Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

Riluzole in Spinal Cord Injury Study (RISCIS)-Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients With Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial.

To date, no drug therapy has shown significant efficacy in improving functional outcomes in patients with acute spinal cord injury (SCI). Riluzole is an approved benzothiazole sodium channel blocker to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) and is of interest for neuroprotection in SCI. In a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT00876889), riluzole was well tolerated with a 2-week treatment at the dose level approved for ALS and exhibited potential efficacy in patients with SCI. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes alter the pharmacokinetics (PK) of therapeutics. In the PK sub-study of the multi-center, randomized, placebo-controlled, double-blinded Riluzole in Spinal Cord Injury Study (RISCIS) Phase II/III trial (ClinicalTrials.gov Identifier: NCT01597518), a total of 32 SCI patients were enrolled, and most of our patients were middle-age Caucasian males with head and neck injuries. We studied the PK and pharmacodynamics (PD) of riluzole on motor recovery, measured by International Standards for Neurological Classification of SCI (ISNCSCI) Motor Score at injury and at 3-month and 6-month follow-ups, along with levels of the axonal injury biomarker phosphorylated neurofilament heavy chain (pNF-H), during the 2-week treatment. PK modeling, PK/PD correlations were developed to identify the potential effective exposure of riluzole for intended PD outcomes. The longitudinal impacts of SCI on the PK of riluzole are characterized. A time-varying population PK model of riluzole is established, incorporating time-varying clearance and volume of distribution from combined data of Phase I and Phase II/III trials. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification to preserve the required therapeutic exposure of riluzole. The PD of riluzole and the relationship between PK and neurological outcomes of the treatment were established. The time course of efficacy in total motor score improvement (ΔTMS) and pNF-H were monitored. A three-dimensional (3D) PK/PD correlation was established for ΔTMS at 6 months with overall riluzole exposure area under the curve for Day 0-Day14 (AUCD0-D14) and baseline TMS for individual patients. Patients with baseline TMS between 1 and 36 benefited from the optimal exposure range of 16-48 mg*h/mL. The PD models of pNF-H revealed the riluzole efficacy, as treated subjects exhibited a diminished increase in progression of pNF-H, indicative of reduced axonal breakdown. The independent parameter of area between effective curves (ABEC) between the time profiles of pNF-H in placebo and treatment groups was statistically identified as a significant predictor for the treatment effect on the biomarker. A mechanistic clinical outcomes (CO)/PD (pNF-H) model was established, and the proposed structure demonstrated the feasibility of PK/PD/CO correlation model. No appreciable hepatic toxicity was observed with the current riluzole treatment regimen. The development of effective treatment for SCI is challenging. However, the future model-informed and PK-guided drug development and regimen modification can be rationally executed with the optimal dosing regimen design based on the developed 3D PK/PD model. The PK/PD/CO model can serve as a rational guide for future drug development, PKPD model refinement, and extension to other studies in SCI settings.

Oligometastatic Parathyroid Carcinoma Presenting as Neck Pain: A Case Report.

BACKGROUND: Parathyroid carcinoma (PC) is an exceedingly rare, slow-growing but progressive endocrine malignancy that represents a diagnostic and therapeutic challenge. Vertebral metastasis of PC is remarkable, with only 3 prior cases of spinal metastasis reported in the literature. CASE DESCRIPTION: A 62-year-old woman presented with 1 week of neck pain radiating down her right arm. Cervical x-ray revealed a lytic lesion of the C4 vertebral body. Lab work revealed hypercalcemia with an elevated parathyroid hormone level. Computed tomography and magnetic resonance imaging revealed frank destruction of the C4 vertebral body and pedicles by PC. She was treated with corpectomy, mass excision, anterior cervical discectomy and fusion, postoperative radiotherapy, and nonspecific inhibitors of active tumor pathways. Her symptoms resolved postoperatively, and she has remained negative for reoccurrence at 15-month follow-up. CONCLUSIONS: To the authors' knowledge, we report the first described cervical spine metastasis of PC. Additionally, we review the treatment of this rare neoplasm in an extremely rare location in the age of tumor sequencing and morphoproteomic analysis.

Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial.

BACKGROUND: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome. METHODS: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. RESULTS: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. CONCLUSIONS: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.

Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent.

Riluzole, a benzothiazole sodium channel blocker that received US Food and Drug Administration approval to attenuate neurodegeneration in amyotrophic lateral sclerosis in 1995, was found to be safe and potentially efficacious in a spinal cord injury (SCI) population, as evident in a phase I clinical trial. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes can alter the pharmacokinetics of therapeutics. A 1-compartment with first-order elimination population pharmacokinetic model for riluzole incorporating time-dependent clearance and volume of distribution was developed from combined data of the phase 1 and the ongoing phase 2/3 trials. This change in therapeutic exposure may lead to a biased estimate of the exposure-response relationship when evaluating therapeutic effects. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification that preserves the required therapeutic exposure of riluzole.

Atlanto-occipital distraction injuries in survivors: craniometrics and associated ligamentous, spinal cord, and blunt cerebrovascular injury.

PURPOSE: Newer classification systems for upper cervical spine trauma now include ligamentous injury in addition to fracture and dislocation patterns. Assessment of associated ligamentous injury, spinal cord injury (SCI), and blunt cerebrovascular injuries (BCVI) in patients with atlanto-occipital distraction injuries (AODI) are critical for management. We aim to determine the incidence of ligamentous injury, SCI, and BCVI in patients with AODI and assess how craniometrics perform in diagnosis of AODI. MATERIALS AND METHODS: We performed an IRB-approved retrospective analysis of 35 cases of diagnosed AODI over a period of 8 years. Imaging was analyzed by two experienced neuroradiologists for craniometric measurements, ligamentous injury, SCI, and BCVI. Craniometric measurements were compared to 35 age-matched controls with normal atlanto-occipital joint. RESULTS: Out of 35 patients diagnosed with AODI, 27 were adults and 8 belonged to pediatric age group. The mean age of presentation was 29.4 years with a male/female ratio of 22:13. The basion-dental interval (70.4%) and the combined condylar sum (74.1%) were the most sensitive craniometric measurements for diagnosis of AODI. Alar ligament (83%) and the tectorial membrane (89%) injuries were most commonly injured ligaments. Three adult patients sustained SCI and 10 patients had BCVI. Majority of BCVI involved the internal carotid artery followed by the vertebral artery. CONCLUSIONS: The combination of craniometric indices with assessment of ligamentous injuries provides higher diagnostic accuracy for AODI. Alar ligament and tectorial membrane injuries have high association with AODI. There is high association of SCI and BCVI in AODI survivors.

Fewer Cardiopulmonary Complications and Shorter Length of Stay in Anterolateral Thoracolumbar Spine Exposures Using a Small-Incision Specialized Retractor System.

Objectives: One of the challenges of spine surgery is the need for adequate exposure of the anterolateral spinal column. Improved retractor systems with integrated lighting minimize the need for large thoracotomy, flank, or abdominal incisions. In 2013, we began using the NuVasive MaXcess® system via a minimal-access lateral incision for thoracic and thoracolumbar spine exposures. These small-access approaches may not offer adequate exposure when bleeding and other complications arise. We sought to determine the feasibility and outcomes of a minimal-access retractor during anterolateral spine exposures. Methods: An institutional-review-board-approved retrospective chart review was performed of all patients who underwent anterolateral thoracic and lumbosacral spine exposure at an academic hospital between December 1999 and April 2017. Cervical and posterior spine exposures were not included. Information regarding patient demographics, comorbid conditions, operative techniques, exposure, estimated blood loss, length of stay, and intraoperative and postoperative complications was collected. Data for standard exposure vs. minimally invasive exposures were compared. Results: Between December 1999 and April 2017, 223 anterolateral spinal exposures were performed at our institution. Of those, 122 (54.7%) patients had true lateral exposures, with 22 (18%) using the minimally invasive retractor. The mean age of our patient population was 57 years (19-89), with 65 (53%) men and a mean body mass index of 29.0 (17.4-58.6). In the standard exposure group, complications occurred in 22 (22%) patients, whereas only two (9%) complications occurred in the minimal-access group. There were no significant differences in overall intraoperative and postoperative complications, except for cardiopulmonary complications, which were reduced in the minimally invasive group (p < 0.019). Patients with minimally invasive exposure had a significantly shorter length of stay than those with standard exposure (7 vs. 13 days, p = 0.001). Conclusions: Minimal-access techniques using advanced retractor systems are both feasible and safe compared to standard techniques allowing for similar lateral spine exposure, but with smaller incisions, fewer cardiopulmonary complications, and shorter lengths of stay.

Integrating Health System Preparedness and Community Resilience: Using the CMS Preparedness Rule as a Focusing Event.

This commentary discusses the prospect and value of using the preparedness rule developed and implemented by the Centers for Medicare and Medicaid Services as a focal point for better integrating health system preparedness into broader community resilience efforts, whether at the local or international level. Much attention has been given to the idea that community resilience requires extensive collaboration and coordination between actors across sectors, elements that are vital to effective emergency preparedness in health care as well. To facilitate improved fiscal sustainability, the federal government has since 2012 been encouraging healthcare coalitions to pursue nonprofit status. Building such organizations for the long term will require coalitions to become more proactive in involving organizations outside of the health sector. The preparedness rule has done much to encourage more dialogue between health system actors, and we argue that this momentum should be carried forward to generate a broader discussion of the importance of health preparedness to community resilience. The value of embedding preparedness planning into larger community resilience initiatives is discussed.

Increased Levels of Circulating Glial Fibrillary Acidic Protein and Collapsin Response Mediator Protein-2 Autoantibodies in the Acute Stage of Spinal Cord Injury Predict the Subsequent Development of Neuropathic Pain.

Neuropathic pain develops in 40-70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1-41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). Results from study 1 indicated that GFAPab were present in 34 of 80 (42.5%) patients, but circulating levels did not correlate with the occurrence of neuropathic pain. In study 2, longitudinal plasma samples and clinical data were collected from 38 acute SCI patients. The level of GFAPab measured at 16 ± 7 days post-SCI was found to be significantly higher in patients that subsequently developed neuropathic pain (within 6 months post-SCI) than patients who did not (T = 219; p = 0.02). In study 3, we identified CRMP2 as an autoantibody target (CRMP2ab) in 23% of acute SCI patients. The presence of GFAPab and/or CRMP2ab increased the odds of subsequently developing neuropathic pain within 6 months of injury by 9.5 times (p = 0.006). Our results suggest that if a causal link can be established between these autoantibodies and the development of neuropathic pain, strategies aimed at reducing the circulating levels of these autoantibodies may have therapeutic value.

Early chemoprophylaxis is associated with decreased venous thromboembolism risk without concomitant increase in intraspinal hematoma expansion after traumatic spinal cord injury.

BACKGROUND: After traumatic spinal cord injury (SCI), there is increased risk of venous thromboembolism (VTE), but chemoprophylaxis (PPX) may cause expansion of intraspinal hematoma (ISH). METHODS: Single-center retrospective study of adult trauma patients from 2012 to 2015 with SCI. EXCLUSION CRITERIA: VTE diagnosis, death, or discharge within 48 hours. Patients were dichotomized based on early (≤48 hours) heparinoid and/or aspirin PPX. Intraspinal hematoma expansion was diagnosed intraoperatively or by follow-up radiology. We used multivariable Cox proportional hazards to estimate the effect of PPX on risk of VTE and ISH expansion controlling for age, injury severity score (ISS), complete SCI, and mechanism as static covariates and operative spine procedure as a time-varying covariate. RESULTS: Five hundred one patients with SCI were dichotomized into early PPX (n = 260 [52%]) and no early PPX (n = 241 [48%]). Early PPX patients were less likely blunt injured (91% vs 97%) and had fewer operative spine interventions (65% vs 80%), but age (median, 43 vs 49 years), ISS (median 24 vs 21), admission ISH (47% vs 44%), and VTE (5% vs 9%) were similar. Cox analysis found that early heparinoids was associated with reduced VTE (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.16-0.84) and reduced pulmonary embolism (PE) (HR, 0.20; 95% CI, 0.06-0.69). The estimated number needed to treat with heparinoids was 10 to prevent one VTE and 13 to prevent one PE at 30 days. Early aspirin was not associated with reduced VTE or PE. Seven patients (1%) had ISH expansion, of which four were on PPX at the time of expansion. Using heparinoid and aspirin as time-varying covariates, neither heparinoids (HR, 1.90; 95% CI, 0.32-11.41) nor aspirin (HR, 3.67; 95% CI, 0.64-20.88) was associated with ISH expansion. CONCLUSION: Early heparinoid therapy was associated with decreased VTE and PE risk in SCI patients without concomitant increase in ISH expansion. LEVEL OF EVIDENCE: Therapeutic, level IV.

Human neural progenitors derived from integration-free iPSCs for SCI therapy.

As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

Communicating Hydrocephalus Due to Traumatic Lumbar Spine Injury: Case Report and Literature Review.

: Hydrocephalus is a rare complication of traumatic spine injury. A literature review reflects the rare occurrence with cervical spine injury. We present a case of traumatic injury to the lumbar spine from a gunshot wound, which caused communicating hydrocephalus. The patient sustained a gunshot wound to the lumbar spine and had an L4-5 laminectomy with exploration and removal of foreign bodies. At the time of surgery, the patient was found to have dense subarachnoid hemorrhage in the spinal column. He subsequently had intermittent headaches and altered mental status that resolved without intervention. The headaches worsened, so a computed tomography scan of the brain was obtained, which revealed hydrocephalus. A ventriculoperitoneal shunt was placed, and subsequent computed tomography scan of the brain showed reduced ventricle size. The patient returned to rehabilitation with complete resolution of hydrocephalus symptoms. Intrathecal hemorrhage with subsequent obstruction or decreased absorption of cerebrospinal fluid at the distal spinal cord was thought to lead to communicating hydrocephalus in this case of lumbar penetrating trauma. In patients with a history of hemorrhagic, traumatic spinal injury who subsequently experience headaches or altered mental status, hydrocephalus should be included in the differential diagnosis and adequately investigated.

Identification of autoantibodies to glial fibrillary acidic protein in spinal cord injury patients.

Traumatic spinal cord injury (SCI) is a devastating injury causing significant morbidity and mortality. Experimental studies have demonstrated that SCI induced cellular damage and disruption of the blood-spinal cord barrier can initiate an autoimmune response. This response is thought to be pathogenic and contribute to poor outcome. The objective of this research was to investigate whether human SCI mounts an autoimmune response to self-antigens. Plasma samples were collected longitudinally from SCI patients (n=18) at acute (T1, <48 h) and subacute (T2, 2-4 weeks) time points to probe western blots of human brain homogenates in order to screen patients for the presence of putative autoantibodies. To identify the corresponding antigens, two-dimensional gel electrophoresis, western blot and liquid chromatography coupled with mass spectrometry (LC-MS/MS) analyses were performed. We found that four of 18 patients (22%) had novel immunoreactive bands ranging in size from 36 to 42 kDa present in subacute, but not in acute, plasma samples suggesting postinjury production. To identify the cross-reacting antigens, we separated brain proteins by two-dimensional gel electrophoresis and identified nine immunoreactive spots. Amino acid sequence analysis of these spots identified peptides that mapped to glial fibrillary acidic protein. Our results suggest that ∼ 22% of SCI patients generated autoantibodies to glial fibrillary acidic protein. Future studies will be required to determine whether these autoantibodies contribute to the pathogenic sequelae of SCI.

The peacock's train (Pavo cristatus and Pavo cristatus mut. alba) II. The molecular parameters of feather keratin plasticity.

Thermal activation analysis of plastic deformation of peacock tail feathers, by temperature changes and stress relaxation, gave for the keratin cortex an activation enthalpy of 1.78 ± 0.89 eV and an activation volume of 0.83 ± 0.13 nm³, for both the blue and the white subspecies. These values suggest that breaking of electrostatic bonds is responsible for plasticity in feather keratin. These might be bonds between keratin and nonkeratinous matrix or keratin-keratin cross-links. The mechanical properties of the rachis cortex are surprisingly uniform along the length of the feathers.

Complex dynamics and synchronization of delayed-feedback nonlinear oscillators.

We describe a flexible and modular delayed-feedback nonlinear oscillator that is capable of generating a wide range of dynamical behaviours, from periodic oscillations to high-dimensional chaos. The oscillator uses electro-optic modulation and fibre-optic transmission, with feedback and filtering implemented through real-time digital signal processing. We consider two such oscillators that are coupled to one another, and we identify the conditions under which they will synchronize. By examining the rates of divergence or convergence between two coupled oscillators, we quantify the maximum Lyapunov exponents or transverse Lyapunov exponents of the system, and we present an experimental method to determine these rates that does not require a mathematical model of the system. Finally, we demonstrate a new adaptive control method that keeps two oscillators synchronized, even when the coupling between them is changing unpredictably.

Optimizing workflow and knowledge in healthcare through innovation.

People's desire is to stay healthy during the entire course of their live. Innovations in medicine in care and technology have always contributed significantly to meet this desire as close as possible. Today, healthcare systems are faced with huge additional challenges. The focus of nearly every healthcare debate is on costs. But is this debate target-oriented and does it support the struggle for further enhancing the quality of care? The implementation of IT assisted workflow and knowledge supporting tools throughout the entire healthcare process--prevention to cure--leads to care which would be much more focused on people's needs and efficiency. The information gained from monitoring and wearable devices has to be included to these tools for delivering comprehensive patient information to the point of care. Then the puzzle of the different components in healthcare linked by IT will be complete, and the care process could be continuously optimized in an efficient way.

New solutions for personalised health management: citizens' needs, healthcare changes, and market perspectives round table debate.

The aim with the round table was to give additional inputs and views to the specific technology oriented presentations focusing on issues dealing with the need, patients' view, the use and the business opportunities relating to wearable eHealth systems for personalised health management. Wearable eHealth systems for personalised health management are targeting citizens, patients at health risks and patients enrolled in open care or home care for monitoring, treatment or follow up. The developments so far show promises for these group categories, and in addition, could support developments in health care organisations and systems. However, the ethical issues and data privacy nature have to be seriously taken into account. The market is not yet developed, and this is the situation both in Europe and in the US. To be able to give the customers solid product information a standardised test bed for new equipment and services might speed up the market development. In the round table discussion it was highlighted that one has to differ between needs and demands. Needs are related to the prevalence of the diseases, the health risks, etc. Demands are more related to market developments and customers' willingness to pay for the new products and services. Further, technical interoperability was seen as a fundamental prerequisite for market acceptance. As wearable eHealth systems for personalised health management differ completely from traditional way of deliver healthcare, new reimbursement systems have to be developed and implemented.

[Studies of Coxiella burnetii infections in dairy herds with special regard to infections in men]. / Coxiella burnetii-Infektionen in Milchviehbetrieben unter besonderer Berücksichtigung von Infektionen bei Menschen.

Investigations of 1167 dairy cows out of 105 herds with fertility disorders on secretion of Coxiella burnetii (C. burnetii) by the genitals as well as serological studies of these animals using ELISA demonstrated that C. burnetii infections are significantly associated with abortions but not with repeated inseminations without success or vaginal excretions. The demonstration of an increased risk of infections for persons caring for those dairy herds could be shown by a total of 253 serological studies. A comparison of these studies of farmers caring for dairy herds suffering from abortions a seroprevalence of > or = 20% showed that these persons revealed significantly more frequent antibodies against C. burnetii than farmers of the group compared with. Further studies showed that in herds suffering from abortions a seroprevalence of > or = 20% means an additional risk of infections of farmers. Vice versa abortions of the cows in herds with a seroprevalence of > or = 20% imply an additional infectious risk.

Financial analysis projects clear returns from electronic medical records.

Implementing an electronic medical record (EMR) is a major initiative that should be undertaken only after a thoughtful analysis of the costs and benefits involved. Unfortunately, demonstrating financial returns on an EMR often is regarded as an inexact science at best, which has caused many healthcare executives to avoid adopting this technology. With the right approach, however, it is possible to demonstrate convincingly that the financial benefits will far outweigh the costs. To do this, it is necessary to involve representatives from operational areas throughout the organization, because they are best able to identify the potential for cost savings and additional revenue opportunities.