BACKGROUND & AIMS: BACKGROUND:Older people constitute a significant proportion of the total population and their number is projected to increase by more than half by 2030. This increasing probability of late survival comes with considerable individual, economic and social impact. Physical activity (PA) can influence the ageing process but the specific relationship with healthy ageing (HA) is unclear. METHODS:We conducted a systematic review and meta-analysis of longitudinal studies examining the associations of PA with HA. Studies were identified from a systematic search across major electronic databases from inception as January 2017. Random-effect meta-analysis was performed to calculate a pooled effect size (ES) and 95% CIs. Studies were assessed for methodological quality. RESULTS:Overall, 23 studies were identified including 174,114 participants (30% men) with age ranges from 20 to 87 years old. There was considerable heterogeneity in the definition and measurement of HA and PA. Most of the identified studies reported a significant positive association of PA with HA, six reported a non-significant. Meta-analysis revealed that PA is positively associated with HA (ES: 1.39, 95% CI=1.23-1.57, n=17) even if adjusted for publication bias (ES: 1.27, 95% CI=1.11-1.45, n=20). CONCLUSIONS:There is consistent evidence from longitudinal observational studies that PA is positively associated with HA, regardless of definition and measurement. Future research should focus on the implementation of a single metric of HA, on the use of objective measures for PA assessment and on a full-range of confounding adjustment. In addition, our research indicated the limited research on ageing in low-and-middle income countries.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Semen quality, a predictor of male fertility, has been suggested declining worldwide. Among other life style factors, male coffee/caffeine consumption was hypothesized to influence semen parameters, but also sperm DNA integrity. To summarize available evidence, we performed a systematic review of observational studies on the relation between coffee/caffeine intake and parameters of male fertility including sperm ploidy, sperm DNA integrity, semen quality and time to pregnancy. METHODS:A systematic literature search was performed up to November 2016 (MEDLINE and EMBASE). We included all observational papers that reported the relation between male coffee/caffeine intake and reproductive outcomes: 1. semen parameters, 2. sperm DNA characteristics, 3. fecundability. All pertinent reports were retrieved and the relative reference lists were systematically searched in order to identify any potential additional studies that could be included. RESULTS:We retrieved 28 papers reporting observational information on coffee/caffeine intake and reproductive outcomes. Overall, they included 19,967 men. 1. Semen parameters did not seem affected by caffeine intake, at least caffeine from coffee, tea and cocoa drinks, in most studies. Conversely, other contributions suggested a negative effect of cola-containing beverages and caffeine-containing soft drinks on semen volume, count and concentration. 2. As regards sperm DNA defects, caffeine intake seemed associated with aneuploidy and DNA breaks, but not with other markers of DNA damage. 3. Finally, male coffee drinking was associated to prolonged time to pregnancy in some, but not all, studies. CONCLUSIONS:The literature suggests that caffeine intake, possibly through sperm DNA damage, may negatively affect male reproductive function. Evidence from epidemiological studies on semen parameters and fertility is however inconsistent and inconclusive. Well-designed studies with predefined criteria for semen analysis, subject selection, and life style habits definition, are essential to reach a consistent evidence on the effect of caffeine on semen parameters and male fertility.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Current knowledge of the natural outcomes of untreated women in preterm labour is both incomplete and outcomes vary significantly between the available studies. The aim of this study was to systematically review outcomes of preterm labour without tocolysis and determine if outcome variation could be accounted for by differences in study populations. Such data could potentially assist in the interpretation of intervention trials that do not include a no-treatment arm. METHODS:Included studies reported outcomes of women in clinically diagnosed preterm labour without tocolytic treatment between 1950 and 2011. Studies that were limited to preterm prelabour rupture of membranes, recurrent preterm labour or in which the women without tocolysis represented a potentially biased subgroup, or were not tocolysed because of contraindications were excluded. Study quality, design, and population characteristics were abstracted. Outcomes included pregnancy prolongation and the proportion of women undelivered at 48-72 h, 7 days, and term. Study characteristics associated with differing odds of preterm birth were explored through logistic regression. RESULTS:Three hundred and eighty-five citations were initially identified, of which 26 were included encompassing 1383 women. The percentage of patients who were undelivered at 48-72 hours was 62.8%, at 7 days 53.4% and 40.4% delivered at term, though the range was very wide. Characteristics associated with decreased odds of delivery were not consistent among reported outcome measures. CONCLUSIONS:Most women without tocolysis do not deliver within 7 days, although the range is very wide. The majority of this variation is unrelated to reported differences in study design or reported population characteristics.

背景与目标：

BACKGROUND & AIMS: :Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status.

背景与目标： 维生素d缺乏与骨质疏松症有关，被认为会增加患癌症和CVD的风险。尽管有这些潜在的健康影响，但人口水平和关键亚组中维生素d状况的数据有限。本研究的目的是检查世界范围内25-羟基维生素d (25(OH)D) 水平的模式，并评估年龄，性别和地区的差异。在使用Medline和EMBASE数据库的系统文献综述中，我们确定了在44个国家进行的195项研究，涉及168 000多名参与者。在整个研究中，平均人口水平25(OH) d值差异很大 (范围为4·9-136·2 nmol/l)，37·3% 的研究报告平均值低于50 nmol/l。在北美观察到最高的25(OH) d值。尽管在亚洲/太平洋和中东/非洲地区观察到与年龄相关的差异，在其他地方没有观察到它们，在任何地区也没有观察到性别相关的差异。研究之间的实质性异质性排除了对人口水平总体维生素d状况的结论。然而，探索性分析，建议来自世界各地的几个地区的新生儿和住院老人似乎普遍处于较低的25(OH) d值的较高风险中。需要在人口水平和关键亚组中详细了解全球范围内的维生素d状况，以告知公共卫生政策制定以降低潜在健康后果的风险维生素d水平不足。

BACKGROUND & AIMS: INTRODUCTION:Suicide is known as a major health concern worldwide. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in suicide behavior. Therefore, this factor has been proposed as a biomarker for suicide behavior. Clinical studies have measured BDNF concentrations at central and peripheral levels. As a consequence, the aim of this study was to assess BDNF levels in blood plasma and serum to see whether there is a difference in concentrations in patients with suicide behavior when compared to those in controls, using a meta-analysis approach. METHODS:We conducted a systematic review and meta-analysis. The search strategy was performed using three databases: PubMed, EBSCO and ScienceDirect. The meta-analysis included a total of nine case-control studies, six measured the BDNF level in serum and three in plasma in suicide behavior. RESULTS:A decrease in BDNF levels in plasma was observed (d = -0.73, 95% CI -1.42 to -0.03 pg/ml). In the case of serum concentrations, no BDNF differences were encountered between cases and controls (d = 0.09, 95% CI -0.31 to 0.13 ng/ml, p(Q) = .92). CONCLUSIONS:According to the results found in the present meta-analysis, the plasma BDNF level could be suggest as a potential biomarker in suicide behavior. However, since the number of studies included in the analysis is limited, a larger number is necessary to determine conclusively the role of BDNF as a biomarker in suicide behavior.

背景与目标：

BACKGROUND & AIMS: :This article systematically reviews the literature pertaining to correlates of body dissatisfaction during pregnancy. A total of 8 electronic databases were searched and 251 papers identified, 56 of which met inclusion criteria. Full text scrutiny of these papers reduced the final list of reviewed papers to 22. Results of the review highlight that psychological factors were associated with body dissatisfaction during pregnancy, and noted the surfeit of studies examining the relationship was between body dissatisfaction and depression. It is concluded that the prevention of heightened body dissatisfaction during the reproductive phase will only be effective when models of risk factors have been examined systematically and rigorously.

背景与目标： : 本文系统地回顾了有关怀孕期间身体不满的相关文献。共检索8个电子数据库，鉴定出251篇论文，其中56篇符合纳入标准。对这些论文的全文审查将审查论文的最终清单减少到22篇。审查的结果强调，心理因素与怀孕期间的身体不满有关，并指出了大量研究身体不满与抑郁之间关系的研究。结论是，只有在系统和严格地研究了危险因素模型后，预防生殖阶段身体不满情绪加剧才有效。

BACKGROUND & AIMS: AIMS:Lack of adherence to smoking cessation medication regimens is assumed to play a significant role in limiting their effectiveness. This study aimed to assess evidence for this assumption. METHODS:A systematic search was conducted, supplemented by expert consultation, of papers reporting on randomized trials and observational studies examining the association between adherence to cessation medication and the success of quit attempts. To rule out reverse causality, only studies where adherence was assessed prior to relapse were included. Five studies met the inclusion criteria and results were extracted independently by two researchers. Heterogeneity between studies precluded a pooled analysis of the data. RESULTS:Studies varied widely with regard to both the definition of adherence and outcome measures. The included studies only addressed adherence to nicotine replacement therapy. One study of lozenge use found that the amount of medication used between 1 and 2 weeks after the quit date predicted abstinence at 6 weeks [adjusted odds ratio (OR) for 'high' versus 'low' lozenge use 1.25; 95% confidence interval (CI) = 1.05-1.50; P < 0.02]. Similarly, one study found a significant impact of oral nicotine consumption during the first week on abstinence at 4 weeks (adjusted OR per additional mg/day = 1.05; CI = 1.01-1.10). Another study found that participants using nicotine replacement therapy for at least 5 weeks were significantly more likely to self-report continuous abstinence at 6 months. The remaining two studies failed to find a significant effect of treatment duration on outcome at 1 and 2 years but had very low power to detect such an effect. CONCLUSIONS:There is modest evidence to support the assumption that lack of adherence to nicotine replacement therapy regimens undermines effectiveness in clinical studies.

背景与目标：

BACKGROUND & AIMS: :Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.

背景与目标： : 急性髓系白血病 (AML) 的缓解后治疗仍然存在问题。已证明，年轻患者在诱导治疗后可以通过积极的缓解后疗法维持更长的完全缓解 (CR): 异体 (allo)，自体 (auto) 干细胞移植 (SCT) 或强化化疗 (ICC)。我们研究的目的是确定比较这三种治疗方案的最重要的随机和对照研究，以便根据循证医学 (EBM) 规则得出结论和可能的AML缓解后治疗建议。我们对文献进行了详尽的分析，在电子数据库中或在已识别文章的参考文献中进行搜索 (手工搜索)。我们在MEDLINE计算机数据库中搜索了通过2005年1月1985年的报告，并选择了针对年龄小于65岁的新诊断AML的成年人进行的临床试验进行分析。研究设计必须满足严格的方法学标准，并且必须将全球死亡率和/或无病生存率作为主要结果。总的来说，我们发现了7750篇论文; 通过使用限制 “临床试验” 作为出版类型，“所有成人19岁”，我们能够选择344篇论文。其中，基于两个主要的临床问题进行了进一步的选择: 1) 在改善首次CR的成年AML患者的DFS和/或OS方面，auto-SCT是否优于ICC/no其他疗法？2) 在改善首次CR的成年AML患者的DFS和/或OS方面，allo-SCT是否优于auto-SCT/其他治疗选择？关于第一个查询，临床试验数据并未明确支持auto-SCT优于ICC的可能优势; 没有证据表明auto-SCT在OS方面优于化疗。然而，在过去几年中，报告的TRM已大大减少。因此，CR中适合auto-SCT的患者百分比增加了。此外，关于不同患者亚组中auto-SCT和化疗之间比较的稀缺数据无法提示高风险，标准风险或低风险AML患者的差异化方法。来自文献的数据表明，患有不利风险疾病的患者更常接受allo-SCT治疗，而低风险疾病的患者更常接受强化强化化疗。关于第二个查询，对来自主要前瞻性研究的有关allo-SCT在先前未经治疗的AML中的作用的数据的解释并不容易。第一个问题是缺乏真正的随机临床试验; 实际上，根据报道的研究，AML患者通常根据供体的可用性接受allo-SCT (所谓的 “遗传随机化”)。第二个问题是经常缺乏治疗分析的意图。尽管方法上有局限性，但可以在供体分析与无供体分析以及风险组中比较allo-SCT与auto-SCT。任何试验都没有证明同种异体移植对生存率的总体益处。总之，EBM方法强调了在已发表的关于AML巩固治疗的研究中观察到的局限性; 从非随机和随机研究中提出的一些建议是足够的，但不是结论性的。这一点，加上研究AML生物异质性的内在复杂性，可能是为AML巩固治疗得出确凿证据的主要障碍。这些观察结果应计划解决有关AML治疗的新的随机研究; 但是，由于遗传亚组的出现和针对特定异常的新药的出现，这些试验可能应直接针对单个实体进行设计。这样，AML的治疗最终可以成为每个特定AML子集的治疗方法，具有其独特的生物学，分子和预后特征。

BACKGROUND & AIMS: BACKGROUND:Since the 1970s, many countries have employed the use of the General practitioner group practice, but there is contrasting evidence about its effectiveness. A systematic review was performed to assess whether group practice has a more positive impact compared with the single-handed practice on different aspects of health care. METHODS:A systematic review was conducted by querying electronic databases and reviewing articles published between 1990 and 2012. A quality assessment was performed. The effect of group practice was evaluated by collecting all items analysed by the articles into four main categories: (1) studies of quality (measured in terms of clinical processes) and productivity (measured in terms of throughput), named "Clinical process measures and throughput"; (2) studies exploring physician's opinion--"Doctor's perspective"; (3) studies looking into the use of innovation, information and communication technology (ICT) and quality assurance--"Innovation, ICT and quality assurance"; (4) studies focused on patient's opinion--"Patient's perspective". The results were synthesized according to three levels of scientific evidence. RESULTS:A total of 26 studies were selected. The most studied category was Clinical process measures and throughput (58%). A positive impact of group medicine on "Clinical process measures and throughput", "Doctor's perspective", "Innovation, ICT and quality assurance" was found. There was contrasting evidence considering the "Patient's perspective". CONCLUSIONS:Group practice might be a successful organizational requirement to improve the quality of clinical practice in Primary Health Care. Further comparative studies are needed to investigate the impact of organizational and professional determinants such as physician's economic incentives, mode of payment, size of the groups and multispecialty on the effectiveness of medical primary care.

背景与目标：

BACKGROUND & AIMS: :We performed a structured literature review of published studies from 2000-2007 that measured the acceptability and acceptance (uptake) of urine testing for C. trachomatis among asymptomatic men. Studies were categorized as three types: (a) non-STD clinic venues where men were approached in person and offered testing on site (urgent care clinics, freestanding clinics or health screening settings, corrections, community centers); (b) delivery of testing kits to men at their homes; and (c) qualitative measurement related to men's experience of screening. When offered in established nonhome-based settings (clinics, schools, corrections), acceptability and consequent uptake of testing by men is generally good (mid-60% range). However, acceptance rates even in these settings vary widely and are influenced by venue, provider, and a diversity of other factors. Acceptance of home-based testing invitations, including direct mailing of test kits, is considerably lower. Attitudinal characteristics of men who decline testing primarily include low self-perception of risk for asymptomatic infection and perceived inconvenience of providing test specimens. Given these findings, testing strategies targeting asymptomatic men in established community and clinic settings are most likely to yield relatively high acceptance rates. However, barriers to both implementation and uptake remain, even when such testing is free. Interventions to enhance uptake of testing in asymptomatic men should be developed and selected with underlying C. trachomatis population prevalence in mind.

背景与目标： : 我们对2000-2007年发表的研究进行了结构化文献综述，这些研究测量了无症状男性中沙眼衣原体尿液检测的可接受性和接受度 (摄取)。研究分为三种类型 :( a) 非性病诊所，亲自接触男性并在现场提供测试 (紧急护理诊所、独立诊所或健康筛查环境、矫正、社区中心); (b) 向男性在家中提供测试包; (c) 与男性筛查经验相关的定性测量。当在既定的非家庭环境 (诊所，学校，矫正) 中提供时，男性对测试的可接受性和随之而来的接受程度通常是良好的 (60% 左右)。但是，即使在这些设置中，接受率也相差很大，并且受场地，提供商和其他多种因素的影响。接受家庭测试邀请，包括直接邮寄测试套件，要低得多。拒绝测试的男性的态度特征主要包括对无症状感染风险的低自我感知和提供测试样本的不便。鉴于这些发现，在既定的社区和诊所环境中针对无症状男性的测试策略最有可能产生相对较高的接受率。然而，即使这种测试是免费的，实施和实施的障碍仍然存在。应制定和选择干预措施，以提高无症状男性的测试水平，并考虑潜在的沙眼衣原体人群患病率。

BACKGROUND & AIMS: OBJECTIVES:Evaluation and comparison of the performance of organized and opportunistic screening mammography. METHODS:Women attending screening mammography in Denmark in 2000. The study included 37,072 women attending organized screening. Among these, 320 women were diagnosed with breast cancer during follow-up. Opportunistic screening was attended by 2855 women with 26 women being diagnosed with breast cancer. Data on women attending screening were linked with information on cancer status. Each woman was followed with respect to diagnosis of breast cancer (invasive as well as in situ) for a period of two years. Screening outcome and cancer status during follow-up were combined to assess whether the result of the examination was true-positive, true-negative, false-positive or false-negative. Based on this classification, age-adjusted sensitivity and specificity of organized and opportunistic screening were calculated. RESULTS:Defining BI-RADS(trade mark) 4-5 as a positive screening outcome, the overall sensitivity of opportunistic screening was 33.6% and the specificity was 99.1%. Using BI-RADS(trade mark) 3-5 as positive, the sensitivity was 37.4% and the specificity was 97.9%. Organized screening (which was not categorized according to BI-RADS(trade mark)) had an overall sensitivity of 67.2% and a specificity of 98.4%. CONCLUSION:Our study showed a considerably higher sensitivity in organized screening than in opportunistic screening, while the specificity was fairly similar in the two settings. The findings support implementation of population-based breast screening programmes, as recommended in the 'European guidelines for quality assurance in breast cancer screening and diagnosis'.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:The authors sought to determine the contribution of delays in care on time to antibiotics for patients admitted from the emergency department (ED) with pneumonia and to identify patients at risk for delayed antibiotics. METHODS:This was a retrospective cohort study of patients admitted to the Hospital of the University of Pennsylvania (HUP) and to Pennsylvania Presbyterian Hospital (Presbyterian) with an admission diagnosis of pneumonia in 2004. RESULTS:A total of 393 patients were included. Ninety percent had antibiotics documented as given in the ED. Eighty-three (43%) of 209 at HUP and 104 (64%) of 161 patients at Presbyterian received antibiotics within four hours. Patients who received antibiotics more than four hours after ED arrival experienced longer waits for radiograph orders (HUP, 54 min [95% confidence interval {CI} = 33 to 76 min]; Presbyterian, 43 min [95% CI = 29 to 58 min]), for radiograph performance (HUP, 21 min [95% CI = 4 to 39 min], Presbyterian, 24 min [95% CI = 8 to 47 min]), for antibiotic orders (HUP, 56 min [95% CI = 38 to 95 min]; Presbyterian, 67 min [95% CI = 33 to 103 min]), and for antibiotic administration (HUP, 28 min [95% CI = 17 to 39 min]; Presbyterian, 30 min [95% CI = 21 to 38 min]). Patients with lower severity scores (p = 0.005) and patients with nonclassic clinical presentations for pneumonia were at increased risk for delayed antibiotics (odds ratio, 2.2; 95% CI = 1.1 to 4.4). CONCLUSIONS:Antibiotic delays for patients admitted with pneumonia occur across multiple care processes. Less severely ill patients and patients with nonclassic presentations are at higher risk for delayed antibiotic administration. Hospitals should consider performing a similar analysis to evaluate hospital-specific and patient-specific care delays.

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BACKGROUND & AIMS: OBJECTIVES:To assess the clinical effectiveness and cost-effectiveness of central venous catheters (CVCs) treated with anti-infective agents in preventing catheter-related bloodstream infection (CRBSI). DATA SOURCES:Major electronic databases were searched from 1985 to August 2005. REVIEW METHODS:The systematic clinical and economic reviews were conducted according to accepted procedures. Only full economic evaluations (synthesis of costs and benefits) comparing the use of anti-infective central venous catheters (AI-CVCs) with untreated CVCs or other treated catheters were selected for inclusion in the economic review. RESULTS:A total of 32 trials met the clinical inclusion criteria. Seven different types of AI-CVC were identified, with the most frequently tested being chlorhexidine and silver sulfadiazine (CHSS) (externally treated), CHSS (externally and internally treated) and minocycline rifampicin (internally and externally treated). In general, the trials were of a poor quality in terms of reported methodology, microbiological relevance and control of confounding variables. The pooled result suggests a statistically significant advantage for AI-CVCs in comparison to standard catheters in reducing CRBSI [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.34 to 0.60, 24 studies, I-squared = 0%, fixed effects]. Analysis by subgroups of catheters demonstrates that antibiotic-treated catheters and catheters treated internally and externally decrease CRBSI rates significantly (OR 0.26, 95% CI 0.15 to 0.46, six studies, I-squared = 0%, fixed effects, and OR 0.43, 95% CI 0.26 to 0.70, nine studies, I-squared = 0%, fixed effects, respectively). Catheters treated only externally demonstrate a wider CI and non-significant effect (OR 0.67, 95% CI 0.43 to 1.06, nine studies, I-squared = 0%, fixed effects). A treatment effect was also found for trials with an average duration of between 5 and 12 days, and for the one study with a mean duration of over 20 days. There was a statistically significant treatment effect for both femoral and jugular insertion sites and for those studies reporting a mix of insertion sites. The treatment effect was not observed in trials using exclusively subclavian insertion sites. Of the four trials that compared treated catheters, one reported a benefit of antibiotic-treated catheters over catheters treated externally with CHSS. All three sensitivity analyses testing for study design differences reported a statistically significant treatment effect. The review was limited owing to the quality of the trials included, marked differences in the definitions and methods of diagnosis of CRBSI, and inconsistent reporting of risk factors and patient population factors. Furthermore, two-thirds of trials were commercially funded. The economic performance (cost-effectiveness and potential cost-savings) of using AI-CVCs to reduce the number of CRBSIs in patients requiring a CVC was also reviewed. Results show that the use of AI-CVCs instead of standard CVCs can lead to a reduction in CRBSIs and decreased medical costs. To complement the reviews, a basic decision-analytic model was constructed to explore a range of possible scenarios for the NHS in England and Wales. Results show that for every patient who receives an AI-CVC there is an estimated cost-saving of 138.20 pounds. The multivariate sensitivity analyses estimate potentially large cost-savings, depending on the size of the population, under a wide range of cost and clinical assumptions. However, those considering the purchase of AI-CVCs should ensure that their patient populations and the important characteristics of local clinical practice are indeed similar to those described in this economic evaluation. CONCLUSIONS:Overall, AI-CVCs are clinically effective and relatively inexpensive and therefore their integration into clinical practice can be justified. However, the use of these anti-infective catheters without the appropriate use of other practical care initiatives will have only a limited success on the prevention of CRBSIs. Comparative trials are required to determine which, if any, of the treated catheters is the most effective. Pragmatic research related to the effectiveness of bundles of care that may reduce rates of CRBSI is also warranted.

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BACKGROUND & AIMS: OBJECTIVES:To assess the proportion of patients lost to programme (died, lost to follow-up, transferred out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub-Saharan Africa, and determine factors associated with loss to programme. METHODS:Systematic review and meta-analysis. We searched PubMed and EMBASE databases for studies in adults. Outcomes were the percentage of patients dying before starting ART, the percentage lost to follow-up, the percentage with a CD4 cell count, the distribution of first CD4 counts and the percentage of eligible patients starting ART. Data were combined using random-effects meta-analysis. RESULTS:Twenty-nine studies from sub-Saharan Africa including 148,912 patients were analysed. Six studies covered the whole period from HIV diagnosis to ART start. Meta-analysis of these studies showed that of the 100 patients with a positive HIV test, 72 (95% CI 60-84) had a CD4 cell count measured, 40 (95% CI 26-55) were eligible for ART and 25 (95% CI 13-37) started ART. There was substantial heterogeneity between studies (P < 0.0001). Median CD4 cell count at presentation ranged from 154 to 274 cells/μl. Patients eligible for ART were less likely to become lost to programme (25%vs. 54%, P < 0.0001), but eligible patients were more likely to die (11%vs. 5%, P < 0.0001) than ineligible patients. Loss to programme was higher in men, in patients with low CD4 cell counts and low socio-economic status and in recent time periods. CONCLUSIONS:Monitoring and care in the pre-ART time period need improvement, with greater emphasis on patients not yet eligible for ART.

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BACKGROUND & AIMS: BACKGROUND:Systematic reviews have gradually replaced single studies as the highest level of documented effectiveness of health care interventions. Systematic reviewing is a new scientific method, concerned with the development and application of methods for identifying relevant literature, analysing the material while increasing validity and precision, and presenting and discussing the results in a way that does justice to the research question and to the available evidence. The objective of this study was to review the systematic reviews in laboratory medicine, to evaluate the methods applied in these reviews and the applicability of guidelines of the Cochrane Methods Working Group on Screening and Diagnostic Tests, and identify areas for future research. METHODS:All the systematic reviews in the field of clinical chemistry and laboratory haematology that could be identified in Medline, EMBASE and other literature databases up to December 1998, were evaluated. RESULTS:We studied 23 reviews of diagnostic trials. Although all reviews share the same basic methodology, there was a wide variation in the methods applied. There was no consensus on the quality criteria for inclusion of primary studies. The results of the primary studies were heterogeneous in most cases. This was partly due to design flaws in the primary studies, but was also inherent in the diverse study designs in diagnostic trials. We observed differences in the analysis of the factors that cause heterogeneity of the results, and in the summary statistics used to pool the data from the primary studies. The additional diagnostic value of a test, after other test results are taken into consideration, was only addressed in one study. CONCLUSION:This overview of 23 reviews of diagnostic trials identifies areas in the methods of systematic reviewing where consensus is lacking, such as quality rating of primary studies, analysis of heterogeneity between primary studies and pooling of data. Guidelines need to be improved on these points.

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