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Cureus Jan 2024Exposure to traumatic stress is common among children. Post-traumatic stress disorder (PTSD) is a debilitating chronic mental disorder that can develop following... (Review)
Review
Exposure to traumatic stress is common among children. Post-traumatic stress disorder (PTSD) is a debilitating chronic mental disorder that can develop following exposure to a traumatic event. Psychopharmacological research in pediatric PTSD is limited. There is some evidence supporting the use of alpha-2 (α) agonists for symptoms associated with PTSD. This systematic review identified published studies evaluating the effectiveness of α agonists in treating PTSD symptoms in children and adolescents. We conducted an extensive literature search on PubMed, MEDLINE, EMBASE, Cochrane Collaboration, and PsycINFO databases for published articles that evaluated the use of αagonists (clonidine and guanfacine) for treating symptoms of PTSD in children and adolescents. The study protocol was registered in Prospero (ID: CRD42021273692) and followed the PRISMA guidelines. A total of 10 published articles about clonidine or guanfacine use in PTSD in children and adolescents were identified. Studies found clonidine effective in reducing PTSD symptoms; however, the effects were variable. Clonidine and guanfacine showed effectiveness in treating nightmares, hyperarousal, aggression, and sleep disturbances and reducing re-experiencing, avoidant, and hyperarousal symptom clusters. No randomized, double-blind, placebo-controlled trials were found during the literature search. α agonists' effectiveness in treating symptoms associated with PTSD in children and adolescents is preliminary. Future placebo-controlled trials are needed to assess the efficacy and safety of α agonists.
PubMed: 38410304
DOI: 10.7759/cureus.53009 -
European Stroke Journal Feb 2024Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the...
Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.
INTRODUCTION
Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM.
PATIENTS AND METHODS
A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo).
RESULTS
Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; < 0.01; = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; < 0.01; = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; < 0.01; = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; < 0.01; = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; < 0.01; = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; = 0.105; = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; < 0.01; = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; = 0.792; = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction.
DISCUSSION AND CONCLUSION
GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.
PubMed: 38400569
DOI: 10.1177/23969873241234238 -
BMJ Open Feb 2024Postoperative nausea and vomiting (PONV) is a leading perioperative morbidity outcome following general anaesthesia. This systematic review aims to identify, appraise...
OBJECTIVES
Postoperative nausea and vomiting (PONV) is a leading perioperative morbidity outcome following general anaesthesia. This systematic review aims to identify, appraise and summarise the evidence synthesis studies of prophylactic interventions that reduce the incidence of paediatric PONV, thereby highlighting knowledge gaps and avenues of future research.
DESIGN
Systematic review using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews 2) tool and the ROBIS (Risk Of Bias In Systematic reviews) tool.
DATA SOURCES
Seven major databases, including MEDLINE and EMBASE, from inception to 23 September 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Evidence synthesis studies of only randomised controlled trials that explored prophylactic interventions for PONV in children undergoing general anaesthesia.
DATA EXTRACTION AND SYNTHESIS
Following screening process by two reviewers, data were extracted from all eligible studies, including demographic parameters and details of interventions. Eligible studies were categorised into 'pharmacological' and 'non-pharmacological' groups and high-risk surgical groups of 'strabismus' and 'tonsillectomy' for qualitative synthesis.
RESULTS
There were 20 evidence synthesis reviews (17 meta-analyses, 2 systematic reviews, 1 network meta-analysis): 14 investigated pharmacological PONV prophylaxis in children, 5 investigated non-pharmacological interventions, 1 studied both pharmacological and non-pharmacological interventions. Monotherapy pharmacological prophylaxis agents, for example, dexamethasone (relative risk (RR) 0.49, 95% CI 0.41 to 0.58), 5-hydroxytryptamine (5-HT) antagonists (OR 0.12, 95% CI 0.07 to 0.20) and α-adrenoreceptor agonists (dexmedetomidine: RR 0.33, 95% CI 0.21 to 0.54), are more effective than placebo. A combination of pharmacological agents provided superior efficacy to monotherapy, particularly dexamethasone and 5-HT antagonists (RR 0.21, 95% credible interval 0.15 to 0.28). Acustimulation practice was consistently favourable in preventing PONV compared with placebo (RR 0.36, 95% CI 0.25 to 0.52).
CONCLUSION
Monotherapy pharmacological prophylaxis is more effective than placebo in reducing the incidence of paediatric PONV, with the efficacy increased further by using combination pharmacotherapy. Further research must compare multiple treatment arms of pharmacological and non-pharmacological prophylaxes for PONV to identify the optimal multimodal prophylaxis regimen.
PROSPERO REGISTRATION NUMBER
CRD42021236698.
Topics: Child; Humans; Antiemetics; Dexamethasone; Incidence; Postoperative Nausea and Vomiting; Serotonin; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38388499
DOI: 10.1136/bmjopen-2022-070775 -
Diabetes, Metabolic Syndrome and... 2024To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes... (Review)
Review
The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
AIM
To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM).
METHODS
Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM.
RESULTS
Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.
PubMed: 38371390
DOI: 10.2147/DMSO.S443396 -
Diabetology & Metabolic Syndrome Feb 2024Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor... (Review)
Review
AIM
Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease.
METHODS
PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury.
RESULTS
The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,- 1.67 (95% CI - 2.27 to - 1.07)], serum creatinine [SMD, - 1.88 (95% CI - 2.91 to - 0.85)], and albuminuria [SMD, - 1.60 (95% CI - 2.16 to - 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, - 0.97 (95% CI - 1.83 to - 0.11)] and albuminuria [SMD, - 2.43 (95% CI - 4.63 to - 0.23)] in renal dysfunction animals compared with the control group.
CONCLUSIONS
The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.
PubMed: 38360685
DOI: 10.1186/s13098-024-01283-2 -
Cardiovascular Diabetology Feb 2024The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality.
METHODS
We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE.
RESULTS
Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D.
CONCLUSIONS
This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines.
Topics: Adult; Aged; Humans; Middle Aged; Canada; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart Failure; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38360604
DOI: 10.1186/s12933-024-02154-w -
Biomedical Reports Mar 2024Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors...
Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials.
Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.
PubMed: 38357229
DOI: 10.3892/br.2024.1732 -
Frontiers in Public Health 2024To systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference, and body weight.
METHODS
A search formula was written using search terms such as "tirzepatide," "overweight," and "obesity." A comprehensive search was conducted on databases such as PubMed, Cochrane Library, Embase, and Web of Science using a computer. Random controlled trial (RCT) literature was selected based on inclusion and exclusion criteria. After extracting the data, literature bias risk assessment and meta-analysis were conducted using RevMan 5.4 software. The search deadline is from the establishment of each database to May 2023.
RESULTS
A total of 12 randomized controlled trials were included, with a total of 11,758 patients. Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = -1.71, 95% CI (-2.46, -0.95), < 0.00001], [MD = -3.99, 95% CI (-3.69, -2.45), < 0.00001], [MD = -4.02, 95% CI (-4.72, -3.31), < 00.00001]. In terms of decreasing waist circumference, tirzepatide has a more significant advantage [MD = -4.08, 95% CI (-5.77, -2.39), < 0.00001], [MD = -7.71, 95% CI (-10.17, -5.25), < 0.00001], [MD = -9.15, 95% CI (-10.02, -8.29), < 0.00001]. In the analysis of body weight, tirzepatide showed a more significant reduction effect compared to the control group [MD = -5.65, 95% CI (-7.47, -3.82), < 0.001], [MD = -10.06, 95% CI (-12.86, -7.25), < 0.001], [MD = -10.63, 95% CI (-12.42, -8.84), < 0.001]. In comparison with placebo, tirzepatide had a prominent advantage in weight loss ≥20% and ≥25% [RR = 30.43, 95% CI (19.56, 47.33), < 0.00001], [RR = 37.25, 95% CI (26.03, 53.30), < 0.00001]. Subgroup analysis showed a dose-dependent therapeutic effect. In terms of safety, compared with the placebo and insulin groups, the incidence of gastrointestinal adverse reactions was markedly higher in the tirzepatide group, slightly higher to the GLP-1 RAs group. The hypoglycemic (<70 mg/dL) risk of tirzepatide was slightly higher to that of placebo and GLP-1 RAs, but significantly lower than that of the insulin group [RR = 0.46, 95% CI (0.36, 0.58), < 0.001]. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events-4, hypersensitivity reactions, and neoplasms did not show significant statistical differences compared to the control group ( > 0.05).
CONCLUSION
Tirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.
Topics: Humans; Body Weight; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-2 Receptor; Hypoglycemic Agents; Insulins; Obesity; Randomized Controlled Trials as Topic
PubMed: 38356942
DOI: 10.3389/fpubh.2024.1277113 -
BMJ Neurology Open 2024The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists...
BACKGROUND
The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications.
METHODS
In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.
RESULTS
74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile.
CONCLUSIONS
COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.
PubMed: 38352047
DOI: 10.1136/bmjno-2023-000573 -
Frontiers in Endocrinology 2024The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes... (Meta-Analysis)
Meta-Analysis
First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis.
BACKGROUND
The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) with low risk of cardiovascular diseases are not clear.
METHODS
PubMed, EMBASE and Cochrane Library databases were searched to identify eligible randomized controlled trials. We used the odds ratio (OR) and mean difference (MD) and the corresponding 95% confidence interval (CI) to assess the dichotomous and continuous variable, respectively.
RESULTS
Thirteen studies involving 2,885 T2DM at low risk of cardiovascular diseases were included. Compared to placebo, first line use of SGLT2i significantly reduced glycosylated hemoglobin type A1C (HbA1c) (MD: -0.72), weight (MD: -1.32) and fasting plasma glucose (FPG) (MD: -27.05) levels. Compared with metformin, SGLT2i reduced body weight (MD: -1.50) and FPG (MD: -10.13) more effectively, with similar reduction for HbA1c (MD: -0.05). No significant increased safety adverse was found for SGLT2i, including nasopharyngitis (OR: 1.07), urinary tract infection (OR: 2.31), diarrhea (OR: 1.18) and hypoglycemia (OR: 1.06). GLP-1RAs significantly reduced HbA1c (MD: -1.13), weight (MD: -2.12) and FPG (MD: -31.44) levels as first-line therapy compared to placebo. GLP-1RAs significantly increased occurrence of diarrhea (OR: 2.18), hypoglycemia (OR: 3.10), vomiting (OR: 8.22), and nausea (OR: 4.41).
CONCLUSION
First line use of SGLT2i and GLP-1RAs is effective in reducing HbA1c, weight, and FPG levels in T2DM patients at low risk for cardiovascular disease. SGLT2i may be superior to metformin in controlling body weight and FPG. GLP-1RAs may increase the occurrence of diarrhea, hypoglycemia, vomiting, and nausea.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (International Prospective Register of Systematic Reviews. https://www.york.ac.uk/inst/crd, CRD42022347233).
Topics: Humans; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diarrhea; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Hypoglycemia; Hypoglycemic Agents; Metformin; Nausea; Sodium; Systematic Reviews as Topic; Vomiting
PubMed: 38348420
DOI: 10.3389/fendo.2024.1289643