London calling Gaza: The role of international collaborations in the globalisation of postgraduate burn care education.

Burn injuries represent a significant epidemiological problem, with the vast majority occurring in low- to middle-income countries. These regions also represent areas where lack of socioeconomic growth and geopolitical instability pose additional barriers not only to healthcare provision but also to the acquisition of continuing professional development. Long-distance, web-based learning programmes ('tele-education') have been identified as a successful and powerful means of propagating up-to-date medical education and training in poor-resource, isolated or conflict-ridden regions. This report evaluates the role of tele-education in delivering a distance-learning Master's degree in Burn Care to a group of 11 healthcare professionals working in the occupied Palestinian territories (OPT), which was funded as part of a collaboration between Queen Mary University of London and IMET-Pal (International Medical Education Trust - Palestine). We present our experience in delivering the programme in a conflict-ridden part of the world, which includes the specific adaptations to tailor the programme to regional needs as well the unique challenges faced by students and faculty in enhancing the educational value of this unique initiative. The academic achievements of this group of healthcare professionals were found to be comparable to historical student cohorts from privileged socioeconomic backgrounds and the majority of students felt that participation in the programme contributed to a direct improvement to their daily burn care practices. The successful outcomes achieved by our students support the constantly emerging evidence that targeted, well-delivered, long-distance learning programmes can become powerful tools in combating inequalities in global healthcare and health education

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases

Parathyroid hormone-related peptide is a regulatory protein implicated in the pathogenesis of bone metastases, particularly in breast carcinoma. Parathyroid hormone-related peptide is widely expressed in primary prostate cancers but there are few reports of its expression in prostatic metastases. The aim of this study was to examine the expression of parathyroid hormone-related peptide and its receptor in matched primary and in bone metastatic tissue from patients with untreated adenocarcinoma of the prostate. Eight-millimetre trephine iliac crest bone biopsies containing metastatic prostate cancer were obtained from 14 patients from whom matched primary tumour tissue was also available. Histological grading was performed by an independent pathologist. The cellular location of mRNA for parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor was identified using in situ hybridization with 35S-labelled probe. Expression of parathyroid hormone-related peptide and its receptor was described as uniform, heterogenous or negative within the tumour cell population. Parathyroid hormone-related peptide expression was positive in 13 out of 14 primary tumours and in all 14 metastases. Receptor expression was evident in all 14 primaries and 12 out of 14 metastases. Co-expression of parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor was common (13 primary tumours, 12 metastases). The co-expression of parathyroid hormone-related peptide and its receptor suggest that autocrine parathyroid hormone-related peptide mediated stimulation may be a mechanism of escape from normal growth regulatory pathways. The high frequency of parathyroid hormone-related peptide expression in metastases is consistent with a role in the pathogenesis of bone metastases

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases

Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P < 0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therap

Uses of population census data for monitoring geographical imbalance in the health workforce: snapshots from three developing countries

BACKGROUND: Imbalance in the distribution of human resources for health (HRH), eventually leading to inequities in health services delivery and population health outcomes, is an issue of social and political concern in many countries. However, the empirical evidence to support decision-making is often fragmented, and many standard data sources that can potentially produce statistics relevant to the issue remain underused, especially in developing countries. This study investigated the uses of demographic census data for monitoring geographical imbalance in the health workforce for three developing countries, as a basis for formulation of evidence-based health policy options. METHODS: Population-based indicators of geographical variations among HRH were extracted from census microdata samples for Kenya, Mexico and Viet Nam. Health workforce statistics were matched against international standards of occupational classification to control for cross-national comparability. Summary measures of inequality were calculated to monitor the distribution of health workers across spatial units and by occupational group. RESULTS: Strong inequalities were found in the geographical distribution of the health workforce in all three countries, with the highest densities of HRH tending to be found in the capital areas. Cross-national differences were found in the magnitude of distributional inequality according to occupational group, with health professionals most susceptible to inequitable distribution in Kenya and Viet Nam but less so in Mexico compared to their associate professional counterparts. Some discrepancies were suggested between mappings of occupational information from the raw data with the international system, especially for nursing and midwifery specializations. CONCLUSIONS: The problem of geographical imbalance among HRH across countries in the developing world holds important implications at the local, national and international levels, in terms of constraints for the effective deployment, management and retention of HRH, and ultimately for the equitable delivery of health services. A number of advantages were revealed of using census data in health research, notably the potential for producing detailed statistics on health workforce characteristics at the sub-national level. However, lack of consistency in the compilation and processing of occupational information over time and across countries continues to hamper comparative analyses for HRH policy monitoring and evaluation

Developing evidence-based ethical policies on the migration of health workers: conceptual and practical challenges

It is estimated that in 2000 almost 175 million people, or 2.9% of the world's population, were living outside their country of birth, compared to 100 million, or 1.8% of the total population, in 1995. As the global labour market strengthens, it is increasingly highly skilled professionals who are migrating. Medical practitioners and nurses represent a small proportion of highly skilled workers who migrate, but the loss of health human resources for developing countries can mean that the capacity of the health system to deliver health care equitably is compromised. However, data to support claims on both the extent and the impact of migration in developing countries is patchy and often anecdotal, based on limited databases with highly inconsistent categories of education and skills. The aim of this paper is to examine some key issues related to the international migration of health workers in order to better understand its impact and to find entry points to developing policy options with which migration can be managed. The paper is divided into six sections. In the first, the different types of migration are reviewed. Some global trends are depicted in the second section. Scarcity of data on health worker migration is one major challenge and this is addressed in section three, which reviews and discusses different data sources. The consequences of health worker migration and the financial flows associated with it are presented in section four and five, respectively. To illustrate the main issues addressed in the previous sections, a case study based mainly on the United Kingdom is presented in section six. This section includes a discussion on policies and ends by addressing the policy options from a broader perspective

Non-standard management of breast cancer increases with age in the UK: a population based cohort of women ⩾65 years

Evidence suggests that compared to younger women, older women are less likely to receive standard management for breast cancer. Whether this disparity persists once differences in tumour characteristics have been adjusted for has not been investigated in the UK. A retrospective cohort study involving case note review was undertaken, based on the North Western Cancer Registry database of women aged ⩾65 years, resident in Greater Manchester with invasive breast cancer registered over a 1-year period (n=480). Adjusting for tumour characteristics associated with age by logistic regression analyses, older women were less likely to receive standard management than younger women for all indicators investigated. Compared to women aged 65–69 years, women aged ⩾80 years with operable (stage 1–3a) breast cancer have increased odds of not receiving triple assessment (OR=5.5, 95% confidence interval (CI): 2.1–14.5), not receiving primary surgery (OR=43.0, 95% CI: 9.7–191.3), not undergoing axillary node surgery (OR=27.6, 95% CI: 5.6–135.9) and not undergoing tests for steroid receptors (OR=3.0, 95% CI: 1.7–5.5). Women aged 75–79 years have increased odds of not receiving radiotherapy following breast-conserving surgery compared to women aged 65–69 years (OR=11.0, 95% CI: 2.0–61.6). These results demonstrate that older women in the UK are less likely to receive standard management for breast cancer, compared to younger women and this disparity cannot be explained by differences in tumour characteristics

Potential use of COX-2–aromatase inhibitor combinations in breast cancer

Cyclooxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Cyclooxygenase-2-positive tumours tend to be larger, higher grade, node-positive and HER-2/neu-positive. High COX-2 expression is associated with poor prognosis. Cyclooxygenase-2 inhibition reduces the incidence of tumours in animal models, inhibits the development of invasive cancer in colorectal cancer and reduces the frequency of polyps in familial adenomatous polyposis (FAP). These effects may be as a result of increased apoptosis, reduced angiogenesis and/or proliferation. Studies of COX-2 inhibitors in breast cancer are underway both alone and in combination with other agents. There is evidence to suggest that combining COX-2 inhibitors with aromatase inhibitors, growth factor receptor blockers, or chemo- or radiotherapy may be particularly effective. Preliminary results from combination therapy with celecoxib and exemestane in postmenopausal women with advanced breast cancer showed that the combination increased the time to recurrence. Up to 80% of ductal carcinomas in situ (DCISs) express COX-2, therefore COX-2 inhibition may be of particular use in this situation. Cyclooxygenase-2 expression correlates strongly with expression of HER-2/neu. As aromatase inhibitors appear particularly effective in patients with HER-2/neu-positive tumours, the combination of aromatase inhibitors and COX-2 inhibitors may be particularly useful in both DCIS and invasive cancer