Background & Aims: Although the clinical phenotype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) has been well described, little is known about disease in PMS2 mutation ...carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. Methods: We performed PMS2 mutation analysis using long-range polymerase chain reaction and multiplex ligation-dependent probe amplification for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. Results: Germ-line PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2-fold higher, and the incidence of endometrial cancer was 7.5-fold higher. In North America, this translates to a cumulative cancer risk to age 70 years of 15%–20% for colorectal cancer, 15% for endometrial cancer, and 25%–32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. Conclusions: PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed.
The availability alongside growing awareness of medicine has led to increased self-treatment of minor ailments. Self-medication is where one 'self' diagnoses and prescribes over the counter medicines ...for treatment. The self-care movement has important policy implications, perceived to relieve the National Health Service (NHS) burden, increasing patient subsistence and freeing resources for more serious ailments. However, there has been little research exploring how self-medication behaviours vary between population groups due to a lack of available data. The aim of our study is to evaluate how high street retailer loyalty card data can help inform our understanding of how individuals self-medicate in England. Transaction level loyalty card data was acquired from a national high street retailer for England for 2012-2014. We calculated the proportion of loyalty card customers (n ~ 10 million) within Lower Super Output Areas who purchased the following medicines: 'coughs and colds', 'Hayfever', 'pain relief' and 'sun preps'. Machine learning was used to explore how 50 sociodemographic and health accessibility features were associated towards explaining purchasing of each product group. Random Forests are used as a baseline and Gradient Boosting as our final model. Our results showed that pain relief was the most common medicine purchased. There was little difference in purchasing behaviours by sex other than for sun preps. The gradient boosting models demonstrated that socioeconomic status of areas, as well as air pollution, were important predictors of each medicine. Our study adds to the self-medication literature through demonstrating the usefulness of loyalty card records for producing insights about how self-medication varies at the national level. Big data offer novel insights that add to and address issues that traditional studies are unable to consider. New forms of data through data linkage may offer opportunities to improve current public health decision making surrounding at risk population groups within self-medication behaviours.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of our study is to examine whether the widening of the distribution of body mass index (BMI) for England can be explained by compositional changes within the population or contextual changes ...in the relationships between explanatory variables and BMI. Race, socio‐economic status, and physical activity were important factors in explaining trends at the 90th centile of BMI, with contextual changes more influential than compositional changes.
While there is increasing international evidence for the widening of the distribution of body mass index (BMI), there has been little attempt to explain this trend. The aim of our study is to examine whether the trend can be explained by compositional changes within the population or contextual changes in the relationships between explanatory variables and BMI. Data from the Health Survey for England for 2002–2004 and 2012–2014 were used. BMI was our outcome variable and explanatory variables included age, sex, race, education, occupation, and physical activity. We examined how predictors of BMI varied at the 10th, 50th, and 90th percentiles using unconditional quantile regressions. Oaxaca‐Blinder type decomposition analysis was then applied to examine whether contextual or compositional explanations accounted for changes in the distribution between time periods. We found that changes in the nature of relationships observed by our coefficient values accounted for the majority of the difference in BMI at the 90th percentile in 2012–2014 compared to 2002–2004. Race, physical activity, and socio‐economic status were the primary reasons for explaining the continued growth of the right tail of the BMI distribution. Compositional changes in the population were less influential, but may have offset some of the contextual changes to relationships. Changing relationships between predictors of BMI reflect systematic changes in the determinants of BMI, leading to the widening of the BMI distribution. Our results demonstrate the importance of multi‐tiered policies aimed at tackling the varying influences across the BMI distribution.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The number of people living with dementia (PLWD) continues to increase, particularly those with severe symptomatology. Severe symptoms and greater ill-health result in more acute care need. Early ...healthcare interventions can prove beneficial. Healthcare use has not been analysed as a holistic set of interlinked events. This study explores different healthcare pathways among PLWD, social or spatial inequalities in healthcare pathways and subsequent mortality risk.
Group-based trajectory models (GBTM) were applied to electronic healthcare records. We generated clusters of PLWD with similar five-year, post-diagnosis trajectories in rates of primary and secondary healthcare use. Potential social and spatial variations in healthcare use clusters were examined. Cox Proportional Hazards used to explore variation in subsequent mortality risk between healthcare use clusters.
Four healthcare use clusters were identified in both early- (n = 3732) and late-onset (n = 6224) dementia populations. Healthcare use variations were noted; consistent or diminishing healthcare use was associated with lower subsequent mortality risk. Increasing healthcare use was associated with increased mortality risk. Descriptive analyses indicated social and spatial variation in healthcare use cluster membership.
Healthcare pathways can help indicate changing need and variation in need, with differential patterns in initial healthcare use post-diagnosis, producing similar subsequent mortality risk. Care in dementia needs to be more accessible and appropriate, with care catered to specific and changing needs. Better continuity of care and greater awareness of dementia in primary can enhance prospects for PLWD. Research needs to further illuminate holistic care need for PLWD, including health and social care use, inequalities in care, health and outcomes.
Abstract
Background
Health Impact Assessment (HIA) is promoted as a decision-informing tool by public health and governmental agencies. HIA is beneficial when carried out as part of policy ...development but is also valuable as a methodology when a policy is being implemented to identify and understand the wider health and well-being impacts of policy decisions, particularly when a decision needs to be taken rapidly to protect the population. This paper focusses on a HIA of the ‘Staying at Home and Social Distancing Policy’ or ‘lockdown’ in response to the COVID-19 pandemic in Wales conducted by the Welsh national public health institute. It describes the process and findings, captures the learning and discusses how the process has been used to better understand the wider health and well-being impacts of policy decisions beyond direct health harm. It also examines the role of public health institutes in promoting and using HIA.
Methods
A HIA was conducted following a standard HIA five step process. A literature review was undertaken alongside 15 qualitative semi-structured interviews with key stakeholders, and relevant health and demographic data were collated. The results were triangulated and analysed to form a holistic assessment of the policy decision and its impacts.
Results
A wide range of major health and well-being impacts of the lockdown in Wales were identified across the determinants of health, which included positive and negative social, economic, environmental and mental well-being impacts beyond the impact on direct health. Populations affected included children and young people, those on low incomes and women as well as those whose health has been directly impacted by COVID-19 such as older people. The work highlighted the benefit that HIA can bring in emphasizing impacts which can inform policy and shared learning with others.
Conclusion
HIA is a largely underused tool to understand the impact of policy and political decisions, particularly when a decision has been taken at speed. This case study highlights how HIA provide evidence and information for advocacy and further work by public health institutes, health agencies and policy makers.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background2015 saw the largest annual spike of mortality rates in England in almost 50 years. We examine whether these changes in mortality rates are associated with an indicator of poor functioning ...of health and social care: delay in hospital discharges.MethodsOffice for National Statistics monthly data of death counts and mortality rates for the period August 2010–March 2016 were compared with delays in discharges from National Health Service (NHS) England data on transfers of care for acute and non-acute patients in England. Autoregressive Integrated Moving Average regression models were used in the analysis.ResultsWe estimate that each additional day an acute admission was late being discharged was associated with an increase in 0.394 deaths (95% CIs 0.220 to 0.569). For each additional acute patient delayed being discharged, we found an increase of 7.322 deaths (95% CIs 1.754 to 12.890). Findings for non-acute admissions were mixed.ConclusionThe increased prevalence of patients being delayed in discharge from hospital in 2015 was associated with increases in mortality, accounting for up to a fifth of mortality increases. Our study provides evidence that a lower quality of performance of the NHS and adult social care as a result of austerity may be having an adverse impact on population health.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Conjugated polymer nanoparticles (CPNs) based on a common solar cell material (PTB7) have been prepared, and their potential in theranostic applications based on bioimaging and photosensitizing ...capabilities has been evaluated. The main absorption and emission bands of the prepared CPNs both fell within the NIR-I (650–950 nm) transparency window, allowing facile and efficient implementation of our CPNs as bioimaging agents, as demonstrated in this work for A549 human lung cancer cell cultures. The prepared CPN samples were also shown to produce reactive oxygen species (ROS) upon photoexcitation in the near-infrared or ultraviolet spectral regions, both in aqueous solutions and in HaCaT keratinocyte cell cultures. Importantly, we show that the photosensitizing ability of our CPNs was largely determined by the nature of the stabilizing shell: coating the CPNs with a Pluronic F-127 copolymer led to an improvement of photoinitiated ROS production, while using polystyrene-co-maleic anhydride instead completely quenched said process. This work therefore demonstrates that the photosensitizing capability of CPNs can be modulated via an appropriate selection of stabilizing material and highlights the significance of this parameter for the on-demand design of theranostic probes based on CPNs.
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IJS, KILJ, NUK, PNG, UL, UM
Policy in all sectors affects health, through multiple pathways and determinants. Health in all policies (HiAP) is an approach that seeks to identify and influence the health and equity impacts of ...policy decisions, to enhance health benefits and avoid harm. This usually involves the use of health impact assessment or health lens analysis. There is growing international experience in these approaches, and some countries have cross-sectoral governance structures that prioritize the assessment of the policies that are most likely to affect health. The fundamental elements of HiAP are inter-sectoral collaboration, policy influence, and holistic consideration of the range of health determinants affected by a policy area or proposal. HiAP requires public health professionals to invest time to build partnerships and engage meaningfully with the sectors affecting the social determinants of health and health equity. With commitment, political will and tools such as the health impact assessment, it provides a powerful approach to integrated policymaking that promotes health, well-being, and equity. The COVID-19 pandemic has raised the profile of public health and highlighted the links between health and other policy areas. This paper describes the rationale for, and principles underpinning, HiAP mechanisms, including HIA, experiences, challenges and opportunities for the future.
The ability to control crystallization reactions is required in a vast range of processes including the production of functional inorganic materials and pharmaceuticals and the prevention of scale. ...However, it is currently limited by a lack of understanding of the mechanisms underlying crystal nucleation and growth. To address this challenge, it is necessary to carry out crystallization reactions in well‐defined environments, and ideally to perform in situ measurements. Here, a versatile microfluidic synchrotron‐based technique is presented to meet these demands. Droplet microfluidic‐coupled X‐ray diffraction (DMC‐XRD) enables the collection of time‐resolved, serial diffraction patterns from a stream of flowing droplets containing growing crystals. The droplets offer reproducible reaction environments, and radiation damage is effectively eliminated by the short residence time of each droplet in the beam. DMC‐XRD is then used to identify effective particulate nucleating agents for calcium carbonate and to study their influence on the crystallization pathway. Bioactive glasses and a model material for mineral dust are shown to significantly lower the induction time, highlighting the importance of both surface chemistry and topography on the nucleating efficiency of a surface. This technology is also extremely versatile, and could be used to study dynamic reactions with a wide range of synchrotron‐based techniques.
Microfluidic sample environments for synchrotron X‐ray analysis are emerging as an important new tool for studying material synthesis. Here, a technique for serial powder diffraction is introduced and used to investigate the nucleation and growth of CaCO3 crystals in the presence of various nucleating agents, where both their surface chemistry and topography are shown to be important to their nucleation efficiency.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Great Recession of 2007–2008 saw the largest period of economic downturn since the Second World War or the Great Depression of the 1930s. Recessions, however, tend not to have a significant ...impact on population health. Rather it is how society and governments respond to a recession that has a larger impact on their populations. The dominant political response to the Great Recession was the introduction of austerity programmes aimed at reducing the size of the state. In this Commentary, I briefly review the state of evidence on the changes in population health during austerity. Although the negative impact of austerity on overall population health has been well documented across Europe, there remains a paucity of evidence on within-country differences in health. The slowing down of improvements in life expectancy, correlated to the level of austerity, raises uncomfortable questions as to whether we are beginning to transition from the era of consistently improving population health to a new age characterised by an instability in population health largely dictated by the social and political determinants of health.
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BFBNIB, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK
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