P-171: Multistate models provide complementary insights into outcomes for patients treated in the UK NCRI Myeloma XI randomised trial

IntroductionAn estimated 69 million traumatic brain injuries (TBI) occur each year worldwide, with most in low-income and middle-income countries. The CRASH-3 randomised trial found that intravenous administration of tranexamic acid within 3 hours of injury reduces head injury deaths in patients sustaining a mild or moderate TBI. We examined the cost-effectiveness of tranexamic acid treatment for TBI.MethodsA Markov decision model was developed to assess the cost-effectiveness of treatment with and without tranexamic acid, in addition to current practice. We modelled the decision in the UK and Pakistan from a health service perspective, over a lifetime time horizon. We used data from the CRASH-3 trial for the risk of death during the trial period (28 days) and patient quality of life, and data from the literature to estimate costs and long-term outcomes post-TBI. We present outcomes as quality-adjusted life years (QALYs) and 2018 costs in pounds for the UK, and US dollars for Pakistan. Incremental cost-effectiveness ratios (ICER) per QALY gained were estimated, and compared with country specific cost-effective thresholds. Deterministic and probabilistic sensitivity analyses were also performed.ResultsTranexamic acid was highly cost-effective for patients with mild TBI and intracranial bleeding or patients with moderate TBI, at £4288 per QALY in the UK, and US$24 per QALY in Pakistan. Tranexamic acid was 99% and 98% cost-effective at the cost-effectiveness thresholds for the UK and Pakistan, respectively, and remained cost-effective across all deterministic sensitivity analyses. Tranexamic acid was even more cost-effective with earlier treatment administration. The cost-effectiveness for those with severe TBI was uncertain.ConclusionEarly administration of tranexamic acid is highly cost-effective for patients with mild or moderate TBI in the UK and Pakistan, relative to the cost-effectiveness thresholds used. The estimated ICERs suggest treatment is likely to be cost-effective across all income settings globally.

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Low Dose Ara-C Versus Low Dose Ara-C and Arsenic Trioxide: the UK NCRI AML16 “Pick a Winner” Comparison.

Blood ◽

10.1182/blood.v114.22.486.486 ◽

2009 ◽

Vol 114 (22) ◽

pp. 486-486

Author(s):

Nigel H. Russell ◽

Robert K Hills ◽

Ann E. Hunter ◽

Donald Milligan ◽

William J. Kell ◽

...

Keyword(s):

High Risk ◽

Arsenic Trioxide ◽

Older Patients ◽

Low Dose ◽

Remission Rate ◽

Randomised Trial ◽

Age Distribution ◽

Significant Proportion ◽

The Uk

Abstract Abstract 486 A significant proportion of older patients with AML are not treated with conventional intensive chemotherapy [1] because they are unfit or not considered likely to benefit from an intensive treatment approach. Their outcomes are poor. Such patients have typically been treated with low-dose Ara-C (LDAC) or best supportive care (BSC) with hydroxyurea, and unrandomised studies of new agents have been used in this population. A recent randomised trial has shown that LDAC is superior to BSC in these patients [2]. Randomised trials are underway to assess the value of other novel treatments compared to LDAC. In an unrandomised phase 2 trial in 64 patients, Roboz et al found encouraging results using the combination of Arsenic Trioxide and LDAC. [3]. The UK NCRI AML16 trial is a programme of development which aims to test novel agents or combinations in untreated older patients with AML or high risk MDS (marrow blasts >10%) following a “pick a winner” design. The intention is to identify a “winner” which will produce a remission rate in excess of 30%, compared with 15-20% with LDAC. Using LDAC as the standard arm,the design allows unpromising treatments to be identified early (typically after 50 patients per arm), so that only those arms which show promise will continue to a trial with OS and DFS as endpoints. We report our experience of LD Ara-C (20mg bd days 1-10 for 4 courses) versus LDAC combined with Arsenic Trioxide (ATO, 0.25 mg/kg d1-5, d9, d11 for 4 courses at 6-8 week intervals). Patient Details: Between December 2006 and until its conclusion in May 2009, 166 patients were randomised, 84 to LDAC plus ATO, 82 to LDAC. The median age was 74 years; 80% of patients were aged over 70 years, 62% were male. There were no differences between the treatment arms with respect to age distribution, gender, performance status, de novo/secondary AML, high risk MDS, presenting WBC or cytogenetic risk group. Follow-up is complete to 1st January 2009, with median follow up for survivors of 8 months (range 0.1-17), at which point 122 patients had been recruited, and there were a total of 60 deaths (LDAC n=25; LDAC+ ATO, n=35). CR status is known on 113 patients. Overall, 24 patients have entered CR/CRi (LDAC n=13, LDAC+ATO n=11) with 8 relapses (2 vs 6; 1 vs 3 patients have died following relapse). The causes of death (60) were:- The DMEC recommended closure of the LDAC + ATO arm of the trial because follow-up data on the first 50 patients per arm showed that ATO had failed to provide the 2.5% improvement in CR/CRi required for continued recruitment and that the required improvement in remission was unlikely with LDAC + ATO. Conclusions: While ATO has a definite role in treating patients with APL, and may be of benefit in combination with other drugs in AML, the combination of LDAC + ATO in this patient population was not beneficial. [1] Juliusson G et al. Blood 2009; 113: 4179—4187 [2] Burnett et al. Cancer 2007 109: 1114—1124 [3] Roboz Gail J et al. Cancer 2008;113(9):2504—11. Disclosures: Off Label Use: Arsenic Trioxide is not licensed in this indication.

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A Comparison of Single Dose Gemtuzumab Ozogamicin 3mg/m2 and 6mg/m2 Combined with Induction Chemotherapy in Younger Patients with AML: Data from the UK NCRI AML17 Trial

Blood ◽

10.1182/blood.v124.21.2308.2308 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2308-2308 ◽

Cited By ~ 1

Author(s):

Alan K Burnett ◽

Nigel Russell ◽

Robert K. Hills ◽

Jamie Cavenagh ◽

Jonathan Kell ◽

...

Keyword(s):

Overall Survival ◽

Single Dose ◽

Induction Chemotherapy ◽

De Novo ◽

Meta Analysis ◽

Randomised Trial ◽

Gemtuzumab Ozogamicin ◽

Platelet Recovery ◽

Grade 3 ◽

The Uk

Abstract On behalf of the UK NCRI AML Study Group. Gemtuzumab Ozogamicin (GO) was the first antibody directed chemotherapy in cancer, but has had a chequered development in AML. We recently completed an individual patient data meta-analysis (Hills et al Lancet Oncology 15 (9): 986-96, 2014) which confirmed, in an analysis of the 5 randomised trials in adults, that simultaneous administration with induction chemotherapy significantly improved survival by reducing relapse risk in favourable and intermediate risk groups, but not in patients with adverse risk. The analysis further suggested that a single dose of 3mg/m2 was as effective at preventing relapse as a 6mg/m2 dose, while having less toxicity, and therefore may be the optimal dose level. A question posed in the UK NCRI AML17 Trial was to directly compare 3mg/m2 with 6mg/m2 to ascertain whether efficacy or toxicity differences overall or within subgroups could be found. Between 06/2009 and 10/2011 788 patients were randomised: the median age was 50yrs (0-81, 29 <16yrs). 86% had de novo, 9% secondary disease and 5% MDS; 53% were male. 13% were favourable/ 69% intermediate, and 18% adverse cytogenetic risk; median presenting WBC was 9.2 (0.4-386); 18% had a FLT3 ITD and 28% had an NPM1c mutation. The associated chemotherapy was DA (3+10) (n=380) or ADE (10+3+5)(n=403); all children received ADE. GO was administered on day one of the induction chemotherapy. WBCs >30 could be cytoreduced with hydroxyurea or the GO delayed till day 4 of chemotherapy. Liver function biochemistry required to be <2XULN. Toxicity was defined as in NCICTC v.3. Results: Eighty-seven percent of patients entered CR/CRi with no difference between the arms overall or with in any demographic subgroup (3mg 89% vs 6mg 85%; OR 1.34 (0.88-2.04), p=0.17). The 30-day (3% vs 7%; OR 2.04 (1.10-3.80), p=0.02) and 60-day mortality (5% vs 9%; OR 1.99 (1.17-3.39), p=0.01) were both increased in the 6mg arm. There were 18 vs 36 deaths within 60 days: causes were infection (10 vs 11); infection+haemorrhage (0 vs 1); haemorrhage 3 vs 4; resistant disease 2 vs 6; veno-occlusive disease 0 vs 5; cardiac 1 vs 3; pulmonary 2 vs 1; renal 0 vs 3; multiple 0 vs 2.Relapse free survival at 3 years was 44% overall and 45% for 3mg and 42% for 6mg (OR 1.11 (0.91-1.35), p=0.3). Overall survival at 3 years was 52% and 53% for 3mg and 50% for 6mg (OR 1.12 (0.91-1.36), p=0.3). There was no difference in mortality after day 60. Allografts were given to 324 patients, 183 in CR1, but the distribution on numbers and transplant type was not different between the arms. Neither the 3mg or 6mg dose caused excess post- transplant toxicity. No subgroup showed any suggestion of response or survival benefit from the 6mg dose with the exception of a non-significant benefit for both response rate (test for heterogeneity p=0.02) and overall survival (test for heterogeneity p=0.04) in the adverse cytogenetics patients (n=133). When grade 3 or 4 toxicities are compared, ALT, creatinine and haematuria in course 1 (7% vs 17%; 1% vs 2%; 1% vs 2% respectively), were the only significant differences in courses 1 & 2. The requirement for red cell and platelet transfusions and days on antibiotics was increased in the 6mg patients in course 1, with slower platelet recovery in course 1. There were no significant grade 3 or 4 toxicity differences or supportive care required in course 2. Central assessment of VOD was confirmed as definite (n=17) or possible (n=5) in 22 of 395 (5.6%) patients on 6mg compared with 2 definite and 0 possible in 2 of 393 on the 3 mg arm (0.5%) (p<0.0001). Conclusion: Although both the 3mg and 6mg dose have provided benefit when combined with induction chemotherapy, in this large randomised trial we found no benefit in giving a single 6mg/m2 dose of GO when compared with 3mg/m2, with the possible exception of in the adverse risk patients who showed no evidence of benefit in the recent meta-analysis. Although the difference in toxicity was modest and VOD, although increased, uncommon, this experience suggests that future studies should focussing on optimising the schedule for GO at the 3mg/m2 dose, such as the fractionated approach developed by the French ALFA Group. Such studies are underway. (We are grateful to CRUK for research funding for this trials and to Pfizer for the provision of gemtuzumab ozogamicin) Disclosures Off Label Use: Gemtuzumab Ozogamicin for AML.

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The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial

The Lancet ◽

10.1016/s0140-6736(08)60348-7 ◽

2008 ◽

Vol 371 (9618) ◽

pp. 1098-1107 ◽

Cited By ~ 652

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Randomised Trial ◽

Breast Radiotherapy ◽

Start Trial ◽

The Uk

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A IMPORTÂNCIA DA ABORDAGEM SISTÊMICA NA ERGONOMIA PARA UM DESIGN FUNCIONAL

Proceedings Systems & Design 2017 ◽

10.4995/sd2017.2017.6648 ◽

2017 ◽

Author(s):

Eliete Auxiliadora Ourives ◽

Attilio Bolivar Ourives de Figueiredo ◽

Luiz Fernando Gonçalves de Figueiredo ◽

Milton Luiz Horn Vieira ◽

Isabel Cristina Victoria Moreira ◽

...

Keyword(s):

Rio De Janeiro ◽

Female Athletes ◽

Randomised Trial ◽

Sao Paulo ◽

Cluster Randomised Trial ◽

Breast Size ◽

São Paulo ◽

Porto Alegre ◽

The Uk ◽

Fitting In

RESUMO A abordagem sistêmica é um processo interdisciplinar, cujo princípio primordial é compreender a interdependência recíproca e relações de todas as áreas e da necessidade de sua integração, permitindo maior aproximação entre os seus limites de estudo. Nesse contexto o olhar sistêmico, da ergonomia, sobretudo no que se refere à segurança, ao conforto e à eficácia de uso, de funcionalidade e de operacionalidade dos objetos, considerando todos os produtos ou sistemas de produtos, como sistema de uso, desde os mais simples aos mais complexos ou sistêmicos, tem como objetivo adequá-los aos seres humanos, tendo em vista as atividades e tarefas exercidas por eles. No que se refere ao design funcional, os conhecimentos da ergonomia, nessa visão sistêmica, relativos à sua metodologia de projeto, são absolutamente necessários, e a sua aplicação aponta a melhor adequação dos produtos aos seus usuários. Como é o caso do vestuário feminino funcional, sobretudo no que se refere a proteção das mamas, que são peças convencionais que necessitam de um correto dimensionamento e especificação dos tecidos e de outros materiais. É um tipo de vestuário que apresenta funcionalidade diversa, como para a proteção física, o aumento do volume da mama, enchimento no bojo de pano, de água, de óleo, estruturado com arame, etc.; para amamentação (sutiã que se abre na frente, em parte ou totalmente); para o design inclusivo (pessoas com deficiência e mobilidade reduzida, no caso de mamas com prótese ou órtese) facilitando com fechamentos e aberturas colocadas em peças de roupas difíceis de manusear, roupas confortáveis e fáceis de vestir. São peças usadas por pessoas com biótipos e percentis antropométricos variáveis e com características corporais que mudam significativamente nas passagens para a adolescência, idade adulta e idosa. As mudanças corporais apresentam diferenças significativas em termos de volume das mamas, nas quais as soluções ergonômicas por uma abordagem sistêmicas que se evidencia mais para a complexidade de uso, são as mais necessárias em termos de atributos como, segurança, conforto, comodidade corporal, facilidade do vestir, funcionalidade, além da estética. Esta pesquisa, embora exploratória e descritiva, não isenta de desafios, tem por objetivo, por meio de dados e informações ergonômicas sistêmicas contribuir com o design funcional, de modo a oferecer subsídios para a confecção de roupas funcionais ou tecnologia vestível, com os atributos citados, respeitando a diversidade e inclusão das pessoas em todas as fases de sua vida, atendendo assim os princípios formais do design. Palavra-chave: Abordagem sistêmica, Ergonomia, Design funcional. REFERENCIAS AROS, Kammiri Corinaldesi. Elicitação do processo projetual do Núcleo de Abordagem Sistêmica do Design da Universidade Federal de Santa Catarina. Orientador: Luiz Fernando Gonçalves de Figueiredo – Florianópolis, SC, 2016. BERTALANFFY, Ludwig V. Teoria geral dos sistemas: fundamentos, desenvolvimento e aplicações. 3. ed. Petrópolis, RJ: Vozes, 2008. BEST, Kathryn. Fundamentos de gestão do design. Porto Alegre: Bookman, 2012. 208 p. CHIAVENATO, I. Gestão de pessoas. 3ª ed. Rio de Janeiro: Elsevier, 2010. CORRÊA, Vanderlei Moraes; BOLETTI, Rosane Rosner. Ergonomia: fundamentos e aplicações. Bookman Editora, 2015.MERINO, Eugenio. Fundamentos da ergonomia. 2011. Disponível em: <https://moodle.ufsc.br/pluginfile.php/2034406/mod_resource/content/1/Ergo_Fundamentos.pdf>. Acesso em: 24 Mar 2017. DIAS E. C. Condições de vida, trabalho, saúde e doença dos trabalhadores rurais no Brasil. In: Pinheiro TMM, organizador. Saúde do trabalhador rural –RENAST. Brasília: Ministério da Saúde; 2006.p. 1-27. GIL, A. C. Como elaborar projetos de pesquisa. 4. ed. São Paulo: Atlas, 2010. GOMES FILHO, J. Ergonomia do objeto: sistema técnico de leitura ergonômica. São Paulo: Escrituras Editora, 2003. GUIMARÃES, L. B. M. (ed). Ergonomia de Processo. Porto Alegre, v.2, PPGE/UFRGS, 2000. IIDA, I. Ergonomia: projeto e produção. 2ª ed rev. e ampl. – São Paulo: Edgard Blucher, 2005. MANZINI, Ezio. Design para inovação social e sustentabilidade: comunidades criativas, organizações colaborativas e novas redes projetuais. Rio de Janeiro: E-Papers, 2008, 104p. MARCONI, M. A.; Lakatos, E. M. Fundamentos de metodologia científica. São Paulo: Atlas, 2007. Pandarum, R., Yu, W., and Hunter, L., 2011. 3-D breast anthropometry of plus-sized women in South Africa. Ergonomics, 54(9), 866–875. McGhee, D.E., Steele, J.R., and Munro, B.J., 2008. Sports bra fitness. Wollongong (NSW): Breast Research Australia. McGhee, D.E., Steele, J.R., and Munro, B.J., 2010. Education improves bra knowledge and fit, and level of breast support in adolescent female athletes: a cluster-randomised trial. Journal of Physiotherapy, 56, 19–24. Pechter, E.A., 1998. A new method for determining bra size and predicting postaugmentation breast size. Plastic and Reconstructive Surgery, 102 (4), 1259–1265. RICHARDSON, R. J. Pesquisa social: métodos e técnicas. 3 ed. São Paulo: Atlas, 2008. RIO, R. P. DO; PIRES, L. Ergonomia: fundamentos da prática ergonômica, 3ª Ed., Editora LTr, 2001. SANTOS, N. ET AL. Antropotecnologia: A Ergonomia dos sistemas de Produção. Curitiba: Gênesis, 1997. VASCONCELLOS, Maria José Esteves de. Pensamento sistêmico: O novo paradigma da ciência. 10ª ed. Campinas, SP: Papirus, 2013. WEERDMEESTER, J. D. e B. Ergonomia Prática. São Paulo: Edgard Blucher, 2001. WHITE, J.; SCURR, J. Evaluation of professional bra fitting criteria for bra selection and fitting in the UK. Ergonomics, 1–8. 2012. WHITE, J.;SCURR, J.; SMITH, N. The effect of breast support on kinetics during overground running performance. Ergonomics, Taylor & Francis. 52 (4), 492–498. 2009.

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Randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain (TOPIC): a pilot study to assess feasibility of a large multicentre trial

BMJ Open ◽

10.1136/bmjopen-2018-023679 ◽

2019 ◽

Vol 9 (7) ◽

pp. e023679

Author(s):

Joyce Yeung ◽

Lee Middleton ◽

Kostas Tryposkiadis ◽

Amy Kerr ◽

Jane Daniels ◽

...

Keyword(s):

Pilot Study ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Randomised Trial ◽

Local Anaesthetics ◽

Chest Wall Resection ◽

Thoracic Epidural ◽

American Society ◽

Randomised Controlled ◽

The Uk

ObjectivesThoracotomy is considered one of the most painful surgical procedures. The incidence of chronic post-thoracotomy pain (CPTP) is up to 50%. Paravertebral blockade (PVB) may be superior to thoracic epidural blockade (TEB) in preventing CPTP. The specific objective of this pilot study was to assess the feasibility of conducting a larger trial to determine whether PVB at thoracotomy is more effective in reducing CPTP compared with TEB.DesignA randomised, parallel, external pilot study was conducted to assess whether a large randomised trial of TEB and PVB with CPTP as the primary outcome is feasible.SettingTwo adult thoracic centres in the UK.ParticipantsAll adult patients admitted for elective open thoracotomy. Participants were excluded if they were American Society of Anesthesiologists physical status IV or V; or if there is contraindication to local anaesthetics; infection near the proposed puncture site; coagulation/thoracic spine disorders; required chest wall resection or emergency thoracic surgery or had a previous thoracotomy.ResultsAll patients presenting for thoracotomy were screened over a 12-month period with 194 found to be eligible. Of these, 69 (36%) were randomised (95% CI 29% to 42%). Discounting five participants who died, 54 of 64 participants (84%) returned questionnaire booklets at 6 months. The number of participants indicating at least a moderate level of chest pain at 6 months was lower with PVB but with high levels of uncertainty (RR: 0.7; 95% CI 0.3 to 1.7 for worst pain; RR: 0.3; 95% CI 0.0 to 2.8 for average pain). There were no safety concerns.ConclusionsA large, multicentre randomised controlled trial of PVB versus TEB is feasible as it is possible to randomise and follow up participants with high fidelity. Pain scores were lower on average with PVB compared with TEB but a much larger trial is required to confirm this reliably.Trial registration numberISRCTN45041624

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