Real-World Treatment of Patients with Multiple Sclerosis per MS Subtype and Associated Healthcare Resource Use: An Analysis Based on 13,333 Patients in Germany.

INTRODUCTION: The aim of this study was to describe the real-word treatment and associated healthcare resource use (HCRU) of multiple sclerosis (MS) patients, as stratified by different MS subtypes. METHODS: All patients with MS continuously insured by two German statutory healthcare insurance funds from 2011 to 2015 were enrolled. These patients were categorized into four subgroups according to their MS type as follows: clinically isolated syndrome (CIS); relapsing remittent MS (RRMS); primary progressive MS (PPMS); and secondary progressive MS (SPMS). Sociodemographic characteristics, treatments, and HCRU for 2015 were analyzed. Treatment cascades for treatment-naïve patients were also determined. RESULTS: A total of 13,333 patients with MS were identified. The largest proportion of patients had RRMS (41.9%), followed by PPMS (17.1%). Mean age of the enrolled patients was 50.2 years, and 70.7% were female. Among all patients, 38.3% of those with CIS, 22.4% with PPMS, 69.6% with RRMS, and 33.9% with SPMS received a prescription of a disease-modifying immunomodulatory agent, with interferon beta-1a being the most frequently prescribed agent. Likewise, 14.5, 18.5, 19.9, and 21.5% of patients with CIS, PPMS, RRMS, and SPMS, respectively, received a flare-up treatment with glucocorticoids. MS-associated overall costs, including indirect costs for MS-associated days absent from work, were € 16,433, with costs related to MS medication (€ 8770; 53.4%) being the main driver of costs in all subgroups. MS-associated costs according to MS subtypes were € 12,427 for CIS patients, € 14,459 for PPMS patients, € 20,583 for RRMS patients, and € 17,554 for SPMS patients. CONCLUSION: Among the four MS subtypes, RRMS patients most often received a disease-modifying immunomodulatory treatment. Consequently, healthcare costs were highest for patients with this MS subtype. Contrary to the treatment guideline, a substantial percentage of patients with CIS, RRMS, and SPMS did not receive any disease-modifying immunomodulatory treatment.

Tibial Implant Fixation Behavior in Total Knee Arthroplasty: A Study With Five Different Bone Cements.

BACKGROUND: The objectives of this study are to (1) evaluate if there is a potential difference in cemented implant fixation strength between tibial components made out of cobalt-chromium (CrCoMo) and of a ceramic zirconium nitride (ZrN) multilayer coating and to (2) test their behavior with 5 different bone cements in a standardized in vitro model for testing of the implant-cement-bone interface conditions. We also analyzed (3) whether initial fixation strength is a function of timing of the cement apposition and component implantation by an early, mid-term, and late usage within the cement-specific processing window. METHODS: An in vitro study using a synthetic polyurethane foam model was performed to investigate the implant fixation strength after cementation of tibial components by a push-out test. A total of 20 groups (n = 5 each) was used: Vega PS CrCoMo tibia and Vega PS ZrN tibia with the bone cements BonOs R, SmartSet HV, Cobalt HV, Palacos R, and Surgical Simplex P, respectively, using mid-term cement apposition. Three different cement apposition times-early, mid-term, and late usage-were tested with a total of 12 groups (n = 5 each) with the bone cements BonOs R and SmartSet HV. RESULTS: There was no significant difference in implant-cement-bone fixation strength between CrCoMo and ZrN multilayer-coated Vega tibial trays tested with 5 different commonly used bone cements. CONCLUSION: Apposition of bone cements and tibial tray implantation in the early to mid of the cement-specific processing window is beneficial in regard to interface fixation in TKA.

Real-world effectiveness and safety of oral anticoagulation strategies in atrial fibrillation: a cohort study based on a German claims dataset.

OBJECTIVE: To compare the real-world effectiveness and safety of non-vitamin-K-antagonist oral anticoagulant (NOAC) treatment in atrial fibrillation (AF) patients with a vitamin-K-antagonist (VKA)-based treatment. METHODS: This was a retrospective analysis of an anonymized claims dataset from 3 German health insurance funds covering the period from January 01, 2010 to June 30, 2014, with a minimum observation time of 12 months. All continuously insured patients with at least 2 outpatient AF diagnoses and/or 1 inpatient respective diagnosis who received at least 1 outpatient prescription of a NOAC or VKA were included. OUTCOMES AND MEASURES: Death, ischemic strokes (IS), non-specified strokes, transient ischemic attacks (TIAs), myocardial infarctions (MIs), arterial embolism (AE), hemorrhagic strokes, severe bleedings, and composite outcomes. Main comparisons were done based on propensity score-matched (PSM) cohorts. Results were reported as incidence rate ratios and hazard ratios (HRs). RESULTS: We assigned 37,439 AF patients to each PSM cohort (NOAC cohort: mean age 78.2 years, mean CHA2DS2VASc score 2.96, mean follow-up 348.5 days; VKA cohort: mean age 78.2 years, mean CHA2DS2VASc 2.95, mean follow-up 365.5 days). NOAC exposure was associated with significantly higher incidence rate ratios; 95% CI/HRs; 95% CI for the following outcomes: death (1.22; 1.17-1.28/1.22; 1.17-1.28), IS (1.90; 1.69-2.15/1.92; 1.69-2.19), non-specified strokes (2.04; 1.16-3.70/1.93; 1.13-3.32), TIAs (1.52; 1.29-1.79/1.44; 1.21-1.70), MIs (1.26; 1.10-1.15/1.31; 1.13-1.52), AE (1.75; 1.32-2.32/1.81; 1.36-2.34) and severe bleeding (1.92; 1.71-2.15/1.95; 1.74-2.20). Multivariable Cox regression analyses and additional sensitivity analysis, including analysis of PSM-matched NOAC/VKA treatment-naive patients, only confirmed the above results. The study was documented under clinicaltrials.gov (NCT02657616). CONCLUSION AND RELEVANCE: A VKA therapy seems to be more effective and safer than a NOAC therapy in a real-world cohort of German AF patients.

Primary stability of tibial plateaus under dynamic compression-shear loading in human tibiae - Influence of keel length, cementation area and tibial stem.

The objective of our study was to evaluate the impact of the tibial keel & stem length in surface cementation, of a full cemented keel and of an additional tibial stem on the primary stability of a posterior stabilised tibial plateau (VEGA® System Aesculap Tuttlingen, Germany) under dynamic compression-shear loading conditions in human tibiae. We performed the cemented tibial plateau implantations on 24 fresh-frozen human tibiae of a mean donor age of 70.7years (range 47-97). The tibiae were divided into four groups of matched pairs based on comparable trabecular bone mineral density. To assess the primary stability under dynamic compression shear conditions, a 3D migration analysis of the tibial component relative to the bone based on displacements and deformations and an evaluation of the cement layer including penetration was performed by CT-based 3D segmentation. Within the tested implant fixation principles the mean load to failure of a 28mm keel and a 12mm stem (40mm) was 4700±1149N and of a 28mm keel length was 4560±1429N (p=0.996), whereas the mean load to failure was 4920±691N in full cementation (p=0.986) and 5580±502N with additional stem (p=0.537), with no significant differences regarding the dynamic primary stability under dynamic compression-shear test conditions. From our observations, we conclude that there is no significant difference between a 40mm and a 28mm tibial keel & stem length and also between a surface and a full cementation in the effect on the primary stability of a posterior stabilised tibial plateau, in terms of failure load, migration characteristics and cement layer thickness including the penetration into the trabecular bone.

Analysis of Carbon Fiber Reinforced PEEK Hinge Mechanism Articulation Components in a Rotating Hinge Knee Design: A Comparison of In Vitro and Retrieval Findings.

Carbon fiber reinforced poly-ether-ether-ketone (CFR-PEEK) represents a promising alternative material for bushings in total knee replacements, after early clinical failures of polyethylene in this application. The objective of the present study was to evaluate the damage modes and the extent of damage observed on CFR-PEEK hinge mechanism articulation components after in vivo service in a rotating hinge knee (RHK) system and to compare the results with corresponding components subjected to in vitro wear tests. Key question was if there were any similarities or differences between in vivo and in vitro damage characteristics. Twelve retrieved RHK systems after an average of 34.9 months in vivo underwent wear damage analysis with focus on the four integrated CFR-PEEK components and distinction between different damage modes and classification with a scoring system. The analysis included visual examination, scanning electron microscopy, and energy dispersive X-ray spectroscopy, as well as surface roughness and profile measurements. The main wear damage modes were comparable between retrieved and in vitro specimens (n = 3), whereby the size of affected area on the retrieved components showed a higher variation. Overall, the retrieved specimens seemed to be slightly heavier damaged which was probably attributable to the more complex loading and kinematic conditions in vivo.

Effects of oxytocin outside pregnancy.

For a long time, oxytocin was regarded as a pregnancy hormone released by the hypophysis to stimulate labour and milk ejection. In the present survey, data have been collected from the literature to show the spectrum of the hitherto known functions of oxytocin outside pregnancy. It is now known that oxytocin receptors can occur almost ubiquitously in the organism, that oxytocin is also formed outside of the brain and that oxytocin has functions in a number of organs. In the first part of the survey, stimuli that contribute to an increase in oxytocin release are compiled. In the second part, details are given on the individual oxytocin targets. Although the majority of findings are based on the results of animal experiments, there are already a number of studies that indicate similar effects of oxytocin in humans. According to the current state of knowledge, oxytocin appears to be involved in functions in the following organs: male and non-pregnant female reproductive tract, pancreas, cardiovascular system, kidney, brain and breast. There are indications that oxytocin may also have actions in other organs. There continues to be a considerable need for research into oxytocin in order to better understand the physiological and pathophysiological actions and to be able to derive possible therapeutic uses. Further light on the spectrum of functions of oxytocin may be cast by the possibility of the use of oxytocin antagonists.

Efficacy of pulsed intravenous immunoglobulin therapy in mixed connective tissue disease.

We describe a 69-year-old patient with long-standing mixed connective tissue disease who suffered from severe skin eruptions that did not respond to various immunosuppressive regimens. Therapy with high-dose intravenous immunoglobulin was successful in controlling the patient's disease without major side effects. We think that this regimen-although expensive-might be an interesting therapeutic option in selected patients with mixed connective tissue disease that is refractory to other treatment modalities.