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Mouser, Nancy Fox. "Peter Hartwig, 1804-1808: Sociological Perspectives in Marginality and Alienation." History in Africa 31 (2004): 263–302. http://dx.doi.org/10.1017/s0361541300003491.
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All social groups make rules and attempt, at some times and under some circumstances, to enforce them. Social rules define situations and the kinds of behavior appropriate to them, specifying some actions as “right” and forbidding others as “wrong.” When a rule is enforced, the person who is supposed to have broken it may be seen as a special kind of person, one who cannot be trusted to live by the rules agreed on by the group. He is regarded as an outsider.But the person who is thus labeled an outsider may have a different view of the matter. He may not accept the rule by which he is being judged and may not regard those who judge him as either competent or legitimately entitled to do so. Hence, a second meaning of the term emerges: the rule-breaker may feel his judges are outsiders.Peter Hartwig was a German seminarian recruited by the Church Missionary Society in 1803 to serve as one of its first two missionaries in Africa. He was sent to Freetown, a settlement established for Africans and people of African descent who had returned to Africa from Britain and the Americas. Hartwig was to reside at Freetown temporarily and to be supervised while there by a locally-based Corresponding Committee composed of Sierra Leone Company officials. The Society directed that, after a year's residence in Sierra Leone, Hartwig and his fellow recruit Melchior Renner would establish a mission among Susu peoples north of Freetown, where they were to convert indigenous Africans to Christianity. Hartwig, however, failed to meet the Society's expectations, violated the norms of the Corresponding Committee that the Society had established at Freetown to guide mission progress, and left the Society's service within three years of reaching the coast. He seemingly had become unable to adjust to changing realities, a wrongdoer and a moral example to other missionaries of what to avoid becoming.3 How are we to interpret his failure from a sociological perspective?
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Swarthout, Todd D., Ana Ibarz-Pavon, Gift Kawalazira, George Sinjani, James Chirombo, Andrea Gori, Peter Chalusa, et al. "A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol." BMJ Open 11, no. 6 (June 2021): e050312. http://dx.doi.org/10.1136/bmjopen-2021-050312.
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IntroductionStreptococcus pneumoniae (the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi’s National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy.MethodsA pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15–24 months, randomised at household level, and schoolgoers 5–10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation.AnalysisThe primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15–24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively.Ethics and disseminationThe study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numberNCT04078997.
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Manjunath, Chandrika, Oluwatomilona Ifelayo, Clarence Jones, Monisha Washington, Stanton Shanedling, Johnnie Williams, Christi A. Patten, Lisa A. Cooper, and LaPrincess C. Brewer. "Addressing Cardiovascular Health Disparities in Minnesota: Establishment of a Community Steering Committee by FAITH! (Fostering African-American Improvement in Total Health)." International Journal of Environmental Research and Public Health 16, no. 21 (October 28, 2019): 4144. http://dx.doi.org/10.3390/ijerph16214144.
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Despite its rank as the fourth healthiest state in the United States, Minnesota has clear cardiovascular disease disparities between African-Americans and whites. Culturally-tailored interventions implemented using community-based participatory research (CBPR) principles have been vital to improving health and wellness among African-Americans. This paper delineates the establishment, impact, and lessons learned from the formation of a community steering committee (CSC) to guide the Fostering African-American Improvement in Total Health (FAITH!) Program, a CBPR cardiovascular health promotion initiative among African-Americans in Minnesota. The theory-informed CSC implementation process included three phases: (1) Membership Formation and Recruitment, (2) Engagement, and (3) Covenant Development and Empowerment. The CSC is comprised of ten diverse community members guided by mutually agreed upon bylaws in their commitment to FAITH!. Overall, members considered the CSC implementation process effective and productive. A CBPR conceptual model provided an outline of proximal and distal goals for the CSC and FAITH!. The CSC implementation process yielded four lessons learned: (1) Have clarity of purpose and vision, (2) cultivate group cohesion, (3) employ consistent review of CBPR tenets, and (4) expect the unexpected. A robust CSC was established and was instrumental to the success and impact of FAITH! within African-American communities in Minnesota.
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Chhagan, Usha, Vuyokazi Ntlantsana, Andrew Tomita, Thirusha Naidu, Bonginkosi Chiliza, and Saeeda Paruk. "Investigating the impact of HIV on patients with first episode psychosis: a study protocol for a longitudinal cohort study." BMJ Open 11, no. 5 (May 2021): e046593. http://dx.doi.org/10.1136/bmjopen-2020-046593.
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IntroductionSouth Africa (SA) has a high HIV prevalence and limited mental healthcare resources. Neuropsychiatric complications such as psychosis onset in people living with HIV (PLWHIV) remains poorly understood. The study aims to compare the socio-demographic, clinical, substance use, cognitive and trauma profile of PLWHIV presenting with first episode psychosis (FEP) to those with the condition but without HIV.Methods and analysisThis study will compare presentation, course, and outcome of a cohort of PLWHIV and FEP with a control group recruited over a 3-year period. We will prospectively test the hypothesis that the 2 groups are socio-demographically, clinically and cognitively distinct at illness presentation, with higher trauma burden and poorer outcomes in those with the dual burden of HIV and FEP. FEP participants, confirmed by a structured neuropsychiatric interview, will have their socio-demographic, psychosis, mood, motor, trauma and substance use variables assessed. A neuropsychological battery will be completed to assess cognition, while quality of life, psychotic symptoms and HIV markers will be measured at 3, 6 and 12 months.Ethics and disseminationThe study protocol has been reviewed and ethics approval obtained from the Biomedical Research Ethics Committee (BC 571/18) of the University of KwaZulu-Natal. The results from this investigation will be actively disseminated through peer-reviewed journal publications and conference presentations.
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Mir, Fatima, Apsara Ali Nathwani, Suhail Chanar, Amjad Hussain, Arjumand Rizvi, Imran Ahmed, Zahid Ali Memon, Atif Habib, Sajid Soofi, and Zulfiqar Ahmed Bhutta. "Impact of pulse oximetry on hospital referral acceptance in children under 5 with severe pneumonia in rural Pakistan (district Jamshoro): protocol for a cluster randomised trial." BMJ Open 11, no. 9 (September 2021): e046158. http://dx.doi.org/10.1136/bmjopen-2020-046158.
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BackgroundPneumonia is a leading cause of death among children under 5 specifically in South Asia and sub-Saharan Africa. Hypoxaemia is a life-threatening complication among children under 5 with pneumonia. Hypoxaemia increases risk of mortality by 4.3 times in children with pneumonia than those without hypoxaemia. Prevalence of hypoxaemia varies with geography, altitude and severity (9%–39% Asia, 3%–10% African countries). In this protocol paper, we describe research methods for assessing impact of Lady Health Workers (LHWs) identifying hypoxaemia in children with signs of pneumonia during household visits on acceptance of hospital referral in district Jamshoro, Sindh.Methods and analysisA cluster randomised controlled trial using pulse oximetry as intervention for children with severe pneumonia will be conducted in community settings. Children aged 0–59 months with signs of severe pneumonia will be recruited by LHWs during routine visits in both intervention and control arms after consent. Severe pneumonia will be defined as fast breathing and/or chest in-drawing, and, one or more danger sign and/or hypoxaemia (Sa02 <92%) in PO (intervention) group and fast breathing and/or chest in-drawing and one or more danger sign in clinical signs (control) group. Recruits in both groups will receive a stat dose of oral amoxicillin and referral to designated tertiary health facility. Analysis of variance will be used to compare baseline referral acceptance in both groups with that at end of study.Ethics and disseminationEthical approval was granted by the Ethics Review Committee of the Aga Khan University (4722-Ped-ERC-17), Karachi. Study results will be shared with relevant government and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals.Trial registration numberNCT03588377.
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Mann, S. G., E. V. Raikina, and I. M. Yunusova. "The spectrum of genetic variants of the a- and b-globin clusters in patients with hemoglobinopathies living in the Republic of Dagestan." Pediatric Hematology/Oncology and Immunopathology 19, no. 3 (October 9, 2020): 50–53. http://dx.doi.org/10.24287/1726-1708-2020-19-3-50-53.
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Hemoglobinopathies are a group of hereditary hemolytic anemias common in the countries of the Mediterranean, Southeast Asia and Africa, where malaria was previously common. Due to population migration and an increase in the number of mixed marriages, hemoglobinopathies are also relevant to Russia. Among the Russian Federation's subjects, the Republic of Dagestan is the most endemic region for the incidence of hemoglobinopathies. This study aimed to identify the spectrum of mutations in patients with hemoglobinopathies living in the Republic of Dagestan. The research was approved by Independent ethic committee and the academic board of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia). Material from 100 patients was sent for molecular genetic research to the Laboratory of Molecular Biology, Federal State Budget Scientific Institution Scientific Research Center for Surgery named after Dmitry Rogachev. Genetic variants of the genes of the a- and b-globin clusters were determined using multiplex ligase-dependent amplification of samples and Sequencing by the Sanger method. Eighteen genetic variants with different frequencies were detected. The mutation frequency of the b-globin cluster was 62.5%, the a-globin cluster was 23.2%, and the variants leading to the appearance of abnormal hemoglobin were 14.3%. The five most common genetic variants among this cohort were also identified: CD8(-AA) and IVSI-110 (G>A), -(a) 3.7 and -(a) 20.5 and the CD6 variant GAG>GTG [Glu>Val] leading to abnormal hemoglobin S.
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Denisova, T. S., and S. V. Kostelyanets. "Warlords to Politicians: The Transformation of Rebel Leaders in Africa (on the Example of Sierra Leone)." Outlines of global transformations: politics, economics, law 13, no. 3 (August 20, 2020): 214–31. http://dx.doi.org/10.23932/2542-0240-2020-13-3-12.
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The paper analyzes the processes of transformation of leaders of rebel movements and tribal militias (warlords) into leaders of political parties and senior government officials after the end of the Civil War (1991‑2002) in Sierra Leone. It is argued that the opportunities for an anti‑government (or, on the contrary, pro‑government) armed group to become an officially recognized political organization, and for erstwhile field commanders to become its leaders, emerge either in the event of a rebel victory or after the signing of a peace agreement (as it happened in Sierra Leone) and the beginning of the integration of former militants into the post‑war society. It is usually the implementation of disarmament, demobilization and reintegration programs that allows former rebels and their leaders to escape punishment for crimes committed during conflicts. At the same time, the opportunity to “earn forgiveness” is not the only incentive for a warlord to evolve into a peacetime politician. Indeed, gaining political power in African countries entails access to various sources of enrichment, and since running armed groups requires their leaders to possess organizational and entrepreneurial skills and charisma ‑ naturally, along with less positive character traits ‑ many warlords who have not yet fulfilled their political ambitions or secured their financial situation try to “adapt” their wartime skills and experience to peaceful life. A proven way of gaining power peacefully is by participating in presidential and parliamentary elections. It is assumed that the development of a political career by former rebels in the context of peacebuilding should prevent the unfolding of another spiral of violence, but this is far from always the case: accustomed to achieving goals by military means, they often attempt to solve political issues through violence in peacetime. The paper considers the reasons for certain former rebel leaders to remain committed to peacebuilding and for other warlords to prove unable to achieve political goals by peaceful means.
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Heeney, Matthew M., David C. Rees, Mariane de Montalembert, Isaac Odame, R. Clark Brown, Yasser Wali, Thu Thuy Nguyen, Du Lam, Raquel Merino Herranz, and Julie Kanter. "Study Design and Initial Baseline Characteristics in Solace-Kids: Crizanlizumab in Pediatric Patients with Sickle Cell Disease." Blood 136, Supplement 1 (November 5, 2020): 22–24. http://dx.doi.org/10.1182/blood-2020-137081.
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Background: Sickle cell disease (SCD) is a group of genetic blood disorders characterized by hemolytic anemia, multi-organ damage and acutely painful events (vaso-occlusive crises [VOCs]) that can cause life-threatening complications. Vaso-occlusion is mediated, in part, by P-selectin, an adhesion molecule expressed on endothelial cells and platelets. Adults and children with SCD have similar P-selectin expression levels; however, disease severity worsens with increasing age because of cumulative endothelial damage caused by repeated vaso-occlusion events. Crizanlizumab is a humanized anti-P-selectin monoclonal antibody that binds P-selectin and blocks its interaction with its ligands. SUSTAIN, a Phase 2 study in adults with SCD, has shown that crizanlizumab, compared with placebo, is well tolerated and significantly decreases the number of VOCs requiring a healthcare visit (Ataga et al. N Engl J Med 2017). Aim: To describe the design of the first crizanlizumab study in pediatric patients (pts) with SCD and report demographics and baseline characteristics of a subset of enrolled pts (aged 6 to <18 yr) (ClinicalTrials.gov: NCT03474965). Methods: Primary objectives of this Phase 2, multicenter, open-label study are to confirm crizanlizumab dosing and assess safety. Pts aged 6 mo to <18 yr with a confirmed SCD diagnosis (any genotype) and ≥1 VOC within the preceding 12 mo are included. The study will enroll ≥100 pts in 3 age groups: Group 1 (G1; 12 to <18 yr), 2 (G2; 6 to <12 yr), and 3 (G3; 6 mo to <6 yr). Crizanlizumab is administered intravenously on weeks 1 and 3, and every 4 weeks thereafter for up to 2 years. Dose confirmation is being determined by single- and multiple-dose pharmacokinetic (PK) data and key safety data. Steady state PK, pharmacodynamic (PD) and safety data are used to validate the confirmed dose or prompt modifications, if required. Secondary objectives include assessment of crizanlizumab efficacy, measured by annualized rate of VOCs leading to a healthcare visit (clinic, emergency room [ER] or hospital), and annualized rate of VOCs managed at home. VOC subcategories (uncomplicated pain crisis, acute chest syndrome, hepatic and splenic sequestration, and priapism), overall hospitalizations and ER visits and dactylitis events are also assessed. Safety measures include frequency and severity of adverse events. Long-term PK and PD will also be characterized by measuring pre-dose concentrations and percentage of P-selectin inhibition prior to each study drug dose. Part A in each age group will confirm PK dose, beginning with ≥8 pts in G1. If unconfirmed, dose will be adjusted based on population PK model, and ≥8 additional pts enrolled. Once dose is confirmed, recruitment will be expanded for long-term safety and efficacy evaluation of the PK confirmed dose (Part B). This process will then repeat for G2 then G3 (2 to <6 yr). Subsequently, ≥6 G3 pts aged 6 mo to <2 yr will be enrolled, with only pre-dose PK/PD samples collected. Pts on hydroxyurea, L-glutamine or an erythropoietin-stimulating agent must have received the treatment for ≥6 mo prior to screening with no dosage or schedule adjustments during the study. Pts not currently on such drugs must have been off them for ≥6 mo prior to screening. Pts who have received prior crizanlizumab treatment are excluded from the trial. Results: As of January 28, 2020, 59 pts were enrolled: 46 pts in G1 (11 pts in Part A and 35 pts Part B) and 13 pts in G2 Part A. Pt demographics are available for Part A in G1 and 2 (Table), based on 2 Data Monitoring Committee analyses. The median age of G1 was 17.0 yr (range 13-17), 6 (54.5%) were male and 11 (100%) were Black/African American. 9 (81.8%) had HbSS disease, 1 (9.1%) HbSC and 1 (9.1%) HbSβ0. The median age of G2 was 9.0 yr (range 6-11), 8 (61.5%) were male, 7 (53.8%) were Black/African American, 4 (30.8%) were White, and 2 were of multiple race, specifically 'White, Asian' (n=1, 7.7%) and 'White, Black/African American' (n=1, 7.7%). 12 (92.3%) pts had HbSS disease and 1 (7.7%) had HbSC. Conclusions: This study aims to address an unmet treatment need in pediatric pts, exploring appropriate dosing and the safety of crizanlizumab. The annualized rates of VOCs, hospitalizations and ER visits will be assessed as secondary objectives. The primary analyses for Parts A and B of G1 and 2, and then G3, will occur consecutively when all pts enrolled in each group have either completed 26 weeks of treatment or discontinued the study treatment. Disclosures Heeney: UpToDate: Patents & Royalties: Author royalties; Micelle: Consultancy, Other; Keros: Consultancy; Novartis: Consultancy, Other; AstraZeneca: Consultancy, Other; Cyclerion: Consultancy, Other; Forma Therapeutics: Consultancy; Dova: Consultancy; Global Blood Therapeutics: Consultancy; Emerging Therapy Solutions (ETS): Consultancy. Rees:Alnylam Pharmaceuticals: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AstraZeneca: Other: Data monitoring committee membership; Emmanus Medical: Consultancy, Honoraria; TauRx: Other: Data And Safety Monitoring. de Montalembert:Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees. Odame:Novo Nordisk: Other: Study Advisory Board; Global Blood Therapeutics: Other: Study Data Safety Monitoring Board; Novartis: Other: Study Steering Committee. Wali:Novartis: Research Funding. Nguyen:Novartis: Current Employment. Lam:Novartis: Current Employment. Herranz:Novartis: Current Employment. Kanter:NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; bluebird bio, inc: Consultancy, Honoraria; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Guidepoint Global: Honoraria; Cowen: Honoraria; Jeffries: Honoraria; Wells Fargo: Honoraria; Medscape: Honoraria; GLG: Honoraria; Sanofi: Consultancy. OffLabel Disclosure: Crizanlizumab is a monoclonal antibody to P-selectin indicated in the USA for the prevention of vaso-occlusive crises in patients aged 16 years and over with sickle cell disease. This abstract described the new pediatric trial of crizanlizumab, which is not indicated for patients aged less than 16 years of age
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Ferhanoglu, Burhan, Tae Min Kim, Amado Karduss, David Brittain, Gayane Tumyan, Mubarak Al Mansour, Marta Zerga, et al. "Results from the International, Multi-Center, Retrospective B-Holistic Study: Describing Treatment Pathways and Outcomes for Classical Hodgkin Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 32–34. http://dx.doi.org/10.1182/blood-2020-134885.
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Background: Despite therapeutic advances in classical Hodgkin lymphoma (cHL), only half of patients with relapsed/refractory (R/R) cHL are cured with salvage chemotherapy followed by stem cell transplantation (SCT). Most studies to date have been undertaken in Europe or North America and data on treatment patterns and clinical outcomes from other regions are limited. We present the results from the B-CD30+ HOdgkin Lymphoma International Multi-center Retrospective Study of Treatment PractIces and OutComes (B-HOLISTIC), which assessed cHL treatment pathways, clinical outcomes and healthcare resource utilization across East Asia, Latin America, Middle East, South Africa, Australia and Russia (data as of 04 March 2020). Methods: Data were collected retrospectively for patients (≥18 years) diagnosed with stage IIB-IV cHL or R/R cHL between 01 January 2010 and 31 December 2013, until death or last follow-up (whichever occurred first) across 13 countries. Patients with initial diagnosis of cHL and subsequent progression to R/R cHL were included in both groups, provided R/R cHL was diagnosed within the study period. The primary endpoint was progression-free survival (PFS) in patients with R/R cHL. Secondary endpoints included overall survival (OS), best clinical response, and adverse events (AEs). Results: In total, 1703 patients were enrolled from East Asia (n=426), Latin America (n=366), Middle East and South Africa (n=694), Australia (n=56) and Russia (n=161): 1598 and 426 patients were eligible for the cHL and R/R cHL groups (321 patients in the cHL group progressed to R/R cHL and were included in both groups). Median study follow-up was 65.2 and 53.2 months for the cHL and R/R cHL groups. Baseline patient characteristics are shown in Table 1. All patients in the cHL group received first-line chemotherapy: the most common regimens were ABVD (1363/1598; 85.3%) and BEACOPP (104/1598; 6.5%). First-line radiotherapy was given to 357/1598 (22.3%) patients in the cHL group. For R/R cHL, intensive chemotherapy was used as first-line salvage in 372/426 (87.3%) patients: the most common regimens were ESHAP (98/372; 26.3%) and DHAP (65/372; 17.5%), with an overall response rate of 62.0% (complete remission in 30.8% and partial remission in 31.2%). Of the 426 patients with R/R cHL, 292 (68.5%) were eligible for SCT at relapse/refractory diagnosis; 10 patients who were initially ineligible for SCT subsequently became eligible. In total, 222/302 (73.5%) eligible patients underwent SCT; 63/222 (28.4%) patients relapsed after SCT. Median PFS (95% CI) for the R/R cHL group was 13.2 (9.9-20.2) months following initial therapy (Figure 1), with estimated 1-, 3- and 5-year PFS rates of 51.2%, 38.7%, and 33.9%, respectively (Table 2). Median PFS was not reached for the first-line cHL group. Factors for PFS in the R/R cHL group are shown in Table 3. Median OS was not reached for both groups. All-cause, any grade AEs were reported by 783/1598 (49.0%) patients with cHL and by 233/426 (54.7%) patients with R/R cHL. Serious AEs were reported by 303/1598 (19.0%) patients with cHL and by 103/426 (24.2%) patients with R/R cHL: the most common (≥2.0%) were febrile neutropenia, pneumonia and pyrexia for cHL, and febrile neutropenia and pyrexia for R/R cHL. Conclusion: Results from B-HOLISTIC show that PFS rates remain low in patients with R/R cHL receiving salvage therapy; the greatest risk was among patients with inadequate response to salvage chemotherapy. The low PFS rates highlight the importance of considering novel targeted therapies to address unmet medical needs. PFS rates in patients with cHL were comparable with previous studies from Italy, Spain, and Israel (Avigdor A et al. EHA 2020) and the ECHELON-1 study (Bartlett NL et al. ASH 2019). The higher OS rates compared to PFS rates may be related to the effect of modern salvage regimens. Approximately half of patients with R/R cHL underwent SCT which may support the use of targeted therapies. Overall, these results from 2010-2013 show that despite the differences in healthcare systems, ethnicities and treatment patterns in B-HOLISTIC, clinical outcomes remain consistent. The authors note that given that the management of high-risk cHL has changed dramatically since 2013, further investigation in diagnostic criteria, response assessment and treatment patterns is needed. Study support: Data analysis (IQVIA) and medical writing (Synergy Vision) funded by Takeda Pharmaceuticals. Disclosures Ferhanoglu: Takeda: Other: Advisory Board; Abbvie: Other: Advisory Board; Roche: Other: Advisory Board; Janssen: Other: Advisory Board. Kim:Novartis: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Voronoi: Consultancy; Boryung: Consultancy; AstraZeneca: Consultancy; Takeda: Consultancy. Karduss:Takeda: Honoraria. Rivas-Vera:Takeda: Current Employment, Other: Steering Committee in Clinical Research; Roche: Consultancy. Lim:National Cancer Centre Singapore: Current Employment. Yeh:AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees. Abdillah:Takeda: Current Employment. Huang:Takeda: Current Employment. Dalal:Takeda: Current Employment, Current equity holder in publicly-traded company. Wan:Takeda: Current Employment. Hertzberg:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support; Gilead: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Trompetter, Linda, Arthur Breese, James Calderone, Grace S. Fisher, Rodrigo Gereda, Mari King, Richard Kramer, et al. "Focus Group Study of Diverse Local Populations and Their Health Care Experiences in Northeastern Pennsylvania." Californian Journal of Health Promotion 3, no. 3 (September 1, 2005): 73–126. http://dx.doi.org/10.32398/cjhp.v3i3.650.
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This investigation was conducted through the support of the College Misericordia Diversity Institute and a grant from the Blue Ribbon Foundation of Blue Cross of Northeastern Pennsylvania. Focus group participants were 49 adults from seven minority populations residing in northeastern Pennsylvania’s Luzerne and Lackawanna counties. Data was collected by 11 focus group leaders who were members of a Blue Ribbon Grant Core Committee at College Misericordia in 2004. The seven populations studied were African Americans, Arabic Muslims, Asian-Chinese and Korean, Gay and Lesbian, Hispanic, Jewish, and Asian Indian. A 30-question survey was used to collect data during one to two hour focus group interviews. Through content analysis, six problematic issues faced by many of the participants were identified. All of the findings were validated by a review process. The six issues faced by the 7 groups were: 1) Economics, Education, and Employment Influence Life for Newcomers, 2) Customs and Traditions Sometimes Sacrificed- The Influence of American Culture, 3) Socialization Often Limited to Same Population Group, 4) Mixed Acceptance Level from Area Natives, 5) Bilingual Challenges Impede Optimal Inclusion, 6) Health Care Access Problems. The aforementioned cross-groups study is explored in this report. The study also yielded seven other reports (one for each diverse population) which provide a description of that particular focus group’s perspective on topics such as religion, food, family, customs, and health care (see Appendices A, B, C, D, E, F, and G). Findings of this study are being disseminated in a local effort to educate health care professionals. Future research will be needed to determine if progress is being made in fulfilling the health care needs of all diverse populations living in Luzerne and Lackawanna County, as well as other parts of northeastern Pennsylvania.
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DeBaun, Michael R., Najibah Aliyu Galadanci, Shehu U. Abdullahi, Musa A. Tabari, Shehi Abubakar, Raymond Belonwu, Auwal Salihu, et al. "Acceptability and Safety of Hydroxyurea for Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria." Blood 124, no. 21 (December 6, 2014): 4021. http://dx.doi.org/10.1182/blood.v124.21.4021.4021.
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Abstract Background: Nigeria has the highest prevalence of sickle cell disease (SCD), a common cause of pediatric ischemic stroke. In sub-Saharan Africa monthly blood transfusions for primary stroke prevention carries risks; hydroxyurea (HU) may be an alternative. We conducted the first, US NIH funded, SCD feasibility trial in sub-Saharan Africa (5R21NS080639-02) to: 1) assess the acceptability and willingness of families to participate in a HU trial; 2) develop a safety protocol for using HU in a trial setting in sub-Saharan Africa; and 3) prepare for a definitive phase III Trial. In the Sickle Cell Disease Stroke Prevention in Nigeria (SPIN) trial, our primary hypothesis in the internal feasibility trial is that 80% adherence for daily HU administration is feasible. Procedure: The internal pilot is a single site; single arm trial enrolling 40 children aged 5 to 12 years with hemoglobin SS or SB0 thalassemia at risk of developing stroke with a high transcranial Doppler (TCD) velocity in the middle cerebral artery (MCA) ≥ 200 cm/sec. Each participant is scheduled to receive low dose HU therapy (~20mg/kg/day) for 36 months. Acceptability was determined by the number of families who consented for screening. The adherence rate of HU was based on monthly parental assessment of the Morisky Medical Adherence Sore (MMAS) and monthly complete blood count (CBC) to monitor the serial change in mean corpuscular volume (MCV) from baseline level. Assessment of toxicity attributable to HU was based on comparing adverse events between the HU and control groups. Controls were identified as participants that met the criteria for the trial, but had TCD measurements < 200 cm/sec. From Baby HUG, adverse events were defined as hospitalization for any cause, severe anemia and myelosuppression (severe neutropenia and thrombocytopenia based on monthly CBC). Results: A total of 269 participants were approached, of which 96% (23 of 24) and 86% (211 of 245) with an elevated or normal TCD measurement agreed to enroll in the HU therapy or control groups with a median age of 8 and 7.6 years, respectively. At the current milestone, 100% of the participants enrolled in the treatment arm demonstrated at least average to high monthly adherence rate (MMAS of 6-8 points). This adherence rate was consistent with an increase in MCV from baseline to 3 months after starting HU therapy with a minimum increase in MCV of at least 3 fl in 8 of 11 participants. One child on HU therapy was hospitalized for 5 days for hypovolemia and dehydration associated with cholera. The table below shows no excessive rate of adverse events when HU therapy and control groups are compared. Conclusion: These early results demonstrate the ability for a sub-Saharan African clinical research team to plan and initiate a complex SCD trial. Our preliminary data provide strong evidence for acceptability and potential safety of low dose HU therapy in Nigerian children with SCD. Completion of the internal pilot should provide sufficient evidence to pursue a phase III trial of low dose HU therapy to prevent strokes in children living in sub-Saharan Africa. Table. Rates of Hospitalization within the first 12 months of the SCD Stroke Prevention in Nigeria (SPIN) Trial. Reason for Hospitalization Hydroxyurea Therapy Group (15 total person years; n = 23) Rate per 100 patient years Control Group (52 total person years; n = 211) Rate per 100 patient years Acute Chest Syndrome 0 2 Osteomyelitis 0 2 Infection requiring hospitalization 0 6 Pain requiring hospitalization 0 72 Transfusion 0 8 Malaria requiring hospitalization 7 34 Fever requiring hospitalization 7 0 Other reasons for hospitalizations 0 10 Disclosures Neville: American Academy of Pediatrics; Food and Drug Administration; NICHD: Membership on an entity's Board of Directors or advisory committees; Children's Oncology Group; Therapeutic Advances in Childhood Leukemia; Neuroblastoma/Medulloblastoma Treatment Consortium; Pediatric Oncology Experimental Therapeutics Investigators Consortium; Midwest Cancer Alliance; Dell; Braden's Hope Foundation: Research Funding; Sanofi; Novartis; Amgen; Medimmune; United Therapeutics; Bristol Myers Squibb: IND for hydroxyurea, IND for hydroxyurea Other.
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Mok, Christine. "East West Players and After: Acting and Activism." Theatre Survey 57, no. 2 (April 13, 2016): 253–63. http://dx.doi.org/10.1017/s0040557416000107.
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“Where are all the Asian actors in mainstream New York theatre?” What began as a plaintive status update on Facebook launched a full-scale investigation by Asian American actors that culminated in a report titled “Ethnic Representation on New York City Stages” and the formation in the fall of 2011 of an advocacy group, the Asian American Performers Action Coalition (AAPAC). AAPAC's findings were disheartening. In the preceding five years, Asian Americans had received only 3 percent of all available roles in not-for-profit theatre and only 1.5 percent of all available roles on Broadway. The percentage of roles filled by African American and Latino actors, in contrast, had increased since 2009. According to the report, “Asian Americans were the only minority group to see their numbers go down from levels set five years ago.” The data AAPAC compiled were both surprising in their concreteness and unsurprising in their bleakness. The Facebook query sparked an active digital conversation that touched a collective sense of discord just below the surface for many Asian American theatre artists, especially actors. Ralph Peña, artistic director of Ma-Yi Theatre Company, invited key Facebook commenters to hold a more formal conversation about access, embodiment, and Asian American representation. This group, many of whom were artists in midcareer, trained at top conservatories, and fostered in New York City's vibrant Asian American theatre community, became the Steering Committee of AAPAC. The members of the Steering Committee channeled their frustration and anger into archive fever by researching and documenting ethnic representation on Broadway and in sixteen of the largest not-for-profit theatres in New York City over a five-year period. In front of an audience of three hundred, members of AAPAC presented their findings at a roundtable at Fordham University on 13 February 2012 that included prominent artistic directors, agents, directors, casting directors, and producers and was moderated by David Henry Hwang. With the report in hand, AAPAC members roused the New York theatre community with a series of town hall–style meetings and urged theatrical production gatekeepers to do, if not better, then, something.
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Chandler, Jessica, Luke Sox, Kinsey Kellam, Lauren Feder, Lynne Nemeth, and Frank Treiber. "Impact of a Culturally Tailored mHealth Medication Regimen Self-Management Program upon Blood Pressure among Hypertensive Hispanic Adults." International Journal of Environmental Research and Public Health 16, no. 7 (April 6, 2019): 1226. http://dx.doi.org/10.3390/ijerph16071226.
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Background: Uncontrolled hypertension (HTN) and medication nonadherence are more prominent among Hispanics compared to non-Hispanic whites and African Americans. Advances in wireless health technology enable real-time monitoring of medication adherence (MA) and blood pressure (BP), facilitating timely patient–provider communication including tailored reinforcement/motivational feedback to patients and quicker titration changes by providers. The purpose of the current study was to conduct a 9-month smartphone-enabled efficacy trial addressing MA and BP control among Hispanic adults with uncontrolled HTN and poor MA. Methods: The research design was a 9-month, two-arm efficacy trial including an experimental (Smartphone Med Adherence Stops Hypertension, SMASH) group and an enhanced standard care (ESC) group. SMASH participants utilized a SMASH app which interfaced with a Bluetooth-enabled BP monitor for BP self-monitoring and an electronic medication tray. The ESC participants received text messages including links to PDFs and brief video clips containing healthy lifestyle tips for attention control. Results: Participants were 54 Hispanic adults (mean age: 46.5 years) with uncontrolled HTN. They were randomly assigned to either the SMASH (n = 26) or ESC group (n = 28). At baseline, no participants had controlled systolic BP (SBP). Baseline group averages for SBP between the SC and SMASH groups did not differ (150.7 and 152.3 mmHg, respectively; p = 0.53). At the 1, 3, 6, and 9-month time points, SBP averages were significantly lower in the SMASH versus SC groups (month 1: 125.3 vs. 140.6; month 3: 120.4 vs. 137.5, month 6: 121.2 vs. 145.7 mmHg; month 9: 121.8 vs. 145.7, respectively; all p-values <0.01). At months 3, 6, and 9 there was a significant difference between the percentage of participants meeting the 7th Joint National Committee cutoffs for SBP control in the SC and SMASH groups (month 3: 62.5 vs. 92.0%; month 6: 57.9 and 94.4%, month 9: 27.8 and 92.3%, respectively; all p-values ≤0.01). Average medical regimen adherence, as indicated by timestamped medication intake and BP monitoring for the SMASH group, ranged from 89.1 to 95.2% across the 9-month trial. Conclusion: Our findings indicate that our culturally tailored smartphone-enabled medical regimen self-management program may be an effective solution for the promotion of MA, resulting in statistically and clinically significant reductions in SBP among Hispanic adults with uncontrolled HTN.
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Gakunga, Robai, Zipporah Ali, Anne Korir, Asaph Wang’ombe Kinyanjui, Emily Ochieng’, Nancy Gikaara, Florence Maluni, and Sujha Subramanian. "Social determinants and individual health-seeking behaviour among women in Kenya: protocol for a breast cancer cohort feasibility study." BMJ Open 9, no. 1 (January 2019): e023171. http://dx.doi.org/10.1136/bmjopen-2018-023171.
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IntroductionA catastrophic 35% increase in the burden of breast cancer in Kenya has been predicted by 2025. Mitigating this burden is critical, and local research is necessary to generate the evidence to inform policy, public health and medical practice. Most of the knowledge available has been derived from studies in high-income countries that are not directly applicable due to economic, social, cultural and ethnic differences. At the time of writing this paper, we had no knowledge of any longitudinal cohort studies in sub-Saharan Africa of both breast cancer survivors and a matching cohort of women who have never had a diagnosis of cancer. We aim to assess feasibility of cohort studies in Kenya that consider clinical characteristics social determinants and individual health seeking behaviour.Methods and analysisThis study aims to inform best practices for initiating a longitudinal cohort study in Kenya. It is a two-pronged, prospective mixed methods study of women with and without a diagnosis of breast cancer with baseline data collection and one follow-up data collection approximately 3 months later by telephone. Quantitative and qualitative data will be collected concurrently, analysed separately and together to enrich understanding of concepts by triangulation. We aim to include 800 women aged 30–60 years: 400 in the survivorship cohort and 400 in the non-cancer cohort. Two focus group discussions from each cohort will be carried out to enhance understanding of concepts and to guide recommendations.Ethics and disseminationIndependent ethical approval was obtained from Kenyatta National Hospital-University of Nairobi Ethics and Research Committee and the Research Triangle Institute International. Only consenting participants will be enrolled. Counselling support, debriefing discussions and referrals for formal support services will be available for both participants and research assistants. Findings will be disseminated through publications, websites and presentations.
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Angelucci, Emanuele, David Bowen, Silvia M. M. Magalhães, Tomasz Lawniczek, Shyanne Douma, Peter Jakobs, and Guillermo Garcia-Manero. "A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Deferasirox (Exjade®) in Patients with Low/Intermediate-1 Risk MDS and Transfusional Iron Overload." Blood 114, no. 22 (November 20, 2009): 4854. http://dx.doi.org/10.1182/blood.v114.22.4854.4854.
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Abstract Abstract 4854 Background Approximately 60–80% of patients with myelodysplastic syndromes (MDS) require ongoing red blood cell (RBC) transfusions due to impaired hematopoiesis. Iron chelation therapy has been extensively studied in thalassemia major patients; however, there are fewer data available on the efficacy and safety in transfusion-dependent patients with MDS who have a completely different clinical scenario (Angelucci E and Di Tucci AA. Leuk Res 2009;33:743–4). Increasing evidence is being reported in the literature on the rate and site of iron accumulation (Di Tucci AA et al. Haematologica 2008;93:1385–8), on the impact of transfusion dependency and iron overload on survival (Malcovati L. Leuk Res 2007;31:S2–6, Sanz G et al. Blood 2008;112(11):Abst 640) and on the efficacy of deferasirox (Exjade®) in removing iron in MDS patients. Nevertheless, the possibility to modify clinical outcome by iron chelation in MDS patients is still debated (DeLoughery TG. Am J Hematol 2009;84:263–4). Recent retrospective and prospective non-randomized data (Rose C et al. Blood 2007:110(11);Abst 249) suggest that iron chelation could have a positive impact. A Phase III, prospective, randomized, double-blind, placebo-controlled, parallel-group design clinical trial has therefore been planned to assess the effects of iron chelation therapy with deferasirox on clinical outcomes in patients with MDS (Low/Int-1 risk) and transfusional iron overload. Methods For inclusion, patients must be chelation-naïve, aged ≥18 years with Low/Int-1 risk MDS and serum ferritin (SF) levels of >1000–<2500 ng/mL with a history of multiple transfusions (20–50 RBC units) and anticipated to be transfused at least 8 times annually during the study. In a recruitment period of 2 years, 630 patients from approximately 126 centers (sites within North America, Europe, South Africa, Australia and Asia) will be assigned to the deferasirox or placebo group in a 2:1 ratio. Deferasirox starting dose will be 10 mg/kg/day for 2 weeks, followed by 20 mg/kg/day (Figure). Dose adjustments of 5–10 mg/kg/day (range 0–40 mg/kg/day) may be performed after 3 months based on SF trends. A composite primary efficacy endpoint (‘event-free survival’) has been designed including death, cardiac and hepatic non-fatal events. The cardiac non-fatal events include 1) echo-cardiographic evidence of worsening cardiac function based on left ventricular ejection fraction, 2) hospitalization for congestive cardiac failure. Hepatic events are defined as increase in transaminases and bilirubin or cirrhosis. For any of the composite primary endpoints, detailed definition criteria have been established. Any event which could potentially fulfill the criteria for one of the components of the composite primary endpoint will be reported to the Endpoint Adjudication Committee (EAC). The end of the study treatment will occur when the patient experiences any non-fatal component of the composite primary end point confirmed by the EAC (with subsequent unblinding of the study treatment to investigator and patient). Secondary efficacy and safety endpoints include: overall survival, development of hypothyroidism, worsening of glucose metabolism, time to MDS progression or acute leukemia, hematological function expressed by blood transfusions, time to relevant increase of SF, renal dysfunction, newly occurring severe neutropenia or thrombocytopenia, major gastrointestinal bleeding and time to study drug discontinuation. The duration of the study is planned until 244 events of the primary efficacy endpoint have been observed, with two interim analyses (reviewed by an external Data Monitoring Committee). First patient first visit is expected in November 2009. Conclusions This prospective multicentre study has been designed to investigate the clinical benefit of chelation therapy with deferasirox in patients with MDS, a matter that has assumed increasing relevance during recent years. Disclosures Bowen: Novartis: Honoraria, Research Funding. Magalhães:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Research Funding. Lawniczek:Novartis Pharma AG: Employment. Douma:Novartis Pharma AG: Employment. Jakobs:Novartis Pharma AG: Employment.
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Inusa, Baba, Raffaella Colombatti, David C. Rees, Matthew M. Heeney, Carolyn C. Hoppe, Bernhards Ogutu, Hoda M. Hassab, et al. "Geographic Differences in Phenotype and Treatment of Children with Sickle Cell Anemia from the Multinational DOVE Study." Blood 128, no. 22 (December 2, 2016): 3653. http://dx.doi.org/10.1182/blood.v128.22.3653.3653.
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Abstract Background: Sickle cell anemia (SCA) is characterized by significant phenotypic variability. DOVE1 was a Phase 3, double-blind, randomized, parallel-group, placebo-controlled, multinational study that investigated the efficacy and safety of prasugrel, a P2Y12 adenosine diphosphate receptor antagonist, for reduction of vaso-occlusive crises (VOCs), a composite of painful crisis or acute chest syndrome, in 2- to <18-year-olds with SCA (age cohorts: 2 to <6 years, 6 to <12 years, and 12 to <18 years) (NCT01794000). Methods: DOVE was conducted at 51 sites in 13 countries across 4 continents. A total of 341 subjects were randomized (prasugrel, n=171; placebo, n=170) and SCA genotypes (homozygous hemoglobin S; hemoglobin Sβ0 thalassemia) were included. Eligibility required ≥2 VOCs in the prior year. Baseline clinical and laboratory characteristics and study endpoints were compared by region. Since no overall treatment effect was found, data provided reflect the combined 341 subjects (Americas, N=57; sub-Saharan Africa [SSA], N=148; North Africa/Middle East, N=110; Europe, N=26). Results: Per regional enrollment, the largest proportion of subjects were 6 to <12 years in SSA (48.6% [n=72]), 12 to <18 years in the Americas (45.6% [n=26]) and North Africa/Middle East (58.2% [n=64]), but more evenly divided among the 3 age groups in Europe (30.8-34.6% [n=8-9]). Self-reported racial groupings differed by region (p<0.001): 100% white in North Africa/Middle East; 100% black in SSA; 19.2% white, 76.9% black, and 3.8% multiple in Europe; and 1.8% white, 96.4% black, and 1.8% multiple in the Americas. Mean body mass index was <17 in SSA and Europe (15.3 and 16.6 kg/m2) but >18 in North Africa/Middle East and the Americas (18.3 and 18.1 kg/m2) (p<0.001). Mean blood pressures were lowest in SSA (systolic: 99.0 vs. 105.4-108.0 mmHg, p=0.004; diastolic: 58.3 vs. 60.4-62.9 mmHg, p=0.003). The proportion of subjects with history of acute chest syndrome prior to enrollment was lower in SSA (6.1%) than other regions (18.2-66.7%, p<0.001). Mean number of VOCs in the year prior to enrollment was higher in the Americas than other regions (5.8 vs. 3.2-3.4, p=0.041). Hydroxyurea (HU) use at baseline varied by region: 91.2% in the Americas, 72.7% in North Africa/Middle East, 42.3% in Europe, and 6.8% in SSA (p<0.001). For subjects not on HU at baseline (Table 1), mean hemoglobin at baseline was lowest in SSA (7.6 g/dL); reticulocyte count was lowest in the Americas (214.8 billion/L) and highest in Europe (327.8 billion/L) (p=0.004). For all geographic regions, the most frequent serious adverse events (SAEs) were classified as blood and lymphatic system disorders, with the highest percentage reported as painful crisis. The second most frequent SAEs in SSA, North Africa/Middle East, and Europe were various infections and infestations. The second most frequent in the Americas was respiratory, thoracic, and mediastinal disorders; all were reported as acute chest syndrome. The overall rate of VOCs (events per patient-year) was 3.2 in Europe, 3.0 in the Americas, 2.6 in SSA, and 2.0 in North Africa/Middle East. The percentage of patients hospitalized for VOCs was greatest in Europe (76.9%) compared to other regions (28.4-57.9%); however, mean hospital stay per VOC was similar across regions (5.3-6.2 days). The percentage of VOCs causing hospitalization was highest in Europe (67.7%), followed by North Africa/Middle East (48.7%), the Americas (46.5%), and SSA (26.4%). In SSA, the majority of VOCs were managed as outpatient hospital visits (67.9%), whereas other regions more frequently used inpatient hospital visits (33.2-55.2%). Regardless of region, almost all VOCs were treated with analgesics (overall: 99.5%) and approximately half were treated with intravenous (IV) fluids (overall: 54.4%). In contrast, the proportion of VOC-related transfusions was greater in North Africa/Middle East and Europe (18.6% and 18.8%) than in the Americas and SSA (10.0% and 6.4%). Conclusions: In the DOVE study, management of VOCs with analgesics and IV fluids was similar across regions. However, there were regional differences in VOC-related hospitalizations and transfusions that may reflect differences in culture, utilization of resources, disease severity, or a combination of factors. References: 1Heeney MM, et al. A multinational trial of prasugrel for sickle cell vaso-occlusive events. N Engl J Med. 2016;374:625-635. Disclosures Colombatti: Eli Lilly and Company: Research Funding. Heeney:Eli Lilly and Company: Research Funding; Sancilio and Company: Consultancy, Research Funding; Pfizer: Research Funding. Hoppe:Eli Lilly and Company: Consultancy. Ogutu:Eli Lilly and Company: Research Funding. Hassab:Eli Lilly and Company: Research Funding. Zhou:Eli Lilly and Company: Employment, Other: Minor Shareholder. Yao:Eli Lilly and Company: Employment. Brown:Eli Lilly and Company: Employment, Other: Minor Shareholder. Heath:Eli Lilly and Company: Employment. Jakubowski:Eli Lilly and Company: Employment, Other: Minor Shareholder. Abboud:Eli Lilly and Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; MAST Therapeutics: Research Funding; Novartis: Honoraria.
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Zinzani, Pier Luigi, Radhakrishnan Ramchandren, Armando Santoro, Ewa Paszkiewicz-Kozik, Robin Gasiorowski, Nathalie A. Johnson, José S. R. de Oliveira, et al. "Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study." Blood 136, Supplement 1 (November 5, 2020): 19–20. http://dx.doi.org/10.1182/blood-2020-139416.
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Introduction: Patient-reported outcomes (PROs) in cHL are lacking, particularly those collected prospectively in clinical trials. Additionally, patients (pts) with cHL can experience B symptoms, such as fever, night sweats, and weight loss, that can result in decreased HRQoL. KEYNOTE-204 (NCT02684292), an open-label, international, randomized, phase 3 study, demonstrated that the PD-1 inhibitor pembrolizumab exhibited statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs BV in pts with R/R cHL. The current analysis of KEYNOTE-204 evaluated PROs associated with symptoms of R/R cHL (ie, fatigue, nausea/vomiting, and pain) based on the EORTC QLQ-C30 scale and evaluated the effects of pembrolizumab and BV on the presence and resolution of B symptoms. Methods: Eligible pts were aged ≥18 years, had measurable disease, had ECOG PS 0 or 1, and were R/R cHL after autologous stem cell transplantation (auto-SCT) or were ineligible for auto-SCT. Both BV-naive and BV-exposed pts were eligible. Pts were randomized 1:1 to pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) or BV 1.8 mg/kg IV Q3W and were stratified by prior auto-SCT (yes vs no) and status after first-line therapy (primary refractory vs relapsed <12 months vs relapsed ≥12 months after end of first-line therapy). Symptoms associated with cHL were evaluated as protocol-specified exploratory endpoints using symptom scales of the EORTC QLQ-C30 instrument. EORTC QLQ-C30 was applied electronically at baseline and every 6 weeks up to week 24 and every 12 weeks thereafter. Higher scores on the EORTC QLQ-C30 symptom scales indicated worse symptoms. The analysis population included pts who received ≥1 dose of study treatment and completed ≥1 HRQoL assessment. Both HRQoL and B-symptom data were collected prior to the start date of study drug. Time to first B symptoms was estimated using the Kaplan-Meier method, and treatment differences were evaluated using a stratified Cox proportional hazards model. Rate of resolution of B symptoms was evaluated using the Mantel-Haenszel relative risk test. Results: Of 304 randomized pts, 296 were included in the PRO analysis (pembrolizumab, 146; BV, 150). Compliance rates were >90% for both groups at baseline and remained high (>80%) at week 24. Mean (SD) baseline EORTC QLQ-C30 scores for fatigue, nausea/vomiting, and pain were 34.9 (24.2), 4.0 (10.3), and 24.6 (25.6), respectively, for the pembrolizumab group and 35.3 (25.6), 8.8 (20.0), and 24.3 (27.5), respectively, for the BV group. At week 24, the mean (SD) baseline EORTC QLQ-C30 fatigue, nausea/vomiting, and pain scores were 21.8 (20.8), 3.6 (10.1), and 12.5 (18.9), respectively, for the pembrolizumab group and 31.4 (17.2), 5.9 (14.0), and 17.4 (20.7), respectively, for the BV group. Improvements in fatigue and pain scores with pembrolizumab were observed at week 6 and remained stable up to week 48; BV exhibited a stable effect up to week 48. No differences were observed over time for pembrolizumab and BV for the nausea/vomiting score. Of 300 pts treated, 78 (pembrolizumab, 42; BV, 36) experienced B symptoms at baseline. Of these 78 pts, 33 (42.3%), 63 (80.8%), and 26 (33.3%) exhibited fever, night sweats, and weight loss, respectively. Of pts who did not experience B symptoms at baseline, 10/106 (9.4%) in the pembrolizumab group and 14/116 (12.1%) in the BV group had symptoms during treatment; median time to first B symptom was not reached in either group (hazard ratio 0.44 [95% CI 0.18-1.04]; two-sided P=0.062). For pts who had B symptoms at baseline, 40/42 (95.2%) in the pembrolizumab group and 27/36 (75.0%) in the BV group experienced resolution of symptoms during the study (risk ratio 1.27 [95% CI 1.05-1.52]; two-sided P=0.013). Conclusion: In pts with R/R cHL, pembrolizumab monotherapy demonstrated early and sustained improvement over BV in HRQoL fatigue and pain measures associated with cHL that were stable over time, whereas the nausea/vomiting measure was stable over time for both pembrolizumab and BV. Additionally, B symptoms were more likely to resolve in pembrolizumab vs BV-treated pts. Taken together, these data along with clinically meaningful improvements in PFS support pembrolizumab as a preferred treatment option for pts whose disease relapses after auto-SCT or who are ineligible for auto-SCT. Disclosures Zinzani: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics, an AbbVie Company, Janssen, Bristol-Myers Squibb: Consultancy; Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Santoro:Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees. Paszkiewicz-Kozik:Roche, Takeda, Celgene: Other: Travel/Accommodations/Expenses. Gasiorowski:MSD, Takeda, Novartis, AbbVie: Honoraria. Johnson:Roche/Genentech, Merck: Honoraria; AbbVie: Research Funding; Roche/Genentech, Merck, Bristol-Myers Squibb, AbbVie: Consultancy. Perini:Janssen, Takeda: Honoraria; AbbVie, Janssen: Speakers Bureau. Dickinson:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. McDonald:venetoclax advisory board in South Africa (in CLL context): Consultancy; Alberts Cellular Therapy: Current Employment. Ozcan:Janssen: Other: Travel support, Research Funding; F. Hoffmann-La Roche Ltd: Other: Travel support, Research Funding; Bayer: Research Funding; AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Archigen Biotech: Research Funding; Celgene: Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Amgen: Honoraria, Other: Travel support; Bristol Myers Squibb: Other: Travel support; Jazz Pharmaceuticals: Other; Sanofi: Other; Abdi Ibrahim: Other. Sekiguchi:Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon, Daiichi Sankyo, and Bristol-Myers Squibb: Research Funding. Raut:Merck & Co., Inc.: Current Employment. Giezek:Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA: Current Employment. Kuruvilla:Merck: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy; AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding; Celgene Corporation: Honoraria; Bristol-Myers Squibb Company: Consultancy; TG Therapeutics: Honoraria; Novartis: Honoraria; Antengene: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria.
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Shah, Jatin J., Rafat Abonour, Brian G. M. Durie, Jayesh Mehta, Mohit Narang, Howard Terebelo, Cristina J. Gasparetto, et al. "Connect MM®—the Multiple Myeloma (MM) Disease Registry: Interim Analysis of Overall Survival and Outcomes in Patients with High-Risk Disease." Blood 124, no. 21 (December 6, 2014): 2106. http://dx.doi.org/10.1182/blood.v124.21.2106.2106.
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Abstract Background: MM treatment (Tx) advances have greatly improved clinical outcomes for patients (pts). A recent study demonstrated improved survival in MM through the past decade attributable to the impact of initial therapy with lenalidomide, bortezomib, and thalidomide. The greatest impact was observed in older pts (Kumar, et al. Leukemia, 2014). Connect MM, the first and largest prospective, observational, US-based, multicenter registry was designed to characterize pts, Tx patterns, and outcomes in newly diagnosed MM (NDMM). Methods: This ongoing registry was initiated in September 2009. Eligible pts with NDMM (diagnosis must have occurred within 2 mos of study entry) were enrolled at 234 US sites. Data were collected at baseline and each subsequent quarter using an electronic case report form. The initial enrollment includes all pts who had provided informed consent as of November 1, 2012 (N = 1493). The data cutoff for this analysis was Dec 10, 2013. A total of 1444 pts were treated and were included in overall survival (OS) analyses. Survival was examined for all treated pts adjusting for pt and Tx characteristics including age, autologous stem cell transplant (ASCT) status, gender, race, disease risk factors (International Myeloma Working Group [IMWG] high risk vs. non-high risk), and therapy received (triplet vs. non-triplet) among others. Triplet therapy was defined as any combination of 3 or more drugs during the first Tx regimen. OS was estimated using Kaplan-Meier methods and comparisons across groups were assessed used the log-rank test. Results: At the time of data cutoff, 1493 pts were enrolled with 1444 having received Tx. Of the treated pts 253 pts (18%) had IMWG high-risk disease and 108 pts (7%) had del(17p) at baseline. Median age was 67 y (range, 24-94 y), 57.2% were male, and 81.9% were white. Median follow-up was 29 mos (0-49.4 mos). The median OS for all treated pts was 44.4 mos. When assessed by age group, OS was significantly different (log-rank P < .0001) with a median of 47.6 mos for pts aged < 65 y (n = 632), 45.0 mos for those aged 65 to < 75 y (n = 443), and 33.7 mos for those aged ≥ 75 y (n = 369). OS was significantly longer for pts with ASCT vs. no ASCT (P < .0001), but not different by gender (P = .962) or race (Caucasian vs. African American vs. other; P = .250). Three-year OS probabilities by subgroup are listed in Table 1. When considering risk factors, IMWG risk was borderline significant (high vs. non-high; P = .106), and presence of del(17p) by cytogenetics and FISH was associated with significantly shortened OS (P = .005; Figure 1A). Interestingly, use of triplet therapy vs. non-triplet therapy was associated with significantly prolonged OS regardless of IMWG risk (non-high: P < .0001; high: P = .003; Figure 1B). However, no improvement was noted for triplet vs. non-triplet therapy in pts with del(17p). By multivariate analysis, the significant (P < .05) factors impacting OS were age (in 10-yr increments), International Staging System (ISS) disease stage, ECOG performance status, history of diabetes, anemia, renal function, and platelet count. Conclusions: This interim analysis based on initially treated pts demonstrated that age, ISS stage, and co-morbidities impact OS irrespective of IMWG cytogenetic risk. Triplet Tx was associated with significantly longer OS in pts regardless of IMWG risk status. This is the largest prospective pt cohort with high-risk disease including del(17p). Pts with high-risk disease did not have significantly lower OS vs. pts without high-risk features. Pts with del(17p) (p53 deletion) continue to have shorter OS approaching 3 y and increased survival with use of triplet therapy. Table 1. Kaplan-Meier Estimated 3-Y OS Probability Patients 3-y OS Probability (%) (95% CI) All (N = 1444) 62.6 (59.5-65.8) < 65 y (n = 632) 69.8 (65.2-74.3) 65 to < 75 y (n = 443) 65.0 (59.4-70.6) ≥ 75 y (n = 369) 47.2 (40.7-53.8) Gender Male (n = 831) 62.1 (57.9-66.3) Female (n = 613) 63.4 (58.7-68.2) Race Caucasian (n = 1191) 61.8 (58.3-65.3) African American (n = 183) 64.4 (55.4-73.5) Other (n = 27) 77.6 (57.3-98.0) ASCT Yes (n = 494) 77.1 (72.5-81.7) No (n = 950) 54.2 (50.0-58.3) Triplet therapy Yes (n = 778) 69.3 (65.3-73.3) No (n = 666) 54.8 (49.9-59.6) IMWG risk High (n = 253) 59.0 (51.6-66.4) Standard (n = 566) 66.3 (61.4-71.2) Low (n = 86) 75.7 (63.6-87.8) del(17p) Present (n = 108) 52.7 (41.8-63.6) Absent (n = 1336) 63.4 (60.1-66.7) Figure 1 Figure 1. Disclosures Shah: Celgene Corp: Consultancy, Research Funding. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Durie:Celgene Corp: Export Board Committee Other, Membership on an entity's Board of Directors or advisory committees; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees; IRC J&J: Membership on an entity's Board of Directors or advisory committees. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Rifkin:Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy.
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Lythgoe, Mark, Maximilian Julve, Jonathan Krell, Philip Savage, Petros Grivas, and Ali Raza Khaki. "Racial diversity and reporting in FDA registration trials for genitourinary (GU) cancers from 2006-20." Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021): 22. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.22.
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22 Background: GU cancers account for 1 in 5 of new cancer diagnoses in the USA. Significant racial disparities exist in terms of incidence, treatment and outcomes. Current FDA clinical trial guidance advises race reporting as a minimum of 5 categories (White/Caucasian, Black, Asian, American Indian or Alaskan Native [AIAN] and Native Hawaiian or Pacific Islander [NHPI]). Guidelines from the International Committee of Medical Journal Editors (ICMJE) recommend that authors should as a minimum, provide descriptive data for variables such as race and ethnicity. We analysed racial diversity in GU registration trials and compliance with FDA/ICMJE guidance in reporting. Methods: A retrospective review of new market authorisations in GU cancers from Jan 2006 to Oct 2020 was conducted utilizing the FDA website. Clinical trials cited on the licensing label for market authorization were recorded and corresponding registration trial publication identified. If race was unreported or partially reported (defined ≤3 groups), then the trial report on clinicaltrials.gov or FDA website was analysed. Total proportion of racial group participation and the proportion of registration trials with adequate reporting was determined. Results: We identified 42 new licensing indications, involving 33 unique drugs. Overall 30,316 patients participated in GU cancer registration trials; 21,068 (69.5%) White or Caucasian, 2516 (8.3%) Asian, 621(2%) Black or African American, 92 (0.3%) AIAN, 17 (0.1%) NHPI, 558 (1.8%) other or multiple races and 5463 (18%) unknown. Table shows breakdown by tumour group. Race reporting occurred in 23 (55%) registration trial publications, of which 5 provided only limited information (e.g. Caucasian only). For studies where no race information was reported, a further 10 (24%) had information within the trial report. In the 5 years prior to the introduction of FDA guidance in 2016 only 30% of registration studies met FDA/ICJME requirements. Since 2016 this has improved significantly to 60%. Conclusions: Despite the higher incidence of GU cancers in non-white populations, this study has revealed the relative over-representation of white participants in GU registration trials. The inclusion of black trial participants is in particular disproportionately low when compared to the burden of disease in this population group. Recruitment of black and other minority participants should be a research priority. [Table: see text]
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Malpica Castillo, Luis E., Daniel J. Enriquez, Denisse A. Castro, Camila Peña, Henry Idrobo, Lorena Fiad, Maria Prates, et al. "Epidemiology, Clinical Features, and Outcome of HTLV-1-Related Adult T-Cell Leukemia/Lymphoma in Latin America: A Study from the Latin American Group of Lymphoproliferative Disorders (GELL)." Blood 136, Supplement 1 (November 5, 2020): 18–21. http://dx.doi.org/10.1182/blood-2020-140630.
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INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a mature peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America, and Western Africa. In Latin America (LA), Peru and Brazil have the highest prevalence of HTLV-1-related diseases, however, data on ATLL in other LA countries is scarce. ATLL carries a dismal prognosis and is essentially incurable by conventional drugs. We describe the epidemiology, clinical features, treatment, and disease outcome of ATLL encountered in 11 countries in LA. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL cases were classified according to the Shimoyama criteria into acute (A), lymphomatous (L), chronic (C) and smoldering (S). Treatment approaches used as first-line therapy were: 1) chemotherapy alone; 2) combined chemotherapy with zidovudine/interferon-alpha (AZT-IFN); and 3) AZT-IFN alone, as previously done with Miami cohort (Malpica and Ramos et al. Blood Advances 2018). Treatment response was assessed according to Tsukasaki et al. (JCO 2009) criteria. To be classified as complete response (CR), partial response and stable disease, these had to persist for a period of at least 4 weeks. Survival curves were estimated using the Kaplan-Meier method and Log rank test. RESULTS: A total of 253 pts with ATLL were identified. Two hundred twenty six pts (L=122, A=73, C=26, S=5) had sufficient data for analysis. Demographic and clinical features are shown in Figure 1 and Table 1. Median age at diagnosis was 57 years, with a female predominance in A (58%) and S (100%) types. Most ATLL pts were from Peru (n=159, 63%) followed by Chile (n=44, 17%), Argentina (n=20, 8%) and Colombia (n=17, 7%). B symptoms were high present in A, L and C types (73%, 72%, 58% vs. 8% S type, respectively, p=0.011). Hypercalcemia was highly associated with A type (57% vs. L 27%, p=0.014). The PIT score yielded to a more aggressive risk classification compared to the IPI score (high-risk: 55% vs. 29%, respectively, p<0.001). Strongyloidiasis (n=5) and pneumocystis jirovecii pneumonia (n=5) were the most commonly observed co-infections at diagnosis. Commonly affected extranodal sites other than bone marrow in all subtypes were skin 25% (n=63) and liver 9% (n=24). The therapy approach used during the first 2 therapy evaluations are summarized in Table 2. The median survival (MS) times were 4.3 months, 7.9 months, 21.1 months, and not reached for A, L, C and S form, with 4-year survival of 8%, 22%, 40% and 80%, respectively (Figure 2). First-line AZT-IFN resulted in overall response (OR) rate of 63% (CR 24%) for A (n=8) and 75% (CR 50%) for L (n=8), respectively (Table 3). The OR rates after first-line multi-agent chemotherapy alone for A vs. L were 21% (CR 8%) and 41% (CR 29%), respectively (Table 3). The most commonly used regimens were CHOP/CHOP-like (n=117, 59%) and CHOEP (n=40, 20%) regimens with OR rates of 29% (CR 12%) and 60% (CR 42%), respectively (Table 3). Progression-free survival (PFS) rates in pts with aggressive ATLL who achieved CR after chemotherapy vs. AZT-IFN (alone or in combination with chemotherapy) were 2.8 months vs. 30.4 months for A (n=8) type and 67.1 months vs. 17.7 months for L (n=30) type, respectively (Figure 3). Only 2 pts with L type underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) with PFS of 12 and 17 months (Table 4). CONCLUSION: ATLL continues to carry a dismal outcome with conventional therapies thus urging the development of novel approaches. Our study found that Latin American ATLL variant presents at a younger age, has a female predominance, high incidence of L type, low incidence of indolent types and lower survival rates, suggesting that Latin American ATLL variant presents earlier and more aggressively than in Japanese pts. AZT-IFN produced durable responses in A type patients who achieved CR as compared to chemotherapy alone. Chemotherapy responses were more durable in L types who achieved CR as compared to A type. In conclusion, in the management of aggressive ATLL, chemotherapy remains the preferred choice for L type (with consideration of allo-HSCT upfront), while AZT-IFN is a good option to attempt for A type upfront. Figure Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau. Altamirano:Hospital Nacional Guillermo Almenara Irigoyen: Other: Servicio de Hematologia. Perini:Abbvie: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria. Castillo:Janssen: Consultancy, Research Funding; Abbvie: Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding. Ramos:NIH: Research Funding. Villela:Roche: Other: advisory board, Speakers Bureau; amgen: Speakers Bureau.
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Malpica Castillo, Luis E., Denisse A. Castro, Camila Peña, Henry Idrobo, Daniel J. Enriquez, Lorena Fiad, Maria Prates, et al. "Impact of Cutaneous Involvement on the Clinical Outcome of Adult T-Cell Leukemia/Lymphoma: A Study from the Latin American Group of Lymphoproliferative Disorders (GELL)." Blood 136, Supplement 1 (November 5, 2020): 20–23. http://dx.doi.org/10.1182/blood-2020-140393.
Full textAbstract:
INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, Western Africa, the Caribbean basin and South America. Cutaneous signs of ATLL are varied and may consist of macules (M), plaques (P), multiple papules (MP), tumoral nodules (TN), erythroderma (E) or mixed-lesions (≥2 predominant lesions, ML). M and P forms are believed to carry a better prognosis. However, data on cutaneous presentation of ATLL remains scarce. Herein, we report cases of ATLL with cutaneous involvement diagnosed in 4 Latin American countries over the last 3 decades. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL subtypes were classified according to the Shimoyama criteria into acute, lymphomatous, chronic and smoldering. Primary cutaneous tumoral (PCT) variant was classified according to the 2019 International Revised ATLL Consensus. We designed 2 cohorts: the first, ATLL pts with cutaneous involvement, and the second, matched cases without cutaneous involvement. We determined the type of skin lesion as well as the survival associated with the various types of skin lesions. We compared the frequency of clinical features using Fisher's exact test. Treatment response was assessed according to Tsukasaki et al. (JCO 2009) criteria. To be classified as complete response (CR), partial response, and stable disease, these had to persist for a period of at least 4 weeks. We analyzed survival data according to ATLL subtype, cutaneous involvement status, and type of skin lesion using the Kaplan-Meier method and Log rank test. RESULTS: A total of 169 pts with ATLL were identified; 63 had cutaneous involvement and 106 did not. Clinical features are shown in Table 1. In both groups the median age was 57 years with a female predominance. Cutaneous involvement was most frequently found in acute (41%) and lymphomatous (37%) ATLL pts. The E (24%) and P (22 %) types were the most frequent skin lesions. Disease stage, presence of B symptoms, hypercalcemia, ECOG ≥2, elevated LDH, and IPI/ PIT score were not different among groups. Table 2 and Table 3 summarize the first-line therapy used and response rates. The use of first-line zidovudine plus interferon alpha (AZT-IFN), regardless of the type of skin lesion, resulted in relatively high response rates [overall response (OR) 100%, n=8; CR 62.5%] as compared to multi agent-chemotherapy (OR 33.3%, n=12). Overall, the presence of cutaneous involvement was associated with better overall survival (OS) compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p<0.01; 1-year OS 53% vs. 27%, respectively, p=0.012) (Figure 1). PCT pts had better outcome compared to acute and lymphomatous ATLL forms (1-year OS 75% vs. 39% vs. 25%, respectively, p=0.002). The presence of P and MP skin lesions was associated with better OS compared to other subtypes (1-year OS: P/MP 65% vs. others 41%, respectively, p=0.027) (Figure 2, supplemental figure 1). In a multivariate analysis, hypercalcemia was an independent poor prognostic factor for survival among ATLL pts with cutaneous involvement (aHR 3.99 [95% CI: 139-11.45], p=0.01) (supplemental figure 2). One patient with lymphomatous ATLL and plaque lesions underwent allogeneic stem cell transplant with high-dose chemotherapy after achieving CR with AZT-IFN; patient remains alive and progression-free for 17 months. Illustrative cases of cutaneous ATLL are shown in Figure 3. CONCLUSION: In Latin American pts with aggressive ATLL, cutaneous involvement appears to be associated with better survival compared to non-cutaneous involvement. PCT subtype, an ATLL variant characterized by isolated skin lesions with no organ involvement and poor outcome, appeared to have a better prognosis compared to acute and lymphomatous ATLL forms. P and MP skin lesions were both associated with better survival. Hypercalcemia was found as an independent prognostic factor for survival in pts with cutaneous involvement. Finally, AZT-IFN appears to be reasonable first-line option for aggressive ATLL subtypes with cutaneous involvement regardless of the type of skin lesion at diagnosis, based on the relatively high response rates observed in this subset; further investigation in randomized clinical trials is needed. Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Takeda: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Altamirano:Hospital Nacional Guillermo Almenara Irigoyen: Other: Servicio de Hematologia. Perini:Abbvie: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria. Castillo:Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Research Funding; Kymera: Consultancy; TG Therapeutics: Research Funding; Janssen: Consultancy, Research Funding. Ramos:NIH: Research Funding. Villela:amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau.
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Shatola, Ashley, Ann M. Brunson, Theresa H. M. Keegan, Ted Wun, and Anjlee Mahajan. "Fragmentation of Care for Young Adults with Sickle Cell Disease in California." Blood 134, Supplement_1 (November 13, 2019): 4667. http://dx.doi.org/10.1182/blood-2019-121901.
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Background: Sickle Cell Disease (SCD) predominantly affects people of African ancestry, causing significant morbidity and mortality. In high-income countries children, who are more likely to receive comprehensive care than adults, have better health care outcomes. Young adults (YA) are in a period of transition from pediatric to adult models of care and the effect of receiving care at multiple medical facilities (fragmentation) during this time on outcomes has not been well-described. In this study we sought to examine fragmentation of care for YA SCD patients and the association of fragmentation on mortality. Methods: Using a previously published definition, longitudinal records from the California Patient Discharge, Emergency Department, and Ambulatory Surgery datasets were used to identify SCD patients from 1991-2016. SCD patients were placed into three different age cohorts: children (10-17), YA (18-25) and adults (26-33). Each patient required the full 7 year follow up time in each age category; patients could be in multiple age cohorts. Patients with no inpatient admissions were excluded. The number of inpatient admissions during each age group period was used as a measure of disease severity (<10, 10-19, 20-29, ≥30). SCD specialty care centers (SCD SC) were determined using all SCD inpatient admissions; facilities in the top 5% based on number of unique SCD patients seen were considered SCD SC. Patients were classified as always, sometimes and never seen at SCD SC facilities in each age group. We classified care fragmentation by the number of facilities an individual received inpatient care (1, 2, 3-4 or ≥5 unique facilities) during their time in each age group. Descriptive statistics were used to describe patients' characteristics by age group. Multivariable Poisson regression was used to identify risk factors associated with fragmented care. Multivariable Cox regression was used to determine the impact of fragmented care, disease severity and care at SCD SC on all-cause mortality, conditional on surviving to 26 years of age for the YA group. Results We identified a cohort of 6,977 unique SCD patients: 1,019 children, 1,122 YAs and 1,015 adults. The YA cohort consisted of predominately African Americans (91.3%) with 43.9% male and 56.1% female. Forty-two % YAs had Medi-Cal followed by 26.7% with private insurance as first reported health insurance. Forty-four % (494) had <10, 20.1% (226) had 10-19, 11.1% (125) had 20-29 and 24.7% (277) had ≥30 inpatient admissions while in the YA age period. Twenty-two % (248) YAs were seen at 1, 25.8% (290) were seen at 2, 30.2% (339) were seen at 3-4, and 21.8% (245) were seen at > 5 inpatient facilities. YAs and older adults were seen at a similar number of facilities while children were seen at less (Figure 1). In multivariable regression models among YAs, those with private insurance (vs. Medi-Cal) were at lower risk of fragmentation (Incident Rate Ratio (IRR)=0.85, CI 0.78-0.93, p=0.0002), while those without insurance were at a higher risk (IRR 1.45, CI 1.22-1.72, p<0.0001). Patients with more admissions (vs. <10) were at higher risk of fragmentation (IRR for 10-19 =1.42, CI 1.29-1.57; IRR for 20-29 1.49, CI 1.33-1.67, IRR for >30 admissions 2.13, CI 1.98-2.43 p<0.0001). Patients who were sometimes admitted to an SCD SC (IRR=2.19, CI 1.98-2.43, p<0.0001) or never (IRR=1.15, CI 1.15-1.46, p<0.0001) were at increased risk of fragmented care compared to those who were always admitted to an SCD SC. In the multivariable mortality model, YAs with increasing number of admissions, regardless of location, were at increased risk of death (10-19 HR 2.36, CI 1.13-4.91 p=0.022; 20-29 HR 4.25, CI 2.03-8.92, p=0.0001; > 30 admissions HR 7.79, CI 4.09-14.83, p<0.0001). Fragmentation of care and always or sometimes being admitted to an SCD SC were not associated with mortality. Conclusion Most young adult SCD patients (78%) received inpatient care at >1 facility. Of all age groups, children were most likely to be seen at only 1 facility, suggesting that fragmentation of care begins in early adulthood. Young adults without insurance, patients with more frequent admissions and those who did not always receive care at an SCD SC were at higher risk for fragmented care. Young adults with more frequent admissions were also at an increased risk of mortality. The effect of specialty centers and more consistent location of care on health-related outcomes for patients with SCD requires further study. Disclosures Wun: Janssen: Other: Steering committee; Pfizer: Other: Steering committee.
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Drasar, Emma, Jie Jiang, Kate Gardner, Jo Howard, Tom Vulliamy, Nisha Vasavda, and Swee Lay Thein. "Telomere Lengths Correlate With Inflammatory Markers In Sickle Cell Disease." Blood 122, no. 21 (November 15, 2013): 2230. http://dx.doi.org/10.1182/blood.v122.21.2230.2230.
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Abstract Telomeres are DNA protein structures that protect chromosome ends from degradation and fusion and are essential for maintenance of genomic integrity. Shortened telomere length has been found in DNA from patients with inherited conditions associated with premature cellular aging and acquired disorders such as cardiovascular heart disease. In vitro studies have shown that telomeres are highly susceptible to oxidative stress. We hypothesize that the elevated level of reactive oxygen species and oxidative stress generated by ongoing hemolysis in sickle cell disease (SCD) could predispose to shorter telomeres in white blood cells (WBCs), and that telomere length could be a marker of SCD severity. The study population included 126 healthy controls of mixed ethnicities and 426 patients of African descent with SCD of mixed genotypes (291 HbSS, 112 HbSC, 16 HbSβ+ thalassaemia and 7 HbSβ0 thalassemia) recruited from King’s College and Guy’s and St Thomas’ hospitals (King’s College Hospital Local Research Ethics Committee protocol 07/H0606/165). Ages ranged from 6 to 86 years for the control group and 17 to 81 years for the SCD group. Clinical and steady state laboratory data were collected from the electronic patient records and sickle cell database. Telomere length measurement was performed on DNA extracted from peripheral blood leucocytes using a monochrome multiplex quantitative polymerase chain reaction technique adapted from the method as described by Richard Cawthon (Cawthon 2009). The method compares telomere repeat sequence copy number (T) to albumin (a single copy gene, S) copy number within the same DNA sample. Three reference DNA samples were included in each run as internal quality controls. The sample DNAs were assayed in duplicate and the standard curve DNAs, in triplicate. Polymerase chain reaction was performed using a Rotorgene 6000 (Corbett Life Sciences) after which data were analysed using Rotorgene 6000 series software version 1.7. For each sample, telomere length was expressed as telomere to single copy gene ratio (TSR) which is based on the delta Ct (Cttelomere / Ctsingle-gene) derived from the standard curve. To make comparable the results from different runs, the results were approved only if the relative TSRs of the validation reference samples fell within a 5% variation. Regression analysis was performed correcting for age, gender, alpha genotype, and hydroxyurea (HU) therapy at the time of sample collection. Laboratory variables were only available for the SCD group. 57/301 (19%) of sickle cell anemia (SCA, including HbSS and HbSβ0) patients had received HU treatment for at least 3 months prior to sample collection. TSRs for the controls, study group and sub-groups was significantly negatively associated with age as has previously been shown in healthy controls and disease states (Fig 1) (p<0.0001 in all groups). Contrary to our expectations, mean TSR was significantly longer (p<0.0001) in patients with SCD (mean 2.37 range 0.14 to 4.87) compared to controls (mean 1.80 range 0.87 to 4.17). Further, within the SCD group, TSR was significantly longer (p<0.0001) in patients with SCA (mean 2.44 range 0.14 to 4.87) compared to those with HbSC (2.19 range 0.35 to 3.46). The association with sickle genotype persisted with regression analysis (p = 0.001). We postulate that the longer telomeres in patients with SCD are due to increased telomerase activity related to the underlying inflammation. This suggestion is supported by the: 1) positive association of TSR with WBC (R = 0.19 p = 0.001) and neutrophil count (R = 0.14 p = 0.02) which persisted with regression analysis (WBC, p = 0.003 and neutrophil count, p = 0.049); 2) longer TSRs in patients with SCA when compared to patients with HbSC disease who have less inflammation; 3) significantly shorter telomeres in patients on HU therapy compared to the untreated group (regression analysis p = 0.004), we propose that this is due to the anti-inflammatory effects of HU via suppression of WBC count and down-regulation of cytokines. These results could have significant implications for our understanding of the pathophysiology of SCD, particularly the role that inflammation plays in chronic organ damage in this patient group. To validate the hypothesis, future work would include correlation of telomere length with both telomerase activity and organ damage in patients with SCD. Disclosures: Howard: Sangart: Membership on an entity’s Board of Directors or advisory committees.
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Weiss, Jamine, Amy Kolwaite, Meghan Lyman, Getachew Kassa, Miriam Rabkin, Anna Maruta, Marita Murrman, Hassan Benya, and Christiana Conteh. "The Design and Implementation of an IPC Certificate Course: Experiences From Sierra Leone." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s498. http://dx.doi.org/10.1017/ice.2020.1177.
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Background: Trained infection prevention and control (IPC) practitioners are critical to reducing healthcare-associated infections (HAI) and improving patient safety. Despite having HAI rates 3 times higher than high-income countries, many low- and middle-income countries (LMICs) lack trained IPC professionals. During the 2014–2016 Ebola outbreak in West Africa, the Sierra Leone Ministry of Health and Sanitation (MoHS) recognized this need and appointed and trained IPC focal persons at all district hospitals. Following the outbreak, MoHS requested assistance from the US CDC to develop and implement a comprehensive IPC training program for IPC specialists. Methods: The CDC, alongside its partners, convened a multidisciplinary team to develop an IPC certificate course. ICAP led the curriculum development process using a “backwards design” approach, starting with development of competencies and learning objectives, then designing an evaluation framework and learning strategies, and finally, identifying course content. The curriculum was based on existing resources, primarily designed for high-income countries, which were adapted to the Sierra Leone context and aligned with national IPC policies and guidelines. Additionally, an IPC steering committee, led by MoHS, was established to provide national leadership and oversight and make country-level decisions regarding accreditation and career pathways for IPC specialists. Results: The course includes three 2-week workshops over 6 months consisting of classroom didactics and hands-on activities. Topics include standard and transmission-based precautions, microbiology, laboratory, HAI, quality improvement, leadership, and scientific writing. Between sessions, participants conduct IPC activities at their work site and share results during subsequent workshops. Participants receive electronic tablets, which contain course content, assessment tools, and references, to upload their work into a cloud-based storage system for facilitators to provide feedback. They also receive in-person mentorship and connect with peers through a group messaging platform to share lessons learned. Participants’ knowledge and skills are assessed using a before-and-after test and observing them perform IPC practices using standardized checklists. The first cohort of 25 participants will complete the course in November 2019. Conclusions: The IPC certificate course is the first comprehensive, competency-based IPC training in Sierra Leone. Successes, challenges, sustainability, and lessons learned remain to be determined; however, based on similar models, the course has the potential to significantly improve IPC in Sierra Leone. Additionally, it is a model that can be replicated in other resource-limited settings.Funding: NoneDisclosure:None
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Gagnepain-Lacheteau, A., and S. Vougier. "The My Child Matters Program for Fighting Paediatric Cancer in Low- and Middle-Income Countries." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 237s. http://dx.doi.org/10.1200/jgo.18.95200.
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Background and context: 20% of the children with cancer live in the high-income countries, where the survival rate is 80%, while 80% live in low- and middle-income countries, where the survival rate is <40%, and even lower in the poorest countries. Aim: In 2006 Sanofi Espoir Foundation launched the My Child Matters program, to give all the children with cancer, wherever they live, the same chance to have access to diagnosis and care. Strategy/Tactics: This program is based on public–private partnerships in the field of pediatric oncology in low- and middle-income countries. Program/Policy process: The program works with calls for projects, with 3-year-cycle grants founded by Sanofi Espoir Foundation. The first call for projects was launched in December 2005 in 10 countries, leading to 14 projects supported by the foundation. The last call for project was launched in 2015, the next one is expected at the end of 2018. The projects are various, according to the local needs, strengths and opportunities, and can focus on early diagnosis improvement, psychosocial support, treatment abandonment reduction, capacity building, cancer registries, development of palliative care and pain management or a holistic approach. They are selected by an international expert committee. The engineering involves the medical direction of Sanofi Espoir, a scientific overview in partnership with St. Jude Children’s Research Hospital, a mentoring program with the commitment of various international experts and some training sessions for the team. Strong partnerships are established with UICC, SIOP, St. Jude Children’s Research Hospital, Alliance Mondiale Contre le Cancer (French branch of INCTR), Groupe Franco Africain d'Oncologie Pédiatrique and some local associations and foundations. Outcomes: 58 projects implemented in 42 countries in Asia, Africa and Latin America. 18 on-going projects; 75,000 children cared for; 20,000 healthcare professionals trained; ∼100 scientific articles related to the My Child Matters have been published. An ancillary call for projects, dedicated to the nurses in pediatric oncology, have been launched as well in 2015. What was learned: At the local level, the team leadership, the efficacy of the mentor–mentee duo, the commitment of the local government, the partnerships with local associations are decisive in succeeding and reaching a sustainable model. At the international level, reinforcing partnerships with NGO and other foundations increases the opportunities of collaborations for improving the life of children with cancer and contributing to reach the SDG 3.
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Raghavan, Derek, Darcy L. Doege, Mellisa S. Wheeler, John D. Doty, James Oliver, Edward S. Kim, Kathryn Finch Mileham, and Daniel R. Carrizosa. "Effectiveness of mobile computerized tomographic (CT) lung scanning unit for early diagnosis of lung cancer in under-served populations." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 6567. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.6567.
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6567 Background: The National Lung Screening Trial (NLST) demonstrated that screening high-risk patients with low-dose CT (LDCT) of the chest reduces lung cancer mortality compared to screening with chest x-ray. Uninsured and Medicaid patients lack access to this hospital-based screening test due to geographic isolation/socio-economic factors. We hypothesized that a mobile screening unit would improve access and confer benefits demonstrated by the NLST to this under-served group, which is most at risk of lung cancer deaths. Methods: In collaboration with Samsung Inc, we inserted a BodyTom portable 32 slide low-dose CT scanner into a 35-foot coach, reinforced to avoid equipment damage, to function as a mobile lung scanning unit. The unit includes a waiting area, high speed wireless internet connection for rapid image transfer, and electronic tablets to deliver smoking cessation and health education programs and shared decision-making video aids. It has been certified as a lung cancer screening Center of Excellence by Lung Cancer Alliance. We employed the LUNG RADS approach to lesion classification, yielding high sensitivity and specificity in assessment. All films were reviewed by a central panel of oncologists, pulmonologists and radiologists. The protocol was approved by Chesapeake IRB, which oversees all LCI cancer trials. Interim analysis at this time was approved by the Oversight Committee. Results: We screened 470 under-served smokers between 4/2017-1/2019; M:F 1.1:1, mean age 61 years (range 55-64), with average pack year history of 45.7 (30-150) (25% African-American; 3% Hispanic; 65% rural; 100% uninsured, under-insured or Medicaid - NC Medicaid does not cover lung cancer screening). Patients over the age of 64 years were excluded as they are covered by Medicare for lung cancer screening. We found at initial screen 35 subjects with LUNG RADS 4 lesions, 49 subjects with LUNG RADS 3 lesions, 10 lung cancers (2.1%), including 4 at stage I-II. 4 non-lung cancers were identified and treated. Other incidental non-oncologic findings are the subject of another presentation. Conclusions: In this small sample using the first mobile low dose CT lung screening unit in the United States, the initial cancer detection rate is comparable to that reported in the NLST but with marked improvement of screening rates in underserved groups and with better anticipated outcomes at lower cost than if they had first presented with metastatic disease.
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Ndou, Moffat Maitele. "Mental illness, harassment and labour laws: Some thoughts on harassment by employees suffering from mental illness." Obiter 41, no. 3 (January 1, 2021): 538–54. http://dx.doi.org/10.17159/obiter.v41i3.9578.
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Section 23 of the Constitution of the Republic of South Africa, 1996 provides that everyone has the right to fair labour practices. Section 9 of the Constitution prohibits unfair discrimination directly or indirectly against anyone on one or more grounds, including among others disability. In terms of section 6(1) of the Employment Equity Act (EEA), no person may unfairly discriminate, directly or indirectly, against an employee, in any employment policy or practice, on one or more grounds, including among others disability or on any other arbitrary ground. Section 6(1) applies to employees, which includes applicants; but it is only limited to conduct occurring within the scope of an “employment policy or practice”. In Marsland v New Way Motor & Diesel Engineering (2009) 30 ILJ 169 (LC), the court concluded that discrimination based on the fact that a person suffers from a mental health problem, has the potential to impair the fundamental dignity of that person as a human being, or to affect them in a comparably serious manner. Consequently, discrimination based on mental illness must be treated as a prohibited ground of discrimination. However, as it was pointed out in Hoffmann v South African Airways 2001 (1) SA 1 (CC), it may in some instances be justified to discriminate on the ground of mental illness, if it is proved that the discrimination is based on an inherent requirement of a job. Section 15 of the EEA requires that, when the employer implements affirmative action measures, he/she must make reasonable accommodation for people from designated groups, in order to ensure that they enjoy equal opportunities and are equitably represented in the workforce of a designated employer. Section 1 defines “reasonable accommodation” as “any modification or adjustment to a job or to the working environment that will enable a person from a designated group to have access to or participate or advance in employment”. Section 6(3) of the EEA provides that harassment is a form of discrimination and is prohibited among others on the ground of disability or any other arbitrary ground. Harassment is also a form of misconduct. The employer is required to take reasonable steps to prevent harassment and failure to do so, the employer is liable for such harassment. Where an employee who has a mental illness, commits an act of harassment against another employee, the employer should take into account its duty to reasonably accommodate the offending employee, the duty to take steps to prevent harassment and the fact that it may be automatically unfair to dismiss an employee for misconduct which was committed because of mental illness.
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Abdullahi, Shehu Umar, Surayya M. Sunusi, Mohammed Sani Abba, Saifuddeen Sani, Aisha Galadanci, Hauwa Inuwa, Binta W. Jibir, et al. "Low- Versus Moderate-Dose Hydroxyurea for Secondary Stroke Prevention in Children with Sickle Cell Disease in Sub-Saharan Africa: Final Results of a Randomized Controlled Trial, Sprint Trial." Blood 136, Supplement 1 (November 5, 2020): 5–6. http://dx.doi.org/10.1182/blood-2020-142896.
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Introduction Strokes are a preventable cause of neurological morbidity and premature death, particularly in children with sickle cell anemia (SCA) living in low-resource countries. If untreated, 50% of children with SCA their first overt ischemic stroke will have a recurrent stroke within two years of the event. In high-income countries, ASH 2020 guidelines recommend indefinite regular blood transfusion therapy for secondary stroke prevention (Blood Adv. 2020). Unfortunately, regular blood transfusion therapy is not a feasible option for children with SCA in sub-Saharan Africa due to the high cost of monthly blood transfusion, limited blood supply, and unsafe transfusion practices. Also, children who receive regular blood transfusions will ultimately require daily iron chelation at a cost that is prohibitive to most families in low-income settings. One randomized controlled trial provided evidence that HU therapy may be an effective therapy for secondary prevention of strokes when compared to no therapy (Blood. 2012;119(17):3925-3932). In the SWiTCH trial, the incidence rate of stroke recurrence in the group randomly allocated to receive maximum tolerated dose HU therapy was significantly higher than the group randomly assigned to receive blood transfusion therapy (5.6 and 0 events per 100 person-years, respectively, but considerably lower when compared to children not treated with any treatment, approximately 28 events per 100 person-years (Niger Postgrad Med J. 2013;20(3):181-187). Given the practical limitations for regular blood transfusion therapy, we tested the hypothesis that for secondary stroke prevention among children with SCA and acute overt ischemic stroke, fixed moderated dose HU therapy (~20 mg/kg/day) results in 80% relative risk reduction when compared to fixed low-dose HU therapy (10 mg/kg/day) in a randomized controlled trial (SPRINT Trial; NCT02675790). Methodology In phase III controlled trial, partially blind d controlled trial, we randomly assigned children 1 - 16 years of age with SCA and a new-onset of ischemic stroke (within 1 month) to receive fixed moderate-dose HU therapy at 20 mg/kg/day or fixed-low dose HU therapy at 10 mg/kg/day) with a monthly follow-up for at least 36 months. The primary endpoint was a recurrence of overt stroke or transient ischemic attack. Myelosuppression was assessed with monthly CBCs. Adherence to hydroxyurea was based on an increase in MCV from baseline and monthly pill count return, as a percent of dispensed pills. Results A total of 101 children with SCA were randomly assigned to fixed low- (~10 mg/kg/day) or moderate- (~20 mg/kg/day) dose hydroxyurea. The mean age was 6.6 years; 55.4% were males, and the median follow up was 1.6 years (IQR 1.0 - 2.3). The DSMB stopped the trial early due to the futility of the primary endpoint. In the fixed low- and moderate-dose groups, the incidence rates of recurrent strokes per 100 person-years were 7.1 and 6.0, respectively, incidence rate ratio of 0.85 (95% CI: 0.20 - 3.34), p=0.999. The incidence rates of mortality per 100 person-years in the fixed low dose and moderate- fixed-dose groups were 2.38 and 3.63, respectively, with an incidence rate ratio of 1.53 (95% CI: 0.18 - 18.30), p=0.98. No participant had hydroxyurea therapy stopped because of myelosuppression. As a measure of adherence, MCV from baseline to endpoint increased 6.2 fl and 13.3 fl in the fixed low- and moderate-dose groups, respectively, p=0.025; returned pills during the trial were 3.3% and 3.5% in the fixed low- and moderate-dose groups, respectively, p= 0.76. Conclusion For secondary stroke prevention, in a randomized controlled trial in children with SCA and new onset of ischemic strokes, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of stroke recurrence. Fixed low-dose hydroxyurea for secondary prevention of strokes in Nigeria provided similar stroke recurrence rate, when compared to the SWiTCH Trial (Blood. 2012;119(17):3925-3932) with the maximum tolerated dose of hydroxyurea of 7.0 and 5.7 events per 100 person-years, respectively. For secondary stroke prevention, in low-income settings without access to indefinite regular blood transfusion therapy, fixed low-dose hydroxyurea of at least 10 mg/kg/day with biannual CBC is a new evidence-based strategy to prevent strokes and minimize unnecessary laboratory testing. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell
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Caron, David D., Joan Fitzpatrick, and Ron C. Slye. "Republic of South Africa v. Grootboom. Case No. CCT 11/00. 2000 (11) BCLR 1169 and Minister of Health v. Treatment Action Campaign. Case No. CCT 8/02." American Journal of International Law 97, no. 3 (July 2003): 669–80. http://dx.doi.org/10.2307/3109853.
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Republic of South Africa v. Grootboom. Case No. CCT 11/00. 2000 (11) BCLR 1169. Constitutional Court of South Africa, October 4, 2000.Minister of Health v. Treatment Action Campaign. Case No. CCT 8/02. At <http://www.concourt.gov.za>.Constitutional Court of South Africa, July 5, 2002.Two cases decided by the Constitutional Court of South Africa in 2000 and 2002 implement several economic, social, and cultural rights guaranteed by the Constitution of South Africa. The decisions illuminate the role in such reasoning of human rights treaties to which South Africa is a state party or a signatory. They also analyze General Comment No. 3 of die UN Committee on Economic, Social and Cultural Rights (Committee). These cases, Republic of South Africa v. Grootboom, decided October 4,2000, and Minister of Health v. Treatment Action Campaign, decided July 5, 2002, illuminate questions concerning both die jusdciability of economic, social, and cultural rights—at least as incorporated into Soudi Africa's Bill of Rights, sections 7 through 39 of its Constitution—and the concept of “minimum core obligations” as developed by the Committee.
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Malpica Castillo, Luis E., Camila Peña, Christine Rojas, Pilar León, Brady E. Beltrán, Denisse A. Castro, Yesenia M. Huerta- Collado, et al. "Identifying a Simple Clinical Prognostic Model for Aggressive Adult T-Cell Leukemia/Lymphoma in Latin American Population and Its Validation: A Large International Study of the Latin America Working Group for Lymphomas (GELL)." Blood 134, Supplement_1 (November 13, 2019): 4045. http://dx.doi.org/10.1182/blood-2019-122976.
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Background : Adult T-cell leukemia/lymphoma (ATLL) is an aggressive, peripheral T-cell neoplasm associated with the human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America and Western Africa. In Latin America, highest prevalence is found in Haiti, Jamaica, Dominican Republic, Brazil and Peru. ATLL has a poor prognosis, with shorter overall survival (OS) relative to other peripheral T-cell lymphomas. Although current prognostic models require extensive radiologic and laboratory investigations, oftentimes they are not readily available in most Latin American countries, hence, a simple prognostic model is useful. We aim to identify and then validate a simple clinical prognostic model for ATLL in the Latin American population by analyzing clinical parameters and only laboratory tests that are widely available across Latin American countries. Patients and Methods : We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1987 and December 2018. Aggressive ATLL cases were classified according to the Shimoyama criteria into acute (A) and lymphomatous (L). Cox regression modeling was performed on several clinical and laboratory parameters in two independent cohorts: first, a learning cohort (LC) of ATLL pts diagnosed and managed at two tertiary hospitals in Chile and Peru, and then a cohort of ATLL pts from a tertiary hospital in Miami was used to validate the model (validation cohort, VC). OS curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted. Results : A total of 149 pts (A=55, L=94) in the LC, and 101 pts (A=58, L=43) in the VC were identified, with 101 and 94 pts receiving therapy in each cohort, respectively. Clinical features are shown in Table 1. In both cohorts, there was a young (<60 years, LC=51%, VC=64%), and female predominance (LC=52%, VC=61%). Pts in the LC had a better performance status compared to the VC (ECOG ≥2, LC=50% vs. VC=76%). Pts in the VC had advanced stages of disease (stage III/IV, LC=88% vs. VC=97%), and ≥1 extranodal involvement (LC=17% vs. VC=76%) compared to the LC. High LDH, low serum albumin (<3.5 g/dL), bone marrow involvement and anemia (hemoglobin <10 g/dL) were no different in both cohorts. The calculated International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PTI) scores are presented in Table 1. Most pts in the VC had high risk IPI and PIT scores (High risk: IPI LC=21% vs. VC=62%; PIT LC=38% vs. VC=51%) compared to the LC that had more low and low/intermediate IPI and PIT scores (Low risk: IPI LC=13% vs. VC=0%; PIT LC=5% vs. VC=0%; Low/intermediate risk: IPI LC=26% vs. VC=7%; PIT LC=23% vs. VC=16%). The median OS was 6 and 8.4 months in the LC and VC, respectively (Figure 1). In the univariate and multivariate analysis, ECOG ≥2 and serum albumin <3.5 g/dL were both associated with a worse OS (Table 2). When adjusted to IPI and PIT scores, serum albumin <3.5 g/dL was a negative prognostic factor, independent of IPI score, and a trend in PIT score, in the LC (adjusted for IPI: HR 1.71, 95% CI 1.06-2.75; p=0.03 / PIT: HR 1.56, 95% CI 0.95-2.56; p=0.07), but independent prognostic factor from both, IPI and PIT scores, in the VC (adjusted for IPI: HR 2.45, 95% CI 1.41-4.24; p=0.001 / PIT: HR 2.43, 95% CI 1.44-4.08; p=0.001) (Figure 2). Comparable results were found when investigating by ATLL subtype, with results trending towards significance for OS, IPI and PIT scores in the LC, but then validated in the VC (Figure 3). Conclusions : To the best of our knowledge, this is the largest retrospective study evaluating the clinical features of HTLV-1 related ATLL and impact on disease outcome in Latin America. We have validated a simple prognostic model in pts with aggressive ATLL. Our results suggest that a serum albumin level of less than 3.5 g/dL is a reliable, and independent prognostic factor for survival in aggressive ATLL. This prognostic model could be used to complement or modify existing and widely used international prognostic indexes for lymphoma. This simple paradigm could be useful in validating treatment outcomes after chemotherapy or highly needed new approaches for ATLL in prospective studies, particularly in developing countries where the absence of sophisticated laboratory and imaging tests hinder treatment decisions. Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Abello:Takeda: Other: Participation in advisory board meeting. M:Merck-Sharp-Dome: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Roche-Mexico: Consultancy, Speakers Bureau.
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Abdullahi, Shehu Umar, Binta W. Jibir, Halima Bello-Manga, Safiya Gambo, Hauwa Inuwa, Aliyu Gaya Tijjani, Aisha Amal Galadanci, et al. "Randomized Controlled Trial of Fixed Low-Vs Moderate-Dose Hydroxyurea for Primary Stroke Prevention in Sub-Saharan Africa: Final Results of the Spring Trial." Blood 136, Supplement 1 (November 5, 2020): 4–5. http://dx.doi.org/10.1182/blood-2020-141436.
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Introduction: In children with sickle cell anemia (SCA) without transcranial Doppler (TCD) screening, the incidence rates of ischemic strokes is approximately the same among children living in low- and high- low-resource settings (Pediatr Neurol. 2019;95:73-78.) with a prevalence of ~ 11%. However, in high-income settings, the standard use of TCD ultrasonography, coupled initially with monthly blood transfusion therapy has dropped the stroke prevalence to < 1%. In a low-income setting, such as Nigeria, where 50% of children in the world with SCA are born (150,000 per year), initial monthly blood transfusion therapy is not practical for most children. In the Stroke Prevention in Nigeria (SPIN) Feasibility Trial (NCT01801423), fixed moderate-dose hydroxyurea was associated with a decreased rate of strokes in children with SCA and abnormal time-averaged mean of the maximum velocity (TAMMV) TCD measurements (≥200cm/sec) when compared to no treatment in the STOP Trial, 0.76 and 10.7 strokes per 100 person-years, repsectively (Am J Hematol. 2020). Based on the success of the SPIN trial, plus the challenges of real-world implementation of a government-supported primary stroke prevention programs for estimated 40,0000 children with SCA in three states in Nigeria, we tested the hypothesis that fixed-moderate dose (~20 mg/kg/day) hydroxyurea therapy for primary stroke prevention results in a 66% relative risk reduction (9 to 3 events per 100 person-years) when compared to fixed low-dose hydroxyurea (~10 mg/kg/day) therapy in a randomized controlled trial (The SPRING Trial; NCT02560935). Methods: In this partial-blind controlled phase III trial, we randomly assigned children between 5 and 12 years of age with SCA and a TCD time-averaged mean of the maximum velocity (TAMMV) ≥ 200 cm/sec measured independently twice or TAMMV ≥220 cm/sec once at study screening to receive fixed low-dose or fixed moderate-dose hydroxyurea. The primary endpoint was a clinical stroke or a transient ischemic attack (TIA). Myelosuppression was assessed with monthly complete blood counts (CBCs). Adherence to hydroxyurea was primarily based on an increase in MCV from baseline and monthly pill count return as a percent of dispensed pills. Hemoglobin F levels were measured at baseline, annually and upon trial exit. To evaluate the safety of hydroxyurea in the trial, children attending the same SCA clinics with TCD (TAMMV) <200 cm/sec at study screening were prospectively followed with biweekly phone calls and annual research visits. Results: A total of 220 children (mean age: 7.5 years, 51.8% female) were randomly assigned to fixed low- (10 mg/kg/day) or moderate- (20 mg/kg/day) dose hydroxyurea, and were followed for a median of 2.4 years (IQR 2.0-2.8). NINDS Clinical Trials leaders stopped the trial early because of futility for the primary outcome. In the fixed low- and moderate-dose hydroxyurea groups, the incidence rates of strokes per 100 person-years were 1.19 and 1.92 respectively, with an incidence rate ratio of 1.60 (95% CI: 0.31-10.34), p = 0.768. The incidence rate ratio of mortality when comparing the children treated with low- and moderate- fixed-dose hydroxyurea to the non-elevated TCD group (no hydroxyurea therapy, n= 211) was 1.97 (95% CI: 0.64-6.02) and 0.47 (95% CI: 0.05-2.38), p = 0.265 and 0.545, respectively. Returned pills during the trial was 5.4% and 4.8% in the fixed low- and moderate-dose groups, respectively, p= 0.144. MCV from baseline to endpoint increased 1.5fl and 7.2 fl in the fixed low- and moderate-dose groups, respectively, p<0.001. Upon exit from the trial 29.4% and 66.7% of the fixed- low and moderate -dose groups, respectively, had either hemoglobin level ≥ 9.0 g/dl, or a fetal hemoglobin level ≥ 20%. Conclusions: For primary stroke prevention in children with SCA, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of strokes. Both fixed low- and moderate -dose hydroxyurea doses are superior to no treatment for primary stroke prevention with abnormal TCD values. In partnership with Katsina, Kano, and Kaduna health department's leaders in Nigeria, 9 distinct SCA and primary stroke prevention clinics have been established, with the provision of free fixed low-dose hydroxyurea therapy (Bond Chemical, Nigeria; $0.15 per 500 mg) for abnormal TCD values, and biannual CBCs as standard care ,for over 40,000 children with SCA. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell
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Ogu, Ugochi Olivia, Ashley Buscetta, Elena Crouch, Shuo You, Christopher Bradford, Moonseong Heo, Khadijah Abdallah, Giacomo Vinces, Vence L. Bonham, and Caterina Minniti. "Coagulation Profile of Sickle Cell Patients with Leg Ulcers." Blood 132, Supplement 1 (November 29, 2018): 2380. http://dx.doi.org/10.1182/blood-2018-99-113184.
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Abstract BACKGROUND Leg ulcers are a serious complication of Sickle Cell Disease (SCD), often linked to a hemolytic phenotype that includes priapism, pulmonary hypertension (PH) and renal disease. In the SCD pathogenesis, hemolysis and ischemia-reperfusion injuries lead to white blood cell (WBC), platelet and endothelial cell activation, pro-inflammatory cytokine production and subsequent activation of coagulation that tips the balance towards a prothrombotic and inflammatory state. Decreased levels of the naturally occurring anticoagulants (NOACs): protein C (PC), protein S (PS), antithrombin III (ATIII), have been observed in patients with SCD in steady state, with some reports stating no differences between steady state and crisis. This occurs due to decreased production, increased consumption, or a combination of both. However, the definite mechanisms have not yet been elucidated. Factor V Leiden (FVL) and prothrombin G20210A mutations are rare in African Americans and in patients with SCD. We speculated that patients with leg ulcers would have a more pronounced pro-thrombotic phenotype than patients who never developed them. METHODS 127 adults with and without SCD leg ulcers were evaluated at steady state in the prospective cross-sectional INSIGHTS study - Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers (ClinicalTrials.gov Identifier NCT02156102). At the time of enrollment, a clinical examination and a comprehensive past medical history were completed. Routine blood work including a full coagulation profile and analysis of blood clotting genetic mutations (thrombophilia genetic tests) were obtained. Laboratory results were compared between groups with and without leg ulcers using Chi-square or Fisher exact tests. Multivariable logistic regression analysis was conducted to test whether deep venous thrombosis (DVT) and pulmonary embolism (PE), clinical surrogates of a prothrombotic phenotype, were associated with the decreased NOACs (PC, PS), or leg ulcer. RESULTS The study cohort consisted of 109 adults with Hb SS, 10 with Hb SC, 5 with Hb S beta thalassemia zero, and 3 with Hb S beta thalassemia plus. Of these, there were 35 subjects with leg ulcers. NOACs were found to be decreased in the sub-group of subjects with leg ulcers. Among those with leg ulcers, 49% had functional PC levels that were below the normal range, compared to 27% of those without leg ulcers (p=0.022) 74% had functional PS levels below the normal range, compared to 51% of study patients without leg ulcers (p=0.018); 23% had AT III levels below the normal range, compared to 17% of SCD patients without leg ulcers (p=0.482); and 29% tested positive for lupus anticoagulant (LA), compared to 25% of SCD patients without leg ulcers (p=0.682). Among the leg ulcer cohort, none of the subjects had the prothrombin gene mutation, while 3 subjects without leg ulcers were heterozygous for it. None of the subjects in our cohort had FVL mutation. The multivariable analysis showed that none of PC, PS, or leg ulcer was significantly associated with either DVT or PE. CONCLUSIONS In SCD patients with leg ulcers, PC and PS levels are significantly lower than in SCD patients without leg ulcers. Additionally, in SCD patients with leg ulcers, there is a trend towards decreased levels of AT III and increased LA positivity. FVL and prothrombin gene mutations were rare in our cohort, consistent with the general population. The above findings did not correlate clinically with a history of DVT/PE in the same population. Our results of decreased NOACs confirm previous reports from our group that demonstrated similar findings. Of greater significance, however, is our finding that sickle cell patients with leg ulcers have further decreased levels of the NOACs compared to their counterparts without leg ulcers. This finding lends credence to the hypothesis that sickle cell patients with leg ulcers have a procoagulant phenotype (Am J Hematol. 2011 Aug; 86: 705-8, Am J Hematol. 2014 Jan; 89: 1-6). Whether this translates to an increased risk of thromboembolic events remains uncertain. From our findings, it may not be the case for DVTs and PEs. However, further studies evaluating other clinical manifestations such as priapism, PH, stroke, avascular necrosis, and retinopathy, are still needed. Future directions include further correlation with the above-mentioned manifestations to provide a more comprehensive picture. Disclosures Minniti: Bluebird Bio: Other: Adjudicating Committee; Global Blood Therapeutics: Research Funding; Bayer: Research Funding; Teutona: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.
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Baughn, Linda B., Dirk Larson, Mei-Yin Polley, Kathryn E. Pearce, Eran Elhaik, Michael L. Baird, Colin Colby, et al. "Genomic Abnormalities Among African Individuals with Monoclonal Gammopathies Using Calculated Ancestry." Blood 132, Supplement 1 (November 29, 2018): 4458. http://dx.doi.org/10.1182/blood-2018-99-117382.
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Abstract Monoclonal gammopathies, including multiple myeloma (MM), represent a group of plasma cell (PC) disorders that comprise of mostly incurable hematopoietic malignancies with an increasing incidence in the US. Previous epidemiological studies demonstrated a 2-3 fold higher incidence of monoclonal gammopathy of undetermined significance (MGUS) and a similarly higher incidence of MM along with a ~4-year younger age of onset among African Americans (AA) compared to European Americans (EAs) (Fonseca, Leukemia, 2017). This suggests a possible ancestral-associated genetic predisposition of AAs to the development of monoclonal gammopathies (Landgren, Blood, 2006). When access to care is equal, AAs have a better overall survival compared to EAs suggesting that AAs may have a genetic predisposition that renders them better responders to treatment or have more favorable cytogenetic subtypes of MM (Waxman, Blood, 2010). Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry. We hypothesize that quantifying genetic ancestry is necessary to fully understand the genetic mechanisms of racial disparities of monoclonal gammopathies. We describe our study of 881 patients with monoclonal gammopathies who had undergone uniform testing to identify MM-specific cytogenetic abnormalities. DNA from the bone marrow samples was genotyped on the Precision Medicine Research Array. Biogeographical ancestry was assessed using the Geographic Population Structure Origins tool, which provides the ancestral breakdown of 36 admixture components for each individual representing different geographic regions and outputs admixture proportions corresponding to those ancestries (Elhaik, Nat Commun, 2014). We evaluated whether an increase in the percentage of African Ancestry altered the odds of any primary cytogenetic abnormality. We demonstrated that a 10% increase in the percentage of African ancestry was associated with a 6% increase in the odds of detecting either an t(11;14), t(14;16) or t(14;20) (odds ratio = 1.06, 95% CI: 1.02 - 1.11; p-value = 0.05). Although we observed an increase in the odds of each of the individual translocations with 10% increase in African ancestry, l t(11;14) (OR=1.03) t(14;16) (OR=1.11) and t(14;20) (OR=1.10), these three abnormalities were combined to achieve greater statistical power. The differences in cytogenetic abnormalities were most striking among individuals with ≥80.0% African (n=120) compared to individuals with <0.1% African ancestry (n=235). Using these cutoff values comparing the ≥80.0% and <0.1% African ancestry cohorts, there was a higher prevalence of t(11;14), t(14;16) and t(14;20) (51% vs. 33%, respectively, p-value=0.008) and a lower prevalence of trisomies (with or without IgH translocations) (48.3% vs. 61.3%, respectively, p-value=0.066). In addition, the ≥80% African ancestry cohort also displayed a slightly lower prevalence of monosomy 13/13q deletion compared to the cohort with <0.1% African ancestry (34.2% vs. 38.7%, respectively, p-value=0.021). Further, we observed a significantly higher prevalence in the proportion of females with monoclonal gammopathies among the ≥80% African ancestry cohort compared to the cohort with <0.1% African ancestry (56.7% vs. 42.1%, respectively, p-value=0.028). We complement our past studies that relied on self-reported race and characterized patients' demographic and uniformly collected cytogenetic data in relation to genetically defined African ancestry. We demonstrate the prevalence of having one of three specific subtypes (i.e., t(11;14), t(14;16), or t(14;20)) was significantly higher in those with highest (≥80%) compared to lowest (<0.1%) African ancestry demonstrating African ancestry is associated with a subtype distribution of MM that differs from non-African individuals. These differences were only revealed after analysis of individuals with the highest and lowest percentage of African ancestry. Since 38.3% of the individuals with ≥80% African ancestry have the favorable t(11;14) translocation (in comparison to 26.8% of <0.1% African individuals), this finding may explain improved survival with equal access to care. Understanding the genetic mechanisms of this disparity is a fundamental step to understanding differences in incidence and outcomes of patients with monoclonal gammopathies. Disclosures Elhaik: DNA Diagnostics Center: Consultancy. Baird:DNA Diagnostics Center: Employment. Cerhan:Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding; Celgene: Research Funding. Stewart:Amgen Inc., BMS, Celgene, Takeda, Roche, Seattle Genetics, Janssen, Ono: Consultancy; Amgen Inc., Celgene, Roche, Seattle Genetics: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Kumar:Novartis: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding.
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Coates, Laura C., Vinod Chandran, Alexis Ogdie, Denis O’Sullivan, Mel Brooke, Ingrid Steinkoenig, Philip J. Mease, Christopher T. Ritchlin, and Arthur Kavanaugh. "International Treatment Recommendations Update: A Report from the GRAPPA 2016 Annual Meeting." Journal of Rheumatology 44, no. 5 (May 2017): 684–85. http://dx.doi.org/10.3899/jrheum.170144.
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At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the treatment recommendations committee summarized its work and presented its plans for future updates. The committee announced a partnership between GRAPPA and Guideline Central to develop a pocket reference guide to the treatment recommendations. Because key new data appear regularly, the group discussed publishing periodic updates of the recommendations online through the GRAPPA Website as well as a goal of publishing another major update of the recommendations in 2020. The committee also announced that 2 GRAPPA members were awarded a grant from the International League of Associations for Rheumatology to look at potential adaptations of international treatment recommendations for resource-poor settings, particularly in South America and Africa.
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Masursky, H., K. Aksnes, G. E. Hunt, M. Ya Marov, P. M. Millman, D. Morrison, T. C. Owen, et al. "Working Group for Planetary System Nomenclature (Committee Of The Executive)." Transactions of the International Astronomical Union 19, no. 1 (1985): 725–26. http://dx.doi.org/10.1017/s0251107x00006829.
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Since the last General Assembly in Patras, Greece, we have held three meetings of the Working Group. The 10th Meeting was held in Mzkheta, the ancient capital of Georgia, USSR, hosted by their Academy of Sciences on April 3-7, 1984. All members except one, who was represented by a member of his Task Group, were present at the very productive meeting.
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Mohty, Mohamad, Evangelos Terpos, Maria-Victoria Mateos, Antonio Palumbo, Sandra Lejniece, Meral Beksac, Mohamed Amine Bekadja, et al. "Analysis of Final Data from the Multinational, Non-Interventional, Observational Emmos Study (NCT01241396) in Patients (Pts) with Multiple Myeloma (MM) in Real-World Clinical Practice." Blood 126, no. 23 (December 3, 2015): 3034. http://dx.doi.org/10.1182/blood.v126.23.3034.3034.
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Abstract Background A lack of objective data exists on differences in treatment practices and outcomes for MM between countries. The EMMOS study aimed to document and describe current treatment regimens and disease progression patterns of MM pts at different stages of the disease in real-world medical practice. Methods Adult pts initiating any new MM therapy, irrespective of treatment line at study entry or therapy type received, were eligible for inclusion in the EMMOS registry. A multi-staged pt/site recruitment model was applied to minimize selection bias; enrollment was stratified by country, region, and practice type. Pts' medical/disease features, treatment history, and remission status were recorded at baseline. Prospective data on treatment, efficacy, and safety were collected electronically every 3 mos until 2 yrs after the last pt enrolled. Responses were investigator-assessed (no predefined criteria). Here we report data from the final analysis of EMMOS. Pts were grouped according to receipt of high-dose chemotherapy/stem cell transplantation in any treatment line (SCT pts, non-SCT pts). Within a given line, pts may have received induction, SCT, consolidation, and/or maintenance therapy; if multiple drug combinations were used within a line, the line grouping was based on the combination received in cycle 1. Results 2358 pts were enrolled between Oct 2010-Oct 2012 in 22 countries in Europe and Africa; the last pt completed follow-up in Oct 2014. Of these, 775 pts had undergone SCT in any treatment line. Baseline characteristics in the prospective phase by starting line are shown in the Table. As expected, there was a higher proportion of younger pts (≤65 yrs) in the SCT vs non-SCT group across all treatment lines, and in both groups a higher proportion of pts in 4th + vs earlier lines with ISS stage III disease. While cytogenetics were evaluated in a small number of pts overall (670/2358 [28%]), these assessments were performed significantly more frequently in SCT vs non-SCT pts (p<0.0001). In 380 prospective 1st line (L1) SCT pts, 299 (79%) underwent SCT-based treatment in L1; induction was with a bortezomib (btz)-based combination in 83% (47% btz without immunomodulatory drug [IMiD]; 36% btz + IMiD), IMiD in 11%, and other (ie. no btz/IMiD) in 6%. In 81 SCT pts who received non-SCT-based treatment in L1 (21%), 36% received btz without IMiD, 40% other, and 17% IMiD-based combinations. In 345 pts receiving L2, most frequent therapies were btz without IMiD (45% of pts), IMiD without btz (30%), other (13%), and btz + IMiD (12%); non-btz/IMiD combinations were increasingly prevalent in pts receiving L3 or L4 (24% and 40%, respectively). In the non-SCT population, 58% of pts received a btz-based combination in L1, most frequently btz without IMiDs (54%). In pts receiving L2, btz or IMID were equally represented (39%); in L3, non-SCT pts were most likely to receive other therapies (39%) versus 27% btz without IMiD and 32% IMiD without btz. Based on preliminary data, mean EQ5D score at baseline was 0.316 (range -0.594, 0.731) in the overall pt population, which increased slightly to 0.410 (-0.429, 0.731) at 12 mos and was largely comparable between countries. Resource utilization (hospitalization, ICU, ER visit, outpatient visit, full-time care) appeared highest in Germany (67.6 records per pt) and lowest in Croatia (7.5 per pt), with those in Germany spending a mean of 12.1 days in hospital per stay. Efficacy/safety data will be presented at the meeting. Conclusion This large, real-world, observational study provides for the first time a comprehensive picture of the baseline characteristics and therapy of MM pts treated in Europe, the Middle-East, and Africa. These data provide a framework towards the design of future protocols aiming to improve outcomes in MM. Table. Baseline characteristics by starting line Non-SCT pts SCT pts L1 (n=897) L2 (n=319) L3 (n=184) L4+ (n=166) Total* (N=1566) L1 (n=378) L2 (n=161) L3 (n=107) L4+ (n=120) Total* (N=775) Age ≤65 yrs, % 36 34 35 39 36 87 76 72 71 80 ISS Stage II/III, % 36/44 34/47 43/38 22/52 35/44 33/35 44/27 34/26 23/48 34/34 Salmon-Durie Stage 2/3, % 28/64 25/66 24/71 29/62 27/65 22/68 25/67 20/65 11/81 20/69 Bone lesion history, % 64 72 75 70 68 66 74 77 80 71 Cytogenetics assessed, % 24 19 19 14 21 51 35 43 33 44 Del 17p 8 8 9 13 8 10 7 4 13 9 t(4,14) 6 7 9 4 6 7 14 13 8 9 ISS, International staging system; L, line *17 non-SCT and 9 SCT pts were enrolled but did not receive a line of therapy within 75 days of baseline Disclosures Mohty: Celgene: Honoraria; Janssen: Honoraria. Terpos:Amgen: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Mateos:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Array BioPharma: Consultancy; Onyx Pharmaceuticals: Consultancy; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Genmab A/S: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy; Sanofi Aventis: Consultancy. Lejniece:Amgen: Honoraria; Sandoz: Honoraria. Beksac:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dimopoulos:Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Onyx: Honoraria; Celgene: Honoraria; Genesis Pharma: Research Funding. De Stefano:Shire: Speakers Bureau; Roche: Research Funding; Bruno Farmaceutici: Research Funding; Janssen Cilag: Research Funding; Amgen: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Celgene: Speakers Bureau. Salwender:Celgene: Honoraria; Janssen Cilag: Honoraria; Bristol Meyer Sqibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Pečeliūnas:Johnson & Johnson: Honoraria, Research Funding. Willenbacher:CTI: Consultancy, Other: Travel, Accommodations, Expenses; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Amgen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. Da Silva:Janssen Pharmaceuticals: Research Funding. Louw:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Nemet:Sanofi: Honoraria; Pliva: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Potamianou:Janssen: Employment. Couturier:Janssen-Cilag: Employment. Olie:Johnson & Johnson: Equity Ownership; Janssen-Cilag: Employment. Feys:Janssen Pharmaceutica N.V.: Employment, Equity Ownership. Thoret-Bauchet:Janssen-Cilag: Employment.
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Bernsen, Sidney, John Zudans, Thomas Vogan, Tom Ruggiero, and Aaron Kureck. "A Group Effort that Grew." Mechanical Engineering 136, no. 05 (May 1, 2014): 42–45. http://dx.doi.org/10.1115/1.2014-may-3.
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This article discusses why it is essential to develop new codes and standards for nuclear power industry. The reason for developing new codes for nuclear power sector is simple to understand. It has to do with the fundamental purpose of all standards: Standards exist to serve not only all the stakeholders in an industry – manufacturers, regulators, insurers, operators of equipment, but also the members of the general public who happen to be in the neighborhood. Standards support prosperity and, more important than that, they maintain public safety. Presently, different committees are working on the next generation of their standards in the nuclear power sector. They are incorporating recent experience and integrating new technologies, from materials to theoretical tools. The ASME/ANS Nuclear Risk Management Committee is currently expanding the scope of the standard to cover risk at shutdown and include long-term maintenance of containment and releases to the public after an accident. In addition, requirements for advanced reactors and the lessons learned from the Fukushima accident are under development.
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Ip, Andrew, Michael C. Churnetski, Oscar Calzada, Andres Chang, Yuan Liu, Nassoma Bumpers, Deborah Leeson, et al. "The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study." Blood 132, Supplement 1 (November 29, 2018): 5911. http://dx.doi.org/10.1182/blood-2018-99-119757.
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Abstract Background: Based on cohort studies and a limited number of prospective studies, physical activity (PA) can improve quality of life (QoL) in non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and patients (pts) undergoing autologous stem cell transplant (ASCT). There are also data to suggest that survival (Pophali et al, ASH 2017) is improved with increased PA in NHL pts. After ASCT, it is known that QoL and physical function will decrease. PA has been linked to improved QoL outcomes for pts undergoing ASCT. Recently, evidence shows fitness trackers can help monitor and improve adherence to PA in cancer pts. We aim to study the feasibility of a PA intervention in NHL/MM patients undergoing ASCT and to assess the use of smart watches in this setting to monitor PA. Methods: We included MM and NHL pts undergoing ASCT. Key inclusion criteria included ECOG < 2 and ability to complete a 6 minute walk test (6MWT). Pts were asked to adhere to a PA program of 150 minutes a week on a stationary bicycle or by walking, recording data in a diary and by wearing a smart watch provided to them. Data were collected from date of hospitalization to discharge, with research staff checking on pts at least twice a week to ensure adequate data collection and adherence. Feasibility of the intervention was assessed by average weekly minutes of PA performed by self-report. Validation of moderate intensity PA was attempted by heart rate (HR) monitoring (goal 40% of HR reserve) by the smart watch. QoL was assessed from FACT-lymphoma and FACT-MM surveys prior to transplant and around day 30 post ASCT. Clinical outcomes measured include time to neutrophil engraftment (≥0.5 10E3/mcL) and physical function (6MWT). Survey scores and 6MWT distances were compared using Wilcoxson rank sum tests. Historical controls at Emory matched for age, disease status, conditioning, stem cells infused, and use of stimulating factor were used to compare median time to neutrophil engraftment. Results: Since April 2018, 10 pts have enrolled and completed the PA intervention. Median age was 62, 70% were males, 40% had NHL, 50% were African American, and 50% were Caucasian. All pts were chemotherapy sensitive at time of transplant. Conditioning regimens included BEAM (30%), Melphalan (60%) and Busulfan/cyclophosphamide/etoposide (10%). Granulocyte colony stimulating factor was used in 60% of pts. Median follow up was 22 days. Six of 9 (67%) patients were able to adhere to a PA regimen while hospitalized by self-report, with one patient having incomplete PA data. Eight of ten patients wore their watch regularly for HR analysis. Six of these eight patients (75%) consistently reached HR goal during their PA. Of the 6 patients who met PA goal by self-report, 4 (67%) consistently met HR goals during PA (sample data, figure 1). QoL scores measured by FACT-lymphoma and FACT-MM showed no significant decrease in total score from pre-intervention to post-discharge follow up (median score difference -2.5 points, p-value=0.72, table 1). Individual sections of FACT surveys showed no significant differences except emotional well-being (median score difference, -3 points, p=0.008, table 1). Physical function by 6MWT decreased by a median of 97 meters (pre-test median of 435 meters, post-test median of 333.5 meters, p-value=0.016, table 1). Compared to 20 historical controls, median time to engraftment was similar (12 days vs 12.5 days). Conclusion: Our findings support the feasibility of studying an inpatient PA intervention for ASCT pts using traditional and novel methods. Nearly 70% of pts who participated were successful in adhering to a PA regimen of 150 minutes of exercise. Ongoing assessment by research staff to encourage pts to adhere to prescribed exercise, as well as use of a smart watch to validate PA by HR data was feasible. QoL results are consistent with prior PA studies in ASCT pts, with no significant decrease in overall QoL by day +30. Additional analyses from this study, including a flow-based panel to measure the impact of PA on immune reconstitution post ASCT, will be presented at the meeting. We plan to utilize the findings from this feasibility study to construct a randomized study of PA in ASCT assessing QoL as a primary outcome. Disclosures Calzada: Seattle Genetics: Research Funding. Nooka:Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hofmeister:Bristol-Myers Squibb: Research Funding; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Allen:Merck: Research Funding; Bayer: Consultancy. Kaufman:Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Janssen: Consultancy; BMS: Consultancy; Roche: Consultancy. Blum:Morphosys: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Lonial:Amgen: Research Funding. Waller:Cambium Medical Technologies: Consultancy, Equity Ownership; Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celldex: Research Funding; Kalytera: Consultancy. Flowers:Celgene: Research Funding; Millennium/Takeda: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Pharmacyclics/ Janssen: Consultancy; Eastern Cooperative Oncology Group: Research Funding; V Foundation: Research Funding; Denovo Biopharma: Consultancy; Spectrum: Consultancy; Abbvie: Consultancy, Research Funding; OptumRx: Consultancy; Abbvie: Research Funding; Gilead: Research Funding; Karyopharm: Consultancy; BeiGene: Research Funding; Bayer: Consultancy; Janssen Pharmaceutical: Research Funding; Gilead: Consultancy; Genentech/Roche: Research Funding; Pharmacyclics: Research Funding; National Cancer Institute: Research Funding; Burroughs Wellcome Fund: Research Funding; Genentech/Roche: Consultancy. Cohen:Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding.
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Qian, Wei, Jianying Zhou, Roberto Rosato, Jenny Chang, and Ann Anselme. "437 Adenovirus IL-12 and Docetaxel in Combination with Anti-PD1 as an Effective Treatment Strategy for TNBC." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A463. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0437.
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BackgroundIn 2020, over 42,000 women in the US are expected to die from Breast Cancer (BC). Triple Negative Breast Cancer (TNBC), a subtype defined by lack of estrogen receptor (ER), progesterone receptor (PR) and HER2 amplification, account for 15–20% of all BC. TNBC is more prevalent in pre-menopausal African-American and Hispanic women. Currently, chemotherapy is the standard of care for TNBC. Unfortunately, despise the high rate of initial response to neo-adjuvant chemotherapy, TNBC have higher rates of distant recurrence, and few (less than 30%) of the patients survive more than 5 years. Even though this subtype express high levels of PD-L1, the response to checkpoint inhibitor therapy have been modest. We hypothesized that the induction of cell death (Docetaxel) coupled with an immuno-activated milieu (locally injected adv.IL-12) would prime the tumor to respond to Anti-PD1 therapy. In this study, we investigated the effects of initially treating TNBC with a single dose of Docetaxel and adv.IL-12, followed by Anti-PD1 in syngeneic models.MethodsSyngeneic E0771 and 4T1 cell lines were injected in the mammary fat pad of C57BL/6, and Balb/c mice respectively. On day 0, mice in the Triple Combo group received a single dose (20 mg/kg) of Docetaxel and an intratumoral injection (1.25 × 109) of mAdv.IL-12 (a replication defective adenoviral vector containing mouse IL-12 cDNA under the transcriptional control of Rous sarcoma virus long terminal repeat) (provided by Dr. Chen), followed by IP injection Anti-PD1 (InVivoMab anti-mouse PD-1 CD279) on days 3,5,7,10,12, and 14. The other groups, received single therapy following the same procedure. On day 19, Tumor Infiltrating Lymphocytes (TILS) were isolated by Ficoll gradient and submitted for immuno-phenotyping by CyTOF analysis to the HMRI ImmunoMonitoring Core, in addition, tumor lysates were used to measure cytokine expression using Millipore Sigma’s Milliplex MAP Mouse Cytokine/Chemokine Magnetic Beads panel (cat: MCYTMAG-70K). Survival status over time, as well as tumor volume (measured every 3 days) were monitored in both models.ResultsTriple combination inhibited tumor growth in the 4T1 model while significantly delaying E0771 tumor progression. Triple Combo (TC) group had significantly higher number of TILS in both models, while the phenotype and cytokine expression significantly differed. In 4T1, TC increase the infiltration of both CD8 and CD4 effector cells, while significantly decreasing neutrophils. The levels of G-CSF, Rantes were significantly upregulated in this model, while pro-tumorigenic cytokines such as IL-6, LIF, IL-1b, and anti-inflammatory cytokines such as IL-9 and IL-10 were downregulated. In E0771, only effector, and IFN-g producing CD8 levels were increased in TC group. Although TC treated animals survived an average of 18 days more than single Doc treated animals, levels of IL-6, IL-1b, LIF, KC, TNFa and VEGF levels were higher at the end of the study.ConclusionsAd.IL-12 plus Docetaxel followed by Anti-PD1 therapy appears to only be beneficial to a specific subgroup of TNBC. We are actively studying the molecular difference between the two models used in this study, as well as investigating the clinical relevance of these markers using our extensive repertoire of PDXs in a humanized mice model.Ethics ApprovalThe study was approved by the Houston Methodist Research Hospital IACUC committee AUP: 0320-0023
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Chitimira, Howard. "Some Comments on the Enforcement Committee's Jurisdiction in the Adjudication and Settlement of Market Manipulation Cases: Pather and Another v Financial Services Board and Others [2014] 3 All SA 208 (GP)." Journal of African Law 62, no. 3 (September 10, 2018): 471–82. http://dx.doi.org/10.1017/s0021855318000190.
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AbstractThe article examines the court judgment in Pather and Another v Financial Services Board and Others [2014] 3 All SA 208 (GP) to explore the Enforcement Committee (EC)’s jurisdiction to settle market abuse cases in South Africa.
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Minta, Michael D. "Diversity and Minority Interest Group Advocacy in Congress." Political Research Quarterly 73, no. 1 (December 10, 2019): 208–20. http://dx.doi.org/10.1177/1065912919885024.
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This paper examines the role that racial and ethnic diversity plays in improving the legislative success of minority interest groups. Relying on campaign contributions and lobbying expenditures to explain minority interest groups’ influence on legislators’ behavior is not sufficient, because most minority organizations are public charities, or 501(c)(3) organizations, and as such are both banned by federal law from making candidate contributions and limited in how much they can spend on federal lobbying. I argue, however, that the inclusion of more blacks and Latinos on congressional committees enhances the lobbying influence—and thus the legislative success—of civil rights organizations in Congress. Using data from lobbying disclosure reports on bills supported by black American and Latino civil rights groups in the 110th Congress (2007–2008) and 111th Congress (2009–2010), as well as House markup data, I find that National Association for the Advancement of Colored People (NAACP), Leadership Conference on Civil and Human Rights (LCCR), and UnidosUS-supported bills referred to House committees with greater proportions of racial and ethnic minorities received more markups than did bills referred to House committees with less diversity. Diversity is significant in predicting committee attention even when accounting for possible confounding factors, including committee jurisdiction and the ideological composition of committee membership.
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Ismail and Salahuddin. "Contribution of School Committees in the Operation of Education in Junior High School 3 Sigli." Britain International of Linguistics Arts and Education (BIoLAE) Journal 2, no. 1 (March 20, 2020): 353–61. http://dx.doi.org/10.33258/biolae.v2i1.206.
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School committees are formed as advisory bodies (Advisory Agency) and also as supporting (supporting agencies) as well as controlling (controlling agency) in the context of educational transparency, as well as mediators between the government (executive) and the community in the education unit. Based on empirical data, the school committee of Junior High School 3 Sigli has not shown an optimal contribution in the administration of education, especially in the teaching and learning process. School committees contribute more dominantly when there is education assistance provided by the government. The purpose of this research is to analyze the contribution of the school committee as an educational consideration body, as an educational support body and to analyze the contribution of the school committee as an education control body at Junior High School 3 Sigli. The approach used in this research is qualitative, while data collection techniques are carried out through observation, interviews, focus group discussion (FGD) and documentation. The results showed that the contribution of the school committee as an educational consideration body at the Junior High School 3 Sigli had not gone perfectly, both with regard to planners, executors and managers. While the contribution of the school committee with regard to supporting bodies as government partners has also not gone well, because what is highlighted by the school committee is only when there is financial assistance. While the contribution of the school committee as a partner with the community and also a partner with the school is quite good, so is the contribution of the school committee as an education control body. The conclusion of the study shows that the contribution of Junior High School 3 Sigli committee can improve the quality of education, although it is related to the educational consideration body its contribution is not yet perfect, but with the contribution of the school committee as a support body and education control body, it has a positive impact on the smooth and comfortable teaching and learning process.
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Sharman, Jeff P., Anthony Mato, Neil E. Kay, Thomas J. Kipps, Nicole Lamanna, Mark Weiss, Chadi Nabhan, et al. "Demographics By Age Group (AG) and Line of Therapy (LOT) in Chronic Lymphocytic Leukemia (CLL) Patients (Pts) Treated in US Practices from the Connect® CLL Registry." Blood 124, no. 21 (December 6, 2014): 3338. http://dx.doi.org/10.1182/blood.v124.21.3338.3338.
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Abstract Introduction: CLL pts who qualify for participation in clinical trials are often thought of as a highly selected population. Therefore whether safety and efficacy data from these trials can be generalized to all CLL pts treated in the community setting is unknown. Prospective, observational studies can provide significant insight into pt and disease characteristics as well as practice patterns in different clinical settings. Here we report on baseline demographics and clinical characteristics for 1495 pts who participated in the Connect CLL observational study and were followed prospectively. Methods: Connect®CLL is a non study-specific intervention treatment registry which collects data on the management and outcomes of CLL pts in clinical, academic and community practices in the US. Clinical information was prospectively collected for pts treated in community (n=1312), academic (n=155), or government (n=28) centers in the US between March 2010 – Jan 2014. Pts eligible for treatment or on treatment not more than 2 months were eligible for enrollment. Here we report on the baseline demographics and clinical characteristics of a large CLL cohort stratified by AG, LOT and type of treatment center. Results: In total,1,495 pts were accrued with a median age at enrollment of 69 (range 22–99). Pts were Caucasian (92.2%), African American (6.9%), and male (63.7%). Median duration from diagnosis until initial therapy was 3.7 years (range 0-32). Age of enrolled pts was as follows; 527 pts age <65 years (AG1; 35%); 511 age 65–75 (AG2; 34%); and 457 age ≥75 (AG3; 31%) at the time of enrollment. Eight hundred and ninety-four pts (60%) were treated with front-line therapy (LOT1); 259 pts (17%) treated with second-line therapy (LOT2); and 342 pts (23%) treated beyond second-line therapy (LOT≥3). Patient age: Pt age was associated with significant variation in several clinical variables: Charlson comorbidity index (CCI) score ≥3 (AG 1-3 35/46/52%; p<0.0001), ECOG PS = 0 (AG1-3 60, 48, 33%, p<0.0001) and mean creatinine clearance (CrCl) decreased (AG 1-3 101/74/53 mL/min; p<0.0001). Line of therapy: Differences in baseline characteristics were observed between pts enrolled at LOT1 (previously untreated) and LOT2/≥3 (relapsed). Median age of pts accrued at LOT1 was 68 vs. 70 years for pts enrolled at LOT2/≥3 (p=0.007). ECOG PS = 0 was more frequent at LOT1 (50%) vs. LOT2/≥3 (42%) (p=0.0057). CCI ≥3 at LOT1 was 41% vs 48% at LOT2/≥3 (p=0.0072). When adjusted for differences in age, logistic regression also demonstrated significant differences in performance status (PS=0; p=0.02) and CCI (p=0.03) stratified by LOT. Treating institution: Baseline characteristics also differed by type of treating institution. Median age was 63 vs 70 at academic vs non-academic (p<0.0001). Pts treated at academic sites also had lower CCI (CCI≤2; 72.9% vs 54.2%, academic vs non-academic) and higher median CrCl (86.4 vs 71.4) (p=0.0017). In this registry, only 16% of patients under age 75 had CCI <= 2, CrCl >= 70 mL/min, ECOG 0-1; 18% of patients on LOT1 and 12% of pts on LOT=2 would satisfy these criteria. They represent 36% of eligible pts from academic treating institutions and 13% from community/government centers. Only 20% of patients on LOT1 would satisfy enrollment criteria for CLL8 (FCR vs. FC; Hallek; Lancet 2010) CLL 10 (BR vs FCR; NCT00769522). which did not have enrollment restrictions for age. Conclusions:Baseline characteristics of pts with CLL vary by age, LOT, and type of treatment center. In this large prospective observational study, our data confirms that older pts typically have a worse ECOG PS, more medical comorbidities, more advanced disease when initiating therapy and a lower probability of being treated at an academic medical center. Based on inclusion criteria used for entry in either CLL10 or CLL8, fewer than 20% of pts satisfy age, renal clearance, and fitness profile to be considered suitable for aggressive chemoimmunotherapy in the front line setting. This observation supports the notion that current clinical trial data might not always be applicable to the general CLL population seen in the community and argues for designing clinical trials that are more generalizable to the broader pt population. Disclosures Sharman: Gilead: Research Funding; Calistoga: Honoraria; Phamacyclics: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; TG therapeutics: Research Funding; Roche: Research Funding. Mato:Millennium: Speakers Bureau; Celgene: Speakers Bureau; Genentech: Speakers Bureau. Kay:Celgene: Research Funding. Kipps:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lamanna:Genentech-Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Weiss:Celgene: Consultancy; Phamacyclics: Consultancy; Gilead: Consultancy. Nabhan:Celgene: Honoraria, Research Funding. Flinn:Celgene: Research Funding. Grinblatt:Celgene: Honoraria, Speakers Bureau. Kozloff:Celgene: Consultancy. Farber:Alexion: Equity Ownership, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau; Janssen/Pharmacyclics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees. Sullivan:Celgene: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Flowers:TG Therapeutics: Research Funding; Phamacyclics: Research Funding; Acerta: Research Funding; Abbvie: Research Funding; Infinity: Research Funding; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Spectrum: Research Funding; Gilead: Research Funding; Genentech: Unpaid consultancy Other; Millennium: Research Funding, Unpaid consultancy, Unpaid consultancy Other; Seattle Genetics: Consultancy; Prescription Solutions: Consultancy; Celgene: Unpaid consultancy Other.
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Golding, Paul, and Lisa Facey-Shaw. "GraceKennedy Group: The new Chief Information Officer and IT Governance." Journal of Information Technology Teaching Cases 9, no. 2 (May 17, 2019): 44–57. http://dx.doi.org/10.1177/2043886919850034.
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Grace Kennedy Group was the fourth largest Jamaican company listed on the Jamaican Stock Exchange by market capitalization in 2016. The company operated in several market segments focusing mainly on foods and financial services industries. Geographically, GraceKennedy Group had a diversified revenue stream operating across the Caribbean, Central and North America, Europe and Africa. Diversification had led to a diverse set of Information Technology platforms to serve the needs of the various subsidiaries of GraceKennedy Group. With the emergence of new technological trends like big data, social and cloud computing, the Group’s Audit Committee in 2014 conducted a risk profile around the company’s IT governance structure. The Committee recommended a change in the decentralized model of IT governance and the hiring of a Chief Information Officer to inter alia, strategically using IT to create value and to coordinate system security. The Chief Information Officer position was externally advertised; however, after several interviews, the Chief Executive Officer decided to offer the position to Robert Sutherland the then general manager of one of its subsidiaries. Sutherland was a former chairman of the Business Technology (BizTech) Council which was established in 2006 to oversee the delivery of IT services within the group and to provide guidance to the business leadership on enterprise-wide related matters such as the strategic use of IT. The case focuses on the issues faced by a newly promoted Chief Information Officer, in an environment in which the Chief Executive Officer has articulated the need for a new, transformative, strategic and value creating vision for IT.
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Hemann, Brian A., Steven J. Durning, William F. Kelly, Ting Dong, Louis N. Pangaro, and Paul A. Hemmer. "Referral for Competency Committee Review for Poor Performance on the Internal Medicine Clerkship is Associated With Poor Performance in Internship." Military Medicine 180, suppl_4 (April 1, 2015): 71–76. http://dx.doi.org/10.7205/milmed-d-14-00575.
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ABSTRACT Purpose: To determine how students who are referred to a competency committee for concern over performance, and ultimately judged not to require remediation, perform during internship. Methods: Uniformed Services University of the Health Sciences' students who graduated between 2007 and 2011 were included in this study. We compared the performance during internship of three groups: students who were referred to the internal medicine competency committee for review who met passing criterion, students who were reviewed by the internal medicine competency committee who were determined not to have passed the clerkship and were prescribed remediation, and students who were never reviewed by this competency committee. Program Director survey results and United States Medical Licensing Examination (USMLE) Step 3 examination results were used as the outcomes of interest. Results: The overall survey response rate for this 5-year cohort was 81% (689/853). 102 students were referred to this competency committee for review. 63/102 students were reviewed by this competency committee, given passing grades in the internal medicine clerkship, and were not required to do additional remediation. 39/102 students were given less than passing grades by this competency committee and required to perform additional clinical work in the department of medicine to remediate their performance. 751 students were never presented to this competency committee. Compared to students who were never presented for review, the group of reviewed students who did not require remediation was 5.6 times more likely to receive low internship survey ratings in the realm of professionalism, 8.6 times more likely to receive low ratings in the domain of medical expertise, and had a higher rate of USMLE Step 3 failure (9.4% vs. 2.8%). When comparing the reviewed group to students who were reviewed and also required remediation, the only significant difference between groups regarding professionalism ratings with 50% of the group requiring remediation garnering low ratings compared to 18% of the reviewed group. Conclusions: Students who are referred to a committee for review following completion of their internal medicine clerkship are more likely to receive poor ratings in internship and fail USMLE Step 3 compared to students whose performance in the medicine clerkship does not trigger a committee review. These findings provide validity evidence for our competency committee review in that the students identified as requiring further clinical work had significantly higher rates of poor ratings in professionalism than students who were reviewed by the competency committee but not required to remediate. Additionally, students reviewed but not required to remediate were nonetheless at risk of low internship ratings, suggesting that these students might need some intervention prior to graduation.
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Stander, Melanie, Lee Alan Wallis, and Wayne Patrick Smith. "Hospital Disaster Planning in the Western Cape, South Africa." Prehospital and Disaster Medicine 26, no. 4 (August 2011): 283–88. http://dx.doi.org/10.1017/s1049023x11006571.
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AbstractIntroduction: The aim of this study was to describe the current state of disaster preparedness in hospitals in the public sector in the Western Cape, South Africa with the advent of the FIFA 2010 Soccer World Cup. The objectives included the completion of a self-reported assessment of readiness at all Western Cape public sector hospitals, to identify best practice and shortfalls in these facilities, as well as putting forward recommendations for improving disaster preparedness at these hospitals.Methods: The National Department of Health, as part of the planning for the FIFA 2010 World Cup, appointed an expert committee to coordinate improvements in disaster medicine throughout the country. This workgroup developed a Self Reported Hospital Assessment Questionnaire, which was sent to all hospitals across the country. Data only were collected from public hospitals in the Western Cape and entered onto a purpose-built database. Basic descriptive statistics were calculated. Ethical approval was obtained from the Health Sciences Faculty Research Committee of the University of Cape Town.Results: Twenty-seven of the 41 (68%) public hospitals provided completed data on disaster planning. The study was able to ascertain what infrastructure is available and what planning already has been implemented at these institutions.Recommendations: Most hospitals in the Western Cape have a disaster plan for their facility. Certain areas need more focus and attention; these include: (1) increasing collaborative partnerships; (2) improving HAZMAT response resources; (3) specific plans for vulnerable populations; (4) contingency plans for communication failure; (5) visitor, media and VIP dedicated areas and personnel; (6) evacuation and surge capacity plans; and (7) increased attention to training and disaster plan exercises.
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Olukoju, Ayodeji. "The Pressure Group Activity of Federated Chambers of Commerce: The Joint West Africa Committee and the Colonial Office, c. 1903–1955." African Economic History 46, no. 2 (2018): 93–116. http://dx.doi.org/10.1353/aeh.2018.0007.
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PERKINS, JAMES. "THE CONGO OF EUROPE: THE BALKANS AND EMPIRE IN EARLY TWENTIETH-CENTURY BRITISH POLITICAL CULTURE." Historical Journal 58, no. 2 (May 11, 2015): 565–87. http://dx.doi.org/10.1017/s0018246x14000260.
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AbstractThis article explores early twentieth-century British political and humanitarian engagement with the Balkans. It focuses on the Balkan Committee, a liberal pressure group that served as the main hub for British interest in the region in the decade before the First World War. Whilst drawing attention to the specific challenges presented by the Balkans to the British liberal mind, it is argued that the Balkan Committee was part of a wider movement of humanitarianism and political activism that encompassed both continental and colonial questions. The issues around which the committee campaigned are related to humanitarian protests against the use of forced labour in Africa, in particular the Congo Reform Association, as well as to the Persia Committee, formed in protest against the 1907 Anglo-Russian agreement. This approach highlights how ‘Europe’ and empire were interconnected agendas within an overarching liberal-internationalist worldview and reformist conscience, despite the different cultural lenses through which humanitarian questions in different parts of the globe were viewed. It is suggested that research into British interaction with the Balkans offers a fruitful means by which to integrate historical analysis of the continental and imperial aspects of Britain's external relations in the ‘age of empire’.
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Anderson, M. E., J. E. Almond, F. J. Evans, and J. A. Long. "Devonian (Emsian-Eifelian) fish from the Lower Bokkeveld Group (Ceres Subgroup), South Africa." Journal of African Earth Sciences 29, no. 1 (July 1999): 179–93. http://dx.doi.org/10.1016/s0899-5362(99)00088-3.
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Callaghan, C. C., P. G. Eriksson, and C. P. Snyman. "The sedimentology of the Waterberg Group in the Transvaal, South Africa: an overview." Journal of African Earth Sciences (and the Middle East) 13, no. 1 (January 1991): 121–39. http://dx.doi.org/10.1016/0899-5362(91)90047-3.
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