Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.     

Does our current understanding of the molecular basis of immune tolerance predict new therapies for autoimmune disease?

The creation of specific immune tolerance has often been referred to as the ultimate goal of immunotherapy, because it would allow autoimmune disease to be reversed without the need for nonspecific and potentially harmful immunosuppressive therapy. Studies performed during the past decade have been immensely fruitful in terms of advances in our understanding of the cellular and molecular mechanisms of immune tolerance, and have paved the way for successful exploitation of these mechanisms for therapeutic purposes. Important developments include an increased understanding of central and peripheral tolerance, and treatment strategies that mimic the mechanisms behind deletion of self-reactive cells, the identification of crucial gene products that are involved in the induction of anergy, and the characterization of regulatory T cells and protocols for their induction and expansion for therapeutic applications. These landmarks of immune-tolerance research are summarized and their potential use in the immunotherapy of autoimmune disease discussed.     

The effect of mild whole-body hyperthermia on systemic levels of TNF-alpha, IL-1beta, and IL-6 in patients with ankylosing spondylitis

Serial mild whole-body hyperthermia is a widely used balneotherapy modality for clinically inactive ankylosing spondylitis (AS) in rehabilitative medicine. Thus far, the mechanisms of its favorable influence on the symptoms of AS are not completely understood. We therefore analyzed the effect of mild whole-body hyperthermia on the systemic levels of pivotal proinflammatory cytokines. Twelve male subjects with AS and 12 healthy control subjects received nine cycles of whole-body hyperthermia (target body core temperature, 38.5°C; duration, 50 min). Serum samples were taken at the beginning of the last cycle and at 1, 6, and 24 h for measurement of tumor necrosis factor α, interleukin 1β and interleukin 6. Significant differences of cytokine levels were found between both groups. In AS patients, hyperthermia caused a significant reduction of all cytokines by 40–50%. Thus, serial mild whole-body hyperthermia in AS results in heat-induced changes of the proinflammatory cytokine network.     

Developing the concept of adoptive cellular gene therapy of rheumatoid arthritis

Progressive destruction of articular cartilage and bone is the pivotal problem of rheumatoid arthritis (RA). Joint destruction is the cause of severe disability and determines the long-term outcome of disease. Conventional therapy does not control this destructive process sufficiently and the anti-rheumatic drugs available today can cause severe systemic adverse effects. Local application of chondroprotective and osteoprotective agents by means of gene therapy would be an attractive alternative to conventional therapy of RA and could provide long-term expression of the therapeutic agents and minimize systemic adverse effects. For this purpose, we have developed the concept of adoptive cellular gene therapy. This treatment strategy is based on using genetically engineered cells that home specifically to sites of autoimmune inflammation and thus allow local delivery of therapeutic gene products. Ex vivo transduction of these cells avoids systemic exposure of the host to the transgene-encoding vector and thus adds to the safety of this approach. In this article of the CIS Spring School in Autoimmune Diseases 2005 proceedings, we review our work on developing the strategy of adoptive cellular gene therapy and summarize recent advances in the evaluation of therapeutic effects and the identification of novel therapeutic targets.     

Evaluation of a special concept of physical therapy in spondyloarthritis: German multimodal rheumatologic complex treatment for spondyloarthritis

Clinical Rheumatology - Multimodal rheumatologic complex treatment (MRCT) is a specific concept of German inpatient care focusing on physical therapy for patients with rheumatic diseases suffering...     

Access to contraceptive services among unmarried young people in the north-east of China

Objective The concerns about the potential threats of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have increased, since, in China, there is a lack of sexual education and condom use is rare. A community-based survey was conducted in September 2001 in Changchun city among 1227 unmarried young people aged 15-24 years (619 males and 608 females) to assess risky sexual practices and the obstacles to accessing appropriate contraceptive and other services. Method The study comprised a survey employing self-administered questionnaires, as well as key informant interviews, focus group discussions and in-depth interviews. This paper investigates the factors associated with young people's access to contraceptive services. Results Results showed that 16% of young people had experienced premarital sexual intercourse and, among them, only 48.2% used contraceptive methods during the first sexual intercourse; 29.9% used a condom. Drug stores were the main source of contraceptives. Conclusions While data are sparse, findings suggest that the hostile and judgmental attitudes of providers, as well as the lack of counseling and privacy, were the key obstacles that unmarried youth encountered in their search for contraceptive services. Findings suggest the need for a reorientation of the contraceptive services to focus on unmarried youth, and generally to make contraceptive services more accessible to young people.     

Gene therapy in autoimmune disease

Recent work on gene therapies for autoimmune disease has continued to provide insight into the pathogenesis of autoimmunity. Reliable, effective and targeted gene therapy applications have been achieved by using transduced dendritic cells and antigen-specific T cells as delivery vehicles. Bioluminescence imaging has been implemented to visualize cell trafficking and homing in vivo. As a first step into human gene therapy, a phase I clinical trial for assessing the feasibility and safety of gene transfer has been completed in a group of rheumatoid arthritis patients.