Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III,randomized, observer-blind,multicenter, parallel-group study

BackgroundBroad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1 year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013.MethodsWe compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM₁₉₇) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria–tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM₁₉₇ or PRP-T vaccines. The primary endpoint was the “long-term seroprotection rate”, defined as the group proportion with anti-PRP antibody titers ⩾1.0 μg/mL, after the primary series.ResultsLong-term seroprotection rates were 99.3% in the PRP-CRM₁₉₇ group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM₁₉₇ group – PRP-T group) was 3.7% (95% confidence interval: 0.099–7.336), demonstrating that PRP-CRM₁₉₇ vaccine was non-inferior to PRP-T vaccine (p < 0.0001). Furthermore, the “short-term seroprotection rate” (anti-PRP antibody titer ⩾0.15 μg/mL) before booster vaccination was higher in the PRP-CRM₁₉₇ group than in PRP-T. Concomitant administration of PRP-CRM₁₉₇ vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM₁₉₇ vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles.ConclusionThe immunogenicity of PRP-CRM₁₉₇ vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1 year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.Clinical trial registry: Registered on ClinicalTrials.gov: NCT01379846     

Using stories to battle unintentional injuries: Narratives in safety and health communication

After 14 years of rising death rates due to unintentional injuries in the U.S., it is time to ask how safety messages can be redesigned to have a greater impact on risky behavior. To this end, many researchers have called for a new, narrative approach to prevention messages—based on persuasive stories about people who have suffered injuries and illnesses in the past. Still, there is scant evidence that story-based communications are more effective than equivalent non-narrative messages at changing actual (rather than self-reported) safety and health behavior. Our research examined the impact of injury stories on actual safety behavior in a controlled experimental setting at a US university. Teams of participants assembled a product (a child's swing) using written instructions. The instructions contained safety messages targeting assembly mistakes that have been linked to serious injuries in children who play on swings. Participant teams were randomly assigned to three conditions: assembly instructions containing story-based safety messages, instructions with concrete (but non-anecdotal) safety messages, and instructions with traditional abstract safety messages. After adjustment for covariates, story-based messages resulted in a 19 percent improvement in safety behavior, compared with non-narrative communications. Importantly, injury stories did not create undue fear of the message object, demonstrating that brief anecdotes about accident victims can convince people to take reasonable precautions without creating unwarranted alarm about risks.     

Guidelines and recommendations for MR imaging safety and patient management III. Questionnaire for screening patients before MR procedures

The authors present the third installment of the guidelines and recommendations from the Safety Committee of the Society for Magnetic Resonance Imaging (now the Society of Magnetic Resonance) concerning various issues related to the safety and management of patients undergoing magnetic resonance (MR) procedures. This document was developed to provide standardized and consistent information for use by health practitioners involved in screening patients or other individuals for MR procedures.     

Ex vivo evaluation of ferromagnetism,heating, and artifacts produced by heart valve prostheses exposed to a 1.5-T MR system

Ex vivo testing techniques were used to determine the ferromagnetic qualities of, presence of heating in, and artifacts produced by 13 different heart valve prostheses exposed to a 1.5-T (64-MHz) magnetic resonance (MR) system. None of the heart valve prostheses showed a measurable deflection in the 1.5-T static magnetic field. Only minimal artifacts were produced during MR imaging with a fast spoiled GRASS (gradient-recalled acquisition in the steady state) pulse sequence. The largest temperature changes measured during a “worst case” MR imaging sequence (estimated average specific absorption rate, 2.5 W/kg; estimated spatial peak specific absorption rate, 7.6 W/kg) were +0.2°C with the implant imaged “in air” and +0.3°C with the implant imaged in normal saline. Therefore, MR procedures performed with a 1.5-T (64-MHz) MR system may be performed safely in patients with any of the 13 different heart valve prostheses evaluated in this study.     

Peripheral nerve stimulation during MRI: Effects of high gradient amplitudes and switching rates

The application of high gradient amplitudes and switching rates for MRI and spectroscopy, resulting in short rise times for the gradient field and high changes of the magnetic flux density in the patient, is known to possibly evoke peripheral nerve stimulation (PNS) in patients. These effects have been studied on 20 volunteers under different experimental circumstances. The results of these measurements are partially in line with earlier findings reported in the literature. New information is found for the dependence of the PNS threshold level as a function of the rise time of the gradient waveform. The PNS threshold level, expressed in terms of dB/dt, is found to be proportional with t^?05, where t is the switch time for the gradients. Indications are found that |B|, the modulus of the gradient vector field, is more closely related to the PNS threshold level than B_z, the imaging component of the gradient field. From the experiments, it is furthermore concluded that only for the imaging protocols characterized by the application of long bipolar repetitive gradient pulse trains, such as echo-planar imaging, PNS is expected at the reported threshold levels. For the protocols based on spin echo, turbo spin echo, inversion recovery, fast field echo, etc., characterized by shorter gradient pulse trains, the threshold levels are expected to be much higher.     

外用他克莫司和吡美莫司的安全性

他克莫司和吡美莫司是新型钙调磷酸酶抑制剂药物,其外用制剂可用于治疗特应性皮炎。近年来,对这两种药物的安全性存有争议。现有的资料表明,外用他克莫司和吡美莫司安全性高,不引起皮肤萎缩,经皮吸收极少,无明显的系统免疫抑制作用,不会引起皮肤或系统的感染和肿瘤的发病率升高。     

Safety evaluation of surgical materials by cytotoxicity testing

The cytotoxicity of three kinds of commercially available absorbable hemostats [oxidized cellulose (Surgicel, gauze and cotton types), microfibrillar collagen (Avitene), and cotton-type collagen (Integran)] and one adhesion barrier [sodium hyaluronate and carboxymethyl-cellulose membrane (Seprafilm)] were comparatively assessed by a colony assay using V79 cells and a minimum essential medium (MEM) elution assay in combination with a neutral red assay using L929 cells. Strong cytotoxicity was detected for Surgicel by both the MEM elution assay and the colony assay. For Avitene, both methods revealed weak cytotoxicity. For Seprafilm, no cytotoxicity was detected by the MEM elution assay, while a moderate degree of cytotoxicity was observed in the colony assay. For Integran cytotoxicity was not detected by either the MEM elution or the colony assay. The results of the different methods showed some inconsistency in terms of the degree of cytotoxicity of the materials. It is proposed that the combination of two or more sensitive cytotoxicity testing methods for the evaluation of biomaterials is necessary to avoid false-negative results for biomaterials at the preclinical stage. Furthermore, investigation of the correlation between the cytotoxicity and the extraction period of the surgical materials is helpful for predicting the effect of prolonged in vivo use of biomaterials on surrounding cells, tissues, and organs.     

上海社区老年人用药安全及影响因素分析

目的：了解上海社区老年人群的用药安全情况及其影响因素，方法：以整群抽样的方法抽取上海市黄浦区两个居民委员会2985名60岁以上的居民进行问卷调查，了解其疾病和用药情况，用药反应，对安全用药的知识，态度，行为，以及影响其用药行为的因素，结果：被调查中高血压、冠心病、消化系统疾病和呼吸系统疾病的患病率分别为35．93％、10．67％、5．70％和3．71％。抗高血压药，心脑血管病药，消化系统疾病和呼吸系统疾病的患病率分别为35．93％、10．67％、5．70％和3．71％，抗高血压药、心脑血管病药，消化系统药和抗生素的使用率分别为31．72％、16．20％、2．43％和2．11％，过去30天内，51．33％的被调查用过药物，用药不良反应发生率为2．06％，对用药安全的正确知识，态度，行为率分别为71．62％、69．39％及60．67％，影响药物选择的因素中医生占88．19％，结论：老年人的用药安全仍存在问题，有待改进，医生是影响老年人药选择的最主要因素。     

Application of Animal Toxicology Data to Clinical Study of Experimental Drugs

The pharmaceutical industry performs safety studies in animals to underwrite administration of new chemical entities to man. Early clinical evaluation of drugs in volunteers is performed, generally, using highdose acute studies in rodents and 1-month repeat dose studies in one rodent species and one non-rodent species as a basis for risk assessment. Results from the 1-month toxicology studies enable a ceiling for initial clinical doses to be set and give some indication of the major target organs for toxicity. Extrapolation of these results to man helps determine the preliminary safety endpoints, including clinical chemistry parameters, for use in early clinical studies in man.Originally presented at ECCP 93.