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There is a lack of knowledge about the health consequences of politically initiated forced permanent rehousing (FPR) of residents in social housing areas. This study investigates if FPR is associated with the contact frequency with general practitioner (GP) and the proportion of residents who use antidepressants. The study included 432 rehoused residents matched 1:2 with remaining residents and residents from a comparable neighbouring area without exposure to rehousing. For GP contact frequency, we conducted a difference-in-difference analysis while the proportion of residents who used antidepressants was investigated through descriptive statistics. We found high GP contact frequency in the three groups, but no significant differences. Further, we found a low proportion of residents who used antidepressants in all groups, but a small increase from baseline to follow-up. Our results thus suggest that FPR neither affected the rehoused residents' GP contact frequency nor the proportion who used antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Empirical evaluation of inverse probability weighting (IPW) for self-selection bias correction is inaccessible without the full source population. We aimed to: (i) investigate how self-selection biases frequency and association measures and (ii) assess self-selection bias correction using IPW in a cohort with register linkage., Methods: The source population included 17 936 individuals invited to the Copenhagen Aging and Midlife Biobank during 2009-11 (ages 49-63 years). Participants counted 7185 (40.1%). Register data were obtained for every invited person from 7 years before invitation to the end of 2020. The association between education and mortality was estimated using Cox regression models among participants, IPW participants and the source population., Results: Participants had higher socioeconomic position and fewer hospital contacts before baseline than the source population. Frequency measures of participants approached those of the source population after IPW. Compared with primary/lower secondary education, upper secondary, short tertiary, bachelor and master/doctoral were associated with reduced risk of death among participants (adjusted hazard ratio [95% CI]: 0.60 [0.46; 0.77], 0.68 [0.42; 1.11], 0.37 [0.25; 0.54], 0.28 [0.18; 0.46], respectively). IPW changed the estimates marginally (0.59 [0.45; 0.77], 0.57 [0.34; 0.93], 0.34 [0.23; 0.50], 0.24 [0.15; 0.39]) but not only towards those of the source population (0.57 [0.51; 0.64], 0.43 [0.32; 0.60], 0.38 [0.32; 0.47], 0.22 [0.16; 0.29])., Conclusions: Frequency measures of study participants may not reflect the source population in the presence of self-selection, but the impact on association measures can be limited. IPW may be useful for (self-)selection bias correction, but the returned results can still reflect residual or other biases and random errors., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: To describe the current content of low back pain (LBP) care in Danish general practice, the patients' self-management activities, and the clinicians' experienced barriers to providing best practice care., Methods: This cross-sectional observational study included adults with LBP seeking care in Danish general practice from August 2022 to June 2023. Patient-reported information included demographics, pain intensity, medical history, treatments, and self-management strategies. Clinicians provided data specific to each consultation, detailing the content of these consultations, and barriers to best practice in the specific cases., Results: The study involved 71 clinicians from 42 general practice clinics, with patient-reported data from 294 patients, and clinician-reported data from 283 (95%) consultations. The mean age for the included patients was 53 years, 56% were female, and 31% had been on sick leave for LBP during the previous 3 months. Moreover, 44% had seen two or more healthcare professionals in the previous month, 55% had previously undergone diagnostic imaging for LBP, 81% reported using any type of analgesics, and 14% reported using opioids. The majority (91%) reported engaging in self-management activities to alleviate pain. Consultations typically included a physical examination (84%), information about the cause of the pain (74%), and management advice (68%), as reported by clinicians or patients. In general, clinicians reported consultation elements more frequently than patients. Clinicians reported providing best practice care in 84% of cases, with time constraints (23%) and patient expectations (10%) being the most common barriers., Conclusions: This study provides detailed insights into the management of LBP in Danish general practice. It reveals a complex landscape of patient engagement, varying management strategies, and differing perceptions of care content between patients and clinicians. Patients were often engaged in self-management activities and clinicians reported few barriers to providing best practice care., (© 2024 The Author(s). Musculoskeletal Care published by John Wiley & Sons Ltd.)

Ischemic heart disease (IHD) causes mortality and morbidity. High levels of occupational physical activity (OPA) increases IHD risk, and occupational lifting (OL) is suggested as a detrimental OPA exposure. This study investigated the association between accumulated OL throughout working life, and risk for IHD, and potential sex and hypertension differences. Data from Copenhagen Ageing and Midlife Biobank linked to register-based information on incident IHD during 9 years follow-up in the Danish National Patient Registry were included. The outcome was the odds of IHD from baseline (2009-2011) to end of follow-up (2018), among participants without IHD at baseline. Accumulated OL was assessed by linking occupational codes to a Job Exposure Matrix, creating a measure in ton-years (lifting 1,000 kg/day/year). Multivariable logistic regression tested associations between level of accumulated OL and IHD, among the 6,606 included individuals (68% men). During follow-up, 7.3% men and 3.6% women were hospitalized with IHD. Among all participants, the odds for IHD were 47% (OR 1.47, 95% CI 1.05-2.06) higher among those with ≥5 to <10 ton-years, 39% (OR 1.39, 95% CI 1.06-1.83) higher among those with ≥10 to <30 ton-years, and 62% (OR 1.62, 95% CI 1.18-2.22) higher among those with ≥30 ton-years, compared to no accumulated OL. However, these increased odds were in the same direction in the fully-adjusted model but statistically insignificant, ≥5 to <10 ton-years OR 1.28, 95% CI 0.88-1.88; ≥10 to <30 ton-years OR 1.20, 95% CI 0.85-1.69; and ≥30 ton-years OR 1.22, 95% CI 0.81-1.84. No statistically significant interactions, nor any associations, between OL and sex, or hypertension were seen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife., Methods: A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions)., Results: Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015)., Conclusions: Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty., (© 2024. The Author(s).)

Area regeneration of deprived neighborhoods is being used to reduce health inequality, socioeconomic deprivation and ethnic segregation. This quasi-experimental study examines if long-term graded exposure to urban regeneration is associated with primary healthcare-seeking behavior among residents. We compared general practitioner (GP) contacts from 2015-2020 in two adjacent, deprived social housing areas, one exposed to area regeneration. Populations were into Western and non-Western males and females aged 15 years and older (N = 3,960). Mean annual GP contact frequency for each group were estimated and a difference-in-difference (DiD) analysis was conducted with adjustments for propensity scores based on baseline characteristics. GP contact frequency increased for all groups across time with a systematically higher level and faster increase in the control groups. In particular, the mean difference between the exposed and control area for Western women increased from -4.67 to -5.76 annual contacts across the period. The mean differences in contact frequency increased for all groups but results of the DiD analyses were insignificant. In conclusion, an increasing gap in GP contact frequency, with the highest levels in the control area, was observed for all comparisons across time. More long-term research is needed to understand how the increasing gaps evolve.

Background: Partnership break-up and living alone is associated with several negative health-related outcomes. Little is known about the association with physical functional ability in a life course perspective. The aim of this study is to investigate (1) the association between number of partnership break-ups and years living alone across 26 years of adult life respectively and objectively measured physical capability in midlife, (2) how the joint exposure of accumulated break-ups or years living alone respectively, and education relates to physical capability in midlife and (3) potential gender differences., Methods: Longitudinal study of 5001 Danes aged 48-62. Accumulated number of partnership break-ups and years living alone were retrieved from national registers. Handgrip strength (HGS) and number of chair rises (CR) were recorded as outcomes in multivariate linear regression analyses adjusted for sociodemographic factors, early major life events and personality., Results: Increasing number of years living alone was associated with poorer HGS and fewer CR. Concomitant exposure to short educational level and break-ups or long duration of time living alone respectively was associated with poorer physical capability compared with the groups with long educational level and no break-ups or few years lived alone., Conclusion: Accumulated number of years living alone but not break-ups was associated with poorer physical functional ability. Joint exposure to a high number of years lived alone or break-ups respectively and having a short education was associated with the lowest levels of functional ability, which points towards an important target group for interventions. No gender differences were suggested., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Area deprivation is associated with adverse mental health outcomes. In Denmark, urban regeneration is being used to dissolve concentrated socio-economic area deprivation and ethnic segregation. However, evidence on how urban regeneration affects mental health of residents is ambiguous partly due to methodological challenges. This study investigates if urban regeneration affects users of antidepressant and sedative medication among residents in an exposed and control social housing area in Denmark., Methods: Using a longitudinal quasi-experimental design we measured users of antidepressant and sedative medication in one area undergoing urban regeneration compared with a control area. We measured prevalent and incident users from 2015 to 2020 among non-Western and Western women and men and used logistic regression to measure annual change in users over time. Analyses are adjusted for a covariate propensity score estimated using baseline socio-demographic characteristics and general practitioner contacts., Results: Urban regeneration did not affect the proportion of prevalent nor incident users of antidepressant and sedative medication. However, levels were high in both areas compared with the national average. Descriptive levels of prevalent and incident users were generally lower among residents in the exposed area compared with the control area for most years and stratified groups confirmed by the logistic regression analyses., Conclusion: Urban regeneration was not associated with users of antidepressant or sedative medication. We found lower levels of antidepressant and sedative medication users in the exposed area compared with the control area. More studies are needed to investigate the underlying reasons for these findings, and whether they could be related to underuse., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aims to describe demographics, social relations and health in an ethnically diverse social housing area selected to undergo large structural changes and compare it to the surrounding municipality. Furthermore, to explore the association between social relations and self-rated health (SRH) and the interaction with country of origin in both populations., Methods: Data sources include a multilingual interviewer-driven survey study in a social housing area (N = 209) and a municipal health survey (N = 1,638) among residents aged 45 + years. Information on social relations include contact frequency with and support from family, friends, and neighbors. Descriptive and multivariate logistic regression analyses adjusted for age, sex, and country of origin are presented, as well as joint effect analyses of social relations and country of origin on SRH., Results: In the social housing area, 38.8% of the respondents reported poor SRH compared to 19.5% in the municipality. In both study populations low contact frequency was associated with poor SRH, however insignificantly in the social housing area compared to the municipality sample, OR = 1.50 (0.65-3.46) vs. OR = 2.42 (1.70-3.45). Joint exposure to having non-Western background and low contact frequency was strongly associated with poor SRH in the social housing area, OR = 6.28 (1.80-21.89) but less so in the municipality, OR = 3.67 (1.55-8.69). The same tendency was seen regarding low support from social relations., Conclusions: This study provides insight to a population that is generally underrepresented in survey studies. In the social housing area, approximately twice as many reported poor SRH compared to the municipality data. In both populations, low contact frequency and low support were associated with poor SRH. Residents with weak social relations and non-Western origin simultaneously were more likely to report poor SRH in the social housing area specifically but less so in the municipality, indicating a higher vulnerability among the residents in the social housing area., (© 2023. The Author(s).)

Objectives: Due to increasing pressure on healthcare resources, knowledge of factors that affect healthcare utilization (HCU) is important. However, the evidence of a longitudinal association between loneliness and social isolation respectively, and HCU is limited. The present prospective cohort study investigated the association of loneliness and social isolation with HCU in the general population over time., Method: Data from the 2013 Danish "How are you?" survey (n = 27.501) were combined with individual-level register data with almost complete follow-up over a 6-year follow-up period (2013-2018). Negative binomial regression analyses were performed while adjusting for baseline demographics and preexisting chronic disease., Results: Loneliness measured was significantly associated with more general practice contacts (incident rate ratio [IRR] = 1.03, 95% confidence interval [CI] [1.02, 1.04]), more emergency treatments (IRR = 1.06, [1.03, 1.10]), more emergency admissions (IRR = 1.06, [1.03, 1.10]), and hospital admission days (IRR = 1.05, [1.00, 1.11]) across the 6-year follow-up period. No significant associations were found between social isolation and HCU with one minor exception, in which social isolation was associated with fewer planned outpatient treatments (IRR = 0.97, [0.94, 0.99]). Wald test demonstrated that the association of loneliness with emergency admissions and hospital admissions days was not significantly different from the effects of social isolation on those outcomes., Conclusions: Our findings suggest that loneliness slightly increased the number of general practice contacts and emergency room treatments. Overall, the effects of loneliness and social isolation on HCU were small. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Urban regeneration often intends to improve the physical, economic, and social environment of disadvantaged neighborhoods. However, evidence on the consequences of such interventions on place-based social relations is limited in Scandinavia. This study investigates the relationship between urban regeneration and diverse forms of place-based social relations among middle-aged and older social housing residents in Denmark. A longitudinal multi-method design was applied using data from administrative registers and semi-structured individual interviews. The quantitative results showed small changes in household-restricted place-based social relations, whereas participants in the qualitative sample described the disruption of place-based social relations to negatively affect their well-being., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To document the challenges of developing and executing an interviewer-driven survey questionnaire in an ethnically diverse and deprived social housing area undergoing reconstruction in Denmark. Methods: The survey was initially planned to be conducted in three waves (before, during and after reconstruction of the housing area), based on a questionnaire covering health, wellbeing and social relations. The first two waves took place in 2018 and 2019 (invited n =~600 per wave) and the third wave will be conducted once the reconstruction is finalised. The approach to the third wave is under revision by the research team. The questionnaire was translated from Danish into the seven most common languages in the housing area. A bilingual interview team went door to door interviewing residents. Field notes were collected systematically during each wave to document the process. Results: The response rates were 35% ( n =209) and 22% ( n =132) for waves 1 and 2, respectively. There was an overall decrease in response rates between waves 1 and 2 for all language groups, but particularly for Arabic and Turkish-speaking men. The most frequently stated reasons for non-participation included illness and language barriers. The key lessons learnt were that overcoming linguistic and cultural barriers to conducting research among residents in this social housing area requires time and resources. Conclusions: Several challenges are associated with conducting a survey in ethnically diverse and deprived social housing areas. Documenting the challenges and learning from experience are both important, in order to include this hard-to-reach population in health research.

Background: Social integration and perceived neighborhood environment are recognized as important social determinants of health. However, little is known about the association between social integration and perceived neighborhood environment among underrepresented population groups, such as residents in disadvantaged neighborhoods, in public health research. The aim of this study is to: 1) Describe the levels of social integration and 2) Investigate the association between social integration and neighborhood dissatisfaction and unsafety among middle-aged and older social housing residents., Methods: A multilingual face-to-face interviewer-administrated survey questionnaire was conducted among 206 residents aged 45 years and above (response rate: 34.1%) of various nationalities in disadvantaged socioeconomic positions in a social housing area in Denmark. The assessment of social integration was based on cohabitation status, frequency of face-to-face and non-face-to-face interaction with social relations and participation in local association activities. Neighborhood dissatisfaction measured the level of dissatisfaction with the neighborhood, and neighborhood unsafety assessed the level of unsafety being outdoors in the neighborhood. Descriptive statistics were conducted to illustrate respondent characteristics and the distribution of social integration among the study population. Logistic regression models were applied to analyze associations between social integration and neighborhood dissatisfaction and unsafety, adjusted for age, sex, country of origin, educational attainment and employment status., Results: In total, 23.8% of the respondents reported low levels of social integration. A medium level of social integration was associated with higher odds of neighborhood dissatisfaction (OR: 2.36; 95% CI: 1.04-5.38) compared to the highest level of integration. A low frequency of face-to-face interaction was associated with higher odds of neighborhood dissatisfaction (OR: 2.65; 95% CI: 1.16-6.06) and neighborhood unsafety (OR: 2.41; 95% CI: 1.04-5.57) compared to the highest frequency of face-to-face interaction., Conclusions: Almost one-fourth of respondents reported low levels of social integration. A medium level of social integration was associated with neighborhood dissatisfaction. A low frequency of face-to-face interaction was associated with neighborhood dissatisfaction and unsafety. The results suggest that targeted health promotion interventions designed to foster face-to-face interaction, hold potential to reduce neighborhood dissatisfaction and unsafety among residents in disadvantaged neighborhoods., (© 2022. The Author(s).)

Burning candles at home emit small particles and gases that pollute indoor air. Exposure to fine particles in outdoor air has been convincingly linked to cardiovascular and respiratory events, while the associations with fine and ultrafine particles from candle burning remain unexplored. We examined the association between the use of candles and incident cardiovascular and respiratory events. We collected data on 6757 participants of the Copenhagen Aging and Midlife Biobank cohort recruited in 2009 and followed them up for the first hospital contact for incident cardiovascular and respiratory events until 2018. We investigated an association between the self-reported frequency of candle use in wintertime and cardiovascular and respiratory events, using Cox regression models adjusting for potential confounders. During follow-up, 1462 and 834 were admitted for cardiovascular and respiratory events, respectively. We found null associations between candle use and a hospital contact due to cardiovascular and respiratory events, with hazard ratios (HRs) and 95% confidence intervals (CI) of 0.97 (95% CI: 0.84, 1.11) and 0.98 (95% CI: 0.81, 1.18), respectively, among those using candles >4 times/week compared with <1 time/week. For cause-specific cardiovascular diseases, HRs were 1.10 (95% CI: 0.85, 1.43) for ischemic heart disease and 1.18 (95% CI: 0.77, 1.81) for myocardial infarction. For chronic obstructive pulmonary disease, HR was 1.26 (95% CI: 0.81, 1.97). We found no statistically significant associations between candle use and the risk of cardiovascular and respiratory events. Studies with improved exposure assessments are warranted., (© 2022 The Authors. Indoor Air published by John Wiley & Sons Ltd.)

This study reports on a health promotion intervention (HPI), where graphic facilitation (GF) was used as an innovative method to enable participation in a co-design process in a multi-ethnic and disadvantaged neighbourhood in Denmark. The aim was to enable middle-aged and older residents to participate in the research process of planning and evaluating the HPI, as well as in the activities it constituted. GF was used to document statements and inputs from residents through visual meeting minutes and resident experiences with coronavirus disease 2019 (COVID-19) lockdown were drawn by a graphic facilitator. We use the ladder of participation as a framework to unfold the participation enabled by GF. During the HPI, data were produced through ethnographic field studies in and outside the neighbourhood and in design workshops with residents. The study finds that GF helped in reaching a target group difficult to engage in research and that the engagement of a graphic facilitator shifted the power-balance between the researchers and the residents, redistributing expertise. Carrying out GF in a HPI is a collaborative endeavour and in addition to research competences, it requires the artistic and relational skills of a graphic facilitator. The co-created process of the visual minutes and COVID-19 experiences created a sense of ownership and encouraged the residents to reflect on their interaction with the researchers. The redistribution of expertise was conditioned by the power dynamics present and GF helped unfold these dynamics. This is especially important in an HPI engaging socio-economically vulnerable populations., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Frequent nighttime smartphone use can disturb healthy sleep patterns and may adversely affect mental health and wellbeing. This study aims at investigating whether nighttime smartphone use increases the risk of poor mental health, i.e. loneliness, depressive symptoms, perceived stress, and low life satisfaction among young adults. High-dimensional tracking data from the Copenhagen Network Study was used to objectively measure nighttime smartphone activity. We recorded more than 250,000 smartphone activities during self-reported sleep periods among 815 young adults (university students, mean age: 21.6 years, males: 77%) over 16 weekdays period. Mental health was measured at baseline using validated measures, and again at follow-up four months later. Associations between nighttime smartphone use and mental health were evaluated at baseline and at follow-up using multiple linear regression adjusting for potential confounding. Nighttime smartphone use was associated with a slightly higher level of perceived stress and depressive symptoms at baseline. For example, participants having 1-3 nights with smartphone use (out of 16 observed nights) had on average a 0.25 higher score (95%CI:0.08;0.41) on the Perceived stress scale ranging from 0 to 10. These differences were small and could not be replicated at follow-up. Contrary to the prevailing hypothesis, nighttime smartphone use is not strongly related to poor mental health, potentially because smartphone use is also a social phenomenon with associated benefits for mental health., (© 2022. The Author(s).)

This study aimed to examine the extent to which allostatic load (AL), measured in midlife, mediates the association between educational attainment in young adulthood and self-rated health (SRH) in midlife among women and men. The study used data from the Copenhagen Aging and Midlife Biobank (CAMB; n = 5467 participants, aged 48-62 years, 31.5% women). Educational attainment was assessed as years of education. SRH was assessed with one item: 'In general, how would you say your health is?' with response options from "excellent" to "poor". AL mediated 31.7% and 19.7% of the association between educational attainment and SRH in women and men, respectively. We observed that higher educational attainment was associated with better SRH and lower AL in both women and men. Our study showed that AL partly mediates the association between educational attainment in young adulthood and SRH in adulthood among both men and women. This study indicates that educational attainment in young adulthood affects health throughout life. Such knowledge of a potential mediator may be important in breaking the social heritage., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Findings about the relationship between individuals' social relations and general practitioner (GP) contact are ambiguous as to whether weak social relations are associated with an increased or decreased consultation pattern. Furthermore, social relations may affect GP contact differently for men compared to women, between socioeconomic groups and according to perceived need. The overall aim of the study is to examine the association between functional aspects of social relations, perceived emotional and instrumental social support, the tendency to consult a GP and the frequency of GP contact., Methods: The study comprised 6911 individuals aged 49-61 at baseline from the Copenhagen Aging and Midlife Biobank (CAMB). We conducted a two-part regression to explore the association between perceived emotional and instrumental social support and GP contact (tendency and frequency), controlling for age, sex, occupational social class, cohabitation status and number of morbidities., Results: Results show no overall effect of the perceived social support aspects of social relations on GP contact independent of health-related needs., Conclusions: Our results do not support that perceived social support, reflecting functional aspects of social relations, are associated with general practitioner contact among middle-aged people., Trial Registration: The study has been registered and approved by the Danish Data Protection Agency and the local ethical committee (approval No.H-A-2008-126 and No. 2013-41-1814)., (© 2022. The Author(s).)

Ambient air pollution causes a range of adverse health effects, whereas effects of indoor sources of air pollution are not well described in high-income countries. We compared hazards of ambient air pollution and indoor sources with respect to important biomarkers of cardiorespiratory effects in terms of lung function and systemic inflammation in a middle-aged Danish cohort. Our cohort comprised 5199 men and women aged 49-63 years at the recruitment during April 2009 to March 2011, with information on exposure to second-hand smoke (SHS) and use of candles, wood stove, kerosene heater and gas cooker as well as relevant covariates. Ambient air pollution exposure was assessed as 2-year mean nitrogen dioxide (NO 2 ) at the address (mean ± SD: 17.1 ± 9.9 μg/m 3 ) and 4-day average levels of particulate matter with diameter <2.5 μm (PM 2.5 ; mean ± SD: 12.5 ± 6.0 μg/m 3 ) in urban background. Lung function was assessed as % predicted forced expiratory volume in the first second (FEV1) and inflammatory markers comprised interleukin-6 (IL-6), IL-10, IL-18, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hs-CRP). We used random-effect regression models controlling for potential confounders as well as models with further adjustment for self-reported health or for all other exposures. In models adjusted for confounders FEV1 was inversely associated with exposure to NO 2 , (-0,83% per 10 μg/m 3 ; 95% CI: -1.26; -0.41%), SHS (-0.56% per 1 of 5 categories increment; 95% CI: -0.89; -0.23%), and gas cooker without hood (-0.89%; 95% CI: -1.62; -0.17%), whereas use of wood stove and candles showed positive associations, although these attenuated by mutual adjustment for all exposures or self-reported health. IL-6 showed positive associations with NO 2 (6.30% increase in log-transformed values per 10 μg/m 3 ; 95% CI: 3.54; 9.05%), PM 2.5 (7.82% per 10 μg/m 3 ; 95% CI: 3.35; 12.4%), SHS (4.38% per increase of 1 of 5 categories; 95% CI: 2.22; 6.54%) and use of kerosene (13.8%; 95% CI: 2.51; 25.1%), whereas the associations with use of wood stove and candles were inverse. PM 2.5 and NO 2 showed positive associations with IFN-γ and TNF-α, while PM 2.5 further associated with IL-10 and IL-18. Hs-CRP was inversely associated with use of candles. These results suggest that the levels of exposure to ambient air pollution and SHS are more harmful than are the levels of exposure to indoor combustion sources from candles and wood stoves in a high-income setting., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: The ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using various health indicators as well as changes in these indicators for predicting mortality remains unclear. The aim of this study was to investigate whether changes in health indicators such as frailty and physical performance improve mortality predictions in old age., Methods: This is a population based prospective cohort study on 995 community-dwelling people aged 68-92 years from the Longitudinal Aging Study Amsterdam. Two measurements at a three-year interval (1995/1996 and 1998/1999) were available for the frailty index, frailty phenotype, grip strength, walking speed, and Mini-Mental State Examination (MMSE). Cox regression was used to analyze mortality risks associated with the current health status and changes in health, with mortality data up to 2017. The extent to which these health indicators improved mortality predictions compared to models with age and sex only was assessed by the area under the receiver operating characteristic curve (AUC)., Results: The AUC of age and sex for five-year mortality was 72.8% (95% CI 69.0 - 76.5) and was the lowest in the oldest old (age > 80.5 years). The added AUC of the current status of health indicators ranged from 0.7 to 3.3%. The added AUC of the three-year change was lower, ranging from -0.0 to 1.1%, whereas the added AUC of three-year change and current status combined was similar to current status alone, ranging from 0.6 to 3.2%. Across age, the added AUC of current status was highest in the oldest old, however there was no such pattern using three-year change. Overall, the frailty index appeared to improve mortality predictions the most, followed by the frailty phenotype, MMSE, grip strength, and walking speed., Conclusions: Current health status improved mortality predictions better than changes in health. Its contribution was highest in the oldest old, but the added value to models with age and sex only was limited., (© 2022. The Author(s).)

Background: Partnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups or years lived alone across 26 years of adult life are associated with levels of inflammation, and if vulnerability with regards to gender or educational level can be identified., Methods: 4835 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48-62 years were included. Data on accumulated numbers of partnership breakups and years living alone were retrieved from a national standardised annual register. Inflammatory markers interleukin 6 (IL-6) and high sensitivity C-reactive protein (hsCRP) were measured in blood samples. Multivariate linear regression analyses were adjusted for age, educational level, early major life events, body mass index, chronic diseases, medicinal intake affecting inflammation, acute inflammation and personality scores., Results: For men, an association was found between an increasing number of partnership breakups or number of years living alone and higher levels of inflammatory markers. No such association was found for women, and no evidence of partnership breakups and educational level having a joint effect was found for either gender., Conclusion: The findings suggest a strong association between years lived alone or accumulated number of partnership breakups and low-grade inflammation for middle-aged men, but not for women. Among those of either sex with a lower level of education, no specific vulnerability to accumulated years lived alone or number of breakups was identified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

During biologics development, manufacturers must demonstrate clearance of host cell impurities and contaminants to ensure drug purity, manufacturing process consistency, and patient safety. Host cell proteins (HCPs) are a major class of process-related impurities and require monitoring and documentation of their presence through development and manufacturing. Even in residual amounts, they are known to affect product quality and efficacy as well as patient safety. HCP analysis using enzyme-linked immunosorbent assay (HCP-ELISA) is the standard technique, due to its simple handling, short analysis time, and high sensitivity for protein impurities. Liquid chromatography mass spectrometry (LC-MS) is an orthogonal method for HCP analysis and is increasingly included in regulatory documentation. LC-MS offers advantages where HCP-ELISA has drawbacks, e.g., the ability to identify and quantify individual HCPs. This article summarizes the available knowledge about monitoring HCPs in biologics and presents the newest trends in HCP analysis with current state-of-the-art HCP measurement tools. Through case studies, we present examples of HCP control strategies that have been used in regulatory license applications, using an MS-based coverage analysis and HCP-ELISA and LC-MS for HCP quantification. This provides novel insight into the rapid evolving strategy of HCP analysis. Improvements in technologies to evaluate HCP-ELISA suitability and the implementation of orthogonal LC-MS methods for HCP analysis are important to rationally manipulate, engineer, and select suitable cell lines and downstream processing steps to limit problematic HCPs., (© 2021. The Author(s).)

Background: The potential association between level of education and age-related cognitive decline remains an open question, partly because of a lack of studies including large subsamples with low education and follow-up intervals covering a substantial part of the adult lifespan., Objectives: To examine cognitive decline assessed by a comprehensive clinical test of intelligence over a 35-year period of follow-up from ages 50 to 85 and to analyze the effect of education on trajectories of cognitive decline, including the effects of selective attrition., Methods: A longitudinal cohort study with a 35-year follow-up of community dwelling members of the Glostrup 1914 cohort. The study sample comprised 697 men and women at the 50-year baseline assessment and additional participants recruited at later follow-ups. Verbal, Performance, and Full Scale IQs were assessed using the Wechsler Adult Intelligence Scale at ages 50, 60, 70, 80, and 85. To be able to track cognitive changes between successive WAIS assessments, all IQs were based on the Danish 50-year norms. Information on school education was self-reported. The association between education and cognitive decline over time was examined in growth curve models. Selective attrition was investigated in subsamples of participants who dropped out at early or later follow-ups., Results: The trajectories for Verbal, Performance, and Full Scale IQ showed higher initial cognitive performance, but also revealed steeper decline among participants with a formal school exam compared to participants without a formal exam. Verbal IQ showed the largest difference in level between the two educational groups, whereas the interaction between education and age was stronger for Performance IQ than for Verbal IQ. In spite of the difference in trajectories, higher mean IQ was observed among participants with a formal school exam compared to those without across all ages, including the 85-year follow-up. Further analyses revealed that early dropout was associated with steeper decline, but that this effect was unrelated to education., Conclusion: Comprehensive cognitive assessment over a 35-year period suggests that higher education is associated with steeper decline in IQ, but also higher mean IQ at all follow-ups. These findings are unlikely to reflect regression towards the mean, other characteristics of the employed test battery or associations between educational level and study dropout., Competing Interests: The authors have declared that no competing interests exist.

Aims: To investigate the effects of objectively measured smartphone interactions on indicators of mental well-being among men and women in a population of young adults. Methods: A total of 816 young adults (mean±SD age 21.6±2.6 years; 77% men) from the Copenhagen Network Study were followed with objective recordings of smartphone interactions from calls, texts and social media. Participants self-reported on loneliness, depressive symptoms and disturbed sleep at baseline and in a four-month (interquartile range 75-163 days) follow-up survey. Multiple linear regression was used to analyse the association between smartphone interactions and mental well-being separately for men and women. Results: A higher number of smartphone interactions was associated with lower levels of loneliness at baseline and the same pattern appeared for depressive symptoms, although this was less pronounced. A high level of smartphone interaction was associated with lower levels of disturbed sleep for men, but not for women. In follow-up analyses, a high versus low level of smartphone interaction was associated with an increase in loneliness and depressive symptoms over time for women, but not for men. Conclusions: Smartphone interactions are related to better mental well-being, which may be attributed to the beneficial effects of an underlying social network. Over time, accommodating a large network via smartphone communication might, however, have negative effects on mental well-being for women.

Background: Research suggests that loneliness and social isolation (SI) are serious public health concerns. However, our knowledge of the associations of loneliness and SI with specific chronic diseases is limited., Purpose: The present prospective cohort study investigated (a) the longitudinal associations of loneliness and SI with four chronic diseases (cardiovascular disease [CVD], chronic obstructive pulmonary disease [COPD], diabetes mellitus Type 2 [T2D], and cancer), (b) the synergistic association of loneliness and SI with chronic disease, and (c) baseline psychological and behavioral explanatory factors., Methods: Self-reported data from the 2013 Danish "How are you?" survey (N = 24,687) were combined with individual-level data from the National Danish Patient Registry on diagnoses in a 5 year follow-up period (2013-2018)., Results: Cox proportional hazard regression analyses showed that loneliness and SI were independently associated with CVD (loneliness: adjusted hazard ratio (AHR) = 1.20, 95% confidence interval [CI; 1.03, 1.40]; SI: AHR = 1.23, 95% CI [1.04, 146]) and T2D (loneliness: AHR =1.90, 95% CI [1.42, 2.55]; SI: AHR = 1.59, 95% CI [1.15, 2.21]). No significant associations were found between loneliness or SI and COPD and cancer, respectively. Likewise, loneliness and SI did not demonstrate a synergistic effect on chronic disease. Multiple mediation analysis indicated that loneliness and SI had an indirect effect on CVD and T2D through both baseline psychological and behavioral factors., Conclusion: Loneliness and SI were independently associated with a diagnosis of CVD and T2D within a 5 year follow-up period. The associations of loneliness and SI with CVD and T2D were fully explained by baseline psychological and behavioral factors., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We investigated whether midlife forgetfulness was prospectively associated with changes in social relations at work (SRW) among occupationally active individuals in Denmark., Methods: We analyzed data of 2339 men and women participating in the first (1990) and second (1995) survey of the Danish Work Environment Cohort Study, responding to questions on working environment, SRW, and forgetfulness. We used multiple linear regression analysis while adjusting for potential confounders., Results: At baseline (1990), 517 (22.1%) study participants were categorized as forgetful. Forgetfulness was prospectively associated with a decline in one of the investigated items reflecting a negative aspect of SRW (experiencing teasing, regression coefficient = 0.07, 95% CI: 0.03 to 0.11), while no association was observed with positive aspects of SRW., Conclusions: Our findings did not support the hypothesis that memory problems such as midlife forgetfulness negatively affect SRW.

Background: An association between education and dementia is well-established but it is unclear whether education is associated with dementia after accounting for early life cognitive ability and whether there is a joint effect, such that the risk associated with one of the exposures depends on the value of the other. We examined separate and joint associations of adolescent cognitive ability and educational attainment with risk of dementia among Danish men born between 1939 and 1959., Methods: Men (N = 477,421) from the Danish Conscription Database were followed for dementia from the age 60 for up to 17 years via patient and prescription registry linkages. Exposure measures included cognitive ability assessed at the conscript board examination around age 18 and highest educational level (low: 0-10 year, medium: 10-13 years, high: ≥13 years) at age 30 from registry records. Associations with dementia diagnosis were estimated in Cox proportional hazards models adjusted for birth year and age at conscript board examination. Interaction was assessed on the multiplicative scale by including a product term between the two exposure measures and on the additive scale by calculating relative excess risk due to interaction (RERI) between different levels of the exposure measures., Results: Compared to men in the high education group hazard ratio [HR] for men in the medium and low group were 1.21 (95% confidence interval [CI]: 1.13, 1.30) and 1.34 (95% CI: 1.24, 1.45), respectively when not adjusting for cognitive ability. Additional adjustment for cognitive ability attenuated the magnitude of the associations, but they remained significant (education medium: HR = 1.10, 95% CI: 1.02, 1.19 and education low: HR = 1.12, 95% CI: 1.02, 1.22). A 10% higher cognitive ability score was associated with a 3.8% lower hazard of dementia (HR = 0.962; 95% CI: 0.957, 0.967), and the magnitude of the association only changed marginally after adjustment for education. Men in the low education group with relatively low cognitive ability were identified as a high-risk subgroup for dementia. The increased risk associated with exposure to both risk factors did, however, not significantly depart from the sum of risk experienced by men only exposed to one of the risk factors (estimates of RERI were not significantly different from 0) and no significant evidence of either additive or multiplicative interactions was found., Conclusions: In conclusion, the results suggest that education and cognitive ability protect against the risk of dementia independently of one another and that increases in educational attainment may at least partially offset dementia risk due to low cognitive ability., Competing Interests: The authors have declared that no competing interests exist.

Monitoring host cell proteins (HCPs) is one of the most important analytical requirements in production of recombinant biopharmaceuticals to ensure product purity and patient safety. Enzyme-linked immunosorbent assay (ELISA) is the standard method for monitoring HCP clearance. It is important to validate that the critical reagent of an ELISA, the HCP antibody, covers a broad spectrum of the HCPs potentially present in the purified drug substance. Current coverage methods for assessing HCP antibody coverage are based on 2D-Western blot or immunoaffinity-purification combined with 2D gel electrophoresis and have several limitations. In the present study, we present a novel coverage method combining ELISA-based immunocapture with protein identification by liquid chromatography-tandem mass spectrometry (LC-MS/MS): ELISA-MS. ELISA-MS is used to accurately determine HCP coverage of an early process sample by three commercially available anti-Escherichia coli HCP antibodies, evading the limitations of current methods for coverage analysis, and taking advantage of the benefits of MS analysis. The results obtained comprise a list of individual HCPs covered by each HCP antibody. The novel method shows high sensitivity, high reproducibility, and enables tight control of nonspecific binding through inclusion of a species-specific isotype control antibody. We propose that ELISA-MS will be a valuable supplement to existing coverage methods or even a replacement. ELISA-MS will increase the possibility of selecting the best HCP ELISA, thus improving HCP surveillance and resulting in a final HCP profile with the lowest achievable risk. Overall, this will be beneficial to both the pharmaceutical industry and patient safety., (© 2020 American Institute of Chemical Engineers.)

Objectives: The aims of this study were to describe changes in height during childhood and to investigate potential changes in the proportion of children attaining final height in childhood and in correlations between child and adult height across birth cohorts., Methods: We included 363 059 children (179 906 girls) from the Copenhagen School Health Records Register, who were born between 1930 and 1989, with height measurements at ages 7, 10, or 13 years. Linkages to data resources containing adult height values between ages 18 and 69 years were possible for a subpopulation of 96 133 individuals (23 051 women). Birth years were categorized as 1930 to 1939, 1940 to 1949, and 1950 to 1989. Descriptive height statistics were estimated by birth years and birth cohorts. Height correlations were examined using sex- and age-specific partial Pearson correlation analyses and meta-regression techniques., Results: Across 60 birth years, mean child heights at age 7 increased by 2.9 cm in girls and 3.0 cm in boys, and adult heights increased as well. The proportions of children attaining final height by age 13 remained low across the birth cohorts; nonetheless, there was a significant increase from 0.7% to 1.5% in girls only (P < .0001). Both child-child and child-adult height correlations were strong and remained relatively stable across birth cohorts., Conclusions: Mean child and adult height increased during the study period, but the proportion of children attaining final height at age 13 remained low. Child-child and child-adult height correlations were largely unchanged across birth cohorts., (© 2019 Wiley Periodicals, Inc.)

Background: There is general agreement that non-specific low back pain is best understood within a biopsychosocial understanding of health. However, clinicians and patients seemingly adhere to a biomedically derived diagnostic model, which may introduce misperceptions of pain and does not inform treatment or prognosis., Objective: To explore, from the perspective of health-care practitioners, how persistent non- specific low back pain may be communicated in a way that moves beyond a biomedical diagnosis., Design: An explorative qualitative investigation using a constructivist diagnostic framework., Methods: Focus group and individual interviews of 10 purposefully selected chiropractors, physio-therapists and general practitioners were codified and thematically analysed., Results: Four themes emerged: "Clinicians' nuanced understanding of back pain"; "The challenges of shared decision-making"; "Cultural barriers to moving beyond biomedicine"; and "More than a label - individual explanations for pain". Pain and disability were perceived as products of multiple bio-psycho-social factors. Clinicians identified the impact of multiple social actors, an unhealthy work culture, and the organization of the medical system on the notion of pain and suffering., Conclusion: Clinicians perceived a need to communicate the complexity of non-specific low back pain in order to help patients make sense of their condition, rather than applying diagnostic labelling. There are multiple barriers to integrating a constructivistic diagnostic framework that need to be overcome.

Emerging evidence points towards a lower quality of life, fragile social relations and suboptimal health behavior and status of residents living in social housing areas characterized by ethnic diversity and socioeconomic deprivation. Community-based health promotion interventions developed in collaboration with the target group and adjusted to the local context can affect the acceptance of and engagement in such interventions. However, few studies have investigated the potential of community-based interventions in deprived social housing areas. This study explores residents' perspectives on engagement in a community-based health promotion intervention focusing on enhancing social relations. The study builds on qualitative methods including participant observations combined with pre- and post-intervention interviews with a selected group of residents ( n = 9). Data were thematically analyzed with focuses on participation in an everyday life context, concepts of othering, and territorial stigmatization. Engagement in the intervention was motivated by the need to establish and enhance social relations, and to explore the world outside the housing area. However, barriers including cultural and language differences among residents, and competing contextual factors, challenged engagement. We conclude that participatory community-based interventions have a potential to enhance social relations in deprived social housing areas. However, adequate support and efforts to overcome the identified barriers are needed.

Objective: How are trajectories of mobility limitations (MLs) among older adults associated with mortality? Do social factors modify these associations? Method: Group-based trajectory modeling was used to identify four trajectories of MLs over a period of 4.5 years among 3,055 older Danes. Mortality analyses were conducted using additive hazard regression models. Results: Compared to older adults without MLs, older adults with high level of MLs who experienced further increase in MLs were associated with the most additional deaths followed by older adults with no MLs at baseline who later experienced limitations and older adults with a medium ML level at baseline who later experienced further increase in limitations. Men and 80-year olds experienced more additional deaths following adverse ML trajectories than women and 75-year olds. Discussion: Trajectories that led to higher ML levels were associated with most additional deaths especially among men and in the oldest age group.

The association between social relations and health outcomes is well described, but pathways are relatively poorly understood. Inflammation has been suggested as a potential physiological pathway, linking social relations to adverse health outcomes. However, previous studies have shown ambiguous results and have for the vast majority been based on studies small in sample size. The aim of the present study is to examine the association between comprehensive measures of structural and positive as well as negative functional aspects of social relations, across four relational domains-partner/spouse, children, other family and friends, and the level of systemic low-grade inflammation in a large population-based middle-aged cohort and to examine variation by gender and socioeconomic position in these associations. The study comprised of 5576 participants in the Copenhagen Aging and Midlife Biobank. The inflammatory biomarkers collected in late midlife included C-reactive protein, Interleukin-6, and TNF-alpha. Multiple linear regression models were implemented to explore associations between social relations and inflammatory measures controlling for gender, age, socioeconomic position, marital status, early major lifeevents and morbidity. Results show weak and ambiguous associations in all analyses. There were no strong indications of interaction with socioeconomic position. Concluding cautiously, men appear to be more vulnerable toward living alone and low contact frequency with family compared to women as regards high level of low-grade inflammation. In conclusion, this large-scale population-based study among middle-aged men and women showed no association between social relations and low-grade inflammation., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Springer Nature B.V. 2020.)

Context: Many assume that having poor physical health in old age lowers life satisfaction, but in fact there are large differences in life satisfaction among older people who experience disability., Objective: To investigate whether psychosocial factors modify the negative association between disability and life satisfaction in older people and whether these differ across the life course., Design: Cross sectional study., Setting: 66,561 community-dwelling Survey of Health, Ageing, and Retirement in Europe (SHARE) participants aged 50-106 with a mean age of 67.8 ± 9.9 (SD) years from 17 European countries and Israel., Methods: Psychosocial factors included depression (EURO-D scale), perceived loneliness, having a spouse, having children, contact with children, and participation in social activities. Disability was assessed by limitations in (Instrumental) Activities of Daily Living ((I)ADL) and life satisfaction by Cantril's ladder. We also ran the analyses with the Control Autonomy Self-realization Pleasure (CASP-12) Index, a normative measure of quality of life. We used multiple linear regressions to estimate associations and proportion of variance explained., Results: The variance in life satisfaction that could be attributed uniquely to ADL and IADL disability was 0.17% and 0.33% respectively (both p < 0.001). The impact of (I)ADL disabilities on life satisfaction was strongest at age 50 and gradually decreased with increasing age (p trend < 0.001). Mental health explained more variance; 5.75% for depressive symptoms and 2.50% for loneliness and for social resources this ranged from 0.09% to 0.47% (all p < 0.001). While disability has a negative effect on life satisfaction, the effect was not stronger in older persons who were depressed, neither in those who felt lonely nor in those without social resources. Similar outcomes were found when using CASP-12 as the explained variable., Conclusion: The impact of (I)ADL disabilities on life satisfaction in community-dwelling older people decreases with age. These associations are not affected by psychosocial factors and these patterns cannot be explained by people changing their norms and values., Competing Interests: The authors have declared that no competing interests exist.

Background: Social inequality in ischaemic heart disease has been related to socioeconomic position in childhood, early adulthood and late adulthood. However, the impact of relative level of accumulated income periods across adult life course and the potential gender and age differences have not been investigated. The aim was to investigate the association between relative level of accumulated income across the life course and acute myocardial infarction (AMI) from age 60+ years and to study if the associations differ by gender and in different age groups (30-39 years, 40-49 years and 50-59 years)., Methods: All Danes born 1935-1954 (N=1 235 139) were followed up in registers for incident AMI (42 669 cases). The accumulated proportional deviation from median equivalised income (APDMEI) for each gender/age/calendar year strata was constructed and divided in quartiles. The associations were analysed by means of Cox's proportional hazard models., Results: Among men, those in the lowest APDMEI quartile had an HR 1.40 (1.35-1.45) of AMI compared with the highest quartile. Those in the second and third highest quartiles had HR of 1.24 (1.20-1.28) and 1.14 (1.10-1.18), respectively. Among women, the lowest quartile had an HR of 1.78 (1.69-1.88), the second 1.45 (1.37-1.53) and the third 1.19 (1.13-1.26). The social gradient was similar across the different age groups., Conclusion: The risk of AMI increased with lower levels of relative accumulated income across the life course. While men generally had a higher risk of AMI, the social gradient was steeper in women. There was no indication of a specific sensitive age period for exposure to relative level of accumulated income., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Stress and mental health problems impede social functioning and may also complicate relationship formation with peers. The aim was to investigate whether high perceived stress among young adults is associated with social interaction behaviour both via face-to-face interaction and via smartphone interaction. The data was derived from the Copenhagen Network Study, where 535 first-year students (mean age 21.3, 77% male) self-reported on perceived stress at baseline and were subsequently followed for three months with continuous Bluetooth recordings of face-to-face interactions and smartphone interactions (calls and texts) measuring the network size, frequency, and duration of interactions. Logistic regression was used to assess associations between perceived stress (high/low) and social interactions adjusting for sex, age, and personality traits. Participants with high perceived stress were more likely to engage in a larger call and text network and have a higher call and text frequency compared to individuals with low perceived stress. We found a non-statistically significant tendency that participants with a high perceived stress level spend less time meeting face to face with peers. Stressed students engage in frequent smartphone interaction which may be explained by a social support seeking behaviour, or it may be that accommodating a large network via the smartphone is stress-inducing., Competing Interests: The authors have declared that no competing interests exist.

This study assesses the associations between annual measures of economic hardship (EH) across 22 years of adulthood and objective measures of early ageing in a Danish late-middle-aged population ( N  = 5575). EH (years < 60% of the National median equivalized household disposable income) was experienced by 18% during 1987-2008. Four or more years in EH (reference = null years in EH) was related to poorer physical capability (chair rise: - 1.49 counts/30 s [95% confidence interval (CI) - 2.36, - 0.61], hand grip strength: - 1.22 kg [95% CI - 2.38, - 0.07], jump height: - 1.67 cm [95% CI - 2.44, - 0.91] and balance: 18% [95% CI 9, 28]), poorer cognitive function (Intelligenz-Struktur-Test: - 1.50 points [95% CI - 2.89, - 0.12]) and higher inflammatory levels (C-reactive protein: 22% [95% CI 4, 44], and Interleukin-6: 23% [95% CI 10, 39]). Comparing four EH trajectories, people with a high versus low probability of EH over time had poorer physical capability (chair rise: - 1.70 counts/30 s [95% CI - 3.38, - 0.01], grip: - 4.33 kg [95% CI - 6.50, - 2.16], jump: - 1.68 cm [95% CI - 3.12, - 0.25] and balance: 31% [95% CI 12, 52]). No associations were observed with tumour necrosis factor-α. Results were adjusted for sex, age, long-term parental unemployment/financial problems, education, baseline income and cohort. This study suggested EH for four or more years to be associated with poorer physical capability, cognitive function and increased inflammatory levels in midlife. High probability of EH across adulthood was similarly related to poorer physical capability and CRP, but not cognitive function and the remaining inflammatory markers. In conclusion, preventive initiatives focusing on reducing the burden of sustained economic hardship may lead to increased healthy ageing., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Springer Nature B.V. 2019.)

Objective: Investigate direct and indirect associations between markers of socioeconomic position (SEP) across the life course and midlife cognitive ability while addressing methodological limitations in prior work. Method: Longitudinal data from the Danish Metropolit cohort of men born in 1953 ( N = 2,479) who completed ability tests at age 12, 18, and 56-58 linked to register-based information on paternal occupational class, educational attainment, and occupational level. Associations were assessed using structural equation models, and different models were estimated to examine the importance of accounting for childhood ability and measurement error. Results: Associations between adult SEP measures and midlife ability decreased significantly when adjusting for childhood ability and measurement error. The association between childhood and midlife ability was by far the strongest. Discussion: The impact of adult SEP on later life ability may be exaggerated when not accounting for the stability of individual differences in cognitive ability and measurement error in test scores.

Purpose: To assess the association between exposure to physical workload throughout working life and risk of mobility limitations in midlife in a population-based Danish cohort., Methods: The study was cross-sectional with a retrospective exposure assessment, and data were from a questionnaire used in the Copenhagen Aging and Biobank. Cumulative physical workload was estimated by combining information about the participants' employments and data from a job exposure matrix. Daily amount of lifting was standardised in ton-years (lifting 1000 kg/day/year) and grouped in 5 exposure groups (no/minor (1-2 ton-years)/low (3-10 ton-years)/moderate (11-20 ton-years)/high exposure (> 20 ton-years)). The outcome was self-reports of mobility limitations (running 100 m, walking 400 m, and climbing stairs to the 2nd floor) in midlife. The association between exposure and outcome was analysed using logistic regression models., Results: We included 4996 men and 2247 women, mean age 56 years. 21% of men and 10% of women were in the highest exposure-group (> 20 ton-years). Higher cumulative exposure was associated with higher odds for mobility limitations. Exposure to more than 20 ton-years compared to no exposure increased the odds for limitations in walking, age-adjusted odds ratio (OR) 3.2 (95% CI: 2.4-4.3) for men, 2.3 (1.4-3.8) for women. Corresponding results for running: 2.5 (2.2-3.0) for men, 1.6 (1.2-2.2) for women, and for limitations in climbing stairs: 4.2 (3.3-5.2) for men, 1.7 (1.2-2.4) for women. Results were attenuated when confounders were added., Conclusions: Exposure to physical workload throughout working life is associated with higher odds for mobility limitations in midlife.

Introduction: Residential areas constitute an important arena for health, well-being and social relations. Structural interventions such as demolition and area renewal have been used to reduce inequality in health and well-being in disadvantaged areas. However, the effects of larger structural interventions are inconclusive. In a longitudinal perspective, this study aims to analyse how large-scale structural changes in an ethnic diverse social housing area are associated with the residents' health, well-being and social relations., Methods and Analysis: In this multimethods study, we examine this aim among middle-aged and older residents in a multiethnic social housing area in a Danish municipality by the inclusion of comprehensive survey (in 2018, 2019 and 2020), register (yearly 2015-2025) and qualitative (2018-2020) data. Municipal Health Profile survey data from 2017 and 2021 will be used for comparison. The area will undergo large structural changes in the built environment during 2018-2021. A 'natural experiment' (n=6000) compares differences in health and social outcomes across the study period between the study area and a similar neighbouring area not undergoing structural changes. Through user engagement in the design of the study, throughout the different phases of the study and in the two co-created interventions embedded in the study design, a focus on empowerment and recognition of the resources and perspectives of residents are encouraged., Ethics and Dissemination: The study is registered in the University of Copenhagen's record of biobanks and research projects containing personal data and will be conducted in accordance with the principles of the Helsinki Declaration. Residential and municipal representatives and local non-governmental organisations are engaged in the design and execution of the study to ensure the usefulness, reflexive interpretation of data, and relevance of interventions. Results will be published in international peer-reviewed scientific journals, presented at conferences and as short reports through the use of both written and visual outputs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Positive feelings about work and family responsibilities benefit psychological well-being, but their physical health effects remain unexplored. The study assessed whether meaningful work and reward from taking care of family benefitted physical health to the same degree as mental health. Participants were 181 Danes aged 49-51. Participants reported on working conditions, providing care to family, depressive symptoms, and perceived stress. Physical health was operationalized as a physiological dysregulation (e.g., hypertension, high levels of blood sugar and cholesterol, high body mass index). A multidimensional index of physiological dysregulation was created using parameters of cardiovascular, metabolic, and immune function. As expected, meaningful work and sense of reward from taking care of family members were associated with better mental health. However, in women, the very same factors were positively associated with higher physiological dysregulation. We conclude that work and family factors promoting psychological well-being may have physical health trade-offs, particularly in women., Competing Interests: The authors have declared that no competing interests exist.

Background: Microbial exposures early in life have been found to be associated with lower levels of inflammation in adulthood; however, the role of prenatal exposure to infection on offspring inflammatory profiles is unexplored. The aim was to study if maternal infections during pregnancy are associated with inflammation among offspring in later life and to determine if there are sensitive periods of exposure., Methods: The study was comprised of 1719 participants in the Copenhagen Aging and Midlife Biobank (CAMB) who were also members of the Copenhagen Perinatal Cohort (CPC). When the CPC was established, information on maternal infections during pregnancy was prospectively collected by a trained medical doctor. The inflammatory measures collected in late midlife included, C-reactive protein (CRP), Interleukin-6 (IL-6), TNF-alpha (TNF-α) and Interleukin-10 (IL-10). Multivariable ordinary least squared regression models were implemented to explore associations between maternal infection and inflammatory measures in offspring, controlling for maternal smoking, pre-pregnancy body mass index, age, marital status and parity., Results: Maternal infection was associated with a 7% lower CRP level (95% CI, - 17,5%) among offspring compared with offspring born to women without an infection and similarly an 8% lower level of IL-6 (95% CI -15,1%), and a 9% lower level of IL-10 (95% CI, - 23,20%). However, differences did not reach significance. The effects of infection during the first trimester did not differ from infections later in the pregnancy., Conclusions: Our results suggested that prenatal exposure to infection may be associated with lower levels of inflammatory markers among adult offspring. Additional prospective studies are needed to further explore this finding., Competing Interests: The CAMB received ethical approval from the Scientific Ethics Committee Denmark (Protocol # H-A-2008-126).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: It is hypothesised that hostility accentuates the association between stressful conditions and health. This study aims to test this hypothesis by analysing the joint effect of unemployment and hostility on all-cause mortality among men and women., Methods: The population was 3677 men and 4138 women from the Danish workforce who participated in a survey in 2000. The joint exposure variable was defined as 1) employed, not hostile, 2) unemployed, not hostile, 3) hostile and employed, 4) unemployed and hostile. Outcome was defined as all-cause mortality between 2000 and 2014. Data was analysed with Cox proportional hazards models with age as the underlying time scale. The interaction between unemployment and hostility was studied using the synergy index., Results: Compared to employed non-hostile men, men who were both hostile and unemployed were at markedly higher risk of premature death with a hazard ratio (HR) of 3.19 (95% CI 2.22-4.69). A similar picture was found for hostile and unemployed women, with a HR of 1.97 (95% CI 1.24-3.12). However, the mortality in men and women exposed to both did not exceed what was expected from the combination of their individual effects. Hence, we did not find that hostility enhances the association between unemployment and all-cause mortality., Conclusion: Men and women exposed to both unemployment and hostility were at markedly high risk of premature mortality. However, this study did not support the hypothesis that the deleterious health effect of the combination of unemployment and hostility exceeds their individual effects.

Purpose: First, to investigate associations between mobility limitations and use of general practitioners and hospitalizations of acute care sensitive conditions, respectively. Second, to investigate whether these associations vary by socio-demographic factors., Methods: The study included 3574 females and males aged 75 or 80 years from the Danish Intervention Study on Preventive Home Visits. Fixed-effects logistic and poisson regression models were applied to study the relationship between mobility limitations (measured two-four times) and general practitioner consultations and hospitalizations with acute care sensitive conditions each subsequent year, respectively., Results: Each additional mobility limitation was associated with 15% higher odds of general practitioner home consultation (Odds ratio 1.15, 95% CI 1.07;1.23) and 4% increased incidence rate of general practitioner consultations among those with ≥ 1 consultation (Incidence rate ratio 1.04, 95% CI 1.03;1.04). There were no associations between mobility limitations and whether older adults had at least one general practitioner consultation nor acute care sensitive condition hospitalization. Test of interactions (p < 0.03) showed that more mobility limitations were associated with greater incidence rate of general practitioner consultations among males compared to females, married compared to unmarried, and older adults with high compared to low financial assets., Conclusions: Older adults with more mobility limitations had more often a general practitioner home consultation. Mobility limitations were not associated with whether older adults had at least one general practitioner consultation, but increased mobility limitations were associated with higher contact rate among those who had ≥ 1 consultation, especially among males and older adults who were married or had high financial assets.

Purpose: Only a few studies have investigated the impact of negative aspects of social relations on cognitive function, and they have shown mixed results. Conflicts at work are part of the negative aspects of social relations, but the impact of experiencing conflicts at work has not yet been investigated as a risk factor for dementia. Therefore, we investigated whether experiencing prolonged or serious conflicts with a supervisor or colleagues at work was associated with incident dementia in old age., Methods: We analyzed data of 6,436 men and women from the third survey of the Copenhagen City Heart Study. At baseline in 1991-1994, the participants reported whether they had ever had a prolonged or serious conflict at work. The participants were followed until 2014. We used Poisson regression to estimate incidence rate ratios (IRR) and their 95% confidence intervals (CI)., Results: After adjusting for potential confounders, the IRR for dementia was 1.53 (95% CI 0.77-3.03) among participants who had reported having prolonged or serious conflicts both with a supervisor and colleagues compared with participants who had never had such conflicts. In separate analyses stratified by sex, the IRRs were 2.14 (95% Cl 0.97-4.71) for men and 0.98 (95% Cl 0.29-3.32) for women., Conclusions: Our findings did not support an overall association between experiencing prolonged or serious conflicts at work and incident dementia. However, because of the large differences in the point estimates for men and women, future research could aim at investigating potential sex differences regarding the association between conflicts at work and dementia.

Background: The concept of social foreground describes how adult offspring's socioeconomic resources may influence older adults' health and several studies have shown an association between socioeconomic position of adult offspring and the health of their older parents. However, little is known about the factors that generate these associations. We study 1) how adult offspring's social class is associated with physical function (PF) among older adults, 2) whether geographical closeness and contact frequency with offspring modify the association, and 3) whether intergenerational social mobility of offspring is associated with PF of older adults., Method: Data are obtained from the 2002 (n = 621) and 2011 (n = 931) waves of the Swedish Panel Study of Living Conditions of the Oldest Old. Multivariable linear regression models were employed and adjusted for own and partner's prior social class and offspring's age and gender., Results: Compared to offspring with non-manual occupation, offsprings with manual occupation was associated with poorer PF in older adults (-0.14, CI95%:-0.28;0.00). In stratified analyses, offspring's social class was only associated with older adults' PF among those who lived geographically close. Contact frequency between the offspring and the older adults did not modify the associations. Older adults whose offspring experienced downward intergenerational social mobility were associated with the poorest PF., Conclusion: This study supports evidence of a relationship between social foreground and older adults' PF where geographical closeness and social mobility are important components., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Despite the current evidence of a high prevalence of forgetfulness in middle-aged individuals, and the evidence of a link between midlife memory complaints and biological changes in the brain, no previous study has yet investigated midlife forgetfulness in relation to risk of dementia in old age., Aims: We investigated whether midlife forgetfulness was an indicator of an increased risk of dementia in old age., Methods: We used data from 3,136 employed men and women who participated in the Danish Work Environment Cohort Study in 1990. These data were linked to Danish national registers. Participants were asked whether their closest relative had ever told them that they were forgetful. Incidence rate ratios (IRR) were estimated using Poisson regression analysis., Results: At baseline, 749 (24%) study participants were categorized as forgetful, and 86 (2.7%) participants were diagnosed with dementia during a total of 31,724 person-years at risk. After adjusting for sociodemographic factors, comorbidities, and work-related factors, midlife forgetfulness was associated with a higher risk of dementia (IRR = 1.82; 95% CI: 1.12-2.97)., Conclusions: This study is the first to investigate midlife forgetfulness and dementia, and the results suggest that midlife forgetfulness is an early indicator of an increased risk of dementia in old age., (© 2019 S. Karger AG, Basel.)

[This corrects the article DOI: 10.1371/journal.pone.0205019.].

Background: Numerous risk prediction models use indicators of health to predict mortality in old age. The added value to mortality predictions based on demographic variables is unknown., Objective: To evaluate the accuracy of health indicators in predicting all-cause mortality among individuals aged 50+ using area under receiver operating characteristic curve (AUC). Specifically, to assess the added value of health indicators relative to demographic variables., Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. There were no restrictions on study designs, follow-up duration, language, or publication dates. We also examined the quality of studies using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies., Results: Out of 804 studies investigating all-cause mortality in older persons, 16 studies were eligible. In community-dwelling populations, the accuracy of demographic variables and health indicators combined ranged from AUC 0.71 to 0.82, indicating modest ability to predict mortality. Age contributed the most to mortality prediction (AUC 0.65 to 0.78) and compared to age and sex, the added values of genetics, physiology, functioning, mood, cognition, nutritional status, subjective health, disease, frailty, and lifestyle ranged from AUC 0.01 to 0.10. The lack of validation samples made it difficult to assess their true added value. Findings were similar in institutionalized populations. Heterogeneity of the studies prevented us from performing a meta-analysis., Conclusion: Age and sex contributed the most to mortality predictions in old age while the added value of health indicators is likely to be limited., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Earlier studies report inconsistent associations between education and cognitive aging. We assessed the association, accounting for selective dropout due to death or dementia, and, in a subsample, accounting for confounding by early-life intelligence. Data from the Danish component of the Survey of Health, Ageing and Retirement in Europe (n = 3,400) were linked to registry data (education records, dementia diagnoses, and mortality) and the Danish Conscription Database (youth intelligence measurements for 854 men). Word recall and verbal fluency were assessed up to 4 times over 10 years (2004-2013) and combined by averaging the z scores. We fitted a joint model linking a time-to-event model for dementia or death to a linear mixed-effects model for cognitive change. Rate of cognitive decline was slower among people with high education compared with low education (β = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth intelligence did not attenuate the association between education and cognitive decline (crude β = 0.136, 95% CI: 0.028, 0.244 vs. adjusted β = 0.145, 95% CI: 0.022, 0.269). The results suggest that higher education may slow cognitive decline in later life. In this sample, results changed little when accounting for selective attrition and confounding by intelligence.