Age, sex, and socioeconomic differences in multimorbidity measured in four ways:UK primary care cross-sectional analysis

Background: Multimorbidity poses major challenges to healthcare systems worldwide. Definitions with cut-offs in excess of ≥2 long-term conditions (LTCs) might better capture populations with complexity but are not standardised. Aim: To examine variation in prevalence using different definitions of multimorbidity. Design and setting: Cross-sectional study of 1 168 620 people in England. Method: Comparison of multimorbidity (MM) prevalence using four definitions: MM2+ (≥2 LTCs), MM3+ (≥3 LTCs), MM3+ from 3+ (≥3 LTCs from ≥3 International Classification of Diseases, 10th revision chapters), and mental–physical MM (≥2 LTCs where ≥1 mental health LTC and ≥1 physical health LTC are recorded). Logistic regression was used to examine patient characteristics associated with multimorbidity under all four definitions. Results: MM2+ was most common (40.4%) followed by MM3+ (27.5%), MM3+ from 3+ (22.6%), and mental–physical MM (18.9%). MM2+, MM3+, and MM3+ from 3+ were strongly associated with oldest age (adjusted odds ratio [aOR] 58.09, 95% confidence interval [CI] = 56.13 to 60.14; aOR 77.69, 95% CI = 75.33 to 80.12; and aOR 102.06, 95% CI = 98.61 to 105.65; respectively), but mental–physical MM was much less strongly associated (aOR 4.32, 95% CI = 4.21 to 4.43). People in the most deprived decile had equivalent rates of multimorbidity at a younger age than those in the least deprived decile. This was most marked in mental–physical MM at 40–45 years younger, followed by MM2+ at 15–20 years younger, and MM3+ and MM3+ from 3+ at 10–15 years younger. Females had higher prevalence of multimorbidity under all definitions, which was most marked for mental–physical MM. Conclusion: Estimated prevalence of multimorbidity depends on the definition used, and associations with age, sex, and socioeconomic position vary between definitions. Applicable multimorbidity research requires consistency of definitions across studies

Integrating numerical cognition research and mathematics education to strengthen the teaching and learning of early number

BACKGROUND: Research into numerical cognition has contributed to a large body of knowledge on how children learn and perform mathematics. This knowledge has the potential to inform mathematics education. Unfortunately, numerical cognition research and mathematics education remain disconnected from one another, lacking the proper infrastructure to allow for productive and meaningful exchange between disciplines. The present study was designed to address this gap. AIM: This study reports on the design, implementation, and effects of a 16-week (25-hour) mathematics Professional Development (PD) model for Kindergarten to Grade 3 educators and their students. A central goal of the PD was to better integrate numerical cognition research and mathematics education. SAMPLE: A total of 45 K-3 educators and 180 of their students participated. METHODS: To test the reproducibility and replicability of the model, the study was carried out across two different sites, over a two-year period, and involved a combination of two different study designs: a quasi-experimental pre-post-research design and a within-group crossover intervention design. RESULT: The results of the first implementation (Year 1), indicated that compared to a control group, both teachers and students benefited from the intervention. Teachers demonstrated gains on both a self-report measure and a test of numerical cognition knowledge, while students demonstrated gains in number line estimation, arithmetic, and numeration. In Year 2, teachers in the intervention group demonstrated greater improvements than the control group on the self-report measure, but not the test of numerical cognition knowledge. At the student level, there was some evidence of gains in numeration. CONCLUSION: The current PD model is a promising approach to better integrate research and practice. However, more research is needed to determine in which school contexts the model is most effective

Heat shock proteins expressed in the marsupial Tasmanian devil are potential antigenic candidates in a vaccine against devil facial tumour disease

The Tasmanian devil (Sarcophilus harrisii), the largest extant carnivorous marsupial and endemic to Tasmania, is at the verge of extinction due to the emergence of a transmissible cancer known as devil facial tumour disease (DFTD). DFTD has spread over the distribution range of the species and has been responsible for a severe decline in the global devil population. To protect the Tasmanian devil from extinction in the wild, our group has focused on the development of a prophylactic vaccine. Although this work has shown that vaccine preparations using whole DFTD tumour cells supplemented with adjuvants can induce anti-DFTD immune responses, alternative strategies that induce stronger and more specific immune responses are required. In humans, heat shock proteins (HSPs) derived from tumour cells have been used instead of whole-tumour cell preparations as a source of antigens for cancer immunotherapy. As HSPs have not been studied in the Tasmanian devil, this study presents the first characterisation of HSPs in this marsupial and evaluates the suitability of these proteins as antigenic components for the enhancement of a DFTD vaccine. We show that tissues and cancer cells from the Tasmanian devil express constitutive and inducible HSP. Additionally, this study suggests that HSP derived from DFTD cancer cells are immunogenic supporting the future development of a HSP-based vaccine against DFTD.Cesar Tovar, Amanda L. Patchett, Vitna Kim, Richard Wilson, Jocelyn Darby, A. Bruce Lyons, Gregory M. Wood

Socio-economic impact of Foot-and-Mouth Disease outbreaks and control measures:An analysis of Mongolian outbreaks in 2017

Mongolia is a large landlocked country in central Asia and has one of the highest per capita livestock ratios in the world. During 2017 reported Foot and Mouth disease (FMD) outbreaks in Mongolia increased considerably, prompting widespread disease control measures. This study estimates the socio‐economic impact of FMD and subsequent control measures on Mongolian herders. The analysis encompassed quantification of the impact on subsistence farmers’ livelihoods and food security and estimation of the national level gross losses due to reaction and expenditure during 2017. Data were collected from 112 herders across eight Provinces that reported disease. Seventy of these herders had cases of FMD, while 42 did not have FMD in their animals but were within quarantine zones. Overall, 86/112 herders reported not drinking milk for a period of time and 38/112 reduced their meat consumption. Furthermore, 55 herders (49.1%) had to borrow money to buy food, medicines and/or pay bills or bank loans. Among herders with FMD cases, the median attack rate was 31.7%, 3.8% and 0.59% in cattle, sheep and goats respectively, with important differences across Provinces. Herders with clinical cases before the winter had higher odds of reporting a reduction in their meat consumption. National level gross losses due to FMD in 2017 were estimated using government data. The estimate of gross economic loss was 18.4 billion Mongolian‐tugriks (US$7.35 million) which equates to approximately 0.65% of the Mongolian GDP. The FMD outbreaks combined with current control measures has negatively impacted herders’ livelihoods (including herders with and without cases of FMD) which is likely to reduce stakeholder advocacy. Possible strategies that could be employed to ameliorate the negative effects of the current control policy were identified. The findings and approach are relevant to other FMD endemic regions aiming to control the disease

Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up: a retrospective cohort study using linked data

BACKGROUND: To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical-mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. METHODS: In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). FINDINGS: Our analyses included data for 1 675 585 individuals (811 393 [48·4%] men and 864 192 [51·6%] women) with a median age of 51·0 years (IQR 37·0-65·0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13·23 years (SD 0·80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12·38 years (0·00), and with a loss of 12·95 years (0·06) when preceded by psychosis and 13·45 years (0·13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. INTERPRETATION: The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death. FUNDING: Health Data Research UK

The New Political Economy of EU State Aid Policy

Despite its importance and singularity, the EU’s state aid policy has attracted less scholarly attention than other elements of EU competition policy. Introducing the themes addressed by the special issue, this article briefly reviews the development of EU policy and highlights why the control of state aid matters. The Commission’s response to the current economic crisis notably in banking and the car industry is a key concern, but the interests of the special issue go far beyond. They include: the role of the European Commission in the development of EU policy, the politics of state aid, and a clash between models of capitalism. The special issue also examines the impact of EU policy. It investigates how EU state aid decisions affect not only industrial policy at the national level (and therefore at the EU level), but the welfare state and territorial relations within federal member states, the external implications of EU action and the strategies pursued by the Commission to limit any potential disadvantage to European firms, and the conflict between the EU’s expanding legal order and national

Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up : a retrospective cohort study using linked data

Funding: This work was supported by Health Data Research UK (HDRUK) Measuring and Understanding Multimorbidity using Routine Data in the UK (MUrMuRUK; award numbers HDR-9006 and CFC0110). HDRUK is funded by the UK Medical Research Council (MRC), Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. This work also was co-funded by the MRC and NIHR (grant number MR/S027750/1). The work was supported by the Administrative Data Research (ADR) Wales programme of work, part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1). RKO is supported by a Springboard award (SBF006\1122) funded by the Academy of Medical Sciences, Wellcome Trust, Government Department of Business, Energy and Industrial Strategy, British Heart Foundation, and Diabetes UK. SS is part funded by the NIHR Applied Research Collaboration West Midlands, the NIHR Health Protection Research Unit (HPRU) in Gastrointestinal Infections, and the NIHR HPRU in Genomics and Enabling Data.Background To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical–mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. Methods In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). Findings Our analyses included data for 1 675 585 individuals (811 393 [48·4%] men and 864 192 [51·6%] women) with a median age of 51·0 years (IQR 37·0–65·0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13·23 years (SD 0·80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12·38 years (0·00), and with a loss of 12·95 years (0·06) when preceded by psychosis and 13·45 years (0·13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. Interpretation The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death.Publisher PDFPeer reviewe

A second transmissible cancer in Tasmanian devils.

Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.We thank Bill Brown, Phil Iles, Billie Lazenby, Jacinta Marr, Jane McGee, Sarah Peck, Holly Wiersma and Phil Wise for assistance with sample collection and curation. Adrian Baez-Ortega, Andrew Davis, Jo Hanuszewicz, Gina Kalodimos, Amanda Patchett, Narelle Phillips, Elizabeth Reid Swainscoat, Jim Richley, Rachel Stivicic and Jim Taylor assisted with surveying, laboratory analysis, data processing and display. We are grateful for support received from Mike Stratton, the Wellcome Trust Sanger Institute (WTSI) sequencing and informatics teams and the WTSI Cancer Genome Project. This work was supported by a Wellcome Trust Investigator Award (102942/Z/13/Z) and by grants from the Australian Research Council (ARC-DP130100715; ARC-LP130100218). Support was provided by Dr Eric Guiler Tasmanian Devil Research Grants and by the Save the Tasmanian Devil Program. JMCT was partly supported by a Marie Curie Fellowship (FP7-PEOPLE- 2012-IEF, 328364). Sequences associated with this paper have been deposited in Genbank with accession numbers KT188437 and KT188438

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7–12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery