A Questionnaire Survey on Long-Term Outcomes in Cats Breed-Screened for Feline Cardiomyopathy

Simple Summary Feline cardiomyopathy (FCM) is a serious, potentially fatal disease in cats. There is an international screening program that aims to identify pedigree cats affected with FCM, as the disease is believed to be inherited in some cat families. Using a self-reporting questionnaire, this study explored the long-term outcomes of cats breed-screened for FCM. We found that approximately 9.3% of the cats developed FCM at some time-point of which approximately 50% were diagnosed within the screening program and 50% of these cats at the first breed-screen occasion. For cats that did develop FCM, there was a significantly higher risk for a cardiac related death and also a shorter time to all-cause mortality, compared to cats that did not develop FCM. Frequency and types of non-cardiac disease were similar in all screen classification groups. The large proportion of cats that did develop FCM later in life, despite normal previous screen results, underscores the value of repeated breed-screenings later in life to identify cats that develop FCM. Feline cardiomyopathy (FCM) is an important contributor to feline morbidity and mortality. This explorative follow-up questionnaire study was aimed at investigating the long-term outcome in cats breed-screened for FCM (BS-FCM) in three Nordic countries. Records of cats with >= 1 BS-FCM between 2004-2015 were included. Of the 1113 included cats, 104/1113 (9.3%) had developed FCM at some time-point. Fifty-nine of the 104 (56.7%) FCM cats were diagnosed within the screening program (Screen(FCM)), and 33/59 (55.9%) of these were diagnosed at the first BS-FCM. Screen(FCM) cats or with an owner-reported FCM diagnosis at a later time-point had a higher risk of cardiac-related death compared to cats that never developed FCM. A shorter lifespan was found in Screen(FCM) cats compared to those with normal screen results (p < 0.001). Times to all-cause mortality were shorter (p < 0.001) in cats that developed FCM at any time-point compared to those that did not. Non-cardiac morbidities were similar in all screen classification groups. The large proportion of cats that developed FCM at a later time-point underscores the need for repeated screenings later in life. Cats that developed FCM at any time-point had a shorter lifespan, with a similar proportion and in line with the nature of non-cardiac morbidities, compared to those without FCM

Mapping variability in allocation of Long-Term Care funds across payer agencies in OECD countries

Introduction: Long-term care (LTC) is organized in a fragmented manner. Payer agencies (PA) receive LTC funds from the agency collecting funds, and commission services. Yet, distributional equity (DE) across PAs, a precondition to geographical equity of access to LTC, has received limited attention. We conceptualize that LTC systems promote DE when they are designed to set eligibility criteria nationally (vs. locally); and to distribute funds among PAs based on needs-formula (vs. past-budgets or government decisions). Objectives: This cross-country study highlights to what extent different LTC systems are designed to promote DE across PAs, and the parameters used in allocation formulae. Methods: Qualitative data were collected through a questionnaire filled by experts from 17 OECD countries. Results: 11 out of 25 LTC systems analyzed, fully meet DE as we defined. 5 systems which give high autonomy to PAs have designs with low levels of DE; while nine systems partially promote DE. Allocation formulae vary in their complexity as some systems use simple demographic parameters while others apply socio-economic status, disability, and LTC cost variations. Discussion and conclusions: A minority of LTC systems fully meet DE, which is only one of the criteria in allocation of LTC resources. Some systems prefer local priority-setting and governance over DE. Countries that value DE should harmonize the eligibility criteria at the national level and allocate funds according to needs across regions

The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human

BackgroundDilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.MethodsWe performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.ResultsOur results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.ConclusionsCollectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies

Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines

IntroductionThe correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification.MethodsGenetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant.ResultsTwo variants, MYBPC3:c.91G &gt; C [A31P] and MYBPC3:c.2453C &gt; T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G &gt; A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance.DiscussionRoutine genetic testing is advised solely for the MYBPC3:c.91G &gt; C [A31P] in the Maine Coon and MYBPC3:c.2453C &gt; T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial

Economic perspectives on the obesity epidemic

This thesis takes its starting point in the large spread and rise in obesity prevalence that have been observed around the world, making obesity an increasing public health concern. The thesis consists of an introductory chapter, which justifies the study of obesity from economic perspectives and puts the subsequent studies in context, and four studies that address obesity from different economic perspectives. The first study follows a cohort of Swedish women, aged 20-68 in 1980/81, to analyze income-related inequalities in obesity. Using a version of the concentration index, it finds that the risk of obesity is concentrated among the poorer, but over time, as the cohort ages, inequality declines, because in absolute terms obesity prevalence increases uniformly across the income distribution. The study uses a long-run income measure, and shows that long-run inequality differs substantially from short-run inequality. The second study uses U.S. cross-sectional data between 1960 and 2008 to study time trends in obesity, severe obesity, and body-mass index for different educational, income, and racial/ethnic groups. It shows that, with some exceptions, the greatest part of the increases in body-mass index and obesity over time are shared by individuals in all subgroups of society, despite well-known baseline disparities (particularly among women). This result has implications for our understanding of the kinds of societal changes that have really had an impact on individual decision making and thereby caused the obesity epidemic. Plausible explanations for the obesity epidemic must be consistent with universal trends and should not affect particular socioeconomic groups only. The third study has more of a methodological nature and examines whether measures of socioeconomic disparities in body-mass index and obesity are biased because self-reported weight and height tend to have errors (misreporting), and because body-mass index does not take body composition into account (misclassification). Among women, different educational groups misreport differently, leading to underestimation of the education disparity when using self-reported information. Male disparities are more sensitive to the definition of obesity. Estimating the risk of obesity defined by using waist circumference gives rise to an educational gradient, which is not present when using body-mass index to classify men. Finally, the fourth study continues the discussion about decision making and explanations for the obesity epidemic. It takes the view that institutions may shape individual behavior through norms and habits, and explores the role of economic freedom at the macroeconomic level as one such institution. The main empirical analysis uses a panel of 31 high-income countries and data for the period 1983 to 2008, and finds a positive and statistically significant relationship between the level of economic freedom and both the level of, and five-year change in, BMI

Recent PhDs

This section consists of an overview (names, universities, thesis title and abstracts) of new PhD:s within the field of health economics in the Nordic countries. Published: December 2017

Deltidsarbete bland kvinnor i Sverige - vad påverkar val av arbetstid?

English title: Part-time work among women in Sweden – what influences choice of working hours? In the 1960s and 70s a large growth in part-time work amongst women in the Swedish labour market took place. A net inflow of workers into the labour market has been suggested as the main source. However, part-time work is still a common phenomenon among Swedish women; in 2004 almost 40% of all women worked part-time, and women are clearly dominating the part-time sector. A gradual changeover from house work to market work is hardly a valid explanation anymore. The purpose of this essay is to examine factors that contribute to women’s decision to work part-time in modern society. A time allocation model and a family model form the theoretical background. Productivity in both house and market work, preferences and comparative advantages are factors which are emphasised by theory. Education level, family situation, age and job qualification are concrete examples of this. An initial illustration with aggregated data from 1987-2004 also gives an idea that these are aspects which differ among women who work part- and full time. Based on micro data from 1996-2003 from the Swedish Labour Force Surveys, estimations of probit models suggest that the probability to work part-time increases if a woman is married, has a child or is co-habiting and has a child. Branch of industry also seems to have considerable effect, and having an unqualified job (reflecting education and wage) increases the probability of part-time. Hence, since it is indicated that there are mostly poorly educated women in lower position jobs who work part-time, it seems reasonably to infer that many of these women have limited opportunities to be self-sufficient. To a larger extent, they depend on income from somewhere else; a partner or the state. The data processing and modelling further imply that the choice between so-called short and long part-time work as well as men’s choice of working hours are made on a somewhat different basis. Certainly, men and women have closed in on each other regarding working hours. Nevertheless family and type of job still seem to be important factors for the choice, in spite of several policy changes along with increased wages and higher education for women. Wage differences and values are discussed as conceivable and important explanations, and thereby also as potential areas for action

More equal but heavier: A longitudinal analysis of income-related obesity inequalities in an adult Swedish cohort.

Using longitudinal data over a 17-year period for a Swedish cohort aged 20-68 in 1980/1981, this study analyses income-related inequalities in obesity. By using the concentration index and decomposition techniques we answer the following questions: We find that among females, inequalities in obesity favour the rich, but the inequality declines over time. Income itself is the main driving force behind obesity inequality, whereas being single (as opposed to being married or cohabiting) is an important counteracting factor. The main reason for the reduced obesity inequality over time is increased obesity prevalence, because in absolute terms obesity has increased uniformly across income groups. Because the income elasticity of obesity is the single most important contributor to the inequality, policies directed towards this factor might be the most effective for reducing obesity inequality. Our main income variable is within-individual mean of income, and we thereby focus on long-run inequality and are able to standardize for income mobility. The results show that inequality based on short-run income differs substantially from inequality based on long-run income. For males we find similar inequality trends as for women, although less pronounced. This difference between men and women should be taken into account when evaluating obesity reducing policies

Bigger bodies: Long-term trends and disparities in obesity and body-mass index among U.S. adults, 1960-2008.

Increasing obesity rates and corresponding public health problems are well-known, and disparities across socioeconomic groups are frequently reported. However, the literature is less clear on whether the increasing trends are specific to certain socioeconomic groups and whether disparities in obesity are increasing or decreasing over time. This knowledge sheds light on the understanding of the driving forces to the ongoing worldwide increases in obesity and body-mass index and gives guidance to plausible interventions aiming at reverting weights back to healthy levels. The purpose of this study is to explore long-term time trends and socioeconomic disparities in body-mass index and obesity among U.S. adults. Individual level data from ten cycles of the National Health and Nutrition Examination Survey between 1960 and 2008 are used to estimate adjusted time trends in the probabilities of obesity and severe obesity and in measured body-mass index for three racial/ethnical groups, for three educational groups, and for four levels of income, stratified by gender. Time trends in the probabilities of obesity and severe obesity are estimated by linear probability models, and trends at the 15th, 50th and 85th percentiles of the adjusted body-mass index distribution are estimated by quantile regression. Divergent time trends for the different socioeconomic groups are estimated by interaction terms between socioeconomic status and year. The results show that, with some exceptions, increases in both obesity, severe obesity and body-mass index are similar across the different racial/ethnic, educational and income groups. We conclude that the increase in body-mass index and obesity in the United States is a true epidemic, whose signal hallmark is to have affected an entire society. Accordingly, a whole-society approach is likely to be required if the increasing trends are to be reversed