Search

Objective Fluoropyrimidine chemotherapy is a first-line treatment for many gastrointestinal (GI) cancers, however, cardiotoxicity concerns may limit administration in patients with pre-existing cardiovascular disease (CVD). This study investigated the association of pre-existing CVD with use of fluoropyrimidine chemotherapy in tumour-eligible GI cancer patients.Methods and analysis National cancer registry data from the Virtual Cardio-Oncology Research Initiative from England between 2014 and 2018 was used to identify GI cancer patients eligible to receive fluoropyrimidine chemotherapy. Linkage to Hospital Episode Statistics and CVD registry data were used to ascertain prior CVD and outcomes. Primary outcome was first administration of fluoropyrimidine chemotherapy following cancer diagnosis. Cox proportional hazard models determined HR and 95% CIs for the association between initiation of fluoropyrimidine treatment and prior CVD.Results 112 726 eligible patients were identified (median age 71 years (IQR 62–80), 39.7% female). 33 026 (29.3%) had pre-existing CVD. 73 392 (65.1%) patients had a diagnosis of colorectal, 23 208 (20.6%) oesophageal, 14 788 (13.1%) gastric and 1338 (1.2%) small bowel cancer. Individuals with pre-existing CVD had a 27% reduced rate of receiving fluoropyrimidine chemotherapy (HR, 0.73; 95% CI 0.70 to 0.75) on multivariable analysis. Significantly reduced rates of fluoropyrimidine administration were found across all subtypes of pre-existing CVD.Conclusions GI cancer patients with all types of pre-existing CVD are less likely to receive fluoropyrimidine chemotherapy despite eligibility. This suggests widespread caution regarding administration of fluoropyrimidines across this population; further research is needed to assess whether such conservatism is justified.

Focuses on the interrelation between the literary writings of Mark Rutherford and D.H. Lawrence. Assessment on the temperamental similarity in the writings; Establishment of socio-historic and personal relationship; Complexities in the vision and character studies.

In the Victorian period, the anxiety induced by old age and by the fear of death seems to have been particularly widespread. Indeed, in the context of a relentless secularisation of world views, man’s uncertainties about his personal fate after death were bound to increase. At the beginning of the period, it is true, a rising fear concerning man’s as well as the world’s salvation was counteracted, at least to a certain extent, by a belief in progress, particularly in the field of science. Although man’s survival as an individual was more and more often put into question, it remained possible to believe in an endless improvement of human societies and the world in general. Gradually, however, the fear of a final degeneration of our world began to be induced by scientific knowledge itself, particularly by discoveries in the field of thermodynamics, which predicted the extinction of the sun as well as the thermal death of the universe.To what extent did traditional uncertainties concerning man’s salvation increase in this context? How did these fears often secularise themselves, opening the way to our contemporary « existential anguish » ? Such are some of the questions which are raised in this paper through a study of the autobiographical and fictional writings of William Hale White (« Mark Rutherford »).

Abstract Background Duchenne muscular dystrophy (DMD) is a rare, muscle‐degenerative disease predominantly affecting males. Natural history models capture the full disease pathway under current care and combine with estimates of new interventions’ effects to assess cost‐effectiveness by health technology decision‐makers. These models require mortality estimates throughout a patient's lifetime, but rare disease datasets typically contain relatively few patients with short follow‐ups. Alternative (published) sources of mortality data may therefore be required. Methods The Clinical Practice Research Datalink (CPRD) was evaluated as a source of mortality and natural history data for future economic evaluations of health technologies for DMD and rare diseases in general in the UK population. This retrospective longitudinal cohort study provides flexible parametric estimates of mortality rates and survival probabilities in the current UK DMD population through primary/secondary records in the CPRD since 1990. It also investigates clinically significant milestones such as corticosteroid use, spinal surgery, and cardiomyopathy in these patients. Results A total of 1121 male patients were included in the study, observed from 0.7 to 48.9 years. Median life expectancy was 25.64 years (95% confidence interval 24.73, 26.47), consistent with previous global estimates. This has improved to 26.47 (25.16, 27.89) years in patients born after 1990. The median ages at corticosteroid initiation, spinal surgery, ventilation, and cardiomyopathy diagnosis were 6.06 years (5.77, 6.29), 14.79 years (14.29, 15.09), 16.97 years (16.50, 18.31), and 15.26 years (14.22, 16.70), respectively. Conclusions Estimates of mortality in UK‐based DMD patients are age‐specific in a uniquely large and nationally representative sample from the CPRD.

In his fictional autobiographical writings, William Hale White describes the agonies of religious doubt in the middle of the 19th century. But he also adopts a sociological approach in many of his narratives, in which the fragmentation of the British religious scene is described with great subtlety, and even irony. This article studies this dimension of his writings, proposing a few more contemporary perspectives concerning the differences that have characterized the link between religion and politics in France and in Great Britain.

Discusses the Protestant/Calvinist spiritual autobiographies. `The Autobiography of Mark Rutherford, Dissenting Minister' and `Mark Rutherford's Deliverance,' by William Hale White, and another autobiography by William Cowper.

Assumes that the novels of fictional author Mark Rutherford are major texts in the history of fiction, challenging the organicist aesthetic of conservative modernism as well as demanding a re-reading of nineteenth-century history. Explanation on the three problems to which Spinoza provides answers which open up the conditions on which Rutherford texts are produced; Information on "Catharine Furze," the most overtly anti-Spinozan text published in the year before the second edition of "Ethic"; Ways of reading the book "The Autobiography."

Evaluates the revisions to the second edition preface of William Hale White's translation of Spinoza's `Ethic.' Fictions published by White between 1881 and 1896; Analysis of the changes between the prefaces to the second and fourth editions of White's `Ethic'; Influence of Spinoza on White's fourth edition of `Ethic.'

Nowadays, two conceptions of secularization oppose each other. The first one perceives the “exit from religion” as well as the advent of a radically new moral and intellectual order as a process of iconoclastic abolition and complete inversion of the initial, foundational religious order. Largely inherited from the Enlightenment and the positivist tradition, it hypostatizes the oppositional paradigm of a radical break with the past and places the advent of modernity under the aegis of the tabula rasa and of a radical inversion of the inaugural religious determinations. On the other hand, the second one tends to understand the development of ideas as well as of psychological and social realities by reducing them to more essential continuities. It addresses the question of the preservation of structural schemes that have been inherited from the original religious logic by referring to a few examples borrowed from White’s writings, showing, among other things, how he was tempted to make of science -- and even of professional involvement -- a genuine inner-worldly substitutionary vocation, of secular literature a source of moral and axiological inspiration.

Abstract Background Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC). Methods One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan–Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate. Results Multivariate analysis showed that both the amount of total cfDNA (p value = 0.024, HR = 1.199, CI = 1.024–1.405) and the number of CTCs (p value = 0.001, HR = 1.243, CI = 1.088–1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value = 0.042, HR = 1.193, CI = 1.007–1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS. Conclusion Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.

Between 1881 and 1896 William Hale White (1831-1913), creating the persona Mark Rutherford (1830-c.18807) - pseudonym is so weak a term as to be positively misleading, wrote six interlinked fictions: [...]