The Importance of Clinical Pharmacists in Improving Blood Glucose and Lipid Levels in Patients with Diabetes and Myocardial Infarction.

Purpose: The aim of this study was to evaluate whether intervention by clinical pharmacists can improve blood glucose and lipid levels in diabetic patients with complex medical conditions. Methods: The retrospective database included 138 patients with diabetes who had presented with acute myocardial infarction (AMI) between January 2019 and October 2021. Blood glucose and lipid levels were measured within 12 weeks and 78 weeks of follow-up. Propensity score matching (PSM) was used to balance the confounding effects of patients' characteristics. Results: A total of 138 eligible patients were assigned to either the intervention group (n = 47) or the usual care group (n = 91). After the intervention, there were significant improvements in blood glucose (glycosylated hemoglobin-HbA1C % from 9.0 to 8.3; fasting blood glucose-FBG mmol/L from 11.3 to 7.1; postprandial blood glucose-PBG mmol/L from 17.0 to 12.1; p < 0.001) and lipid levels (total cholesterol-TC from 4.9 to 3.5, low-density lipoprotein cholesterol-LDL-C from 3.0 to 1.8, p < 0.001, mmol/L) in both follow-up periods. The blood glucose effects were most pronounced in the PBG control rate (76.9% vs 54.0%) before PSM, while HbA1C% and PBG control rate after PSM were significantly higher in the intervention group (HbA1C% rate: 65.6% vs 38.5%; PBG rate: 79.2% vs 45.8%; p < 0.05, intervention vs non-intervention). Subgroup analysis further confirmed the improvement of blood glucose and lipid mainly in patients with higher baseline FBG (≧10mmol/L) and moderate follow-up duration (4-12 weeks). Conclusion: The intervention of clinical pharmacists in multidisciplinary team can significantly improve blood glucose and lipid levels in complex type 2 diabetic patients, especially those with high baseline FBG and moderate follow-up durations.

Influence and mechanism of sodium-glucose cotransporter-2 inhibitors on the cardiac function: study protocol for a prospective cohort study.

Background: Acute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism. Methods: This study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level. Discussion: This study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.

System Dynamic Model Simulates the Growth Trend of Diabetes Mellitus in Chinese Population: Implications for Future Urban Public Health Governance.

Objectives: To simulate the growth trend of diabetes mellitus in Chinese population. Methods: The system dynamic modeling methodology was used to establish a population prediction model of diabetes with or without cardiovascular diseases. Lifestyle therapy and the use of metformin, acarbose, and voglibose were assumed to be intervention strategy. The outcomes will be examined at 5, 15, and 30 years after 2020. Results: The projected number of diabetic population in China would increase rapidly from 141.65 million in 2020 to 202.84 million in 2050. Diabetic patients with cardiovascular disease would rapidly increase from 65.58 million in 2020 to 122.88 million by 2050. The annual cost for the entire population with diabetes mellitus in China would reach 182.55 billion by 2050. When the treatment of cardiovascular disease was considered, expenditure was 1.5-2.5-fold higher. Lifestyle therapy and the use of metformin, acarbose and voglibose could effectively slow the growth of the diabetic population. Conclusion: The diabetic population in China is expected to increase rapidly, and diabetic patients with cardiovascular disease will increase greatly. Interventions could delay it.

Comparative efficacy and safety of JAK inhibitors as monotherapy and in combination with methotrexate in patients with active rheumatoid arthritis: A systematic review and meta-analysis.

Background: We aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid arthritis (RA). Methods: Medline, EMBASE, and Cochrane Library were systematically searched to identify relevant randomized controlled trials (RCTs). Pooled analysis was conducted using random-effects model, along with the risk difference (RD) and 95% confidence intervals (CIs). Results: Three RCTs, including 2,290 patients, were included. JAKi (tofacitinib, baricitinib, and filgotinib) plus MTX displayed a higher proportion of patients meeting the American College of Rheumatology (ACR) criteria than JAKi alone at week 52 (ACR20 RD 0.032; 95% CI -0.027 to 0.091; ACR50 RD 0.050; 95% CI 0.003 to 0.097; ACR70 RD 0.056; 95% CI 0.012 to 0.100). Similar results were observed for ACR20/50/70 at week 24. No significant difference was found between two regimens for the proportion of patients achieving Health Assessment Questionnaire disability index (HAQ-DI) improvement ≥ 0.22 at weeks 24 and 52. Regarding low disease activity and remission achievement, JAKi in combination with MTX, contributed higher response rates than JAKi alone at weeks 24 and 52. Compared with JAKi monotherapy, combination therapy had a higher risks of treatment-emergent adverse events (TEAEs) and adverse events (AEs) leading to study discontinuation. Conclusion: JAKi combined with MTX demonstrated superiority to JAKi monotherapy in terms of ACR responses, low disease activity and remission achievement. The two regimens presented comparable physical functioning measured by HAQ-DI improvement and similar tolerability, except for high risks of TEAEs and AEs leading to study discontinuation in combination therapy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288907.

Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients. METHODS: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included. RESULTS: Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e' ratio, E/e' and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: -6.319 g, -10.850 to -1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: -9.134 mL, -15.808 to -2.460; LVESV: -8.440 mL, -15.093 to -1.787; LAVI: -2.791 mL/m2, -.554 to -1.027; E/e': -1.567, -2.440 to -0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment. CONCLUSIONS: Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).

Sulfonylureas Use Is Not Associated With Increased Infarct Size in Patients With Type 2 Diabetes and ST-Segment Elevation Myocardial Infarction.

Aims: This retrospective study assessed the association between sulfonylureas use and infarct size in patients with type 2 diabetes (T2DM) and ST-segment elevation myocardial infarction (STEMI) by myocardial enzymology indexes and cardiac magnetic resonance (CMR) imaging. Methods: Patients presenting STEMI between July 2013 and August 2019 were included in a retrospective database at our institution. Antidiabetic agents used before STEMI were recorded. Patients with maximum recorded troponin I (max cTNI) and creatine phosphokinase isoenzyme (CK-MB) within the first 72 h of chest pain onset were selected. Infarct size was quantified by CMR imaging, and cardiovascular outcomes were also obtained at 30 days and 6 months follow-up. Multivariable regression models explored potential risk factors associated with infarct size and clinical outcomes. Results: A total of 254 T2DM and STEMI patients were included, with 101 sulfonylurea users and 153 non-users. Sulfonylureas users were not associated with higher max cTnI and max CK-MB compared to non-users. Among 65 CMR patients, no significant differences in infarct size were detected between sulfonylureas users and non-users. Whereas, the incidence of microvascular obstruction (MVO) was higher in patients receiving sulfonylureas than those taking non-sulfonylureas (88.0 vs. 62.5%, p = 0.023). No higher cardiovascular events of sulfonylureas users vs. non-users were observed, except for heart failure events (24.0 vs. 2.5% at 30 days, p = 0.011; 28.0 vs. 2.5% at 6 months, p = 0.004). Multivariable regression analyses verified that sulfonylureas users increased the risks of MVO. Conclusions: Sulfonylureas use did not associate with larger infarct size in patients with T2DM and STEMI. A potentially higher incidence of MVO in sulfonylurea users was found. Notably, since most patients presented after a relatively long period of ischemia and glibenclamide was not used by the included patients in this observational study, the results of this study should not be extrapolated to clinical settings with short periods of ischemia or to patients using glibenclamide.

High-dose sodium-glucose co-transporter-2 inhibitors are superior in type 2 diabetes: A meta-analysis of randomized clinical trials.

AIM: To determine the overall efficacy of high- versus low-dose sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D). MATERIAL AND METHODS: A literature search using MEDLINE, EMBASE and the Cochrane Library was performed from 1 January 2006 to 23 September 2020. Random effects models were used to calculate mean differences (MDs) and pooled relative risk (RR). Prespecified subgroup analyses for each SGLT2 inhibitor, follow-up and controls were performed. Leave-one-out sensitivity and meta-regression analyses were conducted. RESULTS: A total of 51 randomized controlled trials involving 23 989 participants (weighted mean age, 58.9 years; men, 58.8%) were eligible for our meta-analysis. For glycaemic regulation ability, a significant reduction in HbA1c (MD -0.080%, 95% confidence interval [CI] -0.100 to -0.060), fasting plasma glucose (MD -0.227 mmol/L, 95% CI -0.282 to -0.173) and postprandial plasma glucose (MD -0.834 mmol/L, 95% CI -1.268 to -0.400) levels was observed in the high-dose SGLT2 inhibitor group. Treatment with high-dose SGLT2 inhibitors enabled easier achievement of the target (HbA1c <7%) than low-dose SGLT2 inhibitors (RR 1.148, 95% CI 1.104 to 1.193). High-dose SGLT2 inhibitor-based treatment resulted in more efficient regulation of body weight and blood pressure (body weight: MD -0.346 kg, 95% CI -0.437 to -0.254; systolic blood pressure: MD -0.583 mmHg, 95% CI -0.903 to -0.263; diastolic blood pressure: MD -0.352 mmHg, 95% CI -0.563 to -0.142). The results were similar in sensitivity analyses. CONCLUSIONS: The overall efficacy of SGLT2 inhibitors, mainly canagliflozin, dapagliflozin and empagliflozin, was found to be dose dependent.

Intervention by clinical pharmacists can improve blood glucose fluctuation in patients with diabetes and acute myocardial infarction: A propensity score-matched analysis.

Acute phase hyperglycemia and exaggerated glucose fluctuation may be associated with poor outcomes in diabetic patients after acute myocardial infarction (AMI). This study aimed to determine whether intervention by clinical pharmacists can mitigate blood glucose and glucose fluctuations in these fragile patients. This retrospective study enrolled patients with diabetes and AMI, from 1 January 2019 to 30 June 2020 in our institution. Blood glucose and glucose fluctuations were calculated before and after the pharmacist's intervention and between patients who underwent intervention and those who did not. Propensity score matching (PSM) was used to reduce the impact of patient characteristics on the results. A total of 170 patients were included in our primary analysis, including 29 patients who received the pharmacist intervention and 141 patients who did not. After the pharmacist's intervention, blood glucose (fasting blood glucose-FBG, from 11.9 to 9.8; postprandial blood glucose-PBG, from 15.3 to 13.2; mean blood glucose-BG, 14.5 to 12.3 mmol/L; p < .001), and glucose fluctuations (standard deviation of blood glucose-SDBG, from 3.8 to 3.0, mmol/L, p = .005) were significantly improved. Before PSM, no clear effects were found in intervention versus nonintervention patients, in terms of blood glucose and glucose fluctuation indicators, except for FBG (9.3 vs. 8.0. mmol/L, p = .005). Further analysis indicated a high incidence of FBG <7.8 mmol/L in nonintervention versus intervention patients (51.5% vs. 27.6%, p = .003). After PSM, a significant reduction in blood glucose fluctuation (SDBG, 3.0 vs. 4.1, p = .031; PBGE, 2.1 vs. 4.1, p = .017; LAGE, 4.7 vs. 7.2, mmol/L, p = .004), and PBG (11.1 vs. 13.0, mmol/L, p = .048) was observed in the intervention group than in the nonintervention group. The clinical pharmacist intervention contributed to improved outcomes, specifically, in reducing blood glucose fluctuations and potential hypoglycemia risk.

Sodium-Glucose Co-Transporter 2 Inhibitors Use Improves the Satisfaction With Anti-diabetic Agent Treatment: A Questionnaire-based Propensity Score-matched Study.

Background: Specific safety issues with sodium-glucose co-transporter-2 (SGLT2) inhibitors such as infection, fractures, worsening of renal function and euglycemic ketoacidosis have been raised. Concerns about adverse events might limit the use of this drug class. The satisfaction with SGLT2 inhibitors treatment in Chinese patients with type 2 diabetes mellitus (T2DM) is unknown. Material and Methods: Patients with T2DM who visited the hospital between October 2019 and June 2020 were included in this retrospective analysis. Patients were divided into SGLT2 inhibitors used group or not. The Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS) questionnaire and self-reported AEs were obtained at 3 months of follow-up. Propensity score matching (PSM) was performed to adjust for confounding factors. Univariate and multivariable linear regression models were used to explore potential risk factors associated with overall satisfaction. Results: A total of 145 T2DM patients were included, with 76 SGLT2 inhibitors users and 69 non-users. Patients administered with SGLT2 inhibitors presented with increased overall satisfaction (mean [SE]: 22.8 [0.67] vs. 20.6 [0.64], p = 0.016) and overall satisfaction rate (n [%]: 40 [52.6%] vs 21 [30.4%], p = 0.007) when compared to other anti-diabetic agents. The use of SGLT2 inhibitors significantly improved satisfaction of glycemic control ability (mean [SE]:3.9 [0.12] vs. 3.5 [0.12], p = 0.027), diabetic symptom's control ability (3.5 [0.15] vs. 3.0 [0.15], p = 0.027), glycemic control speed (3.9 [0.11] vs. 3.4 [0.12], p = 0.011), medication tolerability (3.9 [0.10] vs. 3.5 [0.12], p = 0.012), and overall satisfaction (4.0 [0.11] vs. 3.6 [0.12], p = 0.037), but it did not improve satisfaction of medication effect on bodyweight (3.8 [0.11] vs. 3.4 [0.11], p = 0.166). After adjusting confounding factors (47 patients for each group), consistent results were obtained. No significant differences of self-reported clinical AEs were observed between SGLT2 inhibitors users and non-users. Multivariable regression analyses verified that the use of SGLT2 inhibitors was associated with increased levels of satisfaction. Conclusions: The use of SGLT2 inhibitors was associated with increased levels of satisfaction in T2DM patients, but not associated with overall clinical safety. Self-reported AEs were not related to the satisfaction with the use of anti-diabetic agents.

Efficacy and Safety of Ertugliflozin in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of ertugliflozin in patients with type 2 diabetes. Methods: MEDLINE, EMBASE, and Cochrane Library were searched (July 31, 2021) for phase II/III randomized clinical trials, which reported the efficacy and safety of ertugliflozin. Continuous variables were calculated as weighted mean difference (WMD) and associated 95% confidence intervals (CIs); dichotomous data were expressed as risk ratios (RRs) with 95% CIs. Results: Nine randomized clinical trials including 5638 type 2 diabetes patients were included. For efficacy, ertugliflozin significantly reduced HbA1c (%) (WMD -0.452%; 95% CI -0.774 to -0.129), fasting plasma glucose (FPG) (WMD -0.870 mmol/L; 95% CI -1.418 to -0.322), body weight (WMD -1.774 kg; 95% CI -2.601 to -0.946), and blood pressure levels (systolic blood pressure: WMD -2.572 mmHg; 95% CI -3.573 to -1.571 and diastolic blood pressure: WMD -1.152 mmHg; 95% CI -2.002 to -0.303) compared with placebo and other hypoglycaemic agents. Compared with placebo, ertugliflozin was superior in reducing HbA1c (%) (WMD -0.641%) and FPG (WMD -1.249 mmol/L). And compared with active agents, ertugliflozin also could decrease HbA1c by 0.215% and FPG by 0.266 mmol/L. The interactive effect between different controls was significant (P interaction of 0.039). For safety, similar to other sodium-glucose cotransporter type-2 inhibitors, ertugliflozin mainly increased the risk of genital mycotic infection (RR: 4.004; 95% CI 2.504-6.402). There was no significant difference in the incidence of any adverse events (AEs), AEs related to study drug, serious AEs, deaths, and discontinuations due to AEs. Results were consistent with the most primary outcomes in subgroups analysis and sensitivity analysis. Conclusion: Ertugliflozin was relatively effective and tolerated in patients with type 2 diabetes compared with placebo or other hypoglycaemic agents, except for a high risk of genital mycotic infection. Systematic Review Registration: (ClinicalTrials.gov), identifier (CRD42020206356).

Dapagliflozin Modulates the Fecal Microbiota in a Type 2 Diabetic Rat Model.

Background: The gut microbiota is recognized as a major modulator of metabolic disorders such as type 2 diabetes. Dapagliflozin, sodium glucose cotransporter 2 inhibitors (SGLT2i), enhances renal glucose excretion, and lowers blood glucose levels. The study aimed to determine the effects of dapagliflozin on fecal microbiota in a type 2 diabetic rat model. Methods: Four-week-old male Sprague Dawley rats (n = 24) were fed a high-fat diet (HFD) for 8 weeks and then given a single dose of STZ injection (30 mg/kg, i.p). They were randomly divided into three groups (n = 8). Each group received intragastric infusion of normal saline (2 ml, 0.9%) or metformin (215.15 mg/kg/day) or dapagliflozin (1 mg/kg/day) for 4 weeks. Blood glucose levels and plasma insulin levels were detected during intragastric glucose tolerance. Fecal samples were collected to access microbiome by 16S ribosomal RNA gene sequencing. Results: Dapagliflozin significantly decreased fasting and postprandial blood glucose levels as metformin in type 2 diabetic rats (P < 0.001). Enterotype was composed of Ruminococcaceae after treatment of dapagliflozin, whereas Ruminococcaceae and Muribaculaceae were the main enterotypes following metformin treatment. Dapagliflozin did not increase the abundance of beneficial bacteria including Lactobacillaceae and Bifidobacteriaceae. However, these were increased in the metformin group. It is surprising to find that Proteobacteria (especially Desulfovibrionaceae) were enriched in the dapagliflozin group. Conclusion: Dapagliflozin and metformin exerted complementary effects on the main beneficial bacteria. A combination of these two drugs might be beneficial to improve the structure of fecal microbiota in the treatment of type 2 diabetes.

Clinical Adverse Events of High-Dose vs Low-Dose Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes: A Meta-Analysis of 51 Randomized Clinical Trials.

AIMS: The aims of this work are to assess the clinical adverse events (AEs) of high-dose vs low-dose sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 2020, for identifying eligible randomized clinical trials (RCTs) that reported AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects models was used to obtain summary relative risks (RRs) with associated 95% CIs. Prespecified subgroup analyses according to individual SGLT2 inhibitors and follow-up duration, and leave-one-out sensitivity analysis were conducted. RESULTS: A total of 51 RCTs involving 24 371 patients (12 208 received high-dose and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the heterogeneity among included studies was relatively low (I2 < 50% for each outcome). No significant differences between high-dose and low-dose SGLT2 inhibitors were observed for overall safety (including any AEs, serious AEs, AEs leading to discontinuation, and death) and specified safety (including infections and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and nutrition), except for a mild increase in risk for AEs related to study drugs (RR: 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR: 1.17; 95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes. CONCLUSIONS: This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.

The Successful Rapid Adjustment of Blood Glucose in a Patient With Acute Coronary Syndrome, Renal Insufficiency, and Diabetes: A Case Report of Management Coordinated by Clinical Pharmacists and Clinicians.

Diabetes is a major cause of cardiovascular mortality in most countries. Intensive management of blood glucose is pivotal for alleviating disease progress and minimizing cardiovascular complications. In this study, we report a case of successful control of high blood glucose in a diabetes patient with acute coronary syndromes (ACS), hypertension, and renal insufficiency. This patient had five years of diabetes history and was hospitalized through an ACS emergency. Coronary angiography showed an acute anterior myocardial infarction (Killip Level I). The patient had extremely high blood glucose that ranged from 19.4 to 28.2 mmol/L on the first day in the hospital and experienced significant blood glucose fluctuations in the following three days. After two rounds of clinical pharmacist consultation, the patient's fasting blood glucose (FBG) target was achieved on the seventh day of his hospitalization and was well controlled afterward. The patient's postprandial blood glucose (PBG) target was achieved on the ninth day of hospitalization, and he was discharged when his blood glucose was well controlled and cardiac function had been fully assessed. Hence, we summarize a protocol that could be used to quickly adjust high blood glucose in hospitalized patients and report a new blood glucose management model coordinated by clinical pharmacists and clinicians.

Pleural Effusion Due to Use of Pioglitazone: A Case Report.

Background: Pioglitazone is an effective treatment option in clinical practice for managing type 2 diabetes mellitus. It is challenged by a lot of adverse effects, primarily body weight gain, peripheral edema, as well as congestive heart failure. Case Report: This is a case of a 76-year-old woman with no evidence of cardiac disease, who developed edema as well as bilateral pleural effusion after using pioglitazone. She got a weight decrease and complete resolution of the pleural effusion after stopping use of pioglitazone and rational use of diuretics. Conclusion: Common side effects of pioglitazone have been widely reported. However, little attention was drawn on pleural effusion in diabetic patients with no pre-existing heart dysfunction. In this case, we show the use of pioglitazone results in pleural effusion, with emphasis on the clinical recognition and management.

Insulin Autoimmune Syndrome After Exposure to Clopidogrel: A Case Report.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia that is characterized by hyperinsulinemia, hypoglycemia, and a high autoantibody titer. About 50% of patients with IAS have taken a medication containing sulfhydryl (-SH) groups. We present a case of IAS that developed after taking clopidogrel, a drug with an active metabolite that contains an SH-group. CASE REPORT: IAS was suspected in a 63-year-old Chinese man because of high concentrations of insulin and C-peptide during hypoglycemic episodes, and positivity for anti-insulin autoantibody (IAA). During his first episode of hypoglycemia, no trigger medication was identified and prednisone therapy was effective. However, imaging examination revealed a colonic carcinoma and the patient was discharged to undergo surgery. He had no episodes of hypoglycemia for 10 weeks after discontinuation of the prednisone, but then hypoglycemia recurred. A review of his medication revealed that he had taken a 10-day course of clopidogrel just before the recurrence. Therefore, a specialized multidisciplinary team consisting of endocrinologists, dieticians, and clinical pharmacists took charge of his management. Prednisone therapy was restarted and tapered off over 16 weeks. The patient also consumed small, frequent, low-carbohydrate meals and was instructed to avoid trigger medications. No further episodes of hypoglycemia were detected. His insulin and C-peptide concentrations and his anti-IAA index normalized during the follow-up period. CONCLUSION: SH-group-containing drugs might induce or exacerbate hypoglycemia in patients with a history of IAS. Furthermore, patients with IAS can benefit from multidisciplinary team management. We suggest herein an evaluation process for patients suspected of IAS.

Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.

Background: Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. Methods and Findings: We systematically searched MEDLINE, EMBASE, and Cochrane Library (5th Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, P < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, P < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, P < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, P < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, P < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, P < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, P < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, P < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, P < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, P < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, P < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, P < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, P < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Conclusion: Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.

Protocol for a systematic evaluation of pediatric pharmacy development and pediatric pharmacy experts' research area in China.

BACKGROUND: The pediatric pharmacy research status of children's hospitals in China is still unknown. Our previous findings suggest the regional differences in academic level in tertiary (grade III level A) children's hospitals in China. METHODS: This systemic evaluation described in this protocol will be conducted to follow the Cochrane Handbook. We will perform a systemic literature search of relevant databases including Chinese databases (CNKI, Wanfang Data, VIP Paper Check System) and English databases (Medline, EMbase, Cochrane Library) from inception to December 31, 2018. The search strategy will be enacted according to the guidance offered from the Cochrane Handbook. Two rounds of searches will be conducted to prevent the omission of relevant literature. A pre-set grading standard will be used to give calculation weight (W) to evaluate the quality of each article. Data synthesis will be performed using STATA software (version 13.1, Statacorp, College Station, Texas). Pediatric pharmacy development index (PPDI) of each hospital will be used to evaluate the pediatric pharmacy development in each tertiary children's hospitals. The cumulative calculation weight (∑W) and annual calculation weight (∑yearW) will be used to evaluate the academic level of pharmaceutical departments in different tertiary children's hospitals. Subgroup analysis will be performed to compare the number of different types of articles published between different hospitals base on different research areas such as policy research, basic research, and clinical research. RESULTS: In this article, we will evaluate pediatric pharmacy development and the research area of pediatric pharmacy experts in China. Based on the results from this research, we will analyze the professional backgrounds of pediatric pharmacy experts from 23 tertiary children's hospitals in China. According to the contents and research directions of literature published by the pediatric pharmacy experts in these 23 hospitals, we will determine the professional field of pediatric pharmacy experts and establish an expert database. In the process of formulating the related national or local policies in the future, the expert database will be selected accurately to reach the expert consensus. CONCLUSION: Our study will provide a comprehensive picture of pediatric pharmacy development in China. The pediatrics pharmacy expert's database constructed by this study will be used to build consensus on pediatric pharmacology in the future.

α4ß7 integrin inhibitors: a patent review.

INTRODUCTION: The α4ß7 integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for α4ß7 integrin. Areas covered: This article will highlight the progress that has been made in the discovery and development of α4ß7 integrin inhibitors, and their use in the treatment of inflammatory bowel diseases, multiple sclerosis, asthma, hepatic disorders, human immunodeficiency virus, allergic conjunctivitis and type 1 diabetes. Expert opinion: α4ß7 integrin inhibitors have attracted much interest for their clinical implication. Natalizumab and Vedolizumab are monoclonal antibodies (mAbs) successfully utilized clinically. Natalizumab is a mAbs of α4-subunit blocking both α4ß1 and α4ß7 integrin. Vedolizumab selectively targets the α4ß7 integrin. Several mAbs are still in the process of research and development. Among these mAbs, etrolizumab selectively against the ß7-subunit and AMG-181 specifically against the α4ß7 integrin are the most promising anti-α4ß7 integrin antibodies. Despite the unclear development stage of TR-14035 and R411, several low molecular compounds show bright future of further development, such as AJM300 and CDP323. In addition, results from laboratory data show that peptide inhibitors, such as peptide X, are effective α4ß7 integrin inhibitors.

Clinical adverse effects of sodium-glucose cotransporter 2 inhibitors: Protocol for a systematic review and meta-analysis.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral antidiabetic drugs, which mainly increase urinary glucose excretion through reducing renal glucose reabsorption. There is still a concern about the overall safety profile of SGLT2 inhibitors. In this systematic review and meta-analysis, we will assess the clinical adverse effects of SGLT2 inhibitors in type 2 diabetes mellitus. METHODS: This systemic review and meta-analysis described in this protocol will be conducted to follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We will search Medline, EMbase, the Cochrane library and the ClinicalTrials.gov Website from 1946 to June 2018. Studies will be screened by title, abstract, and full text independently in duplicate. Double-blinded, placebo-controlled, and randomized controlled trials reporting safety data of SGLT2 inhibitors will be eligible for inclusion. Outcomes will include adverse events (AEs) varying degrees and AEs occurring in ≥3% patients or AEs aroused concerns by the Food and Drug Administration (FDA). The assessment of risk bias and data synthesis will be performed using STATA software (version12, Statacorp, College Station, TX). Outcomes will be reported by risk ratios for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes and their 95% confidence intervals. Subgroup, sensitivity, regression analyses will be performed to evaluate intertrial heterogeneity and bias of the results. I statistic will be used to evaluate heterogeneity among studies. RESULTS: This systemic review and meta-analysis will evaluate AEs occurring in ≥3% patients or AEs aroused concerns by the FDA of SGLT2i as compared to placebo. CONCLUSION: Our study will provide a comprehensive picture of AEs of SGLT2 inhibitors.