临床药学实习模式设计与实践

目的:探索临床药学专业毕业生临床实践实习创新模式.方法:比较目前国内实习培养模式.结果:提出了可行性的临床药学专业实习生临床实践部分的培养模式.新培养模式是通过革新传统模式,培训与实践相结合的方法,引导实习生快速掌握临床实践基本技能,具有提出、分析、解决临床问题的能力.以新的评价与考核制度,激励教学相长,实现培养目标....     

Fulfilment of expectations on birth and the postpartum period – A Swedish cohort study

BackgroundThe fulfilment of birth expectations is important to women and strongly related to birth satisfaction.ObjectiveThe aim of this study was to investigate women’s expectations and experiences of birth and the postnatal period and associated factors. An additional aim was to explore if women's expectations were fulfilled.MethodsA longitudinal cohort study of 280 women where 226 were followed up two months after birth. Data were collected using questionnaires. Odds ratios with a 95% confidence interval were calculated between the explanatory background variables and expectations/experiences.ResultsThe majority (79%) rated continuity as important, but few (32%) actually had a known midwife assisting during birth. Positive birth expectations were found in 37% and a positive birth experience in 66%. Many women (56%) preferred a short postnatal stay, and 63% went home within 24 h. Thirty-six percent preferred postnatal home visits, but only eight women (3.5%) received this. Breastfeeding expectations were high with 86% rating it as important but after birth 63% reported exclusively breastfeeding. Only a few background factors were associated with women’s expectations and experiences. Most likely to be fulfilled were women’s expectations for a vaginal birth (83%), a positive birth experience (71%) and short length of postnatal stay (67%). Postnatal home visits (96%) and continuity of care (73%) were not fulfilled.ConclusionsPregnant women’s expectations about continuity are fulfilled only to a minor degree. The fulfilment of postnatal expectations varied and the preference for a short postnatal stay was fulfilled whereas home visits were not.     

术中按需喷洒与术前口服二甲硅油 在肠镜检查中的作用研究

〔摘 要〕 目的：探讨术中按需喷洒与术前口服二甲硅油在肠镜检查中的应用效果。 方法：选取 2020 年 1 月至 2021 年 6 月于萍乡市人民医院行肠镜检查的无明显症状患者 90 例，按随机数字表法分为两组，对照组和观察组各 45 例。两组均 使用聚乙二醇电解质散清洁肠道，对照组术前口服二甲硅油，观察组术中按需喷洒二甲硅油。比较两组患者肠道清洁分级、 气泡分级、二甲硅油用量、肠镜检查操作时间、结肠息肉检出率及患者满意度。 结果： 两组患者肠道清洁分级相比，差异无 统计学意义（P ＞ 0.05）。观察组患者气泡分级 1 级率为 80.00 %，高于对照组的 62.22 %，差异具有统计学意义（P ＜ 0.05）。 观察组患者二甲硅油用量为（14.58 ± 2.01）mL，少于对照组的（22.35 ± 2.65）mL，进、退镜时间分别为（8.89 ± 1.14）min、 （8.33 ± 1.08）min，短于对照组的（9.76 ± 1.27）min、（10.27 ± 2.04）min，差异有统计学意义（P ＜ 0.05）。观察组患者 结肠息肉检出率、患者满意度为 17.78 %、97.78 %，高于对照组的 4.44 %、82.22 %，差异具有统计学意义（P ＜ 0.05）。 结论：术中按需喷洒二甲硅油在肠镜检查中效果更佳，可减少二甲硅油用量，提高视野清晰度，缩短肠镜检查操作时间， 并利于结肠息肉的检出，提高患者满意度。     

Evaluating the MoA/human relevance framework for F-344 rat liver epithelioid granulomas with mineral oil hydrocarbons

Toxicology feeding studies of mineral oil hydrocarbons (MOHs), within the carbon number range C₂₂–C₂₈, results in species-specific epithelioid granulomas in the liver of F-344 rats but not in other rat strains, or species. While MOH has been detected, and some pathological effects have been shown to occur in other organs/tissues of F-344 rats and other rat strains/species, it is generally accepted that the effect of toxicological concern is species-specific inflammatory liver granuloma. As oil retention and other MOH-related nontoxic pathological changes in the liver are observed in humans, some have hypothesized that the potential for oil accumulation over a lifetime, through dietary sources, may predispose humans to similar liver effects as observed in F-344 rats. To address this concern, a mode of action/human relevance framework (MoA/HRF) analysis for MOH-induced epithelioid granuloma in the F-344 rat model was developed. The key events for the development of liver epithelioid granulomas were identified as increased MOH intestinal absorption, preferential tissue retention and ultimately formation of necrotic granulomas encased by infiltrating inflammatory lymphocytes. The hypothesized MoA was evaluated using the modified Bradford Hill considerations for causality and was considered to be established in the F-344 rodent model. However, key strain/species differences in the rate of intestinal absorption, tissue retention of MOH and inflammatory response to MOH in the liver were identified. Overall, the F-344 rat MoA was not considered to be relevant to humans, consistent with data showing no evidence for the formation of epithelioid granulomas with humans even in cases of massive ingestion of MOHs.     

Semi‐linear mode regression

In this paper, I estimate the slope coefficient parameter β of the regression model , where the error term e satisfies almost surely and ? is an unknown function. It is possible to achieve ‐consistency for estimating β when ? is known up to a finite‐dimensional parameter. I present a consistent and asymptotically normal estimator for β, which does not require prescribing a functional form for ?, let alone a parametrization. Furthermore, the rate of convergence in probability is equal to at least , and approaches if a certain density is sufficiently differentiable around the origin. This method allows both heteroscedasticity and skewness of the distribution of . Moreover, under suitable conditions, the proposed estimator exhibits an oracle property, namely the rate of convergence is identical to that when ? is known. A Monte Carlo study is conducted, and reveals the benefits of this estimator with fat‐tailed and/or skewed data. Moreover, I apply the proposed estimator to measure the effect of primogeniture on economic achievement.     

Protein kinase inhibitors of the quinazoline class exert anti-cytomegaloviral activity in vitro and in vivo

Cytomegalovirus infection is associated with severe disease in immunocompromised individuals. Current antiviral therapy faces several limitations. In a search of novel drug candidates, we describe here the anti-cytomegaloviral properties of two compounds of the chemical class of quinazolines, gefitinib (Iressa) and Ax7396 (RGB-315389). Both compounds showed strong inhibitory effects in vitro against human and animal cytomegaloviruses with IC(50)s in a low micromolar range. Cytotoxicity did not occur at these effective concentrations. The antiviral mode of action was based on the inhibition of protein kinase activity, mainly directed to a viral target kinase (UL97/M97) in addition to cellular target candidates. This was demonstrated by a high sensitivity of the respective protein kinases in vitro and by infection experiments with viral mutants carrying genomic alterations in the ORF UL97/M97 modulating viral drug sensitivity. In a guinea pig model, gefitinib showed inhibition of cytomegaloviral loads in blood and lung tissue. Importantly, the rate of mortality of infected animals was reduced by gefitinib treatment. In contrast to the in vitro data, Ax7396 showed no significant antiviral activity in a mouse model. Further in vivo analyses have to assess the potential use of gefitinib in the treatment of cytomegalovirus disease.     

Is inhalation exposure to formaldehyde a biologically plausible cause of lymphohematopoietic malignancies?

The United States Environmental Protection Agency (EPA) recently proposed a hypothetical mode of action (MOA) to explain how inhaled formaldehyde (FA) might induce leukemia, lymphoma and a variety of other lymphohematopoietic (LHP) malignancies in occupationally exposed workers. The central hypothesis requires that B lymphocytes or hematopoietic progenitor cells (HPC) present at the "portal of entry (POE)" undergo sustained mutagenic change as a result of direct FA exposure. These modified cells would then migrate back to the bone marrow or primary lymphatic tissue and subsequently develop into specific LHP disease states. Chemical interaction at the POE is an absolute requirement for the hypothesized MOA as there is no convincing evidence that inhaled FA causes distant site (e.g., bone marrow) toxicity. The purpose of this review is to critically evaluate this proposed MOA within the context of the existing data concerning the toxicokinetic and biological properties of FA, the current understanding of the induction of chemically-induced leukemias and lymphomas, as well as within EPA's specific guidelines for evaluating the MOA of chemically-induced cancers. Specifically, we examine the scientific support for the hypothesis that FA exposure may induce carcinogenic transformation of localized lymphocytes or peripheral hematopoietic progenitor cells (HPC) in the absence of discernable systemic hematopoietic toxicity (i.e., peripheral transformation). While little or no empirical evidence exists upon which to fully evaluate the proposed hypothesis, available data does not support the proposed concept of "peripheral transformation" at the chemical entry site. Numerous animal bioassays evaluating chronic inhalation of FA clearly do not support this hypothesis since no properly conducted study as ever shown an increase in any LHP malignancy. Moreover, the notion that FA can cause any LHP malignancy is not supported with either epidemiologic data or current understanding of differing etiologies and risk factors for the various hematopoietic and lymphoproliferative malignancies. It is therefore concluded that existing science does not support the proposed MOA as a logical explanation for proposing that FA is a realistic etiological factor for any LHP malignancy.     

Evidence-based dose-response assessment for thyroid tumorigenesis from acrylamide

Acrylamide is commonly found in various foods. Cancer studies in rats have reported increases in tumors of the thyroid, mammary tissues, tunica vaginalis of the testis, and sometimes tumors at other sites. We review relevant studies on acrylamide’s DNA toxicity, tumor formation and the manner of its tumor formation. We find, as do others, that glycidamide (a metabolite of acrylamide) causes point mutations, but acrylamide does not. We also find that thyroid tumors are most consistently sensitive in rats, being evoked in each of four long-term experiments. We evaluate the common manners of this tumor formation in the thyroid, including both mutagenicity and thyroid growth-stimulation. Consistent with the overall weight of the evidence, we conclude that both of these manners or modes of action may be occurring. We conservatively assume that the mutagenic mode of action determines the low-dose–response and we conclude that growth stimulation likely dominates the response at higher doses. Following US EPA guidelines, we determined that the probit model best reflects the overall data set; this model is also preferred because it better reflects the underlying “decoupled” biology of contributions from potentially two modes of action. We use the probit model to identify a health-protective, linear cancer slope factor (SF) of 0.030 (mg/kg-day)⁻¹ for the low area of the dose–response curve associated with possible mutagenicity. We also identify a Reference Dose (RfD) in the range of 0.05–0.02 mg/kg-day for the high area of the dose–response curve associated with the growth stimulation. This latter value can be used to determine the upper range of risk. This dose–response assessment is briefly summarized in light of other related work.