Efficacy of Live Attenuated Dengue Vaccines: CYD-TDV; TDV (TAK-003) and TV003/TV005

Highlight:Differences in the efficacy of CYD-TDV versus the other TAK-003 and TV003/TV005 were discussed.One licensed dengue vaccine is CYD-TDV (Dengvaxia). Abstract:Dengue fever is the most common tropical disease, but there still remains no specific therapy that can overcome it. Special attention needs to be paid to this disease, because there were large increases in incidence in the last decade. As an effective preventive strategy, finding a new vaccine for dengue fever with higher potentiation and efficacy is highly necessary to stop dengue transmission especially in the endemic area. Vaccine triggers an immune response, so that it can create a robust immune response when infected. Nowadays, there is only one licensed dengue vaccine that is CYD-TDV (Dengvaxia). However, this vaccine still has many weaknesses, namely its dependency on the serostatus of the recipient. There are also other dengue vaccines that are in ongoing clinical testing and have promising results, TDV (TAK-003) and TV003/TV005. These three vaccines are live attenuated vaccines with various results. This review discussed differences in the efficacy of CYD-TDV against the other TAK-003 and TV003/TV005; considering the known and unknown various factors.

Abstract 103: A Meta Analysis of Antibiotic Envelope Use to Prevent Cardiac Implantable Electronic Device Infections

Introduction: Cardiac Implantable Electronic Device (CIED) infections are a major source of morbidity, mortality and increased healthcare cost. There are several well established risk factors associated with increased infection. An antibiotic coated envelope has been developed as an infection prevention intervention. Hypothesis: Whether antibiotic coated envelope is an effective preventive strategy against Cardiac Implantable Electronic Device Infections. Methods: 6 trials comparing use of antibiotic envelope to control, including 1 randomized trial and 5 cohort studies were selected using PubMed and Embase data bases through May 2019. The efficacy end point was prevention of CIED Infection. Outcomes were combined using random effects model and estimated by odds ratio with 95% confidence intervals (CI). Results: In our analysis of total 12,024 patients undergoing CIED implantation, 5,844 patients received antibiotic envelope while 6,180 patients were included in the control group. Antibiotic envelope was superior to control in reducing the risk of device infection (OR 0.40 CI [0.17-0.95], p=0.04). Conclusions: The use of antibiotic envelope in Cardiac Implantable Electronic Devices (CIED) is associated with reduced incidence of CIED infection.

Comparative effectiveness of pharmacologic and endoscopic interventions for prevention of post-ERCP pancreatitis: a network meta-analysis

Background and study aims While several interventions may decrease risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, it remains unclear whether one strategy is superior to others. The purpose of this study was to compare the effectiveness of pharmacologic and endoscopic interventions to prevent post-ERCP pancreatitis among high-risk patients. Methods A systematic review was performed to identify randomized controlled trials from PubMed, Embase, Web of Science, and Cochrane database through May 2017. Interventions included: rectal non-steroidal anti-inflammatory drugs (NSAIDs), aggressive hydration with lactated ringerʼs (LR) solution, and pancreatic stent placement compared to placebo. Only studies with patients at high-risk for post-ERCP pancreatitis were included. Bayesian network meta-analysis was performed and relative ranking of treatments was assessed using surface under the cumulative ranking (SUCRA) probabilities. Results We identified 29 trials, comprising 7,862 participants comparing four preventive strategies. On network meta-analysis, compared with placebo, rectal NSAIDs (B = – 0.69, 95 % CI [–1.18; – 0.21]), pancreatic stent (B = – 1.25, 95 % CI [–1.81 to –0.69]), LR (B = – 0.67, 95 % CI [–1.20 to –0.13]), and combination of LR plus rectal NSAIDs (B = – 1.58; 95 % CI [–3.0 to –0.17]), were all associated with a reduced risk of post-ERCP pancreatitis. Pancreatic stent placement had the highest SUCRA probability (0.81, 95 % CI [0.83 to 0.80]) of being ranked the best prophylactic treatment. Conclusions Based on this network meta-analysis, pancreatic stent placement appears to be the most effective preventive strategy for post-ERCP pancreatitis in high-risk patients.

Switching to a Healthy Diet Prevents the Detrimental Effects of Western Diet in a Colitis-Associated Colorectal Cancer Model

Inflammatory bowel disease increases the odds of developing colitis-associated cancer. We hypothesized that Western-style diet (WD) aggravates azoxymethane (AOM)/dextran sulfate sodium salt (DSS)-induced colitis-associated tumorigenesis and that switching to the standard AIN93G diet will ameliorate disease symptoms even after cancer initiation. Female BALB/c mice received either WD (WD group) or standard AIN93G diet (AIN group) for the whole experimental period. After five weeks, the mice received 12.5 mg/kg AOM intraperitoneally, followed by three DSS cycles. In one group of mice, the WD was switched to AIN93G the day before starting the first DSS cycle (WD/AIN group). Feeding the WD during the whole experimental period aggravated colitis symptoms, shortened the colon (p < 0.05), changed microbiota composition and increased tumor promotion. On molecular level, the WD reduced proliferation (p < 0.05) and increased expression of the vitamin D catabolizing enzyme Cyp24a1 (p < 0.001). The switch to the AIN93G diet ameliorated this effect, reflected by longer colons, fewer (p < 0.05) and smaller (p < 0.01) aberrant colonic crypt foci, comparable with the AIN group. Our results show that switching to a healthy diet, even after cancer initiation is able to revert the deleterious effect of the WD and could be an effective preventive strategy to reduce colitis symptoms and prevent tumorigenesis.

Epidural filling with crystal-colloid solution prevented accidental dural- puncture-induced headache after cesarean section

Background: Post dural puncture headache (PDPH) is a common anaesthetic complication caused by spinal puncture or accidental dural puncture during intraspinal anesthesia operation. There is no panacea, either preventive or therapeutic for PDPH. Methods: This study retrospectively collected and analyzed data on the clinical features and outcomes of 20 puerperants with accidental dural punctures. Seventeen individuals received crystal-colloid solution fillers and three did not. Results: The average epidural catheter retaining time was 35.97 hours; the average frequency of epidural filling was 2.65 times, with an average volume of 65.88 ml per fill. One patient developed tinnitus and three complained of head swelling during filling. The average bed-stay was 72.65 hours, with intravenous infusion volume of 2308.82 ml per day in the first three postoperative days. Two patients complained of slight dizziness and mitigation, and five felt weak. One individual had intermittent headaches and dizziness till the seventh postoperative day. Conclusions: Epidural injection of crystal-colloid solution combined with hydration is an effective preventive strategy for PDPH after cesarean section based on this observational study.

Contrast-Induced Acute Kidney Injury: Review and Practical Update

Contrast-induced acute kidney injury (CI-AKI) is an important consideration in patients undergoing cardiac catheterization. There has been a continuous strive to decrease morbidity and improve procedural safety. This review will address the pathophysiology, predictors, and clinical management of CI-AKI with a concise overview of the pathophysiology and a suggested association with left atrial appendage closure. Minimizing contrast administration and intravenous fluid hydration are the cornerstones of an effective preventive strategy. A few adjunctive pharmacotherapies hold promise, but there are no consensus recommendations on prophylactic therapies.

Defining Substrate Specificity in the CTX-M Family: the Role of Asp240 in Ceftazidime Hydrolysis

ABSTRACT The natural diversification of CTX-M β-lactamases led to the emergence of Asp240Gly variants in the clinic that confer reduced susceptibility to ceftazidime (CAZ). In this study, we compared the impact of this substitution on CAZ and ceftazidime-avibactam (CZA) MICs against isogenic Escherichia coli strains with different porin deficiencies. Our results show a noticeable increase in CAZ resistance in clones expressing Asp240Gly-harboring CTX-M when combined with OmpF porin deficiency. Kinetic analysis revealed that the kcat/Km for CAZ was 5- to 15-fold higher for all Asp240Gly variants but remained 200- to 725-fold lower than that for cefotaxime (CTX). In vitro selection of CAZ-resistant clones yielded nonsusceptible CTX-M producers (MIC of >16 μg/ml) only after overnight incubation; the addition of avibactam (AVI) decreased MICs to a susceptible range against these variants. In contrast, the use of CZA as a selective agent did not yield resistant clones. AVI inactivated both CTX-M-12 and CTX-M-96, with an apparent inhibition constant comparable to that of SHV-2 and 1,000-fold greater than that of PER-2 and CMY-2, and k2/K for CTX-M-12 was 24- and 35-fold higher than that for CTX-M-96 and CTX-M-15, respectively. Molecular modeling suggests that AVI interacts similarly with CTX-M-96 and CTX-M-15. We conclude that the impact of Asp240Gly in resistance may arise when other mechanisms are also present (i.e., OmpF deficiency). Additionally, CAZ selection could favor the emergence of CAZ-resistant subpopulations. These results define the role of Asp240 and the impact of the -Gly substitution and allow us to hypothesize that the use of CZA is an effective preventive strategy to delay the development of resistance in this family of extended-spectrum β-lactamases.

Impact of an influenza vaccine educational programme on healthcare personnel

SUMMARYInfluenza vaccination has been shown to be the most effective preventive strategy to reduce influenza-related morbidity and mortality in high-risk groups. Despite healthcare personnel (HCP) being considered part of such high-risk groups, their vaccination coverage is low in Europe. In January 2012, we distributed an 18-question survey regarding influenza vaccination to HCP at Gregorio Marañon Paediatric Hospital, in Madrid, Spain. After we documented that only ~30% of HCP were vaccinated an educational programme was implemented in October 2012 before the next influenza season. In January 2013, the same survey delivered again to all HCP documented a significant increase in vaccination rates (from 30% to 40%, P = 0·007) mainly among physicians and for patients' protection. In summary we found that a simple and inexpensive educational programme significantly improved the uptake of influenza vaccination in HCP in our centre. Nevertheless, vaccination rates remained low, and broader and updated campaigns are needed to overcome perception barriers.