难治性狼疮性肾炎多靶点治疗前瞻性临床研究

目的以静脉环磷酰胺(CTX)冲击后续硫唑嘌呤(Aza)维持治疗为对照,前瞻性研究普乐可复(FK506)、霉酚酸酯(MMF)联合激素治疗狼疮性肾炎(LN)的疗效和安全性. 方法经肾活检诊断为Ⅳ、Ⅳ+Ⅴ、Ⅲ+Ⅴ型和Ⅴ型活动性LN 92例,男女比例为1676,年龄在12～60岁,随机分为多靶点治疗组(诱导期FK506剂量为3～4 mg/d,MMF剂量为0.75～1.0 g/d;维持期剂量FK506剂量为1.5～2.0 mg/d,MMF剂量为0.5～0.75 g/d)和CTX-Aza组[诱导期采用IVC治疗0.5～1.0 g/m2BSA,1/月,维持期予Aza治疗1～2 mg/(kg·d)].总疗程18个月,诱导期初定6个月;若6个月内未达完全缓解(CR),诱导期延长至9个月.两组患者均采用静脉甲基泼尼松龙冲击治疗后口服泼尼松[起始剂量0.6 mg/(kg·d)]治疗.主要评价指标为诱导治疗期完全缓解率(CR,定义为尿蛋白定量＜0.4 g/24h,尿红细胞＜10万/ml,无管型尿和白细胞尿,血白蛋白≥35 g/L,SCr正常或上升不超过基础值的15%. 结果(1)多靶点治疗组Ⅳ型LN诱导治疗期CR率与CTX-Aza组差异无统计学意义(75.0% vs 60.0%,P＞0.05).(2)多靶点治疗组Ⅳ+Ⅴ型LN诱导治疗期CR率显著高于CTX-Aza组(75.0% vs 16.7%.P＜0.05).并且治疗9个月时多靶点治疗组尿蛋白正常的患者比例也显著高于CTX-Aza组(72.7% vs 16.7%,P＜0.05).(3)多靶点治疗组,Ⅳ型、Ⅳ+Ⅴ型LN患者诱导治疗期CR率都较高,均为75.0%,其次是Ⅲ+Ⅴ型(66.7%).Ⅴ型LN诱导治疗期CR率最低,仅16.7%,显著低于Ⅳ型、Ⅳ+Ⅴ型LN(P＜0.05).(4)诱导治疗期由6个月延长至9个月后,多靶点治疗组Ⅳ+Ⅴ型LN、CTX-Aza组Ⅳ型和Ⅳ+Ⅴ型LN的CR率有所增加.(5)多靶点治疗组24例患者在诱导治疗完成后接受重复肾活检,结果显示肾组织AI评分均值由9.0±4.0降至2.1±1.7(P＜0.01),AI≥8分的患者比例也由75%降至4.2%(P＜0.01).同时肾组织CI评分均值由0.7±1.0增至2.2±1.3(P＜0.01),CI≥3分的患者比例从12.5%增加至37.5%(P＜0.05).(6)多靶点治疗组的不良反应包括肝酶升高、胃肠道症状、白细胞减少、感染、脱发、血压升高、糖代谢异常等,未见月经紊乱和停经报告.多靶点治疗组胃肠道症状、WBC减少、上呼吸道感染的发生率显著低于CTX-Aza组(P＜0.05);血压升高发生率则高于CTX-Aza组(17.74% vs 0%,P＜0.05). 结论多靶点诱导治疗对Ⅳ型、Ⅳ+Ⅴ型和Ⅲ+Ⅴ型LN均有显著疗效,并且不良反应较少,安全性较高.     

全国初治涂阴肺结核病例登记现状分析

目的 分析全国各省初治涂阴肺结核病例登记现状,为评价初治涂阴肺结核病例诊断质量提供依据.方法 根据2004-2005年全国结核病防治规划报表中初治涂阴和初治涂阳肺结核病例登记资料,分析各省2年初治涂阴肺结核病例登记率变化和增长幅度;统计各省及不同地区初治涂阴与初治涂阳肺结核病例登记率;对各省初治涂阴与初治涂阳肺结核病例登记率进行直线回归分析.结果 2005年全国登记初治涂阴肺结核病例316 405例,登记率为24.27/10万,各省登记率在6.01/10万～72.17/10万;2005年登记初治涂阴病例数比2004年增加了19.9%,其中2个省登记数呈负增长,其余各省登记数增长了0.5%～62.3%;2005年全国初治涂阳病例登记率是涂阴病例登记率的1.5倍,其中23个省初治涂阳病例登记率高于涂阴病例登记率,8个省相反;初治涂阴病例占初治涂阳病人登记率的比例,京津沪地区为149.28%,非项目地区为83.6%,项目地区为50.3%;对涂阳和涂阴病例登记率进行直线回归分析,回归方程y=22.342＋0.563 6x.结论 对初治涂阴肺结核患者实行免费政策后,全国涂阴肺结核病例登记率提高.但各省初治涂阴病例登记率和增长幅度以及涂阴病例登记率与涂阳病例登记率的比例悬殊.由于涂阴病例诊断困难,对于涂阴病例登记率高或增长幅度大的地区,特别在DOTS执行时间短和人力资源有限的地区,应对涂阴病例诊断质量予以进一步检查和评价.     

中国10省(市)流感成年人住院病例的临床特征及重症危险因素分析

目的 了解中国10省(市)严重急性呼吸道感染(SARI)住院病例哨点监测纳入的流感成年人住院病例的临床特征及重症危险因素。方法 对2009年12月至2014年6月中国10省(市)SARI哨点监测医院纳入的符合SARI定义的≥15岁病例进行流行病学和临床信息调查,采集呼吸道标本进行流感病毒核酸检测。按检测结果将病例分为流感住院组和非流感住院组,分析两组人口统计学信息、临床和流行病学特征,并分析重症危险因素。结果 10家哨点医院共纳入3 071例SARI成年人病例,其中实验室确诊240例(7.8%),以A(H1N1)pdm2009和A(H3N2)亚型流感病毒为主。病例年龄M为63岁,≥65岁老年人占47.1%。144例(60.0%)患有至少1种慢性基础性疾病,流感病例肺气肿比例(7.9%)高于非流感病例(3.8%),差异有统计学意义(χ²=3.963,P=0.047)。19.4%的流感育龄妇女为孕妇,240例流感病例中仅有1.1%在过去一年接种过流感疫苗。流感住院病例中咽痛、呼吸困难所占比例高于非流感住院病例。17.5%的流感病例收入重症监护室治疗,与非流感住院病例间的差异无统计学意义(P=0.160)。23.1%的流感病例在发病后使用了抗病毒药物治疗,高于非流感住院组(4.8%),差异有统计学意义(P<0.001)。流感住院病例中41.5%出现并发症,病毒性肺炎比例明显高于非流感组(P<0.001)。危险因素分析显示,发病入院时间>7 d(RR=1.673,95%CI:1.071～2.614)、患有哮喘(RR=15.200,95%CI:1.157～199.633)、免疫抑制疾病(RR=5.250,95%CI:1.255～21.960)、怀孕(RR=21.000,95%CI:1.734～254.275)是流感重症的危险因素。结论 成年人流感住院病例主要集中在≥65岁组,流感疫苗接种率极低、抗病毒药物使用不足,应推荐孕妇、老年人、慢性病病例等高危人群每年进行流感疫苗预防接种,流感住院病例应及早应用抗病毒药物。     

山东省泰安市2015—2019年输入性疟疾病例实验室诊断与复核结果分析

省、市、县三级实验室分别采用镜检法、胶体金法及巢式PCR法对泰安市2015-2019年输入性疟疾进行诊断与复核。共诊断与复核输入性疟疾病例122例,其中镜检法和胶体金法的符合率分别为94.3%(115/122)和95.9%(117/122),镜检阴性率为5.7%(7/122),均为恶性疟;胶体金法阴性率为4.1%(5/122),3例非恶性疟和2例恶性疟阴性,3种检验方法符合率差异有统计学意义(P <0.05)。其中恶性疟和间日疟诊断符合率最高,均达100%,对卵形疟诊断符合率最低,仅为12/18,对4种疟原虫实验室诊断符合率差异有统计学意义(P <0.01)。医疗机构中初诊合格率为94.3%(115/122),市、县级疾病预防控制机构复核合格率分别为97.5%(119/122)和95.1%(116/122),差异无统计学意义(P> 0.05)。今后应继续加强市、县级疟疾实验室镜检人员技能培训,积极开展疟疾核酸检测,以进一步提升医疗及疾病预防控制机构的疟疾诊断水平。     

输入性间日疟2例

湖北省五峰县是以间日疟为主的低疟区,通过综合防治,1990年初已基本消灭疟疾.此后末冉发现本地新感染病例,偶有未经正规治疗而复发病例,其症状轻微、不典型.2007年7月,发现2例从海南省打工返乡的间日疟输入性病例,报告如下.     

Microbial DNA in human nucleic acid extracts: Recoverability of the microbiome in DNA extracts stored frozen long-term and its potential and ethical implications for forensic investigation

Human DNA samples can remain unaltered for years and preserve important genetic information for forensic investigations. In fact, besides human genetic information, these extracts potentially contain additional valuable information: microbiome signatures. Forensic microbiology is rapidly becoming a significant tool for estimating post-mortem interval (PMI), and establishing cause of death and personal identity. To date, the possibility to recover unaltered microbiome signatures from human DNA extracts has not been proven. This study examines the microbiome signatures within human DNA extracts obtained from six cadavers with different PMIs, which were stored frozen for 5–16 years. Results demonstrated that the microbiome can be co-extracted with human DNA using forensic kits designed to extract the human host’s DNA from different tissues and fluids during decomposition. We compared the microbial communities identified in these samples with microbial DNA recovered from two human cadavers donated to the Forensic Anthropology Center at Texas State University (FACTS) during multiple decomposition stages, to examine whether the microbial signatures recovered from “old” (up to 16 years) extracts are consistent with those identified in recently extracted microbial DNA samples. The V4 region of 16 S rRNA gene was amplified and sequenced using Illumina MiSeq for all DNA extracts. The results obtained from the human DNA extracts were compared with each other and with the microbial DNA from the FACTS samples. Overall, we found that the presence of specific microbial taxa depends on the decomposition stage, the type of tissue, and the depositional environment. We found no indications of contamination in the microbial signatures, or any alterations attributable to the long-term frozen storage of the extracts, demonstrating that older human DNA extracts are a reliable source of such microbial signatures. No shared Core Microbiome (CM) was identified amongst the total 18 samples, but we identified certain species in association with the different decomposition stages, offering potential for the use of microbial signatures co-extracted with human DNA samples for PMI estimation in future. Unveiling the new significance of older human DNA extracts brings with it important ethical-legal considerations. Currently, there are no shared legal frameworks governing the long-term storage and use of human DNA extracts obtained from crime scene evidence for additional research purposes. It is therefore important to create common protocols on the storage of biological material collected at crime scenes. We review existing legislation and guidelines, and identify some important limitations for the further development and application of forensic microbiomics.     

Electrolyte analysis of pleural effusion for discrimination between seawater and freshwater drowning in decomposed bodies

ObjectiveThe diagnosis of drowning is an important issue in forensic investigations. Moreover, discriminating between seawater and freshwater drowning is crucial to identify where the drowning occurred. The present study aimed to investigate electrolyte concentrations in pleural fluid in decomposed bodies in late postmortem intervals and derive cut-off values for the diagnosis of seawater and freshwater drowning.Study designData were collected from 44 seawater drowning cases, 60 freshwater drowning cases, and 30 non-drowning cases with pleural effusion which served as controls. The levels of sodium ion (Na⁺), potassium ion (K⁺), and chloride ion (Cl⁻) of pleural fluid were measured, and two indices were calculated: summation of Na⁺ and K⁺ levels (SUM _Na + K), and summation of Na⁺, K⁺, and Cl⁻ levels (SUM _{Na + K + Cl}). The means of the three ion concentrations and two indices significantly differed between the three groups (p < 0.0001).ResultsThe receiver operating characteristic analysis revealed that the sensitivity and specificity were both 1.000 for SUM _{Na + K + Cl} of 288.3 mEq/L between the seawater and control groups. The Na⁺ value of 109.0 mEq/L also had a high sensitivity of 0.977 and a specificity of 0.933 in the seawater and control groups. The sensitivity and specificity were 0.967 and 1.000, respectively, for SUM _Na + K of 123.2 mEq/L between the freshwater and control groups.ConclusionThe electrolyte concentrations in pleural effusion may be useful for the diagnosis of drowning in decomposed bodies with a longer postmortem interval.     

A nationwide population-based study of the familial aggregation of Type 1 (insulin-dependent) diabetes mellitus in Denmark

Summary The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0–19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r=0.5, p=0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p<0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986–1989) an increasing trend in incidence was observed. However, an increase in incidence compared to previous Danish data from the 1970s and 1980 s could not be demonstrated.The Danish Study Group of Diabetes in Childhood is an association of paediatricians with a special interest in diabetes research. For participating departments in the present study see Acknowledgements     

The perception of shared medical decision making of expert and lay people: Effects of observing a movie clip depicting a medical consultation

Objective

To test for differences between experts and lay people in assessment of the degree to which a doctor engaged in a shared decision making (SDM) with a patient using the OPTION scale and a movie clip as stimulus material.

Methods

A segment of the movie ‘Wit’, depicting the communication of the diagnosis and the therapy proposed of a cancer, was shown to (a) university students with no knowledge about doctor–patient communication; (b) nurses working in medicine departments; (c) advanced medical students; (d) hospital physicians. The participants were asked to complete the OPTION scale which measures the extent to which physicians involve patients in medical decisions. An analysis of variance was used to compare OPTION scores across the four groups and to compare males and females.

Results

Being female [F_(1,190) = 11.9; p < .001] and being familiar with medical issues [F_(3,190) = 11.09; p < .001] were both significantly associated with a negative evaluations of the doctor's ability to involve the patient in the SDM.

Conclusion

Lay people and males (including male experts), are less demanding regarding SDM abilities.

Practice implications

A more systematic use of videos and the OPTION scale as validated outcome measure could be helpful educational strategy for the teaching of SDM.     

2016-2018年长沙市人群及活禽市场环境H5N6亚型禽流感病毒监测分析

目的开展2016-2018年长沙市人群感染和活禽市场(live poultry markets,LPMs)环境污染H5N6亚型禽流感病毒(avian influenza virus,AIV)监测,为防控人感染H5N6亚型AIV提供实验室数据。方法采集2016-2018年长沙市流感样病例和不明原因肺炎病例咽拭子6909份及LPMs环境样品1719份,利用实时RT-PCR进行A型、H5、H7、H9和N6亚型AIV核酸扩增,并对82份AIV核酸阳性样品进行高通量核苷酸测序,然后对测序结果进行BLAST比对和氨基酸(amino acids,aa)关键位点分析。结果从6909份病例的咽拭子样品中检出H5N6亚型AIV核酸阳性1份,从1719份LPMs环境样品中检出A型AIV核酸阳性927份(53.93%),H5N6亚型AIV核酸阳性193份(11.23%)。高通量核苷酸测序获得14株H5N6亚型AIV的基因组序列,aa关键位点分析显示病毒血凝素(hemagglutinin,HA)蛋白连接肽第338~347位出现6个碱性aa,对禽表现为高致病性的分子特征,受体结合位点(receptor binding site,RBS)第238~240位aa(对应H3型流感病毒第226~228位编码aa)为QSG或QRG,受体特征为禽源。神经氨酸酶(neuraminidase,NA)蛋白第290位耐药基因位点aa未出现R290K突变现象,对NA抑制剂(达菲/磷酸奥司他韦)敏感;病毒PB2蛋白发生E627K和D701N(I)突变,表明病毒致病力强。结论长沙市人群感染H5N6亚型AIV为偶发,LPMs环境H5N6亚型AIV污染较重,需要进一步加强LPMs环境AIV监测。