Factors determining disease duration in Alzheimer's disease:a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression

Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks-30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration. © 2014 R. A. Armstrong.

Heparanase and COX-2 expression as predictors of lymph node metastasis in large, high-grade breast tumors

Background/Aim: Heparanase (HPA) contributes to breast cancer metastasis by facilitating the breakdown of the basement membrane and extracellular matrix. High expression of HPA is thought to be associated with increased nodal involvement and poor survival in patients with breast cancer. Overexpression of cyclooxygenase-2 (COX-2) in breast cancer is associated with indicators of poor prognosis such as lymph node metastasis, poor differentiation, and large tumor size. The underlying mechanism by which HPA and COX-2 overexpression increases the metastatic potential of breast cancer is not fully-understood. To enhance our understanding over these mechanisms, we aimed to investigate the relationship between the size of the tumor and HPA expression, tumor grade as well as lymph node status in patients with breast cancer. Materials and Methods: Immunohistochemical analysis of HPA and COX-2 expression was performed on 246 breast tumor samples. The expression of HPA was correlated with COX-2 expression, tumor grade, lymph node status, oestrogen receptor status. Results: The overexpression of HPA and COX-2 was associated with increased likelihood of lymph node positivity in large, high-grade tumors. High-grade tumors with size greater than 20 mm, that overexpressed HPA, were 4-times more likely to be associated with lymph node involvement (OR 4.71, CI 1.21-18.25). Whereas, tumors greater than 20 mm in size were 5-times more likely to metastasize to the regional lymph nodes, if associated with overexpression of COX-2 (OR 5.5, CI 1.2-24.8). Conclusion: Expression of HPA appears to be a key mechanism by which large, highgrade breast tumors metastasize to regional lymph nodes, while COX-2 overexpression may be an independent predictor of lymph node positivity.

A diszkrét kiválasztási modell becslése Cox-regresszióval (Parameter estimation for multinomial discrete choice model using Cox-regression)

Considering the so-called "multinomial discrete choice" model the focus of this paper is on the estimation problem of the parameters. Especially, the basic question arises how to carry out the point and interval estimation of the parameters when the model is mixed i.e. includes both individual and choice-specific explanatory variables while a standard MDC computer program is not available for use. The basic idea behind the solution is the use of the Cox-proportional hazards method of survival analysis which is available in any standard statistical package and provided a data structure satisfying certain special requirements it yields the MDC solutions desired. The paper describes the features of the data set to be analysed.

Gyógyszerek terjedésének vizsgálata Cox-regresszióval

A szerzők célja azon tényezők azonosítása, amelyek szignifikánsan befolyásolják új, innovatívnak számító készítmények terjedési folyamatát. A gyógyszercégek számára a terjedési folyamat ismerete a marketing-költségvetés célirányos elköltése miatt fontos. Ezen túl, a tényezők ismerete költséghatékonyabb egészségügyi gazdálkodást és pontosabb gyógyszerhasználati előrejelzést tehet lehetővé, valamint segíthet a terjedési folyamat felgyorsításában is. Tanulmányukban a két legsikeresebb orális antidiabetikum terjedési folyamatát veszik górcső alá. A túlélési analízis eszköztárába tartozó semi-paraméteres modellek az új gyógyszerek elfogadásáig eltelt időtartamra ható tényezők szakszerű vizsgálatát teszik lehetővé, amelyek közül választásunk Cox regressziós modelljére esett. A Cox-modellt alkalmazva mind az Eucreas, minda Janumet gyógyszerek esetében négy olyan változót azonosítottak, amelyek szignifikánsan befolyásolták az új gyógyszer felírásának az esélyét. Mindkét készítmény esetében szignifikáns változónak bizonyult a felírt gyógyszermárkák száma, illetve az inzulinos kezelésben részesülő betegek aránya. A kapott összefüggések javarészt összhangban vannak a hasonló nemzetközi kutatások eredményeivel.

Queilite actínica: expressão imuno-histoquímica da cox-2 e avaliação do diclofenaco sódico gel como uma terapia alternativa

Actinic cheilitis (AC) is a potentially malignant disorder which affects the lip vermilion and results from chronic exposure to sunlight. Currently, it is not possible to predict which cases of AC may progress to squamous cell carcinoma, and therefore, some biomolecular markers have been researched. Cyclooxygenase 2 (COX-2) is an enzyme associated with inflammatory response which is overexpressed in oral cancer; however, little is known about the role of this protein in actinic cheilitis. About the treatment of this lesion, currently available therapeutic modalities to AC may cause cytotoxic effects and deleterious results to patients. Therefore, the aim of this study was to evaluate the immunoexpression of COX-2 in AC of different risks of malignant transformation and analyse, through clinical follow-up, the efficacy of diclofenac sodium 3% gel in the treatment of this condition. Epithelial immunoexpression of COX-2 was analysed semi-quantitatively in 90 cases of AC classified as low risk (n = 55) and high risk (n = 35) of malignant transformation, in which the scores were assigned: (0) 0 to 5% of positive cells - Negative; (1) 6 to 30% of positive cells - Low expression; (2) 31 to 100% of positive cells - High expression. The chi-square test of Pearson was conducted to verify possible associations between immunoexpression of COX-2 and histologic grade of actinic cheilitis. The weighted kappa coefficient denoted a good interobserver agreement (0.677). Nineteen patients diagnosed with AC were instructed to perform topical application of the gel three times a day for a period of 90 days. In each biweekly visit, a follow-up record was accomplished through digital photographs and after treatment was completed, two researchers analysed all the images to assess clinical aspects of the lip. Furthermore, tolerability to the drug and patient satisfaction after treatment were evaluated. COX-2 was overexpressed in 74.4% of AC cases. Both low and high-risk groups revealed predominance of score 3, followed by scores 2 and 1. There was no significant association (p = 0.315) between COX-2 expression and histological grading. Among the total number of participants of this clinical study, ten showed total remission of all clinical features of the lesion and three had partial improvement of these characteristics. One participant presented worsening of the clinical condition. In five cases, the treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding analysis of satisfaction and tolerability to the drug, most patients were fully satisfied with the therapy (n = 11) and reported that the drug was not irritating to the lips (n = 9). Our study demonstrates that high expression of COX-2 is common in AC; however, this protein was not associated with malignant transformation risk of the analysed cases. Topical application of diclofenac sodium 3% gel provided a convenient and well tolerated approach in most cases, and may be a promising alternative for the treatment of actinic cheilitis.

Probabilistic methods for seasonal forecasting in a changing climate: Cox-type regression models.

For climate risk management, cumulative distribution functions (CDFs) are an important source of information. They are ideally suited to compare probabilistic forecasts of primary (e.g. rainfall) or secondary data (e.g. crop yields). Summarised as CDFs, such forecasts allow an easy quantitative assessment of possible, alternative actions. Although the degree of uncertainty associated with CDF estimation could influence decisions, such information is rarely provided. Hence, we propose Cox-type regression models (CRMs) as a statistical framework for making inferences on CDFs in climate science. CRMs were designed for modelling probability distributions rather than just mean or median values. This makes the approach appealing for risk assessments where probabilities of extremes are often more informative than central tendency measures. CRMs are semi-parametric approaches originally designed for modelling risks arising from time-to-event data. Here we extend this original concept beyond time-dependent measures to other variables of interest. We also provide tools for estimating CDFs and surrounding uncertainty envelopes from empirical data. These statistical techniques intrinsically account for non-stationarities in time series that might be the result of climate change. This feature makes CRMs attractive candidates to investigate the feasibility of developing rigorous global circulation model (GCM)-CRM interfaces for provision of user-relevant forecasts. To demonstrate the applicability of CRMs, we present two examples for El Ni ? no/Southern Oscillation (ENSO)-based forecasts: the onset date of the wet season (Cairns, Australia) and total wet season rainfall (Quixeramobim, Brazil). This study emphasises the methodological aspects of CRMs rather than discussing merits or limitations of the ENSO-based predictors.

Paul Cox: miracle maker

A conference and series of screenings convened by myself and Elizabeth Presa in order to honour and celebrate the life and work of filmmkaer Paul Cox.

Paul Cox, 1940-2016

Obituary for Australian filmmaker Paul Cox

Quantificação de riscos climáticos via modelos de regressão de Cox.

O gerenciamento de riscos climáticos requer informação sobre estados futuros de variáveis climáticas, geralmente representada por funções de distribuição de probabilidade acumulada (FDPA, P(Y?y) ou por sua funções complementares (P(Y>y)), ditas funções probabilidade de exceder (FPE). Uma variedade de métodos estatísticos tem sido utilizada para estimação de FPE, incluindo, modelos de regressão linear múltipla, regressão logística e métodos não paramétricos (MAIA et al, 2007; LO et al, 2008). Apesar de parecer intuitivo que a incerteza associada às estimativas das FPE é fundamental para os tomadores de decisão, esse tipo de informação raramente é fornecido. Modelos estatísticos de previsão baseados em séries históricas da variável de interesse (chuva, temperatura) e de preditores derivados de estados do oceano e da atmosfera (índices climáticos tais como: temperaturas da superfície do mar ? TSM, índice de oscilação sul, IOS, El Nino/Oscilação Sul - ENSO) se constituem em alternativas promissoras para auxílio às tomada de decisão, em escalas locais e regionais. O uso de tais indicadores permite incorporar mudanças de padrão derivadas de mudanças climáticas em modelos estatísticos que utilizam informação histórica. Neste trabalho, mostramos como o Modelo de Regressão de Cox (MRC; COX, 1972), tradicionalmente utilizado para modelagem de tempos de falha, em investigações na área médica e em ciências sociais, pode ser de grande utilidade para avaliação probabilística de riscos climáticos, mesmo para variáveis que não representam tempos de falha tais como chuva, produtividade de culturas, lucros, entre outras. O MRC pode ser utilizado para avaliar a influência de preditores (índices climáticos) sobre riscos de interesse (representados pelas FPE), estimar FPE para combinações específicas de preditores e incertezas associadas além de fornecer informação sobre riscos relativos, de grande valor para tomadores de decisão. Apresentamos dois estudos de caso nos quais o Modelo de Cox foi usado para investigar: a) o efeito do IOS e de um índice derivado de TSM do Pacífico sobre o início da estação chuvosa em Cairns (Austrália) e b) a influência o índice Nino 3.4, derivado de estados da TSM no Pacífico Equatorial sobre o chuva acumulada no período de Março a Junho em Limoeiro do Norte (Ceará, Brasil). O objetivo da apresentação desses estudos é meramente didático, para demonstrar o potencial do método proposto como ferramenta de auxílio à tomada de decisão.

Quantificação de riscos climáticos via modelos de regressão de COX.

2008