A scoping review of fair machine learning techniques when using real-world data.

OBJECTIVE: The integration of artificial intelligence (AI) and machine learning (ML) in health care to aid clinical decisions is widespread. However, as AI and ML take important roles in health care, there are concerns about AI and ML associated fairness and bias. That is, an AI tool may have a disparate impact, with its benefits and drawbacks unevenly distributed across societal strata and subpopulations, potentially exacerbating existing health inequities. Thus, the objectives of this scoping review were to summarize existing literature and identify gaps in the topic of tackling algorithmic bias and optimizing fairness in AI/ML models using real-world data (RWD) in health care domains. METHODS: We conducted a thorough review of techniques for assessing and optimizing AI/ML model fairness in health care when using RWD in health care domains. The focus lies on appraising different quantification metrics for accessing fairness, publicly accessible datasets for ML fairness research, and bias mitigation approaches. RESULTS: We identified 11 papers that are focused on optimizing model fairness in health care applications. The current research on mitigating bias issues in RWD is limited, both in terms of disease variety and health care applications, as well as the accessibility of public datasets for ML fairness research. Existing studies often indicate positive outcomes when using pre-processing techniques to address algorithmic bias. There remain unresolved questions within the field that require further research, which includes pinpointing the root causes of bias in ML models, broadening fairness research in AI/ML with the use of RWD and exploring its implications in healthcare settings, and evaluating and addressing bias in multi-modal data. CONCLUSION: This paper provides useful reference material and insights to researchers regarding AI/ML fairness in real-world health care data and reveals the gaps in the field. Fair AI/ML in health care is a burgeoning field that requires a heightened research focus to cover diverse applications and different types of RWD.

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

INTRODUCTION: Little is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D). METHODS: Participants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005-2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model. RESULTS: Among 1393 participants, 104 developed dementia over a 4-year median follow-up. Metformin was significantly associated with a lower risk of dementia in the overall population (RD, -3.2%; 95% CI, -6.2% to -0.2%). We identified four subgroups with varied risks for dementia, defined by neuropsychiatric disorders, non-steroidal anti-inflammatory drugs, and antidepressant use. DISCUSSION: Metformin use was significantly associated with a lower risk of dementia in individuals with T2D, with significant variability among subgroups.

Heterogeneous treatment effects of sodium-glucose cotransporter 2 inhibitors on risk of dementia in people with type 2 diabetes: A population-based cohort study.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.

The efficacy and safety of prophylactic antibiotics for post-acute stroke infection: A systematic review and meta-analysis.

AIMS: Infections are common complications after stroke and associated with unfavourable outcomes. We aimed to evaluate the efficacy and safety of prophylactic antibiotics for post-acute stroke infection. METHODS: We searched PubMed, Embase, the Cochrane Library, SinoMed, China National Knowledge Infrastructure, WanFang Data, China Science and Technology Journal Database, and clinical trial register platforms from inception to 15 February 2022. We included randomized clinical trials that evaluated the efficacy and safety of prophylactic antibiotics. Primary outcomes were mortality rate and incidence of pneumonia. The pooled risk ratio (RR) and mean differences with 95% confidence interval (CI) were calculated using the random or fixed-effect model depending on heterogeneity. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Twelve studies (4809 participants) were included. There was no significant difference in the mortality rate (12 trials, n = 4740, RR 1.03 [95% Cl: 0.91-1.16], high-quality evidence), incidence of pneumonia (7 trials, n = 4352, RR 0.94 [95% CI: 0.79-1.11], high-quality evidence) and the incidence of adverse events between the prophylactic antibiotics and control groups. Prophylactic antibiotics significantly reduced the incidence of infections (8 trials, n = 4517, RR 0.72 [95% CI: 0.58-0.89], moderate-quality evidence) and urinary tract infections (7 trials, n = 4352, RR 0.39 [95% CI: 0.3-0.49], moderate-quality evidence). None of the subgroup analyses showed a significant difference in mortality or the incidence of pneumonia. CONCLUSION: For acute stroke patients, prophylactic antibiotics were significantly associated with fewer incidences of any infections and urinary tract infections without significant differences in mortality rate and pneumonia.

Airy-Talbot plasmon: an accelerating self-imaging surface wave.

In this Letter, a new class of an accelerating self-imaging surface plasmonic wave, the Airy-Talbot plasmon, is introduced for the first time, to the best of our knowledge. Our research shows that such a surface wave propagates at the interface between metal (silver) and a dielectric material (air) and causes a strong interference along curved trajectories, which generates the Talbot effect in the surface. The propagation properties have potential value in nanoscale plasmonic devices. A scheme for generating this novel plasmon theoretically is proposed, and we prove it by finite difference time-domain numerical simulations.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. SEARCH METHODS: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. SELECTION CRITERIA: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. MAIN RESULTS: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. AUTHORS' CONCLUSIONS: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

Effects of sodium-glucose cotransporter 2 inhibitors on risk of venous thromboembolism in patients with type 2 diabetes: A systematic review and meta-analysis.

It has been reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors could increase blood viscosity, which may further increase risk of venous thromboembolism (VTE). Therefore, we conducted this meta-analysis to evaluate the association between SGLT2 inhibitors and risk of VTE in patients with type 2 diabetes. We systematically searched electronic databases up to April 2019 to identify randomized trials that reported the events of VTE in SGLT2 inhibitors group and control group (placebo or other active antidiabetic drugs). The primary outcome was VTE, and secondary outcomes included deep venous thrombosis (DVT) and pulmonary embolism (PE). A fixed-effects meta-analysis was performed to calculate the risk ratio (RR) with 95% CI. In total, 29 randomized trials involving 56 035 patients with type 2 diabetes were included. Incidence of VTE was not significantly different between SGLT2 inhibitors group and control group (128/32 038 vs 92/23 997), yielding an RR of 0.98 (95% CI, 0.75-1.28). Similarly, null associations were observed in the subgroup analyses. Our cumulative meta-analysis demonstrated the stability of our overall result over time. There was no significant association between SGLT2 inhibitors and risk of both DVT (17 trials; 31/17 442 vs 15/10 930; RR, 1.06; 95% CI, 0.60-1.89) and PE (19 trials; 56/26 118 vs 41/19 517; RR, 0.99; 95% CI, 0.67-1.46). Low statistical heterogeneity and no evidence of publication bias were observed. Current evidence from randomized trials found no association between SGLT2 inhibitors and risk of VTE among patients with type 2 diabetes.

Effect of short-term vitamin D supplementation after nonsurgical periodontal treatment: A randomized, double-masked, placebo-controlled clinical trial.

OBJECTIVES: This trial aimed to evaluate the efficacy and safety of vitamin D supplementation on the residual moderate and deep pockets following nonsurgical periodontal therapy. BACKGROUND: Vitamin D supplementation has potential effects on periodontitis, but current evidence remains inconclusive. METHODS: After 3 months of nonsurgical periodontal treatment, 360 patients with moderate or severe periodontitis were randomly assigned to 2000 international unit (IU)/d vitamin D3, 1000 IU/d vitamin D3, or placebo. Clinical periodontal examinations, including probing depth (PD), bleeding index (BI), plaque index (PLI), attachment loss (AL), and alveolar crest height (ACH), were performed at baseline and after 3 months of intervention. RESULTS: There was a slight but significant decrease in AL and PD in both vitamin D groups compared with placebo group for moderate and deep pockets. About 2000 IU/d vitamin D3 group, 1000 IU/d vitamin D3 group, and placebo group all decreased the AL for both moderate pockets (-0.4 mm vs -0.4 mm vs -0.3 mm) and deep pockets (-1.1 mm vs -1.1 mm vs -1.0 mm) (all P < .05). Similarly, PD was also decreased in these three groups for both moderate pockets and deep pockets (all P < .05). In addition, vitamin D supplementation was well tolerated, and no adverse events were reported. CONCLUSIONS: Although statistically significant differences were observed in favor to vitamin D supplementation, the magnitude of effect size tended to be modest with limited clinical relevance and the long-term efficacy and safety warrant further investigation.

Pancreatic safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

PURPOSE: This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence. RESULTS: Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence). CONCLUSIONS: Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.

Effects of sodium glucose cotransporter 2 inhibitors on risk of dyslipidemia among patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Sodium glucose cotransporter 2 (SGLT2) inhibitors are shown to cause small, but significant changes of lipid profiles, we aim to investigate whether such altered lipid profiles can be translated into clinically meaningful changes in dyslipidemia. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with placebo or other oral glucose-lowering drugs in patients with type 2 diabetes mellitus and reported the events of dyslipidemia. A random-effect meta-analysis was performed to calculate the pooled estimates with risk ratio (RR) for dyslipidemia risk and weighted mean difference for lipid profiles with their 95% confidential intervals (CIs). RESULTS: Of 2427 studies identified, 15 RCTs involving 7578 patients were included. This meta-analysis found no association between SGLT2 inhibitors and risk of dyslipidemia (RR: 1.13; 95% CI: 0.91-1.40). However, SGLT2 inhibitors were significantly associated with increases in total cholesterol by 0.15 mmol/L, low-density lipoprotein cholesterol by 0.12 mmol/L, and high-density lipoprotein cholesterol by 0.07 mmol/L while they can significantly decrease triglycerides by -0.12 mmol/L compared to controls. CONCLUSIONS: SGLT2 inhibitors were not associated with increased risk of dyslipidemia. Further trials with longitudinal assessment are needed to assess the effect of SGLT2 inhibitors on trajectories of changes of lipid metabolism.

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.

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.

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.

Comparisons of diabetic retinopathy events associated with glucose-lowering drugs in patients with type 2 diabetes mellitus: A network meta-analysis.

AIM: To assess the comparative effects of glucose-lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random-effects pairwise and network meta-analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta-analysis found that DPP-4i (OR, 1.20; 95% CI, 0.87-1.65), GLP-1RA (OR, 1.19; 95% CI, 0.94-1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49-1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP-4i in the pairwise meta-analysis (OR, 1.27; 95% CI, 1.05-1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01-2.76). CONCLUSIONS: Current evidence indicates that the association between DPP-4i, GLP-1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in large-scale, well-designed studies.

Use of antihypertensive drugs and risk of keratinocyte carcinoma: A meta-analysis of observational studies.

PURPOSE: Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta-analysis of observational studies. METHODS: We systematically reviewed observational studies published through August 2016 and reported the KC risk (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) associated with antihypertensive drugs, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-adrenergic blocking agents (ß-blockers), and calcium channel blockers (CCBs). Random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). RESULTS: Ten eligible studies were included. Compared with nonuse, diuretic use was significantly associated with increased risk of both BCC (OR, 1.10; 95% CI, 1.01-1.20) and SCC (OR, 1.40; 95% CI, 1.19-1.66). Use of ß-blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with ß-blockers was 1.09 (95% CI, 1.04-1.15) and with CCBs was 1.15 (95% CI, 1.09-1.21). Use of ACE inhibitors or ARBs was associated with decreased risk of both BCC (OR, 0.53; 95% CI, 0.39-0.71) and SCC (OR, 0.58; 95% CI, 0.42-0.80) in high-risk individuals. CONCLUSIONS: Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high-risk individuals. ß-blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.

Clinical features and treatment of pediatric patients with drug-induced anaphylaxis: a study based on pharmacovigilance data.

We assessed the clinical features and treatment of pediatric patients with drug-induced anaphylaxis in clinical settings. Pediatric drug-induced anaphylaxis cases collected by the Beijing Pharmacovigilance Database from 2004 to 2014 were analyzed. A total of 91 cases were identified. Drug-induced anaphylaxis was primarily caused by antibiotics (53%). Children of 0-5 years were more likely to develop cyanosis symptoms than children of 13-17 years (OR = 5.14, 95%CI [1.74, 15.20], P = 0.002). Children of 13-17 years were more likely to develop hypotension than children of 6-12 years (OR = 11.79, 95%CI [2.28, 60.87], P = 0.002), and to manifest both neurological symptoms (OR = 3.56, 95%CI [1.26, 10.08], P = 0.015) and severe anaphylaxis than children of 0-5 years (OR = 15.46, 95%CI [1.85, 129.33], P = 0.002). Supratherapeutic doses of epinephrine were more likely with intravenous (IV) bolus (92%) in contrast to either intramuscular (IM) (36%, OR = 19.25, 95%CI [1.77, 209.55], P = 0.009) or subcutaneous (SC) injections (36%, OR = 19.80, 95% CI [1.94, 201.63], P = 0.005). Only 62 (68%) patients received epinephrine treatment as the first-line therapy. CONCLUSION: This study demonstrates that antibiotics were the most common cause of pediatric drug-induced anaphylaxis. Children may present with different anaphylactic signs/symptoms based on age groups. Epinephrine is under-utilized and provider education on the proper management of drug-induced anaphylaxis is warranted. What is Known: • The most common causes of anaphylaxis in children are allergies to foods. Drugs are the second most common cause of pediatric anaphylaxis. • IM epinephrine is the recommended initial treatment of anaphylaxis. What is New: • Drug-induced anaphylaxis in pediatric patients has age-related clinical features. • IV bolus epinephrine was overused and associated with supratherapeutic dosing.

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.

Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the Beijing Pharmacovigilance Database.

BACKGROUND: Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. METHODS: DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine. RESULTS: DIA was primarily caused by antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients received epinephrine treatment. Patients who received epinephrine were more likely to experience wheezing (p < 0.001) and respiratory arrest (p < 0.001). Among 518 patients with a complete record of the epinephrine administration route, the percentage of patients receiving it by intramuscular (IM) injection, subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients with a record of both the administration route and the dosing, an overdose was more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; p < 0.001) or SC injection (43.7%; p < 0.001). Among the patients analyzed for CAE (n = 349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were overdosed with epinephrine. CONCLUSION: Underuse, inappropriate IV bolus use, and overdosing were the 3 major problems with epinephrine use in DIA in China. Educational training for health care professionals on the appropriate use of epinephrine in managing anaphylactic reactions is suggested.

Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials.

AIM: To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. RESULTS: In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. CONCLUSIONS: The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.

Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose.