Meta‐analysis of the association between sodium‐glucose co‐transporter‐2 inhibitors and risk of skin cancer among patients with type 2 diabetes

A slight increase in melanoma risk was observed among sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitor users in the regular reports. However, the association remains uncertain. To address this issue, we performed a systematic search of electronic databases up to May 2, 2018 and a meta‐analysis of 21 randomized controlled trials (RCTs) involving 20 308 patients. We did not find a significant increase in risk of melanoma among SGLT‐2 inhibitor users (Peto odds ratio [OR], 2.17; 95% confidence interval [CI], 0.80‐5.89; I2, 0%). Similar results were observed in the subgroup analyses according to the type of SGLT‐2 inhibitor, type of control, ages of patients, race/ethnicity, and trial durations. For non‐melanoma skin cancer risk, no significant difference was observed when all trials were combined (Peto OR, 0.70; 95% CI, 0.47‐1.07; I2, 0%), while a significantly decreased risk was observed among trials with duration <52 weeks (Peto OR, 0.12; 95% CI, 0.02‐0.59; I2, 0%). No evidence of publication bias was detected in the analyses. Current evidence from RCTs did not support a significantly increased risk of skin cancer associated with SGLT‐2 inhibitors

SGLT2 inhibitor plus DPP‐4 inhibitor as combination therapy for type 2 diabetes: A systematic review and meta‐analysis

To assess the efficacy and safety of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors plus a dipeptidyl peptidase‐4 (DPP‐4) inhibitor in patients with type 2 diabetes mellitus (T2DM), we performed a systematic review and meta‐analysis of 14 randomized controlled trials (RCTs) involving 4828 patients. Compared with a DPP‐4 inhibitor, SGLT2 inhibitor/DPP‐4 inhibitor combination therapy was significantly associated with a decrease in glycaemic control (HbA1c, −0.71%; fasting plasma glucose [FPG], −25.62 mg/dL; postprandial plasma glucose, −44.00 mg/dL), body weight (−2.05 kg) and systolic blood pressure (−5.90 mm Hg), but an increase in total cholesterol (TC) of 3.24%, high‐density lipoprotein of 6.15% and low‐density lipoprotein of 2.55%. Adding a DPP‐4 inhibitor to an SGLT2 inhibitor could reduce HbA1c by −0.31%, FPG by −8.94 mg/dL, TC by −1.48% and triglycerides by −3.25%. Interestingly, low doses of an SGLT2 inhibitor in the combination has similar or even better efficacy in some aspects than high doses. Similar adverse events were observed for the combination therapy, with the exception of genital infection vs DPP‐4 inhibitor (risk ratio [RR], 5.31) and consistent genital infection vs an SGLT2 inhibitor (RR, 0.61). Further studies are warranted to confirm these results

Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: A systematic review and meta-analysis

Background Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent. Objective To assess the association between voriconazole use and risk of SCC. Methods We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with a 95% confidence interval (CI). Results Of the 8 studies involving a total of 3710 individuals with a lung transplant or hematopoietic cell transplant that were included in the qualitative analysis, 5 were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36-2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole use was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09-2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41-1.71). Limitations There were some heterogeneities in the retrospective observational studies. Conclusions Our findings support an increased risk of SCC associated with voriconazole in individuals with a lung transplant or hematopoietic cell transplant. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC

Statin use and non-melanoma skin cancer risk: a meta-analysis of randomized controlled trials and observational studies

Background Existing evidence of the association between statin use and non-melanoma skin cancer (NMSC) risk has been inconsistent. Objective To maximize statistical power to synthesize prospective evidence on this relationship. Materials and Methods PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov were systematically searched up to December 11, 2016. A random-effects meta-analysis was conducted to calculate summary estimates. Results Our meta-analysis of 14 randomized controlled trials (RCTs) including 63,157 subjects showed no significant association between statin use and NMSC risk (RR = 1.09, 95%CI = 0.85–1.39). However, meta-analysis of four observational studies including 1,528,215 participants showed significantly increased risk of NMSC among statin users compared to non-users (RR = 1.11, 95%CI = 1.02–1.22). Furthermore, ever using lipophilic statins (RR = 1.14, 95%CI = 1.04–1.24) or lower-potency statins (RR = 1.14, 95%CI = 1.03–1.26), as well as usage of any statin longer than one year (RR = 1.14, 95%CI = 1.09–1.18) were significantly associated with increased NMSC risk based on observational studies. Conclusions Evidence from observational studies supported an association between statin use and increased NMSC risk. This finding should be interpreted with caution due to modest number of included studies, possible between-study heterogeneity and inherent limitations of observational studies

Effect of Sodium–Glucose Cotransporter 2 Inhibitors on Diabetic Ketoacidosis Among Patients With Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials

SCI(E)[email protected]

Use of Antihypertensive Drugs and Risk of Malignant Melanoma: A Meta-analysis of Observational Studies

Introduction Several antihypertensive drugs are photosensitizing and may promote the development of malignant melanoma (MM), but evidence remains inconsistent. We sought to quantify the association between use of antihypertensive drugs and MM risk. Methods We systematically searched PubMed, Embase, and CENTRAL from inception to August 17, 2017 to identify observational studies that reported the MM risk associated with the use of antihypertensive drugs. A random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). Results Overall, we included eight observational studies (two cohort studies and six case–control studies). Compared with non-use, use of diuretics (OR 1.10; 95% CI 1.03–1.17) or β-adrenergic blocking agents (OR 1.19; 95% CI 1.04–1.37) was significantly associated with increased risk of MM. The use of angiotensin-converting enzyme inhibitors (OR 1.08; 95% CI 0.95–1.23), angiotensin II receptor blockers (OR 1.12; 95% CI 0.95–1.31), and calcium channel blockers (OR 1.12; 95% CI 0.72–1.74) was not significantly associated with increased risk of MM. Conclusions Current evidence from observational studies suggests that use of diuretics or β-adrenergic blocking agents may be associated with increased risk of MM. Further large well-conducted prospective studies are required to confirm our findings

HieNet: Bidirectional Hierarchy Framework for Automated ICD Coding

International Classification of Diseases (ICD) is a set of classification codes for medical records. Automated ICD coding, which assigns unique International Classification of Diseases codes with each medical record, is widely used recently for its efficiency and error-prone avoidance. However, there are challenges that remain such as heterogeneity, label unbalance, and complex relationships between ICD codes. In this work, we proposed a novel Bidirectional Hierarchy Framework(HieNet) to address the challenges. Specifically, a personalized PageRank routine is developed to capture the co-relation of codes, a bidirectional hierarchy passage encoder to capture the codes' hierarchical representations, and a progressive predicting method is then proposed to narrow down the semantic searching space of prediction. We validate our method on two widely used datasets. Experimental results on two authoritative public datasets demonstrate that our proposed method boosts state-of-the-art performance by a large margin

Meta-Analysis of Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes and All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus

The benefit or risk of sodium glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus has not been established. We aimed to assess the comparative CV safety and mortality risk associated with the use of SGLT2 inhibitors. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were systematically searched up to January 27, 2016, to identify randomized controlled trials (RCTs) with the use of SGLT2 inhibitors of at least 24 weeks of duration. The primary outcomes included all-cause mortality and major adverse cardiovascular events. A random-effects network meta-analysis was performed to calculate the odds ratio (OR) with 95% CI. We identified 37 eligible trials involving 29,859 patients that compared 3 SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to placebo and other active antidiabetic treatments. Of all direct and indirect comparisons, only empagliflozin compared with placebo was significantly associated with lower risk of all-cause mortality (OR 0.67, 95% CI 0.56 to 0.81) and major adverse cardiovascular events (OR 0.81, 95% CI 0.70 to 0.93). However, the significant effect of empagliflozin was largely driven by one large randomized trial (EMPA-REG OUTCOME trial). Neither dapagliflozin nor canagliflozin was significantly associated with any harm. In conclusion, current RCT evidence suggests that 3 common SGLT2 inhibitors are not associated with increased risk of all-cause mortality and CV outcomes when used to treat patients with type 2 diabetes mellitus. Although empagliflozin may have a protective effect, further confirmative data from rigorous RCTs are needed

Phosphodiesterase type 5 inhibitors and risk of melanoma: A meta-analysis

Background The association between phosphodiesterase type 5 (PDE5) inhibitors and melanoma risk is controversial. Objective We quantify the association between use of PDE5 inhibitors and melanoma. Methods We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for studies that were conducted up to July 13, 2016, and evaluated the association between PDE5 inhibitors and skin cancer. Random effects meta-analyses were used to calculate the adjusted odds ratio (OR) with the 95% confidence interval (CI). Results Five observational studies were included. Compared with PDE5 inhibitor nonuse, PDE5 inhibitor use was slightly but significantly associated with an increased risk for development of melanoma (OR, 1.12; 95% CI, 1.03-1.21) and basal cell carcinoma (OR, 1.14; 95% CI, 1.09-1.19) but not squamous cell carcinoma. For melanoma risk, none of the prespecified factors (dose of PDE5 inhibitor, study design, and study region) significantly affected the results (P > .05). Our sensitivity analysis confirmed the stability of the results. Limitations We included only observational studies, which had some heterogeneities and inconsistent controlling for potential confounders. Conclusions Use of PDE5 inhibitors may be associated with a slightly increased risk for development of melanoma and basal cell carcinoma but not squamous cell carcinoma. However, further large well-conducted prospective studies with adequate adjustment for potential confounders are required for confirmation

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials

Aims/hypothesis The association between sodium–glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. Methods We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs. Results In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). Conclusions/interpretation Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted