国内中医药非劣效/等效性随机对照试验报告质量评价

目的评价当前中医药非劣效/等效性随机对照试验(RCT)的报告质量。方法计算机检索中医药研究中采用非劣效/等效性试验设计的RCT报告,参照CONSORT声明扩展版——非劣效和等效性随机对照试验的报告标准对纳入的报告进行质量评价。结果共纳入中医药非劣效/等效性RCT报告13篇。报告质量除存在一般RCT常见问题以外,非劣效/等效性试验相关的一些内容报告不够充分:①文题不能反映文献的最重要内容;②背景的介绍比较简单,未明确非劣效/等效性试验的理论基础、参照处理(阳性对照)的有效性等;③全部文献均未说明非劣效/等效性试验的受试者、干预措施和结局是否与既往确立参照处理有效性的试验中用到的相似或相同;④大部分文献未确定非劣效/等效性界值,未进行样本含量的估算;⑤仅半数文献对非劣效/等效性检验方法有所描述;⑥部分文献存在误下非劣效/等效性结论的问题。结论研究者对非劣效/等效性试验理论基础的认识仍需深入,参照CONSORT声明的扩展——非劣效和等效性随机对照试验的报告标准,有助于研究者明确非劣效/等效性RCT设计、实施和报告的重点,重视非劣效/等效性试验报告的相关内容,从根本上提高此类临床试验报告的质量。     

心血管治疗类医疗器械非劣效性试验特点及界值设置的系统评价

目的 系统评价心血管领域以医疗器械为干预的非劣效性试验,调查其试验特征和界值设置情况。方法 计算机检索PubMed、Embase、CENTRAL数据库,搜集心血管领域医疗器械类的非劣效性试验,检索时限均为建库至2023年7月26日。由2名研究者独立筛选文献、提取资料后,对纳入研究的基本特征、非劣效性试验特征和界值特征进行报告。研究使用Excel 2020和R 4.2.1软件进行分析。结果 共纳入214篇研究,其中167篇（78.0%）干预为冠状动脉支架,试验以双臂设计为主（92.9%）,多采用非劣效性绝对界值（96.7%）作为非劣效性的判定依据。150篇（70.1%）研究基于预估的对照组效应值确定非劣效性界值,其中33篇（15.4%）研究未报告预估的对照组效应值来源。非劣效性试验终点结局指标多样且界值设置差异较大,靶病变失败率（2.1%～8.6%）、靶血管失败率（2.5%～19.6%）和主要心血管不良事件发生率（2.1%～10.0%）是研究数量最多的三项定性指标,晚期管腔丢失（0.1～0.4 mm）是研究数量最多的定量指标。所有指标的非劣效性绝对界值转化为相对界值后,范围为1.20～3...     

Statin therapy is associated with fewer deaths in patients with bacteraemia

Objective Beneficial effects with statin use are increasingly reported in a variety of patient groups. There is in vitro and clinical evidence for its antiinflammatory and immunomodulatory therapeutic roles. We aimed to assess the association between statin administration and mortality in bacteraemic patients.Design A retrospective cohort analysis.Setting A 300-bed acute general hospital.Patients and participants All patients (n=438) requiring hospital care for an episode of bacteraemia during the years 2000–2003 were included. Statin use, patient outcome, and clinical and laboratory variables were collected.Interventions None.Measurements and results There was a significant reduction in all-cause hospital mortality (10.6% vs. 23.1%, p=0.022) and death attributable to bacteraemia (6.1% vs. 18.3%, p=0.014) in patients who were receiving statin therapy at the time of bacteraemia (n=66). The reduction in all-cause hospital mortality (1.8% vs. 23.1%, p=0.0002) and death attributable to bacteraemia (1.8% vs. 18.3%, p=0.0018) was more pronounced in the patients who continued to receive statin therapy after the diagnosis of bacteraemia (n=56). The apparent mortality benefit persisted after controlling for differences between the groups. Statin use prior to admission was associated with a reduced adjusted hospital mortality rate (odds ratio 0.39; CI 95% 0.17, 0.91; p=0.029), and continuing statin use after bacteraemia increased this effect (odds ratio 0.06; CI 95% 0.01, 0.44; p=0.0056).Conclusion This retrospective study demonstrates a significant survival benefit associated with continuing statin therapy in bacteraemic patients. The potential for statins as an adjuvant therapy in sepsis warrants further investigation.Electronic Supplementary Material Supplementary material is available in the online version of this article at Work was performed at Ipswich Hospital (Ipswich) and Princess Alexandra Hospital (Brisbane), Australia.This article refers to the editorial at .The authors have no financial interest in the products discussed in this paper. The authors have not received sponsorship or funding or have any conflicts of interest.     

Excess leukocytosis (leukemoid reactions) associated with malignant diseases

Twenty-one patients with malignancy had a peripheral white blood cell count of 50,000/cu mm or more. The malignancies arose from several tissues, especially lung; all were carcinomas except for one osteogenic sarcoma. In no case was there evidence of leukemia as defined by disorderly marrow growth, abnormal chromosomes, or abnormal leukocyte alkaline phosphatase levels. The peripheral blood of these patients showed segmented neutrophils, bands, and occasional metamyelocytes. When young cells such as myelocytes were seen, they did not persist. A high WBC with malignancy is a late phenomenon, usually occurring shortly before death, and does not correlate with any pathologic findings such as necrosis, white cell infiltration of the tumor, or specific inflammatory changes. most of the associated tumors are of giant cell size, but serum showed no evidence of colony stimulating activity. This was true of two tumors reported in the literature, yet the tumors could be shown in vitro to produce colony stimulating activity. The tumor probably does produce some type of granulocytopoietin, but methods for detecting it are presently limited.     

Excess risk of temporomandibular disorder associated with cigarette smoking in young adults

Evidence suggests that the effect of cigarette smoking on chronic pain is stronger in younger than older adults. This case-control study investigated whether age modified an effect of smoking on temporomandibular disorder (TMD) in 299 females aged 18 to 60 years. It also investigated the extent to which this relationship was explained by psychological profile, inflammatory response, and allergy. Cases were defined using the Research Diagnostic Criteria for Temporomandibular Disorders based on clinical examination. Psychological profile was evaluated using standardized instruments. Inflammatory response was evaluated with 11 cytokines isolated in plasma. History of allergy conditions was self-reported. Odds ratios (ORs) for the effect of smoking were calculated using binary logistic regression. Stratified analyses and the likelihood ratio test examined effect modification by smoking. Compared with nonsmokers, ever smokers aged <30 years had higher odds of TMD (OR = 4.14, 95% CI: 1.57, 11.35) than older adults (OR = 1.23, 95% CI: .55, 2.78) (P (effect modification) = .038). Adjustment for psychological profile, cytokines, and history of allergy-like conditions attenuated the effect by 45% to statistical nonsignificance. The main finding was reproduced with secondary analyses of 2 nationally representative surveys of adults conducted in the US and Australia. PERSPECTIVE: This study showed that smoking was associated with TMD risk in females, but only in young adulthood. It replicated this finding in 2 nationally representative surveys of females in the US and Australia. Findings may alert clinicians to recognize that smoking is a concern for TMD in younger female patients.     

替加环素治疗48例异基因造血干细胞移植后感染的安全性

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AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticus-Acinetobacter baumannii complex

OBJECTIVES: To investigate the role of the AdeABC multidrug efflux pump in the decreased susceptibility of clinical isolates of Acinetobacter calcoaceticus-Acinetobacter baumannii complex to tigecycline. METHODS: Gene expression was analysed by Taqman RT-PCR. A single cross-over achieved insertional inactivation of the adeB gene with a suicide plasmid construct carrying an adeB fragment obtained by PCR. Analysis of the adeRS locus was performed by PCR and sequencing. Ribotyping was performed with the RiboPrinter system. MICs were determined by Etest. RESULTS: Expression analysis revealed constitutive overexpression of adeABC in less-susceptible clinical isolates G5139 and G5140 (tigecycline MIC=4 mg/L) when compared with the isogenic clinical isolates G4904 and G5141 (MIC=1.5 mg/L). Insertional mutants GC7945 (adeB knockout in G5139) and GC7951 (adeB knockout in G5140) were obtained, which resulted in tigecycline MICs of 0.5 mg/L. As reported previously, the expression of adeABC is regulated by the two-component signalling system encoded by the adeR and adeS genes. PCR and sequencing analyses revealed an insertion of an IS(ABA-1) element in the adeS gene of G5139 and G5140. CONCLUSIONS: The results of this study suggest that decreased susceptibility to tigecycline in the A. calcoaceticus-A. baumannii complex is associated with the overexpression of the AdeABC multidrug efflux pump.     

Problems associated with randomized controlled clinical trials in breast cancer

The domination of the randomized controlled clinical trial in clinical research in breast cancer is questioned in the context of adjuvant therapy. The criteria for selection of cases by TNM classification are shown to be poorly related to tumour behaviour. The factors that determine outcome — the presence or absence of metastases, their size at the time of presentation of the primary cancer and their growth rate — are not measured. Metastases cannot be detected at sizes below about 10 mm in diameter. This represents about 30 doublings of volume or three-quarters of the life span of the tumour. There is no identifiable starting point for a trial. It is possible to estimate growth rates from the rates of shrinkage in response to primary medical treatment. Modelling of the times at which metastases may appear in the clinic from different possible starting sizes reveals that the usual end points of time from primary diagnosis to metastasis or death have an enormous intrinsic variability. Treatment is merely another confounding variable. The randomized controlled clinical trial is shown to be a poor tool for the investigation of adjuvant treatments. An alternative approach, based upon observation of individual tumour response to primary medical treatment, is commended.