Can different primary care databases produce comparable estimates of burden of disease: results of a study exploring venous leg ulceration

Background. Primary care databases from the UK have been widely used to produce evidence on the epidemiology and health service usage of a wide range of conditions. To date there have been few evaluations of the comparability of estimates between different sources of these data. Aim. To estimate the comparability of two widely used primary care databases, the Health Improvement Network Database (THIN) and the General Practice Research Database (GPRD) using venous leg ulceration as an exemplar condition. Design of study. Cross prospective cohort comparison. Setting. GPRD and the THIN databases using data from 1998 to 2006. Method. A data set was extracted from both databases containing all cases of persons aged 20 years or greater with a database diagnosis of venous leg ulceration recorded in the databases for the period 1998–2006. Annual rates of incidence and prevalence of venous leg ulceration were calculated within each database and standardized to the European standard population and compared using standardized rate ratios. Results. Comparable estimates of venous leg ulcer incidence from the GPRD and THIN databases could be obtained using data from 2000 to 2006 and of prevalence using data from 2001 to 2006. Conclusions. Recent data collected by these two databases are more likely to produce comparable results of the burden venous leg ulceration. These results require confirmation in other disease areas to enable researchers to have confidence in the comparability of findings from these two widely used primary care research resources

Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy

Autophagy is a cell-protective and degradative process that recycles damaged and long-lived cellular components. Cancer cells are thought to take advantage of autophagy to help them to cope with the stress of tumorigenesis; thus targeting autophagy is an attractive therapeutic approach. However, there are currently no specific inhibitors of autophagy. ULK1, a serine/threonine protein kinase, is essential for the initial stages of autophagy, and here we report that two compounds, MRT67307 and MRT68921, potently inhibit ULK1 and ULK2 in vitro and block autophagy in cells. Using a drug-resistant ULK1 mutant, we show that the autophagy-inhibiting capacity of the compounds is specifically through ULK1. ULK1 inhibition results in accumulation of stalled early autophagosomal structures, indicating a role for ULK1 in the maturation of autophagosomes as well as initiation

Maternal health inequalities and GP provision: investigating variation in consultation rates for women in the Born in Bradford cohort

Background The ‘Five Year Forward View’ (NHS England) calls for a radical upgrade in public health provision. Inequalities in maternal health may perpetuate general patterns of health inequalities across generations; therefore equitable access to GP provision during maternity is important. This paper explores variation in GP consultation rates for disadvantaged mothers. Method Data from the Born in Bradford cohort (around 12,000 women), combined with GP records and GP practice variables, were modelled to predict GP consultation rates, before and after adjusting for individual health and GP provision. Results Observed GP consultation rates are higher for women in materially deprived neighbourhoods and Pakistani women. However these groups were found to consult less often after controlling for individual health. This difference, around one appointment per year, is ‘explained’ by the nature of GP provision. Women in practices with a low GP to patient ratio had around 9 fewer consultations over the six year period compared to women in practices with the highest ratio. Conclusions Equitable access to GP services, particularly for women during the maternal period, is essential for tackling deep-rooted health inequalities. Future GP funding should take account of neighbourhood material deprivation to focus resources on areas of the greatest need

The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease

The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea – countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change

β-Catenin is a pH sensor with decreased stability at higher intracellular pH.

β-Catenin functions as an adherens junction protein for cell-cell adhesion and as a signaling protein. β-catenin function is dependent on its stability, which is regulated by protein-protein interactions that stabilize β-catenin or target it for proteasome-mediated degradation. In this study, we show that β-catenin stability is regulated by intracellular pH (pHi) dynamics, with decreased stability at higher pHi in both mammalian cells and Drosophila melanogaster β-Catenin degradation requires phosphorylation of N-terminal residues for recognition by the E3 ligase β-TrCP. While β-catenin phosphorylation was pH independent, higher pHi induced increased β-TrCP binding and decreased β-catenin stability. An evolutionarily conserved histidine in β-catenin (found in the β-TrCP DSGIHS destruction motif) is required for pH-dependent binding to β-TrCP. Expressing a cancer-associated H36R-β-catenin mutant in the Drosophila eye was sufficient to induce Wnt signaling and produced pronounced tumors not seen with other oncogenic β-catenin alleles. We identify pHi dynamics as a previously unrecognized regulator of β-catenin stability, functioning in coincidence with phosphorylation

Ethnic differences in the clustering and outcomes of health behaviours during pregnancy: results from the Born in Bradford cohort

OBJECTIVE. Pregnancy is a time of optimal motivation for many women to make positive behavioural changes. We aim to describe pregnant women with similar patterns of self-reported health behaviours and examine associations with birth outcomes. METHODS. We examined the clustering of multiple health behaviours during pregnancy in the Born in Bradford cohort, including smoking physical inactivity, vitamin d supplementation, and exposure to second hand smoke. Latent class analysis was used to identify groups of individuals with similar patterns of health behaviours separately for White British (WB) and Pakistani mothers. Multinomial regression was then used to examine the association between group membership and birth outcomes, which included preterm birth and mean birth weight. RESULTS. For WB mothers, offspring of those in the ‘Unhealthiest’ group had lower mean birth weight than those in the ‘Mostly healthy but inactive’ class, although no association was observed for preterm birth. For Pakistani mothers, group membership was not associated with birth weight differences, although the odds of preterm birth was higher in ‘Inactive smokers’ compared to the ‘Mostly healthy but inactive’ group. CONCLUSION. The use of latent class methods provides important information about the clustering of health behaviours which can be used to target population segments requiring behaviour change interventions considering multiple risk factors. Given the dominant negative association of smoking with the birth outcomes investigated, latent class groupings of other health behaviours may not confer additional risk information for these outcomes

Models for Access to Maternal Smoking cessation Support (MAMSS): a study protocol of a quasi-experiment to increase the engagement of pregnant women who smoke in NHS Stop Smoking Services

Background: Maternal smoking is a key cause of poor outcomes for mothers, babies and children and Wales has higher rates of smoking in pregnancy than any other UK country. Despite various improvements within the NHS Stop Smoking Service to strengthen the intervention for pregnant women, referrals and successful quit attempts for this group have continued to remain extremely low. A key element of UK national guidance for smoking cessation during pregnancy is to provide a flexible and tailored service to help increase levels of engagement. This study aims to test the effectiveness of three different models of service delivery to address the gap in the evidence base about how to deliver a flexible, tailored smoking cessation service to pregnant women. Methods: This study will adopt a quasi-experimental design over a 12 month period. The setting is four of Wales’ seven Health Boards using an integrated approach between maternity services, local public health teams and the NHS Stop Smoking Service. Core recommendations from UK public health guidance are being implemented across intervention and usual care sites. Stop smoking support for pregnant women in intervention sites is being delivered more flexibly than in usual care sites. Both qualitative and quantitative approaches will be adopted to capture important contextual information and consider multiple perspectives. A health economic analysis will be undertaken using a cost-consequences analysis approach. The primary outcome measure is engagement with stop smoking services (defined as having at least one face-to-face therapeutic contact with a clinician). Discussion: Supporting pregnant women to stop smoking is a challenging area of public health. The proposed study will address several areas where there are key evidence gaps relating to smoking cessation interventions for pregnant women. Specifically, how best to encourage pregnant women to attend a specialist stop smoking support service, how to deliver the service and who should provide it

A clarion call for aeolian research to engage with global land degradation and climate change

This editorial represents a clarion call for the aeolian research community to provide increased scientific input to the Intergovernmental Panel on Climate Change (IPCC) and the United Nations Convention to Combat Desertification (UNCCD) and an invitation to apply for ISAR funding to organize a working group to support this engagement

Influence of muscle mass in the assessment of lower limb strength in COPD: validation of the prediction equation

Absence of established reference values limits application of quadriceps maximal voluntary contraction (QMVC) measurement. The impact of muscle mass inclusion in predictions is unclear. Prediction equations encompassing gender, age and size with (FFM+) and without (FFM−), derived in healthy adults (n=175), are presented and compared in two COPD cohorts recruited from primary care (COPD-PC, n=112) and a complex care COPD clinic (COPD-CC, n=189). Explained variance was comparable between the prediction models (R2: FFM+: 0.59, FFM−: 0.60) as were per cent predictions in COPD-PC (88.8%, 88.3%). However, fat-free mass inclusion reduced the prevalence of weakness in COPD, particularly in COPD-CC where 11.9% fewer were deemed weak