Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.

Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB-06-002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB-06-002 who continued receiving taliglucerase alfa in extension Study PB-06-003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB-06-003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30-33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, -1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), -19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, -51.5% (±8.1%; n = 10); and CCL18 concentration, -36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment-related adverse events were mild or moderate and transient. The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661-665, 2016. © 2016 Wiley Periodicals, Inc

A population-based study of communicative participation in preschool children with speech-language impairments

Aim. To develop statistical models of preschoolers’ communicative participation development and explore variations by level of function. Methods. This was a secondary analysis of data from a longitudinal study of preschoolers with speech and language delays (N = 46,872, M age = 41.76, SD age = 11.92; 67% male) accessing publicly-funded services in Ontario Canada. Two measures were used: Focus on the Outcomes of Communication Under Six (FOCUS), measuring changes in communicative participation skills, and the Communication Function Classification System (CFCS), classifying communication function into one of five levels. We used mixed effects modeling to fit growth curves for each CFCS level. Models allowed for variation in initial FOCUS scores at 18 months, rate of growth with age, and rate of acceleration/deceleration with age. Results. Starting FOCUS score (18 months) varied inversely with CFCS level at entry to the program. Growth was initially rapid and then levelled off for children in levels I-III. Growth was less rapid for children in level IV, but levelled off, and was slow but continual for children in level V. Interpretation. This work can help us to move beyond traditional impairment-based thinking and shows that children can make meaningful communicative changes regardless of their function

Factors Contributing to Preschoolers\u27 Communicative Participation Outcomes: Findings From a Population-Based Longitudinal Cohort Study in Ontario, Canada

Purpose. To identify predictors of communicative participation outcomes for a large cohort of preschoolers with communication disorders. Method. A secondary analysis of longitudinal program evaluation data from Ontario Canada’s Preschool Speech and Language Program (PSLP). Data available for 46,872 children 18-67 months of age (M = 41.76 mo, SD = 11.92, 68% male) were previously used to predict children’s communicative participation skill development in five levels of function. Demographic and intervention-based variables were added to the models to identify new predictors of growth. Results. Three demographic and three intervention-based variables were statistically significant predictors of children’s communicative participation outcomes. Clinically significant predictors included participation in an early learning environment, receipt of speech-language interventions, and the amount of time spent in intervention. These variables impacted predicted outcomes differently depending on a child’s level of communicative function. Conclusions. This population-based study of preschoolers with speech and language disorders identified predictors of growth in communicative participation skills – an outcome important and meaningful to families but, not often explored. A broad picture emerged of factors that may influence the development of communicative participation skills, and may be used to predict outcomes for preschoolers. Given the large sample size, these robust findings may be used to predict outcomes outside the PSLP as well

Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187

Phase diagram of the Shastry-Sutherland Compound SrCu2(BO3)2 under extreme combined conditions of field and pressure

Motivated by the intriguing properties of the Shastry-Sutherland compound SrCu2(BO3)2 under pressure, with a still debated intermediate plaquette phase appearing at around 20 kbar and a possible deconfined critical point at higher pressure upon entering the antiferromagnetic phase, we have investigated its high-field properties in this pressure range using tunnel diode oscillator (TDO) measurements. The two main new phases revealed by these measurements are fully consistent with those identified by infinite Projected Entangled Pair states (iPEPS) calculations of the Shastry-Sutherland model, a 1/5 plateau and a 10 x 2 supersolid. Remarkably, these phases are descendants of the full-plaquette phase, the prominent candidate for the intermediate phase of SrCu2(BO3)2. The emerging picture for SrCu2(BO3)2 is shown to be that of a system dominated by a tendency to an orthorhombic distortion at intermediate pressure, an important constraint on any realistic description of the transition into the antiferromagnetic phase

Using knowledge brokers to facilitate the uptake of pediatric measurement tools into clinical practice: a before-after intervention study

<p>Abstract</p> <p>Background</p> <p>The use of measurement tools is an essential part of good evidence-based practice; however, physiotherapists (PTs) are not always confident when selecting, administering, and interpreting these tools. The purpose of this study was to evaluate the impact of a multifaceted knowledge translation intervention, using PTs as knowledge brokers (KBs) to facilitate the use in clinical practice of four evidence-based measurement tools designed to evaluate and understand motor function in children with cerebral palsy (CP). The KB model evaluated in this study was designed to overcome many of the barriers to research transfer identified in the literature.</p> <p>Methods</p> <p>A mixed methods before-after study design was used to evaluate the impact of a six-month KB intervention by 25 KBs on 122 practicing PTs' self-reported knowledge and use of the measurement tools in 28 children's rehabilitation organizations in two regions of Canada. The model was that of PT KBs situated in clinical sites supported by a network of KBs and the research team through a broker to the KBs. Modest financial remuneration to the organizations for the KB time (two hours/week for six months), ongoing resource materials, and personal and intranet support was provided to the KBs. Survey data were collected by questionnaire prior to, immediately following the intervention (six months), and at 12 and 18 months. A mixed effects multinomial logistic regression was used to examine the impact of the intervention over time and by region. The impact of organizational factors was also explored.</p> <p>Results</p> <p>PTs' self-reported knowledge of all four measurement tools increased significantly over the six-month intervention, and reported use of three of the four measurement tools also increased. Changes were sustained 12 months later. Organizational culture for research and supervisor expectations were significantly associated with uptake of only one of the four measurement tools.</p> <p>Conclusions</p> <p>KBs positively influenced PTs' self-reported knowledge and self-reported use of the targeted measurement tools. Further research is warranted to investigate whether this is a feasible, cost-effective model that could be used more broadly in a rehabilitation setting to facilitate the uptake of other measurement tools or evidence-based intervention approaches.</p

La medida de la participación de los niños en las actividades de ocio y tiempo libre: validez de constructo del Cape y del Pac

Se necesitan medidas de la participación de los niños en las actividades de ocio y tiempo libre, psicométricamente fuertes, tanto para la práctica clínica como para la investigación. Este artículo proporciona información acerca de la validez de constructo del Children’s Assessment of Participation and Enjoyment (CAPE) y de su instrumento complementario, el Preferences for Activities of Children (PAC). Estas medidas son apropiadas para niños y jóvenes con y sin discapacidad de edades comprendidas entre los 6 y 21 años. Proporcionan información acerca de seis dimensiones de la participación (diversidad, intensidad, dónde, con quién, disfrute y preferencia) y dos categorías de actividades de ocio y tiempo libre: (i) actividades formales e informales; y (ii) cinco tipos de actividades (tiempo libre, actividad física, social, basada en habilidad y autosuperación). Este artículo proporciona información sobre el desempeño de los resultados de los tipos de actividad del CAPE y PAC a partir de los datos de un estudio en el que participaron 427 niños con discapacidad física de edades comprendidas entre los 6 y 15 años. Los resultados de Intensidad, disfrute y preferencia correlacionaron significativamente con las variables ambientales, de la familia y del niño, como se esperaba. Las predicciones también fueron apoyadas en lo que respecta a las diferencias en las puntuaciones medias para los niños frente a las niñas y a los niños en diversos grupos de edad. La información fundamenta la validez de constructo de las medidas. Se exponen la utilidad clínica e investigadora de las medidas

Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

Objective: Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Materials and methods Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18–55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Results: Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of −1.6 (1.1) to −0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Conclusions: Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1

Nutrition, information and household behavior: Experimental evidence from Malawi

Incorrect knowledge of the health production function may lead to inefficient household choices and thereby to the production of suboptimal levels of health. This paper studies the effects of a randomized intervention in rural Malawi that, over a six-month period, provided mothers of young infants with information on child nutrition without supplying any monetary or in-kind resources. A simple model first investigates theoretically how nutrition and other household choices including labor supply may change in response to the improved nutrition knowledge observed in the intervention areas. We then show empirically that the intervention improved child nutrition, household food consumption and consequently health. We find evidence that labor supply increased, which might have contributed to partially fund the increase in food consumption. This paper is the first to study whether non-health choices, particularly parental labor supply, might be affected by parents' knowledge of the child health production function