含灯盏花中成药DNA提取及其分子鉴定

目的:优选适用于含灯盏花中成药的DNA提取方法和聚合酶链式反应(PCR)扩增引物,并通过测序和系统发育分析实现对其原料灯盏花的分子鉴定。方法:采用4种十六烷基三甲基溴化铵(CTAB)改良方法对3种含灯盏花的中成药进行DNA提取,测定DNA的纯度和浓度。采用内转录间隔区(ITS)、matK、psbA-trnH、rbcL位点通用引物对提取的中成药DNA进行PCR扩增,并对PCR扩增最佳位点进行测序,通过构建系统发育树进行分子鉴定。结果:4种CTAB改良方法均能获得含灯盏花中成药DNA,其中CTAB改良方法一提取的DNA质量浓度显著高于其他改良方法;PCR扩增中以matK位点2对引物(matKXF/matK5R或matK3F/matK1R)最佳,可通过1次PCR成功获得具有单一条带且浓度较高的PCR产物,序列与灯盏花对照药材同源性为100%,系统发育树显示可与同属其他植物区分。结论:通过CTAB改良方法一可以有效提取含灯盏花中成药样品的DNA,采用matK位点引物matKXF/matK5R或matK3F/matK1R进行1次PCR扩增并对产物进行测序,通过序列比对可完成其原料灯盏花的鉴定。     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

基于预防接种异常反应补偿的山东省卡介苗淋巴结炎经济负担测算

目的了解山东省卡介苗(BCG)淋巴结炎经济负担情况。方法以2011年5月至2019年12月山东省304例申请省级补偿的BCG淋巴结炎病例为对象,收集患者基本情况、预防接种相关情况、门诊(住院)病历和收费票据等相关资料,对其直接经济负担(包括直接医疗费用和直接非医疗费用)、间接经济负担和总经济负担进行测算,比较不同特征病例经济负担的差异。结果304例BCG淋巴结炎患者月龄的M(Q1,Q3)为3(2,4)月,其中男性239例(78.6%),淋巴结破溃71例(23.4%),手术227例(74.7%)。单纯门诊、单纯住院和门诊后住院病例分别占25.7%(78例)、7.2%(22例)和67.1%(204例)。贴现后单例直接、间接和总经济负担的M(Q1,Q3)分别为9910(5713,16074)、2081(1547,3122)和12262(7694,18571)元。直接医疗费用占直接经济负担的89.4%,直接经济负担占总经济负担的84.9%,80.0%病例的总经济负担仅占其补偿金额的20.0%左右,只有2.3%的病例总经济负担占补偿金额的60.0%以上。单纯住院和门诊后住院病例的直接、间接和总经济负担高于单纯门诊病例,手术病例的直接、间接和总经济负担高于非手术病例,淋巴结未破溃病例的直接和总经济负担高于破溃病例(均P<0.05)。结论山东省BCG淋巴结炎病例经济负担受诊疗方式的影响,且以直接医疗费用为主。     

Novel glucose-lowering drugs for non-alcoholic fatty liver disease

BACKGROUNDThe efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown.AIMTo evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments.METHODSElectronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline.RESULTSNineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups.CONCLUSIONTreatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.     

Efficacy of m-Health for the detection of adverse events following immunization – The stimulated telephone assisted rapid safety surveillance (STARSS) randomised control trial

IntroductionPassive surveillance is recommended globally for the detection of adverse events following immunisation (AEFI) but this has significant challenges. Use of Mobile health for vaccine safety surveillance enables a consumer-centred approach to reporting. The Stimulated Telephone Assisted Rapid Safety Surveillance (STARSS) a randomised control trial (RCT) sought to evaluate the efficacy and acceptability of SMS for AEFI surveillance.MethodsMulti-centre RCT, participants were adult vaccinees or parents of children receiving any vaccine at a trial site. At enrolment randomisation occurred to one of two SMS groups or a control group. Prompts on days 2, 7 and 14 post-immunisation, were sent to the SMS group, to ascertain if a medical event following immunisation (MEFI) had occurred. No SMS’s were sent to the control participants. Those in the SMS who notified an MEFI were pre-randomised to complete a computer assisted telephone interview or a web based report to determine if an AEFI had occurred whilst an AEFI in the controls was determined by a search for passive reports. The primary outcome was the AEFI detection rate in the SMS group compared to controls.ResultsWe enrolled 6,338 participants, who were equally distributed across groups and who received 11,675 vaccines. The SMS group (4,225) received 12,675 surveillance prompts with 9.8% being non-compliant and not responding. In those that responded 90% indicated that no MEFI had been experienced and 184 had a verified AEFI. 6 control subjects had a reported AEFI. The AEFI detection rate was 13 fold greater in the SMS group when compared with controls (4.3 vs 0.3%).ConclusionWe have demonstrated that the STARSS methodology improves AEFI detection. Our findings should inform the wider use of SMS-based surveillance which is particularly relevant since establishing robust and novel pharmacovigilance systems is critical to monitoring novel vaccines which includes potential COVID vaccines.     

The safety of BCG revaccination: A systematic review

IntroductionRevaccination with Bacillus Calmette-Guérin (BCG) vaccine is not generally recommended due to a lack of proven efficacy of repeat doses for protection against tuberculosis. However, there is a growing interest in the use of BCG vaccine for its ‘off-target’ effects which might involve revaccination. We did a systematic review of the safety of BCG revaccination.MethodsMEDLINE (1946 to March 2020) and the BCG World Atlas (updated 2017) were searched, limiting to studies of BCG administration by the intradermal or percutaneous route. Adverse events as well as patient and vaccine characteristics were reviewed.ResultsThe search identified 388 articles, of which 24 met the inclusion criteria. These reported 22 studies comprising eight randomised trials, four case-control studies, four observational studies and six case series or reports. Overall, there was evidence for a small increase in the rate of mild local and systemic reactions. No serious adverse events were reported in immunocompetent individuals.ConclusionsEvidence to date suggests that revaccination with BCG vaccine carries minimal risk. Future studies of BCG vaccine for novel applications should report adverse event data stratified by prior BCG vaccination status.     

Pre-vaccination vulnerability and suspected adverse events following HPV vaccination. A case-control study nested in the Danish national birth cohort

Previous studies have indicated that girls experiencing suspected adverse events (AE) following HPV vaccination were more vulnerable prior to vaccination. However, no study has previously investigated differences in vulnerability using prospectively collected self-reported measures of vulnerability. The objective of this study therefore was to describe the distribution of biological and psychosocial indicators of vulnerability in girls referred to a hospital setting due to suspected adverse events and compare it with a sample of non-referred HPV vaccinated girls.The study was conducted as a case control study based within the Danish National Birth Cohort. Cases were defined as HPV vaccinated girls referred to a hospital setting between 2015 and 2017 due to suspected adverse events (n = 80), and 5 controls were randomly selected from the remaining source population, matched to cases on age at vaccination, region of residence and year of vaccination. The final study population consisted of 480 girls. Prior exposures were based on information gathered from an 11 year follow up of the DNBC and included information on self-rated health, frequent health complaints, medication use, bullying, stressful life events and physical activity. Conditional logistic regression analysis was used to estimate the association between each exposure and referral.The percentage of individuals in the exposed category of each exposure was generally higher for cases than controls. Particularly, the odds of being referred were higher for those with low self-rated health compared to high (OR [95%-CI] 2.43 [1.07–5.5]1), those being bullied (OR 3.19 [1.17–8.73]), and those who had taken medication (OR 2.22 [1.32–3.67]).Overall, these results indicated that girls experiencing suspected AE following HPV vaccination were more vulnerable prior to vaccination.     

Addressing alcohol and other drug use among young people from migrant and ethnic minority backgrounds: Perspectives of service providers in Melbourne,Australia

Young people from migrant and ethnic minority backgrounds are recognised as emerging priority populations for reducing alcohol and other drug (AOD)-related harms in Australia. Limited research has investigated how service providers address AOD challenges in migrant communities. In this qualitative study, we interviewed 15 service providers from AOD, migrant support, community and other health services in a diverse region of Melbourne. Interviews explored the challenges that service providers faced and the strategies they implemented to engage with young migrants in relation to AOD use. Thematic analysis was used to generate four themes: stigma as a barrier to service delivery, intergenerational differences between young people and parents, the need for outreach and establishing trust and understanding over time. Service providers believed that stigma prevented many young people from migrant backgrounds having open conversations about their AOD use with family members and professionals. Participants perceived that some parents had less AOD-related knowledge and lower English language proficiency than their children creating challenges for effective communication. Service providers recognised the importance of engaging with young people in settings where they felt comfortable rather than expecting them to approach their service. Participants also acknowledged the need to invest time in establishing trust and understanding with young migrants so they could facilitate conversations about AOD use as relationships evolved. Although service providers had a strong understanding of young people's needs, they found it challenging to build relationships in the context of funding and time constraints. Our results indicate the need for long-term funding and timelines that enable service providers to build strong relationships with young migrants, their families and their broader cultural communities to facilitate access to AOD support.     

洛匹那韦/利托那韦联合干扰素治疗新型冠状病毒肺炎的疗效

目的　探讨洛匹那韦/利托那韦联合干扰素治疗新型冠状病毒肺炎（新冠肺炎）的有效性及安全性。方法　选取2020年1月3日—4月7日于我中心住院治疗的62例新冠肺炎确诊患者作为研究对象,并将其分为治疗组（43例）和对照组（19例）,其中对照组采用常规对症支持治疗,治疗组在对照组常规治疗基础上使用洛匹那韦/利托那韦抗病毒治疗;同时,根据患者临床分型对上述患者实施非重症组与重症组亚组分析。比较对照组和治疗组核酸转阴时间、住院时间、退热时间、症状缓解时间及药物不良反应发生情况。结果　在非重症组患者中,治疗组与对照组在退热时间、症状缓解时间、核酸转阴时间及住院时间方面的差异均无统计学意义（P均＞0.05）;而在重症组患者中,治疗组核酸转阴时间显著长于对照组[（23.62±2.12 ）d vs.（9.25±0.95）d],差异有统计学意义（P＜0.05）。在药物不良反应方面,治疗组腹泻发生率为46.5%,显著高于对照组,差异有统计学意义（P＜0.05）,但均为轻到中等程度腹泻,经对症治疗后腹泻症状消失。结论　洛匹那韦/利托那韦联合干扰素治疗新冠肺炎非重症患者效果不明显,治疗重症患者,核酸转阴时间更长,虽临床应用总体安全性较好,但存在腹泻等不良反应,不推荐使用。