Design and rationale of a randomized, double-blind, placebo-controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT-CLI).

BACKGROUND: Critical limb ischemia (CLI) is the end-stage of peripheral artery disease. Only about two thirds of patients with CLI can be revascularised, one third progresses to leg amputation with high associated morbidity and mortality. Therapeutic angiogenesis with bone marrow cells has shown promising improvement in less severe stages of peripheral ischemia. Our study evaluates the therapeutic value of bone marrow cell induced angiogenesis and arteriogenesis in severe, limb-threatening ischemia. PATIENTS AND METHODS: the BONe Marrow Outcome Trial in Critical Limb Ischemia (BONMOT-CLI) is a investigator-initiated, double-blinded, 1:1 randomized, placebo-controlled multi-centre study at 4 sites in Germany. Only patients with no option for revascularisation or after failed revascularisation will be included. A total of 90 patients is to be included. One arm with 45 subjects will be treated with a concentrate of autologous bone marrow cells which will be injected at 40 sites into the ischemic limb. In the placebo arm, study subjects will undergo a sham bone marrow punction and 40 saline injections. At three months, a combined primary endpoint of major amputation or persisting critical limb ischemia (no clinical or perfusion improvement) will be evaluated. Secondary endpoints are death, changes in perfusion, quality of life, walking distance, minor amputations, wound healing, collateral density and cancer incidence. Post-study follow-up is up to two years. CONCLUSIONS: The results of this first randomized placebo-controlled trial for autologous bone marrow cell therapy in CLI will clarify the value of this new therapeutic modality in a patient population with no other alternatives except major amputation.

Feasibility of using the TOSCA telescreening procedures for diabetic retinopathy.

AIMS: The TOSCA project was set up to establish a tele-ophthalmology service to screen for diabetic retinopathy (DR) in Europe. The aim of this study was to determine the feasibility of establishing telemedicine-based digital screening for detecting DR and to evaluate the satisfaction of both patients and healthcare professionals with the screening procedures used within the TOSCA project. METHODS: The study was a non-randomized, multicentre study carried out in four different countries over a period of 3 months. Patients (n = 390) with diabetes aged > 12 years were included. Two digital retinal images per eye (macular and nasal) were taken and exported to a central server. Patients were asked to complete a questionnaire to assess satisfaction. Accredited graders carried out grading remotely and the results were reported back to the referring centre. Previously graded patient data chosen randomly to represent examples of both DR and no DR were also sent anonymously to the grading centre at a frequency of approximately every 10 patients. RESULTS: Most (99%) of the images were assessable enabling a retinopathy grade to be assigned to the patient. Patients found the retinal photography procedures acceptable; only 6% in one centre would not recommend the procedure. Healthcare professionals (photographers and graders) were also satisfied with the overall procedures. The average time taken to grade each patient was approximately 5 min. CONCLUSIONS: This study demonstrated that it is feasible to electronically transmit and grade retinal images remotely using the TOSCA process. Built-in quality assurance procedures proved acceptable.

A telemedical approach to the screening of diabetic retinopathy: digital fundus photography.

OBJECTIVE: The importance of screening for diabetic retinopathy has been established, but the best method for screening has not yet been determined. We report on a trial of assessment of digital photographs by telemedicine compared with standard retinal photographs of the same fields and clinical examination by ophthalmologists. RESEARCH DESIGN AND METHODS: A total of 129 diabetic inpatients were screened for diabetic retinopathy by slit-lamp biomicroscopy performed by an ophthalmologist and by two-field 50 degrees non-stereo digital fundus photographs assessed by six screening centers that received the images by electronic mail. Conventional 35-mm transparencies of the same fields as the digital photographs were assessed by a retinal specialist and served as the reference method for detection of diabetic retinopathy. Slit-lamp biomicroscopy was the reference method for the detection of macular edema. RESULTS: The prevalence of any form of diabetic retinopathy was 30% (n = 35); of sight-threatening retinopathy including macular edema, the prevalence was 6% (n = 7). The assessment of digital images by the six screening centers resulted in a median sensitivity of 85% and a median specificity of 90% for the detection of moderate nonproliferative or sight-threatening diabetic retinopathy. Clinically significant macular edema (n = 4) was correctly identified in 15 of the 24 grading reports. An additional seven reports referred the patients for further investigation because of concurrent diabetic retinopathy. CONCLUSIONS: Telescreening for diabetic retinopathy by an assessment of two-field 50 degrees non-stereo digital images is a valid screening method. Although detection of clinically significant macular edema using biomicroscopy is superior to digital or standard non-stereo photographs, only few patients with sight-threatening diabetic retinopathy are missed.

Telemedical care reduces hypoglycemias and improves glycemic control in children and adolescents with type 1 diabetes.

Education programs for intensive insulin therapy were found to be valuable in improving glycemic control, but, due to low prevalence of type 1 diabetes in children and adolescents, access to those programs varies considerably in rural areas. We report on a telemedical care program that overcomes geographical isolation of patients on intensive insulin therapy. Sixty-one children and adolescents under the age of 26 participated in a telemedical care program. They stored daily information on blood glucose, injected insulin, meals and exercise in a glucosemeter with electronic memory and transferred the data via modem go a remote diabetes center outside of the region. By individual telephone consultations from home, they reviewed the data with a diabetologist at the diabetes center and adjusted their intensive insulin therapy in order to achieve predefined treatment goals. Patients were trained for 19 (6-48) weeks in the program and measured blood glucose 4.9 (1.7-4.9) times daily. Compared to the run-in-period, mean blood glucose had decreased (167 to 158 mg/dL, p < 0.01), standard deviation of blood glucose had decreased (81 to 70 mg/dL, p < 0.001), and frequency of hypoglycemia had decreased (5.2 to 3.3 in 4 weeks, p = 0.01) at the end of the program. The proportion of blood glucose values within the target range (80-180 mg/dL) had increased (47-55%, p < 0.001). HbAlc was reduced by 0.4% (-3.8 to +2.2%, p < 0.05). Telemedical care for intensive insulin therapy is safe, can improve glycemic control, and reduce the number of hypoglycemias in children and adolescents with type 1 diabetes.

[Teleconsultation network for ophthalmology--experiences and results]. / Telekonsultationsnetzwerk für die Ophthalmologie--Erfahrungen und Ergebnisse.

MOTIVATION: Telemedical services for ophthalmology are developed within the OPHTEL project, which has been funded by the European Union and by the Bavarian government in the Bavaria-online initiative. METHODS: Seven private ophthalmologists, one university eye clinic, one clinical Diabetes center and an informatics research institute are connected within a teleconsultation network. Asynchronous (based on Internet E-Mail) and synchronous (based on ISDN-mediated videoconferencing tools) types of teleconsultations are realized. RESULTS: 86 teleconsultations (62 asynchronous, 23 synchronous) took place within the first 10 months. Complex and rare eye diseases as well as interdisciplinary questions (ophthalmology--diabetology) are the main area of medical communication interest. Legal and security problems are discussed. CONCLUSIONS: Telemedical services must be understood as a complete process of medical care on the basis of modern communication technologies, which influences also the management of this process.

Quality of documentation in medical reports of diabetic patients.

In a retrospective analysis of 752 consecutive medical reports of patients with insulin- or non-insulin-dependent diabetes mellitus, we investigated the completeness of documentation of indicators of quality of care. The medical reports are the currently used form of documentation which is sent to the General Practitioner after the patient's discharge from hospital. The indicators of care were data on clinical history, physical examination, laboratory results and secondary complications. The documentation was incomplete; e.g. in 8.0% of insulin-dependent (IDDM) and in 26.4% of non-insulin-dependent diabetics (NIDDM), HbA1c was missing. In 7.6%, the type of diabetes was not stated. The frequency of recorded secondary complications was lower than it has to be expected considering metabolic control and duration of diabetes of the studied group. Documentation was more complete for IDDM patients. The reports of NIDDM patients with incipient or overt diabetic nephropathy revealed less frequent recordings of data on lipid metabolism and blood pressure compared to the group without nephropathy. The documentation of indicators of quality of care in medical reports for general practitioners is incomplete for many diabetic inpatients. Standardized methods of documentation are required urgently.