Digitization of Follow-Up Care in Orthopedic and Trauma Surgery With Video Consultations: Health Economic Evaluation Study From a Health Provider's Perspective.

BACKGROUND: Recommendations for health care digitization as issued with the Riyadh Declaration led to an uptake in telemedicine to cope with the COVID-19 pandemic. Evaluations based on clinical data are needed to support stakeholders' decision-making on the long-term implementation of digital health. OBJECTIVE: This health economic evaluation aims to provide the first German analysis of the suitability of video consultations in the follow-up care of patients in orthopedic and trauma surgery, investigate the financial impact on hospital operations and personnel costs, and provide a basis for decisions on digitizing outpatient care. METHODS: We conducted a randomized controlled trial that evaluated video consultations versus face-to-face consultations in the follow-up care of patients in orthopedic and trauma surgery at a German university hospital. We recruited 60 patients who had previously been treated conservatively or surgically for various knee or shoulder injuries. A digital health app and a browser-based software were used to conduct video consultations. The suitability of telemedicine was assessed using the Telemedicine Satisfaction Questionnaire and the EQ-5D-5L questionnaire. Economic analyses included average time spent by physician per consultation, associated personnel costs and capacities for additional treatable patients, and the break-even point for video consultation software fees. RESULTS: After 4 withdrawals in each arm, data from a total of 52 patients (telemedicine group: n=26; control group: n=26) were used for our analyses. In the telemedicine group, 77% (20/26) of all patients agreed that telemedicine provided for their health care needs, and 69% (18/26) found telemedicine an acceptable way to receive health care services. In addition, no significant difference was found in the change of patient utility between groups after 3 months (mean 0.02, SD 0.06 vs mean 0.07, SD 0.17; P=.35). Treatment duration was significantly shorter in the intervention group (mean 8.23, SD 4.45 minutes vs mean 10.92, SD 5.58 minutes; P=.02). The use of telemedicine saved 25% (€2.14 [US $2.35]/€8.67 [US $9.53]) in personnel costs and increased the number of treatable patients by 172 annually, assuming 2 hours of video consultations per week. Sensitivity analysis for scaling up video consultations to 10% of the hospital's outpatient cases resulted in personnel cost savings of €73,056 (US $ 80,275.39) for a senior physician. A total of 23 video consultations per month were required to recoup the software fees of telemedicine through reduced personnel costs (break-even point ranging from 12-38 in the sensitivity analysis). CONCLUSIONS: Our study supports stakeholders' decision-making on the long-term implementation of digital health by demonstrating that video consultations in the follow-up care of patients in orthopedic and trauma surgery result in cost savings and productivity gains for clinics with no negative impact on patient utility. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023445; https://drks.de/search/en/trial/DRKS00023445.

Economic and Environmental Impact of Digital Health App Video Consultations in Follow-up Care for Patients in Orthopedic and Trauma Surgery in Germany: Randomized Controlled Trial.

BACKGROUND: Following the Riyadh Declaration, digital health technologies were prioritized in many countries to address the challenges of the COVID-19 pandemic. Digital health apps for telemedicine and video consultations help reduce potential disease spread in routine health care, including follow-up care in orthopedic and trauma surgery. In addition to the satisfaction, efficiency, and safety of telemedicine, its economic and environmental effects are highly relevant to decision makers, particularly for the goal of reaching carbon neutrality of health care systems. OBJECTIVE: This study aims to provide the first comprehensive health economic and environmental analysis of video consultations in follow-up care after knee and shoulder interventions in an orthopedic and trauma surgery department of a German university hospital. The analysis is conducted from a societal perspective. We analyze both economic and environmental impacts of video consultations, taking into account the goal of carbon neutrality for the German health care system by 2030. METHODS: We conducted a prospective randomized controlled trial comparing follow-up care with digital health app video consultations (intervention group) to conventional face-to-face consultations in the clinic (control group). Economic impact included the analysis of travel and time costs and production losses. Examination of the environmental impact comprised the emissions of greenhouse gases, carbon monoxide, volatile hydrocarbons, nitrogen oxides, and particulates, and the calculation of environmental costs. Sensitivity analysis included calculations with a higher cost per ton of carbon dioxide equivalent, which gives equal weight to the welfare of present and future generations. RESULTS: Data from 52 patients indicated that, from the patients' point of view, telemedicine helped reduce travel costs, time costs, and production losses, resulting in mean cost savings of €76.52 per video consultation. In addition, emissions of 11.248 kg of greenhouse gases, 0.070 kg of carbon monoxide, 0.011 kg of volatile hydrocarbons, 0.028 kg of nitrogen oxides, and 0.0004 kg of particulates could be saved per patient through avoided travel. This resulted in savings of environmental costs between €3.73 and €9.53 per patient. CONCLUSIONS: We presented the first comprehensive analysis of economic and environmental effects of telemedicine in the follow-up care of patients in orthopedic and trauma surgery in Germany. Video consultations were found to reduce the environmental footprint of follow-up care; saved travel costs, travel time, and time costs for patients; and helped to lower production losses. Our findings can support the decision-making on the use of digital health during and beyond the COVID-19 pandemic, providing decision makers with data for both economic and environmental effects. Thanks to the pragmatic design of our study, our findings can be applied to a wide range of clinical contexts and potential digital health applications that substitute outpatient hospital visits with video consultations. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023445; https://tinyurl.com/4pcvhz4n.

Assessing Telemedicine Efficiency in Follow-up Care With Video Consultations for Patients in Orthopedic and Trauma Surgery in Germany: Randomized Controlled Trial.

BACKGROUND: Telemedicine can help mitigate important health care challenges, such as demographic changes and the current COVID-19 pandemic, in high-income countries such as Germany. It gives physicians and patients the opportunity to interact via video consultations, regardless of their location, thus offering cost and time savings for both sides. OBJECTIVE: We aimed to investigate whether telemedicine can be implemented efficiently in the follow-up care for patients in orthopedic and trauma surgery, with respect to patient satisfaction, physician satisfaction, and quality of care. METHODS: We conducted a prospective randomized controlled trial in a German university hospital and enrolled 60 patients with different knee and shoulder conditions. For follow-up appointments, patients received either an in-person consultation in the clinic (control group) or a video consultation with their physician (telemedicine group). Patients' and physicians' subsequent evaluations of these follow-up appointments were collected and assessed using separate questionnaires. RESULTS: On the basis of data from 52 consultations after 8 withdrawals, it was found that patients were slightly more satisfied with video consultations (mean 1.58, SD 0.643) than with in-clinic consultations (mean 1.64, SD 0.569), although the difference was not statistically significant (P=.69). After excluding video consultations marred by technical problems, no significant difference was found in physician satisfaction between the groups (mean 1.47, SD 0.516 vs mean 1.32, SD 0.557; P=.31). Further analysis indicated that telemedicine can be applied to broader groups of patients and that patients who have prior experience with telemedicine are more willing to use telemedicine for follow-up care. CONCLUSIONS: Telemedicine can be an alternative and efficient form of follow-up care for patients in orthopedic and trauma surgery in Germany, and it has no significant disadvantages compared with in-person consultations in the clinic. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023445; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023445.

Automated analysis of spontaneous eye blinking in patients with acute facial palsy or facial synkinesis.

Although patients with facial palsy often complain of disturbed eye blinking which may lead to visual impairment, a blinking analysis is not part of routine grading of facial palsy. Twenty minutes of spontaneous eye blinking at rest of 30 patients with facial palsy (6 with acute palsy; 24 patients with facial synkinesis; median age: 58 years, 67% female), and 30 matched healthy probands (median age: 57 years; 67% female) was smart phone video recorded. A custom computer program automatically extracted eye measures and determined the eye closure rate (eye aspect ratio [EAR]), blink frequency, and blink duration. Facial Clinimetric Evaluation (FaCE), Facial Disability Index (FDI) were assessed as patient-reported outcome measures. The minimal EAR, i.e., minimal visible eye surface during blinking, was significantly higher on the paretic side in patients with acute facial palsy than in patients with synkinesis or in healthy controls. The blinking frequency on the affected side was significantly lower in both patient groups compared to healthy controls. Vice versa, blink duration was longer in both patient groups. There was no clear correlation between the blinking values and FaCE and FDI. Blinking parameters are easy to estimate automatically and add a functionally important parameter to facial grading.

Numerical simulation of periodic surface structures created by direct laser interference patterning.

Surface structuring using nano-second lasers can be used to enhance certain properties of a material or even to introduce new ones. One way to create these structures efficiently is direct laser interference patterning using different polarization vector orientations of the interfering beams. However, experimentally measuring the fabrication process of these structures is very challenging due to small length and time scales. Therefore, a numerical model is developed and presented for resolving the physical effects during formation the predicting the resolidified surface structures. This three-dimensional, compressible computational fluid dynamics model considers the gas, liquid, and solid material phase and includes various physical effects, such as heating due to the laser beam for both parallel and radial polarization vector orientations, melting, solidification, and evaporation, Marangoni convection, and volumetric expansion. The numerical results reveal a very good qualitatively and quantitatively agreement with experimental reference data. Resolidified surface structures match both in overall shape as well as crater diameter and height, respectively. Furthermore, this model gives valuable insight on different quantities during the formation of these surface structures, such as velocity and temperature. In future, this model can be used to predict surface structures based on various process input parameters.

Test-retest reliability of high-resolution surface electromyographic activities of facial muscles during facial expressions in healthy adults: A prospective observational study.

Objectives: Surface electromyography (sEMG) is a standard method for psycho-physiological research to evaluate emotional expressions or in a clinical setting to analyze facial muscle function. High-resolution sEMG shows the best results to discriminate between different facial expressions. Nevertheless, the test-retest reliability of high-resolution facial sEMG is not analyzed in detail yet, as good reliability is a necessary prerequisite for its repeated clinical application. Methods: Thirty-six healthy adult participants (53% female, 18-67 years) were included. Electromyograms were recorded from both sides of the face using an arrangement of electrodes oriented by the underlying topography of the facial muscles (Fridlund scheme) and simultaneously by a geometric and symmetrical arrangement on the face (Kuramoto scheme). In one session, participants performed three trials of a standard set of different facial expression tasks. On one day, two sessions were performed. The two sessions were repeated two weeks later. Intraclass correlation coefficient (ICC) and coefficient of variation statistics were used to analyze the intra-session, intra-day, and between-day reliability. Results: Fridlund scheme, mean ICCs per electrode position: Intra-session: excellent (0.935-0.994), intra-day: moderate to good (0.674-0.881), between-day: poor to moderate (0.095-0.730). Mean ICC's per facial expression: Intra-session: excellent (0.933-0.991), intra-day: good to moderate (0.674-0.903), between-day: poor to moderate (0.385-0.679). Kuramoto scheme, mean ICC's per electrode position: Intra-session: excellent (0.957-0.970), intra-day: good (0.751-0.908), between-day: moderate (0.643-0.742). Mean ICC's per facial expression: Intra-session: excellent (0.927-0.991), intra-day: good to excellent (0.762-0.973), between-day: poor to good (0.235-0.868). The intra-session reliability of both schemes were equal. Compared to the Fridlund scheme, the ICCs for intra-day and between-day reliability were always better for the Kuramoto scheme. Conclusion: For repeated facial sEMG measurements of facial expressions, we recommend the Kuramoto scheme.

High-resolution surface electromyographic activities of facial muscles during the six basic emotional expressions in healthy adults: a prospective observational study.

High-resolution facial surface electromyography (HR-sEMG) is suited to discriminate between different facial movements. Whether HR-sEMG also allows a discrimination among the six basic emotions of facial expression is unclear. 36 healthy participants (53% female, 18-67 years) were included for four sessions. Electromyograms were recorded from both sides of the face using a muscle-position oriented electrode application (Fridlund scheme) and by a landmark-oriented, muscle unrelated symmetrical electrode arrangement (Kuramoto scheme) simultaneously on the face. In each session, participants expressed the six basic emotions in response to standardized facial images expressing the corresponding emotions. This was repeated once on the same day. Both sessions were repeated two weeks later to assess repetition effects. HR-sEMG characteristics showed systematic regional distribution patterns of emotional muscle activation for both schemes with very low interindividual variability. Statistical discrimination between the different HR-sEMG patterns was good for both schemes for most but not all basic emotions (ranging from p > 0.05 to mostly p < 0.001) when using HR-sEMG of the entire face. When using information only from the lower face, the Kuramoto scheme allowed a more reliable discrimination of all six emotions (all p < 0.001). A landmark-oriented HR-sEMG recording allows specific discrimination of facial muscle activity patterns during basic emotional expressions.

Microangiopathy in Inflammatory Diseases-Strategies in Surgery of the Lower Extremity.

BACKGROUND: Patients with an inflammatory disease frequently develop chronic angiopathy of the capillaries. Due to this pathology, there is an increased rate of complications in lower extremity surgical procedures. It is not uncommon for microangiopathic wound healing disorders to cause deep infections and fistulas, which lead to prolonged courses and hospitalizations. In addition, adhesions and ossifications of the contractile elements occur regularly. This sometimes results in serious limitations of the mobility of the patients. The study aims to present the results of a combination of vacuum and physical therapy. PATIENT AND METHODS: A retrospective study of six patients with systemic sclerosis undergoing joint-related procedures of the lower extremity between 2015 and 2020 was performed. In addition to characterization of the patients and therapy, special attention was paid to cutaneous wound healing, affection of the fascia and displacement layers, and sclerosis of the muscle and tendon insertion. RESULTS: The characterized structures (skin, tendon, fascia) show pathological changes at the microangiopathic level, which are associated with delayed healing and less physical capacity. Early suture removal regularly results in secondary scar dehiscence. With a stage-adapted vacuum therapy with sanitation of the deep structures and later on a dermal vacuum system, healing with simultaneous mobilization of the patients could be achieved in our patient cohort. CONCLUSION: In the case of necessary interventions on the lower extremity, such as trauma surgery, additional decongestive measures in the sense of regular and sustained lymphatic therapy and adapted physiotherapy are indispensable.

Influence of Thoracic Trauma on Fracture Healing in Long Bones-A Retrospective Analysis.

PURPOSE: Pre-clinical studies indicate that concomitant thoracic trauma impairs fracture healing of long bones and reduces callus formation. The aim of this study was to investigate whether patients with accompanying chest trauma suffer from delayed fracture healing of long bones in comparison with patients with fractures of two long bones or isolated fractures. PATIENTS AND METHODS: This is a clinical retrospective study from a level I trauma center. The patients were divided into three groups: (1) thoracic trauma and fracture of a long bone, (2) fractures of two long bones, (3) isolated fracture of a long bone. The fracture consolidation was defined using the radiographic union scale in tibial fractures (RUST). A RUST value of ≥10 six-to-eight months after definitive operative intervention represented complete fracture healing. RESULTS: In the first group 19 (43.2%) fractures did not show full consolidation, in the second group 14 (45.2%) and 13 (41.9%) and in the third group 14 (36.8%). The analysis revealed no statistically significant differences between the groups regarding consolidation of the fractures six-to-eight months after definitive operative intervention (p = 0.84). CONCLUSIONS: Unlike previously reported pre-clinical data, this study did not demonstrate a negative effect on fracture consolidation in long bones when accompanied by thoracic trauma. Furthermore, the results demonstrated that concomitant fractures of two long bones does not have a negative effect on fracture consolidation.

Maximization of Open Hospital Capacity under Shortage of SARS-CoV-2 Vaccines-An Open Access, Stochastic Simulation Tool.

Motive. The Covid-19 pandemic has led to the novel situation that hospitals must prioritize staff for a vaccine rollout while there is acute shortage of the vaccine. In spite of the availability of guidelines from state agencies, there is partial confusion about what an optimal rollout plan is. This study investigates effects in a hospital model under different rollout schemes. Methods. A simulation model is implemented in VBA, and is studied for parameter variation in a predefined hospital setting. The implemented code is available as open access supplement. Main results. A rollout scheme assigning vaccine doses to staff primarily by staff's pathogen exposure maximizes the predicted open hospital capacity when compared to a rollout based on a purely hierarchical prioritization. The effect increases under resource scarcity and greater disease activity. Nursing staff benefits most from an exposure focused rollout. Conclusions. The model employs SARS-CoV-2 parameters; nonetheless, effects observable in the model are transferable to other infectious diseases. Necessary future prioritization plans need to consider pathogen characteristics and social factors.

Long-Term Results of the Modular Physiological Wrist Prosthesis (MPW®) in Patients with Inflammatory Diseases.

The wrist is among the predilection sites of over 90% of cases of rheumatoid arthritis (RA). In advanced cases, total wrist arthroplasty (TWA) is an alternative to arthrodesis. The aim of this study is to present the long-term results of the modular physiological wrist prosthesis (MPW®) and to match them in context with the results of a standard population survey. In a retrospective study with follow-up, patients with an MPW® endoprosthesis were evaluated concerning the clinical and radiological outcome, complications were reviewed (incidence and type), and conversion to wrist fusion was assessed. Patient function measurements included the Mayo wrist score, the patient-specific wrist test, and therefore the DASH score (arm, shoulder, and hand). Thirty-four MPW® wrist prostheses were implanted in 32 patients, including thirty primary implantations and four changes of the type of the endoprosthesis. Sixteen patients (18 prostheses) underwent clinical and radiological follow-up. The average follow-up time was 8.5 years (1 to 16). Poor results of the MPW prosthesis are caused by the issues of balancing with luxation and increased PE wear. Salvage procedures included revision of the TWA or fusion. In successful cases, the flexion and extension movement averaged 40 degrees. The grip force was around 2.5 kg. The common DASH score was 79 points, with limited and problematic joints of the upper extremity. The MPW wrist prosthesis offered good pain relief and functional movement in over 80% of cases. The issues of dislocation and increased PE wear prevent better long-term results, as do the joints affected. A follow-up study with fittings under a contemporary anti-rheumatic therapy with biologicals suggests increasing score results. Type of study/level of evidence: Case series, IV.

The effect of visual feedback on people suffering from chronic back and neck pain - a systematic review.

Objectives: Visual feedback as an intervention for people suffering from chronic back or chronic neck pain is a novel approach based on the person's perception of the painful body part. Visual feedback is an innovative therapeutic approach whose effects have not yet been systematically reviewed specifically for people with chronic back or chronic neck pain. Therefore, a systematic review was performed on the literature to evaluate the effects of visual feedback on pain intensity in people with chronic back or neck pain. Methods: This systematic review investigated the magnitude and clinical relevance of the reported effects, as well as the reporting quality of the included studies. Pain intensity was defined as the outcome of interest to judge the clinical relevance of the findings. The quality of reporting and the risk of bias were assessed. Results: The original search revealed 359 studies of which five were included following screening of the title and abstract, application of the inclusion/exclusion criteria and reading the full texts. All five studies had investigated chronic back pain. Most studies showed either a momentary decrease of pain intensity during the application of a visual feedback method or a habitual decrease after treatment for 2 weeks. Discussion: While visual feedback does appear to alter pain intensity in people with chronic back pain, there is limited evidence from these studies to support visual feedback as an adjunct to therapy. These issues point out that future studies may be indicated.

Evidence of Prolonged Monitoring of Trauma Patients Admitted via Trauma Resuscitation Unit without Primary Proof of Severe Injuries.

Introductio: Although management of severely injured patients in the Trauma Resuscitation Unit (TRU) follows evidence-based guidelines, algorithms for treatment of the slightly injured are limited. METHODS: All trauma patients in a period of eight months in a Level I trauma center were followed. Retrospective analysis was performed only in patients ≥18 years with primary TRU admission, Abbreviated Injury Scale (AIS) ≤ 1, Maximum Abbreviated Injury Scale (MAIS) ≤ 1 and Injury Severity Score (ISS) ≤3 after treatment completion and ≥24 h monitoring in the units. Cochran's Q-test was used for the statistical evaluation of AIS and ISS changes in units. RESULTS: One hundred and twelve patients were enrolled in the study. Twenty-one patients (18.75%) reported new complaints after treatment completion in the TRU. AIS rose from the Intermediate Care Unit (IMC) to Normal Care Unit (NCU) 6.2% and ISS 6.9%. MAIS did not increase >2, and no intervention was necessary for any patient. No correlation was found between computed tomography (CT) diagnostics in TRU and AIS change. CONCLUSIONS: The data suggest that AIS, MAIS and ISS did not increase significantly in patients without a severe injury during inpatient treatment, regardless of the type of CT diagnostics performed in the TRU, suggesting that monitoring of these patients may be unnecessary.

Comparable transforming capacities and differential gene expression patterns of variant FUS/CHOP fusion transcripts derived from soft tissue liposarcomas.

The chromosomal translocation t(12;16)(q13;p11) is a common genetic alteration in myxoid and round-cell liposarcomas. It results in transcription of various chimeric FUS/CHOP fusion transcripts that encode different oncogenic proteins. Recent reports suggest that these may have different neoplastic transformation activities. To audit this hypothesis, we transfected expression plasmids for the two major variant FUS/CHOP transcripts I and II in NIH 3T3 cells and determined the number of outgrowing foci as well as their growth potential in soft agar. In addition, we compared tumour growth in nude mice upon subcutaneous injection of the respective transfectants. No significant differences in transformation assays in vitro and in vivo were observed, suggesting that both variant transcripts confer comparable transforming activities. The histopathological picture of tumours derived from both cell populations resembles high-grade spindle cell sarcomas. This suggests that both FUS/CHOP variants cause similar patterns of differential gene expression. This hypothesis was confirmed by mRNA-expression profiles of the respective cell clones. Strong overexpression of the pentaxin-related gene (PTX), the osteoblast-specific factor 2 (osf-2), the basic Kruppel-like factor (bklf), the leucoprotease inhibitor, and the cyclophilin B were observed in both types of FUS/CHOP-transfected cell clones. Taken together, our data suggest that different FUS/CHOP variants cause transformation of mesenchymal cells via the same pathways with comparable efficacy.

Navigated total hip arthroplasty using a 3-D freehand ultrasound system: technical note and preliminary results.

Ultrasound-navigated cementless total hip arthroplasty (THA) was performed in 10 consecutive patients with primary osteoarthritis of the hip between August 2008 and October 2009 (M:F, 6:4; median age, 61 years; age range, 30-86 years). The pelvic orientation was defined by preoperative digitization and registration of bony landmarks. Cup inclination and anteversion were documented for each patient intraoperatively (epidigitized vs ultrasound-assessed landmarks). The median difference between the palpated and ultrasound anterior pelvic plane was 8° (range, 4°-18°) for pelvic tilt (rotation around the transversal axis), 1° (range, -3° to 2°) for rotation around the longitudinal axis, and 0.25° (range, -2.0° to 5.0°) for rotation around the sagittal axis. The median difference in cup orientation resulting from pelvic tilt error was 6° (range, 3°-13°) for anteversion and 3° (range, -1° to 5°) for inclination. There were no intra- or postoperative complications. The measured width of soft tissue layer anterior to the pelvic symphysis correlated significantly with the measured difference in cup inclination and anteversion. One centimeter of soft tissue anterior to the symphysis resulted in a median 2° (range, 1.75°-2.3°) difference in pelvic tilt. Ultrasound-assisted navigation in THA is a promising technology able to eliminate systematic errors in anterior pelvic plane orientation, in contrast to conventionally navigated THA using percutaneous palpation of landmarks or THA without navigational support.

Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.

BACKGROUND: Early graft function (EGF) has an enduring effect on the subsequent course after kidney transplantation. This study compares quantitative parameters of EGF for the prediction of graft survival. METHODS: We involved 300 consecutive transplant recipients from deceased donors from 1989 to 2005. Urine output during 24 h post-transplant (UO), and serum creatinine after 1 week (Cr7) were taken for explanatory variables. We generated Kaplan-Meier (K-M) estimates of graft survival, by quintiles of the explanatory variable. Cox regression was applied to control for various recipient factors. RESULTS: K-M survival estimates indicate a threshold effect of UO and Cr7, which can dissect the risk of graft failure. The thresholds referring to the 2nd quintile correspond to a UO >630 ml and a Cr7 <2.5 mg/dl and were associated with a proportional hazard ratio of 0.52 (95% CI 0.33-0.84) and 0.34 (95% CI 0.18-0.65), respectively. Combining both of the parameters predicted a 5-year graft survival probability >90%, according to a hazard ratio of 0.21 (95% CI 0.09-0.46). Requirement of dialysis post-transplant lost its discriminatory power and was not a significant explanatory variable in the multivariate analysis. CONCLUSION: Routine parameters for monitoring of EGF display a threshold effect allowing accurate prediction of 5-year graft survival at the earliest point in time. The quantitative threshold levels for an optimum discriminatory power require validation in a larger, preferably multicentre database.