Comparative efficacy and safety of weekly tirzepatide versus weekly insulin in type 2 diabetes: A network meta-analysis of randomized clinical trials.

AIM: To compare the efficacy and safety profiles of recent innovations in type 2 diabetes mellitus (T2DM), which include once-weekly formulations such as tirzepatide, a dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist, and once-weekly insulin options such as icodec and basal insulin Fc. METHODS: A systematic search of the PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The network meta-analysis protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was change in glycated haemoglobin (HbA1c), with change in fasting plasma glucose (FPG), body weight, incidence of hypoglycaemia, and treatment discontinuation as secondary outcomes. RESULTS: Tirzepatide exhibited superior efficacy in reducing HbA1c levels compared with insulin therapies, with the 15-mg dose showing the most significant reduction (mean difference [MD] -1.27, 95% confidence interval [CI] -1.49; -1.0). In terms of FPG reduction, tirzepatide 15 mg ranked highest (MD -0.70, 95% CI -1.05; -0.34), followed by tirzepatide 10 mg and 5 mg. Additionally, tirzepatide led to substantial weight loss, with the 15-mg dose exhibiting the most pronounced effect (MD -12.13, 95% CI -13.98; -10.27). However, a higher incidence of adverse events (AEs) and treatment discontinuation were associated with tirzepatide, particularly at higher doses. CONCLUSION: Tirzepatide, particularly at higher doses, demonstrates superior efficacy in lowering HbA1c and reducing hypoglycaemia risk compared with weekly insulin. However, its use is also associated with a higher incidence of AEs and treatment discontinuation.

Comparative efficacy and safety of weekly dulaglutide versus weekly insulin in type 2 diabetes: A network meta-analysis of randomized clinical trials.

Background: Advancements in type 2 diabetes mellitus (T2DM) therapy, notably with weekly agents like glucagon-like peptide-1 receptor agonists (GLP-RAs) such as dulaglutide, offer promising outcomes in clinical practice. The emergence of once-weekly insulin adds to this therapeutic arsenal. This research aims to explore and compare the efficacy and safety profiles of these agents in diabetes management, facilitating informed decision-making for optimizing their utilization in clinical practice. Methods: A systematic search of PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The research protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was the change in hemoglobin A1C (HbA1c), with secondary outcomes including the change in fasting plasma glucose, body weight, prevalence of hypoglycemia, and treatment discontinuation due to adverse events. The evaluation of bias risk was conducted utilizing the RoB2 tool developed by the Cochrane Collaboration. Statistical analysis was performed using RStudio version 4.3.2 with the meta package version 7.0-0 and the netmeta package version 2.9-0. Confidence in network meta-analysis estimates was evaluated using the CINeMA (Confidence In Network Meta-Analysis). Heterogeneity was assessed by comparing the magnitude of the common between-study variance (τ2) for each outcome with empirical distributions of heterogeneity variances. Results: Dulaglutide 1.5 mg (mg) weekly demonstrated superior reduction in hemoglobin A1C (HbA1c) compared to insulin, with a mean difference (MD) of -0.35 (95 % CI: -0.51 to -0.19). Additionally, Dulaglutide 1.5 mg exhibited greater weight loss, with an MD of -3.12 (95 % CI: -3.55 to -2.68). However, it also showed a higher rate of adverse events, with an odds ratio (OR) of 1.40 (95 % CI: 1.12 to 1.75) compared to insulin. Both doses of Dulaglutide (1.5 mg and 0.75 mg) had lower prevalence of hypoglycemia compared to insulin, with ORs of 0.60 (95 % CI: 0.41 to 0.87) and 0.59 (95 % CI: 0.41 to 0.86), respectively. There was no significant difference in treatment discontinuation among the treatment groups. Conclusion: Dulaglutide, particularly at higher doses, demonstrates superior efficacy in lowering hemoglobin A1C and reducing hypoglycemia risk compared to Icodec insulin in type 2 diabetes management. However, its use is also associated with a higher incidence of adverse events. Clinicians should carefully consider these factors when selecting optimal treatment strategies for patients with type 2 diabetes mellitus.

Triglyceride-Glucose Index for Early Prediction of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of 121,975 Individuals.

Insulin resistance (IR) is a major contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index has recently gained popularity for the assessment of IR and NAFLD due to its ease of acquisition and calculation. Therefore, we conducted this systematic review and meta-analysis to summarize the existing studies in the literature and provide a quantitative assessment of the significance of the TyG index in predicting the incidence of NAFLD. A comprehensive literature search in PubMed, EMBASE, and Web of Science databases from inception until 25 March 2022 was conducted. Published observational studies that evaluated the association between TyG index and NAFLD among the adult population and reported the hazard ratio (HR) or odds ratio (OR) for this association after multivariate analysis were included. The random-effects model was used as the primary statistical analysis model in the estimation of pooled ORs and HRs with the corresponding confidence intervals (CIs). A total of 17 observational studies, including 121,975 participants, were included. For studies analyzing the TyG index as a categorical variable, both pooled OR (6.00, CI 4.12-8.74) and HR (1.70, CI 1.28-2.27) were significant for the association between TyG index and incident NAFLD. For studies analyzing the TyG index as a continuous variable, pooled OR (2.25, CI 1.66-3.04) showed similar results. Consistent results were obtained in subgroup analyses according to the study design, sample size, ethnicity, and diabetic status. In conclusion, our meta-analysis demonstrates that a higher TyG index is associated with higher odds of NAFLD. TyG index may serve as an independent predictive tool to screen patients at high risk of NAFLD in clinical practice, especially in primary care settings. Patients with a high TyG index should be referred for a liver ultrasound and start intense lifestyle modifications. However, further large-scale prospective cohort studies are necessary to validate our findings.

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis.

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

High-Flow Nasal Cannula Versus Noninvasive Ventilation in Patients With COVID-19.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen and noninvasive ventilation (NIV) have been widely used in patients with acute hypoxic respiratory failure (AHRF) due to COVID-19. However, the impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. Therefore, we performed this meta-analysis to evaluate the effect of HFNC versus NIV in COVID-19-related AHRF. METHODS: Several electronic databases were searched through February 10, 2022, for eligible studies comparing HFNC and NIV in COVID-19-related AHRF. Our primary outcome was intubation. The secondary outcomes were mortality, hospital length of stay (LOS), and PaO2 /FIO2 changes. Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% CI were obtained using a random-effect model. Prediction intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Nineteen studies involving 3,606 subjects (1,880 received HFNC and 1,726 received NIV) were included. There were no differences in intubation (RR 1.01 [95% CI 0.85-1.20], P = .89) or LOS (MD 0.38 d [95% CI -0.61 to 1.37], P = .45) between groups, with consistent results on the subgroup of randomized controlled trials (RCTs). Mortality was lower in NIV (RR 0.81 [95% CI 0.66-0.98], P = .03). However, the prediction interval was 0.41-1.59, and subgroup analysis of RCTs showed no difference in mortality between groups. There was a greater improvement in PaO2 /FIO2 with NIV (MD 22.80 [95% CI 5.30-40.31], P = .01). CONCLUSIONS: Our study showed that despite the greater improvement in PaO2 /FIO2 with NIV, intubation rates and LOS were similar between HFNC and NIV. Although mortality was lower with HFNC than NIV, the prediction interval included the null value, and there was no difference in mortality between HFNC and NIV on a subgroup of RCTs. Future large-scale RCTs are necessary to support our findings.

Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis.

BACKGROUND AND AIMS: Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. METHODS: We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥ 3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. RESULTS: We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P = 1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P = 0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P = 0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P = 0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P = 0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P = 0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P = 0.08). CONCLUSIONS: Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.

Lung ultrasound-guided management to reduce hospitalization in chronic heart failure: a systematic review and meta-analysis.

Pulmonary edema is a leading cause of hospital admissions, morbidity, and mortality in heart failure (HF) patients. A point-of-care lung ultrasound (LUS) is a useful tool to detect subclinical pulmonary edema. We performed a comprehensive literature search of multiple databases for studies that evaluated the clinical utility of LUS-guided management versus standard care for HF patients in the outpatient setting. The primary outcome of interest was HF hospitalization. The secondary outcomes were all-cause mortality, urgent visits for HF worsening, acute kidney injury (AKI), and hypokalemia rates. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using random-effect model meta-analysis. A total of 3 randomized controlled trials including 493 HF patients managed in the outpatient setting (251 managed with LUS plus physical examination (PE)-guided therapy vs. 242 managed with PE-guided therapy alone) were included in the final analysis. The mean follow-up period was 5 months. There was no significant difference in HF hospitalization rate between the two groups (RR 0.65; 95% CI 0.34-1.22; P = 0.18). Similarly, there was no significant difference in all-cause mortality (RR 1.39; 95% CI 0.68-2.82; P = 0.37), AKI (RR 1.27; 95% CI 0.60-2.69; P = 0.52), and hypokalemia (RR 0.72; 95% CI 0.21-2.44; P = 0.59). However, LUS-guided therapy was associated with a lower rate for urgent care visits (RR 0.32; 95% CI 0.18-0.59; P = 0.0002). Our study demonstrated that outpatient LUS-guided diuretic therapy of pulmonary congestion reduces urgent visits for worsening symptoms of HF. Further studies are needed to evaluate LUS utility in the outpatient treatment of HF.

Effect of Prone Positioning on Clinical Outcomes of Non-Intubated Subjects With COVID-19.

BACKGROUND: Awake prone positioning (APP) has been recently proposed as an adjunctive treatment for non-intubated coronavirus disease 2019 (COVID-19) patients requiring oxygen therapy to improve oxygenation and reduce the risk of intubation. However, the magnitude of the effect of APP on clinical outcomes in these patients remains uncertain. We performed a comparative systematic review and meta-analysis to evaluate the effectiveness of APP to improve the clinical outcomes in non-intubated subjects with COVID-19. METHODS: The primary outcomes were the need for endotracheal intubation and mortality. The secondary outcome was hospital length of stay. Pooled risk ratio (RR) and mean difference with the corresponding 95% CI were obtained by the Mantel-Haenszel method within a random-effect model. RESULTS: A total of 14 studies (5 randomized controlled trials [RCTs] and 9 observational studies) involving 3,324 subjects (1,495 received APP and 1,829 did not) were included. There was a significant reduction in the mortality rate in APP group compared to control (RR 0.68 [95% CI 0.51-0.90]; P = .008, I2 = 52%) with no significant effect on intubation (RR 0.85 [95% CI 0.66-1.08]; P = .17, I2 = 63%) or hospital length of stay (mean difference -3.09 d [95% CI-10.14-3.96]; P = .39, I2 = 97%). Subgroup analysis of RCTs showed significant reduction in intubation rate (RR 0.83 [95% CI 0.72-0.97]; P = .02, I2 = 0%). CONCLUSIONS: APP has the potential to reduce the in-hospital mortality rate in COVID-19 subjects with hypoxemia without a significant effect on the need for intubation or length of hospital stay. However, there was a significant decrease in the need for intubation on subgroup analysis of RCTs. More large-scale trials with a standardized protocol for prone positioning are needed to better evaluate its effectiveness in this select population.

Hybrid convergent ablation versus endocardial catheter ablation for atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: Endocardial catheter ablation (ECA) for atrial fibrillation (AF) has limited efficacy. Hybrid convergent procedure (HCP) with both epicardial and endocardial ablation is a novel strategy for AF treatment. In this meta-analysis, we aimed to evaluate the efficacy and safety of HCP in AF ablation. METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of HCP compared with ECA for AF. The primary outcome was freedom of atrial arrhythmia (AA). The secondary outcome was the periprocedural complication rate. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: A total of eight studies, including 797 AF patients (mean age: 60.7 ± 9.8 years, 366 patients with HCP vs. 431 patients with ECA alone), were included. HCP showed a higher rate of freedom of AA compared with ECA (RR: 1.48, 95% CI: 1.13-1.94, p = .004). However, HCP was associated with higher rates of periprocedural complications (RR: 3.64, 95% CI: 2.06-6.43; p = .00001). Moreover, the HCP had a longer procedure time and postprocedural hospital stay. CONCLUSIONS: Although hybrid ablation was associated with a higher success rate, this should be judged for increased periprocedural adverse events and extended hospital stay. Prospective large-scale randomized trials are needed to validate these results.

Outcomes of distal versus conventional transradial access for coronary angiography and intervention: An updated systematic review and meta-analysis.

INTRODUCTION: Distal transradial artery access (DTRA) has recently gained attention due to potential benefits in terms of local complications. In this meta-analysis, we aimed to evaluate the utility of DTRA compared to conventional transradial artery access (CTRA) for coronary angiography and intervention. METHOD: Multiple databases were searched from inception through May 2021 for all the studies that evaluated the efficacy and safety of DTRA in the coronary field. The primary outcome was the access success rate. The secondary outcomes were periprocedural local complications (site hematoma, radial artery occlusion, and spasm) and procedural characteristics (cannulation, fluoroscopy, procedure, and radial artery compression times). All meta-analyses were conducted using a random-effect model. RESULTS: A total of 12 studies (including four randomized control trials) with 1634 patients who underwent DTRA vs. 1657 with CTRA were included in the final analysis. The access success rate was similar between the two groups (odds ratio (OR):0.62; 95% confidence interval (CI):0.30-1.26; P = 0.18; I2 = 61%). DTRA was associated with a statistically significant lower rate of radial artery occlusion (OR:0.36; 95% CI: 0.22-0.59; P < 0.001; I2 = 0%) but similar rates of radial artery spasm and site hematoma when compared to CTRA. Regarding the procedural characteristics, despite having a longer canulation time (mean difference (min.) [MD] 0.89, 95% CI 0.36-1.42; P < 0.0001), DTRA was associated with shorter compression time and comparable fluoroscopy and procedure times. CONCLUSIONS: Our meta-analysis demonstrates that the DTRA is effective and safe with superiority in preventing radial artery occlusion when compared to CTRA.

Direct Oral Anticoagulants Versus Warfarin in Morbidly Obese Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis recommended avoiding the use of DOACs in morbidly obese patients (body mass index >40 or weight >120 kg) because of limited clinical data. STUDY QUESTION: Are DOACs effective and safe in morbidly obese patients with nonvalvular atrial fibrillation (NVAF). DATA SOURCES: We performed a comprehensive search for published studies indexed in PubMed/MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials that evaluated the efficacy and safety of DOACs in morbidly obese patients with NVAF. STUDY DESIGN: Information on patient characteristics, comorbidities, primary anticoagulation indications, pharmacologic treatment, and outcomes were collected. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). RESULTS: A total of 10 studies including, 89,494 morbidly obese patients with NVAF on oral anticoagulation therapy (45,427 on DOACs vs. 44,067 on warfarin) were included in the final analysis. The SSE rate was significantly lower in DOACs group compared with warfarin group [odds ratio: 0.71; 95% confidence interval (CI): 0.62-0.81; P < 0.0001; I2 = 0%]. MB rate was also significantly lower in DOACs group compared with the warfarin group (odds ratio: 0.60; 95% CI: 0.46-0.78; P < 0.0001; I2 = 86%). On subgroup analysis, SSE and MB event rates were significantly lower in rivaroxaban and apixaban than warfarin; however, dabigatran showed noninferiority to warfarin in SSE rate but superiority in the safety outcome. CONCLUSIONS: Our meta-analysis demonstrated that DOACs are effective and safe with statistical superiority when compared with warfarin in morbidly obese patients. Large-scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs in this cohort of patients.

Secondary Immune Thrombocytopenia Associated With Asymptomatic COVID-19 Successfully Managed With Intravenous Immunoglobulin and Glucocorticoids.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts of <100 × 109/L with the absence of other blood count abnormalities. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 which is manifested by a severe multisystemic disease. We present the case of a 76-year-old female who presented with ITP associated with COVID-19 and successfully managed with intravenous immunoglobulin and glucocorticoids.

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.

Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways-either via mutations or genomic amplification-confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of PIK3CA in aggressive cancers, most of the available data highlight the important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways are investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of PI3K/AKT/mTOR pathways in major cancer types and examines its association with clinicopathological parameters and prognosis.