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Promoter methylation of matrix metallopeptidase 9 in peripheral blood mononuclear cells: A novel biomarker in a promising source for noninvasive colorectal cancer diagnosis. 外周血单核细胞中基质金属肽酶 9 的启动子甲基化:一种新型生物标记物,有望成为无创结肠直肠癌诊断的来源。
IF 1.3 Pub Date : 2023-10-01 Epub Date: 2022-04-29 DOI: 10.4103/jcrt.jcrt_2188_21
Alireza Shaygannejad, Behnoush Sohrabi, Shima Rahimi Rad, Farzaneh Yousefisadr, Hossein Darvish, Mohsen Soosanabadi

Objectives: Colorectal cancer (CRC) has been described as a "silent disease," which can be readily treated in most patients when discovered in its early stages. Considering the limitations of the current conventional tests for the diagnosis of CRC, researchers strive to find noninvasive and more valid biomarkers for the early detection of CRC. It has been shown that tumor-specific methylation patterns can also be identified in peripheral blood mononuclear cells (PBMCs) and are reliable sources of methylation analysis for CRC screening.

Materials and methods: We carried out a quantitative methylation analysis on matrix metallopeptidase 9 (MMP9) promoter using methylation quantification endonuclease-resistant DNA (MethyQESD) method. A total of 70 patients with CRC and 70 normal controls were enrolled in this study for methylation analysis in the PBMCs.

Results: Our findings discovered a considerable hypermethylation of MMP9 promoter in CRC patients compared with healthy controls (mean: 47.30% and 20.31%, respectively; P > 0.001). The sensitivity and specificity of the MMP9 gene for the diagnosis of CRC were 88% and 78%, respectively. In addition, on the basis of area under the curve values, the diagnostic power of the MMP9 gene was 0.976 (P < 0.001). Moreover, our analysis established that MMP9 methylation was significantly different between the different stages of CRC (P: 0.034).

Conclusions: Our results showed that MMP9 promoter methylation in PBMCs can be used as an outstanding biomarker for CRC diagnosis. Besides, we confirmed that PBMCs are reliable sources of methylation analysis for CRC screening and MethyQESD is an accurate and fast method for quantitative methylation analyses.

目的:结肠直肠癌(CRC)被称为 "沉默的疾病",如果在早期发现,大多数患者都能得到及时治疗。考虑到目前用于诊断 CRC 的常规检测方法的局限性,研究人员努力寻找非侵入性和更有效的生物标志物来早期检测 CRC。研究表明,肿瘤特异性甲基化模式也可在外周血单核细胞(PBMCs)中发现,并且是用于 CRC 筛查的可靠甲基化分析来源:我们采用甲基化定量抗核酸内切酶DNA(MethyQESD)方法对基质金属肽酶9(MMP9)启动子进行了甲基化定量分析。本研究共招募了 70 名 CRC 患者和 70 名正常对照者,对他们的 PBMCs 进行甲基化分析:结果:我们发现,与健康对照组相比,CRC 患者 MMP9 启动子的甲基化程度相当高(平均分别为 47.30% 和 20.31%;P > 0.001)。MMP9 基因对诊断 CRC 的敏感性和特异性分别为 88% 和 78%。此外,根据曲线下面积值,MMP9 基因的诊断能力为 0.976(P < 0.001)。此外,我们的分析还证实,MMP9 甲基化在不同阶段的 CRC 之间存在显著差异(P:0.034):我们的研究结果表明,PBMCs 中的 MMP9 启动子甲基化可作为诊断 CRC 的重要生物标志物。此外,我们还证实了 PBMCs 是用于 CRC 筛查的甲基化分析的可靠来源,而 MethyQESD 是一种准确、快速的甲基化定量分析方法。
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引用次数: 0
Reconciliation of hospital discharge summaries and changes in patient medications 出院总结和患者用药变化的核对
Pub Date : 2016-09-01 DOI: 10.1177/1356262217696416
L. Piggott
Family doctors will regularly have patients who are admitted to hospital. On discharge, many of these patients may have alterations to the medications that require attention by their family doctor, to either start a new repeat prescription or amend previous ones. This action should be clearly documented, so it can be recognised easily that the discharge summary has been reviewed. This study looks at the action taken and coding related to hospital discharge summaries in a general practice in the United Kingdom. The practice was very accurate and safe in making correct changes to medications but had low rates of documenting and coding that the discharge summary has been reviewed and actioned as required. A uniform code was recommended, and required documentation related to discharge summaries included in the practice’s training materials for locum and training doctors.
家庭医生会定期接待住院的病人。出院时,这些患者中的许多人可能会改变药物,需要他们的家庭医生的注意,要么开始新的重复处方,要么修改以前的处方。这一行动应该清楚地记录下来,这样就可以很容易地识别出已经审查了出院摘要。本研究着眼于采取的行动和编码相关的医院出院总结在英国的一般做法。这种做法在正确更改药物方面非常准确和安全,但记录和编码出院总结的比率很低,出院总结已被审查并按要求采取行动。建议制定统一的守则,并要求在实习医生和培训医生的培训材料中包含与出院摘要有关的文件。
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引用次数: 0
Incident reporting and a culture of safety 事故报告和安全文化
Pub Date : 2016-09-01 DOI: 10.1177/1356262216682893
Jonathan E. Hazan
Incident reporting has long been established as a key component of patient safety in almost all healthcare and related settings. The analysis of incidents to determine why they happen and put in place corrective actions enables us to learn from things that go wrong and protect patients from harm in the future. The introduction of electronic incident reporting using web forms to replace paper has improved efficiency and increased the number of reports collected. There still remain significant barriers to learning from incidents, however. These include issues to do with the design of the systems as well as issues concerning organisational culture. This article revisits the background and purpose of incident reporting in healthcare, discusses some of the barriers to effective reporting and suggests some approaches that can increase its usefulness in protecting patients from harm.
在几乎所有医疗保健和相关环境中,事故报告一直是患者安全的关键组成部分。对事件进行分析,以确定事件发生的原因,并采取适当的纠正措施,使我们能够从出错的事情中吸取教训,并在未来保护患者免受伤害。引入电子事故报告,以网络表格取代纸张,提高了效率,并增加了收集的报告数量。然而,从事件中学习仍然存在重大障碍。这些问题包括与系统设计有关的问题以及与组织文化有关的问题。本文回顾了医疗保健中事件报告的背景和目的,讨论了有效报告的一些障碍,并提出了一些可以提高其在保护患者免受伤害方面的有用性的方法。
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引用次数: 7
‘Safe space’ or ‘secret space’? Proposals for safety investigations in England “安全空间”还是“秘密空间”?英国安全调查的建议
Pub Date : 2016-09-01 DOI: 10.1177/1356262217701341
P. Walsh
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引用次数: 0
Killer’s claim dismissed: E H v Dorset Healthcare NHS Foundation Trust (High Court, 19 December 2016 – Jay J) 杀手的索赔被驳回:E H诉多塞特医疗保健NHS基金会信托基金(高等法院,2016年12月19日- Jay J)
Pub Date : 2016-09-01 DOI: 10.1177/1356262217703438a
J. Mead
On the balance of probabilities, the thrombolysis service would have been available to Mr Lowe at Doncaster that morning, within a 3 hour window from the onset of his symptoms. However, whether the claimant would have had a better outcome had he received such treatment divided the relevant experts. Professor Ford, for the claimant, estimated that Mr Lowe would have had a 50% to 60% probability of making a good functional recovery. Dr Hassan, a consultant stroke physician instructed by the trust, considered that the chance of a good outcome would have been between 40% and 50%.
从各种可能性来看,那天早上唐卡斯特的洛伊先生在出现症状后的3小时内就可以接受溶栓治疗。但是,如果索赔人得到这种待遇是否会有更好的结果,有关专家意见不一。福特教授为索赔人估计,洛威先生有50%到60%的可能性能够很好地恢复功能。哈桑医生是一名受信托基金指导的中风顾问医师,他认为获得良好结果的几率在40%到50%之间。
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引用次数: 0
Battram v Dr Geoghegan 巴特拉姆诉纪勤博士
Pub Date : 2016-09-01 DOI: 10.1177/1356262217695626
C. Maunder
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引用次数: 0
Post Brexit crystal ball gazing: What the future holds for Phase I Clinical Trials in the UK 脱欧后的水晶球预测:英国I期临床试验的未来是什么
Pub Date : 2016-09-01 DOI: 10.1177/1356262217702814
G. Matthews, N. Williams
EU Regulation 536/2014 (“Regulations”) is due to take practical effect across the Eurozone by the end of 2017 at the earliest and no later than October 2018 following the implementation of procedural requirements. It will replace the EU Clinical Trials Directive 2001/20/EC. The Regulations are designed to reverse what regulators described as a downward trend in the conduct of clinical trials within Europe because of the “lengthy and cumbersome application process and the failure of the pre-existing regime to accommodate the global scope of clinical trials.” The purpose of the Regulations is to simplify and harmonise the administrative provisions governing clinical trials in the EU. With pleasing Pharmaceutical companies high on the political agenda, the pertinent question that arises is whether patient and public interests will be overlooked to cater to industry concerns? This article will outline the changes effected by the Regulation. It will evaluate the impact these changes will have on patient safety in the context of Phase I or First-in-human (FIH) trials by examining the TGN1412 clinical drug trial (also known as the Northwick Park drug trial). The second part of this article will discuss whether there is a place for the Regulations in the post Brexit landscape. The continuing uncertainty surrounding Brexit means that it remains difficult to come to any definitive conclusions but there are significant issues that require closer examination at this time.
欧盟法规536/2014(“法规”)将在程序要求实施后,最早于2017年底在整个欧元区生效,最迟不迟于2018年10月。它将取代欧盟临床试验指令2001/20/EC。该条例旨在扭转监管机构所描述的在欧洲进行临床试验的下降趋势,因为“漫长而繁琐的申请过程以及现有制度未能适应全球临床试验范围”。该法规的目的是简化和协调管理欧盟临床试验的行政规定。取悦制药公司在政治议程上占据重要地位,随之而来的相关问题是,为了迎合制药行业的担忧,患者和公众的利益是否会被忽视?本文将概述该规例所带来的改变。它将通过检查TGN1412临床药物试验(也称为Northwick Park药物试验)来评估这些变化对I期或首次人体(FIH)试验背景下患者安全性的影响。本文的第二部分将讨论在英国脱欧后的环境中,这些规定是否有一席之地。围绕英国脱欧的持续不确定性意味着仍难以得出任何明确的结论,但目前仍有一些重大问题需要进一步研究。
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引用次数: 1
Ambulance crew not negligent in choice of hospital: Stephen Lowe v Yorkshire Ambulance Service NHS Trust (Sheffield County Court, 12 February 2016 – Recorder P W Miller) 救护人员在医院选择上没有过失:Stephen Lowe诉约克郡救护车服务NHS信托基金(2016年2月12日-谢菲尔德郡法院-记录员P W Miller)
Pub Date : 2016-09-01 DOI: 10.1177/1356262217703438
J. Mead
The claimant lived in Mexborough in Yorkshire. On 19 June 2009 at approximately 07:00, hewas in his kitchen at home when his wife noted that he was neither walking nor talking normally and was showing weakness on the right side. She promptly telephoned for an ambulance. One of the trust’s ambulances arrived at 07:14. It was staffed by two paramedics who examined Mr Lowe and agreed that he had probably suffered a stroke. By 07:20, therefore, they were aware that the patient was in urgent need of emergency medical treatment and that they had, without delay, to decide upon and telephone an alert to the most appropriate accident and emergency (A&E) department. There were only two possibilities: Rotherham District Hospital and Doncaster Royal Infirmary, each of which possessed an A&E department and stroke unit. The crew were very familiar with local traffic conditions and calculated that it would have taken them between 20 and 22min to reach Doncaster, whereas Rotherham could be reached in 5min less. They were also aware that in the event the patient required onward referral to the neurological department at the Royal Hallamshire Hospital in Sheffield, the further ambulance journey would take 10 to 11min from Rotherham but 25 to 26min from Doncaster. An important distinction between the stroke units at the two hospitals was that at certain times of the day Doncaster, but not Rotherham, offered thrombolysis. In 2009, this was a relatively new treatment involving the use of drugs to break down blood clots. However, the service was only available from 08:00 h until 20:00 h at Doncaster, and the ambulance staff knew that prior to 08:00 h, it was not possible to contact the relevant department by telephone. Furthermore, the Ambulance Service’s guidance in respect of the period 20:00 to 08:00 h was to ‘‘Manage the patient as their condition dictates, with a pre-alert to emergency department as per local protocol’’. In view of all the above considerations, the crew took Mr Lowe to Rotherham District Hospital.
索赔人住在约克郡的梅克斯伯勒。2009年6月19日大约07:00时,他正在家中的厨房里,他的妻子注意到他既不能正常行走也不能正常说话,而且右侧出现无力。她立即打电话叫了一辆救护车。信托的一辆救护车在07:14到达。两名医护人员对洛威进行了检查,认为他可能是中风。因此,到07:20,他们意识到病人迫切需要紧急医疗,他们必须毫不拖延地做出决定,并打电话向最合适的事故和紧急情况部门发出警报。只有两种可能:罗瑟勒姆地区医院和唐卡斯特皇家医院,这两家医院都有急症室和中风科。工作人员非常熟悉当地的交通状况,并计算出他们到达唐卡斯特需要20到22分钟,而到达罗瑟勒姆只需5分钟。他们还意识到,如果病人需要转到谢菲尔德皇家哈勒姆郡医院的神经内科,从罗瑟勒姆到唐卡斯特的救护车路程需要10到11分钟,而从唐卡斯特到罗瑟勒姆需要25到26分钟。这两家医院中风科室的一个重要区别是,在一天中的某些时间,唐卡斯特医院提供溶栓治疗,而罗瑟勒姆医院没有。在2009年,这是一种相对较新的治疗方法,涉及使用药物分解血凝块。然而,在唐卡斯特,这项服务只在08:00到20:00之间提供,救护车工作人员知道,在08:00之前,无法通过电话联系相关部门。此外,救护车服务处在20:00至08:00期间的指导方针是"根据病人的情况对其进行管理,并根据当地规程向急诊科发出预先警报"。鉴于上述种种考虑,船员们把洛威先生送到罗瑟勒姆地区医院。
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引用次数: 0
Improving healthcare through the use of ‘medical manslaughter’? Facts, fears and the future 通过使用“医疗过失杀人”来改善医疗保健?事实、恐惧和未来
Pub Date : 2016-09-01 DOI: 10.1177/1356262217696623
M. Brazier, S. Devaney, D. Griffiths, Alex Mullock, Hannah Quirk
The criminal law looks set to play a larger role in regulating healthcare. Until recently, health professionals only faced the prospect of criminal liability if it could be proved that their gross negligence resulted in the death of a patient. In such a case, the professional could face a charge of gross negligence manslaughter (GNM). Prosecutions for ‘medical manslaughter’ have generated concern among doctors worried about what is perceived as a rise in the number of doctors facing criminal prosecution and the impact prosecutions are having on healthcare practice. May more frequent resort to the criminal process damage rather than promote better health care? In seeking to try to answer this question, the first problem is that reliable data in this area about how many prosecutions are brought and how they fare are limited due to the way cases are recorded. What evidence does exist is often based on media reports or samples that are not representative. This paper will argue that, while the real risk of being prosecuted for medical manslaughter remains low, such fears should not be dismissed because, as Donald Berwick has argued, ‘fear is toxic’ – for health professionals and their patients.
刑法似乎将在监管医疗保健方面发挥更大的作用。直到最近,卫生专业人员只有在能够证明他们的重大疏忽导致病人死亡的情况下才面临刑事责任的前景。在这种情况下,专业人员可能面临重大过失杀人罪(GNM)的指控。对“医疗过失杀人罪”的起诉引起了医生们的关注,他们担心面临刑事起诉的医生数量会上升,以及起诉对医疗实践的影响。更频繁地诉诸刑事诉讼损害而不是促进更好的医疗保健?在试图回答这个问题的过程中,第一个问题是,由于案件的记录方式,这一领域关于起诉数量及其进展情况的可靠数据有限。确实存在的证据往往是基于不具代表性的媒体报道或样本。本文将论证,虽然因医疗过失杀人罪被起诉的真正风险仍然很低,但这种恐惧不应该被忽视,因为,正如唐纳德·贝里克(Donald Berwick)所说,“恐惧是有毒的”——对卫生专业人员和他们的病人来说。
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引用次数: 3
Trust liable for brain damage to baby: F E v St George’s University Hospitals NHS Trust (High Court, 18 March 2016 – McGowan J) 对婴儿脑损伤负有责任的信托:F E诉圣乔治大学医院NHS信托(高等法院,2016年3月18日- McGowan J)
Pub Date : 2016-09-01 DOI: 10.1177/1356262217703438b
J. Mead
from an abnormality of the mind, namely paranoid schizophrenia, such that her mental responsibility should be regarded as ‘‘substantially impaired.’’ The claimant pleaded guilty to the offence of manslaughter on the ground of diminished responsibility, and this plea was accepted by the Crown. Mr Justice Jay held that these facts meant that the conviction was conclusive evidence that EH’s mental functioning was substantially impaired at the time of the offence. He also interpreted the sentencing remarks of the trial judge, Mr Justice Foskett, as supporting the interpretation that this case fell towards the lower end of the spectrum of personal responsibility. In his judgment, it was not open to the claimant to undermine or impugn the findings of Foskett J and he therefore proceeded on the basis that the claimant’s personal responsibility was low and/or less than significant. The judge then turned to relevant case-law. In Clunis v Camden and Islington Health Authority [1998] QB 978 Mr Clunis, a man with a history of mental health problems including schizoaffective disorder, killed a man by stabbing him and pleaded guilty to manslaughter on the ground of diminished responsibility. The Court of Appeal struck out the whole of his claim against the Health Authority, holding that it was barred by public policy. There were no discernible matters or aspects of factual differentiation between the present claim and that of Mr Clunis. In Gray v Thames Trains Limited [2009] 1 AC 1339, the claimant developed post-traumatic stress disorder as a result of the Ladbroke Grove rail disaster in 1999. While suffering from this disorder he killed a man. His plea to the offence of manslaughter on the ground of diminished responsibility was accepted by the Crown. The House of Lords held that his claim for loss of liberty, loss of earnings, etc. failed on the basis that he was seeking to obtain compensation for his own criminal conduct. The claimant’s lawyers endeavoured to argue that subsequent observations of the Supreme Court cast doubt upon these rulings, and that therefore it was appropriate for EH’s claim to continue. Mr Justice Jay disagreed. He held that it was clear that these subsequent Supreme Court rulings made no express criticism of either Clunis or Gray. In particular, Clunis had not been expressly disapproved by the Supreme Court. As a consequence, case-law supported the trust’s position and this claim would therefore be struck out. The Judge refused permission for either a ‘‘leap frog’’ appeal to the Supreme Court or a reference to the Court of Appeal. Nicholas Bowen QC and Katie Scott (instructed by Russell-Cooke) appeared for the claimant. Angus Moon QC, Judith Ayling and Cecily White (instructed by DAC Beachcroft) appeared for the trust.
她的精神异常,即偏执型精神分裂症,她的精神责任应被视为“严重受损”。“原告对过失杀人罪表示认罪,理由是责任减轻,这一抗辩被王室接受。杰伊法官认为,这些事实意味着该定罪是确凿的证据,证明EH的精神功能在犯罪时受到严重损害。他还将初审法官Foskett法官的量刑言论解释为支持此案属于个人责任范围低端的解释。在他的判决中,索赔人不能破坏或质疑Foskett J的调查结果,因此他以索赔人的个人责任很低和(或)不太重大为依据进行诉讼。法官随后转向相关的判例法。在Clunis诉Camden和Islington卫生局[1998]QB 978案中,Clunis先生是一名有精神健康问题史的男子,包括精神分裂情感障碍,他用刀刺死了一名男子,并以减轻责任为由承认过失杀人罪。上诉法院驳回了他对卫生局提出的全部索赔,认为这是公共政策所禁止的。现时的申索与克吕尼先生的申索在事实上并无明显的区别。在格雷诉泰晤士火车有限公司[2009]1 AC 1339案中,原告因1999年拉德布罗克格罗夫铁路事故而患上创伤后应激障碍。在患这种疾病期间,他杀了一个人。他以责任减轻为由对过失杀人罪的抗辩被王室接受了。上议院认为,他关于丧失自由、丧失收入等的索赔无效,因为他是在为自己的犯罪行为寻求赔偿。索赔人的律师努力辩称,最高法院随后的意见对这些裁决产生了怀疑,因此EH继续索赔是适当的。杰伊法官不同意。他认为,很明显,最高法院后来的这些裁决并没有对克伦尼斯或格雷作出明确的批评。特别是,最高法院并没有明确反对Clunis。因此,判例法支持信托的立场,因此这一主张将被取消。法官既不允许向最高法院提出“跳蛙”式上诉,也不允许向上诉法院提起上诉。Nicholas Bowen QC和Katie Scott(在Russell-Cooke的指导下)为原告出庭。法律顾问安格斯·穆恩、朱迪思·艾林和塞西莉·怀特(由DAC Beachcroft指示)出席了信托。
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引用次数: 0
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Clinical risk
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