Roles of Community Pharmacists in Screening and Disseminating of Information about Non-Steroidal Anti-Inflammatory Drugs Risks: Implications for Drug Safety Assessment

Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.

Systematic review and meta-analysis on the prophylactic role of non-steroidal anti-inflammatory drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis

AIM: To critically appraise the published randomized, controlled trials on the prophylactic effectiveness of the non-steroidal anti-inflammatory drugs(NSAIDs), in reducing the risk of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis. METHODS: A systematic literature search(MEDLINE, Embase and the Cochrane Library, from inception of the databases until May 2015) was conducted to identify randomized, clinical trials investigating the role of NSAIDs in reducing the risk of post-ERCP pancreatitis. Random effects model of the meta-analysis was carried out, and results were presented as odds ratios(OR) with corresponding 95%CI.RESULTS: Thirteen randomized controlled trials on 3378 patients were included in the final meta-analysis. There were 1718 patients in the NSAIDs group and 1660 patients in non-NSAIDs group undergoing ERCP. The use of NSAIDs(through rectal route or intramuscular route) was associated with the reduced risk of post-ERCP pancreatitis [OR, 0.52(0.38-0.72), P = 0.0001]. The use of pre-procedure NSAIDs was effective in reducing approximately 48% incidence of post-ERCP pancreatitis, number needed to treat were 16 with absolute risk reduction of 0.05. But the risk of post-ERCP pancreattis was reduced by 55% if NSAIDs were administered after procedure. Similarly, diclofenac was more effective(55%) prophylactic agent compared to indomethacin(41%).CONCLUSION: NSAIDs seem to have clinically proven advantage of reducing the risk of post-ERCP pancreatitis.

Italian survey on non-steroidal anti-inflammatory drugsand gastrointestinal bleeding in children

AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in

Impact of discontinuing non-steroidal antiinflammatory drugs on long-term recurrence in colonic diverticular bleeding

AIM: To determine the effect of discontinuing nonsteroidal antiinflammatory drugs(NSAIDs) on recurrence in long-term follow-up patients with colonic diverticular bleeding(CDB).METHODS: A cohort of 132 patients hospitalized for CDB examined by colonoscopy was prospectively enrolled. Comorbidities, lifestyle, and medications(NSAIDs, low-dose aspirin, antiplatelet agents, anticoagulants, acetaminophen, and corticosteroids) were assessed. After discharge, patients were requested to visit the hospital on scheduled days during the followup period. The Kaplan-Meier method was used to estimate recurrence.RESULTS: Median follow-up was 15 mo. The probability of recurrence at 1, 6, 12, and 24 mo was 3.1%, 19%, 27%, and 38%, respectively. Of the 41 NSAID users on admission, 26(63%) discontinued NSAID use at discharge. Many of the patients who could discontinue NSAIDs were intermittent users, and could be switched to alternative therapies, such as acetaminophen or an antiinflammatory analgesic plaster. The probability of recurrence at 12 mo was 9.4% in discontinuing NSAID users compared with 77% in continuing users(P < 0.01, log-rank test). The hazard ratio for recurrence in the discontinuing NSAIDs users was 0.06 after adjusting for age > 70 years, right-sided diverticula, history of hypertension, and hemodialysis. No patients developed cerebrocardiovascular events during follow-up.CONCLUSION: There is a substantial recurrence rate after discharge among patients hospitalized for diverticular bleeding. Discontinuation of NSAIDs is an effective preventive measure against recurrence. This study provides new information on risk reduction strategies for diverticular bleeding.

Non-steroidal anti-inflammatory drugs:What is the actual risk of liver damage?

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.

Impact of topical nonsteroidal anti-inflammatory drugs in prevention of macular edema following cataract surgery in diabetic patients

AIM： To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs（NSAIDs） on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs（ketorolac tromethamine 0.4% and nepafenac 0.1%）. METHODS： Group 1（control） received artificial tears substitute as a placebo group, group 2（nepafenac） received topical nepafenac 0.1%, and group 3（ketorolac） received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months＇ intervals for evaluating cystoid macular edema（CME） development. The main study outcomes were achieving the best corrected visual acuity（BCVA） and change in the central macular thickness（CMT） measured with optical coherence topography（OCT）.RESULTS： Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups（P=0.04）. There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month（P=0.008, 0.027, 0.004）. There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. CONCLUSION： Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.

Maligned non-steroidal anti-inflammatory drugs:Misunderstanding of their safety profile in patients with renal insufficiency

Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.

The Pattern of Eosinophil Count among Nigerians with Frequent Use of the Commonly Available Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-related. Inflammation could be the link between NSAIDs use and eosinophilia. Aims: To compare the pattern of eosinophil count in the peripheral blood of frequent users of NSAIDs and healthy controls. Methodology: Two hundred (one hundred frequent users of NSAIDs and 100 healthy controls) participants who had no known risk factor for kidney disease and had given informed consent were recruited. Blood was taken to determine the white cell count and differentials, serum electrolyte and creatinine, and random blood sugar. Results: The mean age of NSAIDs users was not significantly different from controls, P = 0.3. The mean eosinophil count was higher in males than females. The incidence of eosinophilia in NSAIDs users was 4%. The mean Eosinophil count of NSAIDs users was insignificantly higher than controls, 164.3 ± 51 6 vs 135. 6 ± 53.4, P = 0.4. The mean platelet count of NSAIDs users was significantly higher compared to controls, P = 0.04. The mean hematocrit of NSAIDs users was significantly lower than the controls, P = 0.02. Propionic acid derivatives were associated with the highest eosinophil count. Eosinophil count was positively related to age and serum creatinine and inversely related to blood glucose, hematocrit and glomerular filtration rate. Conclusion: The incidence of eosinophilia was 4%. The eosinophil count was higher in frequent NSAIDs users than occasional and non-users, in males than females and with use propionic acid derivatives compared to other NSAIDs. The Eosinophil count was positively related to age and platelet count. Being commoner in inflammatory states, the tissue destruction associated with elevated EC can be avoided by the prevention and prompt treatment of inflammatory conditions.

Induction of Tolerance to Non Steroidal Anti Inflammatory Drugs Might Be an Alternative Therapeutic in the Painful Crisis of Sickle Cell Disease

Background and Aims: In Ivoirian’s school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may be accompanied by intolerance reactions. When these occur, no codified alternative therapeutic seems to be used to our knowledge. Authors aimed to evaluate the induction of tolerance to NSAIDs as an effective alternative therapeutic. Methods: 22 patients (15 men and 7 women aged from 12 to 39 years with mean age: 22.41 ± 7.88) suffering from vaso-occlusive painful crisis were enrolled. They were known to have a history of sickle cell disease and at least one episode of adverse reactions following the Ibuprofen or Diclofenac intake. A rapid protocol of oral challenge was used in patients to induce tolerance to NSAIDs. The first day, initial doses (8.82 mg for Ibuprofen and 2.20 mg for Diclofenac) were given and gradually increased at intervals of 1 hour over a total period of 6 hours. On the second and third days, the therapeutic dose has been orally administrated with an interval of 6 hours over a period of 12 hours. Results: Despite of some cases of failure that might be related to the severity of symptoms or possible patho-physiological mechanism, more than 80% of patients have successfully tolerated Diclofenac and Ibuprofen. Conclusion: This experience appears to be the first in our context. It might be used as a solution in the lack of alternative therapeutic in the management of vaso-occlusive painful crisis of sickle cell disease as well as in other diseases such as HIV infection where patients often develop intolerance to none alternative antibiotics.

Non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.

Tolerance effects of non-steroidal anti-inflammatory drugs microinjected into central amygdala,periaqueductal grey,and nucleus raphe Possible cellular mechanism

Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs （NSAIDs）, or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic （intraperitoneal） administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.

Doping Control Analysis of 16 Non-Steroidal Anti-Inflammatory Drugs in Equine Plasma Using Liquid Chromatography-Tandem Mass Spectrometry

Non-steroidal anti-inflammatory drugs (NSAIDs) are classified as Class 4 agents by the Association of Racing Commissioners International and are banned in racehorses during competition in Pennsylvania (PA). To control the abuse of these agents in racehorses competing in PA, a forensic method for screening and confirmation of the presence of these agents is needed. Equine plasma (0.5 mL) was acidified with 75 μL 1M H3PO4 to increase recovery of the analytes by liquid-liquid extraction using methyl tert-butyl ether (MTBE). Extracted analytes were separated by reversed-phase liquid chromatography using a C8 column under gradient condition. All 16 analytes were detected, quantified and confirmed using a triple quadrupole tandem mass spectrometry with selected reaction monitoring (SRM) in both negative and positive electrospray ionization modes. The limit of detection, quantification and confirmation of the analytes were 1.0 - 5.0 ng/mL, 1.0 - 5.0 ng/mL and 1.0 - 20 ng/mL, respectively. The linear dynamic range of quantification was 5.0 - 200 ng/mL. The method is routinely used in anti-doping analysis to control the abuse of NSAIDs in racehorses competing in PA.

Do Antineoplastic Drugs Play an Additional Role in the Progression of Non-Compaction Cardiomyopathy? A Case Report

Non-compaction cardiomyopathy is a rare form of cardiomyopathy;its most common clinical manifestations are heart failure (HF), ventricular arrhythmia, thromboembolism, and sudden cardiac death. We report a rare case of a 63-year-old man with chest tightness, worsening lower leg edema, dyspnea, and decreased exercise tolerance. He had a medical history of gastric cancer treated with subtotal gastrectomy and post-operative chemotherapy with paclitaxel and fluorouracil three years ago. At that time, he was diagnosed with non-compaction cardiomyopathy, and the thickened and reticulated trabecular muscle was exclusively confined to left ventricular apex. Five months ago, he was admitted to our hospital with heart failure and treated for dilated cardiomyopathy, echocardiography revealed severe trabecular noncompact myocardium in both ventricles, which was confirmed by cardiac magnetic resonance imaging (CMR). It is generally accepted that non-compacted myocardium forms in the early embryonic stage, which raises a question in our case whether acquired factors, such as antineoplastic drugs, potentially accelerate the pathological progression of non-compaction cardiomyopathy. Considering there are disparities between current screening tools such as echocardiography and CMR regarding diagnostic criteria, multi-detector CT may be an alternative examination method that could provide a new perspective for diagnosis.

Appearance of attenuated intestinal polyposis during chronic non-steroidal anti-inflammatory drugs use

Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.

Kidney Function in Frequent Users of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are used for managing painful conditions. They are available as cheap, over-the-counter drugs, and commonly abused. NSAIDs inhibit prostaglandins (PGs) actions on the kidneys and can cause kidney disease and hypertension, especially when used in excess doses, for prolonged period or in stressed states. Methods: The descriptive study was carried at the Orthopaedic and Family Medicine units of the Federal Medical Centre, Abeokuta. Two hundred respondents participated in the study. One hundred frequent users of NSAIDs (with daily use for ≥ 4 weeks) and age and sex-matched controls with no known risk for kidney disease and had consented were consecutively recruited. Data were entered from history, examination and investigations (urinalysis, serum electrolyte, kidney scan and biopsy). Cases with estimated glomerular filtration rate (eGFR) 2) and dip strip proteinuria ≥ 1+ had kidney biopsy. Statistical analysis was with SPSS 21 software. Student t-test and Chi-square tests were used to compare means and proportions respectively. Pearson’s correlation test was used to determine the strength of association between independent risk factors and kidney dysfunction (KD). Results: Two hundred respondents participated in the study. Fifty one (51) females and Forty nine (49) males were recruited as cases and controls respectively. Thirteen (13) females had KD compared to 9 males, (P = 0.02). The mean age of cases with KD (63.04 yrs ± 4.21) was statistically higher than those without KD (P = 0.01). Majority of the cases were in the working population (30 - 59 yrs). Twenty two (22) frequent NSAIDs users had kidney dysfunction (KD) while six (6%) controls had KD. The proportion of subjects that used herbal medicines was higher in cases with KD than in cases without KD as well as in the controls respectively (P = 0.01). The mean kidney length and cortical thickness were significantly lower in cases with KD than in cases without KD, (P = 0.03) and (P = 0.017) respectively. The independent predictors of KD were increasing age, use of herbal remedies and duration of drug use. Conclusion: The prevalence of KD among frequent NSAIDs users was 22%, higher than controls. Risk factors identified include increasing age, use of herbal medicines, increasing body mass index (BMI), systolic blood pressure (SBP), anaemia, reduced cortical thickness and kidney volume. NSAIDs use in excess doses, prolonged period or in stressed state increases the risk for kidney dysfunction, caution is therefore needed to avoid taking these drugs in these conditions.

Non-coding RNA in drug resistance of gastric cancer

Gastric cancer(GC)is the third leading cause of cancer-related mortality worldwide.The poorly prognosis and survival of GC are due to diagnose in an advanced,non-curable stage and with a limited response to chemotherapy.The acquisition of drug resistance accounts for the majority of therapy failure of chemotherapy in GC patients.Although the mechanisms of anticancer drug resistance have been broadly studied,the regulation of these mechanisms has not been completely understood.Accumulating evidence has recently highlighted the role of non-coding RNAs(ncRNAs),including long non-coding RNAs and microRNAs,in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of GC.We review the literature on ncRNAs in drug resistance of GC.This review summarizes the current knowledge about the ncRNAs’characteristics,their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant GC.

Comparison of extended spectrum β-lactamasesproducing Escherichia coli with non-ESBLsproducing E.coli:drug-resistance and virulence

The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （ESBLs）-producing E.coli and non-ESBLs-producing E.cofi to provide a reference for physicians in management of hospital infection. From October 2010 to August 2011,96 drug-resistant strains of E. coli isolated were collected from the specimens in Qingdao Municipal Hospital, Qingdao, China. These bacteria strains were divided into a ESBLs-producing group and a non-ESBLs-producing group. Drug sensitivity tests were performed using the Kirby-Bauer （K-B） method. Disinfectant gene, qacEAl-sull and 8 virulence genes （CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1） were tested by polymerase chain reaction （PCR）. Among the 96 E.coli isolates, the ESBLs-producing E.coli comprised 46 （47.9%） strains and the non-ESBLs-producing E.cofi consisted of 50 （52.1%） strains. The detection rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA,VT1, est, bfpA, elt, and CNF1 in 46 ESBLs-producing E.coli isolates were 89.1%, 76.1%, 6.5%, 69.6%, 69.6%, 89.1%, 10.9%, 26.1%, 8.7%, and 19.6%, respectively. In the non-ESBLs-producing E.cofi strains, the positive rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1 were 62.0%, 80.0%, 16.0%, 28.0%, 64.0%, 38.0%, 6.0%, 34.0%, 10.0%, and 24.0%, respectively. The difference in the detection rates of multiple drug-resistant strain, hlyA and VT1 between the ESBLs-producing E.cofi strains and the non-ESBLs-producing E.cofi strains was statistically significant （P〈0.05）. The positive rate of multiple drug-resistant strains is higher in the ESBLs-producing strains than in the non-ESBLs-producing strains. The expression of some virulence genes hlyA and VT1 varies between the ESBLs-producing strains and the non-ESBLs-producing strains. Increased awareness of clinicians and enhanced testing by laboratories are required to reduce treatment failures and prevent the spread of multiple drug-resistant strains.

Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China

Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria（NTM） isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. Methods Four macrolides, including clarithromycin（CLAR）, azithromycin（AZM）, roxithromycin（ROX）, and erythromycin（ERY）, were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23 S r RNA and erm, were analyzed with nucleotide sequence analysis. Results Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191 A and T2221 C on rrl were specific for the M. abscessus complex（MABC）. Seven sites, G2140 A, G2210 C, C2217 G, T2238 C, T2322 C, T2404 C, and A2406 G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192 G, T2358 G, and A2636 G, were observed only in M. fortuitum and one site G2152 A was specific for M. gordonae. The genes erm（39） and erm（41） were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. Conclusion The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23 S r RNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.

Type 2 Diabetes Mellitus in Children and Adolescents: Early Prevention and Non-Drug Therapy

The global rate of type 2 diabetes mellitus (T2DM) in youth has increased dramatically in the last 30 years. This increase mirrors the global epidemic of childhood obesity. Studies show that, compared to adults who develop T2DM, youth with T2DM ultimately suffer from more harmful symptoms. The prevalence of T2DM and obesity in youth signals a significant public health issue that financially burdens governments, families, and individuals. Since evidence suggests that T2DM in youth is different from both type 1 and type 2 diabetes in adults, researchers and clinicians face many difficulties in developing new treatments. Most treatment efforts have relied on drugs;however, recent studies suggest that non-drug therapy also effectively reduces obesity and diabetic symptoms. Healthier eating, increased physical exercise, and positive mental health, are often underappreciated factors towards managing obesity. Yet these lifestyle changes empower both young and older patients to independently fight diseases and attain better health. To manage the global health risk of obesity, further research addressing the prevention and nondrug early intervention of T2DM and obesity in youth is urgently needed. The present review focuses on the latest updates in the field.

UPLC-QTOF/MS Method for Screening and Determination of 59 Non-labeled Components in Veterinary Drug Preparations

[Objectives]This study was conducted to provide an accurate and reliable method for rapid high-throughput screening of veterinary drug preparations.[Methods]For the matrixes of veterinary drug preparations,high-performance liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was used to establish a fast screening method for 59 non-standard components in five categories of antiviral agents,aminoglycosides,quinolones,sulfonamides,and tetracyclines in veterinary drugs.The target drugs were separated by a Waters ACQUITY UPLC HSS T3 chromatographic column(50 mm×2.1 mm,1.8μm),and data were collected in the positive ion mode.Good separation of the 59 drugs was achieved within 7 min.[Results]In the concentration range of 0-100 ng/ml,each drug showed a good linear relationship,and the correlation coefficients were all greater than 0.999.The detection limits of the 59 drugs were in the range of 0.1-0.5 mg/ml,and the recovery under the addition concentration of 5 mg/ml was in the range of 85.2%-103.8%.[Conclusions]The method is fast,simple,accurate,and highly sensitive,and is suitable for high-throughput screening and qualitative identification of non-standard components in veterinary drug preparations.