Telemonitoring of patients with Parkinson's disease using inertia sensors.

BACKGROUND: Medical treatment in patients suffering from Parkinson's disease is very difficult as dose-finding is mainly based on selective and subjective impressions by the physician. OBJECTIVES: To allow for the objective evaluation of patients' symptoms required for optimal dosefinding, a telemonitoring system tracks the motion of patients in their surroundings. The system focuses on providing interoperability and usability in order to ensure high acceptance. METHODS: Patients wear inertia sensors and perform standardized motor tasks. Data are recorded, processed and then presented to the physician in a 3D animated form. In addition, the same data is rated based on the UPDRS score. Interoperability is realized by developing the system in compliance with the recommendations of the Continua Health Alliance. Detailed requirements analysis and continuous collaboration with respective user groups help to achieve high usability. RESULTS: A sensor platform was developed that is capable of measuring acceleration and angular rate of motions as well as the absolute orientation of the device itself through an included compass sensor. The system architecture was designed and required infrastructure, and essential parts of the communication between the system components were implemented following Continua guidelines. Moreover, preliminary data analysis based on three-dimensional acceleration and angular rate data could be established. CONCLUSION: A prototype system for the telemonitoring of Parkinson's disease patients was successfully developed. The developed sensor platform fully satisfies the needs of monitoring patients of Parkinson's disease and is comparable to other sensor platforms, although these sensor platforms have yet to be tested rigorously against each other. Suitable approaches to provide interoperability and usability were identified and realized and remain to be tested in the field.

Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients.

OBJECTIVE: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores. METHODS: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months). RESULTS: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores. CONCLUSION: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

B-type natriuretic peptide and severe heart failure at baseline predict overall mortality in incident dialysis patients.

AIMS: The B-type natriuretic peptide (BNP) has become increasingly important as a diagnostic and prognostic method for cardiovascular disease or death. To our knowledge no prospective studies exist to evaluate the value of baseline BNP and baseline heart failure as predictors of overall death in incident rather than prevalent hemodialysis patients with end-stage renal disease (ESRD). METHODS: 255 ESRD patients were included in our observational study with a median observation period of 1.11 years. A Kaplan-Meier survival curve was stratified by BNP concentration (< 340 pg/ml and > or = 340 pg/ml) to estimate the impact on the overall mortality rate. Univariate and multiple Cox regression models were fitted for a variety of covariables including severe heart failure (graded according to the New York Heart Association) to evaluate the independent predictors of death. Association between BNP and four explanatory variables was described in a multiple linear regression model. RESULTS: Survival analysis demonstrated a significantly higher mortality rate in patients with higher BNP values at baseline. The independent predictive value of high BNP concentration at baseline could be statistically confirmed by multiple Cox regression analysis. However, when including the covariates hemoglobin and severe heart failure, significantly associated with BNP, in the same model, severe heart failure rather than BNP becomes a significant predictor of overall death. CONCLUSIONS: A higher BNP level at baseline may be confirmed as an independent predictor of death in the incident dialysis population. However, severe heart failure may affect the impact of BNP on the overall survival rate and thus be a stronger predictor of death than BNP.

Impact of age, body mass index, insulin resistance and proteinuria on the kidney function in obese patients with Type 2 diabetes and renal insufficiency.

AIMS: To date, several different equations to predict the glomerular filtration rate (GFR) in patients with renal insufficiency have been developed for different patients groups. Our aim was to determine the prognostic factors of GFR in our homogenous patient group of obese, water-loaded patients with Type 2 diabetes and renal insufficiency, since we assumed that the endogenous creatinine clearance (ECC) alone may not be an accurate method to predict GFR. METHOD: We recruited 46 obese patients (37 men) with Type 2 diabetes and renal insufficiency in our nephrology center in Mettmann (Germany). However, two male patients were excluded from the analysis due to an outlying insulin level or low inulin clearance. The inulin clearance as a measure of renal function performed by the single shot method was compared with the GFR estimated by ECC, Cystatin C, and MDRD formula. Several multiple regression models were built to test the impact of the prognostic factors age, sex, body mass index (BMI), insulin resistance according to the homeostasis model assessment (HOMA), body water (TBW), brain natriuretic peptide (BNP), and proteinuria on the inulin clearance. In the main regression model to predict the inulin clearance by ECC, only the statistically significant prognostic factors of these models were selected, as well as the interaction between GFR predicted by ECC (GFR_ECC) and BMI. RESULTS: The prognostic factors GFR_ECC, age, BMI, HOMA and proteinuria had a statistically significant impact on the inulin clearance (the gold standard of the GFR) in our patient population (p < 0.05). However, the interaction of GFR_ECC and BMI was not significant (p = 0.06) in our model. The model was validated and considered well-fitted with a coefficient of determination (R2) of 0.69. CONCLUSIONS: The independent prognostic factors to determine GFR in obese, water-loaded diabetic patients are GFR_ECC, age, BMI, HOMA and proteinuria. However, our model should be revalidated and tested in a larger sample size to probably detect an interaction between GFR_ECC and BMI as an additional prognostic factor.

The prognostic value of the C-reactive protein levels in HD patients with death risk from infection.

AIMS: Infection is considered the second leading cause of death in dialysis patients with end-stage renal disease (ESRD). However, infection prevalence as primary cause of death still seems to be underreported in the literature. We investigated the role of C-reactive protein (CRP) levels shortly before death as predictor of dying from an infection as primary cause of death in this patient group. METHOD: Between January 1997 through March 2006, we defined the primary causes of death in 231 of the 481 incident patients in our single-center study, who died during this time and assessed the overall prevalence of infection at different predefined CRP cutpoints (between 2 and 300 mg/l). By means of an adjusted multiple logistic regression model, we calculated the odds ratio of (log) CRP for death in 346 survivors and non-survivors with available CRP levels within 5 days of death. In the 96 non-survivors (i.e. cases) of this group, the association of (log) CRP and causes of death was determined by the multiple linear regression model. RESULTS: Infection as a primary cause of death was initially diagnosed in 42% of the 231 non-survivors by standard parameters and clinically. However, the rate of patients possibly dying from this disease increased accordingly when also including cases without any clinical infection signs but with CRP values higher than a given cutpoint (between 2 and 300 mg/l), e.g. when including all cases with CRP cutpoints higher than 100 mg/l, overall prevalence of infection as cause of death increases to 57% (95% CI = 51-64%). Infection was significantly associated with higher CRP levels compared with cardiac death (p < 0.001), with an odds ratio of log CRP for death of 5.4 (95% CI = 3.8-7.7). CONCLUSIONS: Prevalence of infection as primary cause of death in ESRD patients may be even higher than currently stated in the literature. Therefore, to reduce mortality, infections should be further avoided and controlled in the future.

Successful maintenance of continuous ambulatory peritoneal dialysis in a patient after fungal peritonitis and dialysate leakage.

Fungal peritonitis (FP) and dialysate leakage have often been reported in association with continuous ambulatory peritoneal dialysis (CAPD), which has to be discontinued in many cases due to these complications. This report describes the first case of dialysate leakage into the urinary bladder of a 70-year-old male patient, after the area of the left ureteral ostium had been very deeply resected. The leakage probably led to severe fungal peritonitis developing 1 day after the ostium resection. The ostium resection was performed in November 2003 after detection of a carcinoma in situ (Cis) in this area and after previous bilateral nephroureterectomies due to multifocal urothelial carcinoma in the kidneys, ureters and bladder. In spite of prior fungal peritonitis and dialysate leakage, CAPD could be successfully initiated 41 days after biochemical manifestation of peritonitis and could be maintained in the patient because of the following reasons: early and effective treatment of FP with fluconazole and voriconazole, spontaneous occlusion of the slitted ostium area, allowance of enough healing time after 2 major abdominal surgeries, during which the patient was placed on extracorporal hemodialysis (which had been started 1 day after nephroureterectomy and ended after the antimycotic treatment) and thorough monitoring of the patient after starting CAPD. In January 2004, the patient could be placed on a cycler peritoneal dialysis and was fully rehabilitated 1 year later.

[Telemetric system for measuring the pressure of the tongue on the palate]. / Telemetrisches Messsystem zur Bestimmung des Druckes der Zunge gegen den Gaumen.

The development of the upper jaw during growth is influenced by the function and position of the tongue and perioral soft tissues, and the pressures exerted by them. Accurate determination of the forces exerted by the tongue would provide relevant information about this influence. To date, our ability to obtain continuous recordings of the tongue pressure during certain functions is limited. In this paper, an easy-to-employ and accurate telemetric system for such functional measurements is presented. The system, consisting of four piezoresistive pressure sensors, a microcontroller, a telemetric module and batteries, is integrated within a removable orthodontic plate and transmits the measured data out of the oral cavity to a receiver.

[Piezoresistive sensors for medical applications exemplified by a probe for measure pressure in the rectum]. / Piezoresistive Sensoren für medizinische Anwendungen am Beispiel einer Sonde zur Druckmessung im Enddarm.

We described a pressure sensor probe suitable for assessing dynamic rectal pressure profiles. It comprises 10 piezoresistive sensors mounted in low-temperature co-fired ceramic. To protect against corrosion, the sensors are coated with a biocompatible silicone elastomer. The ceramic measures 4.5 x 5.5 x 1.4 mm. The entire probe has a diameter of 9 mm and a length of 20 cm. A healthy test subject was submitted to rectal manometry. The experimental data and analysis of linearity, hysteresis errors, temperature dependence and reproducibility are discussed. The sensor probe extends classical anorectal manometry, in particular with regard to the diagnosis of rectal motility disorders.

Impact resistance of materials for guards on cutting machine tools--requirements in future European safety standards.

Guards on machine tools are meant to protect operators from injuries caused by tools, workpieces, and fragments hurled out of the machine's working zone. This article presents the impact resistance requirements, which guards according to European safety standards for machine tools must satisfy. Based upon these standards the impact resistance of different guard materials was determined using cylindrical steel projectiles. Polycarbonate proves to be a suitable material for vision panels because of its high energy absorption capacity. The impact resistance of 8-mm thick polycarbonate is roughly equal to that of a 3-mm thick steel sheet Fe P01. The limited ageing stability, however, makes it necessary to protect polycarbonate against cooling lubricants by means of additional panes on both sides.

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part II.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus simultaneously on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain. This part examines pharmacologic methods.

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part I.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care, and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain.

The efficacy, tolerability, and safety of 1200 mg/d of oxaprozin and 1500 mg/d of nabumetone in the treatment of patients with osteoarthritis of the knee.

This 6-week, multicenter, double-masked, placebo-controlled study compared the efficacy, tolerability, and safety of the recommended starting dose of oxaprozin (1200 mg/d) and a 1500-mg/d dose of nabumetone in the treatment of patients with moderate-to-severe osteoarthritis (OA) of the knee. A total of 347 patients with a mean age of 61.1 years were randomized to receive oxaprozin (116 patients), nabumetone (115 patients), or placebo (116 patients). Adults of either sex who were older than 18 years of age were eligible for entry into the study, if they had had OA of the knee for at least 6 months. Efficacy variables included knee pain on weight bearing, knee pain on motion, patients' and physicians' global assessments of OA, pain intensity as measured on a visual analog scale, and time to walk 50 feet as quickly as possible. Efficacy variables were assessed at baseline and at weeks 1, 2, 4, and 6. Between-group differences in efficacy variables were evident by week 1. Mean improvements were significantly greater with oxaprozin than with placebo for all efficacy variables at all time periods, except knee pain on motion at weeks 2 and 4 and time to walk 50 feet at weeks 1, 2, and 4. Mean improvements were significantly greater with nabumetone than with placebo for all efficacy variables at all time periods, except the following: knee pain on weight bearing at weeks 2, 4 and 6; knee pain on motion at weeks 2 and 4; patients' global assessment at week 4; and pain intensity as measured on a visual analog scale at weeks 2 and 4. There were, however, no significant differences between oxaprozin and nabumetone in any of these efficacy variables. Adverse events were reported by 83 (71.6%) patients who took oxaprozin, by 80 (69.6%) patients who took nabumetone, and by 57 (49.1%) patients who took placebo. Adverse events were reported for significantly more patients taking oxaprozin or nabumetone than placebo. However, adverse events tended to be mild or moderate and rarely resulted in patients withdrawing from the study. Combined with the results of an earlier study, the results of this study showed that a 1500-mg/d dose of nabumetone, which is higher than the recommended starting dose of 1000 mg/d, is required for efficacy equivalent to that of the recommended starting dose of oxaprozin, 1200 mg/d, in relieving the symptoms of OA. Thus nabumetone may require dosage titration from the recommended starting dose. Oxaprozin and nabumetone were found to have similar tolerability profiles, as shown by adverse-event monitoring and withdrawal rates, as well as clinically similar safety profiles, as demonstrated by physical examinations, hematologic and biochemical laboratory testing, hemoccult testing, and adverse-event monitoring and symptom assessment.

Tactile optical sensor for use in minimal invasive surgery.

In minimal invasive surgery high sensory palpation of the organs is largely lost. It is the purpose of this work to recover tactile sensing for the surgeon. To achieve this goal, a new tactile optical pressure sensor has been developed which allows to display 64 measuring points on a 0.64 cm2 surface area with a digital resolution of 12 bits. The sensor has been conceived for application in laparoscopic grasping forceps and can also be integrated into a sensing rod, both 15 mm in outside diameter. This optical sensor allows us to display graphically indurations spread in the tissue. Furthermore, the measured values serve to activate a vibrotactile display unit for tactile feedback onto the surgeon's fingertip. In order to obtain further information about the requirements for an analog tactile display, an actuatorarray with 144 pins on a 4 cm2 surface area was built. The array allows various test objects to be recognized in a true scale presentation by exploratory movements of the fingers.

Comparison of the efficacy and safety of oxaprozin and nabumetone in the treatment of patients with osteoarthritis of the knee.

This multicenter, 6-week, double-blind, placebo-controlled, parallel-group study compared the efficacy and safety of oxaprozin 1200 mg once daily with that of nabumetone 1000 mg once daily in patients with moderate-to-severe osteoarthritis (OA) of the knee. To be eligible, patients had to experience a flare of OA within 2 weeks of discontinuing their usual OA medication (nonsteroidal anti-inflammatory drug or analgesic). Eligible patients were assessed at baseline and then randomized to receive oxaprozin (n = 109), nabumetone (n = 110), or placebo (n = 109). Efficacy assessments were performed at weeks 1, 2, 4, and 6. Primary efficacy variables included knee pain on weight bearing, knee pain on motion, and patient's and physician's global assessments of OA. Secondary efficacy variables included pain intensity, time to walk 50 feet, and duration of morning stiffness. Safety was evaluated by use of routine laboratory analyses; physical examination at screening, baseline, and week 6 (or study termination); assessment of symptoms at baseline and at each visit; and testing stools for occult blood at screening and between week 4 and the final visit. Adverse events were monitored throughout the study. Between-group differences in efficacy variables were evident by week 1. The mean change in improvement from baseline with oxaprozin compared with placebo was statistically significant in favor of oxaprozin at weeks 1, 2, 4, and 6 for all primary efficacy variables. The mean change in improvement from baseline with nabumetone compared with placebo, however, was statistically significant only at week 1 for knee pain on motion, patient's global assessment, and physician's global assessment. The mean change in improvement from baseline was statistically significant (P < or = 0.035) in favor of oxaprozin versus nabumetone at weeks 2 and 6 for all four primary efficacy variables and also at week 4 for knee pain on motion. The incidence of adverse clinical events between treatment groups was not statistically significant. However, nine oxaprozin-treated patients had asymptomatic liver enzyme elevations reported as adverse events. Four of these patients had reversible elevations of aspartate aminotransferase and alanine aminotransferase greater than three times the upper limit of normal range (P < 0.05); two of these patients were taking other medications known to induce liver enzyme abnormalities. The study showed that oxaprozin 1200 mg once daily was statistically significantly more efficacious than nabumetone 1000 mg once daily for the treatment of patients with moderate-to-severe OA of the knee. Both drugs were clinically well tolerated.

Histologic effects of different technologies for dissection in endoscopic surgery: Nd:YAG laser, high frequency and water-jet.

Precise cutting combined with reliable coagulation of the margins of the lesion is an important requirement for dissection techniques in endoscopic surgery. These requirements are met by the two most common ancillary energy sources applied for endoscopic dissection today, electrosurgery and "thermal lasers", mostly the Nd:YAG. For the comparison of the histological effects of monopolar and bipolar high frequency with the Nd:YAG laser an experimental in vitro and in vivo study has been performed. In order to evaluate the advantages of non thermal dissection for endoscopic procedures, a water jet cutting system was included in the in vitro study. In parenchymatous tissue the water jet was found to be the least traumatic technique, followed by bipolar high frequency, laser and monopolar high frequency. The water jet was not applicable for intestinal dissection since uncontrolled bloating of the rectal wall with uncontrolled disruption of the tissue layers occurred. A general disadvantage is that secure haemostasis in the line of incision is hard to achieve. In the microscopic comparison of the shape of the incision, the Nd:YAG laser produced the smoothest lesions with well-defined margins. The monopolar technique was more often associated with irregular and sometimes fissured margins. These results were confirmed in the in vivo part of the study (Transanal Endoscopic Microsurgery).

Kinematic problems of manipulators for minimal invasive surgery.

The article discusses handling problems in endoscopic surgery and concepts for the augmentation of instrument dexterity. The authors present a kinematic concept for improved surgical tool positioning and orientation. Using a trunk mechanism it is possible to assure augmented dexterity and stiffness for endoscopic handling. The paper addresses the use of steerable endoscopic instruments in a manipulator system for minimal invasive surgery.

Development of steerable instruments for minimal invasive surgery in modular conception.

The augmenting complexity of minimal invasive interventions requests a continuous improvement of technologies. Extended endoscopic procedures, e.g. laparoscopic-transanal sigmoidectomy or thoracoscopic esophagus dissection require difficult surgical manipulations like mobilisation, sceletonization as well as ligatures and sutures. They are difficult to perform with the present endo-surgical instruments. A major instrumental weakness is represented by the restricted steerability because of the rigid shaft axis and the resulting low degrees of freedom (DOF). Therefore a series of steerable flexible instruments has been developed in interdisciplinary cooperation between surgeons and engineers. The prototypes provide a multi-joint working as the instrument's elbow, which allows to incline the tip around +/- 280 degrees. The second additional DOF is the rotation of the surgical tool. The prototypes have been experimentally tested in laparoscopy and thoracoscopy, showing a clear improvement in the carrying out of complex operative manipulations. The further development is performed in modular conception, including electric drives.

[Color-coded Doppler ultrasonography in early detection of rejection reactions after allogeneic kidney transplantation]. / Farbkodierte Dopplersonographie zur Früherkennung von Abstossungsreaktionen nach allogener Nierentransplantation.

A prospective study of 45 consecutive patients (27 men, 18 women, mean age 42 [22-64] years) who had undergone allogeneic renal transplantation was carried out to ascertain whether rejection of the graft can be detected by routine follow up with colour-coded Doppler ultrasonography even in the presence of acute renal failure requiring dialysis. Conventional diagnostic methods detected 44 episodes of rejection in 33 patients: 26 of these arose in 18 patients with acute renal failure requiring dialysis and 18 in 15 patients who did not require dialysis. Colour-coded Doppler ultrasonography was used to determine the "pulsatility index" (PI) at intervals of 3 to 6 days. 17 of the 18 episodes of rejection occurring in transplant patients with stable serum creatinine levels (3.41 +/- 1.48 mg/dl) were detected by colour-coded Doppler ultrasonography 3.8 +/- 5.6 days earlier than by conventional diagnostic methods, the indicator being the rise in PI (sensitivity 93.8%). 25 of the 26 rejection reactions which arose in patients with oligo-anuria due to post-operative renal failure were detected 2.0 +/- 2.7 days earlier (sensitivity 96%). The rise in PI was greater in episodes of vascular rejection than in purely interstitial rejection episodes (40.9 +/- 73.9% versus 10.0 +/- 8.8% per day). Colour-coded Doppler ultrasonography ia a new, highly sensitive, noninvasive method for the early detection of rejection reactions after renal transplantation. Acute postischaemic renal failure does not reduce its sensitivity.

Free protein S levels are elevated in familial C4b-binding protein deficiency.

In plasma, 40% of the protein S is free and functions as a cofactor for the anticoagulant effects of activated protein C. The remaining 60% of protein S is complexed to C4b-binding protein and is functionally inactive. A family with hereditary C4b binding protein deficiency has been identified with C4b-binding protein levels in an affected father and daughter of 37 micrograms/mL and 23 micrograms/mL, respectively; these values are significantly below the normal range for this protein of 180 micrograms/mL +/- 44 micrograms/mL (mean +/- 2 SD). The total protein S (free + bound) is normal in these individuals (23.2 micrograms/mL and 17.8 micrograms/mL, respectively; normal 19.1 micrograms/mL +/- 6.0 micrograms/mL). The free protein S levels are markedly increased at 22.5 micrograms/mL and 17.4 micrograms/mL, respectively (normal 5.9 micrograms/mL +/- 2.4 micrograms/mL). This experiment of nature shows that total protein S levels in plasma are not affected by the absence of C4b-binding protein and that chronic elevation of free protein S is not associated with increased hemorrhagic tendencies.