Does fully closed-loop automated insulin delivery improve glycaemic control in patients with type 2 diabetes? A meta-analysis of randomized controlled trials.

AIMS: This meta-analysis investigated the efficacy and safety of fully closed-loop automated insulin delivery (AID) in patients with type 2 diabetes. MATERIALS AND METHODS: We systemically searched PubMed, Scopus, Web of Science, and Cochrane Central from inception until April 26, 2023. We included randomized controlled trials (RCTs) comparing fully closed-loop AID versus conventional insulin therapy. The outcomes were pooled as the mean difference (MD) and risk ratio with 95% confidence interval (CI) in the random effect model. Our primary outcome was the proportion of time in the target glucose range (5.6-10 mmol/L, 3.9-10 mmol/L, or 3.9-8 mmol/L, depending on the study). Key secondary outcomes included the proportion of time spent in hyperglycaemia or hypoglycaemia. RESULTS: We included seven RCTs (three crossover and four parallel design), compromising 390 patients. Our analysis showed that compared to the control group, fully closed-loop AID increased the proportion of time spent within the target glucose range by additional 337 min per 24 h (MD = 23.39%, 95% CI [16.64%, 30.14%], p < 0.01), additional 108 min overnight (MD = 22.40%, 95% CI [12.88%, 31.91%], p < 0.01), and additional 258 min during the daytime period (MD = 26.85%, 95% CI [21.06%, 32.63%], p < 0.01). Compared to the control group, the overall time in hyperglycaemia was shortened by 326 min per 24 h (MD = -22.67%, 95% CI [-30.87%, -14.46%], p < 0.01). There was no significant difference between the two groups in terms of overall, overnight, and daytime periods spent in hypoglycaemia. CONCLUSIONS: Our meta-analysis suggests that fully closed-loop AID may improve glycaemic control in patients with type 2 diabetes, particularly for those with more challenging diabetes management. Further research is required to establish the feasibility of implementing these systems in clinical practice. [Correction added on 26 August 2023 after first online publication: Under Results, the first sentence "We included seven RCTs (three crossover and one parallel designs)" has been changed to "We included seven RCTs (three crossover and four parallel designs)".].

Safety of masitinib in patients with neurodegenerative diseases: a meta-analysis of randomized controlled trials.

OBJECTIVES: This meta-analysis aimed to examine the safety of masitinib in patients with neurodegenerative diseases. METHODS: We considered randomized controlled trials (RCTs) comparing different doses of masitinib versus placebo. We performed our analysis using the R (v.4.3.0) programming language and the incidence of adverse events was pooled using risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included five RCTs, focusing on multiple sclerosis (MS), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The meta-analysis revealed a significantly higher incidence of adverse events in the masitinib group compared to the control group, regardless of adverse event grade and masitinib dose (RR = 1.12, 95% CI [1.07 to 1.17], P < 0.01). Adverse events categorized as severe, non-fatal serious, leading to dose reduction, and leading to permanent discontinuation also showed a higher incidence in the masitinib group (P ≤ 0.01). Subgroup analysis for AD and MS supported these findings. The pooled incidence of adverse events, regardless of their grade, was higher in the masitinib group for both the 3 mg/kg/d dose (RR = 1.13, P = 0.01) and the 4.5 mg/kg/d dose (RR = 1.11, P < 0.01). However, there was no significant difference between masitinib 3 mg/kg/d dose and placebo regarding severe and non-fatal serious adverse events for the. CONCLUSION: Masitinib use in neurodegenerative diseases presents safety concerns that may impact patients' quality of life and require management. Further research is recommended to determine the optimal dose with minimal safety concerns in this patient population.

Prevalence and correlates of fatigue in amyotrophic lateral sclerosis: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS). METHODS: Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates. RESULTS: Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI = 40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (< 30) compared to those with higher scores (≥ 30), with a pooled frequency of 62% (95% CI = 43% to 79%) and 43% (95% CI = 37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean (P = 0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS. CONCLUSION: Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.

Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence.

OBJECTIVES: Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib's neuroprotective activities from preclinical to clinical studies. METHODS: This scoping review was conducted following the guidelines described by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies. RESULTS: A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer's disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity. CONCLUSION: The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.

Efficacy and safety of laparoscopic liver resection versus radiofrequency ablation in patients with early and small hepatocellular carcinoma: an updated meta-analysis and meta-regression of observational studies.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths. This study comprehensively compares the safety and efficacy of laparoscopic liver resection (LLR) versus laparoscopic or percutaneous radiofrequency ablation (LRFA or PRFA) in patients with early and small HCC. METHODS: We systematically searched Cochrane Library, PubMed, Scopus, and Web of Science databases to include studies comparing LLR versus LRFA or PRFA in patients with early HCC meets the Milan criteria (defined as solitary nodule < 5 cm or three nodules ≤ 3 cm with no extrahepatic spread or vascular invasion). Pooled results were examined for overall survival, disease-free survival, recurrence-free survival, local, intrahepatic and extrahepatic recurrence rates, and complications. We conducted subgroup analyses based on the type of RFA. Meta-regression analyzed the association between overall survival, local recurrence, and various factors. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. We analyzed the data using the R (v.4.3.0) programming language and the "meta" package of RStudio software. RESULTS: We included 19 observational studies, compromising 3756 patients. LLR showed higher 5-year overall survival compared to RFA (RR = 1.17, 95% CI [1.06, 1.3], P > 0.01). Our subgroup analysis showed that LLR had higher 5-year survival than PRFA (RR = 1.15, 95% CI [1.02, 1.31], P = 0.03); however, there was no significant difference between LLR and LRFA (RR = 1.26, 95% CI [0.98, 1.63], P = 0.07). LLR was associated with higher disease-free survival) RR = 1.19, 95% CI [1.05, 1.35], P < 0.01; RR = 1.61, 95% CI [1.31, 1.98], P < 0.01(and recurrence-free survival) RR = 1.21, 95% CI [1.09, 1.35], P < 0.01; RR = 1.45, 95% CI [1.15, 1.84], P < 0.01(at 1 and 3 years. LLR was associated with lower local (RR = 0.28, 95% CI [0.16, 0.47], P < 0.01) and intrahepatic recurrence (RR = 0.7, 95% CI [0.5, 0.97], P = 0.03) than RFA. However, complications were significantly higher with LLR (RR = 2.01, 95% CI [1.51, 2.68], P < 0.01). Our meta-regression analysis showed that younger patients had higher risk for local recurrence (P = 0.008), while age wasn't significantly linked to overall survival (P = 0.25). Other covariates like total bilirubin, alpha-fetoprotein levels, and tumor size also showed no significant associations with either overall survival or local recurrence. CONCLUSION: LLR offers improved long-term outcomes and lower recurrence rates than PRFA. However, no significant distinctions were observed between LRFA and LLR in overall survival, recurrence-free survival, and local recurrence. More robust well-designed RCTs are essential to validate our findings.

Clinical characteristics, course, and outcomes of amyotrophic lateral sclerosis overlapping with pregnancy: a systematic review of 38 published cases.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease that can overlap with pregnancy, but little is known about its clinical characteristics, course, and outcomes in this context. This systematic review aimed to synthesize the current evidence on ALS overlapping with pregnancy. METHODS: We comprehensively searched four databases on February 2, 2023, to identify case studies reporting cases of ALS overlapping with pregnancy. Joanna Brigs Institute tool was followed to assess the quality of the included studies. RESULTS: Twenty-six articles reporting 38 cases were identified and included in our study. Out of the 38 cases, 18 were aged < 30 years. The onset of ALS was before pregnancy in 18 cases, during pregnancy in 16 cases, and directly after pregnancy in 4 cases. ALS progression course was rapid or severe in 55% of the cases during pregnancy, and this percentage reached 61% in cases with an onset of ALS before pregnancy. While ALS progression course after pregnancy was rapid or severe in 63% and stable in 37% of the cases. Most cases (95%) were able to complete the pregnancy and gave live birth. However, preterm delivery was common. For neonates, 86% were healthy without any complications. CONCLUSION: While pregnancy with ALS is likely to survive and result in giving birth to healthy infants, it could be associated with rapid or severe progression of ALS and result in a worse prognosis, highlighting the importance of close monitoring and counselling for patients and healthcare providers.

Does baricitinib reduce disease activity in patients with systemic lupus erythematosus? A systematic review and meta-analysis of randomized controlled trials.

Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders. This meta-analysis pooled the conflicting results from all published randomized controlled trials (RCTs) about the efficacy and safety of baricitinib in patients with systemic lupus erythematosus (SLE). We systemically searched four electronic databases. RCTs comparing baricitinib versus placebo were included. Our outcomes were pooled as the risk ratio (RR) in the random effects model. Our primary outcome was the proportion of patients who achieved a SLE Responder Index-4 (SRI-4) response. A total of three RCTs, comprising 1849 patients, were included. Baricitinib 4 mg was associated with a significantly higher proportion of patients who attained SRI-4 response at week 24 (RR = 1.19, 95% CI [1.05, 1.35], P < 0.01). However, this did not reach statistical significance with baricitinib 4 mg at week 52 and baricitinib 2 mg at both week 24 and week 52 (RR = 1.13, 95% CI [0.96, 1.34], P = 0.15; RR = 1.09, 95% CI [0.96, 1.24], P = 0.20; RR = 1.05, 95% CI [0.92, 1.19], P = 0.50, respectively). The risk for serious infections was higher in the baricitinib 4 mg group (RR = 2.23, 95% CI [1.13, 4.37], P = 0.02). Baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg might have the potential to reduce SLE disease activity; however, further research is required to evaluate its long-term efficacy. Until higher-quality evidence is developed, the benefits and risks of baricitinib should be considered before initiating its therapy. Key Points • Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders; however, its efficacy in patients with systemic lupus erythematosus (SLE) is still inconclusive. • In our meta-analysis, baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg significantly reduced SLE activity in terms of SRI-4 response at week 24. However, this did not reach statistical significance at week 52. • Further studies are required to investigate the long-term efficacy of baricitinib 4 mg in patients with SLE.

Impact of SGLT2 Inhibitors on Atrial Fibrillation Recurrence after Catheter Ablation in Type 2 Diabetes Mellitus: A Meta-Analysis of Reconstructed Kaplan-Meier Curves with Trial Sequential Analysis.

PURPOSE: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in managing cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is evolving. This meta-analysis seeks to explore the influence of SGLT2i on the recurrence of atrial fibrillation (AF) following catheter ablation (CA) in individuals with T2DM qualitatively and quantitatively. METHODS: A comprehensive literature search was conducted in electronic databases. Studies meeting predefined criteria were included. Individual patient data (IPD) were used from reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals for AF recurrence. IPD meta-analysis was followed by a direct meta-analysis to assess the risk of AF recurrence. RESULTS: A total of five studies [one randomized controlled trial (RCT) and four cohort studies] were included in this study, and five studies were included in the qualitative analysis, while four studies comprising 1043 patients with T2DM were included in the quantitative analysis. The pooled Kaplan-Meier curve based on reconstructed data showed a significantly lower risk of AF recurrence in the SGLT2i group compared with all antidiabetic drugs (log-rank P = 0.00011) and dipeptidyl-peptidase IV inhibitors (DPP4i) (log-rank P = 0.01). Cox regression analysis showed consistent results. Direct meta-analysis showed that SGLT2i, compared with all antidiabetic medications (HR 0.57, 95% CI [0.44, 0.73], I2) and DPP4i (HR 0.41, 95% CI [0.24, 0.70], I2), was associated with a lower risk of AF recurrence. CONCLUSIONS: SGLT2i are associated with a reduced risk of AF recurrence after CA in patients with T2DM. These results suggest that SGLT2i is promising in improving clinical outcomes for this population.

The effect of Empagliflozin on echocardiographic parameters in diabetic patients after acute myocardial infarction: A systematic review and meta-analysis with trial sequential analysis.

Patients with diabetes mellitus (DM) are at higher risk of cardiovascular events, particularly acute myocardial infarction (MI). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can improve cardiac outcomes among heart failure individuals, however, the effects on acute myocardial infarction remain unclear. This meta-analysis investigates the impact of empagliflozin in diabetic patients following acute myocardial infarction. We comprehensively searched PubMed, Scopus, Cochrane, and Web of Science through August 10th, 2023. We included studies comparing empagliflozin versus placebo in diabetes patients with acute myocardial infarction. We used Revman to report the data as mean difference (MD) and 95% confidence interval (CI), and our effect size with a random effects model. Additionally, we performed Trial Sequential Analysis (TSA) to test the robustness of the results. The study protocol was published on PROSPERO with ID: CRD42023447733. Five studies with a total of 751 patients were included in our analysis. Empagliflozin was effective to improve LVEF% (MD: 1.80, 95% CI [0.50, 3.10], p = 0.007), left ventricular end-diastolic volume (LVEDV) (MD: -9.93, 95% CI [-16.07, -3.80], p = 0.002), and left ventricular end-systolic volume (LVESV) (MD: -7.91, 95% CI [-11.93, -3.88], p = 0.0001). However, there was no difference between empagliflozin and placebo groups in terms of NT-pro BNP (MD: - 136.59, 95% CI [-293.43, 20.25], p = 0.09), and HbA1c (MD: -0.72, 95% CI [-1.73, 0.29], p = 0.16). Additionally, empagliflozin did not prevent hospitalization due to heart failure (RR: 0.59, 95% CI [0.16, 2.24], p = 0.44, I-squared = 0%), and mortality (RR: 1.34, 95% CI [0.15,11.90], p = 0.79, I-squared = 25%). Empagliflozin initiation in diabetic patients following acute MI may improve echocardiographic parameters. However, empagliflozin might not be effective in heart failure prevention and optimal glycemic control in this patient population. Further large-scale trials are warranted to ascertain our findings.