Switching From Originator to Biosimilar Human Growth Hormone Using Dialogue Teamwork: Single-Center Experience From Sweden

INTRODUCTION: A new treatment plan was implemented at Skåne University Hospital, on economic grounds, for children requiring recombinant human growth hormone (rhGH) treatment. This involved switching patients from treatment with originator rhGHs to treatment with a biosimilar rhGH, somatropin (Omnitrope(®)), using a Dialogue Teamwork approach. The feasibility of using this approach to implement the switch of treatment was assessed, as well as the impact of the switch on treatment efficacy and cost of therapy. METHODS: As part of the Dialogue Teamwork approach, patients/parents received several opportunities for dialogue and sources of information, including discussions with the Head of Department, the responsible physician and a specialized endocrinology nurse. Height and height standard deviation score (HSDS) data were plotted for each individual patient (N = 98). A modeling approach was also used, to predict growth after switching to biosimilar rhGH; the predictions were then compared to the actual observed height after the switch. Costs to the clinic of rhGH therapy were calculated between May–August 2009 and May–August 2012. RESULTS: Of the 102 patients offered the switch, 98 accepted. Height and HSDS data indicated there was no negative impact on growth velocity after the switch to biosimilar rhGH. Modeling demonstrated that observed growth following the switch was consistent with predicted growth based on data before patients were switched. There were no reports of serious or unexpected adverse drug reactions following the switch to biosimilar rhGH. Following the switch, the cost to the clinic of rhGH treatment decreased from approximately 6 million SEK (May–August 2009) to approximately 4 million SEK (May–August 2012). This corresponds to an annual saving of 6 million SEK (€650,000). CONCLUSION: Patients were successfully switched from originator to biosimilar rhGH (somatropin), with no negative impact on growth, and no serious or unexpected adverse drug reactions. The switch from originator to biosimilar rhGH is associated with substantial cost savings

Developing an Online Critical Care Electroencephalography Curriculum for Epilepsy and Neurophysiology Fellows

Purpose: This project aims to create an Electroencephalography (EEG) curriculum that synthesizes the teachings of current publications and faculty expertise within a single digital platform. The goal is to remedy the unmet need for a centralized resource for learners to use when learning EEG interpretation. Methods: The target learner population is epilepsy and neurophysiology fellows. The platform will be accessible from any computer, tablet, or phone, allowing for mobile, self-paced learning to take place. To date, the curriculum outline has been designed with extensive literature review and collaboration from other institutions, and two pilot modules have been completed using the story-board platform Articulate. Data about efficacy and usefulness will be collected via learner feedback forms when the program goes live. Results and Conclusions: We anticipate that fellows will appreciate the streamlined approach to learning high-yield topics in EEG interpretation. The hope is that the platform will save users time currently spent sifting through textbooks and publications because it incorporates a conglomerate of resources, including qualitative input from experts across the country. That time, in turn, can be spent with more targeted interactions with their teachers (the platform serves as a complement to the existing face-to-face instruction). Learning activities for progress-evaluation will be embedded within each module of the platform with the goal of allowing learners to self-identify areas of improvement to help focus studying efforts. Further results and conclusions will be recorded and updated as progress continues to be made

Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study

Introduction: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). Methods: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of 9 times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects. Results: 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. 5 patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. 11/20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and one patient was not assessable. 12 patients completed all 9 cycles; in those patients, proteinuria decreased from 5.88g/day to 3.37g/day (P = 0.028), Selena-SLEDAI decreased from 17.6 to 11.7. In 13/20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1g/day. Conclusions: Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials

Successful Aging in Philadelphia: Examining the Needs of the Geriatric Community

INTRODUCTION As more adults continue to live until older ages they will have a greater reliance on the formal aging care system and continue to use a large proportion of healthcare resources From 2000 to 2010, the US 65+ population grew 15.1% compared to the total population that grew 9.7%1 CDC estimates that adults who make it to 65 can expect to live for 19 more years, 14 of those in relatively good health2 Adults 65 years and older comprise over 12% of the population of Philadelphia1 In 2002, 19% of Philadelphia’s seniors 65+ lived in poverty, compared to 11% of seniors in the state of Pennsylvania3 Affordable Care Act new requirement for 501 (c)(3) hospitals: conduct a community health needs assessment (CHNA) and adopt an implementation strategy at least once every three years An awareness of geriatric needs by health and social service planners and the city government will help focus on the areas where resources and services need to be allocated Research Question: What are the specific needs of the older population in Philadelphia that need to be addressed in order to facilitate successful aging? Study Objectives: Conduct a small-scale needs assessment of the geriatric population in Philadelphia Lay the groundwork for: Development of more targeted surveys and assessment tools for future investigation Policy and program development Bolstering of aging services Advocacy for the aging population Making Philadelphia a more age-friendly cit

Nouveaux développements de matériaux électroactifs à base de polymères conducteurs électroniques : Vers une intégration dans des systèmes biomédicaux

This PhD work deal with the conception and shaping of actuators based electronic conductive polymers in the context of biomedical use. Currently, while some recurrent problems of lightness, flexibility and robustness can be resolved by these actuators, limitations still restrict their use in biomedical controllable devices.First, our materials composed of interpenetrating polymer networks (IPN) poly (ethylene oxide) (PEO), nitrile butadiene rubber (NBR) and electronically conductive polymer (ECP) (poly (3,4-ethylenedioxythiophene)) (PEDOT) have been studied as a strain sensor. This property is essential to ensure a feedback of our systems in demanding biomedical uses.A third high modulus polymer network, polystyrene (PS), was interpenetrated IPN PEO-NBR in order to improve the forces generated by the actuator. A material combining ionic conductive (PEO), viscoelastic (NBR) and vitreous (PS) properties has been obtained. The detailed characterization of this tri-IPN, the incorporation of the PCE and the study of air-operating performances were then carried out.In continuity and with the collaboration of Pr. J. Madden (Vancouver, Canada), the synthesized material has been used in a particular shaping of catheter. Thus, an electroactive, hollow, flexible, stretchable NBR-PEO-PS-PEDOT tube, with uniform thickness and containing a rigidity gradient has been created in order to solve the various problems associated with this geometry.The last part was dedicated to a more complex and original shaping of our PEO-NBR material. In collaboration with the PERC (Auckland, NZ), electroactive elastomer microfiber mats were prepared by electrospinning. These porous, stretchable and robust materials showed reversible pore size variations in various electrolytes, including biologically compatible. Biomedical applications as filters with controllable porosity or stem cells stimulation could be considered.Ces travaux de thèse s’intéressent à la conception et à la mise en forme d’actionneurs à base de polymères conducteurs électroniques dans l’optique d’une utilisation biomédicale. Actuellement, et alors que certaines problématiques récurrentes de légèreté, de flexibilité et de robustesse peuvent être résolues par ces actionneurs, des limitations restreignent encore leurs utilisations dans des dispositifs biomédicaux contrôlables.En premier lieu, nos matériaux composés de réseaux interpénétrés de polymères (RIP) poly (oxyde d’éthylène) (PEO), caoutchouc nitrile (NBR) et de polymère conducteur électronique (PCE) (poly (3,4-éthylènedioxythiophène)) (PEDOT), ont été étudiés en tant que capteur de déformation. Cette propriété est essentielle pour assurer un retour d’informations de nos systèmes dans des utilisations biomédicales exigeantes.Un troisième réseau de polymère à haut module, le polystyrène (PS), a été interpénétré au RIP PEO-NBR dans le but d’améliorer les forces générées par l’actionnement. Un matériau combinant des propriétés de conduction ionique (PEO), viscoélastiques (NBR) et vitreuses (PS) a alors été obtenu. La caractérisation approfondie de ce tri-RIP, l’incorporation du PCE ainsi que l’étude des performances en actionnement ont alors été réalisée.Dans la continuité et dans le cadre d’une collaboration avec le Pr J. Madden (Vancouver, Canada), le matériau ainsi synthétisé a été utilisé dans une mise en forme particulière de cathéter. Ainsi, un tube électroactif PEO-NBR-PS-PEDOT creux, souple, étirable, d’épaisseur homogène et contenant un gradient de rigidité a été réalisé afin de répondre aux différentes problématiques liées à cette géométrie.Enfin, la dernière partie a été dédiée à une mise en forme plus complexe et originale de notre matériau PEO-NBR. En collaboration avec le PERC (Auckland, N-Z), des tapis de microfibres élastomères électroactifs ont été élaborés par électrofilage. Ces matériaux poreux, étirables et robustes ont montré des changements de taille de pores réversibles dans différents électrolytes, y compris biologiquement compatibles. Des applications biomédicales de type filtre à porosité contrôlable ou la stimulation de cellules souches pourraient alors être envisagées

New Developments in electroactive materials based on electronic conductive polymers : Towards integration into biomedical systems

Ces travaux de thèse s’intéressent à la conception et à la mise en forme d’actionneurs à base de polymères conducteurs électroniques dans l’optique d’une utilisation biomédicale. Actuellement, et alors que certaines problématiques récurrentes de légèreté, de flexibilité et de robustesse peuvent être résolues par ces actionneurs, des limitations restreignent encore leurs utilisations dans des dispositifs biomédicaux contrôlables.En premier lieu, nos matériaux composés de réseaux interpénétrés de polymères (RIP) poly (oxyde d’éthylène) (PEO), caoutchouc nitrile (NBR) et de polymère conducteur électronique (PCE) (poly (3,4-éthylènedioxythiophène)) (PEDOT), ont été étudiés en tant que capteur de déformation. Cette propriété est essentielle pour assurer un retour d’informations de nos systèmes dans des utilisations biomédicales exigeantes.Un troisième réseau de polymère à haut module, le polystyrène (PS), a été interpénétré au RIP PEO-NBR dans le but d’améliorer les forces générées par l’actionnement. Un matériau combinant des propriétés de conduction ionique (PEO), viscoélastiques (NBR) et vitreuses (PS) a alors été obtenu. La caractérisation approfondie de ce tri-RIP, l’incorporation du PCE ainsi que l’étude des performances en actionnement ont alors été réalisée.Dans la continuité et dans le cadre d’une collaboration avec le Pr J. Madden (Vancouver, Canada), le matériau ainsi synthétisé a été utilisé dans une mise en forme particulière de cathéter. Ainsi, un tube électroactif PEO-NBR-PS-PEDOT creux, souple, étirable, d’épaisseur homogène et contenant un gradient de rigidité a été réalisé afin de répondre aux différentes problématiques liées à cette géométrie.Enfin, la dernière partie a été dédiée à une mise en forme plus complexe et originale de notre matériau PEO-NBR. En collaboration avec le PERC (Auckland, N-Z), des tapis de microfibres élastomères électroactifs ont été élaborés par électrofilage. Ces matériaux poreux, étirables et robustes ont montré des changements de taille de pores réversibles dans différents électrolytes, y compris biologiquement compatibles. Des applications biomédicales de type filtre à porosité contrôlable ou la stimulation de cellules souches pourraient alors être envisagées.This PhD work deal with the conception and shaping of actuators based electronic conductive polymers in the context of biomedical use. Currently, while some recurrent problems of lightness, flexibility and robustness can be resolved by these actuators, limitations still restrict their use in biomedical controllable devices.First, our materials composed of interpenetrating polymer networks (IPN) poly (ethylene oxide) (PEO), nitrile butadiene rubber (NBR) and electronically conductive polymer (ECP) (poly (3,4-ethylenedioxythiophene)) (PEDOT) have been studied as a strain sensor. This property is essential to ensure a feedback of our systems in demanding biomedical uses.A third high modulus polymer network, polystyrene (PS), was interpenetrated IPN PEO-NBR in order to improve the forces generated by the actuator. A material combining ionic conductive (PEO), viscoelastic (NBR) and vitreous (PS) properties has been obtained. The detailed characterization of this tri-IPN, the incorporation of the PCE and the study of air-operating performances were then carried out.In continuity and with the collaboration of Pr. J. Madden (Vancouver, Canada), the synthesized material has been used in a particular shaping of catheter. Thus, an electroactive, hollow, flexible, stretchable NBR-PEO-PS-PEDOT tube, with uniform thickness and containing a rigidity gradient has been created in order to solve the various problems associated with this geometry.The last part was dedicated to a more complex and original shaping of our PEO-NBR material. In collaboration with the PERC (Auckland, NZ), electroactive elastomer microfiber mats were prepared by electrospinning. These porous, stretchable and robust materials showed reversible pore size variations in various electrolytes, including biologically compatible. Biomedical applications as filters with controllable porosity or stem cells stimulation could be considered

Assessing river-groundwater exchange fluxes of the Wairau River, New Zealand

Allocation limits in river-recharged aquifers have traditionally been based on static observations of river gains and losses undertaken when river flow is low. This approach to setting allocation limits does not consider the dynamic relationship between river flows and groundwater levels. Predicting groundwater availability based on a better understanding of coupled river - aquifer systems opens the possibility for dynamic groundwater allocation approaches. Numerical groundwater models are most commonly used for regional scale allocation assessments. Using these models for predicting future system states is challenging, particularly under changing management and climate scenarios. The large degree of uncertainty associated with these predictions is caused by insufficient knowledge about the heterogeneity of subsurface flow characteristics, ineffective monitoring designs, and the inability to confidently predict the spatially and temporally varying river - groundwater exchange fluxes. These uncertainties are characteristic to many coupled surface water groundwater systems worldwide. Braided river systems, however, create additional challenges due to their highly dynamic morphological character and mobile beds which also make river flow measurements extremely difficult. This study focuses on the characterization of river - groundwater exchange fluxes along a section of the Wairau River in the Northwest of the South Island of New Zealand. The braided river recharges the Wairau Aquifer which is an important source for irrigation and municipal water requirements of the city of Blenheim. The Wairau Aquifer is hosted by the highly permeable Rapaura Formation gravels that extend to a depth of about 20 to 30 m. However, the overall thickness of the alluvial sequence forming the Wairau Plain may be up to 500 m.The land use in the area is mainly grapes but landsurface recharge to the aquifer is considered to be considerably smaller than the recharge from the Wairau river. This study aims at the assessment of river-groundwater exchange fluxes and presents first results from data mining and analysis of river flow records, stage gaugings, groundwater head data, pumping test, and the sampling of spring flows. In addition, a methodology is presented that will allow the prediction of transient river exchange fluxes by using a Modflow model, global optimisation techniques, and techniques for quantifying predictive uncertainty which have been recently developed (Wöhling et al 2013). A long-term goal of the study is the reduction of predictive uncertainty of model predictions by optimal design of sensor networks as well as the assessment of this utility by different observation types. Preliminary results indicate that about 7 cumec from the Wairau River is recharged to the aquifer under low flow conditions. A similar volume of groundwater re-emerges as springs where groundwater is forced upwards by the confining Dillons Point Formation