Engineering Elephants: Introducing Young Children to Engineering

2011 ◽  
Vol 1320 ◽  
Author(s):  
Emily M. Hunt ◽  
Michelle L. Pantoya ◽  
Abbye M. Reeves
Keyword(s):  
Summer School ◽  
Age Groups ◽  
School Curriculum ◽  
Elementary School District ◽  
Children's Book ◽  
Language Of Science ◽  
Simple Question ◽  
Instructional Aid ◽  
Asking Questions ◽  
Grade 3

ABSTRACTIn this study, the authors focused on children from 2-8 years of age and asked the simple question: what do engineers do? The number one response was: “I don’t know”, the number two response was “they drive a train.” While children are very familiar with professionals such as doctors, teachers, nurses, firefighters and policemen, they are rarely introduced to engineers. With this motivation, the authors developed a novel children’s book on engineering: Engineering Elephants. This book is an outreach tool that introduces children to the dynamic world of engineering design through roller coasters, fireworks, and a plethora of other exciting adventures. The book teaches children about relevant topics such as nanotechnology, renewable energy, and prosthetics by engaging them through an interactive journey of an elephant and his questioning of the world around him. The text was strategically developed using the language of science (asking questions) and introducing vocabulary relevant to science and math using a lyrical pattern. This presentation will highlight the development of this book as an instructional aid but also detail the response of various age groups to engineering activities presented as a companion to this book. In particular, an elementary school district in West Texas designed a 4-5th grade 3-week summer school curriculum around this book. Results from this study will have an impact on future generations by inspiring them to consider the exciting profession of engineering at an early age.

scholarly journals The growth of foot arches and influencing factors

2016 ◽  
Vol 45 (3) ◽  
pp. 111
Author(s):  
Ferial Hadipoetro Idris
Keyword(s):  
Influencing Factors ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Positive Influence ◽  
Older Age ◽  
Optimal Time ◽  
Flat Foot ◽  
Cross Sectional ◽  
Foot Arch ◽  
Grade 3

Background Foot arches are important components for body sup-port. Foot arch deformity caused by growth abnormalities causeserious limitations in daily activities.Objectives To determine the patterns of foot arch growth, factorsinfluencing foot arch growth, and the timing for intervention in er-rant growth patterns.Methods A cross-sectional study evaluated the foot arches of chil-dren aged 0-18 years according to age and sex. Subjects includedhad no evidence of physical abnormality other than flat foot, knock-knee, or bow leg. Subjects were grouped per year of age. Data onfoot arch class, age, sex, weight, height, medial intercondylar dis-tance, and medial intermalleolar distance were recorded. Chi-square test, correlation, binary and linear regressions, general lin-ear model, and contrast matrix were performed.Results In 8376 children aged 0-18 years, flat foot grade 3 hadstable proportions in all age groups. Flat foot grade 2 and 1 hadsmaller proportions in older age groups than in younger ones. Theproportions of normal foot was greater in older age groups. Boysat the age of 7 and girls at 9 have a small percentage of pes cavus.The mean foot arch measurements were consistent with flat footgrade 2 at age 0-3 years, flat foot grade 1 at 4 years, and normalfoot at age 18. Median foot arch measurement of children 0-10years old was consistent with flat foot grade 1, while that of chil-dren 11 years old was consistent with normal foot. Age and heightgave positive influence. Based on these measurements we inferthat the optimal time for intervention is 0-7 years for boys and 0-3years for girls.Conclusion The proportion of flat foot grade 3 is stable through-out age groups, that of flat foot grade 2 and 1 are smaller in olderage groups, and that of normal foot is greater in older age groups.Overgrowth happens in very small percentages after age of 7 inboys and 9 in girls. Age, sex, height, weight, and growth of theknees are influencing factors

Mitral Clefts and Interatrial Septum Defects: 15-Year Results

2003 ◽  
Vol 11 (2) ◽  
pp. 135-138 ◽  
Author(s):  
Kaan Kirali ◽  
Denyan Mansuroğlu ◽  
Yücel Özen ◽  
Nilgün Ulusoy Bozbuğa ◽  
Altuğ Tuncer ◽  
...  
Keyword(s):  
Septal Defect ◽  
Superior Vena ◽  
Age Groups ◽  
Vena Cava ◽  
Interatrial Septum ◽  
Mitral Insufficiency ◽  
Mitral Leaflet ◽  
Anterior Mitral Leaflet ◽  
Adult Age ◽  
Grade 3

Between 1985 and 2002, 60 patients (58% female) with a mean age of 20.3 ± 12.1 years (range, 2–55 years) were treated for anterior mitral leaflet cleft. There was a primum atrial septal defect in 52 patients (87%) and a secundum type in 8 (13%). Concomitant cardiac defects were patent foramen ovale in 6 patients, cleft tricuspid valve in 3, ventricular septal defect in 2, cor triatriatum in 1, and persistent left superior vena cava in 1. Mean grade (1–4) of mitral insufficiency was 2.28 ± 0.74. Atrial septal defects were closed with a pericardial patch in 45 patients, with a prosthetic patch in 11, and primarily in 4. Mitral leaflet clefts were repaired using interrupted sutures. There was no early or late mortality. Two patients (3%) needed a permanent pacemaker. Postoperatively, severe (≥ grade 3) mitral insufficiency developed in 2 patients; valve replacement was performed in one, cleft recurrence and leakage from the patch were treated in the other. Freedom from reoperation was 92.2% ± 5.6% at 15 years. Surgical intervention can be performed for congenital anterior mitral leaflet cleft and interatrial septal defect with good results in both pediatric and adult age groups.

Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 717-717 ◽  
Author(s):  
Barbara F. Eichhorst ◽  
Raymonde Busch ◽  
Clemens M. Wendtner ◽  
Michael Hallek ◽  
Keyword(s):  
Age Groups ◽  
The Elderly ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Binet Stage ◽  
Grade 3

Abstract Introduction: F based regimen have become the standard treatment in CLL at least in younger pts. However, in elderly pts chlorambucil is still frequently used since it is easy to administer and has less side effects. Here we compare the efficacy and toxicity of F administered to younger pts and elderly pts treated between 1999 and 2004 within two phase III trials of GCLLSG. Patients: 362 pts (median age 59 [range 37–65] years) were randomized to F (n=182) or F plus cyclophosphamide (n=180) within the CLL4 trial. 191 elderly pts (median age 71 [range 65–79] years) were treated with F (92 pts) or chlorambucil (99 pts) within the CLL5 protocol. Inclusion criteria were identical in both trials except for age limits. All pts were previously untreated and in advanced stage Binet C or Binet B with symptoms which require therapy or Binet A with severe B-symptoms. In both studies the F regimen consisted of 30 mg/m2/day (d) IV for 5 consecutive days, every 28 d for up to 6 cycles. Anti-infective prophylaxis and growth factors were not given routinely in both trials. Results: Most of patients in both age groups were in Binet stage B (54% of the younger pts and 52% of the elderly), 35% in each age group were in Binet stage C, 11% and 13% respectively in Binet stage A. No significant difference in the main clinical features was observed except for a higher incidence of concomitant disease in the elderly (61% versus 36%, p=0.001). A mean number of 5.2 F courses was administered in the CLL4 trial and 4.9 courses in the CLL5 trial. The mean administered cumulative dose of F per pt was lower in the elderly pts (1076 mg vs. 1194 mg, p= 0.05). Overall response rates were similar in both arms, with 82.9% in the younger group and 85.7% in the elderly. The complete remission rate was 6.7% in the younger patients and 10.4% in the elderly (p= 0.3). After a follow up time of 24 months (mo) the progression-free survival (PFS) was significantly shorter in the elderly group with 18.7 mo compared to 19.8 mo in the younger group after 22 mo observation time (p=0.03). The overall survival (OS) was significantly impaired in elderly pts as well (29 mo versus median not reached, p<0.001). Progressive disease was the main cause of death in both age groups. In each group 3 treatment related deaths occurred due to infection or hemolysis. The incidence of side effects was similar in both age groups. Severe, CTC grade 3 and 4, myelosuppression occurred in 39% of the younger and 41% of the elderly pts. No difference in the rate of leukocytopenia, thrombocytopenia or anemia was oberved as well. The incidence rate and severity of infections was similar in both groups (24% vs. 32% all and 8.7% vs. 6.9% CTC grade 3 and 4). The incidence of second neoplasia was significantly higher in the elderly pts (2.2% vs. 12.2%, p=0.001). In comparison the prevalence rate of neoplasia in the U.S. population peaks at 11% in the age group of 70–79 (SEER cancer statistic review: 1972–2002). Conclusion: F is a well tolerated treatment regimen in first line therapy of elderly pts with CLL. Response rates were similar in both age groups. PFS and OS were significantly shorter in the elderly population. The incidence of second neoplasia was significantly higher in the elderly pts, but is only slightly increased in comparison to the normal population.

Disease Characteristics and Patterns of Care In Elderly Patients (80+ years) with Follicular Lymphoma (FL) In the United States (US); Are Older Patients Treated Differently? Report From the National LymphoCare Study (NLCS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4152-4152
Author(s):  
Chadi Nabhan ◽  
Michelle Byrtek ◽  
Michael Taylor ◽  
Jill Tydell ◽  
Jamie H. Hirata ◽  
...  
Keyword(s):  
Older Patients ◽  
Research Funding ◽  
Age Groups ◽  
Treatment Patterns ◽  
Disease Stage ◽  
Younger Patients ◽  
Disease Characteristics ◽  
Significant Difference ◽  
The Difference ◽  
Grade 3

Abstract Abstract 4152 Background: While FL is the most common low-grade lymphoma in the US, median age was less than 60 in patients enrolled on pivotal studies that led to our understanding of disease biology and optimal therapy. It remains unclear whether similar disease characteristics, presentation, prognostic factors, treatment patterns, and outcomes pertain to older patients with FL. No clear guidelines exist on how older patients should be treated and data is lacking as to whether current practice patterns affect their survival and progression. Previous reports on FL in the elderly have been retrospective and single center-based. Methods: The NLCS is a prospective, longitudinal multicenter, observational study that enrolled consecutive newly diagnosed FL patients from 3/2004 through 3/2007 collecting data on disease and patients' characteristics, treatment patterns, and outcome. Using the NLCS data we analyzed information on disease stage, grade, FL International Prognostic Index (FLIPI), B symptoms, and treatment choice for patients <60 years, 60–69 years, 70–79 years, and 80+ years. Either Chi-square or Fisher's exact comparison was used to assess the correlations depending on the sample size of the test. Results: A total of 2,736 pts were enrolled, of which 1,215 (44%) were < 60, 708 (25%) were between 60–69, 549 (20%) were between 70–79, and 264 (9%) were >80. There was a significant difference in grade distribution across the different age groups (p < 0.0001), with 22% of pts 80+ having grade 3 FL vs 17% pts <60. No significant differences across age groups in B symptoms, extra nodal sites, or LDH values were observed. A significant difference in FLIPI score was seen across the age groups (p < 0.0001) where high-score FLIPI was present in 48% of pts 80+ as opposed to 16% of pts <60, although calculating FLIPI might be confounded by the fact that older patients were more likely to not have received a bone marrow (BM) exam with 66% of pts 80+ not having BM exam vs. only 40% of those <60 (p < 0.0001). The difference in FLIPI was mainly due to lower Hgb values as older patients were more likely to have had Hgb < 12 g/dL than younger patients (31% of pts 80+ vs. 15% of pts <60) and to age being a component of the FLIPI index. The difference in FLIPI score across age groups was also observed in patients with grade 3 FL where 53% of pts 80+ had poor FLIPI vs. 15% of pts <60 (p < 0.0001). A statistically significant difference in treatment patterns was found across age groups (p <0.0001). When treatment was implemented, older patients were more likely to have received rituximab (R) monotherapy (37% of 80+ vs. 12% of <60) and less likely to have received R+Chemotherapy (40% of pts 80+ vs. 64% of pts<60). In addition, more pts 80+ were observed compared to those <60 (23% vs. 16%). These differences persisted even in those with advanced stage (III/IV), grade 3 disease, region of diagnosis, and in poor-risk FLIPI. When chemotherapy was used, older patients were less likely than younger patients to receive anthracyclines (p < 0.0001) (31% of pts 80+ vs. 69% of pts<60). Anthracycline use remained significantly different regardless of disease stage, grade, or FLIPI score. Conclusions: To our knowledge, this is the largest prospective data collection available for FL pts 80+ years of age. We demonstrate that these pts have higher FLIPI score and grade 3 disease. When treatment is initiated, these patients receive R monotherapy more often than their younger counterpart. Anthracycline use in this population is also less common regardless of disease stage, grade, or risk profile. Whether these baseline differences translate into different outcomes remains to be seen. Disclosures: Nabhan: genentech: Research Funding, Speakers Bureau. Byrtek:Genentech: Employment. Taylor:Genentech: Employment. Hirata:Genentech: Employment. Flowers:Genentech/Biogen-Idec (unpaid): Consultancy; Celgene, Intellikine: Consultancy; Millennium: Research Funding.

Young Adults Aged 18 to 30 Years with Hodgkin Lymphoma Can Tolerate a Modified Version of the Combined Modality German Paediatric HD95 Protocol with Minimal Neurotoxicity and Excellent Outcome. Results of the UK NCRN 18–30 Study (CRUK/08/012)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1621-1621
Author(s):  
Kirit M Ardeshna ◽  
Peter Hoskin ◽  
Paul Smith ◽  
Nicholas Chadwick ◽  
Nivette Braganca ◽  
...  
Keyword(s):  
Young Adults ◽  
Conflicts Of Interest ◽  
Vinca Alkaloid ◽  
Age Groups ◽  
Biological Difference ◽  
Excellent Outcome ◽  
Combined Modality ◽  
Grade 3 ◽  
The Uk ◽  
Previous Disease

Abstract Abstract 1621 The outcome for children with Hodgkin's Lymphoma treated using the German-Austrian paediatric risk-adapted combined modality regimen appears superior to that of adults treated with ABVD +/− radiotherapy. Whether this is related to the superiority of the therapy or a biological difference in the disease in the different age groups is unclear. As a preliminary step to try and compare these regimens directly we enrolled 47 patients between 18 and 30 years of age (median 23y range 18–30) recruited from 8 centres across the UK onto the 18–30 study which used a modified version of the HD95 protocol. Patients were allocated to one of three treatment groups according to stage TG1=1A, 1B, 2A (n=16), TG2=2AE, 2B, 3A (n=11) TG3=2BE, 3AE, 3BE, 3B, 4A, 4B (n=20). Patients in TG1 received 2 cycles of OEPA (vincristine 1.5mg/m2 iv d1,d8,d15 (capped at 2mg/dose), etoposide 125mg/m2 iv d1–5, adriamycin 40mg/m2 iv d1 & 15, prednisolone 60mg/m2 po d1–15). Patients in TG2 received 2xOEPA and 2 xCOPP (cyclophosphamide 500mg/m2 iv d1 and 8 vincristine 1.5mg/m2 iv d1,8 (capped 2mg/dose) procarbazine 100mg/m2 po d1–15, prednisolone 40mg/m2 po d1–15). Patients in TG3 received OEPAx2 and COPPx4. All patients (except those in TG1 who were in CR by CT and PET criteria) went on to receive involved site radiotherapy to all sites of previous disease. The dose of radiotherapy was 20Gy for patients in CR and VGPR (>75% reduction) by CT criteria with areas of residual abnormality on scan >50ml receiving a 30Gy boost. Patients with a PR (50–75% reduction) received the same doses if they were PET negative however those who were PET positive received 30Gy to all sites of previous disease. The schedule of vinca alkaloids in HD95 is compressed with those in TG3 receiving 16 doses of vincristine 1.5mg/m2 (max 2mg) given over 6 months compared with 16 doses of vinblastine 6mg/m2 given over 8 months in ABVD. In view of this and the increase in vinca alkaloid related neurotoxicity with age the primary endpoint of this study was to establish the level of neurotoxicity using this paediatric regimen in young adults. 45 patients (23 male) completed therapy. 1 patient was withdrawn after a hypersensitivity reaction to etoposide on d1 OEPA1 and 1 patient withdrew consent prior to starting therapy. Worst neurotoxicity grade was recorded as: 0 (n=8), 1 (n=17), 2 (n=16) 3 (n=4 [with 2 motor in TG1 &TG2, 1 sensory inTG2, 1 ileus inTG3). In 3 of the 4 patients with severe neurotoxicity vincristine was converted to vinblastine 6mg/m2 according to protocol. No progression of the neuropathy was seen and patients were able to complete their scheduled therapy. In one case (TG2) vincristine was omitted in the final cycle. Neurotoxicity grade at last FU was 0 (n=34) 1 (n=8) 2 (n=3). All 4 cases of grade 3 neurotoxicity reverted to grade 0. Seven patients with grade 2 neuropathy had adjustments made to the dose or type of vinca alkaloid at the request of the physician. Current grade of neuropathy at last FU in these 7 patients:0 (n=4) 1 (n=2) 2 (n=1). There were 8 episodes of febrile neutropenia. Other grade 3 toxicities included diarrhoea (n=2), vomiting (n=3), mucositis (n=3), abdominal pain (n=3) and thrombosis (n=2). Bone/joint pain was seen in 4 patients. Two patients (both TG3) have developed proven osteonecrosis. All 45 patients who completed the chemotherapy achieved a CR or PR. Four did not require radiotherapy, 36 required 20Gy and 5 required 30Gy as a baseline dose to previously involved sites. The median follow up to date is 18 months. Four patients have progressed (1=TG2, 3=TG3) giving a 2yr PFS of 89%. All patients are currently alive. Quality of life data has been collected and assessments of late effects are ongoing. In conclusion, young adults aged 18–30 can tolerate a modified HD95 protocol with a minority of patients experiencing grade 3 neurotoxicity which is reversible when adjustments are made. Outcome with this regimen (which contains only 160mg/m2of adriamycin and no bleomycin) seems encouraging and this (or a more up to date German Austrian Paediatric protocol e.g.with dacarbazine replacing procarbazine in an attempt to spare fertility and omission of radiotherapy based on PET scan after OEPA) warrants testing against ABVD in this age group. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Tolerability of Bosutinib and Imatinib in Older Versus Younger Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia–BELA Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4442-4442 ◽  
Author(s):  
Carlo Gambacorti-Passerini ◽  
Tim H Brümmendorf ◽  
Dong-Wook Kim ◽  
Irina Dyagil ◽  
Hagop M Kantarjian ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Age Groups ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Kaplan Meier ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 4442 Bosutinib (BOS) is an orally active, dual Src/Abl kinase inhibitor with activity and manageable toxicity in the phase 3 BELA trial of patients (pts) with newly diagnosed (≤6 mo) chronic phase (CP) chronic myeloid leukemia (CML). The current analysis of the BELA trial summarizes the activity and tolerability of BOS 500 mg/d and imatinib (IM) 400 mg/d among older (≥65 y; BOS n = 30; IM n = 27) versus younger pts (<65 y; BOS n = 220; IM n = 225). Sokal risk scores were balanced between treatment arms but, as expected, higher among older pts (4% low; 72% intermediate; 25% high) versus younger pts (39% low; 44% intermediate; 17% high). Minimum follow-up duration was 24 mo. BOS was discontinued by 37% of pts (57% older vs 35% younger; P = 0.023); difference between age groups was primarily due to adverse events (AEs; 39% vs 22%; most commonly increased alanine aminotransferase [ALT]). IM was discontinued by 27% of pts (35% older vs 28% younger; P= 0.496); disease progression was the primary reason. In the intent-to-treat population, cumulative rate of complete cytogenetic response (CCyR) by 24 mo in older/younger pts was 70%/80% on BOS and 78%/80% on IM. Median time to CCyR was 24.0 wk for older versus 12.7 wk for younger pts on BOS and 24.4 wk versus 24.7 wk on IM; in younger pts CCyR was achieved significantly faster on BOS versus IM (P<0.001). Among older/younger pts with a CCyR, 57%/79% on BOS and 76%/85% on IM were still on treatment and retained their CCyR as of the data cutoff. Cumulative rates of major molecular response (MMR) by 24 mo in older/younger pts were 53%/60% on BOS and 48%/49% on IM. Median time to MMR was 48.1 wk for older versus 48.0 wk for younger pts on BOS and 60.6 wk versus 84.1 wks on IM; for younger pts MMR was achieved significantly faster on BOS versus IM (P<0.001). Among older/younger pts with a MMR, 63%/84% on BOS and 92%/89% on IM were still on treatment and retained their MMR as of the data cutoff. Kaplan-Meier event-free survival in older/younger pts at 2 y was 100%/91% on BOS and 81%/88% on IM. Kaplan-Meier on-treatment transformation to accelerated/blast phase CML by 2 y was 0% for older and 2% (4 transformations) for younger pts on BOS (4 total), and 9% (2 transformations) for older and 5% (11 transformations) for younger pts on IM (13 total). Kaplan-Meier overall survival in older/younger pts at 2 y was 100%/97% on BOS and 92%/95% on IM. The majority of deaths were due to disease progression (BOS, n = 6; IM, n = 10); few deaths due to AEs on BOS (n = 1) or IM (n = 2) were reported, none treatment related. BOS was associated with higher rates of gastrointestinal TEAEs, elevated ALT and aspartate aminotransferase (AST), and pyrexia; IM was associated with higher rates of musculoskeletal TEAEs and edema (Table). Rates of common TEAEs were generally similar or higher among older pts. Pleural/pericardial effusion occurred in 6 (21%) older pts (3/6 with treatment-related events; median event duration, 36.5 d) versus 5 (2%) younger pts (all with treatment-related events) on BOS, and in no IM pts. Overall grade 3/4 TEAEs were more frequent among older pts on both BOS and IM, as was dose modification (Table). Grade 3/4 lab abnormalities of elevated ALT (BOS, 18% older/24% younger; IM, 4% each) and AST (BOS, 7%/12%; IM, 4% each) were more frequent with BOS versus IM, but similar between age groups. Grade 3/4 lab abnormalities of neutropenia were more frequent with IM (23% older/22% younger) versus BOS (11% each) regardless of age; grade 3/4 anemia (6%-14%) and thrombocytopenia (14%-23%) were generally similar regardless of age or treatment arm. In conclusion, BOS demonstrated activity in both older and younger pts with newly diagnosed CP CML. Although the frequency of certain toxicities as well as treatment discontinuations due to TEAEs was higher among older pts, the toxicity profile of BOS remained manageable and distinct from that of IM regardless of age. Event, % BOS IM ≥65 y (n = 28) <65 y (n = 220) ≥65 y (n = 26) <65 y (n = 225) Non-hematologic TEAEsa     Diarrhea 86 68 46 22     Rash 36 22 27 18     Nausea 36 32 31 37     Vomiting 32 32 19 15     Dyspnea 32 5 12 3     Pyrexia 29 17 4 13     Elevated ALT 29 32 15 8     Elevated AST 25 27 15 8     Elevated lipase 25 12 19 10     Headache 21 12 8 12     Asthenia 21 5 4 7     Dyspepsia 14 6 23 5     Muscle spasms 14 3 35 21     Periorbital edema 7 <1 35 12 Any grade 3/4 TEAE 89 65 73 56 Dose reduction due to AE 64 40 42 18 Dose interruption due to AE 89 63 69 42 Treatment discontinuation due to AE 39 22 8 9 All treated pts were included in the safety analyses. a Includes TEAEs reported for ≥20% of older or younger pts. Disclosures: Gambacorti-Passerini: Pfizer Inc: Consultancy, Research Funding; Novartis, Bristol Myer Squibb: Consultancy. Brümmendorf:Bristol Myer Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Patent on the use of imatinib and hypusination: Patents & Royalties. Kim:BMS, Novartis, Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Pfizer Inc: Research Funding. Pavlov:Pfizer Inc: Employment, Equity Ownership. Gogat:Pfizer Inc: Employment, Equity Ownership. Duvillie:Pfizer Inc: Employment. Shapiro:Pfizer Inc: Employment, Equity Ownership. Cortes:Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding.

Phase II Trial of Ofatumumab (OFA) for Older Patients and Patients Who Refuse Fludarabine-Based Regimens with Previously Untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 719-719 ◽  
Author(s):  
Ian W. Flinn ◽  
William N. Harwin ◽  
Patrick Ward ◽  
Habib H. Doss ◽  
Steven W. Papish ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nk Cell ◽  
Single Agent ◽  
Age Groups ◽  
Progression Free Survival ◽  
Response Rates ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Front Line ◽  
Grade 3

Abstract Abstract 719 Background: Fludarabine (FLU), cyclophosphamide and rituximab or other FLU based regimens have shown improvement in response rates, progression-free survival, and in some studies overall survival in patients (pts) with previously untreated CLL or SLL. However, the value of FLU based therapies in older pts is less clear with both clinical trial and retrospective analyses showing no improvement in progression-free and overall survival with FLU based therapy. In contrast, regimens that contain rituximab appear to provide benefit across all age groups. OFA is a fully human Immunoglobulin G1 kappa, monoclonal antibody that targets a unique epitope on the CD20 molecule. Pre-clinical data indicate that OFA has greater NK cell and monocyte mediated killing, complement dependent cytotoxicity, and direct killing against CLL cells. Based on pre-clinical and clinical studies indicating possible increased efficacy of OFA in pts with CLL, our aim was to develop an antibody-only regimen for older pts and pts who refuse FLU-based regimens. Methods: Eligible pts had previously untreated CD20+ B-cell CLL(B-CLL) or SLL according to NCI criteria, ECOG PS of ≤2, and were either ≥ 65 years of age, or pts 18–64 years of age who had declined FLU-based regimens. All pts in this study received OFA as an IV infusion once weekly for a total of 8 weeks. To reduce the possibility of infusion reactions, the first dose of OFA was administered at a dose of 300mg. If the initial 300mg dose of OFA was well tolerated, without occurrence of any infusion associated AEs of ≥ grade 3, subsequent doses of OFA (i.e., Week 2 through Week 8) were given at a dose of 2000mg for cohort 1 and 1000mg for cohort 2. Eight weeks after the 8-week induction treatment (tx) ended; pts were assessed for response to the tx. Pts who progressed received no further tx. Pts who responded to the tx or who did not have disease progression received maintenance therapy - OFA at a dose of 2000mg IV for cohort 1 and 1000mg for cohort 2 every 2 months for 2 years (for a total of 12 doses, in the absence of PD or intolerable toxicity) beginning 3 months after the last dose of OFA. Results: Between 8/2010 and 12/2011, 77 pts were accrued (44 pts on cohort 1, 33 pts on cohort 2), median FU for Cohort 1 was 16.1 months (11.6–20.9) and Cohort 2 7.2 months (3.6–10.7). Median age of cohort 1 was 69 (range 47–88) and cohort 2 was 75 (range 50–93). Rai stage at study entry was I/II/III/IV (cohort 1 15/5/11/14 and cohort 2 9/10/7/7). All pts have completed induction therapy. The most common reason for early discontinuation was due to progressive disease (7 pts). Neutropenia was the most common grade 3/4 hematologic adverse event (10 pts). There were no G3 related non-hematologic AEs in either cohort. Two pts have died (1 due to MI, 1 due to CVA). Response by NCI 1996 criteria and IWCLL 2008 criteria and FISH category are shown below; at the time of this analysis 44 pts on C1 and 22pts on C2 were evaluable for response. Kaplan-Meier estimate of PFS is 74% at 15 months for cohort 1. Time to event data for cohort 2 are immature at this analysis but PFS but will be presented at the meeting. Conclusions: OFA, when given as a single agent, is well tolerated as front-line therapy in pts with CLL/SLL. Response rates and PFS compare favorably to our previous studies with rituximab using the same response criteria, particularly when differences in the age of pts entered onto the study are considered. The optimal single-agent dose of OFA in the front-line setting remains to be determined. Further follow-up of these data my provide insight in the dose/response relationship. Disclosures: Off Label Use: Ofatumumab as front-line treatment for CLL/SLL.

Clinical outcomes and safety in men ≥ 75 and < 75 years with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in the phase 3 PREVAIL trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Julie Nicole Graff ◽  
Giulia Baciarello ◽  
Andrew J. Armstrong ◽  
Celestia S. Higano ◽  
Peter Iversen ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Age Groups ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Treatment Safety ◽  
The Impact

200 Background: In the phase 3 PREVAIL trial, enzalutamide (ENZA), an androgen receptor inhibitor, improved overall survival (OS) and radiographic progression-free survival (rPFS) relative to placebo (PBO) in chemotherapy-naïve men with mCRPC. Methods: PREVAIL randomized 1,717 patients (pts) with asymptomatic or minimally symptomatic chemotherapy-naïve mCRPC 1:1 to ENZA 160 mg daily or PBO. Coprimary endpoints were OS and rPFS. This prespecified analysis evaluated the impact of age (≥ 75 vs < 75 years) on efficacy and safety. Results: In PREVAIL, 609 (35%) pts were aged ≥ 75 years. This older subset had several poorer baseline prognostics relative to those aged < 75 years: worse ECOG performance status (ECOG 1: 45.0% vs 24.7%), higher prostate-specific antigen (PSA; 73.3 vs 37.3 ng/mL) and more cardiovascular disease (26.9% vs 16.5%). In both older and younger pts, ENZA improved OS, rPFS and time to PSA progression (Table). Pts aged ≥ 75 years in both the ENZA and PBO groups combined had a higher rate of grade ≥ 3 adverse events (46% vs 37% in younger pts) and among enzalutamide-treated men more older pts reported falls (any grade; ENZA 19% and PBO 8%) than younger pts (ENZA 7% and PBO 4%). Fewer pts ≥ 75 years received subsequent antineoplastic therapies. Conclusions: In PREVAIL, efficacy outcomes in elderly (≥ 75 years) and younger (< 75 years) pts with chemotherapy-naïve mCRPC were comparable and pts consistently benefited from ENZA treatment. Safety with ENZA was similar in both age groups, although older pts reported a higher incidence of falls and received fewer subsequent antineoplastic therapies. Clinical trial information: NCT01212991. [Table: see text]

scholarly journals Video 2: Busy as a Bee

2020 ◽  
Author(s):  
Ingrid Schudel
Keyword(s):  
Primary School ◽  
Mathematical Reasoning ◽  
School Curriculum ◽  
Number Representation ◽  
Mathematical Literacy ◽  
Intended Audience ◽  
Primary School Teachers ◽  
Language Extension ◽  
Large Numbers ◽  
Grade 3

Intended audience: Year three primary school teachers and learners <br><br>This video is designed to support cross-curriculum teaching for third year primary school learners. The video uses ‘big numbers’ in mathematics to help learners understand how hard bees work to make honey. The video was inspired by the Mathematical Literacy researcher Terezhina Nunes who has demonstrated the incredible power of children’s mathematical reasoning when not necessarily tied up in formal number representation. You can also extend understanding to help learners to appreciate the importance of biodiversity (bees need flowers at all times of the year) and the importance of bees for pollinating food crops (1 in every 3 mouthfuls of food we eat is from a crop pollinated by bees).<br><br>The video is linked to the school curriculum in the following ways:<br>• Mathematics: By Grade 3 learners should “Count confidently, verbally in ones, tens, fives, twos, twenties, twenty-fives, fifties and hundreds to 1000”. This activity extends beyond that – by asking learners to visualise what the number 10 000 might look like.<br>• Life Skills: Science: Learning about ‘animals that help us’<br>• Language extension possibilities. This video also draws on young children’s passion for numbers. As an extension into Languages you can try and get hold of the book: Guess how much I love You which plays with the delight children find in large numbers.<br><br>

scholarly journals Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets

2021 ◽  
Vol 12 ◽  
Author(s):  
Gavin Giovannoni ◽  
Patricia K. Coyle ◽  
Patrick Vermersch ◽  
Bryan Walker ◽  
Julie Aldridge ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lymphocyte Subsets ◽  
Age Groups ◽  
Absolute Lymphocyte Count ◽  
Normal Range ◽  
Patient Groups ◽  
Grade 3 ◽  
Post Hoc ◽  
Effect Of Age ◽  
Combined Data

Cladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This post hoc analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or &gt;50 years) on lymphopenia following CladT 3.5 mg/kg (CladT3.5; cumulative dose over 2 years) treatment over 96 weeks. Both CladT3.5 and placebo were given over Weeks 1 and 5 (Year 1 treatment) and Weeks 48 and 52 (Year 2 treatment) from the start of the studies. Absolute lymphocyte count (ALC) and levels of lymphocyte subsets were examined in 1564 patients (Age ≤50 [placebo: N=566; CladT3.5: N=813]; Age &gt;50 [placebo: N=75; CladT3.5: N=110]). In both age groups, following CladT3.5 treatment, nadir for ALC occurred at Week 9 (8 weeks following start of Year 1 treatment) and Week 55 (7 weeks following start of Year 2 treatment) of the 96-week period; for CD19+ B lymphocytes, nadir occurred at Week 9 (Year 1) and Week 52 (Year 2). For CD4+ T lymphocytes, nadir occurred at Week 16 (Year 1) in both age groups, and at Weeks 60 and 72 (Year 2) in the Age ≤50 and &gt;50 groups, respectively. Nadir for CD8+ T lymphocytes occurred at Week 16 (Year 1) and Week 72 (Year 2) in the Age ≤50 group and levels remained in the normal range; nadir occurred at Week 9 (Year 1) and Week 96 (Year 2) in the Age &gt;50 group. Lymphocyte recovery began soon after nadir following CladT3.5 treatment and median levels reached normal range by end of the treatment year in both age groups. By Week 96, ~25% of patients treated with CladT3.5 reported ≥1 episode of Grade ≥3 lymphopenia (Gr≥3L). The rate of certain infections was numerically higher in older versus younger patients who experienced Gr≥3L. In conclusion, CladT3.5 had a similar effect on ALC and lymphocyte subsets in both younger and older patient groups.

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