Whole body vibration compared to conventional physiotherapy in patients with gonarthrosis: a protocol for a randomized, controlled study

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is the most common degenerative arthropathy. Load-bearing joints such as knee and hip are more often affected than spine or hands. The prevalence of gonarthrosis is generally higher than that of coxarthrosis.</p> <p>Because no cure for OA exists, the main emphasis of therapy is analgesic treatment through either mobility or medication. Non-pharmacologic treatment is the first step, followed by the addition of analgesic medication, and ultimately by surgery.</p> <p>The goal of non-pharmacologic and non-invasive therapy is to improve neuromuscular function, which in turn both prevents formation of and delays progression of OA. A modification of conventional physiotherapy, whole body vibration has been successfully employed for several years. Since its introduction, this therapy is in wide use at our facility not only for gonarthrosis, but also coxarthrosis and other diseases leading to muscular imbalance.</p> <p>Methods/Design</p> <p>This study is a randomized, therapy-controlled trial in a primary care setting at a university hospital. Patients presenting to our outpatient clinic with initial symptoms of gonarthrosis will be assessed against inclusion and exclusion criteria. After patient consent, 6 weeks of treatment will ensue. During the six weeks of treatment, patients will receive one of two treatments, conventional physiotherapy or whole-body-vibration exercises of one hour three times a week. Follow-up examinations will be performed immediately after treatment and after another 6 and 20 weeks, for a total study duration of 6 months. 20 patients will be included in each therapy group.</p> <p>Outcome measurements will include objective analysis of motion and ambulation as well as examinations of balance and isokinetic force. The Western Ontario and McMaster Universities Arthritis Index and SF-12 scores, the patients' overall status, and clinical examinations of the affected joint will be carried out.</p> <p>Discussion</p> <p>As new physiotherapy techniques develop for the treatment of OA, it is important to investigate the effectiveness of competing strategies. With this study, not only patient-based scores, but also objective assessments will be used to quantify patient-derived benefits of therapy.</p> <p>Trial registration</p> <p>Deutsches Register Klinischer Studien (DRKS) DRKS00000415</p> <p>Clinicaltrials.gov NCT01037972</p> <p>EudraCT 2009-017617-29</p

Comparison of standard fusion with a "topping off" system in lumbar spine surgery: a protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Fusion of lumbar spine segments is a well-established therapy for many pathologies. The procedure changes the biomechanics of the spine. Initial clinical benefits may be outweighed by ensuing damage to the adjacent segments. Various surgical devices and techniques have been developed to prevent this deterioration. "Topping off" systems combine rigid fusion with a flexible pedicle screw system to prevent adjacent segment disease (ASD). To date, there is no convincing evidence that these devices provide any patient benefits.</p> <p>Methods/Design</p> <p>The study is designed as a randomized, therapy-controlled trial in a clinical care setting at a university hospital. Patients presenting to the outpatient clinic with degenerative disc disease or spondylolisthesis will be assessed against study inclusion and exclusion criteria. After randomization, the control group will undergo conventional fusion. The intervention group will undergo fusion with a supplemental flexible pedicle screw system to protect the adjacent segment ("topping off").</p> <p>Follow-up examination will take place immediately after treatment during hospital stay, after 6 weeks, and then after 6, 12, 24 and 36 months. Subsequently, ongoing assessments will be performed annually.</p> <p>Outcome measurements will include quality of life and pain assessments using questionnaires (SF-36™, ODI, COMI). In addition, clinical and radiologic ASD, work-related disability, and duration of work disability will be assessed. Inpatient and 6-month mortality, surgery-related data (e.g., intraoperative complications, blood loss, length of incision, surgical duration), postoperative complications, adverse events, and serious adverse events will be documented and monitored throughout the study. Cost-effectiveness analysis will also be provided.</p> <p>Discussion</p> <p>New hybrid systems might improve the outcome of lumbar spine fusion. To date, there is no convincing published data on effectiveness or safety of these topping off systems. High quality data is required to evaluate the benefits and drawbacks of topping off devices. If only because these devices are quite expensive compared to conventional fusion implants, nonessential use should be avoided. In fact, these high costs necessitate efforts by health care providers to evaluate the effects of these implants. Randomized clinical trials are highly recommended to evaluate the benefits or harm to the patient.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01224379">NCT01224379</a></p

Evaluation of efficacy of a new hybrid fusion device: a randomized, two-centre controlled trial

Background: The 360 fusion of lumbar segments is a common and well-researched therapy to treat various diseases of the spine. But it changes the biomechanics of the spine and may cause adjacent segment disease (ASD). Among the many techniques developed to avoid this complication, one appears promising. It combines a rigid fusion with a flexible pedicle screw system (hybrid instrumentation, topping off). However, its clinical significance is still uncertain due to the lack of conclusive data. Methods/ Design: The study is a randomized, therapy-controlled, two-centre trial conducted in a clinical setting at two university hospitals. If they meet the criteria, outpatients presenting with degenerative disc disease, facet joint arthrosis or spondylolisthesis will be included in the study and randomized into two groups: a control group undergoing conventional fusion surgery (PLIF - posterior lumbar intervertebral fusion), and an intervention group undergoing fusion surgery using a new flexible pedicle screw system (PLIF + topping off), which was brought on the market in 2013. Follow-up examination will take place immediately after surgery, after 6 weeks and after 6, 12, 24 and 36 months. An ongoing assessment will be performed every year. Outcome measurements will include quality of life and pain assessments using validated questionnaires (ODI Ostwestry Disability Index, SF-36 (TM) - Short Form Health Survey 36, COMI - Core Outcome Measure Index). In addition, clinical and radiologic ASD, sagittal balance parameters and duration of work disability will be assessed. Inpatient and 6-month mortality, surgery-related data (e.g., intraoperative complications, blood loss, length of incision, surgical duration), postoperative complications (e.g. implant failure), adverse events, and serious adverse events will be monitored and documented throughout the study. Discussion: New hybrid topping off systems might improve the outcome of lumbar spine fusion. But to date, there is a serious lack of and a great need of convincing data on safety or efficacy, including benefits and harms to the patients, of these systems. Health care providers are particularly interested in such data as these implants are much more expensive than conventional implants. In such a case, randomized clinical trials are the best way to evaluate benefits and risks. Trial registration: NCT0185252

Bacterial Peptide Recognition and Immune Activation Facilitated by Human Peptide Transporter PEPT2

Microbial detection requires the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) that are distributed on the cell surface and within the cytosol. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family functions as an intracellular PRR that triggers the innate immune response. The mechanism by which PAMPs enter the cytosol to interact with NLRs, particularly muropeptides derived from the bacterial proteoglycan cell wall, is poorly understood. PEPT2 is a proton-dependent transporter that mediates the active translocation of di- and tripeptides across epithelial tissues, including the lung. Using computational tools, we initially established that bacterial dipeptides, particularly γ-D-glutamyl-meso-diaminopimelic acid (γ-iE-DAP), are suitable substrates for PEPT2. We then determined in primary cultures of human upper airway epithelia and transiently transfected CHO-PEPT2 cell lines that γ-iE-DAP uptake was mediated by PEPT2 with an affinity constant of approximately 193 μM, whereas muramyl dipeptide was not transported. Exposure to γ-iE-DAP at the apical surface of differentiated, polarized cultures resulted in activation of the innate immune response in an NOD1- and RIP2-dependent manner, resulting in release of IL-6 and IL-8. Based on these findings we report that PEPT2 plays a vital role in microbial recognition by NLR proteins, particularly with regard to airborne pathogens, thereby participating in host defense in the lung

Pharmacokinetic profile of zafirlukast.

Item does not contain fulltextZafirlukast is a cysteinyl leukotriene type 1 receptor antagonist that causes bronchodilation and has anti-inflammatory properties. Clinical efficacy has been demonstrated when using oral doses of 20 to 40 mg twice daily. The pharmacokinetics of zafirlukast are best described by a two-compartment model. Maximum plasma concentrations (Cmax) were achieved 3 hours after a single oral dose of 20 or 40 mg to healthy volunteers. The absolute bioavailability of zafirlukast is unknown. However, coadministration of zafirlukast with food reduces bioavailability by approximately 40%. The drug binds to plasma proteins (>99%), predominantly to albumin, and has a mean terminal elimination half-life of approximately 10 hours in both healthy volunteers and patients with asthma. Zafirlukast undergoes extensive hepatic metabolism. Hydroxylation by cytochrome P450 (CYP) 2C9 is the major biotransformation pathway. The metabolites of zafirlukast contribute little to its overall activity. Zafirlukast is mainly eliminated in the faeces, while urinary excretion accounts for <10% of an orally administered dose. Because of its primarily hepatic metabolism, the clearance of zafirlukast is reduced in patients with hepatic impairment. In patients with stable alcoholic cirrhosis, Cmax and area under the plasma concentration-time curve for zafirlukast were increased by 50 to 60% compared with healthy volunteers. Asymptomatic elevations of serum liver enzymes have been reported with high dosages of zafirlukast (80 mg twice daily), returning to normal after cessation of the drug. Inhibition of the CYP2C9 and CYP3A isoenzymes by zafirlukast has been reported in vitro. Zafirlukast interacts with warfarin and produces a clinically significant increase in the prothrombin time, but it does not alter the pharmacokinetics of terfenadine carboxylate, the active metabolite of terfenadine. Plasma concentrations of zafirlukast decreased when the drug was administered concomitantly with erythromycin, terfenadine or theophylline, and increased when it was coadministered with aspirin (acetylsalicylic acid). Theophylline metabolism is unchanged in most cases by zafirlukast, but there is a report of one patient with increased theophylline plasma concentrations when zafirlukast was coadministered. Recently, cases of Churg-Strauss syndrome have been described in patients with asthma receiving zafirlukast treatment. This occurrence in patients being withdrawn from corticosteroid therapy while receiving zafirlukast has been attributed to a previously undiagnosed presence of this syndrome in these patients