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Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.The Cochrane Database of Systematic... Mar 2017Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. While researching the effects of the steroid dexamethasone on premature parturition in fetal sheep in 1969, Liggins found that there was some inflation of the lungs of lambs born at gestations at which the lungs would be expected to be airless. Liggins and Howie published the first randomised controlled trial in humans in 1972 and many others followed.
OBJECTIVES
To assess the effects of administering a course of corticosteroids to the mother prior to anticipated preterm birth on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (17 February 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
We considered all randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following spontaneous labour), regardless of other co-morbidity, for inclusion in this review. Most women in this review received a single course of steroids; however, nine of the included trials allowed for women to have weekly repeats.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
This update includes 30 studies (7774 women and 8158 infants). Most studies are of low or unclear risk for most bias domains. An assessment of high risk usually meant a trial had potential for performance bias due to lack of blinding. Two trials had low risks of bias for all risk of bias domains.Treatment with antenatal corticosteroids (compared with placebo or no treatment) is associated with a reduction in the most serious adverse outcomes related to prematurity, including: perinatal death (average risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.89; participants = 6729; studies = 15; Tau² = 0.05, I² = 34%; moderate-quality); neonatal death (RR 0.69, 95% CI 0.59 to 0.81; participants = 7188; studies = 22), RDS (average RR 0.66, 95% CI 0.56 to 0.77; participants = 7764; studies = 28; Tau² = 0.06, I² = 48%; moderate-quality); moderate/severe RDS (average RR 0.59, 95% CI 0.38 to 0.91; participants = 1686; studies = 6; Tau² = 0.14, I² = 52%); intraventricular haemorrhage (IVH) (average RR 0.55, 95% CI 0.40 to 0.76; participants = 6093; studies = 16; Tau² = 0.10, I² = 33%; moderate-quality), necrotising enterocolitis (RR 0.50, 95% CI 0.32 to 0.78; participants = 4702; studies = 10); need for mechanical ventilation (RR 0.68, 95% CI 0.56 to 0.84; participants = 1368; studies = 9); and systemic infections in the first 48 hours of life (RR 0.60, 95% CI 0.41 to 0.88; participants = 1753; studies = 8).There was no obvious benefit for: chronic lung disease (average RR 0.86, 95% CI 0.42 to 1.79; participants = 818; studies = 6; Tau² = 0.38 I² = 65%); mean birthweight (g) (MD -18.47, 95% CI -40.83 to 3.90; participants = 6182; studies = 16; moderate-quality); death in childhood (RR 0.68, 95% CI 0.36 to 1.27; participants = 1010; studies = 4); neurodevelopment delay in childhood (RR 0.64, 95% CI 0.14 to 2.98; participants = 82; studies = 1); or death into adulthood (RR 1.00, 95% CI 0.56 to 1.81; participants = 988; studies = 1).Treatment with antenatal corticosteroids does not increase the risk of chorioamnionitis (RR 0.83, 95% CI 0.66 to 1.06; participants = 5546; studies = 15; moderate-quality evidence) or endometritis (RR 1.20, 95% CI 0.87 to 1.63; participants = 4030; studies = 10; Tau² = 0.11, I² = 28%; moderate-quality). No increased risk in maternal death was observed. However, the data on maternal death is based on data from a single trial with two deaths; four other trials reporting maternal death had zero events (participants = 3392; studies = 5; moderate-quality).There is no definitive evidence to suggest that antenatal corticosteroids work differently in any pre-specified subgroups (singleton versus multiple pregnancy; membrane status; presence of hypertension) or for different study protocols (type of corticosteroid; single course or weekly repeats).GRADE outcomes were downgraded to moderate-quality. Downgrading decisions (for perinatal death, RDS, IVH, and mean birthweight) were due to limitations in study design or concerns regarding precision (chorioamnionitis, endometritis). Maternal death was downgraded for imprecision due to few events.
AUTHORS' CONCLUSIONS
Evidence from this update supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids could be considered routine for preterm delivery. It is important to note that most of the evidence comes from high income countries and hospital settings; therefore, the results may not be applicable to low-resource settings with high rates of infections.There is little need for further trials of a single course of antenatal corticosteroids versus placebo in singleton pregnancies in higher income countries and hospital settings. However, data are sparse in lower income settings. There are also few data regarding risks and benefits of antenatal corticosteroids in multiple pregnancies and other high-risk obstetric groups. Further information is also required concerning the optimal dose-to-delivery interval, and the optimal corticosteroid to use.We encourage authors of previous studies to provide further information, which may answer any remaining questions about the use of antenatal corticosteroids in such pregnancies without the need for further randomised controlled trials. Individual patient data meta-analysis from published trials is likely to answer some of the evidence gaps. Follow-up studies into childhood and adulthood, particularly in the late preterm gestation and repeat courses groups, are needed. We have not examined the possible harmful effects of antenatal corticosteroids in low-resource settings in this review. It would be particularly relevant to explore this finding in adequately powered prospective trials.
Topics: Adrenal Cortex Hormones; Betamethasone; Dexamethasone; Female; Fetal Organ Maturity; Humans; Hydrocortisone; Infant, Newborn; Lung; Maternal Death; Perinatal Death; Pregnancy; Premature Birth; Prenatal Care; Respiratory Distress Syndrome, Newborn
PubMed: 28321847
DOI: 10.1002/14651858.CD004454.pub3 -
The Cochrane Database of Systematic... Nov 2021About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK₁) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head-to-head comparisons do not allow comparison of all treatments versus another. OBJECTIVES: • In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting in network meta-analysis (NMA) - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy • In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting to treatment combinations including 5-HT₃ receptor antagonists and corticosteroids solely, in network meta-analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs).
SELECTION CRITERIA
We included RCTs including adults with any cancer receiving HEC or MEC (according to the latest definition) and comparing combination therapies of NK₁ and 5-HT₃ inhibitors and corticosteroids for prevention of CINV.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We expressed treatment effects as risk ratios (RRs). Prioritised outcomes were complete control of vomiting during delayed and overall phases, complete control of nausea during the overall phase, quality of life, serious adverse events (SAEs), and on-study mortality. We assessed GRADE and developed 12 'Summary of findings' tables. We report results of most crucial outcomes in the abstract, that is, complete control of vomiting during the overall phase and SAEs. For a comprehensive illustration of results, we randomly chose aprepitant plus granisetron as exemplary reference treatment for HEC, and granisetron as exemplary reference treatment for MEC.
MAIN RESULTS
Highly emetogenic chemotherapy (HEC) We included 73 studies reporting on 25,275 participants and comparing 14 treatment combinations with NK₁ and 5-HT₃ inhibitors. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 704 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with aprepitant + granisetron. Evidence from NMA (39 RCTs, 21,642 participants; 12 treatment combinations with NK₁ and 5-HT₃ inhibitors) suggests that the following drug combinations are more efficacious than aprepitant + granisetron for completely controlling vomiting during the overall treatment phase (one to five days): fosnetupitant + palonosetron (810 of 1000; RR 1.15, 95% confidence interval (CI) 0.97 to 1.37; moderate certainty), aprepitant + palonosetron (753 of 1000; RR 1.07, 95% CI 1.98 to 1.18; low-certainty), aprepitant + ramosetron (753 of 1000; RR 1.07, 95% CI 0.95 to 1.21; low certainty), and fosaprepitant + palonosetron (746 of 1000; RR 1.06, 95% CI 0.96 to 1.19; low certainty). Netupitant + palonosetron (704 of 1000; RR 1.00, 95% CI 0.93 to 1.08; high-certainty) and fosaprepitant + granisetron (697 of 1000; RR 0.99, 95% CI 0.93 to 1.06; high-certainty) have little to no impact on complete control of vomiting during the overall treatment phase (one to five days) when compared to aprepitant + granisetron, respectively. Evidence further suggests that the following drug combinations are less efficacious than aprepitant + granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): aprepitant + ondansetron (676 of 1000; RR 0.96, 95% CI 0.88 to 1.05; low certainty), fosaprepitant + ondansetron (662 of 1000; RR 0.94, 95% CI 0.85 to 1.04; low certainty), casopitant + ondansetron (634 of 1000; RR 0.90, 95% CI 0.79 to 1.03; low certainty), rolapitant + granisetron (627 of 1000; RR 0.89, 95% CI 0.78 to 1.01; moderate certainty), and rolapitant + ondansetron (598 of 1000; RR 0.85, 95% CI 0.65 to 1.12; low certainty). We could not include two treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron) in NMA for this outcome because of missing direct comparisons. Serious adverse events We estimated that 35 of 1000 participants experience any SAEs when treated with aprepitant + granisetron. Evidence from NMA (23 RCTs, 16,065 participants; 11 treatment combinations) suggests that fewer participants may experience SAEs when treated with the following drug combinations than with aprepitant + granisetron: fosaprepitant + ondansetron (8 of 1000; RR 0.23, 95% CI 0.05 to 1.07; low certainty), casopitant + ondansetron (8 of 1000; RR 0.24, 95% CI 0.04 to 1.39; low certainty), netupitant + palonosetron (9 of 1000; RR 0.27, 95% CI 0.05 to 1.58; low certainty), fosaprepitant + granisetron (13 of 1000; RR 0.37, 95% CI 0.09 to 1.50; low certainty), and rolapitant + granisetron (20 of 1000; RR 0.57, 95% CI 0.19 to 1.70; low certainty). Evidence is very uncertain about the effects of aprepitant + ondansetron (8 of 1000; RR 0.22, 95% CI 0.04 to 1.14; very low certainty), aprepitant + ramosetron (11 of 1000; RR 0.31, 95% CI 0.05 to 1.90; very low certainty), fosaprepitant + palonosetron (12 of 1000; RR 0.35, 95% CI 0.04 to 2.95; very low certainty), fosnetupitant + palonosetron (13 of 1000; RR 0.36, 95% CI 0.06 to 2.16; very low certainty), and aprepitant + palonosetron (17 of 1000; RR 0.48, 95% CI 0.05 to 4.78; very low certainty) on the risk of SAEs when compared to aprepitant + granisetron, respectively. We could not include three treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron, rolapitant + ondansetron) in NMA for this outcome because of missing direct comparisons. Moderately emetogenic chemotherapy (MEC) We included 38 studies reporting on 12,038 participants and comparing 15 treatment combinations with NK₁ and 5-HT₃ inhibitors, or 5-HT₃ inhibitors solely. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 555 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with granisetron. Evidence from NMA (22 RCTs, 7800 participants; 11 treatment combinations) suggests that the following drug combinations are more efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days): aprepitant + palonosetron (716 of 1000; RR 1.29, 95% CI 1.00 to 1.66; low certainty), netupitant + palonosetron (694 of 1000; RR 1.25, 95% CI 0.92 to 1.70; low certainty), and rolapitant + granisetron (660 of 1000; RR 1.19, 95% CI 1.06 to 1.33; high certainty). Palonosetron (588 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) and aprepitant + granisetron (577 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) may or may not increase complete response in the overall treatment phase (one to five days) when compared to granisetron, respectively. Azasetron (560 of 1000; RR 1.01, 95% CI 0.76 to 1.34; low certainty) may result in little to no difference in complete response in the overall treatment phase (one to five days) when compared to granisetron. Evidence further suggests that the following drug combinations are less efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): fosaprepitant + ondansetron (500 of 100; RR 0.90, 95% CI 0.66 to 1.22; low certainty), aprepitant + ondansetron (477 of 1000; RR 0.86, 95% CI 0.64 to 1.17; low certainty), casopitant + ondansetron (461 of 1000; RR 0.83, 95% CI 0.62 to 1.12; low certainty), and ondansetron (433 of 1000; RR 0.78, 95% CI 0.59 to 1.04; low certainty). We could not include five treatment combinations (fosaprepitant + granisetron, azasetron, dolasetron, ramosetron, tropisetron) in NMA for this outcome because of missing direct comparisons. Serious adverse events We estimated that 153 of 1000 participants experience any SAEs when treated with granisetron. Evidence from pair-wise comparison (1 RCT, 1344 participants) suggests that more participants may experience SAEs when treated with rolapitant + granisetron (176 of 1000; RR 1.15, 95% CI 0.88 to 1.50; low certainty). NMA was not feasible for this outcome because of missing direct comparisons. Certainty of evidence Our main reason for downgrading was serious or very serious imprecision (e.g. due to wide 95% CIs crossing or including unity, few events leading to wide 95% CIs, or small information size). Additional reasons for downgrading some comparisons or whole networks were serious study limitations due to high risk of bias or moderate inconsistency within networks.
AUTHORS' CONCLUSIONS
This field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematically researched and assessed. For people receiving HEC, synthesised evidence does not suggest one superior treatment for prevention and control of chemotherapy-induced nausea and vomiting. For people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK₁ and 5-HT₃ inhibitors when compared to treatments including 5-HT₃ inhibitors only. Rather, the results of our NMA suggest that the choice of 5-HT₃ inhibitor may have an impact on treatment efficacy in preventing CINV. When interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head-to-head comparisons, and that results of our NMA do not necessarily rule out differences that could be clinically relevant for some individuals.
Topics: Adult; Antiemetics; Antineoplastic Agents; Humans; Nausea; Network Meta-Analysis; Palonosetron; Randomized Controlled Trials as Topic; Vomiting
PubMed: 34784425
DOI: 10.1002/14651858.CD012775.pub2 -
The Cochrane Database of Systematic... Jun 2018Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.
OBJECTIVES
Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.
SEARCH METHODS
We searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature.
SELECTION CRITERIA
We included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients.
DATA COLLECTION AND ANALYSIS
We examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes.
MAIN RESULTS
We included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.No trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).No trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence).
AUTHORS' CONCLUSIONS
There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Haloperidol; Hospitalization; Humans; Male; Olanzapine; Placebo Effect; Randomized Controlled Trials as Topic; Risperidone
PubMed: 29920656
DOI: 10.1002/14651858.CD005594.pub3 -
The Cochrane Database of Systematic... Mar 2018Postoperative nausea and vomiting (PONV) is a common, unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common, unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as an addition to the available treatment strategies. This review was originally published in 2012 and updated in 2017.
OBJECTIVES
The main objective was to establish the efficacy and safety of aromatherapy comparable to standard pharmacological treatments for PONV in adults and children.
SEARCH METHODS
We searched CENTRAL; MEDLINE; Embase; CINAHL; CAM on PubMed; Informit; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles up to March 2017. The original search was performed in August 2011.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat PONV. Interventions were all types of aromatherapy compared to placebo or with standard antiemetics. Primary outcomes were severity and duration of PONV. Secondary outcomes were adverse reactions, use of rescue antiemetics and patient satisfaction.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias in the included studies and extracted data. For dichotomous outcome variables, we used a random-effects model and calculated risk ratio (RR) with associated 95% confidence interval (95% CI). For continuous outcome variables, we used a random-effects model and calculated standardized mean difference (SMD) with associated 95% CI. We used the GRADE software to compile 'Summary of findings' tables.
MAIN RESULTS
We included seven new studies with 663 participants in the 2017 update; five RCTs and two CCTs. These were added to the nine previously included studies (six RCTs and three CCTs with a total of 373 participants) for a total of 16 included studies and 1036 participants in this updated review. The mean age and range data for all participants were not reported for all studies. We identified two registered trials that met the inclusion criteria for this review; however there are no results for these studies yet.Overall, the GRADE assessment of evidence quality ranged from moderate to very low. The method of randomization in 11 of the 12 included RCTs was explicitly stated and adequate. Incomplete or methodologically diverse reporting of data affected the completeness of the analysis. Data on additional aromatherapies were added in the 2017 update (blended aromatherapy products, and peppermint products). Heterogeneity of outcome measures and time points between studies affected the completeness of the analysis.In the summary of the findings of six studies, we did not find aromatherapy to be effective in reducing nausea severity in comparison to placebo (SMD -0.22, 95% CI -0.63 to 0.18, P value = 0.28, 241 participants, level of evidence: low). Those participants receiving aromatherapy were no more likely to be free of nausea at the end of the treatment period than those receiving placebo (RR 3.25, 95% CI 0.31 to 34.33, P value = 0.33, 4 trials, 193 participants, evidence level: very low), however they were less likely to require rescue antiemetics (RR 0.60, 95% CI 0.37 to 0.97, P value = 0.04, 7 trials, 609 participants, evidence level: low). There were no data reported on adverse events or patient satisfaction for this comparison.A specific comparison of peppermint aromatherapy to placebo did not show evidence of an effect on nausea severity at five minutes post-treatment in the pooled results (SMD -0.18, 95% CI -0.86 to 0.49, P value = 0.59, 4 trials, 115 participants, evidence level: low). There were no data reported on nausea duration, use of rescue antiemetics, adverse events or patient satisfaction for this comparison.When we pooled studies comparing isopropyl alcohol to standard antiemetic treatment in a GRADE summary of findings, in terms of nausea duration, there was a significant effect on the time in minutes to a 50% reduction in nausea scores (SMD -1.10, 95% CI -1.43 to -0.78, P value < 0.00001, 3 trials, 176 participants, evidence level: moderate). Fewer participants who received isopropyl alcohol required rescue antiemetics (RR 0.67, 95% CI 0.46 to 0.98, P value = 0.04, 215 participants, 4 trials, evidence level: moderate). Two studies with 172 participants measured patient satisfaction; there were high levels of satisfaction across both aromatherapy and standard treatment groups and no differences found (evidence level: low). There were no data reported on nausea severity or adverse events for this comparison.There was no difference in effectiveness between isopropyl alcohol vapour inhalation and placebo for reducing the proportion of participants requiring rescue antiemetics (RR 0.39, 95% CI 0.12 to 1.24, P value = 0.11, 291 participants, 4 trials, evidence level: very low). There were no data reported on nausea severity, nausea duration, adverse events or patient satisfaction for this comparison.
AUTHORS' CONCLUSIONS
Overall, for nausea severity at the end of treatment, aromatherapy may have similar effectiveness to placebo and similar numbers of participants were nausea-free. However, this finding is based on low-quality evidence and therefore very uncertain. Low-quality evidence also suggests that participants who received aromatherapy may need fewer antiemetic medications, but again, this is uncertain. Participants receiving either aromatherapy or antiemetic medications may report similar levels of satisfaction with their treatment, according to low-quality evidence.
Topics: 2-Propanol; Administration, Inhalation; Antiemetics; Aromatherapy; Controlled Clinical Trials as Topic; Humans; Plant Oils; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Salvage Therapy
PubMed: 29523018
DOI: 10.1002/14651858.CD007598.pub3 -
Alimentary Pharmacology & Therapeutics Sep 2022Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line therapy because of their action on gut dysmotility. In this regard, peppermint oil also has antispasmodic properties.
AIM
To update our previous meta-analysis to assess efficacy and safety of peppermint oil, particularly as recent studies have cast doubt on its role in the treatment of IBS METHODS: We searched the medical literature up to 2nd April 2022 to identify randomised controlled trials (RCTs) of peppermint oil in IBS. Efficacy and safety were judged using dichotomous assessments of effect on global IBS symptoms or abdominal pain, and occurrence of any adverse event or of gastro-oesophageal reflux. Data were pooled using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs).
RESULTS
We identified 10 eligible RCTs (1030 patients). Peppermint oil was more efficacious than placebo for global IBS symptoms (RR of not improving = 0.65; 95% CI 0.43-0.98, number needed to treat [NNT] = 4; 95% CI 2.5-71), and abdominal pain (RR of abdominal pain not improving = 0.76; 95% CI 0.62-0.93, NNT = 7; 95% CI 4-24). Adverse event rates were significantly higher with peppermint oil (RR of any adverse event = 1.57; 95% CI 1.04-2.37).
CONCLUSIONS
Peppermint oil was superior to placebo for the treatment of IBS, but adverse events were more frequent, and quality of evidence was very low. Adequately powered RCTs of peppermint oil as first-line treatment for IBS are needed.
Topics: Abdominal Pain; Humans; Irritable Bowel Syndrome; Mentha piperita; Parasympatholytics; Plant Oils; Treatment Outcome
PubMed: 35942669
DOI: 10.1111/apt.17179 -
International Journal of Molecular... Sep 2022Cancer is one of the leading causes of death in the world, with breast cancer being the most prevalent cancer. Chemotherapy-induced nausea and vomiting (CINV) is one of... (Meta-Analysis)
Meta-Analysis Review
Cancer is one of the leading causes of death in the world, with breast cancer being the most prevalent cancer. Chemotherapy-induced nausea and vomiting (CINV) is one of the most serious side effects of chemotherapy. Because the current CINV treatment option has several flaws, alternative treatment options are required. Ginger has traditionally been used to treat nausea and vomiting, and it also has anticancer properties in breast cancer cells. Based on these findings, researchers investigated whether using ginger to treat CINV in breast cancer patients is both effective and safe. We searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang from inception to June 2022. Outcomes included Rhodes Index Scores of Nausea, Vomiting, and Retching, severity and frequency of CINV. Five RCTs were included. We pooled all included data and performed subgroup analysis by types of CINV. Overall, authors found that ginger was associated with a reduction in CINV. Subgroup and sensitivity analysis revealed that managing severity of acute CINV in breast cancer patients with ginger was efficient. In terms of managing delayed CINV in breast cancer patients, ginger was also statistically significant. The authors concluded that ginger may be helpful in lowering both acute and delayed CINV in breast cancer patients. Since there were no serious side effects, ginger is thought to be safe.
Topics: Antiemetics; Antineoplastic Agents; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Zingiber officinale; Humans; Nausea; Vomiting
PubMed: 36232567
DOI: 10.3390/ijms231911267 -
Nutrients Nov 2022Nausea and vomiting are the most common side effects of chemotherapy. They must be managed because they can increase the risk of malnutrition in patients, which can... (Meta-Analysis)
Meta-Analysis Review
Nausea and vomiting are the most common side effects of chemotherapy. They must be managed because they can increase the risk of malnutrition in patients, which can adversely affect treatment. The objective of this study was to evaluate the effect of ginger supplementation as an adjuvant treatment for alleviating chemo We checked. therapy-induced nausea and vomiting (CINV). This study searched for randomized controlled trials (RCTs) related to ginger supplement intake for CINV in three electronic databases (i.e., Medline (PubMed), Embase, and Web of Science). The search period ranged from each database's first date of service to 5 November 2021. Two investigators independently performed abstract screenings, full-text screenings, data extraction, and risk of bias analyses (ROB). The Cochrane ROB tool was used for the assessment of ROB. This study systematically reviewed 23 RCTs. The effects of ginger supplementation were compared to those of placebo or antiemetic agents. This study conducted a meta-analysis after classifying the effects of ginger supplementation on acute and delayed CINV into subgroups due to the clinical heterogeneity between these RCTs. The results showed that the incidence of acute nausea ( = 0.53), the incidence of delayed nausea ( = 0.31), the incidence of acute vomiting ( = 0.09), and the incidence of delayed vomiting ( = 0.89) were not significantly different between the ginger supplement intake group and the control group. However, it was found that the ginger supplement intake group, which took not more than 1 g of ginger supplementation per day for above four days, had significantly less acute vomiting than the control group (OR 0.30; 95% CI 0.12 to 0.79; = 0.02; I2 = 36%). Ginger supplementation may reduce the incidence of acute chemotherapy-induced vomiting. However, this study could not confirm the effects of ginger supplementation on the incidence of chemotherapy-induced nausea and delayed vomiting. Therefore, it will be necessary to conduct additional studies with sufficient sample sizes using high-quality RCTs to evaluate the effects of ginger supplementations based on the results of this study.
Topics: Humans; Antineoplastic Agents; Zingiber officinale; Nausea; Randomized Controlled Trials as Topic; Vomiting
PubMed: 36501010
DOI: 10.3390/nu14234982 -
Anaesthesia Jul 2021Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is... (Meta-Analysis)
Meta-Analysis
Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.
Topics: Adult; Anesthesia, General; Antiemetics; Female; Humans; Male; Network Meta-Analysis; Postoperative Nausea and Vomiting; Treatment Outcome
PubMed: 33170514
DOI: 10.1111/anae.15295 -
The Cochrane Database of Systematic... Nov 2018Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to the environment. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium. It can profoundly affect both them and their families because it is associated with increased mortality, longer duration of mechanical ventilation, longer hospital and ICU stay and long-term cognitive impairment. It also results in increased costs for society.
OBJECTIVES
To assess existing evidence for the effect of preventive interventions on ICU delirium, in-hospital mortality, the number of delirium- and coma-free days, ventilator-free days, length of stay in the ICU and cognitive impairment.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, Latin American Caribbean Health Sciences Literature, CINAHL from 1980 to 11 April 2018 without any language limits. We adapted the MEDLINE search for searching the other databases. Furthermore, we checked references, searched citations and contacted study authors to identify additional studies. We also checked the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and CenterWatch.com (all on 24 April 2018).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of adult medical or surgical ICU patients receiving any intervention for preventing ICU delirium. The control could be standard ICU care, placebo or both. We assessed the quality of evidence with GRADE.
DATA COLLECTION AND ANALYSIS
We checked titles and abstracts to exclude obviously irrelevant studies and obtained full reports on potentially relevant ones. Two review authors independently extracted data. If possible we conducted meta-analyses, otherwise we synthesized data narratively.
MAIN RESULTS
The electronic search yielded 8746 records. We included 12 RCTs (3885 participants) comparing usual care with the following interventions: commonly used drugs (four studies); sedation regimens (four studies); physical therapy or cognitive therapy, or both (one study); environmental interventions (two studies); and preventive nursing care (one study). We found 15 ongoing studies and five studies awaiting classification. The participants were 48 to 70 years old; 48% to 74% were male; the mean acute physiology and chronic health evaluation (APACHE II) score was 14 to 28 (range 0 to 71; higher scores correspond to more severe disease and a higher risk of death). With the exception of one study, all participants were mechanically ventilated in medical or surgical ICUs or mixed. The studies were overall at low risk of bias. Six studies were at high risk of detection bias due to lack of blinding of outcome assessors. We report results for the two most commonly explored approaches to delirium prevention: pharmacologic and a non-pharmacologic intervention.Haloperidol versus placebo (two RCTs, 1580 participants)The event rate of ICU delirium was measured in one study including 1439 participants. No difference was identified between groups, (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.87 to 1.17) (moderate-quality evidence). Haloperidol versus placebo neither reduced or increased in-hospital mortality, (RR 0.98, 95% CI 0.80 to 1.22; 2 studies; 1580 participants (moderate-quality evidence)); the number of delirium- and coma-free days, (mean difference (MD) -0.60, 95% CI -1.37 to 0.17; 2 studies, 1580 participants (moderate-quality of evidence)); number of ventilator-free days (mean 23.8 (MD -0.30, 95% CI -0.93 to 0.33) 1 study; 1439 participants, (high-quality evidence)); length of ICU stay, (MD 0.18, 95% CI -0.60 to 0.97); 2 studies, 1580 participants; high-quality evidence). None of the studies measured cognitive impairment. In one study there were three serious adverse events in the intervention group and five in the placebo group; in the other there were five serious adverse events and three patients died, one in each group. None of the serious adverse events were judged to be related to interventions received (moderate-quality evidence).Physical and cognitive therapy interventions (one study, 65 participants)The study did not measure the event rate of ICU delirium. A physical and cognitive therapy intervention versus standard care neither reduced nor increased in-hospital mortality, (RR 0.94, 95% CI 0.40 to 2.20, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of delirium- and coma-free days, (MD -2.8, 95% CI -10.1 to 4.6, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of ventilator-free days (within the first 28/30 days) was median 27.4 (IQR 0 to 29.2) and 25 (IQR 0 to 28.9); 1 study, 65 participants; very low-quality evidence, length of ICU stay, (MD 1.23, 95% CI -0.68 to 3.14, I² = 0; 1 study, 65 participants; very low-quality evidence); cognitive impairment measured by the MMSE: Mini-Mental State Examination with higher scores indicating better function, (MD 0.97, 95% CI -0.19 to 2.13, I² = 0; 1 study, 30 participants; very low-quality evidence); or measured by the Dysexecutive questionnaire (DEX) with lower scores indicating better function (MD -8.76, 95% CI -19.06 to 1.54, I² = 0; 1 study, 30 participants; very low-quality evidence). One patient experienced acute back pain accompanied by hypotensive urgency during physical therapy.
AUTHORS' CONCLUSIONS
There is probably little or no difference between haloperidol and placebo for preventing ICU delirium but further studies are needed to increase our confidence in the findings. There is insufficient evidence to determine the effects of physical and cognitive intervention on delirium. The effects of other pharmacological interventions, sedation, environmental, and preventive nursing interventions are unclear and warrant further investigation in large multicentre studies. Five studies are awaiting classification and we identified 15 ongoing studies, evaluating pharmacological interventions, sedation regimens, physical and occupational therapy combined or separately, and environmental interventions, that may alter the conclusions of the review in future.
Topics: Aged; Antipsychotic Agents; Cognition Disorders; Cognitive Behavioral Therapy; Delirium; Female; Haloperidol; Humans; Intensive Care Units; Male; Middle Aged; Physical Therapy Modalities; Randomized Controlled Trials as Topic
PubMed: 30484283
DOI: 10.1002/14651858.CD009783.pub2 -
The Cochrane Database of Systematic... Nov 2017Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone.
OBJECTIVES
To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events.
AUTHORS' CONCLUSIONS
Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.
Topics: Anesthetics, Local; Arm; Dexamethasone; Glucocorticoids; Humans; Injections, Intravenous; Leg; Nerve Block; Neuromuscular Blocking Agents; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors
PubMed: 29121400
DOI: 10.1002/14651858.CD011770.pub2