军队停止卡介苗接种策略的综合性评价

[目的]了解部队卡介苗接种现况及效果,评价停止卡介苗接种策略的可行性.[方法]采用卡痕检查、抗体测定、病例对照研究和发病率比较等综合分析.[结果]老兵卡痕率和结核菌素阳性率均高于新兵(P＜0.01),新兵入伍前卡介苗未初种亦未自然感染者约占20%;病例组卡痕率小于对照组,比数比(OR)为0.42,95%CI为0.23～0.76;卡介苗接种后抗-PPD阳性率高于接种前(P＜0.01),但接种后结核菌素试验阴性与阳性者抗体水平无明显差异;停止卡介苗接种3年,肺结核发病率下降约50%.[结论]卡介苗预防成人结核病仍具有一定效果,但以每年对新兵普查普种作为预防和控制结核病的主要措施已不适用.     

Recombinant BCGs for tuberculosis and bladder cancer

Bacillus Calmette–Guérin (BCG) vaccine is an attenuated live strain of Mycobacterium bovis. It may be the most widely used vaccine in human history and is the only licensed human tuberculosis (TB) vaccine available. Despite its excellent safety history, a century of use in global vaccination programs, and its significant contribution to reducing TB mortality among children, the efficacy of BCG continues to be disputed due to its incomplete protection against pulmonary TB in adults. Still vaccines offer the best chance to contain the ongoing spread of multi-drug resistance TB and disease dissemination. The development of improved vaccines against TB therefore remains a high global priority. Interestingly, recent studies indicate that genetically modified BCG, or administration of existing BCG through alternate routes, or revaccination, offers improved protection, suggesting that BCG is well poised to make a comeback.Intravesical BCG is also the only approved microbial immunotherapy for any form of cancer, and is the first-line therapy for treatment-naïve non-muscle invasive bladder cancer (NMBIC), which represents a majority of the new bladder cancer cases diagnosed. However, almost a third of patients with NMIBC are either BCG unresponsive or have tumor recurrence, leading to a higher risk of disease progression. With very few advances in intravesical therapy over the past two decades for early-stage disease, and a limited pipeline of therapeutics in Phase 3 or late Phase 2 development, there is a major unmet need for improved intravesical therapies for NMIBC. Indeed, genetically modified candidate BCG vaccines engineered to express molecules that confer stronger protection against pulmonary TB or induce potent anti-tumor immunity in NMIBC have shown promise in both pre-clinical and clinical settings. This review discusses the development of second generation, genetically modified BCG candidates as TB vaccines and as anti-tumor adjuvant therapy for NMIBC.     

新生儿接种卡介苗引发淋巴结强反应56例分析

目的总结56例卡介苗所致淋巴结强反应的临床表现,评价局部治疗效果。方法收集2010年1月-2014年5月结核病门诊56例由卡介苗所致淋巴结强反应患儿,根据其临床表现,分别给予热敷、清创引流及敷药等局部治疗,并分析疗效。结果 1)分型:结节未液化型7例,液化型20例,脓肿破溃型23型,术后伤口未愈者6例。2)疗效:7例未液化型经局部热敷,5例结节缩小,2例结节液化;22(20+2)例液化型经穿刺针吸及结节内注射异烟肼,均化脓破溃;45(23+22)例脓肿破溃型经清创引流,利福平外敷,伤口愈合;6例手术后伤口未愈者经清创引流、利福平外敷,伤口愈合。结论新生儿接种卡介苗所致淋巴结强反应临床表现多样,局部治疗效果好。     

丝裂霉素与卡介苗膀胱灌注预防浅表膀胱癌术后复发比较

目的 比较丝裂霉素（MMC）与卡介苗（BCG）膀胱灌注预防浅表膀胱癌术后复发的疗效及毒副作用。方法 回顾分析1996年8月-2006年8月间在我院手术的132例浅表性膀胱癌患者的临床资料。结果 128例患者获随访,中位随访时间62.7（6.6-122.0）个月,总的复发率为21%,从手术到肿瘤局部复发的平均时间为13.8月（3.6-71.8）个月。5年和10年总的无复发生存率为80.7%和71.3%。MMC组与BCG组的总复发率分别为21.8%和18.5%,两组之间无显著差异（P=0.087）。对于高分级肿瘤,MMC组的复发率（24.0%）显著高于BCG组（17.5%）,BCG膀胱灌注能显著降低高分级膀胱肿瘤的术后复发率（P=0.046）。BCG组患者出现膀胱炎等毒副作用的机率较高（P=0.0316）。结论 BCG膀胱灌注预防浅表性膀胱癌术后复发较MMC无明显优势,且出现膀胱炎等毒副作用的机率较高,但可显著降低高分级膀胱肿瘤的术后复发率。     

丝裂霉素与卡介苗膀胱灌注预防浅表膀胱癌术后复发比较

目的比较丝裂霉素(MMC)与卡介苗(BCG)膀胱灌注预防浅表膀胱癌术后复发的疗效及毒副作用。方法回顾分析1996年8月~2006年8月间在我院手术的132例浅表性膀胱癌患者的临床资料。结果128例患者获随访,中位随访时间62.7(6.6~122.0)个月,总的复发率为21%,从手术到肿瘤局部复发的平均时间为13.8月(3.6~71.8)个月。5年和10年总的无复发生存率为80.7%和71.3%。MMC组与BCG组的总复发率分别为21.8%和18.5%,两组之间无显著差异(P=0.087)。对于高分级肿瘤,MMC组的复发率(24.0%)显著高于BCG组(17.5%),BCG膀胱灌注能显著降低高分级膀胱肿瘤的术后复发率(P=0.046)。BCG组患者出现膀胱炎等毒副作用的机率较高(P=0.0316)。结论BCG膀胱灌注预防浅表性膀胱癌术后复发较MMC无明显优势,且出现膀胱炎等毒副作用的机率较高,但可显著降低高分级膀胱肿瘤的术后复发率。     

矽肺大鼠肺脏对不同侵入途径、不同抗原的免疫应答

目的 通过观察矽肺大鼠肺脏对不同途径、不同抗原的免疫应答,探讨矽肺易受感染的免疫学机制。方法分别2次通过气道、腹腔途径给予矽肺大鼠模型及正常对照动物绵羊红细胞(SRBC)或卡介苗(BCG)进行免疫后,再观察皮内注射SRBC及BCG动物迟发性变态反应;实验终期检测血清和肺灌洗回收液特异性IgG水平及细胞因子浓度。结果SRBC免疫后矽肺气道免疫组表现出异常强烈的迟发性变态反应,矽肺气道BCG免疫各组出现相同反应;两种抗原免疫后矽肺动物血清及肺灌洗液特异性IgG水平显著高于正常对照组;BCG免疫动物中,矽肺气道免疫组动物肺灌洗液IFN-γ水平显著高于矽肺腹腔免疫组及正常对照组,3个组的TNF-α水平差异无显著性;SRBC免疫动物3个组的IFN-γ水平差异无显著性。结论矽肺对肺局部以及机体免疫功能具有明显影响,导致对外来抗原产生异常强烈的体液免疫反应和迟发性变态反应;肺局部参与细胞免疫调节的细胞因子对不同抗原有不同反应。     

DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled,double-blind phase 2b trial

BackgroundSRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13–15 years in Tanzania.MethodsAdolescents with a negative T- SPOT.TB^R interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA).ResultsAmong 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03).ConclusionsA three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted.Trial Registration. The trial is registered at ClinicalTrials.gov as NCT02712424.     

Quality of life aspects of bladder cancer: A review of the literature

Not much is generally known regarding the burden imposed by bladder cancer upon patient health-related quality of life (HRQL). The role of HRQL in affecting patient preferences and utility assessment and, ultimately, the selection of therapeutic regimen, or patient satisfaction with that selection, is considered increasingly important by the medical community. Therefore, the main focus of this evaluation was to review the international medical literature to better understand the impact of bladder cancer on patient HRQL. A search was performed using electronic and manual databases for published articles on HRQL and bladder cancer for the years 1966 onward. Thirty-five references dealing with HRQL were analyzed as part of this review. Of these, 29 were published after 1989. Most studies have identified urinary and sexual HRQL domains as being of greatest concern to patients. However, little is known about the short- and long-term impacts of specific therapeutic options for either superficial bladder cancer (SBC) or invasive bladder cancer (IBC). Increased awareness and use of the HRQL instruments such as the FACT-BL as well as the EORTC-QLQ-BLS24 and the EORTC-QLQ-BLM30 (when they are validated for SBC and IBC, respectively), should increase our understanding of the impact of this disease and its management options on patient HRQL.     

Evidence-based prevention (EBP): A review of cytochrome P450 expression in the bronchial epithelium and new approach to lung cancer prevention

The number of fatalities in Japan attributable to lung cancer exceeded 50000 in 2001. It is socially desirable that various markers, which can be utilized for the prevention of lung cancer, be established. We believe that smoking or exposure to carcinogens in air induces mutations in bronchial and alveolar epithelia, leading to the development of lung cancer. It would be useful to have markers of individual differences in susceptibility to chemical carcinogen-induced lung cancer 1) to identify genetic polymorphisms of enzymes metabolizing chemical carcinogens and 2) to investigate the expression of enzymes metabolizing chemical carcinogens. In this paper, we review CYP expression in the bronchial epithelium. CYP1, CYP2 and CYP3 are expressed in the bronchial epithelium. We also show the relationship between the genetic polymorphisms of cytochrome P450 (CYP) and a person’s susceptibility to chemical carcinogen-induced lung cancer. We demonstrate the relationship between cigarette consumption and the CYP expression profile in the bronchial epithelium. To maintain and promote public health, we must apply evidence, such as CYP polymorphisms and CYP profiles to disease prevention and also to aggressively advance evidence-based prevention (EBP) of lung cancer. This article is based upon the research that was given Encouragement Award at the 75th Annual Meeting of the Japanese Society for Hygiene held in Niigata, Japan on March 27–30, 2005.     

宫颈癌患者膀胱充盈状态在首次放射治疗与CT模拟定位间的相对变化

目的:研究宫颈癌患者在首次放射治疗与CT模拟定位时,膀胱充盈状态的变化情况,为进一步提高宫颈癌放射治疗精度提供参考依据.方法:选取医院收治的21例宫颈癌患者,依据首次放射治疗前采集的锥形束CT(CBCT)图像勾画膀胱结构,并最终显示在已配准的CT图像,从中获得膀胱结构在CBCT与定位CT图像中的相对体积、位置差异及形状...     

A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines

Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine.     

A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro

Maturation of dendritic cells (DC) can be triggered in vitro by inflammatory cytokines or Toll-like receptor (TLR) ligands such as CpG or polyI:C. Corresponding, well-characterized agents which can be applied in clinical settings are sparse. We have evaluated a clinical grade, non-toxic analogue of polyI:C, poly(I:C12U) (Ampligen), as a potential adjuvant for cancer immunotherapy, for its ability to drive maturation of human myeloid DC. Our results provide evidence that poly(I:C12U) is effective in inducing optimal phenotypic (elevated levels of MHC-Class I/Class II, CD83, CCR7, CD86 and CD40 molecules) and functional maturation of human DC in vitro, capable of promoting the production of the inflammatory (Th1-type) cytokine IL-12, with significantly lower levels of IL-10 production, compared to that induced by the parent compound polyI:C. Importantly, poly(I:C12U) has a comparable effect on the maturation and function of DC derived either from healthy donors or cancer patients indicating that it is able to overcome any immune suppressive factors associated with the tumour bearing state. These characteristics make poly(I:C12U) a suitable agent for use as an adjuvant in cancer directed immunotherapeutic regimes.     

Quality of life three months and one year after first treatment for early stage breast cancer: Influence of treatment and patient characteristics

This paper reports the quality of life (QoL) of a large cohort of Australian women three and twelve months after surgery for early stage breast cancer (ESBC), and shows that the impact of disease and treatment on QoL differed by age, education and marital status. Eighty-three percent of eligible patients were recruited; 86% had breast conserving surgery and 14% mastectomy. Response rates were 93% (n = 305) at three months and 88% (n = 291) at one year. Quality of life was measured with the EORTC core questionnaire (QLQ-C30) and an ESBC-specific questionnaire. Multilevel analysis was used to estimate the effects and interactions of time, treatment and patient characteristics. Most symptoms declined between three months and one year, but arm and menopausal symptoms persisted. Emotional, social and role functioning improved over time, and fear of disease recurrence diminished. Younger women faired worse than older women on a broad range of QoL dimensions. Single women and those with less education faired worse on a number of dimensions. The negative impact of mastectomy on body image was greatest among married women, particularly young married women. These sociodemographic distinctions are relevant when discussing treatment options with women facing a diagnosis of ESBC. This revised version was published online in June 2006 with corrections to the Cover Date.     

The performative function of expectations in translating treatment to prevention: The case of HIV pre-exposure prophylaxis,or PrEP

This paper is about expectations of oral PrEP, ‘a pill a day’ HIV pre-exposure prophylaxis that could be the first systemic form of HIV prevention for sexual or needle stick exposures. If found safe and effective—a difficult criteria to establish and, as such, is central to this paper—PrEP has the potential to significantly alter HIV prevention, well ahead of a vaccine or topical microbicide. Hence, despite uncertainty about PrEP's viability, the potential significance of its impact on the HIV field requires early planning. In order to address this potentiality, we use a methodological approach drawn from the sociology of expectations to examine interviews with United States-based scientific stakeholders in the trialing of PrEP. We identify how PrEP is anticipated as both stable object and process involving multiple contingencies. These divergent conceptions enable us to illuminate a range of social, cultural, ethical, pharmaceutical and medical possibilities understood to potentially arise with PrEP. Further, they lead us to propose that the multiple contingencies that enact PrEP as an emergent entity offer scope for rethinking PrEP and, more broadly, the challenges of HIV prevention.     

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: A transmission-dynamic modelling study

Background

Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada.

Methods

We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost.

Findings

Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900–24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated.

Interpretation

Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls.     

How quality of life data contribute to our understanding of cancer patients' experiences? A study of patients with lung cancer

A prospective study was conducted to measure quality of life in newly diagnosed lung cancer patients attending a chest clinic in a large teaching and district general hospital in a geographically defined area (northern sector of Glasgow, Scotland). Quality of life was assessed at two points in time, pre-diagnosis (baseline) and 3 months after diagnosis (follow-up) using three standard measures; the Nottingham Health Profile (NHP); the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and its lung cancer supplement (QLQ-LC13). Out of 133 lung cancer patients diagnosed during the study period, 129 patients (97%) were interviewed pre-diagnosis. Of these, only 63% of the patients had an active treatment. Ninety-six patients were alive at follow-up, of whom 82 patients were re-interviewed. Thus, only 82 patients who had complete data were used in the analysis. Comparing patients' pre-diagnosis and follow-up scores on the NHP, only sleep difficulties improved slightly. Patients reported increased perceived health problems of all other characteristics studied (energy, p = 0.0004; physical mobility, p = 0.0008). Similar results were observed on the EORTC questionnaires indicating that patients' functioning and global quality of life had decreased. The only significant improvement after 3 months was seen in patients' cough (p = 0.006). There were marked increases in hair loss (p > 0.0001), constipation (p = 0.007), and sore mouth (p = 0.0004). The findings suggest that patient-centred variables should receive sufficient consideration in the treatment of lung cancer. The study results clearly indicate that information on quality of life contributes to our understanding of patients' experiences of their cancer treatment.     

Improving informed consent: pilot of a decision aid for women invited to participate in a breast cancer prevention trial (IBIS-II DCIS)

Background  Patients and clinicians report difficulties with the process of informed consent to clinical trials and audiotape audits show that critical information is often omitted or poorly presented. Decision aids (DAs) may assist in improving consent.
Aims  This study piloted a DA booklet for a high priority breast cancer prevention trial, IBIS-II DCIS, which compares the efficacy of an aromatase inhibitor (anastrozole) with tamoxifen in women who have had surgery for ductal carcinoma in situ (DCIS).
Method  Thirty-one Australian women participating in the IBIS-I breast cancer prevention trial and who are currently in follow-up agreed to read the IBIS-II DCIS participant information sheet and the DCIS DA booklet, complete a set of standardized questionnaires, and provide feedback on the DA via a semi-structured phone interview.
Results  Women found the DA helpful in deciding about trial participation, reporting that it aided their understanding over and above the approved IBIS-II DCIS participant information sheet and was not anxiety provoking. Women's understanding of the rationale and methods of clinical trials and the IBIS-II DCIS trial was very good; with more than 80% of items answered correctly. The only areas that were not understood well were the concepts of randomization and blinding.
Conclusions  This study suggests that the DA will be acceptable to and valued by potential participants in the IBIS-II DCIS study. The revised DA is currently being evaluated prospectively in a randomized controlled trial. If successful, such DAs could transform the consent process to large clinical trials and may also reduce dropout rates.