Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.     

“肠梗”治疗粘连性肠梗阻425例

本文对采用自行研制的中草药浓缩剂“肠梗”治疗的粘连性肠梗阻４２５例进行临床分析。根据不同的病理及临床特征将其分为三种类型，其中广泛粘连型是“肠梗”治疗的最佳适应症，粘连扭转型是其禁忌证。并对中转手术的指征、时间等问题进行了讨论。认为该方法具有简单易行、安全可靠、成功率高的特点，是一种易于推广的治疗粘连性肠梗阻的有效方法，具有较高的临床实际应用价值     

The quality of acute stroke units on a nation-wide level: the Austrian Stroke Registry for acute stroke units

Concepts for stroke units that cover the acute phase vary. Therefore, the network of acute stroke units that is being set up in Austria in a uniform way is of general interest. This nationwide network has been established in accordance to evidence-based recommendations and prespecified criteria for available resources. The location for such a unit follows a maximum of 90-min isochrones (transport time) to the hospital. The quality of the network is currently documented and the results are reported. A nationwide stroke registry was prospectively performed on 15 stroke units that were already functional in this network. The aim was to document the quality performance of Austrian stroke units, focusing on rapid admissions, ready availability of investigations and therapies performed. Outcome measures were Barthel scale, Rankin score and percentages of complications. Between August 1998 and December 2000, 2,313 patients with ischemic stroke or with primary intracerebral hemorrhage admitted to an Austrian stroke unit within 24 h after onset of symptoms were prospectively included. Forty-three percent of the patients had a moderate or severe stroke. Fifty-seven percent of all patients were admitted to the stroke unit within 3 h after the onset of symptoms. Twenty-seven percent of these patients were brought in by ambulance accompanied by an emergency physician. Two percent of patients were admitted by helicopter. Fifty-four percent of patients had their first brain imaging within 30 min after admission, another 26% within 3 h. Intravenous thrombolysis was performed in 4.1% of patients. The overall stroke-unit mortality was about 6.8% and mortality at 3 months was 12.9%. The outcome at 3 months showed a modified Rankin Scale score of 0 or 1 in 47% of patients, denoting none or mild impairment. This network of acute stroke units is highly efficient in terms of rapid admissions, short intrahospital delays, as well as rapid use of readily available investigations. Stroke units seem to be well accepted by the general public and the medical community because our data show that all types of strokes are treated in Austrian stroke units, including severe strokes. The total number of concurrently treated acute strokes in other institutions across Austria is not known and no formal comparison with other systems of hospitalized care was undertaken, therefore further research is necessary.     

Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations

A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP. It will continue to be important to use complementary methods for mutational analysis.     

Risk of T-cell lymphomas in persons with AIDS

Lymphomas in persons with AIDS are mostly B-cell types, but T-cell lymphomas have also been reported. We examined T-cell lymphoma risk in the 2-year period after AIDS onset by linking 302,834 adults with AIDS to cancer registry data. Of 6,788 cases of non-Hodgkin's lymphoma (NHL) with specified histologies, 96 (1.4%) were T-cell lymphomas. Assessment was based on clinical diagnosis and histology because T-cell marker data were inadequate, but when present, marker data supported the T-cell diagnosis. The relative risk of T-cell lymphoma, estimated by standardized incidence ratio, was 15.0 (95% confidence interval: 10.0--21.7). Risks were increased for all subtypes, including mycosis fungoides, peripheral lymphomas, cutaneous lymphomas, and adult T-cell leukemia/lymphoma (ATLL). HIV-related immunodeficiency could be important, but differences between the population developing AIDS and the general population (e. g., immigration from the Caribbean region for ATLL) might independently increase T-cell lymphoma risk.     

用宿主防御指数辅助诊断中医虚证和不同辩证虚证的探讨

以中医学“虚证”及不同辩证虚证为研究对象，以宿主防御指数为研究总指标，开展了营养学和免疫学的多指标观察，并借助于医学统计学的理论和方法，尝试对中医学“虚证”的诊断。结果显示；虚证患者与正常人相比营养条件差，免疫功能氏下，主要表现为细胞免疫功能低下和免疫调节紊乱，补体主要成分降低，将这些评价指标代入计算机进行逐步判断分析，得出可以判别正常人，气阳虚患者，血阴虚患者的方程式，方程式判别能力Ｆ＝３（Ｐ〈     

化解冲剂对脓毒症大鼠神经肽及细胞因子的调节作用

为阐明传统中医学整体观与现代医学神经内分泌免疫网络学说的一致性。建立了大鼠用人感染模型；动态观察了脓毒症大鼠血浆中β－内啡肽、精氨酸加压素及血管活性肠肽的变化；同时观察了血中单个核细胞分泌肿瘤坏死因子α及白细胞介素６能力的改变；并观察了活化瘀代表方剂“化解冲剂”对上述改变的调节作用。     

Staphylococcal Esx Proteins Modulate Apoptosis and Release of Intracellular Staphylococcus aureus during Infection in Epithelial Cells

The opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell.     

Diabetes distress,but not depressive symptoms,is associated with glycaemic control among Japanese patients with Type 2 diabetes: Diabetes Distress and Care Registry at Tenri (DDCRT 1)

Aims To investigate the association between glycaemic control, diabetes distress and depressive symptoms among Japanese patients with Type 2 diabetes. Methods Cross‐sectional data from 3305 patients with Type 2 diabetes were obtained from a baseline assessment of a diabetes registry at a general hospital in Japan. The Centre for Epidemiologic Studies Depression scale and Problem Areas in Diabetes scale were used to measure depressive symptoms and diabetes‐related distress, respectively. Modified Poisson regression analysis was used to estimate the relative risks for poor glycaemic control across the quartiles of Centre for Epidemiologic Studies Depression scale and Problem Areas in Diabetes scale scores. Results The average age of the participants was 64.9 years and the average HbA_1c level was 58.1 mmol/mol (7.5%). Clinically significant levels of depressive symptoms (Centre for Epidemiologic Studies Depression scale scores ≥ 16) were reported by 27.8% of participants. These scores significantly correlated with Problem Areas in Diabetes scale scores (r = 0.4354, P < 0.0001). Diabetes distress, but not depressive symptoms, was significantly associated with higher HbA_1c levels. The relative risks for poor glycaemic control (HbA_1c≥ 64 mmol/mol; 8.0%), when adjusted for age, sex, BMI, type of diabetes therapy and duration of diabetes, was 67% higher among patients with Problem Areas in Diabetes scale scores in the highest quartile (≥ 26.25) compared with those in the lowest quartile (0–3.75). Conclusion A significant association between glycaemic control and diabetes‐related distress, but not depressive symptoms, was observed in Japanese patients with Type 2 diabetes.