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1.
Clin Oncol (R Coll Radiol) ; 35(12): e708-e719, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37741712

RESUMO

AIMS: To describe the prevalence of cardiovascular disease (CVD), multiple comorbidities and social deprivation in patients with a potentially curable cancer in 20 English Cancer Alliances. MATERIALS AND METHODS: This National Registry Dataset Analysis used national cancer registry data and CVD databases to describe rates of CVD, comorbidities and social deprivation in patients diagnosed with a potentially curable malignancy (stage I-III breast cancer, stage I-III colon cancer, stage I-III rectal cancer, stage I-III prostate cancer, stage I-IIIA non-small cell lung cancer, stage I-IV diffuse large B-cell lymphoma, stage I-IV Hodgkin lymphoma) between 2013 and 2018. Outcome measures included observation of CVD prevalence, other comorbidities (evaluated by the Charlson Comorbidity Index) and deprivation (using the Index of Multiple Deprivation) according to tumour site and allocation to Cancer Alliance. Patients were allocated to CVD prevalence tertiles (minimum: <33.3rd percentile; middle: 33.3rd to 66.6th percentile; maximum: >66.6th percentile). RESULTS: In total, 634 240 patients with a potentially curable malignancy were eligible. The total CVD prevalence for all cancer sites varied between 13.4% (CVD n = 2058; 95% confidence interval 12.8, 13.9) and 19.6% (CVD n = 7818; 95% confidence interval 19.2, 20.0) between Cancer Alliances. CVD prevalence showed regional variation both for male (16-26%) and female patients (8-16%) towards higher CVD prevalence in northern Cancer Alliances. Similar variation was observed for social deprivation, with the proportion of cancer patients being identified as most deprived varying between 3.3% and 32.2%, depending on Cancer Alliance. The variation between Cancer Alliance for total comorbidities was much smaller. CONCLUSION: Social deprivation, CVD and other comorbidities in patients with a potentially curable malignancy in England show significant regional variations, which may partly contribute to differences observed in treatments and outcomes.


Assuntos
Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Doenças Cardiovasculares , Neoplasias do Colo , Neoplasias Pulmonares , Neoplasias Retais , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Comorbidade , Inglaterra/epidemiologia , Doenças Cardiovasculares/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias do Colo/epidemiologia , Privação Social , Sistema de Registros
2.
Perspect Public Health ; 142(4): 213-223, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35801904

RESUMO

AIMS: This article seeks to make the case for a new approach to understanding and nurturing resilience as a foundation for effective place-based co-produced local action on social and health inequalities. METHODS: A narrative review of literature on community resilience from a public health perspective was conducted and a new concept of neighbourhood system resilience was developed. This then shaped the development of a practical programme of action research implemented in nine socio-economically disadvantaged neighbourhoods in North West England between 2014 and 2019. This Neighbourhood Resilience Programme (NRP) was evaluated using a mixed-method design comprising: (1) a longitudinal household survey, conducted in each of the Neighbourhoods For Learning (NFLs) and in nine comparator areas in two waves (2015/2016 and 2018/2019) and completed in each phase by approximately 3000 households; (2) reflexive journals kept by the academic team; and (3) semi-structured interviews on perceptions about the impacts of the programme with 41 participants in 2019. RESULTS: A difference-in-difference analysis of household survey data showed a statistically significant increase of 7.5% (95% confidence interval (CI), 1.6 to 13.5) in the percentage of residents reporting that they felt able to influence local decision-making in the NFLs relative to the residents in comparator areas, but no effect attributable to the NRP in other evaluative measures. The analysis of participant interviews identified beneficial impacts of the NRP in five resilience domains: social connectivity, cultural coherence, local decision-making, economic activity, and the local environment. CONCLUSION: Our findings support the need for a shift away from interventions that seek solely to enhance the resilience of lay communities to interventions that recognise resilience as a whole systems phenomenon. Systemic approaches to resilience can provide the underpinning foundation for effective co-produced local action on social and health inequalities, but they require intensive relational work by all participating system players.


Assuntos
Características de Residência , Determinantes Sociais da Saúde , Humanos , Saúde Pública , Fatores Socioeconômicos , Populações Vulneráveis
3.
Br J Surg ; 108(3): 315-325, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760065

RESUMO

BACKGROUND: Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy. METHODS: This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage. RESULTS: The study recruited 3416 women (median age 77 (range 69-102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains. CONCLUSION: Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/psicologia , Feminino , Humanos , Estudos Longitudinais , Mastectomia , Estudos Prospectivos , Receptores de Estrogênio/metabolismo
4.
Br J Surg ; 108(5): 499-510, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33760077

RESUMO

BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).


Assuntos
Neoplasias da Mama/terapia , Tomada de Decisões , Técnicas de Apoio para a Decisão , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Qualidade de Vida
5.
Br J Clin Pharmacol ; 85(10): 2369-2377, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31276603

RESUMO

AIMS: Bioequivalence (BE) trials aim to demonstrate that the 90% confidence interval of the T/R-ratio of the pharmacokinetic metrics between two formulations (test [T] and reference [R]) of a drug is fully included in the acceptance interval [0.80, 1.25]. Traditionally, the sample size of BE trials is based on a power calculation based on the intrasubject variability coefficient of variation (CV) and the T/R-ratio of the metrics. Since the exact value of the T/R-ratio is not known prior to the trial, it is often assumed that the difference between the treatments does not exceed 5%. Hence, uncertainty about the T/R-ratio is expressed by using a fixed value for the sample size calculation. We propose to characterise the uncertainty about the T/R-ratio by a (normal) distribution for the log(T/R-ratio), with an assumed mean of  log Î¸ = 0.00 (i.e. θ = 1.00) and a standard deviation σu , which quantifies the uncertainty. Evaluating this distribution leads to the statistical assurance of the BE trial. METHODS: The assurance of a clinical trial can be derived by integrating the power over the distribution of the input parameters, in this case, the assumed distribution of the log(T/R)-ratio. Because it is an average power, the assurance can be interpreted as a measure of the probability of success that does not depend on a specific assumed value for the log(T/R)-ratio. The relationship between power and assurance will be analysed by comparing the numerical outcomes. RESULTS: Using the assurance concept, values of the standard deviation for the distribution of potential log(T/R)-ratios can be chosen to reflect the magnitude of uncertainty. For most practical cases (i.e. when 0.95 ≤ Î¸ ≤ 1.05), the sample size is not, or only slightly, changed when σ = |log(θ)|. CONCLUSION: The advantage of deriving the assurance for BE trials is that uncertainty is directly expressed as a parameter of variability.


Assuntos
Ensaios Clínicos como Assunto/métodos , Modelos Estatísticos , Preparações Farmacêuticas/administração & dosagem , Projetos de Pesquisa , Humanos , Preparações Farmacêuticas/metabolismo , Farmacocinética , Probabilidade , Tamanho da Amostra , Equivalência Terapêutica , Incerteza
6.
Clin Oncol (R Coll Radiol) ; 31(7): 444-452, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31122807

RESUMO

AIMS: Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data. MATERIALS AND METHODS: Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation. RESULTS: In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67-0.81). DISCUSSION: Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida
7.
J Reconstr Microsurg ; 34(5): 376-382, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29625504

RESUMO

BACKGROUND: The omental flap is a reliable flap for the coverage of sternal defects. However, little is known about the predictors of mortality and the long-term outcome in such patients. METHODS: We, therefore, performed a retrospective study from 2002 to 2013, including all patients who underwent sternal reconstruction with the omental flap. RESULTS: A total of 50 patients were identified and mean follow-up was 3.8 years. Patient data was collected from the charts and 14 patients were available for telephone interviews. The majority of patients suffered from deep sternal wound infections. There was no complete flap loss and an overall success rate was 96%. In-hospital mortality was 14% and overall survival over follow-up was 50%. Significant predictors of mortality were age > 65, American Society of Anesthesiologists' status, defect size, prolonged ventilation, and the need for tracheotomy. Postoperative quality of life was reduced compared with other cohorts, especially with regard to bodily function. Pain was also a major problem for most patients along with herniation. CONCLUSION: The omental flap is a safe option even in patients with severe comorbidities. However, based on the data in this study, we would recommend the omental flap as a reserve option rather than first-line treatment for sternal defects.


Assuntos
Omento/transplante , Procedimentos de Cirurgia Plástica/métodos , Qualidade de Vida , Esternotomia/efeitos adversos , Retalhos Cirúrgicos/transplante , Infecção da Ferida Cirúrgica/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Omento/cirurgia , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Esternotomia/métodos , Infecção da Ferida Cirúrgica/mortalidade , Infecção da Ferida Cirúrgica/fisiopatologia , Taxa de Sobrevida , Resultado do Tratamento
8.
Ann Oncol ; 29(1): 145-153, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29045530

RESUMO

Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to the first-line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and methods: Eighty-three patients on the first-line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples before progression to study the evolution of mutations on therapy. The frequency of novel mutations was validated in an independent cohort of available baseline plasma samples in the Study of Faslodex versus Exemestane with or without Arimidex (SoFEA) trial, which enrolled patients with prior sensitivity to AI. Results: Of the 39 patients who progressed on the first-line AI, 56.4% (22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9% (9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95% confidence interval 3.7-NA) before clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2% (13/18) patients. Mutations in RAS genes were identified in 15.4% (6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2% (24/113) patients although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival. Conclusions: Cancers progressing on the first-line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , DNA Tumoral Circulante/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , DNA Tumoral Circulante/sangue , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética
9.
Br J Cancer ; 117(7): 925-931, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28797032

RESUMO

BACKGROUND: One-third of new early breast cancer diagnoses occur in women over 70 years old. However, older women are less likely to receive radical curative treatments. This study prospectively evaluated a cohort of older women using a Comprehensive Geriatric Assessment (CGA) to determine whether fitness explained the apparent under-treatment in this patient group. METHODS: In this multi-centre prospective study, patients aged ⩾70 years with Stages I-III breast cancer underwent a pretreatment baseline CGA consisting of eight assessment tools. Patients were defined as 'fit' if they had normal score in seven out of eight of the assessment tools. 'High risk' patients were defined as those with grade 3, ER negative, HER2 positive, or node positive breast cancer. RESULTS: Data on 326 patients were available for full analysis. The median age was 77 years. In all, 182 (56%) of the total population were defined as high risk, with 49%, 61% and 53% of those in the 70-74, 75-84 and ⩾85 years age groups respectively having high risk tumours. A total of 301 patients had sufficient CGA records of whom 131 (44%) were reported as fit, with 34%, 54% and 12% of them in the 70-74, 75-84 and ⩾85 years age groups respectively. More fit than unfit patients underwent primary breast surgery (100% vs 91%, P=0.0002), axillary surgery (92% vs 84%, P=0.0340), and adjuvant chemotherapy for high-risk disease (51% vs 20%, P=0.0001). Rates of adjuvant radiotherapy after wide local excision were not significantly different (88% vs 90% respectively, P=0.8195). CONCLUSIONS: In this study, all women ⩾70 years deemed fit by CGA underwent primary surgery. Nearly 50% of fit women with high-risk disease did not receive adjuvant chemotherapy suggesting under treatment in this group.


Assuntos
Neoplasias da Mama/terapia , Quimioterapia Adjuvante/estatística & dados numéricos , Avaliação Geriátrica , Mastectomia/estatística & dados numéricos , Radioterapia Adjuvante/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Feminino , Mau Uso de Serviços de Saúde , Humanos , Metástase Linfática , Estudos Prospectivos , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Medição de Risco
10.
Clin Oncol (R Coll Radiol) ; 29(9): 609-616, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28592379

RESUMO

AIMS: Treatment decisions for men aged 70 years or over with localised prostate cancer need to take into account the risk of death from competing causes and fitness for the proposed treatment. Objective assessments such as those included in a comprehensive geriatric assessment (CGA) might help to inform the decision-making process. The aim of this study was to describe the CGA scores of a cohort of older men with prostate cancer, evaluate potential screening tools in this population and assess whether any CGA component predicts significant acute radiotherapy toxicity. MATERIALS AND METHODS: This was a prospective cohort study undertaking pretreatment CGA, Vulnerable Elders Survey (VES-13) and G8 assessment in patients aged 70 years and over with localised prostate cancer planned to undergo radical external beam radiotherapy. RESULTS: In total, 178 participants were recruited over a 3 year period and underwent a CGA. Fifty-five (30.1%) participants were defined as having health needs identified by their CGA. Both VES-13 and G8 screening tools showed a statistically significant association with CGA needs (P < 0.001 and X2 = 15.02, P < 0.001, respectively), but their sensitivity was disappointing. There was no association between a CGA (or its components) and significant acute radiotherapy toxicity. CONCLUSIONS: Many older men with localised prostate cancer are vulnerable according to a CGA. The screening tools evaluated were not sufficiently sensitive to identify this group. CGA outcome does not predict for significant acute radiotherapy toxicity.


Assuntos
Avaliação Geriátrica/métodos , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/patologia , Inquéritos e Questionários
12.
Breast ; 30: 13-18, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27569021

RESUMO

OBJECTIVES: To determine the incidence and risk factors for thromboembolic events (TE) and febrile neutropenia (FN) in patients receiving systemic chemotherapy for early breast cancer (EBC). METHODS: 325 patients received FEC75, FEC100-T or ECaP for EBC in 2013. RESULTS: TE occurred in 7.4% and FN in 19.1% of patients. Risk factors for TE were: central venous catheter (p = 0.011). Risk factors for FN were: FEC100-T treatment versus FEC75 and ECaP (p ≤ 0.001); lower pre-treatment neutrophil count (p = 0.009) and poorer performance status (p = 0.012). Two patients died from treatment-related toxicities. CONCLUSION: In real-world experience, the majority of patients completed adequate treatment, despite significant complications.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Embolia Pulmonar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/administração & dosagem , Docetaxel , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Incidência , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Biópsia de Linfonodo Sentinela , Taxoides/administração & dosagem , Tromboembolia/epidemiologia
13.
Clin Oncol (R Coll Radiol) ; 28(9): 597-603, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26936608

RESUMO

AIMS: Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. MATERIALS AND METHODS: In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. RESULTS: In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). CONCLUSION: In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped.


Assuntos
Neoplasias da Mama/radioterapia , Neutropenia Febril/epidemiologia , Obesidade/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Índice de Massa Corporal , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/efeitos adversos , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Dosagem Radioterapêutica , Estudos Retrospectivos
14.
Open Heart ; 3(1): e000344, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26977309

RESUMO

INTRODUCTION: It has been suggested that removal of proinflammatory substances that accumulate in stored donor red cells by mechanical cell washing may attenuate inflammation and organ injury in transfused cardiac surgery patients. This trial will test the hypotheses that the severity of the postoperative inflammatory response will be less and postoperative recovery faster if patients undergoing cardiac surgery receive washed red cells compared with standard care (unwashed red cells). METHODS AND ANALYSIS: Adult (≥16 years) cardiac surgery patients identified at being at increased risk for receiving large volume red cell transfusions at 1 of 3 UK cardiac centres will be randomly allocated in a 1:1 ratio to either red cell washing or standard care. The primary outcome is serum interleukin-8 measured at 5 postsurgery time points up to 96 h. Secondary outcomes will include measures of inflammation, organ injury and volumes of blood transfused and cost-effectiveness. Allocation concealment, internet-based randomisation stratified by operation type and recruiting centre, and blinding of outcome assessors will reduce the risk of bias. The trial will test the superiority of red cell washing versus standard care. A sample size of 170 patients was chosen in order to detect a small-to-moderate target difference, with 80% power and 5% significance (2-tailed). ETHICS AND DISSEMINATION: The trial protocol was approved by a UK ethics committee (reference 12/EM/0475). The trial findings will be disseminated in scientific journals and meetings. TRIAL REGISTRATION NUMBER: ISRCTN 27076315.

15.
Br J Cancer ; 114(3): 262-8, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26757260

RESUMO

BACKGROUND: This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients. METHODS: Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity and clinical outcome data were compared between patients aged below and above 65 years of age. RESULTS: One thousand and four patients were treated in 30 Phase I trials, with 315 (31%) patients aged 65 years and older. Grade 3-5 toxicities (22.8% vs 24.8% (P=0.52)), trial discontinuation (6% vs 4%; P=0.33), and dose interruptions (8.0% vs 8.0% (P=0.96)) were observed at similar rates in patients below and above 65 years of age, respectively. The overall response rate 5.2% vs 4.1%, progression-free survival (PFS) 1.9 vs 3.5 months and clinical benefit rate (CBR) at 6 months 15.2% vs 14.3% were comparable in both groups. To avoid bias due to the potential therapeutic benefit of abiraterone, comparisons were repeated excluding prostate cancer patients with similar results (ORR 4.6% vs 4%, PFS 1.8 vs 3.0 months, CBR at 6 months 13.5% vs 9.5%). Multivariate analysis indicated that the previously identified RMH score (including albumin and lactate dehydrogenase levels) was an accurate predictor of outcome. CONCLUSIONS: Phase I clinical trials should be considered in patients with advanced cancers regardless of age, as older patients who enter these have similar safety and efficacy outcomes as their younger counterparts. The RMH prognostic score can assist in the selection of suitable older patients.


Assuntos
Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase I como Assunto , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Comorbidade , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/epidemiologia , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
16.
Burns ; 42(2): 375-83, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26777455

RESUMO

OBJECTIVE: Despite dramatic improvements in burn care, the major part of the therapy of thermal injuries remains symptomatical in nature. A targeted approach to accelerate angiogenesis and woundhealing and reduce edema formation remains to be found. We therefore aimed to investigate the impact of anti-inflammatory, anti-coagulative and thrombolytic agents on microcirculation after thermal injuries on the mentioned parameters. METHODS: Full thickness burns were inflicted on the ears of hairless mice (n=48). The effects of five intraperitoneal injections of either recombinant tissue plasminogen activator (rtPA), selenium, prednisolone or sodium chloride on microcirculation, edema formation, leukocytes and angiogenesis were investigated over a 13 day period using intravital fluorescent microscopy. RESULTS: Prednisolone slightly improved angiogenesis (100.0% day 0 vs. 91.4% non-perfused area on day 1 post burn, p<0.05) and reduced edema formation (93.3% vs. 123.1% control on day 3, p<0.05). The rtPA-group showed the highest number of sticking leukocytes up to day 7 post burn (233%, 265%, 254% on days 1, 3, and 7, p<0.05 compared to baseline). A post-traumatic expansion of the non perfused area could only be observed in the selenium group (100.0% day 0, 103.1% day 1 post burn). In addition, selenium caused an increase of rolling leukocytes over the complete observation time. CONCLUSION: The often described positive influences of selenium for the treatment of burn patients could not be confirmed, on the contrary we found a post-traumatic expansion of the non perfused area and an increase of leukocytes in this group. The expectations to rtPA did not fulfill. Prednisolone improved angiogenesis and reduced the edema formation, both Parameters are essential for wound healing and survival of burned patients.


Assuntos
Antioxidantes/farmacologia , Queimaduras/patologia , Fibrinolíticos/farmacologia , Glucocorticoides/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Prednisolona/farmacologia , Selênio/farmacologia , Ativador de Plasminogênio Tecidual/farmacologia , Animais , Queimaduras/diagnóstico por imagem , Orelha , Edema/diagnóstico por imagem , Edema/patologia , Microscopia Intravital , Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Pelados , Microcirculação/efeitos dos fármacos , Microscopia de Fluorescência , Proteínas Recombinantes , Pele/diagnóstico por imagem , Pele/patologia
17.
Urologe A ; 55(4): 484-8, 2016 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-26649739

RESUMO

BACKGROUND: Fournier's gangrene is a variant of the necrotizing fasciitis restricted to the perineal and genital region. It presents as an acute life-threatening disease and demands rapid surgical debridement, resulting in large soft tissue defects. Various reconstructive methods have to be applied to reconstitute functionality and aesthetics. The objective of this work is to identify different reconstructive methods in the literature and compare them to our current concepts for reconstructing defects caused by Fournier gangrene. METHODS: Analysis of the current literature and our reconstructive methods on Fournier gangrene. RESULTS: The Fournier gangrene is an emergency requiring rapid, calculated antibiotic treatment and radical surgical debridement. After the acute phase of the disease, appropriate reconstructive methods are indicated. The planning of the reconstruction of the defect depends on many factors, especially functional and aesthetic demands. Scrotal reconstruction requires a higher aesthetic and functional reconstructive degree than perineal cutaneous wounds. In general, thorough wound hygiene, proper pre-operative planning, and careful consideration of the patient's demands are essential for successful reconstruction. CONCLUSIONS: In the literature, various methods for reconstruction after Fournier gangrene are described. Reconstruction with a flap is required for a good functional result in complex regions as the scrotum and penis, while cutaneous wounds can be managed through skin grafting. Patient compliance and tissue demand are crucial factors in the decision-making process.


Assuntos
Desbridamento/métodos , Tratamento de Emergência/métodos , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Urológicos , Terapia Combinada , Estado Terminal , Cistoscopia/métodos , Diagnóstico Diferencial , Técnicas de Diagnóstico Urológico , Emergências , Serviços Médicos de Emergência/métodos , Medicina Baseada em Evidências , Alemanha , Humanos , Masculino , Retalhos Cirúrgicos , Resultado do Tratamento
18.
Zentralbl Chir ; 140(2): 179-85, 2015 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-25874468

RESUMO

The integrity of the thoracic wall and therefore the protection of the thoracic organs is paramount for survival. This integrity can be compromised by various factors, be it tumours, wound-healing disorders or injuries. An adequate surgical therapy for these entities often requires (partial) resections of the thoracic wall resulting in a loss of its protective function. A safe and timely reconstruction of the thoracic wall is therefore mandatory and can be achieved by means of reconstructive procedures. This article therefore aims to illustrate such reconstructive procedures utilising our own clinical cases while also giving a review of the literature in order to construct an algorithm for the reconstruction procedure.


Assuntos
Procedimentos de Cirurgia Plástica/métodos , Parede Torácica/cirurgia , Algoritmos , Humanos , Retalhos Cirúrgicos/cirurgia , Cicatrização/fisiologia
19.
Zentralbl Chir ; 140(2): 201-4, 2015 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-25874470

RESUMO

INTRODUCTION: Chronic pilonidal disease represents an infectious disease of the gluteal cleft that often requires surgical resection. AIM: In this article, several plastic-surgical reconstructions are presented. METHODS AND RESULTS: Based on our experience and the current literature, different plastic surgical reconstructive methods are presented and discussed. Thorough debridement including sinus tracts and follicles represents an important step in the treatment algorithm. Subsequently, wide defects may remain that can require reconstructive surgery with local flaps. These may include a Karydakis procedure, Limberg transposition flap, V-Y advancement or rotation flap. CONCLUSION: After thorough debridement and adherence to plastic surgical principles, sufficient reconstructions can be obtained with the presented methods.


Assuntos
Seio Pilonidal/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Desbridamento/métodos , Humanos , Retalhos Cirúrgicos/cirurgia
20.
Zentralbl Chir ; 140(2): 210-3, 2015 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-25723865

RESUMO

Soft tissue defects after oncological pelvic exenteration still represent a significant problem. Because of the anatomic and functional peculiarities, the reconstruction of defects in the pelvic region is challenging and requires a differentiated approach. In this paper, current strategies and options for reconstructive procedures are presented considering preoperative conditions and factors related to surgical planning. The relevance of interdisciplinary collaboration and the resulting benefits are set out. The inclusion of the plastic surgeon already in the preoperative planning of tumour resection is recommended.


Assuntos
Exenteração Pélvica/métodos , Neoplasias Pélvicas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Terapia Combinada , Comportamento Cooperativo , Humanos , Comunicação Interdisciplinar , Terapia Neoadjuvante , Planejamento de Assistência ao Paciente , Retalhos Cirúrgicos/cirurgia
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