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1.
J Cancer Res Clin Oncol ; 146(5): 1321-1334, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32144533

RESUMO

PURPOSE: Uncertainty exists regarding comparative effectiveness of cetuximab versus bevacizumab in metastatic colorectal cancer (mCRC). We conducted a retrospective head-to-head multi-cohort study comparing clinical outcomes from both antibodies METHODS: Cohorts were defined by treatment line and subgroups by (K)RAS status and tumour sidedness. Among other outcomes, we estimated and compared response rates, progression-free (PFS) and overall survival (OS). RESULTS: Between January 2010 and April 2018, 311 patients were included. Except for (K)RAS mutation status, baseline characteristics were balanced across treatment groups. In the full analysis of first and second-line cohorts, PFS (first-line: HR = 0.85; 95% CI 0.64 to 1.13; P = 0.26; second-line: HR = 1.16; 95% CI 0.74 to 1.83; P = 0.51) and OS (first-line: HR = 0.83; 95% CI 0.61 to 1.15; P = 0.26; second-line: HR = 0.88; 95% CI 0.56 to 1.38; P = 0.58) were similar between bevacizumab and cetuximab arms. In subgroup analyses of first-line therapy, we found a survival difference favouring bevacizumab in right-sided tumours (PFS: HR = 0.52; 95% CI 0.29 to 0.93; P = 0.025; OS: HR = 0.60; 95% CI 0.32 to 1.12; P = 0.11), but not in left-sided (HR = 1.04; 95% CI 0.75 to 1.46; P = 0.81; OS: HR = 0.94; 95% CI 0.65 to 1.36; P = 0.74), or (K)RAS wild-type tumours (PFS: HR = 0.91; 95% CI 0.60 to 1.40; P = 0.67; OS: HR = 0.79; 95% CI 0.50 to 1.25; P = 0.31). Response rates were similar across treatment groups, except for the subgroup of patients bearing right-sided primaries, where bevacizumab performed substantially better. CONCLUSION: This study provides evidence suggesting bevacizumab and cetuximab lead to similar effectiveness outcomes in mCRC, except for right-sided tumours, where cetuximab seemed to show considerably poorer outcomes. Further research is needed to confirm these results.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Estudos de Coortes , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Retais/genética , Neoplasias Retais/patologia , Estudos Retrospectivos
2.
J Cancer Res Clin Oncol ; 145(7): 1719-1728, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037398

RESUMO

PURPOSE: Uncertainty exists regarding Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) of patients with metastatic colorectal cancer (mCRC) treated with cetuximab or bevacizumab. We conducted a prospective cohort study comparing PROs and HRQoL from both therapies. METHODS: We assessed PROs and HRQoL from patients treated with cetuximab or bevacizumab using QLQ-C30 and QLQ-CR29 questionnaires at three sequential time points, including baseline. Global Health Status (GHS), functional and symptom scales, and Overall Treatment Utility (derived from clinical and patient-reported outcomes) were compared for the two treatment strategies. RESULTS: Between January 2017 and April 2018, 44 patients were allocated to cetuximab (n = 19) or bevacizumab (n = 25). Except for RAS mutation status, patient baseline characteristics were generally well balanced across treatment groups. A higher proportion of patients experienced a deterioration in GHS (≥ 10%) in cetuximab arm - 53.8% (95% CI 25.1-80.8%) at 6 weeks and 66.7% (95% CI 29.9-92.5%) at 12 weeks-comparing to bevacizumab cohort: 18.2% (95% CI 5.2-40.3%) at 6 weeks and 12.5% (95% CI:1.6-38.3%) at 12 weeks. Treatment utility rates at 6 and 12 weeks were, respectively, 88.6% and 69.8% for bevacizumab, compared to 49% and 19.1% for cetuximab (p = 0.004), a difference confirmed in subset analyses. CONCLUSIONS: In patients with mCRC, cetuximab-containing regimens led to a progressive negative impact on PROs and global HRQoL, when compared to baseline and bevacizumab. Future research is needed to confirm these results. Our findings demonstrate the value of PROs when assessing comparative effectiveness of different treatment regimens.


Assuntos
Bevacizumab/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/efeitos adversos , Cetuximab/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
3.
Int J Epidemiol ; 47(4): 1255-1263, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860332

RESUMO

Background: The crude death rate (CDR) is one of the defining indicators of humanitarian emergencies. When data from vital registration systems are not available, it is common practice to estimate the CDR from household surveys with cluster-sampling design. However, sample sizes are often too small to compare mortality estimates to emergency thresholds, at least in a frequentist framework. Several authors have proposed Bayesian methods for health surveys in humanitarian crises. Here, we develop an approach specifically for mortality data and cluster-sampling surveys. Methods: We describe a Bayesian hierarchical Poisson-Gamma mixture model with generic (weakly informative) priors that could be used as default in absence of any specific prior knowledge, and compare Bayesian and frequentist CDR estimates using five different mortality datasets. We provide an interpretation of the Bayesian estimates in the context of an emergency threshold and demonstrate how to interpret parameters at the cluster level and ways in which informative priors can be introduced. Results: With the same set of weakly informative priors, Bayesian CDR estimates are equivalent to frequentist estimates, for all practical purposes. The probability that the CDR surpasses the emergency threshold can be derived directly from the posterior of the mean of the mixing distribution. All observation in the datasets contribute to the estimation of cluster-level estimates, through the hierarchical structure of the model. Conclusions: In a context of sparse data, Bayesian mortality assessments have advantages over frequentist ones already when using only weakly informative priors. More informative priors offer a formal and transparent way of combining new data with existing data and expert knowledge and can help to improve decision-making in humanitarian crises by complementing frequentist estimates.


Assuntos
Teorema de Bayes , Análise por Conglomerados , Técnicas de Apoio para a Decisão , Emergências , Mortalidade/tendências , Causas de Morte , Características da Família , Humanos , Inquéritos e Questionários
4.
Implement Sci ; 13(1): 32, 2018 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-29452582

RESUMO

BACKGROUND: Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages. METHODS: We used an over-lapping multi-staged process. We identified evidence-based, candidate delivery mechanisms-mainly audit and feedback, educational outreach and computerised prompts and reminders. We drew upon interviews with primary care professionals using the Theoretical Domains Framework to explore likely determinants of adherence to quality indicators. We linked determinants to candidate BCTs. With input from stakeholder panels, we prioritised likely determinants and intervention content prior to piloting the implementation packages. Our content analysis assessed the extent to which embedded BCTs could be identified within the packages and compared them across the delivery mechanisms and four quality indicators. RESULTS: Each implementation package included at least 27 out of 30 potentially applicable BCTs representing 15 of 16 BCT categories. Whilst 23 BCTs were shared across all four implementation packages (e.g. BCTs relating to feedback and comparing behaviour), some BCTs were unique to certain delivery mechanisms (e.g. 'graded tasks' and 'problem solving' for educational outreach). BCTs addressing the determinants 'environmental context' and 'social and professional roles' (e.g. 'restructuring the social and 'physical environment' and 'adding objects to the environment') were indicator specific. We found it challenging to operationalise BCTs targeting 'environmental context', 'social influences' and 'social and professional roles' within our chosen delivery mechanisms. CONCLUSION: We have demonstrated a transparent process for selecting, operationalising and verifying the BCT content in implementation packages adapted to target four quality indicators in primary care. There was considerable overlap in BCTs identified across the four indicators suggesting core BCTs can be embedded and verified within delivery mechanisms commonly available to primary care. Whilst feedback reports can include a wide range of BCTs, computerised prompts can deliver BCTs at the time of decision making, and educational outreach can allow for flexibility and individual tailoring in delivery.


Assuntos
Fibrilação Atrial/prevenção & controle , Terapia Comportamental/métodos , Diabetes Mellitus/prevenção & controle , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/métodos , Anticoagulantes/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Clínicos Gerais , Humanos , Prescrição Inadequada/prevenção & controle , Planejamento de Assistência ao Paciente
5.
Confl Health ; 10: 15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27441038

RESUMO

BACKGROUND: Complex humanitarian emergencies are characterised by a break-down of health systems. All-cause mortality increases and non-violent excess deaths (predominantly due to infectious diseases) have been shown to outnumber violent deaths even in exceptionally brutal conflicts. However, affected populations are very heterogeneous and refugees, internally displaced persons (IDPs) and resident (non-displaced) populations differ substantially in their access to health services. We aim to show how this translates into health outcomes by quantifying excess all-cause mortality in emergencies by displacement status. METHODS: As standard data sources on mortality only poorly represent these populations, we use data from CEDAT, a database established by aid agencies to share operational health data collected for planning, monitoring and evaluation of humanitarian aid. We obtained 1759 Crude Death Rate (CDR) estimates from emergency assessments conducted between 1998 and 2012. We define excess mortality as the ratio of CDR in emergency assessments over 'baseline CDR' (as reported in the World Development Indicators). These death rate ratios (DRR) are calculated separately for all emergency assessments and their distribution is analysed by displacement status using non-parametric statistics. RESULTS: We found significant excess mortality in IDPs (median DRR: 2.5; 95 % CI: [2.2, 2.93]) and residents (median DDR: 1.51; 95 % CI: [1.47, 1.58]). Mortality in refugees however is not significantly different from baseline mortality in the host countries (median DRR: 0.94, 95 % CI: [0.73, 1.1]). CONCLUSIONS: Aid agencies report the highest excess mortality rates among IDPs, followed by resident populations. In absolute terms however, due to their high share in the total number of people at risk, residents are likely to account for most of the excess deaths in today's emergencies. Further research is needed to clarify whether the low estimates of excess mortality in refugees are the result of successful humanitarian interventions or due to limitations of our methods and data.

6.
Age Ageing ; 45(5): 652-61, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27207749

RESUMO

BACKGROUND AND OBJECTIVES: delirium is a distressing but potentially preventable condition common in older people in long-term care. It is associated with increased morbidity, mortality, functional decline, hospitalization and significant healthcare costs. Multicomponent interventions, addressing delirium risk factors, have been shown to reduce delirium by one-third in hospitals. It is not known whether this approach is also effective in long-term care. In previous work, we designed a bespoke delirium prevention intervention, called 'Stop Delirium!' In preparation for a definitive trial of Stop Delirium, we sought to address key aspects of trial design for the particular circumstances of care homes. DESIGN: a cluster randomized feasibility study with an embedded process evaluation. SETTING AND PARTICIPANTS: residents of 14 care homes for older people in one metropolitan district in the UK. INTERVENTION: Stop Delirium!: a 16-month-enhanced educational package to support care home staff to address key delirium risk factors. Control homes received usual care. MEASUREMENTS: we collected data to determine the following: recruitment and attrition; delirium rates and variability between homes; feasibility of measuring delirium, resource use, quality of life, hospital admissions and falls; and intervention implementation and adherence. RESULTS: two-thirds (215) of eligible care home residents were recruited. One-month delirium prevalence was 4.0% in intervention and 7.1% in control homes. Proposed outcome measurements were feasible, although our approach appeared to underestimate delirium. Health economic evaluation was feasible using routinely collected data. CONCLUSION: a definitive trial of delirium prevention in long-term care is needed but will require some further design modifications and pilot work.


Assuntos
Delírio/prevenção & controle , Instituição de Longa Permanência para Idosos , Acidentes por Quedas/prevenção & controle , Acidentes por Quedas/estatística & dados numéricos , Idoso , Estudos de Viabilidade , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Pessoal de Saúde/educação , Instituição de Longa Permanência para Idosos/economia , Instituição de Longa Permanência para Idosos/organização & administração , Hospitalização/estatística & dados numéricos , Humanos , Assistência de Longa Duração/economia , Assistência de Longa Duração/métodos , Masculino , Qualidade de Vida , Fatores de Risco
7.
Implement Sci ; 11: 25, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26923369

RESUMO

BACKGROUND: There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice. METHODS/DESIGN: The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences. DISCUSSION: ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability. TRIAL REGISTRATION: ISRCTN91989345.


Assuntos
Pesquisa Biomédica/organização & administração , Medicina Baseada em Evidências , Medicina Geral , Avaliação de Programas e Projetos de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fibrilação Atrial/tratamento farmacológico , Biomarcadores , Análise por Conglomerados , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Padrões de Prática Médica , Atenção Primária à Saúde
8.
PLoS Med ; 12(10): e1001887, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26485006

RESUMO

In crisis situations, data are scarce-Peter Heudtlass and colleagues explore ways of best understanding the extra risk of death borne by forced migrants.


Assuntos
Teorema de Bayes , Mortalidade/tendências , Migrantes , Causas de Morte , Humanos , Iraque/epidemiologia , Sudão/epidemiologia , Populações Vulneráveis
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