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51.
Rohi Shah Nomaan Sheikh Jitendra Mangwani Nicolette Morgan Hamidreza Khairandish 《Journal of Clinical Orthopaedics and Trauma》2021,12(1):138
Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC. 相似文献
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ABSTRACTThis work collates data from the analysis of complex mixtures analysed in STRmix during routine no-suspect volume crime work. It interrogates the upload rate for these types of mixtures and which component of the profile has been able to be interpreted for upload. The number of profiles giving multiple uploads and the amount of replicate PCR analysis has been collated. 相似文献
54.
目的 通过观察早产儿不同胎龄Toll样受体9(TLR9)的表达,探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份,按胎龄分为4组,28~31周组,31~34周组,34~37周组,≥37周组,采用流式细胞术和实时荧光定量PCR方法,分别检测其TLR9的蛋白和mRNA表达情况,了解其与胎龄之间的关系,并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组,31~34周组,34~37周组,≥37周组分别为(15.93±6.23)%,(11.63±6.70)%,(13.66±6.88)%,(20.51±12.06)%;其在胎龄28~31周较高,至31~34周逐渐下降至最低,两组差异有统计学意义(P<0.05);34~37周后TLR9阳性细胞率表达逐渐升高,至≥37周达最高,两胎龄组比较,差异具有统计学意义(P<0.05)。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关(r=0.273,P=0.006)。TLR9 mRNA表达在28~31周组,31~34周组,34~37周组,≥37周组分别为(4.95±3.44)%,(8.89±8.49)%,(13.91±10.92)%,(7.19±7.11)%;其在28~36周逐渐升高,与胎龄呈正相关(r=0.355,P< 0.001)。≥37周TLR9 mRNA表达量下降,该值虽高于28~31周,但差异无统计学意义(P>0.05)。相关性分析表明,同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关(r=-0.227,P=0.011)。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异,TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加,TLR9 mRNA在28~36周间随着胎龄的增加而增加。 相似文献
55.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
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Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11. 相似文献
59.
目的:讨论普通变异型免疫缺陷病(common variable immunodeficiency disease,CVID)的发病机制、临床表现及治疗方法。方法:报道1例普通变异型免疫缺陷病合并肝硬化患者并复习相关文献。结果:普通变异型免疫缺陷病是临床少见病,易误诊,病因不清,临床表现复杂,部分患者病程中可出现肝功能异常,甚至并发肝硬化。结论:临床反复感染的患者应考虑CVID的可能,须进一步作血浆免疫球蛋白的检测确诊。对已经确诊患者定期补充静脉丙种球蛋白,同时还应定期检查肝功能。 相似文献
60.
《Saudi Pharmaceutical Journal》2020,28(7):844-849
Epilepsy is a common neurologic disorder, which is efficiently treated with carbamazepine and valproic acid. Moreover, Saudi Ministry of Health implemented a new E-system for Poison Control Centers called Awtar to enhance technology utilization in ensuring patients’ satisfaction and to improve treatment outcomes. Therefore, we conducted this study to assess appropriateness of indication of requests and therapeutic levels of carbamazepine and valproic acid in Tabuk area, North West Saudi Arabia. This is a retrospective observational study conducted in Poison Control & Forensic Chemistry Center, Tabuk, Saudi Arabia. Patients’ data were obtained for years 2018 and 2019. The blood levels of carbamazepine and valproic acid were measured by Therapeutic Drug Monitoring (TDM) Unit. We selected patients treated with either valproic acid or carbamazepine alone without any history of drug allergy. Data of 264 patients were extracted from Awtar E-system. Serum carbamazepine levels were within therapeutic range in 114 patients (75.50%), above-therapeutic range in 13 patients (8.61%) and sub-therapeutic levels in 24 patients (15.89%). Regarding serum valproic acid, it is within therapeutic range in 62 patients (54.87%), above-therapeutic range in 11 patients (9.73%) and sub-therapeutic levels in 40 patients (35.40%). In conclusion, this study gives information about partial appropriateness of usage of carbamazepine and low level of appropriateness of valproic acid. However, more efforts are needed to improve results of appropriateness of indication of antiepileptic drugs. 相似文献