Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo.

The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation

Demographic and psychological predictors of community pharmacists’ cancer-related conversations with patients: a cross-sectional analysis and survey study

BACKGROUND: There is increasing interest in the role of community pharmacy in the early diagnosis and prevention of cancer. This study set out to examine how often community pharmacists (CPs) encourage patients to spot or respond to potential signs and symptoms of cancer, and how often they help people to make an informed decision about taking part in bowel cancer screening. METHODS: Data from 400 UK CPs, who completed the 2018 Cancer Research UK Healthcare Professional Tracker survey, were analysed. The primary outcomes were: ‘how often CPs encourage patients to spot or respond to potential signs and symptoms of cancer’ and ‘how often CPs encourage eligible people to make an informed decision to participate in bowel cancer screening’. Associations between behaviours and demographic and psychological variables (Capability, Opportunity and Motivation) were assessed using multivariate logistic regression. RESULTS: Most (n = 331, 82.8%) CPs reported occasionally, frequently or always encouraging patients to spot or respond to potential signs and symptoms of cancer, while only half (n = 203, 50.8%) reported occasionally, frequently or always helping people make an informed decision to participate in bowel cancer screening. Female sex (aOR: 3.20, 95%CI: 1.51, 6.81; p < 0.01) and increased Opportunity (aOR: 1.72, 95%CIs: 1.12, 2.64; p < 0.05) and Motivation (aOR: 1.76, 95%CIs: 1.37, 2.27; p < 0.001) were associated with encouraging patients to spot or respond to potential signs and symptoms of cancer; all three psychological variables were associated with helping people to make an informed decision to participate in bowel cancer screening (Capability: aOR: 1.39, 95%CIs: 1.26, 1.52, p < 0.001; Opportunity: aOR: 1.44, 95%CIs: 1.11, 1.87; p < 0.01; Motivation: aOR: 1.45, 95%CIs: 1.05, 2.00; p < 0.05). CONCLUSIONS: Most CPs encourage patients to spot or respond to potential cancer symptoms, while only half help them make an informed decision to participate in bowel cancer screening. A multifaceted approach, targeting multiple COM-B components, is required to change these behaviours

Access to interpreting services in England: secondary analysis of national data

Background: Overcoming language barriers to health care is a global challenge. There is great linguistic diversity in the major cities in the UK with more than 300 languages, excluding dialects, spoken by children in London alone. However, there is dearth of data on the number of non-English speakers for planning effective interpreting services. The aim was to estimate the number of people requiring language support amongst the minority ethnic communities in England. Methods: Secondary analysis of national representative sample of subjects recruited to the Health Surveys for England 1999 and 2004. Results: 298,432 individuals from the four main minority ethnic communities (Indian, Pakistani, Bangladeshi and Chinese) who may be unable to communicate effectively with a health professional. This represents 2,520,885 general practice consultations per year where interpreting services might be required. Conclusion: Effective interpreting services are required to improve access and health outcomes of non-English speakers and thereby facilitate a reduction in health inequalities

Strengthening the health system capacity to monitor demographic and population health metrics through surveillance nested on existing government community health structures: A pilot from a rural area of Kenya

Background: The community health strategy (CHS) is a response ofthe Kenyan government to reversal in gains for population healthindicators in the 1990s. CHS’s main aim is to improve health out-comes by bridging the gap between households and the health sys-tem. The key innovation of CHS is the development of capacity tomonitor the population and deliver primary health services at thecommunity level by well-trained community health workers (CHWs).We aimed to evaluate the feasibility of generating reliable de-mographic and household level health information using CHWs in arural area in Kenya.Methods: We trained and supported 100 CHWs to conduct aregistration, enumeration and household health information data collection. They used the standard CHS household registration toolwith items covering demographic, maternal and child health, andsocial determinants of disease aspects of the household. The datawere entered into a relational database and analyzed in Stata v13(Statacorp, College Station, Houston TX, USA). We used Whipple’sindex to assess for age heaping and compared the distribution ofdemographic parameter with those of other surveys in the area (e.g.DHS) and an adjacent HDSS. Overall and category specific de-nominators were used to evaluate the collected household healthinformation.Findings: The population of the area was 16,005 individuals livingin 2,722 households. The median (IQR) number of individuals perhousehold was 6 (4-7). Females comprised of 51% of the populationand 99% provided a date of birth. The median (IQR) age was 17 (8-32) years. There was no age heaping (Whipple’s index was 97),reflecting reasonably accurate age reporting. Children Parents/guardians of 93% of children agedInterpretation: This project demonstrated that it is feasible toidentify and register populations under the existing government CHSstructures as well as generate relatively accurate demographic datawhich can be used as denominators in monitoring and evaluation ofpopulation health programmes. Reporting of maternal health infor-mation was poor and more training is needed to enable CHWs tocollect this information

Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral, and there is evidence that it is associated with an elevated familial risk of breast cancer. Although women with LCIS suffer an increased risk of invasive breast disease, this risk is moderate suggesting that LCIS may result from mutation of a gene or genes conferring a high risk of LCIS, but a lower risk of invasive breast cancer. The high frequency of somatic mutations in E-cadherin in LCIS, coupled with recent reports that germline mutations in this gene can predispose to diffuse gastric cancer, raised the possibility that constitutional E-cadherin mutations may confer susceptibility to LCIS. In order to explore this possibility we have examined a series of 65 LCIS patients for germline E-cadherin mutations. Four polymorphisms were detected but no pathogenic mutations were identified. The results indicate that E-cadherin is unlikely to act as a susceptibility gene for LCIS. © 2000 Cancer Research Campaig

Outcomes of aortic aneurysm surgery in England : a nationwide cohort study using hospital admissions data from 2002 to 2015

Background The United Kingdom aortic aneurysms (AA) services have undergone reconfiguration to improve outcomes. The National Health Service collects data on all hospital admissions in England. The complex administrative datasets generated have the potential to be used to monitor activity and outcomes, however, there are challenges in using these data as they are primarily collected for administrative purposes. The aim of this study was to develop standardised algorithms with the support of a clinical consensus group to identify all AA activity, classify the AA management into clinically meaningful case mix groups and define outcome measures that could be used to compare outcomes among AA service providers. \ud Methods In-patient data about aortic aneurysm (AA) admissions from the 2002/03 to 2014/15 were acquired. A stepwise approach, with input from a clinical consensus group, was used to identify relevant cases. The data is primarily coded into episodes, these were amalgamated to identify admissions; admissions were linked to understand patient pathways and index admissions. Cases were then divided into case-mix groups based upon examination of individually sampled and aggregate data. Consistent measures of outcome were developed, including length of stay, complications within the index admission, post-operative mortality and re-admission. Results Several issues were identified in the dataset including potential conflict in identifying emergency and elective cases and potential confusion if an inappropriate admission definition is used. Ninety six thousand seven hundred thirty-five patients were identified using the algorithms developed in this study to extract AA cases from Hospital episode statistics. From 2002 to 2015, 83,968 patients (87% of all cases identified) underwent repair for AA and 12,767 patients (13% of all cases identified) died in hospital without any AA repair. Six thousand three hundred twenty-nine patients (7.5%) had repair for complex AA and 77,639 (92.5%) had repair for infra-renal AA. Conclusion The proposed methods define homogeneous clinical groups and outcomes by combining administrative codes in the data. These methodologically robust methods can help examine outcomes associated with previous and current service provisions and aid future reconfiguration of aortic aneurysm surgery services

The effects of neo-adjuvant chemotherapy on myeloid cells in high-grade serous ovarian cancer metastases

PhD Thesi

South Korea's automotive labour regime, Hyundai Motors’ global production network and trade‐based integration with the European Union

This article explores the interrelationship between global production networks(GPNs) and free trade agreements (FTAs) in the South Korean auto industry and its employment relations. It focuses on the production network of the Hyundai Motor Group (HMG) — the third biggest automobile manufacturer in the world — and the FTA between the EU and South Korea. This was the first of the EU’s ‘new generation’ FTAs, which among other things contained provisions designed to protect and promote labour standards. The article’s argument is twofold. First, that HMG’s production network and Korea’s political economy (of which HMG is a crucial part) limited the possibilities for the FTA’s labour provisions to take effect. Second, that the commercial provisions in this same FTA simultaneously eroded HMG’s domestic market and corporate profitability, leading to adverse consequences for auto workers in the more insecure and low-paid jobs. In making this argument, the article advances a multiscalar conceptualization of the labour regime as an analytical intermediary between GPNs and FTAs. It also provides one of the first empirical studies of the EU–South Korea FTA in terms of employment relations, drawing on 105 interviews with trade unions, employer associations, automobile companies and state officials across both parties