Survival analysis of time-to-event data in respiratory health research studies

This article provides a review of techniques for the analysis of survival data arising from respiratory health studies. Popular techniques such as the Kaplan–Meier survival plot and the Cox proportional hazards model are presented and illustrated using data from a lung cancer study. Advanced issues are also discussed, including parametric proportional hazards models, accelerated failure time models, time-varying explanatory variables, simultaneous analysis of multiple types of outcome events and the restricted mean survival time, a novel measure of the effect of treatment.

Radiotherapy in the Barwon South Western Region: a rural perspective

Introduction: Cancer-related mortality rates are higher in rural areas compared with urban regions. Whether there are corresponding geographical variations in radiotherapy utilisation rates (RURs) is the subject of this study. Methods: RURs for the regional centre of Geelong and rural areas of the Barwon South Western Region were calculated using a population-based database (2009). Results: Lower RURs were observed for rural patients compared with the Geelong region for prostate cancer (15.7% vs 25.8%, P = 0.02), rectal cancer (32.8% vs 44.7%, P = 0.11), lymphoma (9.4% vs 26.2%, P = 0.05), and all cancers overall (25.6% vs 28.9%, P = 0.06). This lower rate was significant in men (rural, 19.9%; Geelong, 28.3%; P = 0.00) but not in women (rural, 33.6%; Geelong, 29.7%; P = 0.88). Time from diagnosis to radiotherapy was not significantly different for patients from the two regions. Tumour staging within the rural and Geelong regions was not significantly different for the major tumour streams of rectal, prostate and lung cancer (P = 0.61, P = 0.79, P = 0.43, respectively). A higher proportion of tumours were unstaged or unstageable in the rural region for lung (44% vs 18%, P < 0.01) and prostate (73% vs 57%, P < 0.01) cancer. Conclusion: Lower RURs were observed in our rural region. Differences found within tumour streams and in men suggest a complexity of relationships that will require further study.

Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

Restorative care for palliative patients: a retrospective clinical audit of outcomes for patients admitted to an inpatient palliative care unit

BACKGROUND: Restorative care in palliative care is a subset of rehabilitation that aims to improve quality of life through restoration or maintenance of physical functions. Outcomes for restorative care programmes delivered by palliative care units have not adequately been assessed. OBJECTIVES: The objectives are to examine the outcomes of a restorative care programme in an inpatient palliative care unit, including discharge destination, performance status changes and length of stay. METHODS: Retrospective clinical audit of consecutive patients admitted to Calvary Health Care Bethlehem in Melbourne, Australia, principally for restorative care from July 2010 to December 2011. RESULTS: 79 admissions met inclusion criteria. Mean age was 76.5 years (SD=11.14) and 43 (54%) were men. 75 (95%) patients had a malignant diagnosis; of these, the majority had lung cancer (24%). 16 patients (20%) were discharged home, 51 (65%) died and 12 (15%) were transferred. Of the patients discharged home, only 6 (38% of those discharged home) improved their performance status. Those discharged home had a significantly shorter length of stay (17 days compared to 39 days; p<0.05). Patients discharged home also had significantly better Australia-modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups-Activities of Daily Living (RUG-ADL) scores on admission than others (both p<0.05). CONCLUSIONS: The majority of patients referred for restorative care died during admission, with only a minority discharged home. Patients discharged most commonly experienced maintenance and not improvement in performance status. A successful discharge home following restorative care was associated with a shorter length of stay. Implications and recommendations for successful restorative care will be discussed.

Retrospective clinical audit of outcomes for patients admitted to an inpatient palliative care unit for restorative care

Background Restorative care in palliative care is a subset of rehabilitation that aims to improve quality of life through restoration or maintenance of physical functions. Outcomes for restorative care programmes delivered by palliative care units have not adequately been assessed.

Objectives The objectives are to examine the outcomes of a restorative care programme in an inpatient palliative care unit, including discharge destination, performance status changes and length of stay.

Methods Retrospective clinical audit of consecutive patients admitted to Calvary Health Care Bethlehem in Melbourne, Australia, principally for restorative care from July 2010 to December 2011.

Results 79 admissions met inclusion criteria. Mean age was 76.5 years (SD=11.14) and 43 (54%) were men. 75 (95%) patients had a malignant diagnosis; of these, the majority had lung cancer (24%). 16 patients (20%) were discharged home, 51 (65%) died and 12 (15%) were transferred. Of the patients discharged home, only 6 (38% of those discharged home) improved their performance status. Those discharged home had a significantly shorter length of stay (17 days compared to 39 days; p<0.05). Patients discharged home also had significantly better Australia-modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups-Activities of Daily Living (RUG-ADL) scores on admission than others (both p<0.05).

Conclusions The majority of patients referred for restorative care died during admission, with only a minority discharged home. Patients discharged most commonly experienced maintenance and not improvement in performance status. A successful discharge home following restorative care was associated with a shorter length of stay. Implications and recommendations for successful restorative care will be discussed.

Lobectomia por carcinoma brônquico : análise das co-morbidades e o seu impacto na morbi-mortalidade pós-operatória

Objetivo: Analisar o impacto das co-morbidades no desempenho pós-operatório de lobectomia por carcinoma brônquico. Pacientes e Métodos: Entre Janeiro de 1998 e Dezembro de 2004, foram estudados retrospectivamente 493 pacientes submetidos à lobectomia por carcinoma brônquico, dentre os quais 305 preencheram os critérios de inclusão. Todos os pacientes foram submetidos à lobectomias com técnica cirúrgica semelhante. Foi realizada análise das co-morbidades de forma a categorizar os pacientes nas escalas de Torrington-Henderson (PORT) e de Charlson, estabelecendo-se assim grupos de risco para complicações e óbito. Resultados: a mortalidade operatória foi 2,9% e o índice de complicações de 44%. O escape aéreo prolongado foi a complicação mais freqüente (20.6%). A análise univariada mostrou que sexo, idade, tabagismo, terapia neoadjuvante e diabetes apresentaram impacto significativo na incidência de complicações. O índice de massa corporal (23,8 ± 4,4), o VEF1 (74,1±24%), bem como a relação VEF1/CVF (0,65 ± 0,1) foram fatores preditivos da ocorrência de complicações. Ambas as escalas de Charlson e PORT foram eficazes na identificação de grupos de risco e na relação com a morbi-mortalidade (p=0,001 e p<0,001). A análise multivariada identificou que o IMC e o índice de Charlson foram os principais determinantes de complicações, enquanto que o escape aéreo prolongado foi o principal fator envolvido na mortalidade (p=0,01). Conclusão: Valores reduzidos de VEF1, VEF1/CVF e IMC baixo, assim como graus 3-4 de Charlson, e 3 de PORT estão associados a maior número de complicações após lobectomias por carcinoma brônquico. Nesta amostra, o escape aéreo persistente esteve fortemente associado à mortalidade.

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The prevalence of human papillomavirus in the oropharynx in healthy individuals in a Brazilian population

Oncogenic human papillomavirus (HPV), a causative agent of uterine cervical cancer, has also been detected in head and neck squamous cell cancers, especially in squamous cell carcinomas of the tonsils. However, the true HPV prevalence in normal and neoplasic oropharyngeal mucosa remains uncertain. To determine the prevalence of HPV DNA in normal oropharyngeal mucosa of cancer-free individuals, a study was carried out on 50 Brazilian subjects. PCR was performed to identify HPV DNA in samples from four sites in the oropharynx (tonsils, soft palate, base of the tongue, and back wall of the pharynx). For amplification of the HPV DNA, MY09/11 consensus primerswere used, and specific genotypes were identified by dot-blot hybridization or cloning and sequencing. HPV DNA was present in 14.0% of the individuals, and the identified genotypes were 16, 18, 52, and 61. All these types are considered high-risk (HR) HPV. The tonsils and the soft palate were the sites with the highest HPV prevalence. This study shows the prevalence of HR HPV in the oropharynx of normal individuals. However, the prevalence of HPV is still unclear, and if HPV infection in a healthy it is not known individual predisposes to HPV-associated disease such as oropharyngeal cancer. Thus, it is important to assess the prevalence of HPV in cancer-free individuals, in order to compare it with the HPV prevalence in oropharyngeal carcinomas and to attempt to determine the true role of HPV in the development of head and neck squamous cell cancers. (c) 2006 Wiley-Liss, Inc.

Trabalho industrial e câncer de pulmão

Com base em populações hospitalares, foram entrevistados 316 casos e 536 controles para obtenção de informações sobre histórias de trabalho, tabagismo, tabagismo passivo, ocorrência de outros cânceres na família, migração e situação socioeconômica. Os entrevistadores utilizaram um questionário padronizado. Casos e controles foram emparelhados por hospital, sexo e idade. O estudo foi desenvolvido entre 1º de julho de 1990 e 31 de janeiro de 1991 em 14 hospitais da Região Metropolitana de São Paulo, SP (Brasil). Foi elaborada uma classificação por escores como forma de ordenar os indivíduos estudados segundo suas histórias de exposições ocupacionais a cancerígenos, conhecidos para o pulmão, acumulando informações sobre a exposição nos locais de trabalho durante a vida, considerando o tipo de atividade, setor de trabalho e tempo em cada emprego. A análise de regressão logística não-condicional mostrou odds ratio: 1,97 (95% IC: 1,52 a 2,55) para os trabalhadores com maiores escores de exposição. Os resultados permitiram inferir que trabalhadores ligados aos setores de produção de diferentes ramos industriais têm duas vezes o risco de desenvolverem neoplasia pulmonar quando comparados aos trabalhadores envolvidos em atividades não-industriais.

Indoor radon measurements and methodologies in Latin American countries

According to the current international guidelines concerning environmental problems, it is necessary to evaluate and to know the indoor radon levels, specially since most of the natural radiation dose to man comes from radon gas and its progeny. Several countries have established National Institutions and National Programs for the study of radon and its connection with lung cancer risk and public health. The aim of this work is to present the indoor radon measurements and the detection methods used for different regions of Latin America (LA) in countries such as Argentina, Brazil, Ecuador, Mexico, Peru and Venezuela. This study shows that the passive radon devices based on alpha particle nuclear track methodology (NTM) is one of the more generalized methods in LA for long term indoor radon measurements, CR-39, LR-115 and Makrofol being the more commonly used detector materials. The participating institutions and the radon level measurements in the different countries are presented in this contribution. (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Indoor radon measurements in six Latin American countries

Most of the natural radiation dose to man comes from radon gas and its progeny. Several countries have established national institutions and national programs in charge of the study of radon and its connection with lung cancer risk and public health. In this paper an indoor radon measurements in Latin American countries is presented. The participants in this work were from Argentina, Brazil, Ecuador, Mexico, Peru and Venezuela. Many different techniques are used in this common effort, and the indoor radon levels in specific locations in each of the participant countries are presented.

Variation in the CXCR1 gene (IL8RA) is not associated with susceptibility to chronic periodontitis

Background: The chemokine receptor 1 CXCR-1 (or IL8R-alpha) is a specific receptor for the interleukin 8 (IL-8), which is chemoattractant for neutrophils and has an important role in the inflammatory response. The polymorphism rs2234671 at position Ex2+860G > C of the CXCR1 gene causes a conservative amino acid substitution (S276T). This single nucleotide polymorphism (SNP) seemed to be functional as it was associated with decreased lung cancer risk. Previous studies of our group found association of haplotypes in the IL8 and in the CXCR2 genes with the multifactorial disease chronic periodontitis. In this study we investigated the polymorphism rs2234671 in 395 Brazilian subjects with and without chronic periodontitis. Findings. Similar distribution of the allelic and genotypic frequencies were observed between the groups (p > 0.05). Conclusions: The polymorphism rs2234671 in the CXCR1 gene was not associated with the susceptibility to chronic periodontitis in the studied Brazilian population. © 2011 Scarel-Caminaga et al; licensee BioMed Central Ltd.

In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors

Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.

Uso do Rad7 para a caracterização do torônio em águas de estâncias hidrominerais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo comparativo da atividade antiinflamatória e anti-tumoral de proteínas inativadoras de ribossomos extraídas de plantas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)