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Sleep Medicine Reviews Aug 2019Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy...
Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy of pharmacotherapy in adults with OSA and delineate the underlying mechanisms. Seven databases were systematically screened for randomised controlled trials (RCTs) from their inception to September 2018. According to a pre-registered study protocol (PROSPERO-ID-CRD42018086446) network meta-analysis was performed to obtain intervention effects on the apnoea-hypopnoea-index (AHI) based on data extracted from published reports. We identified 58 RCTs (n = 1710 patients) investigating 44 different drugs or drug-combinations. Interventions were classified into seven pathomechanism-groups and summarized narratively. A meta-analysis of 17 trials for seven drugs (acetazolamide, donepezil, mirtazapine, ondansetron, paroxetine, protriptyline, theophylline) indicated a small effect for acetazolamide (mean difference in AHI -9.6/h [-17.7; -1.4]; p = 0.02). In the network meta-analysis (I = 50%) nine drugs (tramazoline, liraglutide, spironolactone/furosemide, acetazolamide, dronabinol, zonisamide, phentermine, spironolactone, and ondansetron/fluoxetine) significantly lowered the AHI compared to placebo. Although some trials indicate favorable outcomes, these results are only valid for distinctive OSA-phenotypes or were not clinically significant. The effect sizes were small, the majority of trials were not adequately powered. There is currently insufficient evidence to recommend any pharmacotherapy for OSA and no phase-III trials are available.
Topics: Adult; Drug Therapy; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive
PubMed: 31075665
DOI: 10.1016/j.smrv.2019.04.009 -
Evidence-based Complementary and... 2019The high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of... (Review)
Review
BACKGROUND
The high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of delirium has become the focus of discussion in recent years. However, a consensus in this respect has yet to be reached.
METHODS
Randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, ClinicalTrials.gov, and Embase databases from their inception through October 12, 2018. We included RCTs of pharmacological prevention for postoperative delirium in adults (at least 18 years), and the Cochrane risk of bias tool was used to evaluate the methodological quality of trials. The primary outcomes were the risk ratios (RRs) of incidence of postoperative delirium, and the secondary outcomes were the RRs of mortality and adverse events in the intervention and control groups.
RESULTS
Thirty-eight trials, which comprised 20302 patients and 18 different drugs, were included in the analysis. Of the 38 studies, 17 were rated as low risk with respect to methodological quality. Dexmedetomidine administration (RR 0.58, 95%CI 0.44-0.76, P<0.01) was associated with a significantly lower incidence of postoperative delirium than the control conditions. However, the findings from the studies with a low risk of bias did not show a significant difference in this beneficial effect (RR 0.64, 95%CI 0.39-1.04, P=0.07). The antipsychotic drugs olanzapine (RR 0.44, 95%CI 0.30- 0.65, P<0.01) and risperidone (RR 0.42, 95%CI 0.19-0.92, P=0.03) had promising effects, but there was a lack of sufficient evidence to obtain a definitive conclusion. The beneficial effect of other drugs, including haloperidol, methylprednisolone, dexamethasone, gabapentin, ketamine, cyproheptadine, donepezil, hypertonic saline, melatonin, nimodipine, ondansetron, pregabalin, rivastigmine, TJ-54, and tryptophan, was not proven on the basis of present evidence.
CONCLUSION
Among the pharmacological prophylactic measures for postoperative delirium, dexmedetomidine, olanzapine, and risperidone showed higher efficacy than other drugs. However, more high-quality evidence is needed to confirm these results.
PubMed: 31001357
DOI: 10.1155/2019/9607129 -
Journal of Perianesthesia Nursing :... Aug 2019Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via... (Meta-Analysis)
Meta-Analysis
PURPOSE
Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via 5HT3 receptor antagonism.
DESIGN
Systematic review and meta-analysis.
METHODS
We identified seven randomized controlled trials by systematically searching electronic databases that compare the efficacy of mirtazapine versus placebo or ondansetron in reducing PONV.
FINDINGS
Mirtazapine reduced PONV overall versus placebo in three studies (risk ratio [RR] = 0.44; 95% confidence interval [CI] 0.32 to 0.62) both on conventional meta-analysis and trial sequential analysis. One study comparing mirtazapine with ondansetron found similar rates of PONV (RR = 0.96; 95% CI 0.48 to 1.94). Mirtazapine reduced preoperative anxiety versus placebo or ondansetron (standardized mean difference -1.4; 95% CI -2.56 to -0.23) but increased sedation (RR = 22.47; 95% CI 5.61 to 89.93). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality of evidence was moderate to low.
CONCLUSIONS
This meta-analysis suggests that mirtazapine reduces PONV overall versus placebo. We found evidence of reduction in preoperative anxiety, although mirtazapine increased the risk of sedation.
Topics: Antiemetics; Humans; Mirtazapine; Postoperative Nausea and Vomiting
PubMed: 30879907
DOI: 10.1016/j.jopan.2018.11.006 -
Journal of Psychiatric Research Jun 2019The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials... (Meta-Analysis)
Meta-Analysis
The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive ondansetron, a potent 5-HT3 receptor antagonist, in the treatment of schizophrenia. Only RCTs examining adjunctive ondansetron for schizophrenia were included. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan, Version 5.3. Study quality was evaluated with the Cochrane risk of bias and the Jadad scale. Data of 5 RCTs (n = 304) covering 149 patients on ondansetron (4-8 mg/day) and 155 patients on placebo were analyzed. Three RCTs reported "randomized allocation" with a specific description; the weighted Jadad score was 3.8. Adjunctive ondansetron outperformed placebo in the reduction of Positive and Negative Syndrome Scale (PANSS) total score [3 RCTs, n = 171; SMD: -1.06 (95%CI: -2.10, -0.02), p = 0.04, I = 85%], the negative [4 RCTs, n = 209; SMD: -0.96 (95%CI: -1.71, -0.22), p = 0.01, I = 80%], and general psychopathology symptom scores [3 RCTs, n = 171; SMD: -0.97 (95%CI: -1.91, -0.02), p = 0.04, I = 82%], but not in the positive (p = 0.05) and depressive symptom scores (p = 0.91). The difference in PANSS total score remained significant after excluding one outlying RCT [2 RCTs, n = 141; SMD: -0.50 (95%CI: -0.84, -0.16), P = 0.004, I = 0%]. Four RCTs examined the effect of ondansetron on cognition applying different instruments yielding conflicting findings. Ondansetron was superior over placebo in improving extrapyramidal symptoms, but no group differences were found in overall discontinuation rate and adverse drug reactions. In conclusion, adjunctive ondansetron appears to be efficacious and safe in improving negative symptoms and general psychopathology. The effect of ondansetron on cognitive impairment in schizophrenia needs to be further explored in large-scale RCTs.
Topics: Antipsychotic Agents; Drug Therapy, Combination; Humans; Ondansetron; Schizophrenia; Treatment Outcome
PubMed: 30878789
DOI: 10.1016/j.jpsychires.2019.02.024 -
Reproductive Toxicology (Elmsford, N.Y.) Jun 2019To investigate whether ondansetron use during pregnancy is associated with increased rates of major or subgroups of malformations. (Meta-Analysis)
Meta-Analysis
AIMS
To investigate whether ondansetron use during pregnancy is associated with increased rates of major or subgroups of malformations.
METHODS
PubMed/MEDLINE, Cochrane and Reprotox databases were searched. Observational studies comprising an exposed and control group (healthy and/or disease-matched) were included.
RESULTS
No significant increased risk for major malformations, heart defects, orofacial clefts, genitourinary malformations or hypospadias were identified in our primary analysis. A significant heterogeneity existed for isolated cleft palate. Elevated point estimates and altered statistical significances were present for some of the outcomes among secondary analyses.
CONCLUSIONS
Ondansetron use during pregnancy was not associated with a significant increase in rate of major or selected subgroups of malformations in our primary analysis. However, results of the secondary analyses warrant the need for continued surveillance. These results may be reassuring for pregnant women in whom ondansetron use is clinically indicated since the absolute risks of possible concerns appear to be low.
Topics: Abnormalities, Drug-Induced; Antiemetics; Case-Control Studies; Cohort Studies; Female; Humans; Ondansetron; Pregnancy; Risk Factors
PubMed: 30849498
DOI: 10.1016/j.reprotox.2019.03.001 -
Expert Opinion on Drug Safety Feb 2019Chemotherapy-induced nausea and vomiting (CINV) are among the most distressing and feared treatment-related adverse effects for cancer patients. Selection of antiemetic... (Meta-Analysis)
Meta-Analysis
Safety of clinical practice guideline-recommended antiemetic agents for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric patients: a systematic review and meta-analysis.
Chemotherapy-induced nausea and vomiting (CINV) are among the most distressing and feared treatment-related adverse effects for cancer patients. Selection of antiemetic agents to prevent CINV should be based on an evaluation of their efficacy and safety. This systematic review and meta-analysis describes the adverse effects associated with antiemetic agents recommended for the prevention of acute CINV in children by clinical practice guidelines (CPGs). Areas covered: A systematic literature search was conducted using four databases to identify papers describing adverse effects in pediatric patients receiving aprepitant, dexamethasone, granisetron, ondansetron, palonosetron, or tropisetron. Meta-analysis was conducted for adverse effects reported in at least three prospective studies with a cumulative incidence of at least 1%. Expert opinion: Antiemetic agents currently recommended by CPGs are relatively safe to use in children. The presence of patient-specific risk factors for rare adverse effects, especially cardiac arrhythmia, should be evaluated when selecting a patient's antiemetic therapy. Evaluation of the long-term safety of CPG-recommended antiemetic agents in pediatric cancer patients is needed.
Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Neoplasms; Practice Guidelines as Topic; Risk Factors; Vomiting
PubMed: 30640557
DOI: 10.1080/14740338.2019.1568988 -
The Cochrane Database of Systematic... Nov 2018In the perioperative period, dexamethasone is widely and effectively used for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the perioperative period, dexamethasone is widely and effectively used for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to facilitate early discharge after ambulatory surgery.Long-term treatment with steroids has many side effects, such as adrenal insufficiency, increased infection risk, hyperglycaemia, high blood pressure, osteoporosis, and development of diabetes mellitus. However, whether a single steroid load during surgery has negative effects during the postoperative period has not yet been studied.
OBJECTIVES
To assess the effects of a steroid load of dexamethasone on postoperative systemic or wound infection, delayed wound healing, and blood glucose change in adult surgical patients (with planned subgroup analysis of patients with and without diabetes).
SEARCH METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, and the Web of Science for relevant articles on 29 January 2018. We searched without language or date restriction two clinical trial registries to identify ongoing studies, and we handsearched the reference lists of relevant publications to identify all eligible trials.
SELECTION CRITERIA
We searched for randomized controlled trials comparing an incidental steroid load of dexamethasone versus a control intervention for adult patients undergoing surgery. We required that studies include a follow-up of 30 days for proper assessment of the number of postoperative infections, delayed wound healing, and the glycaemic response.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies for eligibility, extracted data from relevant studies, and assessed all included studies for bias. We resolved differences by discussion and pooled included studies in a meta-analysis. We calculated Peto odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Our primary outcomes were postoperative systemic or wound infection, delayed wound healing, and glycaemic response within 24 hours. We created a funnel plot for the primary outcome postoperative (wound or systemic) infection. We used GRADE to assess the quality of evidence for each outcome.
MAIN RESULTS
We included in the meta-analysis 37 studies that included adults undergoing a large variety of surgical procedures (i.e. abdominal surgery, cardiac surgery, neurosurgery, and orthopaedic surgery). We excluded one previously included study, as this study was recently retracted. Age range of participants was 18 to 80 years. There is probably little or no difference in the risk of postoperative (wound or systemic) infection with dexamethasone compared with no treatment, placebo, or active control (ramosetron, ondansetron, or tropisetron) (Peto OR 1.01, 95% confidence interval (CI) 0.80 to 1.27; 4603 participants, 26 studies; I² = 32%; moderate-quality evidence). The effects of dexamethasone on delayed wound healing are unclear because the wide confidence interval includes both meaningful benefit and harm (Peto OR 0.99, 95% CI 0.28 to 3.43; 1072 participants, eight studies; I² = 0%; low-quality evidence). Dexamethasone may produce a mild increase in glucose levels among participants without diabetes during the first 12 hours after surgery (MD 13 mg/dL, 95% CI 6 to 21; 10 studies; 595 participants; I² = 50%; low-quality evidence). We identified two studies reporting on glycaemic response after dexamethasone in participants with diabetes within 24 hours after surgery (MD 32 mg/dL, 95% CI 15 to 49; 74 participants; I² = 0%; very low-quality evidence).
AUTHORS' CONCLUSIONS
A single dose of dexamethasone probably does not increase the risk for postoperative infection. It is uncertain whether dexamethasone has an effect on delayed wound healing in the general surgical population owing to imprecision in trial results. Participants with increased risk for delayed wound healing (e.g. participants with diabetes, those taking immunosuppressive drugs) were not included in the randomized studies reporting on delayed wound healing included in this meta-analysis; therefore our findings should be extrapolated to the clinical setting with caution. Furthermore, one has to keep in mind that dexamethasone induces a mild increase in glucose. For patients with diabetes, very limited evidence suggests a more pronounced increase in glucose. Whether this influences wound healing in a clinically relevant way remains to be established. Once assessed, the two studies awaiting classification and three that are ongoing may alter the conclusions of this review.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Blood Glucose; Dexamethasone; Diabetes Mellitus; Glucocorticoids; Humans; Infections; Middle Aged; Postoperative Complications; Randomized Controlled Trials as Topic; Surgical Procedures, Operative; Surgical Wound; Wound Healing
PubMed: 30480776
DOI: 10.1002/14651858.CD011940.pub3 -
Journal of Pain Research 2018An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on... (Review)
Review
BACKGROUND/AIMS
An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on postoperative sore throat (POST).
METHODS
Comprehensive literature search of databases for randomized controlled trials (RCTs), including Embase, PubMed, and Cochrane Library, which evaluate the effect of prophylactic dexamethasone on POST was conducted. RevMan 5.0 and STATA 12.0 software were used to perform meta-analyses.
RESULTS
Fourteen RCTs totaling 1,837 patients were included for analysis. Compared with placebo, a significant reduction in the incidence of POST (OR 0.44, 95% CI 0.33-0.58, <0.00001), hoarseness (OR 0.42, 95% CI 0.31-0.58, <0.00001), and postoperative nausea and vomiting (PONV) (OR 0.06, 95% CI 0.03-0.14, <0.00001) and a comparable incidence of cough (OR 0.59, 95% CI 0.19-1.89, =0.38) was described in patients receiving dexamethasone, with or without concomitant drugs. Dexamethasone ≥0.2 mg/kg had a statistically greater impact on reducing the incidence of POST than dexamethasone 0.1-0.2 mg/kg, while dexamethasone ≤0.1 mg/kg did not. Dexamethasone was as effective as other drugs such as ondansetron, magnesium sulfate, ketamine gargle, betamethasone gel, and ketorolac for reducing POST (OR 0.70, 95% CI 0.46-1.07, =0.10). Dexamethasone plus a different drug was more effective than dexamethasone alone for reducing the incidence of POST at 24 hours (OR 0.40, 95% CI 0.21-0.77, =0.006). Compared with controls, a statistically higher blood glucose level was the only adverse event during the immediate postoperative period in patients receiving dexamethasone.
CONCLUSIONS
Intravenous dexamethasone ≥0.2 mg/kg within 30 minutes before or after induction of general anesthesia should be recommended as grade 1A evidence with safety and efficacy in reducing the incidence of POST, hoarseness, and PONV in patients without pregnancy, diabetes mellitus, or contraindications for corticosteroids.
PubMed: 30425559
DOI: 10.2147/JPR.S172419 -
The Cochrane Database of Systematic... Aug 2018In the perioperative period, dexamethasone is widely and effectively used for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the perioperative period, dexamethasone is widely and effectively used for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to facilitate early discharge after ambulatory surgery.Long-term treatment with steroids has many side effects, such as adrenal insufficiency, increased infection risk, hyperglycaemia, high blood pressure, osteoporosis, and development of diabetes mellitus. However, whether a single steroid load during surgery has negative effects during the postoperative period has not yet been studied.
OBJECTIVES
To assess the effects of a steroid load of dexamethasone on postoperative systemic or wound infection, delayed wound healing, and blood glucose change in adult surgical patients (with planned subgroup analysis of patients with and without diabetes).
SEARCH METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, and the Web of Science for relevant articles on 29 January 2018. We searched without language or date restriction two clinical trial registries to identify ongoing studies, and we handsearched the reference lists of relevant publications to identify all eligible trials.
SELECTION CRITERIA
We searched for randomized controlled trials comparing an incidental steroid load of dexamethasone versus a control intervention for adult patients undergoing surgery. We required that studies include a follow-up of 30 days for proper assessment of the number of postoperative infections, delayed wound healing, and the glycaemic response.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies for eligibility, extracted data from relevant studies, and assessed all included studies for bias. We resolved differences by discussion and pooled included studies in a meta-analysis. We calculated Peto odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Our primary outcomes were postoperative systemic or wound infection, delayed wound healing, and glycaemic response within 24 hours. We created a funnel plot for the primary outcome postoperative (wound or systemic) infection. We used GRADE to assess the quality of evidence for each outcome.
MAIN RESULTS
We included in the meta-analysis 38 studies that included adults undergoing a large variety of surgical procedures (i.e. abdominal surgery, cardiac surgery, neurosurgery, and orthopaedic surgery). Age range of participants was 18 to 80 years. There is probably little or no difference in the risk of postoperative (wound or systemic) infection with dexamethasone compared with no treatment, placebo, or active control (ramosetron, ondansetron, or tropisetron) (Peto OR 1.01, 95% confidence interval (CI) 0.80 to 1.27; 4931 participants, 27 studies; I² = 27%; moderate-quality evidence). The effects of dexamethasone on delayed wound healing are unclear because the wide confidence interval includes both meaningful benefit and harm (Peto OR 0.99, 95% CI 0.28 to 3.43; 1072 participants, eight studies; I² = 0%; low-quality evidence). Dexamethasone may produce a mild increase in glucose levels among participants without diabetes during the first 12 hours after surgery (MD 13 mg/dL, 95% CI 6 to 21; 10 studies; 595 participants; I² = 50%; low-quality evidence). We identified two studies reporting on glycaemic response after dexamethasone in participants with diabetes within 24 hours after surgery (MD 32 mg/dL, 95% CI 15 to 49; 74 participants; I² = 0%; very low-quality evidence).
AUTHORS' CONCLUSIONS
A single dose of dexamethasone probably does not increase the risk for postoperative infection. It is uncertain whether dexamethasone has an effect on delayed wound healing in the general surgical population owing to imprecision in trial results. Participants with increased risk for delayed wound healing (e.g. participants with diabetes, those taking immunosuppressive drugs) were not included in the randomized studies reporting on delayed wound healing included in this meta-analysis; therefore our findings should be extrapolated to the clinical setting with caution. Furthermore, one has to keep in mind that dexamethasone induces a mild increase in glucose. For patients with diabetes, very limited evidence suggests a more pronounced increase in glucose. Whether this influences wound healing in a clinically relevant way remains to be established. Once assessed, the three studies awaiting classification and two that are ongoing may alter the conclusions of this review.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Blood Glucose; Dexamethasone; Diabetes Mellitus; Humans; Infections; Middle Aged; Postoperative Complications; Surgical Procedures, Operative; Surgical Wound; Wound Healing
PubMed: 30152137
DOI: 10.1002/14651858.CD011940.pub2 -
Annals of Clinical Psychiatry :... Aug 2018This systematic review identified published studies that evaluated the use of ondansetron in individuals with psychosis associated with dementia.
BACKGROUND
This systematic review identified published studies that evaluated the use of ondansetron in individuals with psychosis associated with dementia.
METHODS
A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO, and Cochrane Collaboration databases for randomized controlled trials (RCTs), cohort studies, and case reports that evaluated the use of ondansetron for individuals with psychosis associated with dementia. Bibliographic databases of published articles were also searched for additional studies.
RESULTS
A total of 4 studies were identified, all of which were open-label trials of ondansetron for psychosis associated with Parkinson's disease. All trials showed improvements in visual hallucinations and paranoid ideations in most patients, as well as a modest improvement in functioning, but no evidence of cognitive improvement.
CONCLUSIONS
Ondansetron appears to have benefit in improving positive symptoms of psychosis in individuals with Parkinson's disease, but RCTs are needed before routine use is recommended. There is a paucity of evidence for the use of ondansetron for psychosis associated with other forms of dementia.
Topics: Antipsychotic Agents; Cognition Disorders; Dementia; Humans; Ondansetron; Parkinson Disease; Psychotic Disorders
PubMed: 30028894
DOI: No ID Found