Contextual effects in the occurrence of periodontal attachment loss and necrotizing gingival lesions among adolescents

The aim of this study was to assess and quantify the random effects resulting from clustering in the following individual-level periodontal outcomes: presence of clinical attachment loss of ≥ 1 mm (CAL1), presence of clinical attachment loss of ≥ 3 mm (CAL3), and presence of necrotizing ulcerative gingivitis (NUG); or in the following class-level periodontal outcomes: number of students with CAL1, number of students with CAL3, and number of students with NUG. Mixed-effects logistic regression analysis was used to model these outcomes among 9,162 adolescents in 310 classes in 98 schools spread over 20 communes in the Province of Santiago, Chile, who had been examined for clinical attachment level and NUG, and had completed questionnaires on oral health-related behaviors. The results of all six analyses demonstrated statistically significant random effects, which in all analyses were particularly related to the schools, whereas the class effects were smaller and the commune random effects were almost negligible. The random effects were quantified using the median odds ratio (MOR), and the class-level MOR ranged between 1.05 and 1.51, whereas the school-level MOR values ranged from 2.07 to 2.39. The results of the study demonstrate the potential of the application of multilevel modeling to periodontal epidemiologic data, over and beyond the conventional use of the technique to account for the intrinsic sites–teeth–subject hierarchy in periodontal data.     

Liability of Emergency Physicians for Studies Ordered in the Emergency Department: Court Cases and Legal Defenses

Background: Laboratory tests are frequently ordered in the Emergency Department (ED), with results returning at a later time. Emergency physicians (EPs) are frequently held liable when the test results are not followed-up. Methods: Recent legal malpractice cases are presented to provide examples of the medical-legal risks encountered when poor patient outcomes occur because the results of laboratory tests and other studies done in the ED are not followed-up and communicated to the patient. Discussion: Emergency physicians are obligated to follow-up with patients when the results of laboratory and radiographic studies ordered in the ED are returned at a later time, and EPs are liable for any poor outcome if there is no follow-up. Appropriate follow-up mechanisms must be in place to improve patient outcomes and reduce the risk for the physician. Knowledge of the legal concepts of contributory negligence and comparative fault allows EPs to place themselves in an optimal position for a legal defense if a challenge is raised. Conclusion: It is imperative that abnormal results of tests done for ED evaluation and orders must be properly noted and followed-up. Optimal communication and relay of information to both the patient and the primary physician will reduce physician liability and enhance patient outcomes.     

LEGEND,MYTH AND IDEA: ON THE FATE OF A GREAT PAPER

Isabel Menzies Lyth's seminal paper on social systems as a defence against anxiety is so well known and frequently cited that it risks acquiring mythic or legendary status. But what explains its phenomenal influence? In this contribution I suggest that it is a model example of the psychoanalytic case study, deriving its power from a deep engagement with organizational particularities as a basis for general theorizing. Its continued influence depends upon the way in which it is used to conceptualize new organizational experiences. An example from an institutional observation undertaken as part of an advanced social work training at the Tavistock illustrates this. Institutional observation is one of a range of non-clinical psychoanalytically informed methods of training at the Tavistock, and in the final part of the paper I discuss new applications of Menzies Lyth's work that aim to illuminate the irrational forces shaping modern social policy. Death and anxieties about death emerge as a subtext of the present paper, perhaps reflecting the fact that it was prepared as part of a memorial conference to Menzies Lyth herself, and also that the paper taught us to think better about death as an aspect of organizational experience.     

混合血小板凝胶促进新西兰兔创面愈合的实验研究

目的研究人源性混合血小板凝胶对新西兰兔创面愈合的影响。方法采用手工分离的人源性混合血小板为原材料,加入不同激活剂(含有1 000 U/ml、100 U/ml、0 U/ml凝血酶的10%葡萄糖酸钙溶液)制备PG,血小板与激活剂按体积10∶1混合。新西兰兔24只雌雄各半随机分为4组,6只/组,每只制备2个创面,创面采用不同的敷料外敷:对照组敷料为无菌纱布,另3组(实验组)敷料为不同浓度凝血酶的激活剂制备的PG纱布。在术后d5、10、15、20更换敷料并切取病理组织标本,HE染色观察。结果实验组与对照组在创面愈合率的差异上无统计学意义(P>0.05),但肉眼观察创面愈合质量有较明显差异。组织学观察显示,实验组成纤维细胞排列整齐,紧密有序,细胞增生较快,新生血管出现早且丰富,新生皮肤质量明显优于对照组。结论人源性混合血小板凝胶能促进新西兰兔创面愈合,有临床研究和应用价值。     

Comparative subcutaneous repeated toxicity study of enoxaparin products in rats

Enoxaparin is a low-molecular-weight heparin widely used for the prevention and treatment of thromboembolism. With the development of several enoxaparin biosimilars, real medical concerns about their safety and efficacy have been raised. This repeated dose toxicity study consists of preclinical toxicological evaluation of a biosimilar biological version of enoxaparin, the drug product “Enoxa”, compared to the enoxaparin reference drug product, “Lovenox”. Eighty white Wistar rats were treated with “Enoxa” versus the reference product, using subcutaneous therapeutic and toxic doses, varying from 3.5 to 100 mg/kg/day. Dose levels were adjusted and ultimately fixed at 3.5 and 20 mg/kg/day as therapeutic and toxic doses, respectively. A sodium chloride solution (0.9%) was used as the control, and the comparative study was conducted over periods of 14 and 28 days. Comparable effects were observed with few adverse effects at the administration dose of 20 mg/kg/day, for both enoxaparin biosimilar and reference products. Interestingly, mortality started only at high doses of 40 mg/kg/day and reached 25% at 100 mg/kg/day for both products. These results, as part of the recommended biosimilarity monitoring, demonstrated comparable toxicity profiles of “Enoxa” and “Lovenox” products in rats. Continuing investigation of biosimilarity on humans to confirm safety and efficacy is suggested.     

Non-clinical efficacy-related studies for human medicines: An overview and retrospective analysis of data for a group of approved medicines

The lack of efficacy is a major cause of medicine's development failure at the clinical phase, which may lead to question, among other aspects, the translation of the non-clinical data into humans. The objectives of the work here presented were (i) to get an overview (based on public assessment reports) of the nature of the non-clinical efficacy-related studies presented to the regulatory authorities at the marketing authorization application's stage for a group of approved anticancer human medicines (15 in total) and (ii) to conduct a retrospective analysis of such studies in terms of any identified insufficiencies and consistency with the current regulatory non-clinical guidelines. Each medicine has been tested in a number of in vitro assays and animal studies, which, all together, are judged to be capable of providing information on the activity of the active substance and demonstrating an anti-tumour effect, as well as to be generally consistent with the available, although limited detailed, guidance. In spite of this, some aspects were identified which could have a potential impact on the translation on non-clinical data into humans, namely, apparent insufficiencies in terms of animal model/human bridging data/knowledge and in vivo data on pharmacokinetics/pharmacodynamics relationships.     

Long-term stability study and evaluation of intact steroid conjugate ratios after the administration of endogenous steroids

The most frequently detected substances prohibited by the World Anti-Doping Agency (WADA) belong to the anabolic steroids class. The most challenging compounds among this class are the endogenous anabolic steroids, which are detected by quantitative measurement of testosterone (T) and its metabolites with a so-called “steroid profiling” method. The current steroid profile is based on the concentrations and ratios of the sum of free and glucuronidated steroids. Recently, our group developed a steroid profiling method for the detection of three free steroids and 14 intact steroid conjugates, including both the glucuronic acid conjugated and sulfated fraction. The study aimed at evaluating the long-term stability of steroid conjugate concentrations and ratios, and the influence of different endogenous steroids on this extended steroid profile. A single dose of oral T undecanoate (TU), topical T gel, topical dihydrotestosterone (DHT) gel, and oral dehydroepiandrosterone (DHEA) was administered to six healthy male volunteers. One additional volunteer with a homozygote deletion of the UGT2B17 gene (del/del genotype) received a single topical dose of T gel. An intramuscular dose of TU was administered to another volunteer. To avoid fluctuation of steroid concentrations caused by variations in urinary flow rates, steroid ratios were calculated and evaluated as possible biomarkers for the detection of endogenous steroid abuse with low doses. Overall, sulfates do not have substantial additional value in prolonging detection times for the investigated endogenous steroids and administration doses. The already monitored glucuronides were overall the best markers and were sufficient to detect the administered steroids.