experience.
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We also studied the reference lists of published systematic review articles.
SELECTION CRITERIA
Studies evaluating exfoliative cytology in adults with lesions suspicious for BCC, cSCC or melanoma, compared with a reference standard of histological confirmation.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Where possible we estimated summary sensitivities and specificities using the bivariate hierarchical model.
MAIN RESULTS
We synthesised the results of nine studies contributing a total of 1655 lesions to our analysis, including 1120 BCCs (14 datasets), 41 cSCCs (amongst 401 lesions in 2 datasets), and 10 melanomas (amongst 200 lesions in 1 dataset). Three of these datasets (one each for BCC, melanoma and any malignant condition) were derived from one study that also performed a direct comparison with dermoscopy. Studies were of moderate to poor quality, providing inadequate descriptions of participant selection, thresholds used to make cytological and histological diagnoses, and blinding. Reporting of participants' prior referral pathways was particularly poor, as were descriptions of the cytodiagnostic criteria used to make diagnoses. No studies evaluated the use of exfoliative cytology as a primary diagnostic test for detecting BCC or other skin cancers in lesions suspicious for skin cancer. Pooled data from seven studies using standard cytomorphological criteria (but various stain methods) to detect BCC in participants with a high clinical suspicion of BCC estimated the sensitivity and specificity of exfoliative cytology as 97.5% (95% CI 94.5% to 98.9%) and 90.1% (95% CI 81.1% to 95.1%). respectively. When applied to a hypothetical population of 1000 clinically suspected BCC lesions with a median observed BCC prevalence of 86%, exfoliative cytology would miss 21 BCCs and would lead to 14 false positive diagnoses of BCC. No false positive cases were histologically confirmed to be melanoma. Insufficient data are available to make summary statements regarding the accuracy of exfoliative cytology to detect melanoma or cSCC, or its accuracy compared to dermoscopy.
AUTHORS' CONCLUSIONS
The utility of exfoliative cytology for the primary diagnosis of skin cancer is unknown, as all included studies focused on the use of this technique for confirming strongly suspected clinical diagnoses. For the confirmation of BCC in lesions with a high clinical suspicion, there is evidence of high sensitivity and specificity. Since decisions to treat low-risk BCCs are unlikely in practice to require diagnostic confirmation given that clinical suspicion is already high, exfoliative cytology might be most useful for cases of BCC where the treatments being contemplated require a tissue diagnosis (e.g. radiotherapy). The small number of included studies, poor reporting and varying methodological quality prevent us from drawing strong conclusions to guide clinical practice. Despite insufficient data on the use of cytology for cSCC or melanoma, it is unlikely that cytology would be useful in these scenarios since preservation of the architecture of the whole lesion that would be available from a biopsy provides crucial diagnostic information. Given the paucity of good quality data, appropriately designed prospective comparative studies may be required to evaluate both the diagnostic value of exfoliative cytology by comparison to dermoscopy, and its confirmatory value in adequately reported populations with a high probability of BCC scheduled for further treatment requiring a tissue diagnosis.
Topics: Adult; Azure Stains; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Coloring Agents; Cytodiagnosis; Dermoscopy; Humans; Melanoma; Papanicolaou Test; Sensitivity and Specificity; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 30521689
DOI: 10.1002/14651858.CD013187