2012年版欧洲肝病学会慢性乙型肝炎病毒感染管理临床应用指南更新要点

2012年3月,欧洲肝病学会在Journal of Hepatology在线发布《慢性乙型肝炎病毒感染管理临床应用指南》(以下简称《指南》).该《指南》是基于2009版指南更新的,其更新要点如下. 一、流行病学 2012年版《指南》更新了未经治疗的慢性HBV感染随访研究结果,在未经治疗的慢性乙型肝炎(CHB)患者中,5年累计肝硬化发生率为8％～20％;代偿期肝硬化患者中,5年累计失代偿期肝硬化发生率约20％;失代偿期肝硬化患者的5年生存率为14％～35％;肝硬化患者中,每年肝细胞癌(HCC)发生率为2％～5％[1].     

Caspofungin for invasive candidiasis at a tertiary care medical center

Background

Caspofungin is emerging as first-line therapy for invasive candidiasis. Data on the use of caspofungin for treatment for invasive candidiasis are limited to clinical trials and case reports. We report a single-center experience with 104 consecutive courses of caspofungin for the treatment of invasive candidiasis to evaluate a real-world performance of this drug.

Methods

A retrospective chart review of patients receiving caspofungin at a tertiary care medical center was performed. Patient information and microbiologic data were abstracted from patient charts and electronic medical records.

Results

Of 241 patients receiving caspofungin for all indications, 122 (51%) had proven invasive candidiasis. There were 104 treatment courses for candidiasis in 99 patients available for review. Bloodstream (66%) and abdominal infections (25%) were the most common sites of infection. Most infections were non-albicans (80/104, 77%; including patients infected with more than one species). Clinical cure rates at the end of therapy were 83% (57/69) for bloodstream infections and 84% (22/26) for abdominal infections. Caspofungin did not clear candidiasis in 14 episodes (microbiologic cure rate 75%, 42/56).

Conclusions

The clinical use of caspofungin has been successful in the treatment of invasive candidiasis, even in patients with prior antifungal exposure. In this unselected review, caspofungin performed similarly as in clinical trials, and clinicians should consider caspofungin as first-line therapy for invasive candidiasis, particularly non-albicans species.     

Canadian Association of Gastroenterology policy on the application for,and implementation of,clinical practice guidelines

An important mandate of the Canadian Association of Gastroenterology (CAG), as documented in the Association’s governance policies, is to optimize the care of patients with digestive disorders. Clinical practice guidelines are one means of achieving this goal. The benefits of timely, high-quality and evidenced-based recommendations include:

• Enhancing the professional development of clinical members through education and dissemination of synthesized clinical research;
• Improving patient care provided by members by providing focus on quality and evidence;
• Creating legislative environments that favour effective clinical practice;
• Enhancing the clinical care provided to patients with digestive disease by nongastroenterologists; and
• Identifying areas that require further information or research to improve clinical care.

The present document provides the foundation required to ensure that clinical practice guidelines produced by the CAG are necessary, appropriate, credible and applicable. These recommendations should be adhered to as closely as possible to obtain CAG endorsement.     

侵袭性念珠菌病与触珠蛋白基因多态性的相关性研究

目的：检测侵袭性念珠菌病(invasive candidiasis, IC)患者血清中触珠蛋白(haptogliobin,Hp)的含量和表型分布情况,分析 Hp 基因多态性与 IC 的相关性。方法用免疫比浊法分析41例 IC 患者和60例对照者血清中 Hp 的含量,同时用聚丙烯酰胺(PAGE)凝胶电泳法分析两组受试者血清中 Hp 的表型分布情况。结果 IC 组的血清 Hp 含量显著高于对照组(t =5.564,P <0.05)；IC 组的 Hp1-1和 Hp2-1表型分布与对照组间差异无统计学意义(χ2=0.092、0.059,P >0.05),而在 Hp2-2表型分布明显高于对照组,差异有统计学意义(χ2=10.800,P <0.05)。结论带有 Hp2-2表型的人群可能对 IC 有遗传易感性,其血清 Hp 含量增高可能在 IC 发病中起一定作用。     

Treatment of invasive fungal infections in clinical practice: a multi-centre survey on customary dosing,treatment indications,efficacy and safety of voriconazole

Invasive fungal infections are frequent and often deadly complications in patients with malignant hematological diseases. Voriconazole is a third generation triazole antifungal with broad activity against most clinically relevant fungal pathogens. Clinical practice often deviates from insights gained from controlled randomized trials. We conducted a multi-centre survey to evaluate efficacy, safety, treatment indications and dosing of voriconazole outside clinical trials. Patients receiving voriconazole were documented via electronic data capturing. An analysis was conducted after submission of 100 episodes from September 2004 to November 2005. Voriconazole was administered for suspected or proven invasive fungal infection (IFI) (57%), as empirical treatment in patients with fever of unknown origin (21%) and secondary (19%) as well as primary (3%) prophylaxis of IFI. Investigators’ assessment of fungal infection often diverted from EORTC/MSG 2002 criteria. A favorable response was reported in 61.4% for suspected or proven IFI and 52.4% for empirical treatment. Mortality was 15%, 26.7% of which was attributable to IFI. Breakthrough fungal infections occurred in four (21.1%) patients with voriconazole as secondary prophylaxis. Toxicity and adverse events comprised elevated liver enzymes and visual disturbances. Although indications frequently deviated from clinical evidence and legal approval, voriconazole showed efficacy and safety, comparable to major controlled clinical trials. Data from this survey demonstrate the difficulty of putting drugs to their approved use in IFI.     

AGREEing on Canadian cardiovascular clinical practice guidelines

The use of clinical practice guidelines (CPGs), particularly the routine implementation of evidence-based cardiovascular health maintenance and disease management recommendations, affords both expert and nonexpert practitioners the opportunity to achieve better, and at least theoretically similar, patient outcomes. However, health care practitioners are often stymied in their efforts to follow even well-researched and well-written CPGs as a consequence of contradictory information. The purposeful integration and harmonization of Canadian cardiovascular CPGs, regardless of their specific risk factor or clinical management focus, is critical to their widespread acceptance and implementation. This level of cooperation and coordination among CPG groups and organizations would help to ensure that their clinical practice roadmaps (ie, best practice recommendations) contain clear, concise and complementary, rather than contradictory, patient care information. Similarly, the application of specific tools intended to improve the quality of CPGs, such as the Appraisal of Guidelines for Research and Evaluation (AGREE) assessment tool, may also lead to improvements in CPG quality and potentially enhance their acceptance and implementation.     

A review of latest clinical practice guidelines for the management of cancer-associated thrombosis

The management of cancer-associated thrombosis (CAT) poses unique challenges to healthcare professionals. While low‐molecular weight heparins (LMWHs) have long been the gold standard for both the primary and secondary prevention of CAT, results from large randomized controlled trials assessing the benefit of direct oral anticoagulants (DOACs) in both settings have resulted in some paradigm shifts. Herein, we review and compare recommendations from the latest authoritative clinical practice guidelines (CPGs) for the management of CAT and summarize the most recent evidence on available treatment options. A rigorous methodology was used to select high quality CPGs and compare the recommendations across CPGs. Only CPGs focusing on the management of CAT developed by a multidisciplinary international working group and issued or endorsed by national or international scientific societies, or government organizations were eligible for inclusion. The quality of selected CPGs was assessed using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) tool. Four CPGs met the inclusion criteria, including the International Initiative on Thrombosis and Cancer (ITAC), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), and the National Comprehensive Cancer Network (NCCN).     

急性白血病并发慢性播散性念珠菌病的临床研究

目的 提高对急性白血病(AL)并发慢性播散性念珠菌血症(CDC)的了解和认识.方法 回顾性分析我科2004年8月至2005年5月初治并完成诱导化疗的119例AL患者,对确诊合并CDC患者的临床表现、实验室和影像学检查、诊断和治疗进行分析总结.结果 119例患者中3例确诊合并CDC,发生率为2.5%,3例均为AL化疗后中性粒细胞缺乏持续时间＞15 d的患者,2例患者确诊CDC时粒细胞已恢复正常.3例患者均表现为持续发热、肝脾肿大和肝区叩击痛,2例伴咳嗽、咳痰及呼吸困难.2例患者出现碱性磷酸酶增高,3例CT均发现肝脾内多发低密度病灶,2例伴双肺多发结节状斑片状影,1例行MRI检查发现肝、脾、肾脏多发异常信号.2例血培养及1例肝穿刺活检培养发现热带念珠菌生长.2例采用两性霉素B(AmpB)治疗2周仍持续高热,1例改用AmpB胆固醇复合体(ABCD),1例联合伏立康唑治疗后病情好转;1例确诊后应用ABCD治疗45 d(AmpB累积剂量3.45 g)后症状消失,但停药12 d又出现高热,后经伏立康唑治疗后病灶消失.3例患者在治疗CDC同时均进行化疗.结论 CDC的诊断比较困难,目前主张结合临床表现、微生物学、组织病理学及影像学检查综合判断.AmpB是临床上治疗CDC的基本用药,对不耐受或耐药的患者可以使用脂质体AmpB治疗,伏立康唑对难治复发病例疗效满意,可用于二线治疗.另外,AL并发CDC不影响正常化疗的进行.     

A scoping review of best practice guidelines for the dietary management of diabetes in older adults in residential aged care

Over the last two decades guidelines have been published on the subject of the care and liberalised nutrition management of older adults with diabetes in residential aged care, recognising that they may have different needs to those older adults in their own home. This study aimed to scope and appraise these guidelines using the AGREE II tool. Overall physician developed guidelines were more robust, but there was discordance in their recommendations compared to guidelines developed by dietitians; particularly regarding the use of therapeutic diets. A lack of standardised approach has implications for optimal dietary management of diabetes in aged care.     

A decade of respiratory syncytial virus epidemiology and prophylaxis: Translating evidence into everyday clinical practice

Respiratory syncytial virus (RSV) is a common infection in infancy, with nearly all children affected by two years of age. Approximately 0.5% to 2.0% of all children are hospitalized with lower respiratory tract disease, of which 50% to 90% have bronchiolitis and 5% to 40% have pneumonia. Morbidity and mortality are highest in children with nosocomial infection and in those with underlying medical illnesses such as cardiac and chronic lung disease. Aboriginal children residing in remote northern regions are specifically considered to be at high risk for hospitalization due to RSV infection. Thorough hand washing and health education are the principal strategies in primary prevention. In the absence of a vaccine, palivizumab prophylaxis is currently the best intervention to reduce the burden of illness and RSV-related hospitalization in high-risk children. Health care professionals should provide palivizumab prophylaxis cost effectively in accordance with recommendations issued by pediatric societies and national advisory bodies.The present article reviews the epidemiology of RSV infection and the short- and long-term impact of disease in high-risk infants and special populations. Prevention strategies and treatment are discussed based on the existing scientific evidence, and future challenges in the management of RSV infection are addressed.     

Invasive candidiasis in cancer patients: observations from a randomized clinical trial

BACKGROUND: Invasive candidiasis is a common and serious complication of cancer and its therapy. METHODS: We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication. RESULTS: 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors. CONCLUSIONS: Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.     

Critical appraisal of clinical practice guidelines for diagnosis and treatment of hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is the third most common reason for cancer‐related death worldwide. Many countries either lack appropriate clinical practice guidelines for the diagnosis and treatment of HCC or the quality of their guidelines has never been evaluated. The main objective of our work was to identify published HCC guidelines and assess their quality with the Appraisal of Guidelines for Research and Evaluation instrument (AGREE) and their suitability regarding adaptation for future guidelines. Methods: We performed a systematic literature search on HCC clinical practice guidelines of MEDLINE, National Guidelines Clearinghouse and the Guidelines International Network. Methodological quality of selected guidelines was assessed by the AGREE instrument, Version 2001. Results: A total of 286 citations were screened and 32 relevant guidelines were identified. Overall, the guidelines performed well in the clarity and presentation domain with a mean score of 67%, followed by scope and purpose (55%) and rigor of development (50%). In contrast, poor scores were given for the remaining domains: stakeholder involvement (23%), applicability (28%) and editorial independence (31%). According to the AGREE instrument, four guidelines can be strongly recommended, 18 with provisos and alterations while the remaining cannot be recommended for adaptation due to poor methodological quality. Conclusion: Although existing HCC guidelines may accurately reflect agreed clinical practice, many guidelines lack proper methodological quality. Future guidelines should place more emphasis on these methodological shortcomings.     

Discrepancies between primary physician practice and treatment guidelines for Helicobacter pylori infection in Korea

AIM:To evaluate the attitude of primary care physiciansin the diagnosis and treatment of Helicobacter pylori(H pylori) infection.METHODS:Primary care physicians in the Seoulmetropolitan area answered self-administeredquestionnaire from January to March 2003.RESULTS:One hundred and eight doctors responded tothe questionnaire.The most frequent reasons for test-ing H pylori infection were gastric and duodenal ulcers(93.5% and 88.9%,respectively).For patients withHplori positive dyspepsia,28.7% of doctors always triedto eradicate the worm and 34.4% treated selectively.A large proportion (28.7%) of primary care physicianstreated H pylori on a patient's request basis.Only 9.3%of primary care physicians always conducted follow-uptesting after treating H pylori infection.When H pyloriwas not cleared by the first treatment,40.7% of doctorsreused the same regimen,16.7% changed to anothertriple regimen and 25% to a quadruple regimen.CONCLUSION:It has been well documented that theissuance of guidelines alone has little impact on practice.Communication between primary care physicians andgastroenterologists in the form of continuous medicaleducation is required.     

Effects of the 1994 Canadian Cardiovascular Society clinical practice guidelines for congestive heart failure

BACKGROUND: In 1994, the Canadian Cardiovascular Society (CCS) issued practice guidelines for the management of congestive heart failure (CHF), which strongly recommended the use of angiotensin-converting enzyme (ACE) inhibitors. OBJECTIVE: To compare a strategy of active implementation of the CCS guidelines for CHF with the usual passive approach on the use of ACE inhibitors in hospitalized patients with CHF. PATIENTS AND METHODS: The study was conducted in eight Canadian hospitals close to the time of release of the CCS guidelines for CHF in the summer of 1994. The patients comprised those who were admitted to the participating hospitals with a diagnosis of CHF during the study period. Active dissemination included stakeholder development of pocket cards outlining an algorithm for the management of CHF based on the CCS guidelines and was conducted at the two Edmonton, Alberta hospitals. The cards were widely disseminated in conjunction with a series of workshops and presentations. Passive dissemination occurred at six other hospitals, and involved only the distribution of the CCS guidelines in the usual fashion (with no structured dissemination program). The primary outcome measured was the use of ACE inhibitors in the six- to 12-month period before the release of the CCS guidelines, compared with after the release in the active and passive groups. RESULTS: In the active group, hospital records of 1170 patients with CHF were reviewed before, and 1279 were reviewed after, the release of the CCS guidelines. In the passive group, 3436 were reviewed before, and 1912 were reviewed after the release of the guidelines. ACE inhibitor use did not change significantly in the active group (52.4% before versus 50.9% after) or in the passive group (53.4% before versus 56.5% after). CONCLUSIONS: Neither the active nor passive approaches to the dissemination of the CCS guidelines for CHF had any impact on the use of ACE inhibitors in hospitalized patients with CHF. Further efforts to package, deliver and evaluate guidelines are needed.     

Adherence to AASLD guidelines for the treatment of hepatocellular carcinoma in clinical practice: Experience of the Bologna Liver Oncology Group

BackgroundFew data exist on real-life adherence to international guidelines for the treatment of hepatocellular carcinoma. We analysed the rate of adherence to American Association for the Study of Liver Diseases guidelines, to identify reasons for discrepancy with treatments performed in our centre.Methods227 consecutive cirrhotics with a first hepatocellular carcinoma diagnosis (2005–2010) were retrospectively evaluated and stratified based on Barcelona Clinic Liver Cancer system: 126 early, 50 intermediate, 40 advanced, and 11 end stage.ResultsEarly hepatocellular carcinomas were theoretically eligible for resection (n = 27), liver transplantation (n = 36), and percutaneous treatment (n = 63). In practice, 15/27 (55.5%), 31/36 (86.1%), and 22/63 (34.9%) respectively were treated as recommended. Reasons for discrepancy were age/comorbidity, tumour location, ultrasound visibility, surgical contraindications. Transarterial chemoembolisation was performed in 25/126 early hepatocellular carcinomas (19.8%), resection in 11/63 early hepatocellular carcinomas eligible for percutaneous treatment (17.5%). Transarterial chemoembolisation was excluded in 16/50 intermediate hepatocellular carcinomas (32%). Resection or transarterial chemoembolisation was performed in 6/40 advanced hepatocellular carcinomas (15%).ConclusionOverall, 60% of patients were treated according to American Association for the Study of Liver Diseases guidelines. Approximately 28% of hepatocellular carcinomas were “under-treated” and 7% treated more aggressively than recommended. Peculiarities of individual patients can lead the multidisciplinary team to personalise real-life treatments.     

Candidemia and invasive candidiasis in adults: A narrative review

Candidemia and invasive candidiasis are major causes of morbidity and mortality, and their incidence is increasing because of the growing complexity of patients. Five species of Candida (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei) account for more than 90% of all diagnosed cases, but their relative frequency varies depending on the population involved, geographical region, previous anti-fungal exposure, and patient age. The best evidence regarding the anti-fungal treatment for invasive candidiasis comes from randomized controlled trials in which more than 85% of the recruited patients had candidemia. In the case of less frequent forms of invasive candidiasis, the recommendations are based on retrospective studies, meta-analyses (when available) and experts' opinions. A pre-emptive approach based on biomarkers and clinical rules is recommended because of the high rate of infection-related mortality among critically ill patients.     

亚太肝病研究学会代谢相关脂肪性肝病临床诊疗指南(治疗部分)简介

亚太地区55个国家包含全球半数以上人口,2015年调查显示62.6%的全球肝脏相关死亡发生在亚太地区。尽管地区之间在经济、政治及教育领域发展速度差异显著,但是整个亚太地区都在向城市化发展,都面临饮食结构的西化(从农耕文明饮食向能量密集但营养缺失的饮食变化)以及久坐和缺乏锻炼的生活习惯。与欧美发达国家相同,这些转变导致了亚太地区代谢紊乱及其相关疾病患病率升高,当前代谢相关脂肪性肝病(MAFLD,曾用名非酒精性脂肪性肝病)患病率已升高到令人担忧的水平,给患者本人及整个医疗体系都带来巨大的疾病负担。为此,亚太肝病研究学会(APASL)邀请包括我国范建高教授在内23位专家,广泛检索了2020年4月前在PubMed上发布的相关领域文献,撰写系统综述并将其转化为临床实践指南的科学依据,以优化MAFLD患者的评估和管理。指南包含了MAFLD的流行病学、诊断、筛查、评估和治疗等多方面,并依照GRADE系统对证据进行分级。指南旨在指导MAFLD临床实践、提供成人MAFLD最新研究信息,并为特殊群体的治疗提供参考。最终目的是改善患者护理质量、提高疾病认识水平,通过提供以证据为基础的研究数据指导相关决策及减轻医疗保健部门的临床管理负担。