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Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials.Neuropsychopharmacology : Official... Oct 2020Cannabidiol (CBD) is being investigated as a treatment for several medical disorders but there is uncertainty about its safety. We conducted the first systematic review... (Meta-Analysis)
Meta-Analysis
Cannabidiol (CBD) is being investigated as a treatment for several medical disorders but there is uncertainty about its safety. We conducted the first systematic review and meta-analysis of the adverse effects of CBD across all medical indications. Double-blind randomized placebo-controlled clinical trials lasting ≥7 days were included. Twelve trials contributed data from 803 participants to the meta-analysis. Compared with placebo, CBD was associated with an increased likelihood of withdrawal for any reason (OR 2.61, 95% CI: 1.38-4.96) or due to adverse events (OR 2.65, 95% CI: 1.04-6.80), any serious adverse event (OR 2.30, 95% CI: 1.18-4.48), serious adverse events related to abnormal liver function tests (OR 11.19, 95% CI: 2.09-60.02) or pneumonia (OR 5.37, 95% CI: 1.17-24.65), any adverse event (OR 1.55, 95% CI: 1.03-2.33), adverse events due to decreased appetite (OR 3.56, 95% CI: 1.94-6.53), diarrhoea (OR 2.61, 95% CI: 1.46-4.67), somnolence (OR 2.23, 95% CI: 1.07-4.64) and sedation (OR 4.21, 95% CI: 1.18-15.01). Associations with abnormal liver function tests, somnolence, sedation and pneumonia were limited to childhood epilepsy studies, where CBD may have interacted with other medications such as clobazam and/or sodium valproate. After excluding studies in childhood epilepsy, the only adverse outcome associated with CBD treatment was diarrhoea (OR 5.03, 95% CI: 1.44-17.61). In summary, the available data from clinical trials suggest that CBD is well tolerated and has relatively few serious adverse effects, however interactions with other medications should be monitored carefully. Additional safety data from clinical trials outside of childhood epilepsy syndromes and from studies of over-the-counter CBD products are needed to assess whether the conclusions drawn from clinical trials can be applied more broadly.
Topics: Cannabidiol; Double-Blind Method; Humans; Randomized Controlled Trials as Topic
PubMed: 32268347
DOI: 10.1038/s41386-020-0667-2 -
The Patient Jul 2024The history of clinical trials is fraught with unethical practices. Since 1945, robust frameworks have evolved to standardise the collection and reporting of safety... (Review)
Review
BACKGROUND AND OBJECTIVE
The history of clinical trials is fraught with unethical practices. Since 1945, robust frameworks have evolved to standardise the collection and reporting of safety data, most notably, the Common Terminology Criteria for Adverse Events (CTCAE) from the National Cancer Institute; used by investigators to report side effects experienced by participants. As medicine moves into the patient-centred model, interest has been growing to collect data on adverse events directly from participants (patient-reported adverse events). The aim of this systematic scoping review was to investigate the inclusion of patient-reported adverse event data within safety/tolerability analyses and explore the collection and reporting of patient-reported adverse event data.
METHODS AND RESULTS
A database search was undertaken and the Covidence platform was used to manage the review; results were analysed descriptively. Sixty-eight studies were included in the analysis. An increase in the number of studies that incorporate patient-reported adverse event data was seen by year. Seventy instruments were used for the collection of patient-reported adverse event data with recall period, mode, frequency and site of administration varying across studies; the duration of data collection ranged from 28 days to 6 years. Frequently, information on these details was omitted from publications. The number of instruments used by studies to collect patient-reported adverse event data ranged from one to seven instruments.
CONCLUSIONS
Despite growing calls for the inclusion of patient-reported adverse events, this has not yet translated into published reports. The collection and reporting of these data were variable and conducted using instruments that were not designed for purpose. To address these inconsistencies, standardisation of data collection and reporting using a purpose-built validated instrument is required.
Topics: Humans; Neoplasms; Patient Reported Outcome Measures; Clinical Trials as Topic; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions
PubMed: 38589749
DOI: 10.1007/s40271-024-00689-4 -
Indian Journal of Psychological Medicine Jan 2024United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse... (Review)
Review
BACKGROUND AND OBJECTIVE
United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence.
METHODS
A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events.
RESULTS
The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; = 0.30.
CONCLUSIONS
The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.
PubMed: 38524957
DOI: 10.1177/02537176231201326 -
Acta Anaesthesiologica Scandinavica Oct 2022The effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial.
METHODS
We performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized-controlled trials to assess the mortality and safety of CytoSorb® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow-up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI).
RESULTS
Fourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb® was associated with higher mortality at latest follow-up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04-1.49], p = .02, [TSA-adjusted CI, 0.92-1.68]) and at 30-days or in-hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06-1.88], p = .02, [TSA-adjusted CI, 0.44-4.62]). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb®. Certainty of evidence ranged from low to very low.
CONCLUSION
Low certainty of evidence showed that the use of CytoSorb® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high-quality randomized trials to clarify mortality and adverse events related to CytoSorb®.
EDITORIAL COMMENT
Hemoadsorption with CytoSorb® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient-important benefits. The findings from this systematic review and meta-analysis suggests an increased risk of adverse events including mortality. With no apparent benefits and at the same time risk of harm, use of hemoadsorption with CytoSorb® in daily clinical practice cannot be recommended at this time.
Topics: Humans; Cardiac Surgical Procedures; Critical Illness; Randomized Controlled Trials as Topic
PubMed: 35788557
DOI: 10.1111/aas.14115 -
Cancer Cell International Jul 2022Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered... (Review)
Review
BACKGROUND
Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered with DARA IV have not been aggregated. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of DARA IV for AL amyloidosis.
METHODS
We searched Medline, EMBASE, Cochrane Library and Web of Science up to 17 June 2021. Response rates and survival rates, and the corresponding 95% confidence intervals (CIs) were pooled and calculated using a fixed-effects model.
RESULTS
Thirty studies (5 cohort studies and 25 single-arm studies) with 997 patients were included. In patients receiving DARA IV-based treatments, very good partial response or better response rate, complete response rate, very good partial response rate, partial response rate and overall response rate were 66% (95% CI, 62-69%), 30% (95% CI, 23-36%), 40% (95% CI, 33-46%), 17% (95% CI, 14-21%), and 77% (95% CI, 73-80%), respectively. Cardiac and renal responses were 41% (95% CI, 34-49%) and 43% (95% CI, 32-54%), respectively. 58% (95% CI, 49-66%) of patients achieved PFS one year or longer. 2.5% (range, 1-10.0%) of patients experienced grade 3 or 4 adverse events, of which the most common adverse event was lymphocytopenia (range, 13.6-25.0%).
CONCLUSION
This study supports the efficacy and safety of DARA IV for the treatment of patients with AL amyloidosis.
PubMed: 35788237
DOI: 10.1186/s12935-022-02635-6 -
Global Spine Journal Jan 2023Systematic review and meta-analysis. (Review)
Review
STUDY DESIGN
Systematic review and meta-analysis.
OBJECTIVES
Determine if tobacco use is associated with increased risk of postoperative adverse events within 90 days in patients undergoing spinal fusion surgery.
METHODS
Databases were queried to identify cohort studies that directly compared smokers with non-smokers and provided the absolute number of adverse events and the population at risk. Data quality was evaluated using the Quality in Prognosis Studies tool. Risk ratios (RR) and 95% confidence intervals were calculated and compared between studies. The grading of recommendation, assessment, development and evaluation (GRADE) criteria were used to assess the strength of the evidence.
RESULTS
Seventeen studies assessing 37 897 participants met the inclusion criteria. Of these, 10 031 (26.5%) were smokers and 27 866 (73.5%) were nonsmokers. The mean age for the study population was 58 years, and 45% were males. Smoking was not associated with increased risk of one or more major adverse events within 90 days following spine surgery (seven studies, pooled RR 1.13, 95% CI [.75-1.71], I2 = 41%). However, smoking was significantly associated with one or more major adverse events in ≤2 level fusion (three studies, pooled RR 2.46, 95% CI [1.18-5.12], I2 = 0%), but not in fusions of ≥3 levels (four studies, pooled RR .87, 95% CI [.70-1.08], I2 = 0%). Additionally, there was no statistically significant association between smoking and any adverse event, nor increased reoperation risk due to adverse events.
CONCLUSIONS
In this meta-analysis, tobacco use was not associated with a statistically significant increased risk of adverse events within 90 days in patients undergoing spinal fusion surgery. Our results are limited by the variable reporting methodology for both complication rates as well as smoking incidence between the included individual studies.
PubMed: 36367824
DOI: 10.1177/21925682221110127 -
World Journal of Gastroenterology May 2023Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.
AIM
To assess the efficacy and safety of FMT for the treatment of IBS.
METHODS
We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.
RESULTS
Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.
CONCLUSION
We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.
Topics: Humans; Irritable Bowel Syndrome; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Quality of Life; Dysbiosis
PubMed: 37346153
DOI: 10.3748/wjg.v29.i20.3185 -
Frontiers in Pharmacology 2021To evaluate the efficacy and safety of ertugliflozin in patients with type 2 diabetes. MEDLINE, EMBASE, and Cochrane Library were searched (July 31, 2021) for phase... (Review)
Review
To evaluate the efficacy and safety of ertugliflozin in patients with type 2 diabetes. MEDLINE, EMBASE, and Cochrane Library were searched (July 31, 2021) for phase II/III randomized clinical trials, which reported the efficacy and safety of ertugliflozin. Continuous variables were calculated as weighted mean difference (WMD) and associated 95% confidence intervals (CIs); dichotomous data were expressed as risk ratios (RRs) with 95% CIs. Nine randomized clinical trials including 5638 type 2 diabetes patients were included. For efficacy, ertugliflozin significantly reduced HbA1c (%) (WMD -0.452%; 95% CI -0.774 to -0.129), fasting plasma glucose (FPG) (WMD -0.870 mmol/L; 95% CI -1.418 to -0.322), body weight (WMD -1.774 kg; 95% CI -2.601 to -0.946), and blood pressure levels (systolic blood pressure: WMD -2.572 mmHg; 95% CI -3.573 to -1.571 and diastolic blood pressure: WMD -1.152 mmHg; 95% CI -2.002 to -0.303) compared with placebo and other hypoglycaemic agents. Compared with placebo, ertugliflozin was superior in reducing HbA1c (%) (WMD -0.641%) and FPG (WMD -1.249 mmol/L). And compared with active agents, ertugliflozin also could decrease HbA1c by 0.215% and FPG by 0.266 mmol/L. The interactive effect between different controls was significant ( of 0.039). For safety, similar to other sodium-glucose cotransporter type-2 inhibitors, ertugliflozin mainly increased the risk of genital mycotic infection (RR: 4.004; 95% CI 2.504-6.402). There was no significant difference in the incidence of any adverse events (AEs), AEs related to study drug, serious AEs, deaths, and discontinuations due to AEs. Results were consistent with the most primary outcomes in subgroups analysis and sensitivity analysis. Ertugliflozin was relatively effective and tolerated in patients with type 2 diabetes compared with placebo or other hypoglycaemic agents, except for a high risk of genital mycotic infection. (ClinicalTrials.gov), identifier (CRD42020206356).
PubMed: 35126103
DOI: 10.3389/fphar.2021.752440 -
Canadian Journal of Gastroenterology &... 2022While endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool in primary sclerosing cholangitis (PSC), there is conflicting... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
While endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool in primary sclerosing cholangitis (PSC), there is conflicting data on associated adverse events. The aims of this systematic review and meta-analysis are to (1) compare ERCP-related adverse events in patients with and without PSC and (2) determine risk factors for ERCP-related adverse events in PSC.
METHODS
Embase, PubMed, and CENTRAL were searched between January 1, 2000, and May 12, 2021. Eligible studies included adults with PSC undergoing ERCP and reported at least one ERCP-related adverse event (cholangitis, pancreatitis, bleeding, and perforation) or an associated risk factor. The risk of bias was assessed with the Newcastle-Ottawa scale and Cochrane Risk of Bias 2. Raw event rates were used to calculate odds ratios (ORs) and then pooled using random-effects models.
RESULTS
Twenty studies met eligibility criteria, of which four were included in a meta-analysis comparing post-ERCP adverse events in patients with PSC ( = 715) to those without PSC ( = 9979). We found a significant threefold increase in the 30-day odds of cholangitis in PSC compared to those without (OR 3.263, 95% CI 1.076-9.896; =0.037). However, there were no significant differences in post-ERCP pancreatitis (PEP), bleeding, or perforation. Due to limitations in primary data, only risk factors contributing to PEP could be analyzed. Accidental passage of the guidewire into the pancreatic duct (OR 7.444, 95% CI 3.328-16.651; < 0.001; = 65.0%) and biliary sphincterotomy (OR 4.802, 95% CI 1.916-12.033; =0.001; = 73.1%) were associated with higher odds of PEP in a second meta-analysis including five studies.
CONCLUSIONS
In the context of limited comparative data and heterogeneity, PSC patients undergoing ERCP have higher odds of cholangitis despite the majority receiving antibiotics. Additionally, accidental wire passage and biliary sphincterotomy increased the odds of PEP. Future studies on ERCP-related risks and preventive strategies are needed.
Topics: Adult; Catheterization; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Cholangitis, Sclerosing; Humans; Pancreatitis
PubMed: 35910039
DOI: 10.1155/2022/2372257 -
BMC Cancer Oct 2023Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been... (Meta-Analysis)
Meta-Analysis
Incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted antibody-drug conjugates: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been associated with several fatal adverse events, such as pneumonia, interstitial lung disease, and infection. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted ADCs.
METHODS
We performed a systematic search in Embase, PubMed, Web of Science, and Scopus databases from inception to February 1, 2022, and the last search was updated to July 1, 2023. The eligible studies for inclusion in our analysis were limited to RCTs of HER2-targeted ADCs that were approved by the US Food and Drug Administration and examined on cancer patients with available data on fatal adverse events. The protocol for this study was registered in PROSPERO (No. CRD42022331627).
RESULTS
Fifteen studies (13 RCTs) involving 7,277 patients were finally included for meta-analysis. Of these patients, 4,246 received HER2-targeted ADCs and 3,481 received the control treatment. The data were combined using Bayesian hierarchical modeling, which allowed for the estimation of the mean incidence of fatal adverse events to be 0.78% (95% CrI: 0.28-1.37%, τ = 0.006) for the patients treated with HER2-targeted ADCs. The relative risk was 0.80 (95% CrI, 0.5-1.26, τ = 0.17) compared to control patients. Among 43 reported deaths caused by HER2-targeted ADCs, the most common fatal adverse event was respiratory toxicity, including pneumonia, pneumonitis, and interstitial lung disease. On subgroup analysis, no difference in the risk of fatal adverse events was found between different HER2-targeted ADCs or cancer types.
CONCLUSION
Our findings suggest that the risk of fatal adverse events with HER2-targeted ADCs may be lower compared to standard control therapies in cancer patients, and there is no significant difference in risk observed between different HER2-targeted ADCs or cancer types. However, the most common fatal adverse event was respiratory toxicity, suggesting that cancer patients who use the above drugs should strengthen respiratory system monitoring and take preventive measures in some severe cases.
Topics: Humans; Immunoconjugates; Incidence; Randomized Controlled Trials as Topic; Neoplasms; Pneumonia; Lung Diseases, Interstitial
PubMed: 37817092
DOI: 10.1186/s12885-023-11250-1