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 ranged from 19.4 to 28.2 mmol/L on the first day in the hospital, and experienced significant blood glucosefluctuations 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.
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.
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.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.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.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.
Abstract 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).
Background The cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, only limited data and no comparisons have been published on their non-cardiovascular safety, which was the focus of our study. Methods and findings We systematically searched MEDLINE, EMBASE, and Cochrane Library (5th Sep 2018) for 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. 70 researches (83 studies enrolling 36958 patients in 78 publications) were identified. SGLT2 inhibitors was 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. Whereas, 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), 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.
Abstract 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.
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.
The α4β7 integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for α4β7 integrin. Areas covered: This article will highlight the progress that has been made in the discovery and development of α4β7 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: α4β7 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 α4β1 and α4β7 integrin. Vedolizumab selectively targets the α4β7 integrin. Several mAbs are still in the process of research and development. Among these mAbs, etrolizumab selectively against the β7-subunit and AMG-181 specifically against the α4β7 integrin are the most promising anti-α4β7 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 α4β7 integrin inhibitors.
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