重新审视婴幼儿心肺转流中改良超滤的使用

改良超滤(MUF)技术作为心肺转流中节约用血的重要手段之一,具有浓缩血液、清除炎性介质、减轻组织水肿等优点,但随着微小化体外循环技术的应用,MUF在临床应用中的获益性和必要性开始受到各中心的重新审视。本文对近年来MUF的临床使用进展予以综述。     

Cold-passaged isolates and bat-swine influenza a chimeric viruses as modified live-attenuated vaccines against influenza a viruses in pigs

Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.     

The case for a medication first approach to the treatment of opioid use disorder

Background: The opioid addiction and overdose crisis continues to ravage communities across the U.S. Maintenance pharmacotherapy using buprenorphine or methadone is the most effective intervention for Opioid Use Disorder (OUD), yet few have immediate and sustained access to these medications. Objectives: To address lack of medication access for people with OUD, the Missouri Department of Mental Health began implementing a Medication First (Med First) treatment approach in its publicly-funded system of comprehensive substance use disorder treatment programs. Methods: This Perspective describes the four principles of Med First, which are based on evidence-based guidelines. It draws conceptual comparisons between the Housing First approach to chronic homelessness and the Med First approach to pharmacotherapy for OUD, and compares state certification standards for substance use disorder (SUD) treatment (the traditional approach) to Med First guidelines for OUD treatment. Finally, the Perspective details how Med First principles have been practically implemented. Results: Med First principles emphasize timely access to maintenance pharmacotherapy without requiring psychosocial services or discontinuation for any reason other than harm to the client. Early results regarding medication utilization and treatment retention are promising. Feedback from providers has been largely favorable, though clinical- and system-level obstacles to effective OUD treatment remain. Conclusion: Like the Housing First model, Medication First is designed to decrease human suffering and activate the strengths and capacities of people in need. It draws on decades of research and facilitates partnerships between psychosocial and medical treatment providers to offer effective and life-saving care to persons with OUD.     

Advantages of an Anterior-Based Muscle-Sparing Approach in Transitioning From a Posterior Approach for Total Hip Arthroplasty: Minimizing the Learning Curve

BackgroundEnthusiasm for anterior-based approaches for total hip arthroplasty (THA) continues to increase but there is concern for increased complications during the learning curve period associated. This study aimed to investigate if there was a difference in perioperative variables, intraoperative and immediate postoperative complications, or patient-reported outcomes when transitioning from a mini-posterior approach (mPA) to an anterior-based muscle-sparing (ABMS) approach for THA.MethodsRetrospective cohort study on the first 100 primary THA cases (n = 96 patients) of the senior author (August 2016 to August 2017) using the ABMS approach. These cases were compared to primary THA cases done the year prior (July 2015 to July 2016, n = 91 cases in 89 patients) using an mPA. Data were extracted and analyzed via gamma regression with robust standard errors and using generalized estimating equation regression.ResultsWe found no difference in the estimated blood loss (P = .452) and surgical time (P = .564) between the cohorts. The ABMS cases had a slightly shorter length of stay (P = .001) with an adjusted mean length of stay of 1.53 days (95% confidence interval 1.4-1.6) compared to 1.85 days (95% confidence interval 1.8-1.9) in the mPA cases. There was no difference in the frequency of immediate postoperative complications (all, P > .05). There was no difference in the adjusted mean change in patient-reported outcomes (all P > .05). In the ABMS group, there was no difference in surgical time or physical function computerized adaptive test between the first 20 cases (reference) and each subsequent group of 20 cases (all P > .05).ConclusionThis study demonstrates no associated learning curve for an experienced senior surgeon when switching routine THA approach from mPA to ABMS. We advise careful interpretation of our results, as they may not apply to all surgeons and practices.Level of EvidenceLevel III Therapeutic Study: retrospective comparative study.     

美国胃肠病协会关于急性胰腺炎胰腺坏死处理临床实践专家共识更新解读

美国胃肠病协会（AGA）于2019年8月在Gastroenterology（《胃肠病学》）杂志上发表了针对胰腺坏死处理的临床实践专家共识的更新，归纳并总结了当前的临床证据与专家意见，旨在为胰腺坏死这一复杂临床情况的最佳干预提供指导建议。近年来，随着临床实践的不断深入，急性胰腺炎胰腺坏死的处理经历了较大的变革。从一开始的以手术为主的清创策略过渡到现阶段较为成熟的升阶梯治疗模式。针对胰腺坏死的治疗主要包含两个方面：非手术治疗和有创干预。其中，非手术治疗主要包括抗菌治疗和营养支持等。一旦坏死组织发生感染或无菌性坏死使病人产生显著临床症状，提示有强烈干预指征时，此时更多地依赖于有创干预。升阶梯治疗模式的主要内容为：以经皮引流或透壁内镜引流为首要手段，对于引流无法处理的大量固体坏死，可进行经皮微创或经内镜下坏死清除，若微创手段干预无效可进行开放手术清创。关于选择经皮微创阶梯治疗还是经内镜阶梯治疗，目前尚无研究显示两者之间对病死率等主要临床结局产生影响，不同治疗中心可根据各中心的专业特长和医疗资源，合理选择治疗方案。     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

How current risk assessment and risk management methods for drinking water in The Netherlands cover the WHO water safety plan approach

In the Netherlands, safe and sufficient drinking water is provided to the general population by ten drinking water companies. To guarantee safe drinking water the World Health Organization (WHO) developed a Water Safety Plan (WSP), a Risk Assessment and a Risk Management (RA/RM) framework. The objective of the study was to identify legally required RA approaches, to document application of RA/RM activities at Dutch drinking water companies and to determine to what extent these RA/RM activities as a whole cover all the elements of the WHO WSP approach. This study could be of interest to both managers of large water utilities and decision makers.The assessment was performed by means of a policy review and interviews with two to four staff members involved in RA/RM from all ten Dutch drinking water companies combined with a joint workshop. The drinking water companies are well aware of the potential hazards and risks that can influence the drinking water quality. To guarantee the supply of safe and sufficient drinking water, the Dutch drinking water sector uses six different legally required RA/RM approaches. This study shows that by using the six legally required RA/RM approaches, all WSP steps are covered. WSP entails a generic risk assessment for identifying all hazards and hazardous events from source to tap, whereas the six legally required RA/RM each focus on specific risks at an advanced level. Each risk assessment provides information on specific hazards and hazardous events covering a part of the water supply chain. These legal requirements are complemented with additional RA/RM activities at sector and water company level such as codes of practices and standard operating procedures. The outcomes of all RA/RM approaches combined provide information from source to tap. When using multiple RA/RM approaches, it is crucial to share and combine information derived from the different activities.