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Heart Failure Reviews Mar 2024Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a... (Meta-Analysis)
Meta-Analysis Review
Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.
Topics: Adult; Humans; Middle Aged; Cardiomyopathy, Hypertrophic; Heart; Benzylamines; Myocardium; Uracil
PubMed: 38112937
DOI: 10.1007/s10741-023-10375-6 -
Neurosurgery Dec 2023Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH.
METHODS
Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment.
RESULTS
Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76).
CONCLUSION
Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.
Topics: Humans; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial; Dioxanes; Brain Ischemia; Cerebral Infarction
PubMed: 37462365
DOI: 10.1227/neu.0000000000002601 -
Nutrients Sep 2023Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to... (Meta-Analysis)
Meta-Analysis Review
Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to prevent GDM. The present systematic review and meta-analysis aimed to investigate the effect of inositol supplementation in preventing GDM and related outcomes. Systematic search was performed in CENTRAL, MEDLINE, and Embase until 13 September 2023. Eligible randomized controlled trials (RCTs) compared the efficacy of inositols to placebo in pregnant women at high risk for GDM. Our primary outcome was the incidence of GDM, whereas secondary outcomes were oral glucose tolerance test (OGTT) and maternal and fetal complications. (PROSPERO registration number: CRD42021284939). Eight eligible RCTs were identified, including the data of 1795 patients. The incidence of GDM was halved by inositols compared to placebo (RR = 0.42, CI: 0.26-0.67). Fasting, 1-h, and 2-h OGTT glucose levels were significantly decreased by inositols. The stereoisomer myoinositol also reduced the risk of insulin need (RR = 0.29, CI: 0.13-0.68), preeclampsia or gestational hypertension (RR = 0.38, CI: 0.2-0.71), preterm birth (RR = 0.44, CI: 0.22-0.88), and neonatal hypoglycemia (RR = 0.12, CI: 0.03-0.55). Myoinositol decrease the incidence of GDM in pregnancies high-risk for GDM. Moreover, myoinositol supplementation reduces the risk of insulin need, preeclampsia or gestational hypertension, preterm birth, and neonatal hypoglycemia. Based on the present study 2-4 g myoinositol canbe suggested from the first trimester to prevent GDM and related outcomes.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Diabetes, Gestational; Premature Birth; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Randomized Controlled Trials as Topic; Hypoglycemia; Insulin; Inositol
PubMed: 37836508
DOI: 10.3390/nu15194224 -
Hypertension (Dallas, Tex. : 1979) Aug 2023Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included trials published before 2015. We aimed to identify the optimal SBP control targets in patients with type 2 diabetes using a systematic review and network meta-analysis of accumulating evidence.
METHODS
We systematically searched PubMed, Embase, and Cochrane Library from inception to August 29, 2022 for randomized controlled trials comparing different blood pressure targets, antihypertensive agents against placebo, or dual antihypertensive agents against single agent in patients with type 2 diabetes. Network meta-analysis was used to obtain pooled results of direct and indirect comparisons of each 5 mm Hg SBP category in association with clinical outcomes adjusted for baseline risk and intervention duration (PROSPERO [International Prospective Register of Systematic Reviews], CRD42022316697).
RESULTS
We identified 30 trials including 59 934 patients with type 2 diabetes. The mean achieved SBP levels ranged from 117 mm Hg to 144 mm Hg among treatment groups. A total of 7799 major cardiovascular diseases events and 4130 deaths were reported. The lowest risk of major cardiovascular diseases was found in patients with achieved SBP level of 120 to 124 mm Hg. The hazard ratio and 95% CI were 0.73 (0.52-1.02) compared with 130 to 134 mm Hg, 0.60 (0.41-0.85) compared with 140 to 144 mm Hg, and 0.41 (0.26-0.63) compared with ≥150 mm Hg. Similar results were found for cardiovascular diseases components including stroke, myocardial infarction, heart failure, and cardiovascular death. All-cause death was reduced at an achieved SBP <140 mm Hg but further reduction did not show additional benefits.
CONCLUSIONS
Our findings support an intensive blood pressure-lowering strategy to prevent major cardiovascular diseases in patients with type 2 diabetes.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Hypertension; Myocardial Infarction; Network Meta-Analysis
PubMed: 37254768
DOI: 10.1161/HYPERTENSIONAHA.123.20954 -
Diabetology & Metabolic Syndrome Oct 2023To update and assess the efficacy and tolerability of once weekly subcutaneous semaglutide in patients with type 2 diabetes (T2D). (Review)
Review
OBJECTIVES
To update and assess the efficacy and tolerability of once weekly subcutaneous semaglutide in patients with type 2 diabetes (T2D).
MATERIALS AND METHODS
PubMed, Science Direct, Cochrane Library, Clinical trial, Springer, OVID, China National Knowledge Infrastructure (CNKI), WanFang Data and China Science and Technology Journal Database (VIP) were searched from inception to January 18, 2023. Randomized controlled trials (RCTs) comparing subcutaneous semaglutide with placebo or any other antidiabetic agent in adults with T2D were eligible. The risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs) were determined to synthesize the results.
RESULTS
A total of 17 trials enrolling 14,940 T2D patients were included. For efficacy, compared with placebo, semaglutide exhibited beneficial effects on glycosylated hemoglobin A1c (HbA1c) control [MD -0.97%, 95% CI (-1.33, -0.62), I = 91%; MD -1.36%, 95% CI (-1.59, -1.13), I = 84%, semaglutide 0.5 and 1.0 mg, respectively], body weight reduction, blood pressure control. At the same time, subcutaneous semaglutide 0.5 and 1 mg reduced HbA by 0.56% (95% CI 0.32 to 0.80) and 0.63% (95% CI 0.35 to 0.91) compared to other glucose-lowering agents. For tolerability, semaglutide did not increase the incidence of adverse events (AEs) and serious adverse events (SAEs), severe or blood glucose (BG) confirmed hypoglycaemia, acute pancreatitis and diabetic retinopathy compared to placebo or active comparators, but did increase the risk of nausea, diarrhea and vomiting.
CONCLUSIONS
Semaglutide has a better effect on glycaemic control and weight loss than other therapies. Nevertheless, semaglutide was associated with increased incidence of gastrointestinal-related disorders. Further large, multicenter randomized controlled clinical trials are still needed to obtain more robust evidence to better guide clinical treatment decisions.
PubMed: 37891683
DOI: 10.1186/s13098-023-01195-7 -
Journal of Gastrointestinal Surgery :... Nov 2023This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).
METHODS
PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies.
RESULTS
Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis.
CONCLUSIONS
Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.
Topics: Humans; Pouchitis; Metronidazole; Colitis, Ulcerative; Randomized Controlled Trials as Topic; Proctocolectomy, Restorative; Ciprofloxacin; Anastomosis, Surgical
PubMed: 37815701
DOI: 10.1007/s11605-023-05841-3 -
The Journal of Headache and Pain Jul 2023Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network meta-analysis (NMA) is to compare the relative efficacy of treatments for menstrual migraine.
METHODS
We systematically searched databases, including PubMed, EMBASE, and Cochrane, and included all eligible randomized controlled trials in the study. We conducted the statistical analysis using Stata version 14.0, based on the frequentist framework. We used the Cochrane Risk of Bias tool for randomized trials version 2 (RoB2) to assess the risk of bias of the included studies.
RESULTS
This network meta-analysis included 14 randomized controlled trials with 4601 patients. For short-term prophylaxis, frovatriptan 2.5 mg twice daily had the highest probability of effectiveness [OR = 1.87 (95% CI: 1.48 to 2.38)] compared to placebo. For acute treatment, the results showed that sumatriptan 100 mg [OR = 4.32 (95% CI: 2.95 to 6.34)] was the most effective treatment compared to placebo.
CONCLUSIONS
These findings suggest that frovatriptan 2.5 mg twice daily was best for short-term prevention, sumatriptan 100 mg were best for acute treatment. More high-quality randomized trials are required to determine the most effective treatment.
Topics: Humans; Sumatriptan; Network Meta-Analysis; Migraine Disorders; Tryptamines
PubMed: 37400775
DOI: 10.1186/s10194-023-01625-x -
Frontiers in Pharmacology 2023Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse...
Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment. We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis. Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%-81%], the proportion of surgery was 9% (95% CI 7%-12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%-47%), and the adverse events were 4% (95% CI 2%-6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) -2.46, 95% CI -3.30 to -1.63] and the herniated mass volume change (SMD -16.97, 95% CI -23.92 to -10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60-3.85). The results of sensitivity and publication bias analyses showed that the results were robust. Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).
PubMed: 37670940
DOI: 10.3389/fphar.2023.1151998 -
The Journal of Pain Nov 2023Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of TBUP compared to other analgesics or placebo for acute postoperative pain. A systematic search was conducted using Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) until December 26, 2022. The search included randomized controlled trials comparing TBUP versus other analgesics or placebo for acute postoperative pain. A certainty assessment was conducted using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. The protocol for this review was registered on Prospective Register of Systematic Reviews (CRD42022318601). In total, 15 studies involving 1,205 participants were included that compared TBUP versus fentanyl (n = 2), celecoxib (n = 3), placebo (n = 2), tramadol (n = 5), diclofenac (n = 3), parecoxib (n = 1), and flurbiprofen (n = 1). Meta-analyses were conducted for 3 comparators that involved 2 studies each. There was no significant difference in pain between TBUP 10 mcg/h versus fentanyl 25 mcg/h (standardized mean difference [SMD] -.03, 95% confidence interval [CI] -.86 to .81, P = .95, I = 85%). TBUP 10 mcg/h was associated with less pain compared to celecoxib 200 mg twice daily (SMD -.32, 95% CI -.58 to -.05, P = .02, I = 0%) and placebo (SMD -2.29, 95% CI -4.32 to -.27, P = .03, I = 94%). The GRADE assessment showed a very low certainty of evidence for all comparisons. There is insufficient evidence that TBUP improves pain control compared to other analgesics for acute postoperative pain. PERSPECTIVE: This systematic review and meta-analysis compared the use of TBUP to other analgesics for postoperative pain. The results showed that there is insufficient evidence to recommend the use of TBUP in this setting. The findings will help clinicians select the most appropriate opioid regimens for postoperative pain.
Topics: Humans; Celecoxib; Analgesics, Opioid; Pain, Postoperative; Fentanyl; Buprenorphine
PubMed: 37442403
DOI: 10.1016/j.jpain.2023.07.001 -
European Journal of Pediatrics Nov 2023Obesity represents a risk factor for multiple coexisting conditions and complications. Liraglutide is mainly reserved for populations who fail to achieve weight loss... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Obesity represents a risk factor for multiple coexisting conditions and complications. Liraglutide is mainly reserved for populations who fail to achieve weight loss goals with lifestyle changes alone. This study aims to systematically evaluate the safety and effectiveness of liraglutide in weight management in children and youth. A systematic search was performed of PubMed, Embase, Cochrane Library, and Web of Science from inception to February 23rd, 2023. Randomized controlled trials (RCTs) evaluating the effects of liraglutide in children and youth were included. All data analyses were performed using Review Manager 5.3 version. Seven eligible articles were finally included, covering a population of 547 participants. Liraglutide use was associated with reduced body weight (WMD: -2.13 kg; 95%CI: -4.23, -0.03), BMI (WMD: -1.56 kg/m; 95% CI: -2.41, -0.7), and BMI SDS (WMD: -0.17; 95% CI: -0.26, -0.08). Similar associations were found in HbA1c (WMD: -0.29%; 95% CI: -0.52, -0.06) and fasting plasma glucose (SMD: -0.39; 95% CI: -0.64, -0.14). Subgroup analysis shows an improvement in HbA1c control only among children with type 2 diabetes (WMD: -1.06%; 95% CI: -1.44, -0.67). No differences were found in fasting serum insulin, SBP, DBP, HDL, LDL, and TG between liraglutide and placebo. In addition, no difference was found in the frequencies of adverse events, serious adverse events, and adverse events resulting in discontinuation of therapy between liraglutide and placebo treatment groups.
CONCLUSION
Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents.
WHAT IS KNOWN
• A few first-line treatment of these children and adolescents with overweight and obesity is a multi-component lifestyle intervention. • Lifestyle modifications are not suitable for all individuals, therefore, new treatment strategies urgent need to be established.
WHAT IS NEW
• This is the first meta-analysis conducted to assess the efficacy and safety of liraglutide for weight management in children and adolescents. • Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents.
Topics: Adolescent; Child; Humans; Liraglutide; Hypoglycemic Agents; Glycated Hemoglobin; Randomized Controlled Trials as Topic; Obesity
PubMed: 37672063
DOI: 10.1007/s00431-023-05186-8