Absolute risk estimation of new-onset proteinuria in patients with systemic lupus erythematosus: a Danish nationwide cohort study.

OBJECTIVES: Kidney involvement and medical compliance are frequent challenges in systemic lupus erythematosus (SLE). Additional data reporting such as absolute risk estimates may strengthen risk stratification and compliance. This study provides absolute risk estimations of risk of new-onset proteinuria among SLE patients. METHODS: Danish SLE centres provided clinical data on first time observations of proteinuria and other clinical parameters listed in the 1997 American College of Rheumatology Classification Criteria for SLE. Time from first occurring non-renal manifestation to new-onset proteinuria or censoring defined time at risk. Multivariate Cox-regression models were used to identify risk factors for new-onset proteinuria and to calculate risk of proteinuria stratified by risk factor debut age, duration, and sex. RESULTS: The patient population consisted of 586 patients with SLE, mainly Caucasian (94%) women (88%), mean age at inclusion of 34.6 years (standard deviation, SD=14.4 years), observed for a mean of 14.9 years (SD=11.2 years). The cumulative prevalence of proteinuria was 40%. Discoid rash, HR =0.42 (p=0.01) and lymphopenia HR=1.77 (p=0.005) were associated with new-onset proteinuria. Male patients with lymphopenia had the highest predictive risks of proteinuria with a 1-, 5- and 10-year risk of proteinuria ranging from 9-27%, 34-75% and 51-89%, depending on the age at presentation (debut at 20, 30, 40 or 50 years). The corresponding risk profiles for women with lymphopenia were 3-9%, 8-34% and 12-58%, respectively. CONCLUSIONS: Large differences in absolute risk estimates for new-onset proteinuria were identified. The differences may aid risk stratification and patient compliance among high-risk individuals.

Patients' assessment of care for type 2 diabetes: Results of the Patient Assessment of Chronic Illness Care scale in a Danish population.

BACKGROUND: The Patient Assessment of Chronic Illness Care (PACIC) scale is the most appropriate for assessing self-reported experience in chronic care. We aimed to validate the PACIC questionnaire by (1) assess patients' perception of the quality of care for Danish patients with type 2 diabetes, (2) identify which factors are most important to the quality of care designated by the five subscales in PACIC, and (3) the validity of the questionnaire. METHODS: A survey of 7,745 individuals randomly selected from the National Diabetes Registry. Descriptive statistics inter-item and item-rest correlations and factor analysis assessed the PACIC properties. Quality of care was analysed with descriptive statistics; linear and multiple regression assessed the effect of forty-nine covariates on total and subscale scores. RESULTS: In total, 2,696 individuals with type 2 diabetes completed ≥ 50 % of items. The floor effect for individual items was 8.5-74.5 %; the ceiling effect was 4.1-47.8 %. Cronbach's alpha was 0.73-0.86 for the five subscales. The comparative fit index (CFI) and the Tucker-Lewis index (TLI) were 0,87, and 0,84, respectively. Mean PACIC score was 2.44 (± 0.04). Respondents, who receive diabetes care primarily at general practice and outpatient clinics had higher scores compared to those receiving care at a private specialist. Receiving rehabilitation was followed by higher scores in all subscales. Those 70 years or older had lower mean total and subscale scores compared to younger patient groups. A higher number of diabetes visits were associated with higher total scores; a higher number of emergency department visits were associated with lower total scores. The effects of healthcare utilisation on subscale scores varied. CONCLUSIONS: These results provide insight into variations in the quality of provided care and can be used for targeting initiatives towards improving diabetes care. Factors important to the quality of perceived care are having a GP or hospital outpatient clinic as the primary organization. Also having a higher number of visits to the two organizations are perceived as higher quality of care as well as participating in a rehabilitation program. Floor and ceiling effects were comparable to an evaluation of the PACIC questionnaire in a Danish population. Yet, floor effects suggest a need for further evaluation and possible improvement of the PACIC questionnaire in a Danish setting. Total PACIC scores were lower than in other healthcare systems, possible being a result of different contexts and cultures, and of a need for improving diabetes care in Denmark.

Likelihood ratios for evaluating DNA matches obtained from a database search when there is substructure in the population.

DNA database searches are frequently conducted to identify the suspects of crimes. When a match is obtained from such a database search, the evidence must be evaluated. Existing methods for assessment of the DNA evidence in this scenario require assumption of stochastic independence between the profiles in the database. However, when there is substructure in the population, this assumption is violated. The problem of how to account for population substructure in the database search scenario is analyzed and a solution in the form of a bounded estimate for the likelihood ratio is presented. The implications of these methods are investigated in a realistic scenario using published forensic allele frequencies to simulate ten-locus DNA profiles. In the simulated example, it is observed that the strength of the evidence can be inflated by more than a factor of 10 in 11.6% of database search cases if mild population substructure is ignored. With these methods, the magnitude of the subpopulation effect in the database search scenario can be quantified and the weight of the evidence of a DNA match more accurately assessed.

Social disparities in the prevalence of multimorbidity - A register-based population study.

BACKGROUND: Prevalences of multimorbidity vary between European studies and several methods and definitions are used. In this study we examine the prevalence of multimorbidity in relation to age, gender and educational attainment and the association between physical and mental health conditions and educational attainment in a Danish population. METHODS: A cross-sectional design was used to study the prevalence of multimorbidity, defined as two or more chronic conditions, and of comorbid physical and mental health conditions across age groups and educational attainment levels among 1,397,173 individuals aged 16 years and older who lived in the Capital Region of Denmark on January 1st, 2012. After calculating prevalence, odds ratios for multimorbidity and mental health conditions were derived from logistic regression on gender, age, age squared, education and number of physical conditions (only for odds ratios for mental health conditions). Odds ratios for having multimorbidity and mental health conditions for each variable were adjusted for all other variables. RESULTS: Multimorbidity prevalence was 21.6%. Half of the population aged 65 and above had multimorbidity, and prevalence was inversely related to educational attainment: 26.9% (95% CI, 26.8-26.9) among those with lower secondary education versus 13.5% (95% CI, 13.5-13.6) among people with postgraduate education. Adjusted odds ratios for multimorbidity were 0.50 (95% CI, 0.49-0.51) for people with postgraduate education, compared to people with lower secondary education. Among all population members, 4.9% (95% CI, 4.9-4.9) had both a physical and a mental health condition, a proportion that increased to 22.6% of people with multimorbidity. Physical and mental health comorbidity was more prevalent in women (6.33%; 95% CI, 6.3-6.4) than men (3.34%; 95% CI, 3.3-3.4) and approximately 50 times more prevalent among older persons than younger ones. Physical and mental health comorbidity was also twice as prevalent among people with lower secondary education than among those with postgraduate education. The presence of a mental health condition was strongly associated with the number of physical conditions; those with five or more physical conditions had an adjusted odds ratio for a mental health condition of 3.93 (95% CI, 3.8-4.1), compared to those with no physical conditions. CONCLUSION: Multimorbidity prevalence and patterns in the Danish population are comparable to those of other European populations. The high prevalence of mental and physical health conditions highlights the need to ensure that healthcare systems deliver care that takes physical and mental comorbidity into account. Further, the higher prevalence of multimorbidity among persons with low educational attainment emphasizes the importance of having a health care system providing care that is beneficial to all regardless of socioeconomic status.

Grain protein concentration and harvestable protein under future climate conditions. A study of 108 spring barley accessions.

In the present study a set of 108 spring barley (H. vulgare L.) accessions were cultivated under predicted future levels of temperature and [CO2] as single factors and in combination (IPCC, AR5, RCP8.5). Across all genotypes, elevated [CO2] (700 ppm day/night) slightly decreased protein concentration by 5%, while elevated temperature (+5 °C day/night) substantially increased protein concentration by 29%. The combined treatment increased protein concentration across accessions by 8%. This was an increase less than predicted from strictly additive effects of the individual treatments. Despite the increase in grain protein concentration, the decrease in grain yield at combined elevated temperature and elevated [CO2] resulted in 23% less harvestable protein. There was variation in the response of the 108 accessions, which might be exploited to at least maintain if not increase harvestable grain protein under future climate change conditions.

Concurrent elevation of CO2, O3 and temperature severely affects oil quality and quantity in rapeseed.

Plant oil is an essential dietary and bio-energy resource. Despite this, the effects of climate change on plant oil quality remain to be elucidated. The present study is the first to show changes in oil quality and quantity of four rapeseed cultivars in climate scenarios with elevated [CO2], [O3] and temperature (T) combined and as single factors. The combination of environmental factors resembled IPCC's 'business as usual' emission scenario predicted for late this century. Generally, the climate scenarios reduced the average amounts of the six fatty acids (FAs) analysed, though in some treatments single FAs remained unchanged or even increased. Most reduced was the FA essential for human nutrition, C18:3-ω3, which decreased by 39% and 45% in the combined scenarios with elevated [CO2]+T+[O3] and [CO2]+T, respectively. Average oil content decreased 3-17%. When [CO2] and T were elevated concurrently, the seed biomass was reduced by half, doubling the losses in FAs and oil content. This corresponded to a 58% reduction in the oil yield per hectare, and C18:3-ω3 decreased by 77%. Furthermore, the polyunsaturated FAs were significantly decreased. The results indicate undesirable consequences for production and health benefits of rapeseed oil with future climate change. The results also showed strong interactive effects of CO2, T and O3 on oil quality, demonstrating why prediction of climate effects requires experiments with combined factors and should not be based on extrapolation from single factor experiments.

Evaluation of temporal surveillance system sensitivity and freedom from bovine viral diarrhea in Danish dairy herds using scenario tree modelling.

BACKGROUND: The temporal sensitivity of the surveillance system (TemSSe) for Bovine Viral Diarrhea (BVD) in Danish dairy herds was evaluated. Currently, the Danish antibody blocking ELISA is used to test quarterly bulk tank milk (BTM). To optimize the surveillance system as an early warning system, we considered the possibility of using the SVANOVIR ELISA, as this test has been shown to detect BVD-positive herds earlier than the blocking ELISA in BTM tests. Information from data (2010) and outputs from two published stochastic models were fed into a stochastic scenario tree to estimate the TemSSe. For that purpose we considered: the risk of BVD introduction into the dairy population, the ELISA used and the high risk period (HRP) from BVD introduction to testing (at 90 or 365 days). The effect of introducing one persistently infected (PI) calf or one transiently infected (TI) milking cow into 1 (or 8) dairy herd(s) was investigated. Additionally we estimated the confidence in low (PLow) herd prevalence (<8/4109 infected herds) and the confidence in complete freedom (PFree) from BVD (< 1/4109). RESULTS: The TemSSe, the PLow, and the PFree were higher, when tests were performed 365 days after BVD introduction, than after 90 days. Estimates were usually higher for the SVANOVIR than for the blocking ELISA, and when a PI rather than a TI was introduced into the herd(s). For instance, with the current system, the median TemSSe was 64.5 %, 90 days after a PI calf was introduced into eight dairy herds. The related median PLow was 72.5 %. When a PI calf was introduced into one herd the median TemSSe was 12.1 %, while the related PFree was 51.6 %. With the SVANOVIR ELISA these estimates were 99.0 %; 98.9 %, 43.7 % and 62.4 %, respectively. CONCLUSIONS: The replacement of the blocking ELISA with the SVANOVIR could increase the TemSSe, the PLow and PFree remarkably. Those results could be used to optimize the Danish BVD surveillance system. Furthermore, the approach proposed in this study, for including the effect of the HRP within the scenario tree methodology, could be applied to optimize early warning surveillance systems of different animal diseases.

Characterization of the bacterial gut microbiota of piglets suffering from new neonatal porcine diarrhoea.

BACKGROUND: In recent years, new neonatal porcine diarrhoea (NNPD) of unknown aetiology has emerged in Denmark. NNPD affects piglets during the first week of life and results in impaired welfare, decreased weight gain, and in the worst-case scenario death. Commonly used preventative interventions such as vaccination or treatment with antibiotics, have a limited effect on NNPD. Previous studies have investigated the clinical manifestations, histopathology, and to some extent, microbiological findings; however, these studies were either inconclusive or suggested that Enterococci, possibly in interaction with Escherichia coli, contribute to the aetiology of NNPD. This study examined ileal and colonic luminal contents of 50 control piglets and 52 NNPD piglets by means of the qPCR-based Gut Microbiotassay and 16 samples by 454 sequencing to study the composition of the bacterial gut microbiota in relation to NNPD. RESULTS: NNPD was associated with a diminished quantity of bacteria from the phyla Actinobacteria and Firmicutes while genus Enterococcus was more than 24 times more abundant in diarrhoeic piglets. The number of bacteria from the phylum Fusobacteria was also doubled in piglets suffering from diarrhoea. With increasing age, the gut microbiota of NNPD affected piglet and control piglets became more diverse. Independent of diarrhoeic status, piglets from first parity sows (gilts) possessed significantly more bacteria from family Enterobacteriaceae and species E. coli, and fewer bacteria from phylum Firmicutes. Piglets born to gilts had 25 times higher odds of having NNPD compared with piglets born to multiparous sows. Finally, the co-occurrence of genus Enterococcus and species E. coli contributed to the risk of having NNPD. CONCLUSION: The results of this study support previous findings that points towards genus Enterococcus and species E. coli to be involved in the pathogenesis of NNPD. Moreover, the results indicate that NNPD is associated with a disturbed bacterial composition and larger variation between the diarrhoeic piglets.

Fluorescence in situ hybridization investigation of potentially pathogenic bacteria involved in neonatal porcine diarrhea.

BACKGROUND: Neonatal diarrhea is a multifactorial condition commonly present on pig farms and leads to economic losses due to increased morbidity and mortality of piglets. Immature immune system and lack of fully established microbiota at birth predispose neonatal piglets to infection with enteric pathogens. The microorganisms that for decades have been associated with enteritis and diarrhea in suckling piglets are: rotavirus A, coronavirus, enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens type C, Cryptosporidium spp., Giardia spp., Cystoisospora suis and Strongyloides ransomi. However, in recent years, the pig industry has experienced an increased number of neonatal diarrhea cases in which the above mentioned pathogens are no longer detected. Potentially pathogenic bacteria have recently received focus in the research on the possible etiology of neonatal diarrhea not caused by common pathogens. The primary aim of this study was to investigate the role of E. coli, Enterococcus spp., C. perfringens and C. difficile in the pathogenesis of neonatal porcine diarrhea with no established casual agents. Fluorescence in situ hybridization with oligonucleotide probes was applied on the fixed intestinal tissue samples from 51 diarrheic and 50 non-diarrheic piglets collected from four Danish farms during outbreaks of neonatal diarrhea not caused by well-known enteric pathogens. Furthermore, an association between the presence of these bacteria and histological lesions was evaluated. RESULTS: The prevalence of fluorescence signals specific for E. coli, C. perfringens and C. difficile was similar in both groups of piglets. However, Enterococcus spp. was primarily detected in the diarrheic piglets. Furthermore, adherent bacteria were detected in 37 % diarrheic and 14 % non-diarrheic piglets. These bacteria were identified as E. coli and Enterococcus spp. and their presence in the intestinal mucosa was associated with histopathological changes. CONCLUSIONS: The results of this study showed that simultaneous colonization of the intestinal mucosa by adherent non-ETEC E. coli and Enterococcus spp. can be involved in the pathogenesis of neonatal porcine diarrhea. These bacteria should be considered in diagnosis of diarrhea in piglets, when detection of common, well-known enteric agents is unsuccessful.

Trends in overweight and obesity in Danish children and adolescents: 2000-2008--exploring changes according to parental education.

AIMS: To examine the hypotheses that an overall levelling off in the prevalence of overweight and obesity during the period 2000-2008 has occurred, and that increasing social inequality in overweight and obesity exists in a nationally representative sample of Danish children and adolescents. METHODS: The population comprised a random sample of 1849 children aged 4-14 years who participated in the Danish National Survey of Diet and Physical Activity in 2000-2002, 2003-2004 and 2005-2008. Parental education was chosen as an indicator of children's socioeconomic status. Body mass index (BMI) was calculated from parent-reported weight and height. Subjects were classified as overweight and obese according to the International Obesity Task Force age- and gender-specific BMI cut-off values. Crude prevalence estimates and logistic regression models were used to analyse trends in overweight and obesity as the main outcome measures. RESULTS: An increase was found in the crude prevalence of overweight (including obesity) in boys (12.8-21.7%, p = 0.0006), but not in girls (17.6-15.9%, p = 0.56), between 2000-2002 and 2005-2008. The prevalence of overweight increased significantly in boys of parents with low educational level only. A strong inverse social gradient in overweight and obesity was documented for boys and girls during the whole survey period. CONCLUSIONS: The present study showed an increase in the prevalence of overweight in Danish boys, but not in girls. This increase was due to increasing social inequality in overweight among boys. Public health initiatives aimed at preventing and reducing overweight and obesity should consider gender difference and especially target boys with parents of low educational level.

Danish children born to parents with lower levels of education are more likely to become overweight.

AIM: Little is known about whether the socio-economic status of parents is linked to their children becoming overweight. This study examined the association between parents' educational level and overweight Danish children in a nationally representative sample. METHODS: Body mass index was calculated for a random sample of 512 children aged from four to 14 from the Danish National Survey of Diet and Physical Activity 2005-2008. Their parents provided weight and height data during an interview, together with details of their own educational level. Children were classified as overweight/obese in accordance with the International Obesity Task Force. Frequency estimates of prevalence and logistic regression models were used to correlate childhood overweight/obesity with the mothers' and fathers' educational levels as the main outcome measures. RESULTS: Danish mothers tended to be more highly educated than fathers and their educational level was inversely associated with their child being overweight, especially if it was a boy. However, the highest educational level of the parents was the only significant educational variable, suggesting that education was associated with overweight children irrespective of the gender of the parent. CONCLUSION: Public health initiatives should target parents with low educational levels to prevent, and reduce, social inequality in overweight children.

Clusters from chronic conditions in the Danish adult population.

Multimorbidity, the presence of 2 or more chronic conditions in a person at the same time, is an increasing public health concern, which affects individuals through reduced health related quality of life, and society through increased need for healthcare services. Yet the structure of chronic conditions in individuals with multimorbidity, viewed as a population, is largely unmapped. We use algorithmic diagnoses and the K-means algorithm to cluster the entire 2015 Danish multimorbidity population into 5 clusters. The study introduces the concept of rim data as an additional tool for determining the number of clusters. We label the 5 clusters the Allergies, Chronic Heart Conditions, Diabetes, Hypercholesterolemia, and Musculoskeletal and Psychiatric Conditions clusters, and demonstrate that for 99.32% of the population, the cluster allocation can be determined from the diagnoses of 4-5 conditions. Clusters are characterized through most prevalent conditions, absent conditions, over- or under-represented conditions, and co-occurrence of conditions. Clusters are further characterized through socioeconomic variables and healthcare service utilizations. Additionally, geographical variations throughout Denmark are studied at the regional and municipality level. We find that subdivision into municipality levels suggests that the Allergies cluster frequency is positively associated with socioeconomic status, while the subdivision suggests that frequencies for clusters Diabetes and Hypercholesterolemia are negatively correlated with socioeconomic status. We detect no indication of association to socioeconomic status for the Chronic Heart Conditions cluster and the Musculoskeletal and Psychiatric Conditions cluster. Additional spatial variation is revealed, some of which may be related to urban/rural populations. Our work constitutes a step in the process of characterizing multimorbidity populations, leading to increased comprehension of the nature of multimorbidity, and towards potential applications to individual-based care, prevention, the development of clinical guidelines, and population management.

Low-carbon diets across diverse dietary patterns: Addressing population heterogeneity under constrained optimization.

Mathematical optimization is a useful tool for modeling diets that fulfill requirements for health and environmental sustainability, however, population-based optimization approaches fail to account for underlying dietary diversity in populations. This study proposes a methodological approach to consider diverse dietary intake patterns in mathematical optimization of nutritionally adequate low-carbon diets and investigates the differences between different population groups, along with trade-offs between greenhouse gas emission (GHGE) reduction and the inconvenience of dietary changes required to achieve optimized diets. A k-means clustering analysis was applied to individual dietary intake data from Denmark, which resulted in four clusters with different dietary patterns. This was followed by quadratic programming, wherein the total dietary changes required from the observed diet within each cluster were used as a proxy for consumer inconvenience (i.e., "inconvenience index") and were minimized while fulfilling nutrient constraints and incrementally tightened GHGE constraints. Across clusters, a steep increase of the inconvenience index was observed at GHGE levels below approximately 3 kg CO2e/10 MJ, corresponding to GHGE reductions of 24-36 % in different clusters. In all clusters, the optimized diets with nutritional and GHGE constraints showed common traits of increased content of cereals and starches, eggs, and fish and decreased amounts of beef and lamb, cheese, animal-based fats, and alcoholic beverages, but differences across clusters were also observed, maintaining characteristics of the clusters' baselines. When additional health-based targets for food amounts were applied as constraints, the optimized diets converged towards the same type of diet. The total inconvenience of dietary changes required to fulfill constraints differed between clusters, indicating that specific sub-populations may be more effective targets for dietary transition. The method has potential for future integration of more sustainability aspects and different consumer preferences.

Correction: Longitudinal models for the progression of disease portfolios in a nationwide chronic heart disease population.

[This corrects the article DOI: 10.1371/journal.pone.0284496.].

Correction: Longitudinal models for the progression of disease portfolios in a nationwide chronic heart disease population.

[This corrects the article DOI: 10.1371/journal.pone.0284496.].

The Gut Microbiotassay: a high-throughput qPCR approach combinable with next generation sequencing to study gut microbial diversity.

BACKGROUND: The intestinal microbiota is a complex and diverse ecosystem that plays a significant role in maintaining the health and well-being of the mammalian host. During the last decade focus has increased on the importance of intestinal bacteria. Several molecular methods can be applied to describe the composition of the microbiota. This study used a new approach, the Gut Microbiotassay: an assembly of 24 primer sets targeting the main phyla and taxonomically related subgroups of the intestinal microbiota, to be used with the high-throughput qPCR chip 'Access Array 48.48', AA48.48, (Fluidigm®) followed by next generation sequencing. Primers were designed if necessary and all primer sets were screened against DNA extracted from pure cultures of 15 representative bacterial species. Subsequently the setup was tested on DNA extracted from small and large intestinal content from piglets with and without diarrhoea. The PCR amplicons from the 2304 reaction chambers were harvested from the AA48.48, purified, and sequenced using 454-technology. RESULTS: The Gut Microbiotassay was able to detect significant differences in the quantity and composition of the microbiota according to gut sections and diarrhoeic status. 454-sequencing confirmed the specificity of the primer sets. Diarrhoea was associated with a reduced number of members from the genus Streptococcus, and in particular S. alactolyticus. CONCLUSION: The Gut Microbiotassay provides fast and affordable high-throughput quantification of the bacterial composition in many samples and enables further descriptive taxonomic information if combined with 454-sequencing.

Changes in Diet and Physical Activity among 18-65-Year-Olds after the First National COVID-19 Lockdown in Denmark.

COVID-19 lockdowns affected everyday life significantly and made it challenging to achieve or maintain a healthy lifestyle. The aim of the present study was to examine longitudinal changes in Danish adults' eating habits and physical activity (PA) assessed during and after the first national lockdown in 2020. Furthermore, changes in body weight were examined during the first lockdown period. The whole diet (semi-quantitative Food Frequency Questionnaire), sociodemographic factors, moderate-to-vigorous intensity PA (MVPA), leisure screen time, anthropometrics, change in body weight, and stress level were assessed with a self-administered web-based questionnaire among 839 18-65-year-old Danes during and 5-6 months after the lockdown. Both favorable (decreased intake of saturated fat) and unfavorable (decreased intake of whole grain and fish, and increased intake of red meat) changes were found in the diet after the lockdown, while favorable changes in MVPA (increase in couples) and leisure screen time (decrease with a combined effect of family status and education) were found for PA. More Danish adults reported to gain weight (mean 3.0 kg) than to lose weight (mean 3.5 kg) during the first lockdown period (27% vs. 15%). The study showed favorable changes in PA and mixed results regarding diet among Danish adults after the lockdown. Furthermore, the first lockdown period unfavorably impacted the body weight of many Danes.

Longitudinal models for the progression of disease portfolios in a nationwide chronic heart disease population.

BACKGROUND AND AIM: With multimorbidity becoming increasingly prevalent in the ageing population, addressing the epidemiology and development of multimorbidity at a population level is needed. Individuals subject to chronic heart disease are widely multimorbid, and population-wide longitudinal studies on their chronic disease trajectories are few. METHODS: Disease trajectory networks of expected disease portfolio development and chronic condition prevalences were used to map sex and socioeconomic multimorbidity patterns among chronic heart disease patients. Our data source was all Danish individuals aged 18 years and older at some point in 1995-2015, consisting of 6,048,700 individuals. We used algorithmic diagnoses to obtain chronic disease diagnoses and included individuals who received a heart disease diagnosis. We utilized a general Markov framework considering combinations of chronic diagnoses as multimorbidity states. We analyzed the time until a possible new diagnosis, termed the diagnosis postponement time, in addition to transitions to new diagnoses. We modelled the postponement times by exponential models and transition probabilities by logistic regression models. FINDINGS: Among the cohort of 766,596 chronic heart disease diagnosed individuals, the prevalence of multimorbidity was 84.36% and 88.47% for males and females, respectively. We found sex-related differences within the chronic heart disease trajectories. Female trajectories were dominated by osteoporosis and male trajectories by cancer. We found sex important in developing most conditions, especially osteoporosis, chronic obstructive pulmonary disease and diabetes. A socioeconomic gradient was observed where diagnosis postponement time increases with educational attainment. Contrasts in disease portfolio development based on educational attainment were found for both sexes, with chronic obstructive pulmonary disease and diabetes more prevalent at lower education levels, compared to higher. CONCLUSIONS: Disease trajectories of chronic heart disease diagnosed individuals are heavily complicated by multimorbidity. Therefore, it is essential to consider and study chronic heart disease, taking into account the individuals' entire disease portfolio.

Exploring healthy and climate-friendly diets for Danish adults: an optimization study using quadratic programming.

Background: A transition to healthy and sustainable diets has the potential to improve human and planetary health but diets need to meet requirements for nutritional adequacy, health, environmental targets, and be acceptable to consumers. Objective: The objective of this study was to derive a nutritionally adequate and healthy diet that has the least deviation possible from the average observed diet of Danish adults while aiming for a greenhouse gas emission (GHGE) reduction of 31%, corresponding to the GHGE level of the Danish plant-rich diet, which lays the foundation for the current healthy and sustainable food-based dietary guidelines (FBDGs) in Denmark. Methods: With an objective function minimizing the departure from the average observed diet of Danish adults, four diet optimizations were run using quadratic programming, with different combinations of diet constraints: (1) nutrients only (Nutri), (2) nutrients and health-based targets for food amounts (NutriHealth), (3) GHGE only (GHGE), and finally, (4) combined nutrient, health and GHGE constraints (NutriHealthGHGE). Results: The GHGE of the four optimized diets were 3.93 kg CO2-eq (Nutri), 3.77 kg CO2-eq (NutriHealth) and 3.01 kg CO2-eq (GHGE and NutriHealthGHGE), compared to 4.37 kg CO2-eq in the observed diet. The proportion of energy from animal-based foods was 21%-25% in the optimized diets compared to 34% in the observed diet and 18% in the Danish plant-rich diet. Moreover, compared to the average Danish diet, the NutriHealthGHGE diet contained more grains and starches (44 E% vs. 28 E%), nuts (+230%), fatty fish (+89%), eggs (+47%); less cheese (-73%), animal-based fats (-76%), total meat (-42%); and very limited amounts of ruminant meat, soft drinks, and alcoholic beverages (all-90%), while the amounts of legumes and seeds were unchanged. On average, the mathematically optimized NutriHealthGHGE diet showed a smaller deviation from the average Danish diet compared to the Danish plant-rich diet (38% vs. 169%, respectively). Conclusion: The final optimized diet presented in this study represents an alternative way of composing a nutritionally adequate and healthy diet that has the same estimated GHGE as a diet consistent with the climate-friendly FBDGs in Denmark. As this optimized diet may be more acceptable for some consumers, it might help to facilitate the transition toward more healthy and sustainable diets in the Danish population.

Listen Carefully protocol: an exploratory case-control study of the association between listening effort and cognitive function.

INTRODUCTION: A growing body of evidence suggests that hearing loss is a significant and potentially modifiable risk factor for cognitive impairment. Although the mechanisms underlying the associations between cognitive decline and hearing loss are unclear, listening effort has been posited as one of the mechanisms involved with cognitive decline in older age. To date, there has been a lack of research investigating this association, particularly among adults with mild cognitive impairment (MCI). METHODS AND ANALYSIS: 15-25 cognitively healthy participants and 15-25 patients with MCI (age 40-85 years) will be recruited to participate in an exploratory study investigating the association between cognitive functioning and listening effort. Both behavioural and objective measures of listening effort will be investigated. The sentence-final word identification and recall (SWIR) test will be administered with single talker non-intelligible speech background noise while monitoring pupil dilation. Evaluation of cognitive function will be carried out in a clinical setting using a battery of neuropsychological tests. This study is considered exploratory and proof of concept, with information taken to help decide the validity of larger-scale trials. ETHICS AND DISSEMINATION: Written approval exemption was obtained by the Scientific Ethics Committee in the central region of Denmark (De Videnskabsetiske Komiteer i Region Hovedstaden), reference 19042404, and the project is registered pre-results at clinicaltrials.gov, reference NCT04593290, Protocol ID 19042404. Study results will be disseminated in peer-reviewed journals and conferences.