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AIM: Ipragliflozin is a new antidiabetic agent that works through enhancing renal glucose excretion. We aim to synthesize evidence from published randomized controlled trials (RCTs) on the safety and efficacy of ipragliflozin in the management of type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central register of clinical trials using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup and sensitivity analyses were conducted. RESULTS: We included 13 RCTs (N=2535 patients) in the final analysis. The overall effect estimates favoured ipragliflozin 50mg monotherapy group over placebo in terms of: HbA1c (Standardized mean difference (SMD)=-1.20%, 95% Confidence interval (95% CI)=[-1.47, -0.93]; p<0.001), fasting plasma glucose (SMD=-1.30 mg/dL, 95% CI [-1.93, -0.67]; p<0.001), fasting serum insulin (SMD=-1.64 µU/mL, 95% CI [-2.70, -0.59]; p=0.002), and body weight (SMD=-0.85 kg, 95% CI [-1.19, -0.51]; p<0.001). Similarly, better glycemic control and significant body weight reduction compared to placebo were attained in ipragliflozin 50 mg combination with metformin, insulin with/without dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone. Ipragliflozin, either alone or in combination, exhibits acceptable safety profile. CONCLUSION: The presented meta-analysis provides class one evidence that ipragliflozin is safe and effective in the management of T2DM either as monotherapy or an add-on.

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Autoimmune blistering diseases can eventually cause life-threatening complications if left untreated. Although there is no cure for these bullous diseases; their therapy is based on suppressing the immune system to cease the de novo formation of the generated antibodies. The current study aimed to assess the safety and efficacy of using standing alone alternative therapies beyond systemic steroids for management of autoimmune bullous diseases. We searched six literature databases for both randomized and quasi-randomized clinical trials that assessed the efficacy of drugs other than systemic steroids in autoimmune bullous diseases. Outcomes were calculated as odds ratios with 95% confidence-interval. We used the R software to perform conventional and network meta-analyses with a frequentist approach. The network ranking order for 629 bullous pemphigoid patients, from the best to the worst was, clobetasol propionate cream (40 mg; (P-score = .87), clobetasol propionate cream (10-30 mg; P-score = .77), nicotinamide plus tetracycline (P-score = .56), steroids (P-score = .29) and doxycycline (P-score = .01). Limitations of this study are the small sample of the included studies except for blister trial and lack of randomization in most trials. To conclude, Combined doxycycline and nicotinamides are safer and more effective option for extensive bullous pemphigoid patients than the usual use of systemic steroids. For limited disease, topical corticosteroid (40 mg/d) use provides a safer and better response modality than the other proposed treatments.

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Deep brain stimulation (DBS) is a surgical treatment in which stimulation electrodes are permanently implanted in basal ganglia to treat motor fluctuations and symptoms of Parkinson's disease (PD). Subthalamic nucleus (STN) and globus pallidus internus (GPi) are the commonly used targets for DBS in PD. Many studies have compared motor and non-motor outcomes of DBS in both targets. However, the selection of PD patients for DBS targets is still poorly studied. Therefore, we performed this narrative review to summarize published studies comparing STN DBS and GPi DBS. GPi DBS is better for patients with problems in speech, mood, or cognition while STN DBS is better from an economic point of view as it allows much reduction in antiparkinson medications and less battery consumption.

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BACKGROUND: Bone metastasis is reported to be associated with poor quality of life, and increased risk of hospitalization. We aim to synthesize evidence from published randomized controlled trials (RCTs) which compared the efficacy of denosumab versus bisphosphonates in patients with advanced cancers. METHODS: We searched for all published RCTs in the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. Retrieved records were screened for eligibility. Time-to-event data were pooled as hazard ratio (HR) using the generic inverse-variance method and dichotomous data were pooled as relative risk (RR) in a random-effect model. We used Review Manager 5.3 for windows. RESULTS: Six unique RCTs with a total of 7722 patients were included. Overall effect estimates favored denosumab group in comparison to intravenous (IV) bisphosphonates in the following terms: time to first skeletal-related events (HR 0.92, 95% CI [0.86, 0.98], p = 0.01), time to subsequent skeletal-related event (RR 0.92, 95% CI [0.86, 0.99], p = 0.03), and radiation to bone (RR 0.81, 95% CI [0.71, 0.92], p = 0.02). Denosumab group was associated with increased risk of grade 3 or 4 hypocalcaemia (RR 1.99, 95% CI [1.11, 3.54], p = 0.02) and reduced risk of renal impairment or toxicity (RR 0.75, 95% CI [0.61, 0.91], p = 0.003) in comparison to IV bisphosphonates group. Pooled studies were homogenous. CONCLUSION: Denosumab showed a favorable significant impact on delaying the time to first skeletal-related event and reducing the incidence of radiation to the bone event in comparison to bisphosphonates, with similar efficacy regarding overall survival and time to disease progression. Further large-scale and long-term studies are needed to clarify the long-term efficacy and safety of both regimens.

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INTRODUCTION: Sunitinib is an orally delivered tyrosine kinase inhibitor that exhibits antiangiogenic effects. FDA has approved sunitinib for the treatment of metastatic renal cell carcinoma. However, its efficacy for the treatment of advanced breast cancer (ABC) remains controversial. Therefore, we performed this systematic review and meta-analysis to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of sunitinib alone and in combination with chemotherapy for the treatment of ABC. METHODS: We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search of PubMed, SCOPUS, web of knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL) has been conducted using relevant keywords. Studies were screened for eligibility and data were extracted to an online data extraction form. Progression free survival (PFS) and overall survival (OS) were pooled as Hazard ratio (HR) in a meta-analysis model using generic inverse variance method. Objective response rate (ORR) and complications were pooled as relative risk (RR) in a random effect model meta-analysis using Mantel-Haenzel method. RESULTS: Six RCTs, with a total sample size of 2273 patients, met our eligibility criteria and were included in this meta-analysis. Sunitinib monotherapy was not superior to chemotherapy in terms of PFS (HR = 1.00, 95% CI [0.86 to 1.16], P = 0.99), OS (HR = 1.07; 95% CI [0.87 to 1.32], P = 0.5), or ORR (RR = 0.70, 95% CI [0.74 to 1.03], P = 0.07). Sunitinib in combination with chemotherapy did not show superiority to chemotherapy in terms of PFS (HR = 0.99, 95% CI [0.86 to 1.14], P = 0.89) and OS (HR = 1.04, 95% CI [0.85 to 1.28], P = 0.69). However, the ORR favored sunitinib in combination with chemotherapy group (RR = 1.15, 95% CI [1.01 to 1.31]) with a statistically significant P value (P = 0.03). CONCLUSIONS: Current evidence shows that sunitinib, either alone or in combination with chemotherapy, has no clinical benefit for patients with advanced breast cancer. However, previous studies did not considered patient stratification and outcome assessment based on molecular markers. In terms of safety, toxicity was common with sunitinib treatment.

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INTRODUCTION: Coenzyme Q10 (CoQ10) is an antioxidant that enhances the activity of complex I and II in the Electron Transport Chain. Many preclinical and clinical studies evaluated CoQ10 for neuroprotection against Parkinson's disease (PD). The aim of this study is to synthesize evidence from published randomized controlled trials (RCTs) about the benefit of CoQ10 supplementation for patients with Parkinson's disease. METHODS: We followed the PRISMA statement guidelines during the preparation of this systematic review and metaanalysis. A computer literature search for (PubMed, EBSCO, Web of science and Ovid Midline) was carried out. We included RCTs comparing CoQ10 with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III and Schwab and England scores were pooled as standardized mean difference (SMD) between two groups from baseline to the endpoint. RESULTS: Five RCTs (981 patients) were included in this study. The overall effect did not favor either of the two groups in terms of: total UPDRS score (SMD -0.05, 95%CI [-0.10, 0.15]), UPDRS I (SMD -0.03, 95% CI [-0.23, 0.17]), UPDRS II (SMD -0.10, 95%CI [-0.35, 0.15]), UPDRS III (SMD -0.05, 95%CI [-0.07, 0.17]) or Schwab and England score (SMD 0.08, 95%CI [-0.13, 0.29]). CONCLUSION: CoQ10 supplementation does not slow functional decline nor provide any symptomatic benefit for patients with Parkinson's disease.

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